Measuring ability to assess claims about treatment effects: a latent trait analysis of items from the 'Claim Evaluation Tools database using Rasch modelling

Background

The Claim Evaluation Tools database contains multiple-choice items for measuring people's ability to apply the key concepts they need to know to be able to assess treatment claims. We assessed items from the database using Rasch analysis to develop an outcome measure to be used in two randomised trials in Uganda. Rasch analysis is a form of psychometric testing relying on Item Response Theory. It is a dynamic way of developing outcome measures that are valid and reliable.

Objectives

To assess the validity, reliability and responsiveness of 88 items addressing 22 key concepts using Rasch analysis.

Participants

We administrated four sets of multiple-choice items in English to 1114 people in Uganda and Norway, of which 685 were children and 429 were adults (including 171 health professionals). We scored all items dichotomously. We explored summary and individual fit statistics using the RUMM2030 analysis package. We used SPSS to perform distractor analysis.

Results

Most items conformed well to the Rasch model, but some items needed revision. Overall, the four item sets had satisfactory reliability. We did not identify significant response dependence between any pairs of items and, overall, the magnitude of multidimensionality in the data was acceptable. The items had a high level of difficulty.

Conclusion

Most of the items conformed well to the Rasch model's expectations. Following revision of some items, we concluded that most of the items were suitable for use in an outcome measure for evaluating the ability of children or adults to assess treatment claims.

http://ift.tt/2r1N9Az

Reduction Without Elimination: Mental Disorders as Causally Efficacious Properties

Abstract

We argue that any account of mental disorders that meets the desideratum of assigning causal efficacy to mental disorders faces the so-called "causal exclusion problem". We argue that fully reductive accounts solve this problem but run into the problem of multiple realizability. Recently advocated symptom-network approaches avoid the problem of multiple realizability, but they also run into the causal exclusion problem. Based on a critical analysis of these accounts, we will present our own account according to which mental disorders are dispositional properties that are token-identical to physical properties. More specifically, they are analyzed as dispositions to cause the specific set of symptoms. We argue that our account is not only able to account for multiple realizability without running into the causal exclusion problem, but that it also allows for the integration of very different factors into the description and explanation of mental disorders, such as neurological and neurochemical factors on the one side and social and cultural factors on the other. It thereby gives the psychiatric level of causal explanation autonomy while securing the causal efficacy of mental disorders in a causally closed physical world.

http://ift.tt/2rnKHHF

No-report Paradigmatic Ascription of the Minimally Conscious State: Neural Signals as a Communicative Means for Operational Diagnostic Criteria

Abstract

The minimally conscious state (MCS) is usually ascribed when a patient with brain damage exhibits observable volitional behaviors that predict recovery of cognitive functions. Nevertheless, a patient with brain damage who lacks motor capacity might nonetheless be in MCS. For this reason, some clinicians use neural signals as a communicative means for MCS ascription. For instance, a vegetative state patient is diagnosed with MCS if activity in the motor area is observed when the instruction to imagine wiggling toes is given. The validity of using neural signals in ascribing MCS requires a special sort of inference. That is, no-report paradigmatic assessments must have inductively strong ways of inferring a purported informational content from the observed neural signal that grounds the fact that the patient has top-down cognitive control (or residual volition). Shannon's mathematical theory of communication and Bayes' theorem reveals the formal structure of neural communication. On the basis of relevant data from the neuroscience literature, I conclude that the formal structure combined with the data shows that neural signals can be used as a communicative means for operational diagnostic criteria for MCS ascription.

http://ift.tt/2rWEjEa

Spotlight (Lappin-Scott)

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Review of Flexible Temperature Sensing Networks for Wearable Physiological Monitoring

Physiological temperature varies temporally and spatially. Accurate and real-time detection of localized temperature changes in biological tissues regardless of large deformation is crucial to understand thermal principle of homeostasis, to assess sophisticated health conditions, and further to offer possibilities of building a smart healthcare and medical system. Additionally, continuous temperature mapping in flexible and stretchable formats opens up many other potential areas, such as artificially electronic skins and reflection of emotional changes. This review exploits a comprehensive investigation onto recent advances in flexible temperature sensors, stretchable sensor networks, and platforms constructed in soft and compliant formats for wearable physiological monitoring. The most recent examples of flexible temperature sensors are first discussed regarding to their materials, structures, electrical and mechanical properties; temperature sensing network technologies in new materials and structural designs are then presented based on platforms comprised of multiple physical sensors and stretchable electronics. Finally, wearable applications of the sensing network are described, such as detection of human activities, monitoring of health conditions, and emotion-related bodily sensations. Conclusions are made with emphasis on critical issues and new trends in the field of wearable temperature sensor network technologies.

Accurate and real-time detection of localized temperature changes in biological tissues regardless of large deformation is crucial to understand thermal principle of homeostasis and to assess sophisticated health conditions. This review exploits recent advances in flexible temperature sensors, stretchable sensor networks, and platforms constructed in soft and compliant formats for wearable physiological monitoring.

http://ift.tt/2rnqrWs

Wet-Chemical Synthesis of Hollow Red-Phosphorus Nanospheres with Porous Shells as Anodes for High-Performance Lithium-Ion and Sodium-Ion Batteries

Large-volume-expansion-induced material pulverization severely limits the electrochemical performance of red phosphorous (P) for energy-storage applications. Hollow nanospheres with porous shells are recognized as an ideal structure to resolve these issues. However, a chemical synthetic approach for preparing nanostructured red P is always of great challenge and hollow nanosphere structures of red P have not yet been fabricated. Herein, a wet solvothermal method to successfully fabricate hollow P nanospheres (HPNs) with porous shells via a gas-bubble-directed formation mechanism is developed. More importantly, due to the merits of the porous and hollow structures, these HPNs reveal the highest capacities (based on the weight of electrode materials) of 1285.7 mA h g⁻¹ for lithium-ion batteries and 1364.7 mA h g⁻¹ for sodium-ion batteries at 0.2 C, and excellent long-cycling performance.

Preparing nanostructured phosphorus by a chemical synthetic approach is always challenging. A wet solvothermal method is developed to fabricate hollow phosphorous nanospheres (HPNs) with porous shells via a gas-bubble-directed formation mechanism. More importantly, due to the merits of porous and hollow structures, HPNs reveal excellent electrochemical performance as anodes for lithium-ion and sodium-ion batteries.

http://ift.tt/2rWS6e6

Reduced Interface-Mediated Recombination for High Open-Circuit Voltages in CH3NH3PbI3 Solar Cells

Perovskite solar cells with all-organic transport layers exhibit efficiencies rivaling their counterparts that employ inorganic transport layers, while avoiding high-temperature processing. Herein, it is investigated how the choice of the fullerene derivative employed in the electron-transporting layer of inverted perovskite cells affects the open-circuit voltage (V_OC). It is shown that nonradiative recombination mediated by the electron-transporting layer is the limiting factor for the V_OC in the cells. By inserting an ultrathin layer of an insulating polymer between the active CH₃NH₃PbI₃ perovskite and the fullerene, an external radiative efficiency of up to 0.3%, a V_OC as high as 1.16 V, and a power conversion efficiency of 19.4% are realized. The results show that the reduction of nonradiative recombination due to charge-blocking at the perovskite/organic interface is more important than proper level alignment in the search for ideal selective contacts toward high V_OC and efficiency.

Perovskite solar cells have emerged as one of the most promising solar-cell technologies for the next generation of photovoltaics. Despite simple and cheap processing, the solar cells exhibit comparably little loss in open-circuit voltage. An approach to further reduce this loss by optimizing the charge selectivity of the fullerene-based electron contact in efficient devices is shown.

http://ift.tt/2rnhZ9L

Mise en ligne du N° 3, volume 62 (juin 2017) de la revue 'Annales de chirurgie plastique esthétique'

Vol 62 - N°3 - juin 2017 P. 189-267 © 2017, Elsevier Masson SAS

http://ift.tt/2s1sOKU

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) in adults-a case report and literature review

Mild encephalitis/encephalopathy with reversible splenial lesion (MERS) is a rare clinico-radiological entity characterized by the magnetic resonance imaging (MRI) finding of a reversible lesion in the corpus ...

http://ift.tt/2r3mfdB

Flu-like illness, fever, malaise and chills, followed by severe nonpleuritic chest pain and shortness of breath

Chronic migraine headache and acute shortness of breath associated with nausea, vomiting, diaphoresis and increasing retrosternal chest pain..Increased frequency of his migraine headaches associated with vague retrosternal chest pain and epigastric pain...................................................................................................................Flu-like illness, fever, malaise and chills, followed by severe nonpleuritic chest pain and shortness of breath................................................................................Palpitations, fatigue, vague chest discomfort, and cardiomegaly and pulmonary congestion visible on chest radiograph. He had developed a flu-like illness with low-grade fever, chills, myalgia and headache a week earlier. There had been no preceding cough, hemoptysis, orthopnea, paroxysmal nocturnal dyspnea or ankle edema. .....................................................................................................................................Eosinophilic myocarditis (EM)........................................................................................................Therapeutic effect of anti-IL-5 on eosinophilic myocarditis with large pericardial effusion

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Revision and optimization in spinal cord neuromodulation for chronic pain

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): John Lynes, Wesley Chen, Christopher Kalhorn
Despite advances in spinal cord stimulator implantation, inadequate therapeutic response remains a significant issue. Revision procedures aim to improve coverage, whether through revision of existing implants, supplementation with additional hardware, or changing modalities. Inherent challenges in surgical technique and treatment planning have led to techniques and ongoing areas of development and research.



http://ift.tt/2rndQ5U

Introduction

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): Christopher G. Kalhorn




http://ift.tt/2rWmaWZ

Spinal Cord Anatomy, Pain, and Spinal Cord Stimulation Mechanisms

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): Ehsan Dowlati
The effectiveness and mechanisms of spinal cord stimulation described in literature rely on a proper understanding of spinal cord anatomy and pain theory. In this chapter we provide an overview of relevant spinal cord anatomy, pain mechanisms, and theories of pain perception. This includes the gate control theory that is the foundation for spinal cord stimulation as a treatment for chronic pain. Thereafter, we describe the different mechanisms of spinal cord stimulation. Specifically, there are considerations in anatomy, electrophysiology, neurochemistry and neurophysiology of the central nervous system that play a role in how spinal cord stimulation modulates the pain "gate" system.



