Publication date: Available online 22 March 2018
Source:Photodiagnosis and Photodynamic Therapy
Author(s): Maryam Pourhajibagher, Abbas Bahador
BackgroundSeveral microbial species that have been implicated in the pathogenesis of endodontic diseases colonize the infected root canal system. Since the complete removal of endopathogenic agents is essential in endodontic infections therapy, photo-activated disinfection (PAD) is suggested as an alternative method to traditional antimicrobial therapy. Recent studies reported that the molecular methods with low sensitivity and high efficiency to identify fastidious anaerobic endopathogenic microbiota can be replaced by the cultivation-based approaches. This study aimed to validate the multiplex real-time PCR in order to identify six common microorganisms associated with the endodontic infections before and after the PAD.Materials and methodsMicrobial specimens from the root canals of 50 patients with primary and secondary endodontic infections were collected before PAD treatment using sterile paper points. Toluidine blue O (TBO)-mediated PAD was performed on the root canals, followed by resampling. The prePAD- and postPAD-treatment endodontic samples were transferred to a transport medium and six target microorganisms were then identified from the samples using the microbiological culture techniques and multiplex real-time PCR approach.ResultsMultiplex real-time PCR could represent the presence of all target microorganisms in 100% cases before and after the PAD. Before PAD, using the culture method, Enterococcus faecalis (100%) was found to be the most frequent, followed by Veillonella parvula (97.5%), Aggregatibacter actinomycetemcomitans (94.7%), Porphyromonas gingivalis (84.3%), Lactobacillus rhamnosus (84.3%), and Actinomyces naeslundii (66.6%); whereas, after PAD these microbial frequencies changed to 80%, 83.3%, 66.6%, 80%, 66.6%, and 33.3%, respectively. The sensitivity and negative predictive value of the multiplex real-time PCR were 100% before and after the PAD, whereas the highest and the lowest specificities were 100% and 82% before PAD, and 97% and 89% after PAD for E. faecalis and P. gingivalis, respectively. The highest (100%) and the lowest (66%) positive predictive values were for V. parvula and A. naeslundii before and after the PAD, respectively.ConclusionAs observed from the results, multiplex real-time PCR demonstrated high sensitivity and specificity when compared to the culture technique. Therefore, it can prove to be a highly sensitive technique to detect the endodontic infections microflora.
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Πέμπτη 22 Μαρτίου 2018
Diagnostic accuracy of multiplex real-time PCR approaches in compared with cultivation -based detection methods: Monitoring the endopathogenic microbiota pre and post photo-activated disinfection
Editorial Advisory Board
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
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Contents
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
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Calendar
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
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Masthead
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
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Full-Field-of-View Time-Harmonic Elastography of the Native Kidney
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
Author(s): Stephan Rodrigo Marticorena Garcia, Markus Grossmann, Sophia Theresa Lang, Manh Nguyen Trong, Michael Schultz, Jing Guo, Bernd Hamm, Jürgen Braun, Ingolf Sack, Heiko Tzschätzsch
The purpose of this study was to analyze full-field-of-view maps of renal shear wave speed (SWS) measured by time-harmonic elastography (THE) in healthy volunteers in terms of reproducibility, regional variation and physiologic effects. The kidneys of 37 healthy volunteers were investigated by multifrequency THE. The complete renal parenchyma, as well as cortex and medulla, was analyzed. A subgroup was investigated to test reproducibility (n = 3). Significant differences between SWS in cortex, medulla and full parenchyma were observed (2.10 ± 0.17, 1.35 ± 0.11 and 1.71 ± 0.16 m/s, all p values < 0.001) with mean intra-volunteer standard deviations of repeated measurements of 0.04 m/s (1.6%), 0.06 m/s (4.0%) and 0.08 m/s (4.5%), respectively. No effects of kidney anatomy, age, body mass index, blood pressure and heart rate on SWS were observed. THE allows generation of full-field-of-view SWS maps of native kidneys with high reproducibility.
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Focused Ultrasound-Induced Suppression of Auditory Evoked Potentials in Vivo
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
Author(s): Dianne Daniels, Shirley Sharabi, David Last, David Guez, Sharona Salomon, Zion Zivli, David Castel, Alex Volovick, Javier Grinfeld, Itay Rachmilevich, Talia Amar, Sigal Liraz-Zaltsman, Narek Sargsyan, Yael Mardor, Sagi Harnof
The goal of this study was to determine the feasibility of focused ultrasound–based neuromodulation affecting auditory evoked potentials (AEPs) in animals. Focused ultrasound–induced suppression of AEPs was performed in 22 rats and 5 pigs: Repetitive sounds were produced, and the induced AEPs were recorded before and repeatedly after FUS treatment of the auditory pathway. All treated animals exhibited a decrease in AEP amplitude post-treatment in contrast to animals undergoing the sham treatment. Suppression was weaker for rats treated at 2.3 W/cm2 (amplitudes decreased to 59.8 ± 3.3% of baseline) than rats treated at 4.6 W/cm2 (36.9 ± 7.5%, p < 0.001). Amplitudes of the treated pigs decreased to 27.7 ± 5.9% of baseline. This effect lasted between 30 min and 1 mo in most treated animals. No evidence of heating during treatment or later brain damage/edema was observed. These results demonstrate the feasibility of inducing significant neuromodulation with non-thermal, non-invasive, reversible focused ultrasound. The long recovery times may have clinical implications.
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Ultrasound Irradiation Combined with Hepatocyte Growth Factor Accelerate the Hepatic Differentiation of Human Bone Marrow Mesenchymal Stem Cells
Source:Ultrasound in Medicine & Biology, Volume 44, Issue 5
Author(s): Fan Li, Yang Liu, Yingyu Cai, Xin Li, Min Bai, Ting Sun, Lianfang Du
This study investigated the impact of ultrasound (US) irradiation on the hepatic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) induced by hepatocyte growth factor (HGF) and the possible mechanisms. We treated hBMSCs, using HGF with and without US irradiation. Cell viability and stem cell surface markers were analyzed. Hepatocyte-like cell markers and functional markers including α-fetoprotein (αFP/AFP), cytokeratin 18 (CK18), albumin (ALB) and glycogen content were analyzed at the time point of day 1, 3 and 5 after treatment. The involvement of Wnt/β-catenin signaling pathway was evaluated as well. The results showed that the US treatment at 1.0 W/cm2 or 1.5 W/cm2 for 30 s or 60 s conditions yielded favorable cell viability and engendered stem cell differentiation. At day 5, the expressions of AFP, CK18, ALB and the glycogen content were significantly elevated in the US-treated group at both messenger ribonucleic acid and protein levels (all p < 0.05), in comparison with HGF and control groups. Among all the US treated groups, the expression levels of specific hepatic markers in the (1.5 W/cm2 for 60 s) group were the highest. Furthermore, Wnt1, β-Catenin, c-Myc and Cyclin D1 were significantly increased after US irradiation (all p < 0.05), and the enhancements of c-Myc and Cyclin D1 could be obviously impaired by the inhibitor ICG-001 (p < 0.05, p < 0.05), in accordance with decreased ALB and CK18 expression and glycogen content (all p < 0.05). In conclusion, US irradiation was able to promote the hBMSCs' differentiation mediated by HGF in vitro safely, easily and controllably. The activation of Wnt/β-catenin signaling pathway was involved in this process. US irradiation could serve as a potentially beneficial tool for the research and application of stem cell differentiation.
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Ultrasound-Guided Percutaneous Core Needle Biopsy for the Diagnosis of Pancreatic Disease
Source:Ultrasound in Medicine & Biology
Author(s): Ying Huang, Jingwen Shi, Yun-Yun Chen, Kao Li
Few studies have evaluated the performance of percutaneous core needle biopsies of the pancreas. This article is an overview of the advantages, disadvantages, predictive power and complications associated with percutaneous ultrasound-guided core needle biopsies of pancreatic lesions. A comprehensive literature search of Medline (using PubMed as the search engine) and EMBASE was done to identify suitable studies up to March 2017. A study of quantitative pre-operative pancreatic biopsy data was reported. Lesion location, mean or median number of passes, inadequate tissue or technical failures and complications were assessed for all cases by reviewing clinical notes and post-procedural imaging. The analysis included 13 studies, mostly of a retrospective nature. The sensitivity (mean: 94.42%, range: 90%–100%) and specificity (mean: 97.94%, range: 94.7%–100%) of the procedure were high, and the mean accuracy of diagnosis was 95.76 (range: 91–100). Furthermore, the procedure had a high negative predictive value of approximately 76.26%. Of the 13 reported studies, 7.3% were inadequate or technical failure cases. The mean rate of complications was 2.08%, which seemed similar to the lower limit of this rate for endoscopic ultrasound-guided fine-needle aspirations. The risk of tumor seeding with ultrasound-guided core needle biopsies was not reported in the included articles. With the development of technology, ultrasound-guided percutaneous core needle biopsy for pancreatic lesions is increasingly available and has optimal diagnostic power in pancreatic neoplasms.
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Risk prediction for Staphylococcus aureus surgical site infection following cardiothoracic surgery; A secondary analysis of the V710-P003 trial.
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Risk prediction for Staphylococcus aureus surgical site infection following cardiothoracic surgery; A secondary analysis of the V710-P003 trial.
PLoS One. 2018;13(3):e0193445
Authors: Paling FP, Olsen K, Ohneberg K, Wolkewitz M, Fowler VG, DiNubile MJ, Jafri HS, Sifakis F, Bonten MJM, Harbarth SJ, Kluytmans JAJW
Abstract
BACKGROUND: Identifying patients undergoing cardiothoracic surgery at high risk of Staphylococcus aureus surgical site infection (SSI) is a prerequisite for implementing effective preventive interventions. The objective of this study was to develop a risk prediction model for S. aureus SSI or bacteremia after cardiothoracic surgery based on pre-operative variables.
MATERIALS/METHODS: Data from the Merck Phase IIb/III S. aureus vaccine (V710-P003) clinical trial were analyzed. In this randomized placebo-controlled trial, the effect of preoperative vaccination against S. aureus was investigated in patients undergoing cardiothoracic surgery. The primary outcome was deep/superficial S. aureus SSI or S. aureus bacteremia through day 90 after surgery. Performance, calibration, and discrimination of the final model were assessed.
RESULTS: Overall 164 out of 7,647 included patients (2.1%) developed S. aureus infection (149 SSI, 15 bacteremia, 28 both). Independent risk factors for developing the primary outcome were pre-operative colonization with S. aureus (OR 3.08, 95% confidence interval [CI] 2.23-4.22), diabetes mellitus (OR 1.87, 95% CI 1.34-2.60), BMI (OR 1.02 per kg/m2, 95% CI 0.99-1.05), and CABG (OR 2.67, 95% CI 1.91-3.78). Although vaccination had a significant (albeit modest) protective effect, it was omitted from the model because its addition did not significantly change the coefficients of the final model and V710-vaccine development has been discontinued due to insufficient efficacy. The final prediction model had moderate discriminative accuracy (AUC-value, 0.72).
CONCLUSION: Pre-operative S. aureus colonization status, diabetes mellitus, BMI, and type of surgical procedure moderately predicted the risk of S. aureus SSI and/or bacteremia among patients undergoing cardiothoracic surgery.
PMID: 29561866 [PubMed - in process]
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[Effect of ozone on Staphylococcus aureus colonization in patients with atopic dermatitis].
[Effect of ozone on Staphylococcus aureus colonization in patients with atopic dermatitis].
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2018 Feb 28;43(2):157-162
Authors: Lu J, Li M, Huang J, Gao L, Pan Y, Fu Z, Dou J, Huang J, Xiang Y
Abstract
OBJECTIVE: To verify the effect of ozone on Staphylococcus aureus (S. aureus) colonization in patients with atopic dermatitis (AD) and its correlation with the patient's status.
Methods: A total of 12 patients with moderate or severe AD, aged from 6 to 65 years, were recruited from outpatient of the Third Xiangya Hospital. The treatment sides were showered with ozonated water and smeared with ozonated oil for 7 days (twice a day), while the control sides were washed with warm running water and smeared with base oil. At different time points, the severity scoring of atopic dermatitis (SCORAD) scores, sleep and pruritus scores were assessed and compared between the two sides. Meanwhile, plate cultivation was used to quantitatively detect the changes of S. aureus colonization in skin lesions.
Results: After 7 days treatment, erythema and pimples were decreased in the treatment sides. The clear skin texture, smooth skin, improved skin lesions were also observed by dermoscopic examination. The results of reflectance confocal microscopy (RCM) demonstrated that the parakeratosis was improved, the structures were clearer, and the inflammatory cells infiltration was reduced after ozone treatment for 7 days. After ozone treatment for 3 and 7 days, the S. aureus colonization in the treatment sides decreased by (75.55±21.81)% and (97.24±2.64)% respectively. Compared to that of control sides, the percentage of S. aureus colony after ozone treatment for 7 days decreased significantly (P<0.01). After ozone treatment for 7 days, the SCORAD scores, sleep and pruritus scores were significantly decreased (all P<0.01). There was a linear correlation between the decreasing percentage of S. aureus colony and the declining percentage of SCORAD scores in AD patients.
Conclusion: Topical ozone therapy can effectively reduce S. aureus colony in skin lesions and alleviate the severity of AD patients with moderate to severe degree.
PMID: 29559599 [PubMed - in process]
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Surgical site infection related to use of elastomeric pumps in pectus excavatum repair. Lessons learned from root cause analysis.
 | Related Articles |
Surgical site infection related to use of elastomeric pumps in pectus excavatum repair. Lessons learned from root cause analysis.
J Pediatr Surg. 2017 Aug;52(8):1292-1295
Authors: Apelt N, Schaffzin J, Bates C, Brown RL, Mecoli M, Sadhasivam S, Garcia V
Abstract
BACKGROUND: Pectus excavatum repair (PEX) is among the most painful thoracic procedures performed. Continuous peripheral nerve blockade (CPNB) is known to be efficacious in optimizing pain control while limiting narcotic use in adult thoracic procedures. It was introduced in May 2015 as a bridge to oral pain control in children undergoing PEX. Consequently, the surgical site infection (SSI) rate increased from 2.7% to 27.7%.
METHODS: SSI surveillance followed national guidelines. The abrupt increase prompted root cause analysis and cessation of CPNB use. A dynamic systems model of SSI in PEX was developed. Statistical analysis compared SSI outcomes with and without CPNB.
RESULTS: From May 2015 to June 2015, 21 PEX were performed; 11 with CPNB. 6 SSIs were observed. Use of CPNB significantly (p=0.008) increased SSI incidence. Haller index, number of bars, usage of Fiberwire®, methicillin resistant S. aureus colonization and length of stay did not differ. Root cause analysis revealed the proximity of CPNB catheters to the wound, the use of CPNB with implanted hardware and a delayed utilization of CPNB catheters to be of concern.
CONCLUSION: Introduction of CPNB coincided with a significant increase in SSI. Further study is needed to assess the safety of CPNB in pediatric PEX.
LEVEL OF EVIDENCE: Level III treatment study.
PMID: 28087135 [PubMed - indexed for MEDLINE]
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Prognostic and Predictive Factors for Renal Cell Carcinoma
Abstract
Metastatic renal cell carcinoma (mRCC) is an incurable malignancy, characterized by its resistance to traditional chemotherapy, radiation, and hormonal therapy. Treatment perspectives and prognosis of patients with mRCC have been significantly improved by advances in the understanding of its molecular pathogenesis, which have led to the development of targeted therapeutics. Different molecular factors derived from the tumor or the host detected in both tissue or serum could be predictive of therapeutic benefit. Some of them suggest a rational selection of patients to be treated with certain therapies, though none have been validated for routine use. This article provides an overview of both clinical and molecular factors associated with predictive or prognostic value in mRCC and emphasizes that both should be considered in parallel to provide the most appropriate, individualized treatment and achieve the best outcomes in clinical practice.
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Development of decellularized amniotic membrane as a bioscaffold for bone marrow-derived mesenchymal stem cells: ultrastructural study
Abstract
Developing effective stem cell-based therapies requires the design of complex in vitro culture systems for accurate representation of the physiological stem cell niche. Human amniotic membrane (hAM) has been successfully used in clinical grafting applications due to its unique biological and regenerative properties. Decellularized hAM (d-hAM) has been previously applied to the culture of human bone marrow mesenchymal stem cells (hMSCs), promoting their expansion and differentiation into adipogenic and osteogenic lineages. In the present study, hAM was decellularized by NaOH-treatment, to provide the three-dimensional (3D) bioscaffold for culturing hMSCs. The ultrastructural differences between intact hAM and decellularized hAM were characterized using the transmission electron microscope (TEM), as well as the 3D interaction between d-hAM and hMSCs cultured on the membrane. TEM examination of the intact hAM showed many microvilli on the epithelial layer cells, active Golgi apparatus, smooth endolplasmic reticulum and the characteristic pinocytic vesicles. The epithelial layer with its structures was absent in the d-hAM. However, no observable difference was detected in the ultrastructural characteristics of the compact stromal layer of d-hAM compared to intact hAM. Both contained bundles of extra cellular matrix (ECM) proteins, and scattered elastic fibres. Cultured human mesenchymal stem cells (hMSCs) examined by TEM appeared oval to spherical in shape and had a rough and non-uniform surface with distinct protrusions or irregular fillopodia. Their diameter ranged from 20.49 to 21.6 µm. Most of the cellular organelles were also noticed. SEM examination of the prepared samples revealed unique 3D interaction between the hMSC and d-hAM, where the latter seems to envelop the segments of the hMSCs lying on the surrounding membrane. This study shows that the decellularization process affected the epithelial layer only of hAM and had no effect on altering the presence of ECM components present in the stromal layer of the d-hAM. The interaction between hMSCs and d-hAM maybe mediated by hAM components other than human amniotic epithelial cells, such as ECM components or MSCs present in the deeper spongy layer of the membrane or/and the adhesive components of the basement membrane of the removed epithelial layer.
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Are children involved in cyberbullying low on empathy? A systematic review and meta-analysis of research on empathy versus different cyberbullying roles
Source:Aggression and Violent Behavior
Author(s): Izabela Zych, Anna C. Baldry, David P. Farrington, Vicente J. Llorent
Cyberbullying is a relatively new aggressive behavior in which young people repeatedly and intentionally inflict harm on peers, using electronic devices. Cyberbullying has very damaging consequences and studies on the topic are increasing. Nevertheless, there are still gaps in sound knowledge regarding factors that could protect children from being cyberbullies or cybervictims. The current systematic review and meta-analysis was conducted to overcome limitations of previous studies on risk factors to establish if and how empathy is related to the different cyberbullying roles. After exhaustive searches with rigorous inclusion and exclusion criteria, 25 studies were included. Cyberbullying perpetration was found to be related to low empathy (OR = 1.5) and this relationship held also after controlling for covariates (OR = 1.3) but cyber-victimization was not significantly related to empathy (OR = 0.94). There were some indicators that cybervictims could have high empathy, but more research is needed to clarify this relationship. Results are presented also separately for the relationship between affective and cognitive empathy and different cyberbullying roles. There were not enough studies to draw conclusions about the relationship between empathy and being a cyberbully/victim or defender, but some tendencies were found and described. These results have important implications for policy and practice and might be very useful in designing specific tailored programs to prevent cyberbullying.
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Ecological factors associated with pre-dispersal predation of fig seeds and wasps by fig-specialist lepidopteran larvae
Source:Acta Oecologica
Author(s): Finn Piatscheck, Justin Van Goor, Derek D. Houston, John D. Nason
In brood pollination mutualisms, predation of developing fruit can have large negative repercussions for both plant and pollinator population dynamics. The Sonoran Desert rock fig Ficus petiolaris and its highly-coevolved wasp pollinator are subject to frequent attack by lepidopteran larvae that consume fig fruit and the developing seeds and larval pollinators they contain. We used generalized linear mixed models to investigate how the phenology, quantity, and spatial distribution of fig fruits is associated with variation in lepidopteran damage intensity on individual trees at nine geographic locations spanning a 741 km latitudinal transect along Mexico's Baja California Peninsula. We found lepidopteran damage to be strongly positively associated with more synchronous fig crops and larger trees, and only weakly associated with lower local host tree density. These results imply that fruit production that is asynchronous within trees and spread out over time, as observed in several fig species, benefits female and male components of fitness (pollen disperser and seed production, respectively) by reducing pre-dispersal predation by frugivores.
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Value of 18 F–FDG PET/CT for predicting EGFR mutations and positive ALK expression in patients with non-small cell lung cancer: a retrospective analysis of 849 Chinese patients
Abstract
Purpose
Epidermal growth factor receptor (EGFR) mutations and the anaplastic lymphoma kinase (ALK) rearrangement are the two most common druggable targets in non-small cell lung cancer (NSCLC). However, genetic testing is sometimes unavailable. Previous studies regarding the predictive role of 18F–FDG PET/CT for EGFR mutations in NSCLC patients are conflicting. We investigated whether or not 18F–FDG PET could be a valuable noninvasive method to predict EGFR mutations and ALK positivity in NSCLC using the largest patient cohort to date.
Methods
We retrospectively reviewed and included 849 NSCLC patients who were tested for EGFR mutations or ALK status and subjected to 18F–FDG PET/CT prior to treatment. The differences in several clinical characteristics and three parameters based on 18F–FDG PET/CT, including the maximal standard uptake value (SUVmax) of the primary tumor (pSUVmax), lymph node (nSUVmax) and distant metastasis (mSUVmax), between the different subgroups were analyzed. Multivariate logistic regression analysis was performed to identify predictors of EGFR mutations and ALK positivity.