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Chapter 4: Technique of Percutaneous and Laminectomy/Open Approach for Permanent Spinal Cord Implantation (Cervical/Thoracic)

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): Rita Snyder
Spinal cord stimulator implantation may be performed percutaneously or via an open approach. Level-dependent considerations are made depending on optimal lead placement location, in particular with regards to the cervical spine. Following a successful temporary lead trial, a power source is implanted in addition to the permanent electrodes.



http://ift.tt/2rWuK86

Field/peripheral stimulation: Surgical indications & technique

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): Raj N. Parekh
Peripheral stimulation, similar to spinal cord stimulation, is a form of neuromodulation that aims to treat chronic pain by directly targeting peripheral nerves, and thus altering peripheral pain pathways leading to pain relief. Implantation is performed within two stages. The first stage, or trial phase, is performed under local anesthesia and attempts to identify the appropriate peripheral nerve causing pain. The second stage, performed under general anesthesia, involves placement of an internal battery/generator for the implanted electrode. Indications for peripheral stimulation include: migraine, occipital neuralgia, cluster headache, neuropathic facial pain, complex regional pain syndrome, and chronic lower back pain.



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Clinical indications for spinal cord stimulation

Publication date: Available online 25 May 2017
Source:Seminars in Spine Surgery
Author(s): Raj N. Parekh
As a form of neuromodulation, spinal cord stimulation can be used with great efficacy in treating chronic pain symptoms. However, careful consideration in choosing the correct patient is important in ensuring maximal pain relief, and ultimate success of the spinal cord stimulator. The most common indication for spinal cord stimulation in the United States is failed back surgery syndrome. Other indications for spinal cord stimulator placement include complex regional pain syndrome, peripheral vascular disease, refractory angina, and painful diabetic neuropathy.



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Neoadjuvant chemotherapy with trastuzumab, docetaxel, and carboplatin administered every 3 weeks for Japanese women with HER2-positive primary breast cancer: efficacy and safety

Abstract

Background

This phase II neoadjuvant study evaluated the efficacy and safety of a triweekly regimen of docetaxel and carboplatin in combination with trastuzumab (TCbH) in Japanese women with human epidermal growth factor receptor type2 (HER2)-positive primary breast cancer.

Methods

Patients with HER2-positive, stage I–III invasive breast cancer received six courses of trastuzumab (8 mg/kg loading dose, then 6 mg/kg, day 1), docetaxel (75 mg/m², day 1), and carboplatin (area under the curve: 6, day 1) every 3 weeks. The primary endpoint was pathological complete response (pCR) of both breast and axillary lymph node disease.

Results

Fifty patients were enrolled in this study. Median age was 58 (range 32–75) years. All patients underwent definitive surgery. Thirty-three (66%) patients completed the chemotherapy course, while the treatment was delayed or discontinued in the other 17 (34%) patients because of adverse events (AEs). The pCR rate was 52%; the overall response rate was 66%. Grade 3/4 AEs due to nonhematological toxicity were anorexia (4%), diarrhea (2%), and rash (2%), and those due to hematological toxicity were neutropenia (36%), anemia (12%), and thrombocytopenia (2%).

Conclusion

Although the triweekly six-course regimen of TCbH achieved a high pCR rate, hematological AEs frequently occurred during the latter part of the chemotherapy course. One-third of patients experienced delayed or discontinued chemotherapy.

Clinical registration number: http://www.umin.org.auUMIN000013513.

http://ift.tt/2qUUcfO

Functional characterization of rs2229094 (T>C) polymorphism in the tumor necrosis factor locus and lymphotoxin alpha expression in human retina: the Retina 4 project

http://ift.tt/2rFacUD

Randomized comparison of in vivo performance of two point-of-care tear film osmometers

http://ift.tt/2qm1Gpo

The SUPER study: protocol for a randomised controlled trial comparing follicle-stimulating hormone and clomiphene citrate for ovarian stimulation in intrauterine insemination

Objective

To study the effectiveness of four cycles of intrauterine insemination (IUI) with ovarian stimulation (OS) by follicle-stimulating hormone (FSH) or by clomiphene citrate (CC), and adherence to strict cancellation criteria.

Setting

Randomised controlled trial among 22 secondary and tertiary fertility clinics in the Netherlands.

Participants

732 women from couples diagnosed with unexplained or mild male subfertility and an unfavourable prognosis according to the model of Hunault of natural conception.

Interventions

Four cycles of IUI–OS within a time horizon of 6 months comparing FSH 75 IU with CC 100 mg. The primary outcome is ongoing pregnancy conceived within 6 months after randomisation, defined as a positive heartbeat at 12 weeks of gestation. Secondary outcomes are cancellation rates, number of cycles with a monofollicular or with multifollicular growth, number of follicles >14 mm at the time of ovulation triggering, time to ongoing pregnancy, clinical pregnancy, miscarriage, live birth and multiple pregnancy. We will also assess if biomarkers such as female age, body mass index, smoking status, antral follicle count and endometrial aspect and thickness can be used as treatment selection markers.

Ethics and dissemination

The study has been approved by the Medical Ethical Committee of the Academic Medical Centre and from the Dutch Central Committee on Research involving Human Subjects (CCMO NL 43131-018-13). Results will be disseminated through peer-reviewed publications and presentations at international scientific meetings.

Trial registration number

NTR4057.

http://ift.tt/2rniJf8

Effects of continuous positive airway pressure on neurocognitive architecture and function in patients with obstructive sleep apnoea: study protocol for a multicentre randomised controlled trial

Objectives

Many clinical studies have indicated that obstructive sleep apnoea (OSA), the most common chronic sleep disorder, may affect neurocognitive function, and that treatment for continuous positive airway pressure (CPAP) has some neurocognitive protective effects against the adverse effects of OSA. However, the effects of CPAP treatment on neurocognitive architecture and function remain unclear. Therefore, this multicentre trial was designed to investigate whether and when neurocognitive architecture and function in patients with OSA can be improved by CPAP treatment and to explore the role of gut microbiota in improving neurocognitive function during treatment.

Methods/design

This study will be a multicentre, randomised, controlled trial with allocation concealment and assessor blinding. A total of 148 eligible patients with moderate to severe OSA will be enrolled from five sleep centres and randomised to receive CPAP with best supportive care (BSC) intervention or BSC intervention alone. Cognitive function, structure and function of brain regions, gut microbiota, metabolites, biochemical variables, electrocardiography, echocardiography, pulmonary function and arterial stiffness will be assessed at baseline before randomisation and at 3, 6 and 12 months.

Ethics and dissemination

This study has been approved by the Medical Ethics Committee of Shanghai Jiao Tong University Affiliated Sixth People's Hospital (approval number 2015-79). The results from this study will be published in peer-reviewed journals and at relevant conferences.

Trial registration number

NCT02886156; pre-results.

http://ift.tt/2rWdRKV

Longitudinal assessment of brain-derived neurotrophic factor in Sardinian psychotic patients (LABSP): a protocol for a prospective observational study

Introduction

Brain-derived neurotrophic factor (BDNF) plays a crucial role in neurodevelopment, synaptic plasticity and neuronal function and survival. Serum and plasma BDNF levels are moderately, but consistently, decreased in patients with schizophrenia (SCZ) compared with healthy controls. There is a lack of knowledge, however, on the temporal manifestation of this decline. Clinical, illness course and treatment factors might influence the variation of BDNF serum levels in patients with psychosis. In this context, we propose a longitudinal study of a cohort of SCZ and schizophrenic and schizoaffective disorder (SAD) Sardinian patients with the aim of disentangling the relationship between peripheral BDNF serum levels and changes of psychopathology, cognition and drug treatments.

Methods and analysis

Longitudinal assessment of BDNF in Sardinian psychotic patients (LABSP) is a 24-month observational prospective cohort study. Patients with SAD will be recruited at the Psychiatry Research Unit of the Department of Medical Science and Public Health, University of Cagliari and University of Cagliari Health Agency, Cagliari, Italy. We will collect BDNF serum levels as well as sociodemographic, psychopathological and neurocognitive measures. Structured, semistructured and self-rating assessment tools, such as the Positive and Negative Syndrome Scale for psychopathological measures and the Brief Assessment of Cognition in Schizophrenia for cognitive function, will be used.

Ethics and dissemination

This study protocol was approved by the University of Cagliari Health Agency Ethics Committee (NP2016/5491). The study will be conducted in accordance with the principles of good clinical practice, in the Declaration of Helsinki in compliance with the regulations. Participation will be voluntary and written informed consent will be obtained for each participant upon entry into the study. We plan to disseminate the results of our study through conference presentations and publication in international peer-reviewed journals. Access to raw data will be available in anonymised form upon request to the corresponding author.

http://ift.tt/2rWpMbw

Chest pain and shortness of breath in cardiovascular disease: a prospective cohort study in UK primary care

Objective

To determine characteristics associated with monthly chest pain and shortness of breath (SoB) during activity in cardiovascular disease (CVD) and trajectories of these symptoms over 10 months.

Study design and setting

Baseline questionnaire was sent to patients aged ≥40 years from 10 UK general practices. Responders were sent monthly questionnaires for 10 months. For patients with CVD (ischaemic heart disease and heart failure), the association of sociodemographic characteristics, pain elsewhere and anxiety and depression with monthly reports of chest pain and SoB during activity were determined using multilevel, multinomial logistic regression. Common symptom trajectories were determined using dual trajectory latent class growth analysis.

Results

661 patients with CVD completed at least 5 monthly questionnaires. Multiple other pain sites (relative risk ratio: 4.03; 95% CI 1.64 to 9.91) and anxiety or depression (relative risk ratio: 3.31; 95% CI 1.89 to 5.79) were associated with reporting weekly chest pain. Anxiety or depression (relative risk ratio: 4.10; 95% CI 2.72 to 6.17), obesity (relative risk ratio: 2.53; 95% CI 1.49 to 4.30), older age (80+: relative risk ratio: 2.51; 95% CI 1.19 to 5.26), increasing number of pain sites (4+: relative risk ratio: 4.64; 95% CI 2.35 to 9.18) and female gender (relative risk ratio: 1.81; 95% CI 1.20 to 2.75) were associated with reporting weekly SoB. Eight symptom trajectories were identified, with SoB symptoms more common than chest pain.

Conclusions

Potentially modifiable characteristics are associated with the experience of chest pain and SoB. Identified symptom trajectories may facilitate tailored care to improve outcomes in patients with CVD.

http://ift.tt/2rWNcxN

Translation, adaptation and validation of two versions of the Chronic Liver Disease Questionnaire in Malaysian patients for speakers of both English and Malay languages: a cross-sectional study

Objective

We aimed to adapt, translate and validate the Chronic Liver Disease Questionnaire (CLDQ) in Malaysian patients with chronic liver diseases of various aetiologies.

Setting

Tertiary level teaching institution in Malaysia.

Participants

The validation process involved 211 adult patients (English language n=101, Malay language n=110) with chronic liver disease. Characteristics of the study subjects were as follows: mean (SD) age was 56 (12.8) years, 58.3% were male and 41.7% female. The inclusion criteria were patients 18 years or older with chronic hepatitis and/or liver cirrhosis of any aetiology. The exclusion criteria were as follows: presence of hepatic encephalopathy, ongoing treatment with interferon and presence of other chronic conditions that have an impact on health-related quality of life (HRQOL).