Results
EGFR mutations were identified in 371 patients (45.9%). EGFR mutations were found more frequently in females, non-smokers, adenocarcinomas and stage I disease. Low pSUVmax, nSUVmax and mSUVmax were significantly associated with EGFR mutations. Multivariate analysis demonstrated that pSUVmax < 7.0, female sex, non-smoker status and adenocarcinoma were predictors of EGFR mutations. The receiver operating characteristic (ROC) curve yielded area under the curve (AUC) values of 0.557 and 0.697 for low pSUVmax alone and the combination of the four factors, respectively. ALK-positive patients tended to have a high nSUVmax. Younger age and distant metastasis were the only two independent predictors of ALK positivity.
Conclusion
We demonstrated that low pSUVmax is associated with mutant EGFR status and could be integrated with other clinical factors to enhance the discriminability on the EGFR mutation status in some NSCLC patients whose EGFR testing is unavailable.
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Prediction of outcome using pretreatment 18 F-FDG PET/CT and MRI radiomics in locally advanced cervical cancer treated with chemoradiotherapy
Abstract
Purpose
The aim of this study is to determine if radiomics features from 18fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and magnetic resonance imaging (MRI) images could contribute to prognoses in cervical cancer.
Methods
One hundred and two patients (69 for training and 33 for testing) with locally advanced cervical cancer (LACC) receiving chemoradiotherapy (CRT) from 08/2010 to 12/2016 were enrolled in this study. 18F-FDG PET/CT and MRI examination [T1, T2, T1C, diffusion-weighted imaging (DWI)] were performed for each patient before CRT. Primary tumor volumes were delineated with the fuzzy locally adaptive Bayesian algorithm in the PET images and with 3D Slicer™ in the MRI images. Radiomics features (intensity, shape, and texture) were extracted and their prognostic value was compared with clinical parameters for recurrence-free and locoregional control.
Results
In the training cohort, median follow-up was 3.0 years (range, 0.43–6.56 years) and relapse occurred in 36% of patients. In univariate analysis, FIGO stage (I–II vs. III–IV) and metabolic response (complete vs. non-complete) were probably associated with outcome without reaching statistical significance, contrary to several radiomics features from both PET and MRI sequences. Multivariate analysis in training test identified Grey Level Non UniformityGLRLM in PET and EntropyGLCM in ADC maps from DWI MRI as independent prognostic factors. These had significantly higher prognostic power than clinical parameters, as evaluated in the testing cohort with accuracy of 94% for predicting recurrence and 100% for predicting lack of loco-regional control (versus ~50–60% for clinical parameters).
Conclusions
In LACC treated with CRT, radiomics features such as EntropyGLCM and GLNUGLRLM from functional imaging DWI-MRI and PET, respectively, are independent predictors of recurrence and loco-regional control with significantly higher prognostic power than usual clinical parameters. Further research is warranted for their validation, which may justify more aggressive treatment in patients identified with high probability of recurrence.
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The diagnostic value of 18 F–FDG-PET/CT and MRI in suspected vertebral osteomyelitis – a prospective study
Abstract
Purpose
The aim of this study was to determine the diagnostic value of 18F–fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) and magnetic resonance imaging (MRI) in diagnosing vertebral osteomyelitis.
Methods
From November 2015 until December 2016, 32 patients with suspected vertebral osteomyelitis were prospectively included. All patients underwent both 18F–FDG-PET/CT and MRI within 48 h. All images were independently reevaluated by two radiologists and two nuclear medicine physicians who were blinded to each others' image interpretation. 18F–FDG-PET/CT and MRI were compared to the clinical diagnosis according to international guidelines.
Results
For 18F–FDG-PET/CT, sensitivity, specificity, PPV, and NPV in diagnosing vertebral osteomyelitis were 100%, 83.3%, 90.9%, and 100%, respectively. For MRI, sensitivity, specificity, PPV, and NPV were 100%, 91.7%, 95.2%, and 100%, respectively. MRI detected more epidural/spinal abscesses. An important advantage of 18F–FDG-PET/CT is the detection of metastatic infection (16 patients, 50.0%).
Conclusion
18F–FDG-PET/CT and MRI are both necessary techniques in diagnosing vertebral osteomyelitis. An important advantage of 18F–FDG-PET/CT is the visualization of metastatic infection, especially in patients with bacteremia. MRI is more sensitive in detection of small epidural abscesses.
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Comparison of positron emission tomography/computed tomography and magnetic resonance imaging for posttherapy evaluation in patients with advanced cervical cancer receiving definitive concurrent chemoradiotherapy
Abstract
Purpose
Our purpose was to assess the diagnostic performance of positron emission tomography/computed tomography (PET/CT) and pelvic/abdominal magnetic resonance imaging (MRI) after concurrent chemoradiotherapy (CCRT) for posttherapy evaluation in patients with advanced cervical cancer.
Methods
Patients with cervical squamous cell carcinoma, either with advanced FIGO stage or with positive pelvic or para-aortic lymph node (PALN), received PET/CT using [18F]fluorodeoxyglucose and MRI including diffusion-weighted imaging between 2 and 3 months after CCRT completion. PET/CT were interpreted independently by two nuclear medicine physicians and MRI by two radiologists using the same scoring system. Active residual tumor was proven by pathological confirmation or disease progression on imaging studies within one year after CCRT and the disease regions were classified as local, regional, PALN, or distant. Patient-based and region-based comparison was performed using the receiver operating characteristic curve analysis.
Results
The study included 55 patients and 15 (27%) patients had active residual tumor. The diagnostic performance of PET/CT is significantly superior to that of MRI in patient-based analysis (P = 0.025) and in the detection of local (P = 0.045) and regional (P = 0.014) disease. The patient-based sensitivity, specificity, and accuracy of PET/CT are 60%, 100%, and 89% while those of MRI are 27%, 100%, and 80%.
Conclusions
PET/CT is superior to MRI for posttherapy evaluation in patients with advanced cervical cancer 2–3 months after definitive CCRT, mainly for the detection of residual local and regional disease. Patients with negative or equivocal results should be followed up regularly due to suboptimal sensitivities of imaging.
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Interpretation criteria for FDG PET/CT in multiple myeloma (IMPeTUs): final results. IMPeTUs (Italian myeloma criteria for PET USe)
Abstract
ᅟ
FDG PET/CT (18F-fluoro-deoxy-glucose positron emission tomography/computed tomography) is a useful tool to image multiple myeloma (MM). However, simple and reproducible reporting criteria are still lacking and there is the need for harmonization. Recently, a group of Italian nuclear medicine experts defined new visual descriptive criteria (Italian Myeloma criteria for Pet Use: IMPeTUs) to standardize FDG PET/CT evaluation in MM patients. The aim of this study was to assess IMPeTUs reproducibility on a large prospective cohort of MM patients.
Materials and methods
Patients affected by symptomatic MM who had performed an FDG PET/CT at baseline (PET0), after induction (PET-AI), and the end of treatment (PET-EoT) were prospectively enrolled in a multicenter trial (EMN02)(NCT01910987; MMY3033). After anonymization, PET images were uploaded in the web platform WIDEN® and hence distributed to five expert nuclear medicine reviewers for a blinded independent central review according to the IMPeTUs criteria. Consensus among reviewers was measured by the percentage of agreement and the Krippendorff's alpha. Furthermore, on a patient-based analysis, the concordance among all the reviewers in terms of positivity or negativity of the FDG PET/CT scan was tested for different thresholds of positivity (Deauville score (DS 2, 3, 4, 5) for the main parameters (bone marrow, focal score, extra-medullary disease).
Results
Eighty-six patients (211 FDG PET/CT scans) were included in this analysis. Median patient age was 58 years (range, 35–66 years), 45% were male, 15% of them were in stage ISS (International Staging System) III, and 42% had high-risk cytogenetics. The percentage agreement was superior to 75% for all the time points, reaching 100% of agreement in assessing the presence skull lesions after therapy. Comparable results were obtained when the agreement analysis was performed using the Krippendorff's alpha coefficient, either in every single time point of scanning (PET0, PET-AI or PET-EoT) or overall for all the scans together. DS proved highly reproducible with the highest reproducibility for score 4.
Conclusions
IMPeTUs criteria proved highly reproducible and could therefore be considered as a base for harmonizing PET interpretation in multiple myeloma. A prospective clinical validation of IMPeTUs criteria is underway.
http://ift.tt/2FW1klb
Liver metastases from prostate cancer at 11C-Choline PET/CT: a multicenter, retrospective analysis
Abstract
Aim
During our daily clinical practice using 11C-Choline PET/CT for restaging patients affected by relapsing prostate cancer (rPCa) we noticed an unusual but significant occurrence of hypodense hepatic lesions with a different tracer uptake. Thus, we decided to evaluate the possible correlation between rPCa and these lesions as possible hepatic metastases.
Materials and methods
We retrospectively enrolled 542 patients diagnosed with rPCa in biochemical relapse after a radical treatment (surgery and/or radiotherapy). Among these, patients with a second tumor or other benign hepatic diseases were excluded. All patients underwent 11C-Choline PET/CT during the standard restaging workup of their disease. We analyzed CT images to evaluate the presence of hypodense lesions and PET images to identify the relative tracer uptake. In accordance to the subsequent oncological history, five clinical scenarios were recognized [Table 1]: normal low dose CT (ldCT) and normal tracer distribution (Group A); evidence of previously unknown hepatic round hypodense areas at ldCT with normal rim uptake (Group B); evidence of previously known hepatic round hypodense areas at ldCT stable over time and with normal rim uptake (Group C); evidence of previously known hepatic round hypodense areas at ldCT, in a previous PET/CT scan, with or without rim uptake and significantly changing over time in terms of size and/or uptake (Group D); evidence of hepatic round hypodense areas at ldCT with or without rim uptake confirmed as prostate liver metastases by histopathology, triple phase ceCT, ce-ultra sound (CEUS) and clinical/biochemical evaluation (Group E). We evaluated the correlation with PSA level at time of scan, rim SUVmax and association with local relapse or non-hepatic metastases (lymph nodes, bone, other parenchyma).
Results
Five hundred and forty-two consecutive patients were retrospectively enrolled. In 140 of the 542 patients more than one 11C-choline PET/CT had been performed. A total of 742 11C-Choline PET/CT scans were analyzed. Of the 542 patients enrolled, 456 (84.1%) had a normal appearance of the liver both at ldCT and PET (Group A). 19/542 (3,5%) belonged to Group B, 13/542 (2.4%) to Group C, 37/542 (6.8%) to Group D and 18/542 (3.3%) to Group E. Mean SUVmax of the rim was: 4.5 for Group B; 4.2 for Group C; 4.8 for Group D; 5.9 for Group E. Mean PSA level was 5.27 for Group A, 7.9 for Group B, 10.04 for Group C, 10.01 for Group D, 9.36 for Group E. Presence of positive findings at 11C-Choline PET/CT in any further anatomical area (local relapse, lymph node, bone, other extra hepatic sites) correlated with an higher PSA (p = 0.0285). In both the univariate and multivariate binary logistic regression analyses. PSA, SUVmax of the rim, local relapse, positive nodes were not associated to liver mets (Groups D-E) (p > 0.05). On the contrary, a significant correlation was found between the presence of liver metG (group D-E) and bone lesions (p= 0.00193).
Conclusion
Our results indicate that liver metastases in relapsing prostate cancer may occur frequently. The real incidence evaluation needs more investigations. In this case and despite technical limitations, Choline PET/CT shows alterations of tracer distribution within the liver that could eventually be mistaken for simple cysts but can be suspected when associated to high trigger PSA, concomitant bone lesions or modification over time. In this clinical setting an accurate analysis of liver tracer distribution (increased or decreased uptake) by the nuclear medicine physician is, therefore, mandatory.
http://ift.tt/2G4ji14
Favorable versus unfavorable prognostic groups by post-chemoradiation FDG-PET imaging in node-positive esophageal squamous cell carcinoma patients treated with definitive chemoradiotherapy
Abstract
Purpose
Our purpose was to examine the prognostic value of post-CRT PET based on the presence or absence of FDG-avid metastatic lymph node(s) and metabolic response of the primary tumor in patients with clinically node-positive ESCC treated with definitive chemoradiotherapy (dCRT).
Methods
We identified 108 eligible patients treated by chemoradiotherapy (CRT) with or without resection from our prospectively collected database. Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after initial CRT was defined as the Post-CRT PET favorable group (yPET-F), and otherwise as unfavorable group (yPET-U). The Kaplan-Meier method and Cox regression were performed for survival analyses and multivariable analysis, respectively.
Results
The study cohort was comprised of 59 patients receiving dCRT. Forty-five patients receiving trimodality therapy (TMT) comprised the comparative group and four patients were excluded from further analyses for developing interval distant metastasis detected on post-CRT PET scan. The median follow-up for the study cohort was 41 months. On K-M analysis of the study cohort, yPET-F was found to have significantly better OS (2-year: 72.5% vs 13.7%, p < 0.01) and DMFS (2-year: 71.6% vs 36.6%, p = 0.01) than yPET-U. In multivariable analysis, yPET-F remained as a strong independent favorable prognosticator on both OS (HR 0.08, p < 0.01) and DMFS (HR 0.14, p = 0.02) for the dCRT cohort. Compared with TMT cohort, for yPET-U patients, TMT had better OS (p = 0.03) than dCRT-Operable and dCRT-Operable had superior OS (p = 0.04) than dCRT-Unresectable. For yPET-F patients, there was no difference in both OS (p > 0.99) and DMFS (p = 0.92) between these three groups.
Conclusions
Absence of FDG-avid metastatic lymph node with at least partial response of the primary tumor on PET scan after CRT (i.e., yPET-F status) prognosticate for excellent OS and DMFS in cN+ ESCC patients treated with dCRT, and might be comparable to TMT.
http://ift.tt/2FWk306
EANM guideline for radionuclide therapy with radium-223 of metastatic castration-resistant prostate cancer
Abstract
Radium Ra-223 dichloride (radium-223, Xofigo®) is a targeted alpha therapy approved for the treatment of castration-resistant prostate cancer (CRPC) with symptomatic bone metastases and no known visceral metastatic disease. Radium-223 is the first targeted alpha therapy in this indication providing a new treatment option, with evidence of a significant survival benefit, both in overall survival and in the time to the first symptomatic skeletal-related event. The skeleton is the most common metastatic site in patients with advanced prostate cancer. Bone metastases are a clinically significant cause of morbidity and mortality, often resulting in bone pain, pathologic fracture, or spinal cord compression necessitating treatment. Radium-223 is selectively accumulated in the bone, specifically in areas of high bone turnover, by forming complexes with the mineral hydroxyapatite (the inorganic matrix of the bone). The alpha radiation generated during the radioactive decay of radium-223 produces a palliative anti-tumour effect on the bone metastases. The purpose of this guideline is to assist nuclear medicine specialists in evaluating patients who might be candidates for treatment using radium-223, planning and performing this treatment, understanding and evaluating its consequences, and improving patient management during therapy and follow-up.
http://ift.tt/2G5AJ1r
EANM guidelines for radionuclide therapy of bone metastases with beta-emitting radionuclides
Abstract
The skeleton is the most common metastatic site in patients with advanced cancer. Pain is a major healthcare problem in patients with bone metastases. Bone-seeking radionuclides that selectively accumulate in the bone are used to treat cancer-induced bone pain and to prolong survival in selected groups of cancer patients. The goals of these guidelines are to assist nuclear medicine practitioners in: (a) evaluating patients who might be candidates for radionuclide treatment of bone metastases using beta-emitting radionuclides such as strontium-89 (89Sr), samarium-153 (153Sm) lexidronam (153Sm-EDTMP), and phosphorus-32 (32P) sodium phosphate; (b) performing the treatments; and ©) understanding and evaluating the treatment outcome and side effects.
http://ift.tt/2pzuxYq
Complex Interplay between Epitope Specificity and Isotype Dictates the Biological Activity of Anti-human CD40 Antibodies
Publication date: Available online 22 March 2018
Source:Cancer Cell
Author(s): Xiaojie Yu, H.T. Claude Chan, Christian M. Orr, Osman Dadas, Steven G. Booth, Lekh N. Dahal, Christine A. Penfold, Lyn O'Brien, C. Ian Mockridge, Ruth R. French, Patrick Duriez, Leon R. Douglas, Arwen R. Pearson, Mark S. Cragg, Ivo Tews, Martin J. Glennie, Ann L. White
Anti-CD40 monoclonal antibodies (mAbs) that promote or inhibit receptor function hold promise as therapeutics for cancer and autoimmunity. Rules governing their diverse range of functions, however, are lacking. Here we determined characteristics of nine hCD40 mAbs engaging epitopes throughout the CD40 extracellular region expressed as varying isotypes. All mAb formats were strong agonists when hyper-crosslinked; however, only those binding the membrane-distal cysteine-rich domain 1 (CRD1) retained agonistic activity with physiological Fc gamma receptor crosslinking or as human immunoglobulin G2 isotype; agonistic activity decreased as epitopes drew closer to the membrane. In addition, all CRD2-4 binding mAbs blocked CD40 ligand interaction and were potent antagonists. Thus, the membrane distal CRD1 provides a region of choice for selecting CD40 agonists while CRD2-4 provides antagonistic epitopes.
Graphical abstract
Teaser
CD40 agonist mAbs are being investigated for cancer treatment, whereas antagonistic mAbs are under investigation for the treatment of autoimmune and inflammatory conditions. Yu et al. show that the activity of a CD40 mAb is determined by an interplay between the location of its epitope within CD40 and its isotype.http://ift.tt/2IMPPKD
Cerium dioxide (CeO2) nanoparticles decrease arsenite (As(III)) cytotoxicity to 16HBE14o- human bronchial epithelial cells
Publication date: July 2018
Source:Environmental Research, Volume 164
Author(s): Chao Zeng, Chi Nguyen, Scott Boitano, Jim A. Field, Farhang Shadman, Reyes Sierra-Alvarez
The production and application of engineered nanoparticles (NPs) are increasing in demand with the rapid development of nanotechnology. However, there are concerns that some of these novel materials could lead to emerging environmental and health problems. Some NPs are able to facilitate the transport of contaminants into cells/organisms via a "Trojan Horse" effect which enhances the toxicity of the adsorbed materials. In this work, we evaluated the toxicity of arsenite (As(III)) adsorbed onto cerium dioxide (CeO2) NPs to human bronchial epithelial cells (16HBE14o-) using the xCELLigence real time cell analyzing system (RTCA). Application of 0.5 mg/L As(III) resulted in 81.3% reduction of cell index (CI, an RTCA measure of cell toxicity) over 48 h when compared to control cells exposed to medium lacking As(III). However, when the cells were exposed to 0.5 mg/L As(III) in the presence of CeO2 NPs (250 mg/L), the CI was only reduced by 12.9% compared to the control. The CeO2 NPs had a high capacity for As(III) adsorption (20.2 mg/g CeO2) in the bioassay medium, effectively reducing dissolved As(III) in the aqueous solution and resulting in reduced toxicity. Transmission electron microscopy was used to study the transport of CeO2 NPs into 16HBE14o- cells. NP uptake via engulfment was observed and the internalized NPs accumulated in vesicles. The results demonstrate that dissolved As(III) in the aqueous solution was the decisive factor controlling As(III) toxicity of 16HBE14o- cells, and that CeO2 NPs effectively reduced available As(III) through adsorption. These data emphasize the evaluation of mixtures when assaying toxicity.
http://ift.tt/2ucYxib
Particulate nanocomposite from oyster (Crassostrea rivularis) hydrolysates via zinc chelation improves zinc solubility and peptide activity
Publication date: 30 August 2018
Source:Food Chemistry, Volume 258
Author(s): Ziran Zhang, Feibai Zhou, Xiaoling Liu, Mouming Zhao
An oyster protein hydrolysates-zinc complex (OPH-Zn) was prepared and investigated to improve zinc bioaccessibility. Zinc ions chelating with oyster protein hydrolysates (OPH) cause intramolecular and intermolecular folding and aggregation, homogeneously forming the OPH-Zn complex as nanoclusters with a Z-average at 89.28 nm (PDI: 0.16 ± 0.02). The primary sites of zinc-binding in OPH were carboxyl groups, carbonyl groups, and amino groups, and they were related to the high number of charged amino acid residues. Furthermore, formation of the OPH-Zn complex could significantly enhance zinc solubility both under specific pH conditions as well as during simulated gastrointestinal digestion, compared to the commonly used ZnSO4. Additionally, after digestion, either preserved or enhanced antioxidant activity of OPH was found when chelated with zinc. These results indicated that the OPH-Zn complex could be a potential functional ingredient with improved antioxidant bioactivity and zinc bioaccessibility.