Methods

A cross-sectional study was conducted. Cultural adaptation of the English version of the CLDQ was performed, and a Malay version was developed following standard forward–backward translation by independent native speakers. Psychometric properties of both versions were determined by assessing their internal consistency, test–retest reliability and discriminant and convergent validity.

Results

Cronbach's alpha for internal consistency across the various domains of the CLDQ was 0.95 for the English version and 0.92 for the Malay version. Test–retest analysis showed excellent reliability with an intraclass correlation coefficient of 0.89 for the English version and 0.93 for the Malay version. The average scores of both the English and Malay versions of the CLDQ demonstrated adequate discriminant validity by differentiating between non-cirrhosis (English 6.3, Malay 6.1), compensated cirrhosis (English 5.6, Malay 6.0) and decompensated cirrhosis (English 5.1, Malay 4.9) (p<0.001). Convergent validity showed that correlation was fair between the English (=0.59) and Malay (p=0.47) CLDQ versions with the EQ-5D, a generic HRQOL instrument.

Conclusion

The English and Malay versions of the CLDQ are reliable and valid disease-specific instruments for assessing HRQOL in Malaysian patients with chronic liver disease.

http://ift.tt/2rnFuiS

Hereditary and non-hereditary branches of family eligible for BRCA test: cancers in other sites

Abstract

Background

The analysis of relationships of BRCA alterations with cancer at sites other than breast/ovary may provide innovative information concerning BRCA pathogenic role and support additional clinical decisions. Aim of this study is to compare presence of cancers in other sites in members of hereditary (H) and not-hereditary (nH) branches of families of patients eligible to BRCA test.

Methods

We retrospectively analyzed the incidence of cancer in other sites in members of 136 families eligible for hereditary breast/ovarian cancer genetic counseling at Centro Studi Tumori Eredo-familiari of our Institute; we compared the frequency of other cancer types in 1156 members of the H-branch with respect to 1062 members of nH-Branch. The families belonging to a proband case and with informative members in at least three generation entered the present study.

Results

The frequency of other Cancers in members of H-branch was significantly higher than that in members of nH-branch (161 vs 75 cancers; p < 0.0001). In specific, members of H-branch had a significantly higher probability to have more lung cancer (38 vs 9;p < 0.0006), kidney cancer (23 vs 5;p < 0.0005), liver cancer (13 vs 3;p < 0.02) and larynx cancer (14 vs 4;p < 0.03). Interestingly, to belong to H-branch resulted significantly associated with a higher probability of lung cancer (OR 4.5; 2.15–9.38 95%C.I.), liver cancer (OR: 4.02; 1.14–14.15 95% C.I.) and larynx cancer (OR:3.4; 1.12–10.39 95%C.I.) independently from Gender and Age.

Conclusions

Members belonging to the H-branch of families of patients eligible to BRCA test have a higher risk of tumors in lung, larynx and liver. Clinicians should consider the increased risk for these cancers to activate prevention/early diagnosis practices in members of families with breast/ovarian familial cancer syndrome.

http://ift.tt/2rWIDU6

Long-term use of pegylated liposomal doxorubicin to a cumulative dose of 4600 mg/m2 in recurrent ovarian cancer.

Pegylated liposomal doxorubicin (PLD) is used widely in gynecologic oncology and other oncology disciplines. Native doxorubicin use is associated with the potential for significant toxicity. Cardiac toxicity in particular limits lifetime dose. PLD has not been shown to be associated with clinical cardiac toxicity. We report on the long-term use of PLD in a patient with recurrent high-grade serous ovarian cancer to a lifetime dose of 4600 mg/m2. This therapy was associated with long-term stable disease, good performance status, and minimal adverse effects. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qlSrpi

Hypoxia as a target for drug combination therapy of liver cancer.

Hepatocellular carcinoma (HCC) is the third most frequent cause of cancer deaths worldwide. The standard of care for intermediate HCC is transarterial chemoembolization, which combines tumour embolization with locoregional delivery of the chemotherapeutic doxorubicin. Embolization therapies induce hypoxia, leading to the escape and proliferation of hypoxia-adapted cancer cells. The transcription factor that orchestrates responses to hypoxia is hypoxia-inducible factor 1 (HIF-1). The aim of this work is to show that targeting HIF-1 with combined drug therapy presents an opportunity for improving outcomes for HCC treatment. HepG2 cells were cultured under normoxic and hypoxic conditions exposed to doxorubicin, rapamycin and combinations thereof, and analyzed for viability and the expression of hypoxia-induced HIF-1[alpha] in response to these treatments. A pilot study was carried out to evaluate the antitumour effects of these drug combinations delivered from drug-eluting beads in vivo using an ectopic xenograft murine model of HCC. A therapeutic doxorubicin concentration that inhibits the viability of normoxic and hypoxic HepG2 cells and above which hypoxic cells are chemoresistant was identified, together with the lowest effective dose of rapamycin against normoxic and hypoxic HepG2 cells. It was shown that combinations of rapamycin and doxorubicin are more effective than doxorubicin alone. Western Blotting indicated that both doxorubicin and rapamycin inhibit hypoxia-induced accumulation of HIF-1[alpha]. Combination treatments were more effective in vivo than either treatment alone. mTOR inhibition can improve outcomes of doxorubicin treatment in HCC. This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://ift.tt/1iwynXF Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2rFgkfv

A survey of renal impairment pharmacokinetic studies for new oncology drug approvals in the USA from 2010 to early 2015: a focus on development strategies and future directions.

The US Food and Drug Administration (FDA) issued a guidance document in 2010 on pharmacokinetic (PK) studies in renal impairment (RI) on the basis of observations that substances such as uremic toxins might result in altered drug metabolism and excretion. No specific recommendations for oncology drugs were included. We surveyed the publicly available FDA review documents of 29 small molecule oncology drugs approved between 2010 and the first quarter of 2015. The objectives were as follows: (i) summarize the impact of RI on PK at the time of the initial new drug application; (ii) identify limitations of the guidance; and (iii) outline an integrated approach to study the impact of RI on these drugs. Our survey indicates that the current FDA guidance does not appear to provide clear strategic or decision pathways for RI studies in terms of small molecule oncology drugs. The FDA review documents indicate an individualized approach to the review because of the complex pharmacologic nature of these drugs and patient populations. Overall, the strategy for carrying out a RI study during clinical development or as a postmarketing study requires integration with the totality of data, including mass balance, absolute bioavailability, drug-drug interaction, hepatic dysfunction, population PK, exposure-response analysis, the therapeutic window for best guidance, and determination of the optimal doses for special oncology populations. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://ift.tt/1hexVwJ Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2qlZluX

Role of the uridine/cytidine kinase 2 mutation in cellular sensitiveness toward 3'-ethynylcytidine treatment of human cancer cells.

A nucleosidic medicine, 1-(3-C-ethynyl-[beta]-D-ribo-pentofuranosyl)cytosine [3'-ethynylcytidine (ECyd)], is a potent inhibitor of RNA polymerase I and shows anticancer activity to various human solid tumors in vitro and in vivo. ECyd is phosphorylated to 3'-ethyntlcytidine 5'-monophosphate by uridine/cytidine kinase 2 (UCK2) and subsequently further to diphosphate and triphosphate (3'-ethyntlcytidine 5'-diphosphate, 3'-ethyntlcytidine 5'-triphosphate). 3'-Ethyntlcytidine 5'-triphosphate is an active metabolite that can inhibit RNA polymerase I competitively, causing cancer cell death. Here, to identify the UCK2 mutation for detecting responder or nonresponder to ECyd, we investigated the relationship between point mutation of the UCK2 gene and response to ECyd in various human solid tumors. We identified several functional point mutations including the splice-site mutation of the UCK2 gene IVS5+5 G>A. In addition, we found that the IVS5+5 G>A variant generates an aberrant mRNA transcript, namely, truncated mRNA was produced and normal mRNA levels were markedly decreased in the ECyd-resistant cancer cell line HT1080. We concluded that these findings strongly suggest that the IVS5+5 G>A variant would affect the expression level of the UCK2 transcript, resulting in decreased sensitivity to ECyd. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

http://ift.tt/2rFDqTo

Prognostic impact of the cumulative dose and dose intensity of everolimus in patients with pancreatic neuroendocrine tumors

Abstract

The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. One hundred and sixteen patients (62 males and 54 females, median age 55 years) with advanced PNETs were treated with everolimus for ≥3 months. According to a Receiver operating characteristics (ROC) analysis, patients were stratified into two groups, with CD ≤ 3000 mg (Group A; n = 68) and CD > 3000 mg (Group B; n = 48). The response rate and toxicity were comparable in the two groups. However, patients in group A experienced more dose modifications than patients in group B. Median OS was 24 months in Group A while in Group B it was not reached (HR: 26.9; 95% CI: 11.0–76.7; P < 0.0001). Patients who maintained a DI higher than 9 mg/day experienced a significantly longer OS and experienced a trend to higher response rate. Overall, our study results showed that both CD and DI of everolimus play a prognostic role for patients with advanced PNETs treated with everolimus. This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

The aim of this work is to assess if cumulative dose (CD) and dose intensity (DI) of everolimus may affect survival of advanced pancreatic neuroendocrine tumors (PNETs) patients. Median OS was 24 months in Group A (with cumulative dose ≤ 3000 mg) while in Group B (with cumulative dose > 3000 mg), it was not reached (HR: 26.9; 95% CI: 11.0–76.7; P < 0.0001). This should prompt efforts to continue everolimus administration in responsive patients up to at least 3000 mg despite delays or temporary interruptions.

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Demographic and socioeconomic influences on Helicobacter pylori gastritis and its pre-neoplastic lesions amongst US residents

Summary

Background

Gastric infection with Helicobacter pylori (Hp) can lead to chronic inactive gastritis, atrophy and intestinal metaplasia.

Aims

To investigate in a cross-sectional study these changes among different socioeconomic and ethnic groups within the USA.

Methods

We used the Miraca Life Sciences database, an electronic depository of clinicopathological records from patients distributed throughout the USA, to extract data from 487 587 patients who underwent oesophago-gastro-duodenoscopy with biopsy between 1/2008 and 12/2014. We then classified patients into ethnic and socioeconomic categories using previously validated algorithms, as well as ZIP code-based information derived from the 2011-2012 US Census.

Results

The prevalence of Hp increased significantly until the age-group 40-49, before it leveled off and started a gradual decrease. The prevalence of chronic inactive gastritis, atrophy, and intestinal metaplasia increased significantly with age. The prevalence of Hp, chronic inactive gastritis, intestinal metaplasia, and atrophy decreased significantly with the percentage of Whites per ZIP code. The prevalence of all four diagnoses also decreased significantly with rising levels of income or college education. Hp, chronic inactive gastritis, atrophy and intestinal metaplasia were more common among Hispanics and the influence of income or college education less pronounced than in the entire population. Hp, chronic inactive gastritis, atrophy, and intestinal metaplasia were also more common among East-Asians, Hp and atrophy decreasing with rising income but remaining unaffected by levels of college education.

Conclusion

Ethnicity and socioeconomic factors influence the occurrence of Hp gastritis, and its progression to chronic inactive gastritis, atrophy or intestinal metaplasia.

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Keyboard: A Novel Bayesian Toxicity Probability Interval Design for Phase I Clinical Trials

The primary objective of phase I oncology trials is to find the maximum tolerated dose (MTD). The 3+3 design is easy to implement but performs poorly in finding the MTD. A newer design, such as the modified toxicity probability interval (mTPI) design, provides better accuracy to identify the MTD but tends to overdose patients. We propose the keyboard design, an intuitive Bayesian design that conducts dose escalation and de-escalation based on whether the strongest key, defined as the dosing interval that most likely contains the current dose, is below or above the target dosing interval. The keyboard design can be implemented in a simple way, similar to the traditional 3+3 design, but provides more flexibility for choosing the target toxicity rate and cohort size. Our simulation studies demonstrate that compared to the 3+3 design, the keyboard design has favorable operating characteristics in terms of identifying the MTD. Compared to the mTPI design, the keyboard design is safer, with a substantially lower risk of treating patients at overly toxic doses, and has the better precision to identify the MTD, thereby providing a useful upgrade to the mTPI design. Freely available, open-source software facilitates the application of the keyboard design.

http://ift.tt/2qpEuWN

Cytotoxicity of the methanol extracts of Elephantopus mollis, Kalanchoe crenata and 4 other Cameroonian medicinal plants towards human carcinoma cells

Cancer still constitutes one of the major health concerns globally, causing serious threats on patients, their families, and the healthcare system.

http://ift.tt/2rWr6er

Urinary metabolomics study on the protective role of Orthosiphon stamineus in Streptozotocin induced diabetes mellitus in rats via 1H NMR spectroscopy

Orthosiphon stamineus (OS) is a herb known in ethnomedicine for treating diabetes mellitus (DM). In this study, a 1H NMR based urine metabolomics tool has been used for the first time ...

http://ift.tt/2rWMosr

Effects of Dangguibuxue decoction on rat glomerular mesangial cells cultured under high glucose conditions

Dysfunction of glomerular mesangial cells (GMCs) plays an important role in pathogenesis of diabetic nephropathy. Here, we investigated the effects of ...

http://ift.tt/2rn8ZBn

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production

Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause consid...

http://ift.tt/2rWzgno

Investigation of antioxidant, antimicrobial and toxicity activities of lichens from high altitude regions of Nepal

Several lichen species are reported to be used tradiationally in many theraupatic practices. Many lichen species are reported as sources of several bioactive natural compounds. Several lichen species of Nepal ...

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Immune Atlases Created for Kidney, Lung Cancers [News in Brief]

In-depth analyses reveal dysregulated, immunosuppressive landscape in both tumor types.

http://ift.tt/2rWsuhn

Three Drugs Approved for Urothelial Carcinoma by FDA [News in Brief]

Checkpoint inhibitors pembrolizumab, avelumab, and durvalumab add to the list of similar drugs approved for treating bladder cancer.

http://ift.tt/2rnmWPZ

Obesity is Independently Associated With Increased Risk of Hepatocellular Cancer-related Mortality: A Systematic Review and Meta-Analysis.

Objective: Excess body weight is associated with increased risk of developing hepatocellular cancer (HCC), but its effect on HCC-related mortality remains unclear. We performed a systematic review and meta-analysis to assess the association between premorbid obesity and HCC-related mortality. Materials and Methods: Through a systematic literature search-up to March 2016, we identified 9 observational studies (1,599,453 individuals, 5705 HCC-related deaths) reporting the association between premorbid body mass index (BMI), and HCC-related mortality. We estimated summary adjusted hazard ratio (aHR) with 95% confidence intervals (CIs), comparing obese (BMI>30 kg/m2) and overweight (BMI, 25 to 29.9 kg/m2) individuals with normal BMI individuals using random-effects model. Results: On meta-analysis, compared with individuals with normal BMI, obese (aHR, 1.95; 95% CI, 1.46-2.46), but not overweight individuals (aHR, 1.08; 95% CI, 0.97-1.21), had higher HCC-related mortality, with moderate heterogeneity. On subgroup analysis, magnitude of increased mortality was higher in obese men (aHR, 2.50; 95% CI, 2.02-3.09; 3 studies) as compared with obese women (aHR, 1.45; 95% CI, 1.08-1.97; 2 studies). The impact of premorbid obesity on HCC-related mortality was observed only in western populations (aHR, 2.10; 95% CI, 1.77-2.48; 4 studies), but not Asian populations (aHR, 1.10; 95% CI, 0.63-1.92; 1 study). There was limited assessment of competing risk because of advanced liver disease. Conclusions: On the basis of this meta-analysis, premorbid obesity may be independently associated with a 2-fold risk of HCC-related mortality. This association was more pronounced in men and western populations. Strategies targeting obesity-associated metabolic abnormalities may provide novel pathways for HCC therapy. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.

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Impact of the Primary Information Source Used for Decision Making on Treatment Perceptions and Regret in Prostate Cancer.

Objective: To assess the impact of the primary source of information used by prostate cancer patients to select a radiation treatment on their overall treatment experience and on treatment regret. Methods: Patients with low to favorable intermediate-risk prostate cancer treated with stereotactic body radiation therapy, intensity-modulated radiation therapy, or high-dose rate brachytherapy were surveyed. The questionnaire explored the decision-making experience, treatment experience, and treatment regret. Results: In total, 322 consecutive patients were surveyed with an 86% (n=276) response rate. In total, 48% (n=132) selected their radiation oncologist as the primary information source, 23% (n=62) selected their urologist, 16% (n=44) selected the Internet, 6% (n=17) selected other patients, and 8% (n=21) selected other. In total, 39% of patients who selected the Internet as their primary information source reported their actual treatment experience to be worse than expected versus 13% of respondents who selected their urologist, 12% who selected other patients, and 2% who selected their radiation oncologist (P

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Treatment and Outcomes of Primary Urethra Cancer.

Background: Urethral cancer is a rare malignancy, representing

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Prevention of Trastuzumab and Anthracycline-induced Cardiotoxicity Using Angiotensin-converting Enzyme Inhibitors or [beta]-blockers in Older Adults With Breast Cancer.

Purpose: Although clinical trials have provided some data on the benefit of angiotensin-converting enzyme inhibitors (ACEIs) or [beta]-blockers (BBs) in patients with chemotherapy-induced cardiotoxicity, evidence of ACEIs/BBs on prevention of trastuzumab and/or anthracycline-induced cardiotoxicity outside trials is limited. Materials and Methods: A cohort study of 142,990 women (66 y and above) newly diagnosed with breast cancer from 2001 to 2009 was conducted using the Surveillance, Epidemiology, and End Results-Medicare-linked database. The ACEI/BB exposure was defined as filled prescription(s) before or after the initiation of trastuzumab/anthracyclines. The nonexposed group was defined as those who had never been prescribed ACEIs/BBs. Cumulative rates of cardiotoxicity and all-cause mortality were estimated and marginal structural Cox models were used to determine factors associated with cardiotoxicity and all-cause mortality adjusting for baseline covariates and use of chemotherapy. All statistical tests were 2 sided. Results: The final sample included 6542 women. Adjusted hazard ratio for cardiotoxicity and all-cause mortality for the ACEI/BB exposed group were 0.77 (95% confidence interval, 0.62-0.95) and 0.79 (95% confidence interval, 0.70-0.90) compared with the nonexposed group, respectively. Starting ACEIs/BBs=6 months were also associated with decreased risk of cardiotoxicity and all-cause mortality. Baseline characteristics, including age, non-Hispanic black, advanced cancer, region, comorbidity, preexisting cardiovascular conditions, lower socioeconomic status, and concomitant treatment were significantly associated with an elevated risk of all-cause mortality and/or cardiotoxicity (all P

http://ift.tt/2rnh0Gq

Spectrum sensing based on cumulative power spectral density

This paper presents new spectrum sensing algorithms based on the cumulative power spectral density (CPSD). The proposed detectors examine the CPSD of the received signal to make a decision on the absence/prese...

http://ift.tt/2r1H6Mc

Computer-aided detection of breast lesions in DCE-MRI using region growing based on fuzzy C-means clustering and vesselness filter

A computer-aided detection (CAD) system is introduced in this paper for detection of breast lesions in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). The proposed CAD system firstly compensate...

http://ift.tt/2qhIvRO

Novel maximum likelihood approach for passive detection and localisation of multiple emitters

In this paper, a novel target acquisition and localisation algorithm (TALA) is introduced that offers a capability for detecting and localising multiple targets using the intermittent "signals-of-opportunity" ...

http://ift.tt/2r2dkXW

Hybrid digital-analog coding with bandwidth expansion for correlated Gaussian sources under Rayleigh fading

Consider communicating a correlated Gaussian source over a Rayleigh fading channel with no knowledge of the channel signal-to-noise ratio (CSNR) at the transmitter. In this case, a digital system cannot be opt...

http://ift.tt/2qi1DPy

Improving care for people with heart failure in Uganda: serial in-depth interviews with patients’ and their health care professionals

The short prognosis of patients with advanced heart failure (HF) and the associated multidimensional distress as illustrated in literature from high income countries necessitates the integration of palliative ...

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Efficacy of prophylactic splenectomy for proximal advanced gastric cancer invading greater curvature

Abstract

Background

For proximal gastric cancer invading the greater curvature, concomitant splenectomy is frequently performed to secure the clearance of lymph node metastases. However, prognostic impact of prophylactic splenectomy remains unclear. The aim of this study was to clarify the oncological significance of prophylactic splenectomy for advanced proximal gastric cancer invading the greater curvature.

Methods

Retrospective review of 108 patients who underwent total or subtotal gastrectomy for advanced proximal gastric cancer involving the greater curvature was performed. Short-term and long-term outcomes were compared between the patients who underwent splenectomy (n = 63) and those who did not (n = 45).

Results

Patients who underwent splenectomy showed higher amount of blood loss (538 vs. 450 mL, p = 0.016) and morbidity rate (30.2 vs. 13.3, p = 0.041) compared with those who did not undergo splenectomy. In particular, pancreas-related complications were frequently observed among patients who received splenectomy (17.4 vs. 0%, p = 0.003). However, no significant improvement of long-term outcomes were confirmed in the cases with splenectomy (5-year recurrence-free rate, 60.2 vs. 67.3%; p = 0.609 and 5-year overall survival rates, 63.7 vs. 73.6%; p = 0.769). On the other hand, splenectomy was correlated with marginally better survival in patients with Borrmann type 1 or 2 gastric cancer (p = 0.072).

Conclusions

For advanced proximal gastric cancer involving the greater curvature, prophylactic splenectomy may have no significant prognostic impact despite the increased morbidity rate after surgery. Such surgical procedure should be avoided as long as lymph node involvement is not evident.