http://ift.tt/2pxQneG
A comparison of the use of commercial and diluent free LIX84I in poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP)-based polymer inclusion membranes for the extraction and transport of Cu(II)
Publication date: 31 August 2018
Source:Separation and Purification Technology, Volume 202
Author(s): Duo Wang, Robert W. Cattrall, Jie Li, M. Inês G.S. Almeida, Geoff W. Stevens, Spas D. Kolev
The active component of the commercial extractant LIX84I, i.e. 2-hydroxy-5-nonylacetophenone (HNAPO), is usually below 50 wt%. The separation performance of polymer inclusion membranes (PIMs) generally increases with increasing the concentration of their liquid phase, consisting of the extractant (e.g., LIX84I) and a possible plasticizer or modifier. However, the use of high concentrations of the membrane liquid phase leads to worsening of the PIM mechanical stability. Therefore, the only way of increasing the concentration of HNAPO in PIMs without affecting their mechanical stability can be based on using diluent free LIX84I with concentration of HNAPO significantly higher than that in commercial LIX84I. This paper reports on a comparison between the performance of PIMs composed of poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) as the base-polymer, commercial or diluent free LIX84I as the extractant and 2-nitrophenyloctyl ether (NPOE) as the plasticizer when used for the extraction and transport of Cu(II) from ammonium sulfate solutions at pH 8.5. The diluent free LIX84I, obtained by a precipitation method, together with commercial LIX84I were characterized by gas chromatography-mass spectrometry and Fourier transform infrared spectroscopy. The percentage of HNAPO was determined by solvent extraction of Cu(II) and found to be 49 wt% and 72 wt% for the commercial and diluent free LIX84I, respectively. A comparative study between commercial and diluent free LIX84I-based PIMs was performed with regards to the extraction and transport of Cu(II) as well as their long term stability. Unexpectedly, the PIMs containing commercial LIX84I performed slightly better than the PIMs containing diluent free LIX84I in terms of extraction and transport rate of Cu(II). A selectivity study showed that both commercial and diluent free LIX84I-based PIMs had good selectivity for Cu(II) in the presence of Zn(II), Mg(II), Ni(II), and Co(II) in ammonium sulfate solutions, although the PIM containing commercial LIX84I was able to separate Cu(II) faster than the one composed of diluent free LIX84I.
http://ift.tt/2IKY2yZ
Seagrass Halophila stipulacea: Capacity of accumulation and biomonitoring of trace elements
Publication date: 15 August 2018
Source:Science of The Total Environment, Volume 633
Author(s): Giuseppe Bonanno, Salvatore Antonino Raccuia
This study aimed to shed further light on the capacity of the seagrass Halophila stipulacea to accumulate and biomonitor the elements As, Cd, Cr, Cu, Hg, Mn, Ni, Pb, and Zn, present in water and sediments. Results showed that the organs of H. stipulacea accumulate different levels of trace elements, whose concentrations decrease mainly in the order of roots>rhizomes>leaves. The seagrass H. stipulacea showed levels of trace elements similar to those found in other Mediterranean seagrasses, e.g. Posidonia oceanica and Cymodocea nodosa. This study showed that H. stipulacea could act as a promising bioindicator of several elements, present in sediments, including As, Cd, Cu, Mn, Ni and Zn.
Graphical abstract
http://ift.tt/2G5zv6l
Changes in heavy metal bioavailability and speciation from a Pb-Zn mining soil amended with biochars from co-pyrolysis of rice straw and swine manure
Publication date: 15 August 2018
Source:Science of The Total Environment, Volume 633
Author(s): Jun Meng, Mengming Tao, Lili Wang, Xingmei Liu, Jianming Xu
Biochar has been utilized as a good amendment to immobilize heavy metals in contaminated soils. However, the effectiveness of biochar in metal immobilization depends on biochar properties and metal species. In this study, the biochars produced from co-pyrolysis of rice straw with swine manure at 400°C were investigated to evaluate their effects on bioavailability and chemical speciation of four heavy metals (Cd, Cu, Pb and Zn) in a Pb-Zn contaminated soil through incubation experiment. Results showed that co-pyrolysis process significantly change the yield, ash content, pH, and electrical conductivity (EC) of the blended biochars compared with the single straw/manure biochar. The addition of these biochars significantly increased the soil pH, EC, and dissolved organic carbon (DOC) concentrations. The addition of biochars at a rate of 3% significantly reduced the CaCl2-extractable metal concentrations in the order of Pb>Cu>Zn>Cd. The exchangeable heavy metals decreased in all the biochar-amended soils whereas the carbonate-bound metal speciation increased. The increase in soil pH and the decrease in the CaCl2 extractable metals indicated that these amendments can directly transform the highly availability metal speciation to the stable speciation in soils. In conclusion, biochar derived from co-pyrolysis of rice straw with swine manure at a mass ratio of 3:1 could most effectively immobilize the heavy metals in the soil.
Graphical abstract
http://ift.tt/2IGGAf3
Evidence-based adverse outcome pathway approach for the identification of BPA as en endocrine disruptor in relation to its effect on the estrous cycle
Source:Molecular and Cellular Endocrinology
Author(s): Catherine Viguié, Sakina Mhaouty-Kodja, René Habert, Cécile Chevrier, Cécile Michel, Elodie Pasquier
Proper cyclicity is essential to reach successful optimal fertility. In rat and mice, BPA exposure is repeatedly and reliably reported to show an adverse effect on the estrous cycle after exposures at different life stages. In humans, a possible association between modifications of menstrual cycle characteristics (e.g. length of the cycle, duration of menstrual bleeding) and sub-fecundity or spontaneous abortion has been observed. Alterations of ovarian cyclicity can therefore be definitely considered as an adverse health outcome. As a prerequisite for the EU REACH regulation to identify a substance as an endocrine disruptor and thus a SVHC,1 the proof has to be established that the substance can have deleterious health effects resulting from an endocrine mode of action. This review provides an overview of the currently available data allowing to conclude that the adverse effects of BPA exposure on ovarian cyclicity is mediated by an endocrine mode of action.
http://ift.tt/2pD8f95
Cancer Pain Syndromes
Source:Hematology/Oncology Clinics of North America
Author(s): Russell K. Portenoy, Ebtesam Ahmed
Teaser
Patients with cancer experience many acute and chronic pain syndromes, the identification of which may be helpful in the assessment and treatment of pain. Syndromes are defined by the relationship with the cancer, the pain pathophysiology, and the clinical characteristics of the pain. The most common pain syndromes are directly related to the tumor; bone pain syndromes are most common. Neuropathic pain syndromes may involve cancer-related injury at any level of the peripheral nervous system. Treatment-related pain syndromes may follow any type of antineoplastic therapy. This article reviews the phenomenology of common acute and chronic cancer pain syndromes.http://ift.tt/2IKAOZO
Mechanisms of, and Adjuvants for, Bone Pain
Source:Hematology/Oncology Clinics of North America
Author(s): Nicholas Figura, Joshua Smith, Hsiang-Hsuan Michael Yu
Teaser
Metastatic bone pain is a complex, poorly understood process. Understanding the unique mechanisms causing cancer-induced bone pain may lead to potential therapeutic targets. This article discusses the effects of osteoclast overstimulation within the tumor microenvironment; the role of inflammatory factors at the tumor-nociceptor interface; the development of structural instability, causing mechanical nerve damage; and, ultimately, the neuroplastic changes in the setting of sustained pain. Several adjuvant therapies are available to attenuate metastatic bone pain. This article discusses the role of pharmacologic therapies, surgery, kyphoplasty, vertebroplasty, and radiofrequency ablation.http://ift.tt/2HZEbLr
Methadone
Source:Hematology/Oncology Clinics of North America
Author(s): Mary Lynn McPherson, Ryan C. Costantino, Alexandra L. McPherson
Teaser
Methadone is a valuable opioid in the management of patients who have cancer with pain. Methadone is a mu-, kappa-, and delta-opioid agonist, and an N-methyl-D-aspartate receptor antagonist. These mechanisms of action make methadone an attractive option for complex pain syndromes. It is critically important that providers consider a patient's risk status before beginning methadone. Careful consideration must be given to dosing methadone in both opioid-naïve and opioid-tolerant patients, with vigilant monitoring for therapeutic effectiveness and potential toxicity until the patient achieves steady state.http://ift.tt/2IMvmG0
Unusual metastasis of medullary thyroid carcinoma to the breast: A cytological and histopathological correlation
Journal of Cytology 2018 35(2):117-120
Breast metastases are a relatively rare condition and account for approximately 0.5–2% of all breast tumors. Recognition of metastatic tumors in the breast is important because it would prevent unnecessary mutilating surgery and would lead to appropriate treatment of the primary tumor. Breast metastases from medullary thyroid cancer (MTC) are very rare with only 21 reported cases in the literature. Some MTCs mimic primary invasive lobular carcinoma of the breast histopathologically and radiologically, making the distinction between the two diagnostically challenging. We present the case of a 45-year-old female presenting with a lump breast, which was later found out to be metastasis from medullary carcinoma thyroid.
http://ift.tt/2pyuFHG
Utility of cytokeratin7 immunocytochemistry in the cytopathological diagnosis of fibrolamellar hepatocellular carcinoma
Journal of Cytology 2018 35(2):75-78
Objective: To distinguish fibrolamellar hepatocellular carcinoma (FL-HCC) variant from the conventional hepatocellular carcinoma (HCC) by cytology, immunocytochemistry, and morphometry. Study Design: Retrospective detailed cytomorphological, immunocytochemical, and morphometric analysis was performed in 6 cases of FL-HCC reported on fine needle aspiration. Cell block immunocytochemistry (CB-ICC) for CK7 and CD68 was performed in four cases. Morphometry was carried out with Cell A software. Area of the cell, nucleus and nucleolus was measured in 50 nuclei per case in 6 cases each of FL-HCC and HCC. Results: The mean age of patients with FL-HCC was 19 years and all had normal serum alpha-fetoprotein levels. Fine needle aspiration smears showed large polygonal cells with abundant cytoplasm, vesicular nucleus and prominent nucleolus, associated with variably cellular fibrous stromal fragments. Intranuclear inclusions, cytoplasmic eosinophilic inclusions, and bile were also noted. FL-HCC showed strong membrano-cytoplasmic CK7 positivity and cytoplasmic granular and canalicular positivity for CD68. In contrast, HCC showed weak focal positivity for CK7 and only canalicular CD68 positivity. Morphometry revealed that FL-HCC cells were 2.19 times the size of HCC. Conclusion: CK7 immunocytochemistry on cell blocks is useful for confirming and distinguishing it from HCC.