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PTK7 is a novel oncogenic target for esophageal squamous cell carcinoma

Abstract

Background

Overexpression of PTK7 has been found in multiple cancers and has been proposed to serve as a prognostic marker for intrahepatic cholangiocarcinoma. Its role in esophageal cancer, however, remains to be clarified. We hypothesize that PTK7 positively regulates tumorigenesis of esophageal cancer.

Methods

We examined PTK7 expression pattern in human esophageal squamous carcinoma by Oncomine expression analysis and by immunohistochemistry (IHC) staining. We knocked down PTK7 in two esophageal squamous cell carcinoma cell lines, TE-5, and TE-9, by siRNA, and evaluated cell proliferation, apoptosis, and migration ofPTK7-defective cells. Expressions of major apoptotic regulators and effectors were also determined by quantitative real-time PCR in PTK7-defective cells. We further overexpressed PTK7 in the cell to evaluate its effects on cell proliferation, apoptosis, and migration.

Results

Both Oncomine expression and IHC analyses showed that PTK7 is overexpressed in clinical esophageal squamous cell carcinoma tumors. PTK7 siRNA suppressed cell growth and promoted apoptosis of TE-5 and TE-9. PTK7-defective cells further displayed reduced cellular migration that was concomitant with upregulation of E-cadherin. Conversely, overexpression of PTK7 promotes cell proliferation and invasion, while apoptosis of the PTK7-overexpressing cells is repressed. Notably, major apoptotic regulators, such as p53 and caspases, are significantly upregulated in siPTK7 cells.

Conclusions

PTK7 plays an oncogenic role in tumorigenesis and metastasis of esophageal squamous carcinoma. PTK7 achieves its oncogenic function in esophageal squamous cell carcinoma partially through the negative regulation of apoptosis.

http://ift.tt/2s1jQgB

Combining serum miRNAs, CEA, and CYFRA21-1 with imaging and clinical features to distinguish benign and malignant pulmonary nodules: a pilot study

Abstract

Background

Our study was designed to improve the accuracy of determining whether pulmonary nodules are benign or malignant.

Methods

We evaluated the clinical and imaging features and serum markers: neuron specific enolase (NSE), carcino-embryonic antigen (CEA), cytokeratin fragment antigen 21–1 (CYFRA 21–1), miRNA-21-5p, and miR-574-5pof in 39 patients with pathology information. Factors that differed significantly between those with benign versus malignant pulmonary nodules were used to establish a prediction model for identifying malignant nodules.

Results

The studied nodules were 51.3% malignant and 48.7% benign. Age, smoking status, nodule diameter, history of emphysema, vascular sign, burr sign, CYFRA21-1, CEA, miRNA-21-5p, and miRNA-574-5p differed significantly between the benign and malignant nodule groups. Serum levels of CYRFA21-1 and CEA could be used to distinguish between malignant and benign nodules with a positive predictive value (PPV) of 80.0%, a negative predictive value (NPV) of 84.2%, and an area under the receiver operating characteristics curve (AUC) of 0.863. Using the serum levels of miRNA-21-5p and miRNA-574-5p, the PPV was 55%, the NPV was 84.2%, and the AUC was 0.797. When all four serum markers were combined, the PPV was 80%, the NPV was 89.5%, and the AUC was 0.921. We established a prediction model for malignant nodules, including clinical features, imaging features, and serum markers. In cross-validation, the ratio of discriminant conformance was 95%.

Conclusions

Serum levels of miRNA-21-5p and miRNA-574-5p are significantly higher in patients with malignant nodules than in patients with benign nodules and are potential serum biomarkers. Our prediction model could improve malignant nodule diagnosis.

http://ift.tt/2r362F6

Aortic Arch Origin of the Left Vertebral Artery: An Anatomical and Radiological Study with Significance for Avoiding Complications with Anterior Approaches to the Cervical Spine

Abstract

Introduction: Complications from anterior approaches to the cervical spine are uncommon with normal anatomy. However, variant anatomy might predispose one to an increased incidence of injury during such procedures. We hypothesized that left vertebral arteries that arise from the aortic arch instead of the subclavian artery might take a more medial path in their ascent making them more susceptible to iatrogenic injury.

Materials and Methods: Fifty human adult cadavers were examined for left vertebral arteries having an aortic arch origin and these were dissected along their entire cervical course. Additionally, two radiological databases of CTA and arteriography procedures were retrospectively examined for cases of aberrant left vertebral artery origin from the aortic arch over a two-year period.

Results: Two cadaveric specimens (4%) were found to have a left vertebral artery arising from the aortic arch. The retrospective radiological database analysis identified 13 cases (0.87%) of left vertebral artery origin from the aortic arch. Of all cases, vertebral arteries that arose from the aortic arch were much more likely to not only have a more medial course (especially their preforaminal segment) over the cervical vertebral bodies but also to enter a transverse foramen that was more cranially located than the normal C6 entrance of the vertebral artery.

Conclusions: Spine surgeons who approach the anterior cervical spine should be aware that an aortic origin of the left vertebral artery is likely to be closer to the midline and less protected above the C6 vertebral level. This article is protected by copyright. All rights reserved.

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Medical students and professional anatomists do not perceive gender bias within imagery featuring anatomy

Abstract

Previous studies suggest that, while both medical students and professional anatomists recognise the importance of gender issues and do not wish to associate with sexism, most are unaware of the possible negative aspects of sexism within anatomy (Morgan et al., 2014, 2016). To further investigate these issue, we provided second year medical students at Cardiff University (n=293) and at the University of Paris Descartes, Sorbonne Paris Cité (n= 142) and professional anatomists in Europe (n= 208) with a questionnaire inviting them to address the possibility that gender factors within anatomical imagery (both historical and contemporary) hinder the dispassionate representation of anatomy. Ethical approval for the survey was obtained from the universities at both Cardiff and Paris. In the light of previous findings, the hypothesis tested was that medical students and professional anatomists do not perceive a gender bias when reflected in imagery that is based upon anatomical iconography. Our survey results support this hypothesis and suggest that most students and anatomists are unaware of the possible negative aspects of sexism within the culture of anatomy. We consequently recommend that teachers of anatomy and authors of anatomical textbooks should be aware of the possibility of adverse effects on professional matters relating to equality and diversity issues when using imagery. This article is protected by copyright. All rights reserved.

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Assessment of Gene Flow Between Gossypium hirsutum and Gossypium herbaceum: Evidence of Unreduced Gametes in the Diploid Progenitor

In the framework of a gene flow assessment, we investigated the natural hybridization rate between Gossypium hirsutum (AADD genome) and G. herbaceum (AA genome). The latter species, a diploid progenitor of G. hirsutum, is spontaneously present in South Africa. Reciprocal crosses were performed without emasculation between G. herbaceum and G. hirsutum. Neither examination of the morphological characteristics nor flow cytometry analysis of the 335 plants resulting from the G. hirsutum x G. herbaceum cross showed any hybrid features. Of the 148 plants produced from the G. herbaceum x G. hirsutum cross, three showed a hybrid phenotype, and their hybrid status was confirmed by SSR markers. Analysis of DNA content by flow cytometry and morphological traits clearly showed that two of these plants were triploid (AAD). The third plant had a flow cytometry DNA content slightly higher than G. hirsutum. In addition, its morphological characteristics (plant architecture, presence and size of petal spots, leaf shape) led us to conclude that this plant was AAAD thus resulting from fertilization with an unreduced AA gamete of the female G. herbaceum parent. Fluorescent In Situ Hybridization (FISH) and meiotic behavior confirmed this hypothesis. To the best of our knowledge, this is the first description of such gametes in G. herbaceum, and it opens new avenues in breeding programs. Furthermore, this plant material could provide a useful tool for studying the expression of genes duplicated in the A and D cotton genome.

http://ift.tt/2qphyXq

Using RNA-seq for Genomic Scaffold Placement, Correcting Assemblies, and Genetic Map Creation in a Common Brassica rapa Mapping Population

Brassica rapa is a model species for agronomic, ecological, evolutionary and translational studies. Here we describe high-density SNP discovery and genetic map construction for a Brassica rapa recombinant inbred line (RIL) population derived from field collected RNA-seq data. This high-density genotype data enables the detection and correction of putative genome mis-assemblies and accurate assignment of scaffold sequences to their likely genomic locations. These assembly improvements represent 7.1-8.0% of the annotated Brassica rapa genome. We demonstrate how using this new resource leads to a significant improvement for QTL analysis over the current low-density genetic map. Improvements are achieved by the increased mapping resolution and by having known genomic coordinates to anchor the markers for candidate gene discovery. These new molecular resources and improvements in the genome annotation will benefit the Brassicaceae genomics community and may help guide other communities in fine tuning genome annotations.

http://ift.tt/2qUKmdO

Systematic Analysis of the DNA Damage Response Network in Telomere Defective Budding Yeast

Functional telomeres are critically important to eukaryotic genetic stability. Scores of proteins and pathways are known to affect telomere function. Here, we report a series of related genome-wide genetic interaction screens performed on budding yeast cells with acute or chronic telomere defects. Genetic interactions were examined in cells defective in Cdc13 and Stn1, affecting two components of CST, a single stranded DNA (ssDNA) binding complex that binds telomeric DNA. For comparison, genetic interactions were also examined in cells with defects in Rfa3, affecting the major ssDNA binding protein, RPA, which has overlapping functions with CST at telomeres. In more complex experiments, genetic interactions were measured in cells lacking EXO1 or RAD9, affecting different aspects of the DNA damage response, and containing a cdc13-1 induced telomere defect. Comparing fitness profiles across these data sets helps build a picture of the specific responses to different types of dysfunctional telomeres. The experiments show that each context reveals different genetic interactions, consistent with the idea that each genetic defect causes distinct molecular defects. To help others engage with the large volumes of data the data is made available via two interactive web-based tools: Profilyzer and DIXY. One particularly striking genetic interaction observed was that the chk1 mutation improved fitness of cdc13-1 exo1 cells more than other checkpoint mutations (ddc1, rad9, rad17, rad24), whereas in cdc13-1 cells the effects of all checkpoint mutations were similar. We show that this can be explained by Chk1 stimulating resection, a new function for Chk1 in the eukaryotic DNA damage response network.

http://ift.tt/2qpnEr1

Drosophila simulans: A Species with Improved Resolution in Evolve and Resequence Studies

The combination of experimental evolution with high-throughput sequencing of pooled individuals — i.e. Evolve and Resequence; E&R — is a powerful approach to study adaptation from standing genetic variation under controlled, replicated conditions. Nevertheless, E&R studies in Drosophila melanogaster have frequently resulted in inordinate numbers of candidate SNPs, particularly for complex traits. Here, we contrast the genomic signature of adaptation following ~60 generations in a novel hot environment for D. melanogaster and D. simulans. For D. simulans, the regions carrying putatively selected loci were far more distinct, and thus harbored fewer false positives, than those in D. melanogaster. We propose that species without segregating inversions and higher recombination rates, such as D. simulans, are better suited for E&R studies that aim to characterize the genetic variants underlying the adaptive response.

http://ift.tt/2qURved

Early-stage non-small cell lung cancer in the USA: patterns of care and survival among elderly patients at least 80 years old

Abstract

Background

The purpose of this study was to analyze the patterns of care of local therapies and their impact on overall survival (OS) among elderly patients with early-stage non-small cell lung cancer (NSCLC) in the USA.

Methods

The National Cancer Database was queried for patients at least age 80 years with NSCLC diagnosed in 2004–2013 with clinical stage T1–3N0M0. Local therapy was analyzed over time and by age. Multivariable (MVA) models were performed to investigate the impact of prognostic factors on OS.

Results

Among 40,561 patients meeting inclusion criteria, 17,418 (43%), 13,008 (32%), and 10,135 (25%) of patients underwent surgical resection, radiotherapy, and observation, respectively, as their initial mode of local therapy. Overtime, while the utilization of surgical managements generally remained stable, the utilization of conventionally fractionated radiotherapy and observation decreased in favor of stereotactic body radiotherapy (SBRT, p < 0.001). Among operable patients (n = 16,377), after MVA several factors were associated with OS including the choice of local therapy favoring resection over conventionally fractionated radiotherapy and observation (HR compared to lobectomy 1.362, and 2.656, respectively, each p < 0.001). In contrast, there was no statistical difference in OS between resection and SBRT among operable patients (HR for SBRT 1.128, p = 0.156).

Conclusions

The utilization of SBRT as the definitive local therapy in elderly patients with early-stage NSCLC is increasing in the USA. Given its generally favorable toxicity profile, SBRT should be considered in the substantial proportion of elderly patients still not receiving any definitive local therapy. Among medically operable elderly patients, OS was similar between resection and SBRT.

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Clinical outcomes following stereotactic body radiation therapy (SBRT) for non-resectable pancreatic adenocarcinoma

Abstract

Objectives

The purpose of this study was to report on progression-free survival (PFS), overall survival (OS), and related toxicities following stereotactic body radiation therapy (SBRT) for non-resectable pancreatic cancer (PCa).

Methods

The RSSearch® Patient Registry was screened for PCa patients treated with SBRT. The relationship between PFS, OS, and potential prognostic factors were evaluated using the Kaplan-Meier method and continuous log-rank analysis, and the correlation between treatment planning and toxicity incidence was examined by logistic regression.

Results

Sixty patients met inclusion criteria. Twenty-three patients (38.33%) had received adjuvant gemcitabine. Following SBRT, median PFS was 6.07 months (range: 2.33 - 34.4 months) and median OS was 8.55 months (range: 2.66 - 78.53 months). Single-fraction SBRT trended towards poorer median PFS (5.13 vs. 6.76 months; p = 0.0122) with no significant difference in median OS (10.3 vs. 7.17 months; p = 0.8896). PCas located in the head had a significantly higher median OS (9.58 months) as compared to those in the body (5.66 months; p = 0.0376). Adjuvant gemcitabine did not result in superior PFS (5.12 vs. 6.35 months; p = 0.52) or OS (8.67 vs. 7.07 months; p = 0.6010). Eight (13.3%) and six (10%) patients reported acute and late toxicities, respectively, that were all Grade 1 or 2. Single-fraction SBRT was associated with an increased risk of toxicity incidence (5/9 patients vs. 3/51 patients; p = 0.001).

Conclusion

SBRT was well-tolerated by PCa patients with fractionated SBRT trending towards superior PFS and less toxicity as compared to single-fraction SBRT.

http://ift.tt/2r3bFDh

Current practices in the management of stage IB, grade 3 endometrial cancer in the United States

Abstract

Objectives

Endometrial cancer is the most common gynecologic malignancy in the United States (US). Most patients are diagnosed with early stage disease and those with stage IB, grade 3 disease have inferior outcomes. Due to the heterogeneity among these patients, existing data has failed to yield cohesive recommendations to guide management decisions. The present study sought to analyze current practices regarding the use of adjuvant radiation for these patients.

Methods

The Surveillance, Epidemiology, and End Results Program was used to find all cases of endometrial cancer diagnosed between 2009 and 2013 in patients aged 18 or older. Data regarding the age (<60 versus ≥60), race (white versus non-white), tumor size (less than or equal to 4 cm versus >4 cm), type of surgery performed (less than the total hysterectomy and bilateral salpingo-oophrectomy, TH/BSO, versus greater than or equal to TH/BSO), number of nodes examined (<10 versus ≥10), radiation sequence with surgery (none versus adjuvant radiation), and type of radiation (brachytherapy versus external beam radiation versus both) was extracted from the database. We compared type of treatment administered based on the presence of risk factors. We also analyzed survival outcomes based on these clinic-pathologic factors.

Results

There were no differences between patients receiving surgery alone versus adjuvant radiation based on any parameter. Among those who received radiation, we found no differences between the type of radiation administered, except with respect to tumor size. Patients with small tumors (<4 cm) were more likely to be offered VBT alone (p = 0.03). The overall survival (OS) estimate for the group as a whole was 89% at 59 months. The OS for VBT alone and EBRT alone was 89%, while for the combination, it was 91%. Large tumor size and sub-optimal surgery were associated with inferior survival.

Conclusion

The current study highlights the fact that there is tremendous variation in the management of patients with stage IB, grade 3 endometrial cancer. Forty percent of patients in the US are not offered adjuvant radiation, despite inferior outcomes among these patients when treated with surgery alone. Clearly defined, uniform guidelines are needed to standardize management decisions for this group of patients. Uniform practice is especially important to cut costs in medicine and standardize treatment across health networks.

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Middle ear adenomatous neuroendocrine tumors: a 25-year experience at MD Anderson Cancer Center

Abstract

Neuroendocrine tumors are extremely rare in the middle ear. We reviewed our institutional experience with middle ear adenomatous neuroendocrine tumors (MEANTs). We searched our institution's pathology files to identify patients treated from 1990 to 2015 who had lesions classified as middle ear adenomas, adenomatous tumors, adenomatous tumors with neuroendocrine differentiation, carcinoid tumors of the middle ear, low-grade neuroendocrine tumors of the middle ear, and neuroendocrine carcinomas of the middle ear and identified 14 such patients for whom follow-up information was available. Herein, we review the pathology and differential diagnosis of these patients' tumors and discuss the management and follow-up of these patients. Our report adds to the series cases of MEANTs with recurrences, lymph node involvement, distant metastases, and tumor-related deaths. Our experience suggests that, although these tumors have long been considered to be low-aggression neoplasms, long-term follow-up studies to ascertain this supposed benignity are warranted.

http://ift.tt/2r1zJEL

Orbit technique in malrotation with non-obstructive volvulus: A novel technique of devolvulation

Abstract

Introduction

Volvulus may be noted in up to two-thirds of cases involving malrotation beyond infancy. Laparoscopic devolvulation has been described as a frustrating procedure because of restricted visualization. Here, a setup and technique that address these concerns are proposed.

Materials and Surgical Technique

Three boys (median age: 7 years) who had been diagnosed preoperatively with malrotation underwent laparoscopic exploration and devolvulation for volvulus found intraoperatively. The children were placed in a dorsal supine modified lithotomy position. Four 5-mm ports were inserted—one umbilically, one in the suprapubic region, and one in both the right and left iliac. After the volvulus was inspected, the right iliac atraumatic grasper was placed at the root of the mesentery. The bowel was devolvulated counterclockwise with the grasper used as a pivot—that is, the orbit technique. Once derotated, the rest of the operation proceeded with the division of Ladd's bands, the widening of the mesentery, and appendectomy.

Discussion

Devolvulation was successful in all three boys. The orbit technique is a useful devolvulation technique in non-obstructive volvulus when other techniques fail.

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From intraperitoneal onlay mesh repair to preperitoneal onlay mesh repair

Abstract

Laparoscopic repair for ventral and incisional hernias was first reported in the early 1990s. It uses intraperitoneal only mesh placement to achieve a tension-free repair of the hernia. However, in recent years, there has been greater concern about long-term complication involving intraperitoneal mesh placement. Many case reports and case series have found evidence of mesh adhesion, mesh fistulation, and mesh migration into hollow organs including the esophagus, small bowel, and large bowel, resulting in various major acute abdominal events. Subsequent management of these complications may require major surgery that is technically demanding and difficult; in such cases, laparotomy and bowel resection have often been performed. Because of these significant, but not common, adverse events, many surgeons favor open sublay repair for ventral and incisional hernias. Investigators are therefore searching for a laparoscopic approach for ventral and incisional hernias that might overcome the mesh-induced visceral complications seen after intraperitoneal only mesh placement repair. Laparoscopic preperitoneal onlay mesh is one such approach. This article will explore the fundamental of intraperitoneal only mesh placement and its problems, the currently available peritoneal visceral-compatible meshes, and upcoming developments in laparoscopic ventral and incisional hernia repair. The technical details of preperitoneal onlay mesh, as well as its potential advantages and disadvantages, will also be discussed.

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Hybrid approach using laparoscopy and transanal minimally invasive surgery to treat rectal cancer with invasion to the seminal vesicles

Abstract

We treated a 64-year-old man for rectal cancer with direct invasion to the seminal vesicles and no distant metastases by complete resection with laparoscopy and transanal minimally invasive surgery (TAMIS). We inserted the TAMIS device into the anal canal to above the anorectal ring and dissected to prostate level. High ligation of the inferior mesenteric artery and vein was performed by standard medial laparoscopy. The sigmoid and descending colon were mobilized, and in the postrectal space, we dissected to the space made by TAMIS. The membranous peritoneum was dissected on both sides of the rectum to the cul de sac. The peritoneum was dissected anterolaterally to reveal the seminal ducts, which were ligated and dissected on both sides. The seminal vesicles were dissected from the posterior wall of the bladder to the prostate level. The rectal specimen was now fully mobilized. Lower rectal resection with combined laparoscopy and TAMIS provided a better surgical plane than standard laparoscopy.

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Laparoscopic excision of neurogenic retrorectal tumors

Abstract

Retrorectal tumors (RT) are uncommon and usually managed by open surgical excision. Laparoscopic excision for RT has been reported in only a small number of papers. We aimed to assess the laparoscopic approach for RT and to discuss the factors that made this procedure difficult. We performed laparoscopic excision using a five-trocar technique for neurogenic RT in three patients. Tumors were successfully excised laparoscopically in two patients. However, the third patient required open conversion because the tumor was strongly adhered to the sacrum and could not be mobilized by dissection, resulting in poor visualization of the dissected site. Laparoscopic excision for RT provides excellent intraoperative visualization and good cosmesis in selected patients, but firm adherence to the sacrum may cause difficulty with this procedure.

http://ift.tt/2r2C6ZS

Endo-laparoscopic inguinal hernia repair: What is its role?