http://ift.tt/2IIAUBg
Endoscopic ultrasound-guided cytodiagnosis of adrenal histoplasmosis with reversible cd4 t-lymphocytopenia and jejunal lymphangiectasia
Journal of Cytology 2018 35(2):110-113
http://ift.tt/2pAd2qG
Utility of cytospin and cell block technology in evaluation of body fluids and urine samples: A comparative study
Journal of Cytology 2018 35(2):79-82
Background: Cytologic examination of body fluids commonly involves the use of direct or sediment smears, cytocentrifuge preparations, membrane filter preparations, or cell block sections. Cytospin and cell block techniques are extremely useful in improving cell yield of thin serous effusions and urine samples, and ensure high diagnostic efficacy. Materials and Methods: We studied cytospin preparations and cell block sections prepared from 180 samples of body fluids and urine samples to compare the relative efficiency of cell retrieval, preservation of cell morphology, ease of application of special stains, and diagnostic efficacy. Samples were collected and processed to prepare cytospin smears and cell block sections. Results: We observed that overall, cell yield and preservation of individual cell morphology were better in cytospin preparations as compared to cell blocks, while preservation of architectural pattern was better in cell block sections. The number of suspicious cases also decreased on cell block sections, with increased detection of malignancy. It was difficult to prepare cell blocks from urine samples due to low cellularity. Conclusions: Cytospin technology is a quick, efficient, and cost-effective method of increasing cell yield in hypocellular samples, with better preservation of cell morphology. Cell blocks are better prepared from high cellularity fluids; however, tissue architecture is better studied, with improved rate of diagnosis and decrease in ambiguous results. Numerous sections can be prepared from a small amount of material. Special stains and immunochemical stains can be easily applied to cell blocks. It also provides a source of archival material.
http://ift.tt/2ILcF5I
Cystic schwannoma of tongue masquerading as mucocele: A cytological pitfall
Journal of Cytology 2018 35(2):125-126
http://ift.tt/2G5KAnP
Role of endoscopic ultrasound-guided fine-needle aspiration in adrenal lesions: analysis of 32 patients
Journal of Cytology 2018 35(2):83-89
Objective: Endoscopic ultrasound-guided fine-needle aspiration cytology (EUS-FNAC) is a precise and safe technique that provides both radiological and pathological diagnosis with a better diagnostic yield and minimal adverse events. EUS-FNAC led to the remarkable increase in the detection rate of incidentaloma found during radiologic staging or follow-up in various malignancy or unrelated conditions. Aims: We did this preliminary study with an aim to evaluate the role of EUS-FNA in diagnosing and classifying adrenal lesions, clinical impact, and compare the outcome with the previously published literature. Materials and Methods: We included 32 consecutive cases (both retrospective and prospective) of EUS-guided adrenal aspirate performed over a period of 3.3 years. The indications for the aspirate in decreasing order were metastasis (most common carcinoma gall bladder) > primary adrenal mass > disseminated tuberculosis > pyrexia of unknown origin. On EUS, 28 cases revealed space occupying lesion or mass (two cases bilateral) and four cases revealed diffuse enlargement (two cases bilateral) with a mean size of 21 mm. Results: The cytology reports were benign adrenal aspirate (43.8%), metastatic adenocarcinoma (15.6%), histoplasmosis (9.4%), tuberculosis (9.4%), round cell tumor (6.2%), adrenocortical carcinoma (3.1%), and descriptive (3.1%). Three cases (9.4%) yielded inadequate sample. The TNM staging was altered in 22.23% of the cases by result of adrenal aspirate. Conclusions: EUS-FNA of the adrenal gland is a safe, quick, and sensitive and real-time diagnostic technique, which requires an integrated approach of clinician, endoscopist, and cytopathologist for high precision in diagnosis. Although the role of EUS-FNA for right adrenal is not much described, we found adequate sample yield in all the four patients that underwent the procedure.
http://ift.tt/2IIAjQ2
Pilot study of an open-source image analysis software for automated screening of conventional cervical smears
Journal of Cytology 2018 35(2):71-74
Introduction: The Pap stained cervical smear is a screening tool for cervical cancer. Commercial systems are used for automated screening of liquid based cervical smears. However, there is no image analysis software used for conventional cervical smears. The aim of this study was to develop and test the diagnostic accuracy of a software for analysis of conventional smears. Materials and Methods: The software was developed using Python programming language and open source libraries. It was standardized with images from Bethesda Interobserver Reproducibility Project. One hundred and thirty images from smears which were reported Negative for Intraepithelial Lesion or Malignancy (NILM), and 45 images where some abnormality has been reported, were collected from the archives of the hospital. The software was then tested on the images. Results: The software was able to segregate images based on overall nuclear: cytoplasmic ratio, coefficient of variation (CV) in nuclear size, nuclear membrane irregularity, and clustering. 68.88% of abnormal images were flagged by the software, as well as 19.23% of NILM images. The major difficulties faced were segmentation of overlapping cell clusters and separation of neutrophils. Conclusion: The software shows potential as a screening tool for conventional cervical smears; however, further refinement in technique is required.
http://ift.tt/2G5Kc8R
Gata3 immunohistochemical staining is a useful marker for metastatic breast carcinoma in fine needle aspiration specimens
Journal of Cytology 2018 35(2):90-93
Aims: The utility of GATA3 immunohistochemistry (IHC) as an aid to the cytological diagnosis of metastatic breast carcinoma in fine needle aspiration (FNA) specimens was investigated. Materials and Methods: Cell block sections from 111 FNA cases of metastatic malignancy were stained for GATA3, including metastases from 43 breast and 44 nonmammary adenocarcinomas, 19 melanomas, 4 urothelial carcinomas, and 1 thyroid medullary carcinoma. Sites sampled included lymph nodes (87), bone (8), liver (5), lung (6), superficial masses (4), and pelvic mass (1). Results: Ninety-one percent (39/43) of metastatic breast carcinoma cases were positive for GATA3. All estrogen receptor (ER)-positive were also GATA3 positive cases. The majority (9/14; 64%) of ER-negative and 37% (3/8) of triple-negative cases were positive for GATA3. All nonmammary adenocarcinoma cases were negative with the exception of one case of metastatic pancreatic adenocarcinoma. Metastatic melanoma cases were all negative but 75% (3/4) urothelial carcinomas expressed GATA3. Conclusions: GATA3 IHC staining is a useful addition to IHC panels for FNA samples in specific settings such as distinguishing metastatic breast from lung carcinoma or melanoma.
http://ift.tt/2IK54UP
Primary splenic angiosarcoma with liver metastasis: A rare neoplasm diagnosed on fine-needle aspiration cytology and cell block immunocytochemistry
Journal of Cytology 2018 35(2):114-116
Primary splenic angiosarcoma is a rare malignant vascular neoplasm of mesenchymal origin. The tumor is highly aggressive and has a high metastatic potential. It is usually diagnosed on histopathological examination of splenectomy specimen. Only few cases of angiosarcoma diagnosed by fine-needle aspiration (FNA) cytology alone have been reported in the literature. The cytologic features of angiosarcoma are heterogeneous, however, diagnosis can be suggested by FNA when vasoformative features are present. A 55-year-old female presented with abdominal pain and hepatosplenomegaly. Computed tomography scan revealed a heterogeneous splenic lesion with liver metastases. FNA from the splenic and liver lesions showed moderately pleomorphic tumor cells closely associated with anastomosing vascular channels. Cell block immunocytochemistry (ICC) showed tumor cells positive for CD31, CD34, CD68 as well as for CD99. FNA supplemented by cell block ICC can render a definite diagnosis of primary splenic angiosarcoma with liver metastasis.
http://ift.tt/2G4q1YG
Comparison of conventional smear and liquid-based cytology preparation in diagnosis of lung cancer by bronchial wash and transbronchial needle aspiration
Journal of Cytology 2018 35(2):94-98
Introduction: Liquid-based cytology (LBC), initially developed for screening gynecologic specimens, is now being used in nongynecologic aspiration and exfoliative specimens. In this study, the diagnostic yield and utility of thin-prep (TP) was compared with conventional preparations to ascertain its utility in improving the diagnosis of respiratory lesions. Materials and Methods: Bronchial washings (BW) and transbronchial needle aspirates (TBNA) (bronchoscopy/endobronchial ultrasound-guided) from 70 consecutive patients of mediastinal masses and endo/peribronchial growths were included. The diagnostic yields of both conventional smears and thin-prep were compared. Immunocytochemistry (ICC) was performed on direct/cytospin smears of TBNA/BW and TP slides when the tumor could not be subtyped by morphology. Histopathologic correlation was done. Results: Although well-preserved morphological features and cleaner background in TP allowed accurate diagnosis of malignancies, diagnostic yield was comparable to conventional preparations. Immunocytochemistry was successfully employed on TP smears which helped in accurate subtyping of the tumors. Few shortcomings of TP smears were uneven distribution of cells, thick cell clusters, and inadequate cellularity. Conclusion: Liquid-based TP preparation is an effective diagnostic tool for respiratory tract cytology, however, results are comparable to conventional smears.
http://ift.tt/2IKNUGt
Retinoblastoma in an adult
Journal of Cytology 2018 35(2):120-124
Retinoblastoma is a rare malignant tumor of the retina usually seen in children before 5 years of age. The tumor is extremely rare in adults. We report here an unusual case of retinoblastoma in a 55-year-old adult female who presented to us with an orbital mass at a late stage of the disease. Detailed laboratory investigations and imaging studies could not make a precise diagnosis. The treating ophthalmologist suspected primary intraocular tumor, metastatic carcinoma, malignant melanoma, or lymphoma and referred the patient for fine needle aspiration cytology (FNAC). Cytopathological examination of Giemsa-stained FNAC smear was consistent with that of retinoblastoma and established the diagnosis.
http://ift.tt/2pzitX8
Analysis of morphological features of benign and malignant breast cell extracted from fnac microscopic image using the pearsonian system of curves
Journal of Cytology 2018 35(2):99-104
Context: Cytological changes in terms of shape and size of nuclei are some of the common morphometric features to study breast cancer, which can be observed by careful screening of fine needle aspiration cytology (FNAC) images. Aims: This study attempts to categorize a collection of FNAC microscopic images into benign and malignant classes based on family of probability distribution using some morphometric features of cell nuclei. Materials and Methods: For this study, features namely area, perimeter, eccentricity, compactness, and circularity of cell nuclei were extracted from FNAC images of both benign and malignant samples using an image processing technique. All experiments were performed on a generated FNAC image database containing 564 malignant (cancerous) and 693 benign (noncancerous) cell level images. The five-set extracted features were reduced to three-set (area, perimeter, and circularity) based on the mean statistic. Finally, the data were fitted to the generalized Pearsonian system of frequency curve, so that the resulting distribution can be used as a statistical model. Pearsonian system is a family of distributions where kappa (Ò) is the selection criteria computed as functions of the first four central moments. Results and Conclusions: For the benign group, kappa (Ò) corresponding to area, perimeter, and circularity was −0.00004, 0.0000, and 0.04155 and for malignant group it was 1016942, 0.01464, and −0.3213, respectively. Thus, the family of distribution related to these features for the benign and malignant group were different, and therefore, characterization of their probability curve will also be different.