Abstract

Hernia repair techniques vary greatly depending upon the setting, surgeons, insurance reimbursement systems, resources, and logistical capabilities. Open mesh repair is the most frequently used technique.

Choosing the best technique for inguinal hernia repair is a challenge. There is no single technique to manage every type of hernia.

Today, laparoscopy and robotics are at the forefront of advanced surgical tools and offer a range of options for general surgeons who are critically evaluating new procedures. However, before using a new procedure, such as endo-laparoscopic hernia repair, surgeons often ask the rhetorical question, "Why change?" The common considerations are the availability of equipment, familiarity with the anatomy when using these techniques, operative time, cost to the patient, and the potential need to convert to an open procedure. Additionally, we are now seeing a significant shift away from surgeon-defined benefits to patient-defined benefits. As patients become more aware of their options for hernia procedures and share their experiences, more and more patients are likely to demand a particular technique. Hence, hernia surgeons should be educated on the different techniques available for inguinal hernia repair, including endo-laparoscopic procedures. In this article, we review the existing literature on the current role of endo-laparoscopic inguinal hernia repair.

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Issue Information

No abstract is available for this article.

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Application of endobronchial ultrasonography in laparoscopic liver segmentectomy in an animal model

Abstract

Introduction

This study investigated whether laparoscopic ultrasound-guided segment staining and real-time ultrasound-guided hepatectomy, with endobronchial ultrasonography equipped with a guide sheath, would be useful for laparoscopic liver segmentectomy in a porcine model.

Material and Surgical Technique

The abdominal cavity (in two pigs) was reached via a 12-mm umbilical trocar. An artificial tumor was created by radiofrequency ablation within the intended resection area. Portal vein puncture and staining were performed by the endobronchial ultrasonography-guided method. The targeted portal branch was successfully visualized and punctured with a needle through an equipped guide sheath. After targeted segment staining, the liver parenchyma was resected with a bipolar energy device; the regional Glisson's sheath was ligated and cut, and a surgical specimen was extracted. Real-time endobronchial ultrasonography from the cut surface provided information vital for preserving the surgical margin. All procedures were performed laparoscopically.

Discussion

This study demonstrated the technical feasibility of laparoscopic ultrasound-guided portal vein staining and safe surgical resection during laparoscopic liver segmentectomy.

http://ift.tt/2s13Mvj

Tehran's Tie: A simple trick to fix the trocar to the abdominal wall and close the entry site of first trocar in laparoscopic surgery

Abstract

Introduction

Trocar dislodgment can occur frequently during minimally invasive surgery. Closing the entry port at the fascial layer after the end of a long laparoscopic surgery is time-consuming. Here, I introduce Tehran's Tie, a simple trick to overcome these problems.

Materials and Surgical Technique

After the first trocar site has been created with the open technique and before the first port is inserted, the fascial wound is grasped with a loop of nylon thread, similar to a transverse matrix suture. Then, the trocar is inserted through the loop into the abdominal cavity. One thread is tied around the trocar to fix it. Another thread is used to tie and close the fascial defect at the end of laparoscopic surgery.

Discussion

Tehran's Tie is a simple trick for managing the first trocar site in laparoscopic surgery. It is a very useful and easy trick for fixing the first trocar to the abdominal wall and for closing the port site at the end of the procedure.

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The Role of capsule endoscopy and device assisted enteroscopy for small bowel lesions in Hereditary Hemorrhagic Telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal-dominant disorder leading to telangiectases and arteriovenous malformations of the skin, mucosa, and viscera. Telangiectases in the upper gastrointestinal tract are known, but data regarding possible small-bowel involvement are poor.

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Transjugular intrahepatic portosystemic shunt in a patient with Caroli’s disease and portal cavernoma

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Understanding Response Rates to Surveys about Family Members’ Psychological Symptoms after Patients’ Critical Illness

Achieving adequate response rates from family members of critically ill patients can be challenging, especially when assessing psychological symptoms.

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Factors Associated with Pediatric Mortality from Motor Vehicle Crashes in the United States: A State-Based Analysis

To examine geographic variation in motor vehicle crash (MVC)-related pediatric mortality and identify state-level predictors of mortality.

http://ift.tt/2s0Hyd4

Bilateral Finger Swelling in an Adolescent

A 16-year-old boy presented with a 3-month history of increasing swelling of the proximal interphalangeal (PIP) joints of both hands. He had no history of pain, fever, joint stiffness, or skin erythema. Clinical examination revealed bilateral swelling of the PIP joints of the second, third, fourth, and fifth fingers (Figure, A), with no joint tenderness or limitation of movement. Routine laboratory investigations, including complete blood count, C-reactive protein, and erythrocyte sedimentation rate, were normal.

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Safety and Efficacy of Warfarin Therapy in Kawasaki Disease

To describe the safety and efficacy of warfarin for patients with Kawasaki disease and giant coronary artery aneurysms (CAAs, ≥8 mm). Giant aneurysms are managed with combined anticoagulation and antiplatelet therapies, heightening risk of bleeding complications.

http://ift.tt/2r2BaVd

Maternal Nutrition and Child Neurodevelopment: Actions Across Generations

Premature birth remains a major cause of neurodevelopmental morbidity. Multiple factors underlie this morbidity, many of which are not under the control of the health care team; however, nutritional health is one modifiable factor that has a clear impact on the developing brain of the fetus and neonate. The majority of the recent literature on nutrition and neurodevelopment in preterm infants has focused on postnatal nutritional strategies to improve outcomes, whereas older studies have focused on undernutrition of the mother and its role in intrauterine growth restriction and negative consequences on the brain in term infants.

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Prophylactic Indomethacin—Is It Time to Reconsider?

Despite decades of clinical experience, hundreds of publications on the topic, and dozens of randomized trials, the management of patent ductus arteriosus (PDA) in preterm infants remains a subject of uncertainty and controversy. The available evidence has many limitations, among which the pervasive assumption that a persistent PDA must be closed at some point and the paucity of data related to treatment choices beyond the first postnatal week may be the most consequential. Most trials reported to date have focused on treatment assignments within the first 5 days after birth, and open treatment of controls within a few days of randomization may have obscured the risk of longer exposures to the hemodynamic effects of ductal patency.

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Highly recurrent H3F3A mutations with additional epigenetic regulator alterations in giant cell tumor of bone

Abstract

Recurrent H3F3A and IDH2 mutations have been reported in giant cell tumor of bone (GCTB). However, the reported incidences have varied, and other molecular genetic alterations have not been identified due to the small number of cases analyzed with comprehensive methods. Moreover, the relative sensitivities of Sanger sequencing and next-generation sequencing (NGS) for the detection of H3F3A mutations in DNA extracted from archival formalin-fixed paraffin-embedded (FFPE) for clinical diagnosis have not been assessed. To address these issues, we conducted whole-exome sequencing of 7 GCTBs and integrated the previously published genomic sequencing data of 6 GCTBs. We subsequently performed targeted sequencing of an additional 39 GCTBs, including 2 atypical cases and an extremely rare case of primary malignant transformation of GCTB. We also evaluated the sensitivity of Sanger sequencing for detecting H3F3A mutations in FFPE samples that are usually utilized for clinical diagnosis. H3F3A glycine hotspot mutations were the most frequently detected mutations (96%) in the 52 GCTBs by NGS. Of the 50 hotspot mutations, p.G34W was observed in 48 cases and p.G34L/G34R was detected in one. One of two atypical GCTB cases with wild-type H3F3A had a H3F3B mutation (p.G34V). Other mutated genes were not recurrent. Sanger sequencing did not detect H3F3A mutations in 10 of 15 H3F3A NGS mutation-positive FFPE samples. In conclusion, we confirmed that H3F3A is the most frequently mutated GCTB driver gene, and that H3F3A mutations are not present in atypical GCTBs. Sanger sequencing was much less sensitive than targeted NGS for detecting H3F3A mutations in FFPE samples. This article is protected by copyright. All rights reserved.

http://ift.tt/2s0ygh6

Metastatic thyroid carcinoma without identifiable primary tumor within the thyroid gland: a retrospective study of a rare phenomenon

Metastatic papillary thyroid carcinoma without an identifiable primary tumor despite extensive microscopic examination of the thyroid gland is a rare but true phenomenon. We retrieved seven of such cases and described in details the clinical and pathologic features of these tumors. BRAF V600E immunohistochemistry and Sequenom molecular profile were conducted in selected cases. All patients harbored metastatic disease in the central (n=3), lateral (n=3), or both neck compartments (n=1). The histotype of the metastatic disease was papillary thyroid carcinoma (PTC, n=5), poorly differentiated thyroid carcinoma (PDTC) in association with a PTC columnar variant (n=1), and anaplastic thyroid carcinoma (ATC) in association with a PTC tall cell variant (n=1).

http://ift.tt/2r2HvQT

Association of expression of the hedgehog signal with Merkel cell polyomavirus infection and prognosis of Merkel cell carcinoma

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine skin cancer that mostly occurs in the elderly. Merkel cell polyomavirus (MCPyV) is detected in approximately 80% of MCCs and is associated with carcinogenesis. Hedgehog signaling pathway plays a role in human embryogenesis and organogenesis. In addition, reactivation of this pathway later in life can cause tumors. 29 MCPyV-positive and 21 MCPyV-negative MCCs were immunohistochemically stained with primary antibodies for hedgehog signaling (SHH, IHH, PTCH1, SMO, GLI1, GLI2, and GLI3) and evaluated using H-score.

http://ift.tt/2s0NJOj

Diagnostic Utility of IDH1/2 Mutations to Distinguish Dedifferentiated Chondrosarcoma from Undifferentiated Pleomorphic Sarcoma of Bone

Histologically it is nearly impossible to distinguish the dedifferentiated component of dedifferentiated chondrosarcoma from undifferentiated pleomorphic sarcoma of bone when the low-grade cartilaginous component is absent. Previous studies have revealed that isocitrate dehydrogenase 1 (IDH1) and IDH2 mutations are present in a significant number of cartilaginous tumors including the majority of conventional chondrosarcoma and dedifferentiated chondrosarcomas. These mutations have not been studied in undifferentiated pleomorphic sarcomas of bone.

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Down-regulation of polycystin in lymphatic malformations: Possible role in the proliferation of lymphatic endothelial cells

Lymphatic malformations (LMs) are composed of aberrant lymphatic vessels and regarded as benign growths of the lymphatic system. Recent studies have demonstrated that the mutant embryos of PKD1 and PKD2, encoding polycystin-1 (PC-1) and polycystin-2 (PC-2), respectively, result in aberrant lymphatic vessels similar to those observed in LMs. In this study, for the first time, we investigated PC-1 and PC-2 expression and assessed their roles in the development of LMs. Our results demonstrated that PC-1 and PC-2 gene and protein expression were obviously decreased in LMs compared with normal skin tissues.