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Papillary carcinoma thyroid presenting as huge scalp metastases
Journal of Cytology 2018 35(2):126-127
http://ift.tt/2G20q2G
Comparing the efficacy of leishman–giemsa cocktail stain, giemsa stain, and papanicolaou stain in potentially malignant oral lesions: A study on 540 cytological samples
Journal of Cytology 2018 35(2):105-109
Background: This study was planned to compare and evaluate the staining efficacy of Leishman–Giemsa cocktail (LG), Papanicolaou, and Giemsa stain (G) in potentially malignant disorders and malignant lesions. Aims: To evaluate the quality of nuclear and cytoplasmic staining of LG with G, and rapid Papanicolaou stain (Pap) and to compare the total staining efficiency of LG against G and P. Materials and Methods: One hundred and eighty participants were studied under three groups – 60 as healthy controls, 60 with potentially malignant disorders, and 60 with malignant lesions; smears were taken thrice from the buccal mucosa. One smear was fixed with Bio-Fix spray and other two smears were allowed to air dry for 2–3 minutes. Then, the ethyl alcohol-fixed smear was stained with Pap and the two other air-dried smears were stained with G and LG stains. Analysis was done using Friedman test and Wilcoxon Signed Rank Test with SPSS Version 15.0. Results: In the normal group, staining of LG was highly significant (P < 0.001). Among potentially malignant lesions, LG was observed to be highly significant (P < 0.001) when compared with G and was not significant when compared with Pap (P = 0.186). In the malignant group, LG was highly significant (P < 0.001). LG was superior with the highest average staining score of (2.018) than Pap and G. Conclusion: LG cocktail is a better stain with excellent cytoplasmic and nuclear staining intensity compared to Pap and G stains.
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Cytological findings of a rare case of transitional cell carcinoma bladder presenting with supraclavicular lymphnode metastasis
Journal of Cytology 2018 35(2):129-130
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Significance of BRAF V600E Mutation and Cytomorphological Features for the Optimization of Papillary Thyroid Cancer Diagnostics in Cytologically Indeterminate Thyroid Nodules
Exp Clin Endocrinol Diabetes
DOI: 10.1055/a-0588-4885
Background Ultrasound guided fine needle aspiration biopsy with cytologic analysis is an initial step in diagnostic of thyroid nodules. Unfortunately, up to 30% of biopsies are indeterminate and diagnostic surgery is required. The aim of this study was to estimate the diagnostic value of BRAF V600E mutation status combined with cytomorphological features for diagnosis of papillary thyroid cancer (PTC) in cytologically indeterminate thyroid nodules. Methods A prospective study analyzed patients who had ultrasound suspicious thyroid nodules, underwent fine needle aspiration and cytological examination, and were classified according to the Bethesda system. Patients from indeterminate diagnostic categories were examined for BRAF V600E mutation and 22 cytomorphological features, and underwent thyroid surgery. A binary logistic regression model was used to evaluate the diagnostic utility. Results A total of 219 patients met study criteria. After histological examination, 77 (35.2%) patients were diagnosed with PTC and 142 (64.8%) with benign nodular thyroid disease. According to logistic regression model, significant features for PTC diagnosis were: liquid colloid consistency, papillary structures, eosinophilic colloid bodies, and BRAF V600E mutation. Risk groups classified by this model have sensitivity of 80.5% (95% CI: 69.9 to 88.7), specificity of 99.3% (95% CI: 96.1 to 100), positive predictive value of 98.4% (95% CI: 89.8 to 99.8), negative predictive value of 90.4% (95% CI: 85.7 to 93.7), and accuracy of 92.7% (95% CI: 88.4 to 95.8) for PTC diagnosis. Conclusions Evaluation of BRAF V600E mutation status combined with cytomorphological features for diagnosis of PTC in cytologically indeterminate thyroid nodules can significantly improve diagnostic accuracy and reduce the number of diagnostic operations (calculator available at www.ptc-calc.we2host.lt).
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© Georg Thieme Verlag KG Stuttgart · New York
Article in Thieme eJournals:
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Costs of Cancer Care Across the Disease Continuum
AbstractPurpose.The aim of this study was to estimate Medicare payments for cancer care during the initial, continuing, and end‐of‐life phases of care for 10 malignancies and to examine variation in expenditures according to patient characteristics and cancer severity.Materials and Methods.We used linked Surveillance, Epidemiology and End Results‐Medicare data to identify patients aged 66–99 years who were diagnosed with one of the following 10 cancers: prostate, bladder, esophageal, pancreatic, lung, liver, kidney, colorectal, breast, or ovarian, from 2007 through 2012. We attributed payments for each patient to a phase of care (i.e., initial, continuing, or end of life), based on time from diagnosis until death or end of study interval. We summed payments for all claims attributable to the primary cancer diagnosis and analyzed the overall and phase‐based costs and then by differing demographics, cancer stage, geographic region, and year of diagnosis.Results.We identified 428,300 patients diagnosed with one of the 10 malignancies. Annual payments were generally highest during the initial phase. Mean expenditures across cancers were $14,381 during the initial phase, $2,471 for continuing, and $13,458 at end of life. Payments decreased with increasing age. Black patients had higher payments for four of five cancers with statistically significant differences. Stage III cancers posed the greatest annual cost burden for four cancer types. Overall payments were stable across geographic region and year.Conclusion.Considerable differences exist in expenditures across phases of cancer care. By understanding the drivers of such payment variations across patient and tumor characteristics, we can inform efforts to decrease payments and increase quality, thereby reducing the burden of cancer care.Implications for Practice.Considerable differences exist in expenditures across phases of cancer care. There are further differences by varying patient characteristics. Understanding the drivers of such payment variations across patient and tumor characteristics can inform efforts to decrease costs and increase quality, thereby reducing the burden of cancer care.
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Treatment and Survival of Patients with Colon Cancer Aged 80 Years and Older: A EURECCA International Comparison
AbstractBackground.Colon cancer in older patients represents a major public health issue. As older patients are hardly included in clinical trials, the optimal treatment of these patients remains unclear. The present international EURECCA comparison explores possible associations between treatment and survival outcomes in elderly colon cancer patients.Subjects, Materials, and Methods.National data from Belgium, Denmark, The Netherlands, Norway, and Sweden were obtained, as well as a multicenter surgery cohort from Germany. Patients aged 80 years and older, diagnosed with colon cancer between 2001 and 2010, were included. The study interval was divided into two periods: 2001–2006 and 2007–2010. The proportion of surgical treatment and chemotherapy within a country and its relation to relative survival were calculated for each time frame.Results.Overall, 50,761 patients were included. At least 94% of patients with stage II and III colon cancer underwent surgical removal of the tumor. For stage II–IV, the proportion of chemotherapy after surgery was highest in Belgium and lowest in The Netherlands and Norway. For stage III, it varied from 24.8% in Belgium and 3.9% in Norway. For stage III, a better adjusted relative survival between 2007 and 2010 was observed in Sweden (adjusted relative excess risk [RER] 0.64, 95% confidence interval [CI]: 0.54–0.76) and Norway (adjusted RER 0.81, 95% CI: 0.69–0.96) compared with Belgium.Conclusion.There is substantial variation in the rate of treatment and survival between countries for patients with colon cancer aged 80 years or older. Despite higher prescription of adjuvant chemotherapy, poorer survival outcomes were observed in Belgium. No clear linear pattern between the proportion of chemotherapy and better adjusted relative survival was observed.Implications for Practice.With the increasing growth of the older population, clinicians will be treating an increasing number of older patients diagnosed with colon cancer. No clear linear pattern between adjuvant chemotherapy and better adjusted relative survival was observed. Future studies should also include data on surgical quality.
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Families’ Sense of Abandonment When Patients Are Referred to Hospice
AbstractBackground.Terminally ill patients with cancer and their families may have a sense of abandonment when they are referred to hospice. This study aimed to clarify the prevalence of families' sense of abandonment, explore the association between the sense of abandonment and the oncologists' behaviors, and investigate the association between the sense of abandonment and the families' depression and complicated grief.Patients and Methods.This was part of a nationwide self‐reported questionnaire survey of bereaved families of patients with cancer who died in inpatient hospices. We sent questionnaires to 947 bereaved families of patients with cancer who died in 133 certified hospices between May 2012 and January 2014.Results.Among 707 responses obtained, a total of 189 (26.7%) families felt abandoned. The factors significantly associated with a greater sense of abandonment were that the oncologists said there was nothing more to do for the patient, the patient's age of less than 60 years, and being the patient's spouse. The factors significantly associated with a lower sense of abandonment were that the oncologists reassured the patients that they had received the best anticancer treatment, that the oncologists recommended hospices as one potential choice rather than mandatory, and that a palliative care team provided care. Families with a sense of abandonment had higher scores on the Patient Health Questionnaire‐9 (p = .096) and Brief Grief Questionnaire (p < .001).Conclusion.Approximately a quarter of bereaved families had a sense of abandonment, which was associated with a higher rate of complicated grief. Oncologists may reduce the sense of abandonment by reassuring that the patients received the best anticancer treatment, recommending hospices as a potential choice rather than as mandatory, and by not saying there is nothing that can be done for the patients.Implications for Practice.This self‐reported questionnaire study investigated the prevalence of families' feelings of abandonment when they were referred to hospice care, focusing on the association of sense of abandonment and the behavior of their physicians. Nearly a quarter of families felt abandoned by the referral to hospice, and the behavior of some oncologists was associated with the sense of abandonment.
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Serial Troponin for Early Detection of Nivolumab Cardiotoxicity in Advanced Non‐Small Cell Lung Cancer Patients
AbstractBackground.Rare cases of severe myocarditis are reported during treatment with nivolumab. Troponin, a biomarker of cardiac damage, is a key component of the diagnostic workup of many cardiac disorders, including myocarditis. This study investigates the role of troponin to assess cardiac involvement during nivolumab therapy for non‐small cell lung cancer (NSCLC).Materials and Methods.We evaluated 59 NSCLC patients, analyzing serum samples collected within a translational research study. Troponin above the upper normal limit (0.046 ng/mL) was defined as Tn+, whereas normal but detectable troponin (0.015–0.045) was defined as Tndet. Troponin alterations were interpreted on the grounds of the following elements: peak values and time curve, cardiac comorbidities, signs and symptoms coincident to troponin elevation, ECG, echocardiography, and disease progression.Results.No patient had cardiovascular events. Among 362 available blood samples, Tn+ (max 0.317 ng/mL) was found in 13 determinations belonging to 6 patients. Seven other patients had isolated Tndet. In five patients, Tn+ was attributed to cardiac comorbidities, disease progression, or worsening clinical status. One patient without cardiac history and in good clinical condition had a sustained troponin increase—soon after the start of therapy—and after careful evaluation of all relevant elements, it was interpreted as a marker of nivolumab‐related subclinical myocarditis.Conclusion.Tn+ may occur in NSCLC patients treated with nivolumab, but in most cases it does not indicate nivolumab cardiotoxicity. In some cases, however, a careful interpretation of troponin alteration, especially at the beginning of therapy, enables identification of subclinical myocarditis, thus allowing early cardiac treatment.Implications for Practice.Myocarditis is a rare but serious adverse event of immune checkpoint blockade with nivolumab, which needs to be recognized as soon as possible. This article suggests that troponin, a user‐friendly biomarker of myocardial cytotoxicity, might be useful for early detection of immune‐mediated myocarditis. However, because troponin abnormalities might also be related to a number of conditions capable of causing myocardial oxygen demand‐supply mismatch, a careful cardiac assessment should be performed in non‐small cell lung cancer patients in order to properly interpret any troponin increase. According to the available evidence, monitoring troponin during the first weeks of treatment can be considered reasonable.