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High Resolution Manometry in Scleroderma Patients

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Appendiceal Goblet Cell Carcinoid: Common Errors in Staging and Clinical Interpretation with a Proposal for an Improved Terminology

Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term 'carcinoid' may lead to incorrect interpretation as NET. To explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors. Diagnostic terminology, staging and clinical interpretation were evaluated in 58 cases (27 GCC, 31 mixed GCC-AC). Opinions were collected from 23 pathologists using a survey.

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Interferon-Free Regimens in HBsAg/anti-HCV Patients: The Need to Control HBV Replication to Avoid HBV Reactivation

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Features and Treatment of Dapsone-induced Hepatitis, Based on Analysis of 44 Cases and Literature Review

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No Association Between Quick Sequential Organ Failure Assessment and Outcomes of Patients With Cirrhosis and Infections

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Plasma Cystatin C is a predictor of renal dysfunction, ACLF and mortality in patients with acutely decompensated liver cirrhosis

Abstract

Background: The development of acute-on-chronic liver failure (ACLF) in patients with liver cirrhosis is associated with high mortality rates. Renal failure is the most significant organ dysfunction that occurs in ACLF. So far there are no biomarkers predicting ACLF. Aim: To investigate whether Cystatin C (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) can predict development of renal dysfunction (RD), hepatorenal syndrome (HRS), ACLF and mortality, respectively. Methods: We determined the plasma levels of CysC and NGAL of 429 patients hospitalized for acute decompensation of cirrhosis in the CANONIC study. The patients were followed for 90 days. Results: Patients without RD or ACLF at inclusion, but with development of either, had significantly higher baseline concentrations of CysC and NGAL compared to patients without. CysC, but not NGAL was found to be predictive of RD (OR 9.4 [1.8; 49.7]), HRS (OR 4.2 [1.2; 14.8]) and ACLF (OR 5.9 [1.3; 25.9]). CysC at day3 was not found to be a better predictor than baseline CysC. CysC and NGAL were both predictive of 90 days mortality with hazard ratios for CysC of 3.1 (2.1; 4.7), and for NGAL of 1.9 (1.5; 2.4), respectively. Conclusions: Baseline CysC is a biomarker of renal dysfunction, HRS and ACLF and an independent predictor of mortality in patients with acutely decompensated liver cirrhosis. Determining CysC at day 3 did not provide any benefit. While NGAL is also associated with short-term mortality, it fails to predict development of RD, HRS and ACLF. Baseline CysC may add to identify patients at risk earlier and might improve clinical management. This article is protected by copyright. All rights reserved.

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The Expression of MCM7 is a Useful Biomarker in the Early Diagnostic of Gastric Cancer

Abstract

The aim of this study was to investigate the expression of minichromosome maintenance complex component 7 (MCM7) in gastric mucosal lesions, further to find its potential effect as a biomarker to distinguish intraepithelial neoplasia from gastric mucosal lesions. MCM7 and Ki67 were detected in 93 cases of gastric mucosal lesions by immunohistochemistry. MCM7 and Ki67 expression in GT were lowest compared with other groups (P<0.001), meanwhile there were significant differences compared with Group IM and other groups in MCM7 and Ki67 expression (P<0.001). MCM7 and Ki67 expression in GSC were highest (P<0.05). Groups of LGN, HGN and GIC had no significant differences in MCM7 expression (P>0.05), but there was significant difference compared with Group LGN and Group GIC in Ki67 expression (P<0.05). MCM7 expression elevated with tumor grade increasing and had positive correlation with Ki67 significantly (r=0.940, P<0.001). Furthermore, in some cases, some tumor cells were immunoreactive to MCM7 but negative to Ki67. So we concluded that MCM7 is helpful for us to make differential diagnosis in pathological grade, MCM7 combination of Ki67 may serve as more sensitive proliferation markers for evaluation of gastric carcinoma and precancerous lesions.

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Histone H3 K27M mutations in adult cerebellar high-grade gliomas

Abstract

Adult cerebellar high-grade gliomas (HGG) are rare and their molecular basis has not been fully elucidated. Although a diffuse midline glioma H3 K27M-mutant, a recently characterized variant of HGG, was reported to occasionally occur in the cerebellum, adult cases were rarely tested for this mutation; only five mutant cases have been reported to date. It currently remains unknown whether H3 K27M-mutant cerebellar gliomas share common histological features or have a uniformly dismal prognosis. In the present study, we assessed the prevalence of histone H3 K27M mutations in ten adult cerebellar HGG, identifying two H3F3A-mutant cases. One case was a 70-year-old female with a cystic lesion. Histologically, the tumor was considered to be glioblastoma; however, a part of the tumor exhibiting low proliferative activity appeared to be consistent with long-standing H3 K27M-mutant tumors in the literature. Another case was a 69-year-old male. The tumor showed a distinct circumscribed histology with minimal astrocytic differentiation, suggesting a nosological issue in the diagnosis of diffuse midline glioma. More cerebellar tumors need to be tested for H3 K27M mutations to clarify the clinical and histopathological spectra of this tumor.

http://ift.tt/2qhtaRk

Production of a potential liquid plant bio-stimulant by immobilized Piriformospora indica in repeated-batch fermentation process

Piriformospora indica, a mycorrhizal-like fungus able to establish associations with roots of a wide range of plants, supporting plant nutrition and increasing plant resistance and tolera...

http://ift.tt/2rEmI6G

Metabolic engineering of Escherichia coli to high efficient synthesis phenylacetic acid from phenylalanine

Phenylacetic acid (PAA) is a fine chemical with a high industrial demand for its widespread uses. Whereas, microorganic synthesis of PAA is impeded by the formation of by-product phenethyl alcohol due to quick...

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PGPR strain Paenibacillus polymyxa SQR-21 potentially benefits watermelon growth by re-shaping root protein expression

Paenibacillus polymyxa (SQR-21) is not only a plant growth-promoting rhizobacteria, but also an effective biocontrol agent against Fusarium wilt disease of watermelon. For the better unde...

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Finer leaf resolution and steeper beam edges using a virtual isocentre in concurrence to PTV-shaped collimators in standard distance – a planning study

Abstract

Purpose

Investigation of a reduced source to target distance to improve organ at risk sparing during stereotactic irradiation (STX).

Methods

The authors present a planning study with perfectly target-volume adapted collimator compared with multi-leaf collimator (MLC) at reduced source to virtual isocentre distance (SVID) in contrast to normal source to isocentre distance (SID) for stereotactic applications. The role of MLC leaf width and 20–80% penumbra was examined concerning the healthy tissue sparing. Several prescription schemes and target diameters are considered.

Results

Paddick's gradient index (GI) as well as comparison of the mean doses to spherical shells at several distances to the target is evaluated. Both emphasize the same results: the healthy tissue sparing in the high dose area around the planning target volume (PTV) is improved at reduced SVID ≤ 70 cm. The effect can be attributed more to steeper penumbra than to finer leaf resolution. Comparing circular collimators at different SVID just as MLC-shaped collimators, always the GI was reduced. Even MLC-shaped collimator at SVID 70 cm had better healthy tissue sparing than an optimal shaped circular collimator at SID 100 cm.

Regarding penumbra changes due to varying SVID, the results of the planning study are underlined by film dosimetry measurements with Agility™ MLC.

Conclusion

Penumbra requires more attention in comparing studies, especially studies using different planning systems. Reduced SVID probably allows usage of conventional MLC for STX-like irradiations.

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Patterns of local-regional recurrence after conformal and intensity-modulated radiotherapy for head and neck cancer

Abstract

Aim

To evaluate the patterns of loco-regional recurrences in head and neck cancer patients

Methods

Twenty-six out of 112 patients treated with primary or postoperative 3D CRT or IMRT for their primary and recurrent disease between 2007 and 2013 were included. The CT images of recurrent disease were rigidly registered with the primary CT images for each patient. To assess overlaps and overlap localization, the recurrence volume overlapping with the primary target volume was identified. For relapses occurring in the regional lymph nodes, the epicenter distance in recurrences and primary volumes and dose in recurrences were also identified. The recurrences were defined as in-field, marginal or out-of-field.

Results

The majority of the failures occurred within 1 year after completed primary treatment. The dose differences in recurrence volume were not statistically significant when patients were treated with IMRT or 3D CRT. Recurrence in 15/26 of the included patients occurred in the regional lymph nodes located fully or partly inside the primary target volume or the elective lymph node region. The majority of recurrences were recognized as in-field, independent of the primary treatment.

Conclusion

Recurrence in the majority of the patients occurred in the regional lymph nodes located in high dose area. The cause of recurrence may be due to inadequate total dose in the primary treatment and/or lack of optimal primary diagnosis leading to inadequate primary target delineation.

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C10ORF10/DEPP-mediated ROS accumulation is a critical modulator of FOXO3-induced autophagy

Abstract

Background

Neuroblastoma is the most common solid tumor in childhood and develops from undifferentiated progenitor cells of the sympathetic nervous system. In neuronal tumor cells DNA-damaging chemotherapeutic agents activate the transcription factor FOXO3 which regulates the formation of reactive oxygen species (ROS) and cell death as well as a longevity program associated with therapy resistance.

We demonstrated before that C10ORF10/DEPP, a transcriptional target of FOXO3, localizes to peroxisomes and mitochondria and impairs cellular ROS detoxification. In the present study, we investigated the impact of FOXO3 and DEPP on the regulation of autophagy. Autophagy serves to reduce oxidative damage as it triggers a self-degradative process for the removal of aggregated or misfolded proteins and damaged organelles.

Methods

The effect of FOXO3 and DEPP on autophagy induction was analyzed using live cell fluorescence microscopy and immunoblot analyses of SH-EP cells transfected with a plasmid for EYFP-LC3 and with siRNAs specific for LC3, respectively. ROS steady-state levels were measured with reduced MitoTrackerRed CM-H2XROS. Cellular apoptosis was analyzed by flow cytometry and the caspase 3/7 assay.

Results

We report for the first time that DEPP induces ROS accumulation and thereby mediates the formation of autophagosomes as inhibition of ROS formation by N-acetyl-cysteine completely blocks autophagy. We further demonstrate that H₂O₂-treatment triggers autophagy-induction by FOXO3-mediated DEPP expression. Importantly, knockdown of DEPP was sufficient to efficiently inhibit autophagy-induction under different stress conditions such as serum starvation and genotoxic stress, suggesting that DEPP expression is critical for the initiation of autophagy in neuroblastoma. FOXO3-triggered autophagy partially protects neuroblastoma cells from cell death. Consistent with this concept, we demonstrate that inhibition of autophagy by LC3-knockdown significantly increased etoposide- and doxorubicin-induced apoptosis. These results were also confirmed by the use of the autophagy-inhibitor chloroquine that significantly enhanced the chemotherapeutic effect of etoposide and doxorubicin in neuronal tumor cells.

Conclusion

Targeting FOXO3/DEPP-triggered autophagy is a promising strategy to sensitize neuroblastoma cells to chemotherapy.

http://ift.tt/2ql0Zwx