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Prognostic Factors and Efficacy of First‐Line Chemotherapy in Patients with Advanced Thymic Carcinoma: A Retrospective Analysis of 286 Patients from NEJ023 Study
AbstractBackground.The prognostic factors and the efficacy of first‐line chemotherapy remain unclear in patients with advanced thymic carcinoma.Materials and Methods.We conducted a multi‐institutional retrospective study named NEJ023 for patients with advanced thymic carcinoma. All patients without any indication of curative treatment were treated with chemotherapy from 1995 to 2014 at 40 institutions of the North East Japan Study Group.Results.A total of 286 patients with advanced thymic carcinoma were analyzed. First‐line chemotherapy included platinum‐based doublets in 62.2% of the patients, monotherapy in 3.5%, and other multidrug chemotherapy (e.g., cisplatin, doxorubicin, vincristine, and cyclophosphamide [ADOC]) in 34.3%. The median follow‐up period was 55.5 months, and the median overall survival (OS) from the start of first‐line chemotherapy was 30.7 months (95% confidence interval, 25.9–35.9 months). There was no significant difference in OS among different first‐line chemotherapy regimens (e.g., between carboplatin/paclitaxel and ADOC, median OS: 27.8 vs. 29.9 months). Masaoka‐Koga stage IVa and volume reduction surgery were favorable prognostic factors for OS in the multivariate analysis using the Cox proportional hazards model.Conclusion.The efficacy of each first‐line chemotherapy regimen for advanced thymic carcinoma did not vary significantly. Our results might support the adequacy of the use of carboplatin/paclitaxel as first‐line chemotherapy for these patients.Implications for Practice.Because of its rarity, there is limited information about prognostic factors and efficacy of chemotherapy in patients with advanced thymic carcinoma. This is the largest data set for those patients treated with chemotherapy. This study suggests there is no significant difference in efficacy between carboplatin/paclitaxel and cisplatin/doxorubicin/vincristine/cyclophosphamide for advanced thymic carcinoma. This result can support the adequacy of the selection of platinum doublets as treatment for those patients, rather than anthracycline‐based multidrug regimen.
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Regulation of human dendritic cell immune functions by ion channels
Source:Current Opinion in Immunology, Volume 52
Author(s): Christophe Vandier, Florence Velge-Roussel
Dendritic cells (DCs) are highly specialized antigen-presenting cells (APCs) able to induce both specific immunity and immune tolerance. Using information gathered from the tissue where they reside, DCs adjust their functional activity to ensure that protective immunity is favoured while unwanted or exaggerated immune responses are prevented. The remarkable ability of these cells to induce, enhance and orient the immune response, while at the same time maintaining self-tolerance, makes them key players in the immune system. Despite the fact that the role of Ca2+ has been clearly established in human DC functions, the link between ion homeostasis, mainly Ca2+, and DC functions is not fully understood. After all, a growing number of works clearly show the role of SOCE and associated channels in the maturation step, and those of K+ channels in migration. This review highlights the key papers published over the past few years and summarizes prospects for the near future.
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The relationship between urban form and air pollution depends on seasonality and city size
Abstract
Understanding how urban form is related to air pollution is important to urban planning and sustainability, but the urban form-air pollution relationship is currently muddled by inconsistent findings. In this study, we investigated how the compositional and configurational attributes of urban form were related to different air pollution measures (PM2.5, API, and exceedance) in 83 Chinese cities, with explicit consideration of city size and seasonality. Ten landscape metrics were selected to quantify urban form attributes, and Spearman's correlation was used to quantify the urban form-air pollution relationship. Our results show that the urban form and air pollution relationship was dominated by city size and moderated by seasonality. Specifically, urban air pollution levels increased consistently and substantially from small to medium, large, and megacities. The urban form-air pollution relationship depended greatly on seasonality and monsoons. That is, the relationship was more pronounced in spring and summer than fall and winter, as well as in cities affected by monsoons. Urban air pollution was correlated more strongly with landscape composition metrics than landscape configuration metrics which seemed to affect only PM2.5 concentrations. Our study suggests that, to understand how air pollution levels are related to urban form, city size and seasonality must be explicitly considered (or controlled). Also, in order to mitigate urban air pollution problems, regional urban planning is needed to curb the spatial extent of built-up areas, reduce the degree of urban fragmentation, and increase urban compactness and contiguity, especially for large and megacities.
http://ift.tt/2G3OsWh
Incidences of mortality of Indian peafowl Pavo cristatus due to pesticide poisoning in India and accumulation pattern of chlorinated pesticides in tissues of the same species collected from Ahmedabad and Coimbatore
Abstract
Incidences of mortality of Indian peafowl Pavo cristatus, the national bird (Schedule I Indian Wild Life Protection Act 1972), are rampant in India. Between January 2011 and March 2017, around 550 peafowl in 35 incidences were reported dead across the country. Due to the non-availability of fresh carcases, poisoning could not be confirmed. Birds which died due to kite string injuries in Ahmedabad (15) and accidents in Coimbatore (5) were tested for residues of chlorinated pesticides, namely hexachlorocyclohexane (HCH), dichloro-diphenyl-trichloroethane (DDT), endosulfan, heptachlor, dicofol, dieldrin and cholipyrifos. The liver, kidney and muscle were the tissues considered to document pesticide load. Total load ranged from BDL to 388.2 ng/g. DDT (95%) and HCH (80%) were detected more frequently. DDT (40%) and endosulfan (26%) contributed maximum to the total pesticide load followed by HCH (21%). Pesticide accumulation pattern among the organs was in the order of liver (123.9 ng/g) > kidney (91.9 ng/g) > muscle (19.5 ng/g) with significant difference (p < 0.05). Peafowl from Ahmedabad had significantly (p < 0.05) higher level of total pesticide (149.0 ng/g) than birds from Coimbatore (47.8 ng/g). Although varying levels of chlorinated pesticide were detected, they were below reported toxic limits. Nevertheless, persistence of chlorinated pesticides and poisoning due to modern pesticides across the entire distribution range of Peafowl in India is a cause for concern.
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Mechanical Allodynia Predicts Better Outcome of Surgical Decompression for Painful Diabetic Peripheral Neuropathy
J reconstr Microsurg
DOI: 10.1055/s-0038-1636938
Background To determine the role of mechanical allodynia (MA) in predicting good surgical outcome for painful diabetic peripheral neuropathy (DPN). Methods A series of 192 patients with painful DPN were collected in this study, with 148 surgical patients and 44 patients in the control group. Both groups were further divided into subgroups based on the presence of MA on admission. Clinical evaluations including the visual analog scale (VAS), the Hospital Anxiety and Depression Scale (HADS), nerve conduction velocity (NCV), and high-resolution ultrasonography (cross-sectional area, CSA) were performed preoperatively and postoperatively. Results The levels of VAS and HADS and the results of NCV and CSA were improved in the surgical group (P < 0.05). In the surgical subgroups, pain reduction, psychiatric amelioration, improvement in NCVs, and the restoration of the CSA were observed in patients with signs of MA (P < 0.05), whereas only pain reduction, psychiatric amelioration, and restoration of the CSA were noted in patients without signs of MA (P > 0.05). Furthermore, better pain reduction was achieved in patients with MA when compared with those without MA (P < 0.05). Conclusions MA is proved to be a reliable predictor of good surgical outcome for painful DPN.
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A Temporal Transcriptional Switch Governs Stem Cell Division, Neuronal Numbers, and Maintenance of Differentiation
Publication date: Available online 22 March 2018
Source:Developmental Cell
Author(s): Natalia Mora, Carlos Oliva, Mark Fiers, Radoslaw Ejsmont, Alessia Soldano, Ting-Ting Zhang, Jiekun Yan, Annelies Claeys, Natalie De Geest, Bassem A. Hassan
The importance of producing the correct numbers of neurons during development is illustrated by both evolutionary enhancement of cognitive capacities in larger brains, and developmental disorders of brain size. In humans, increased neuronal numbers during development is speculated to partly derive from a unique subtype of neural stem cells (NSCs) that undergo a phase of expansion through symmetric self-amplifying divisions before generating neurons. Symmetric amplification also appears to underlie adult neural stem maintenance in the mouse. However, the mechanisms regulating this behavior are unclear. We report the discovery of self-amplifying NSCs in Drosophila and show that they arise by a spatiotemporal conversion of classical self-renewing NSCs. This conversion is regulated by a temporal transition in the expression of proneural transcription factors prior to cell division. We find a causal link between stem cell self-amplification and increased neuronal numbers. We further show that the temporal transcriptional switch controls both stem cell division and subsequent neuronal differentiation.
Teaser
Mora et al. discover neural stem cells in the Drosophila brain that divide symmetrically to double their numbers before generating one of the largest neuronal lineages in the fly. Atonal, the transcription factor that regulates stem cell doubling, also programs the maintenance of a differentiated state in their daughter neurons.http://ift.tt/2FVKaEC
The Circadian Clock Sets the Time of DNA Replication Licensing to Regulate Growth in Arabidopsis
Publication date: Available online 22 March 2018
Source:Developmental Cell
Author(s): Jorge Fung-Uceda, Kyounghee Lee, Pil Joon Seo, Stefanie Polyn, Lieven De Veylder, Paloma Mas
The circadian clock and cell cycle as separate pathways have been well documented in plants. Elucidating whether these two oscillators are connected is critical for understanding plant growth. We found that a slow-running circadian clock decelerates the cell cycle and, conversely, a fast clock speeds it up. The clock component TOC1 safeguards the G1-to-S transition and controls the timing of the mitotic cycle at early stages of leaf development. TOC1 also regulates somatic ploidy at later stages of leaf development and in hypocotyl cells. The S-phase is shorter and delayed in TOC1 overexpressing plants, which correlates with the diurnal repression of the DNA replication licensing gene CDC6 through binding of TOC1 to the CDC6 promoter. The slow cell-cycle pace in TOC1-ox also results in delayed tumor progression in inflorescence stalks. Thus, TOC1 sets the time of the DNA pre-replicative machinery to control plant growth in resonance with the environment.
Graphical abstract
Teaser
Fung-Uceda et al. show that the circadian clock sets the time of the cell cycle to accurately regulate the number and size of plant cells in synch with the environment. By regulating DNA replication, the clock is able to control not only plant growth but also tumor progression.http://ift.tt/2G4idGm
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Summary Insulinomas are rare neuroendocrine tumours that classically present with fasting hypoglycaemia. This case report discusses an un...
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