bluuebunny/crossref_metadata_2025 huggingface dataset:
A worldwide collaboration to harmonize guidelines for the long‐term follow‐up of childhood and young adult cancer survivors: A report from the international late effects of Childhood Cancer Guideline Harmonization Group
Authors: Kremer Leontien C.M. , Mulder Renée L. , Oeffinger Kevin C. , Bhatia Smita , Landier Wendy , Levitt Gill , Constine Louis S. , Wallace W. Hamish , Caron Huib N. , Armenian Saro H. , Skinner Roderick , Hudson Melissa M.
Published: January 2013

Childhood and young adult cancer survivors should receive optimum care to reduce the consequences of late effects and improve quality of life. We can facilitate achieving this goal by international collaboration in guideline development. In 2010, the International Late Effects of Childhood Cancer Guideline Harmonization Group was initiated. The aim of the harmonization endeavor is to establish a common vision and integrated strategy for the surveillance of late effects in childhood and young adult cancer survivors. With the implementation of our evidence‐based methods, we provide a framework for the harmonization of guidelines for the long‐term follow‐up of childhood and young adult cancer survivors. Pediatr Blood Cancer 2013; 60: 543–549. © 2012 Wiley Periodicals, Inc.
Antidepressant use among survivors of childhood, adolescent and young adult cancer: A report of the childhood, adolescent and young adult cancer survivor (CAYACS) research program
Authors: Deyell Rebecca J. , Lorenzi Maria , Ma Suli , Rassekh Shahrad R. , Collet Jean‐Paul , Spinelli John J. , McBride Mary L.
Published: January 2013

Background

Although survivors of childhood, adolescent, and young adult (AYA) cancer are at risk for late psychological sequelae, it is unclear if they are more likely to be prescription antidepressant users than their peers.

Procedure

All 5‐year survivors of childhood or AYA cancer diagnosed before age 25 years in British Columbia from 1970 to 1995 were identified. Those with complete follow‐up in the provincial health insurance registry from 2001 to 2004 were included (n = 2,389). A birth‐cohort and gender‐matched set of population controls 10 times the size of the survivor group was randomly selected (n = 23,890). All prescriptions filled between 2001 and 2004 were identified through linkage to the provincial prescription drug administrative database. Logistic regression analyses determined the impact of cancer survivorship on the likelihood of ever filling an antidepressant prescription.

Results

After adjusting for sociodemographic factors, survivors of childhood and AYA cancer were more likely to have filled an antidepressant prescription compared to controls (OR 1.21, 95% CI 1.09–1.35). Cancer survivors had an increased likelihood of using all categories of antidepressants, and of using drugs from two or more antidepressant categories, compared to peers (OR 1.31, 95% CI 1.11–1.55 [≥2 antidepressant categories]). Treatment was not a significant predictor of antidepressant use. Female survivors, those in young adulthood and those more than 20 years post‐treatment had increased antidepressant use.

Conclusions

Survivors of childhood and AYA cancer are more likely to fill antidepressant prescriptions compared to peer controls. This may indirectly reflect an increased underlying prevalence of mental health conditions among survivors. Pediatr Blood Cancer 2013; 60: 816–822. © 2012 Wiley Periodicals, Inc.
Pathological fracture as the presenting feature in pediatric osteosarcoma
Authors: Lee Ryan K.L. , Chu Winnie C.W. , Leung Joyce H.Y. , Cheng Frankie W.T. , Li C.K.
Published: January 2013

Background

Pathological fracture is an uncommon presentation in patients with long bone osteosarcoma.

Procedures

We retrospectively reviewed the database of all patients with histologically proven osteosarcoma under the age of 18 years from 1991 to 2011 in a tertiary pediatric oncology referral center. Five patients with pathological fractures as the first presentation of osteosarcoma were identified. The treatment strategies and complications were evaluated. Ten sex‐, age‐, and site‐ matched osteosarcoma patients without pathological fracture were selected as controls. The incidence of distant metastases and outcome, including local recurrence and survival, were compared between the index (with pathological fracture) and the control (without pathological fracture) groups.

Results

In the index group, all five patients were boys and the mean age of onset was 13.1 years (range 9.2–14.9). Three patients (60%, 3/5) received amputation and two (40%) had wide local excision of the tumor. Pathological fracture group showed higher rate of lung (60% vs. 10%, P = 0.04) and bone (60% vs. 10%, P = 0.04) metastases at presentation, and shorter overall 5‐year survival (P = 0.04) than the control group. There was no significant difference of local recurrence (20%, P = 1.00) between these two groups regardless of the type of operation.

Conclusion

Osteosarcoma complicated by pathological fracture as first presentation had higher incidence of lung and bone metastases at presentation and worse survival rate when compared with patients without pathological fracture. Pediatr Blood Cancer 2013; 60: 1118–1121. © 2012 Wiley Periodicals, Inc.
High frequency of streptococcal bacteraemia during childhood AML therapy irrespective of dose of cytarabine
Authors: Johannsen Katrine Helle , Handrup Mette Møller , Lausen Birgitte , Schrøder Henrik , Hasle Henrik
Published: January 2013

Background

High‐dose cytarabine has been associated with a high frequency of viridans group streptococcal (VGS) bacteraemia. VGS bacteraemia causes considerable morbidity and mortality. The Nordic Society of Paediatric Haematology and Oncology (NOPHO)‐AML protocols use higher cumulated doses of cytarabine and more chemotherapy series (n = 6) than other protocols with the potential increased risk of severe VGS infections.

Procedure

Medical records of all Danish children enrolled on the NOPHO‐AML‐2004 protocol between January 2004 and September 2011 (n = 45) were retrospectively reviewed and all febrile episodes were registered.

Results

Following 236 courses of chemotherapy, 112 positive blood cultures were registered. VGS were found in 38% of all positive blood cultures. Infectious episodes with VGS resulted in more days of fever and intravenous antibiotic therapy compared with infections caused by other microorganisms. VGS were involved in 45% of all episodes categorized as sepsis (n = 51) and in 67% of life‐threatening bloodstream infections (n = 9). Penicillin resistance was found in 40% of the VGS strains. No significant difference was observed in the proportion of VGS isolated following courses with low‐dose cytarabine versus courses with high‐dose cytarabine.

Conclusions

VGS were the most commonly isolated pathogens causing the most severe infections and the majority of life‐threatening infections. A substantial proportion of the strains were resistant to penicillin. The high rate of VGS seemed independent of high‐dose cytarabine but was more likely caused by the intensive chemotherapy treatment leading to severe mucositis and neutropenia. Pediatr Blood Cancer 2013; 60: 1154–1160. © 2012 Wiley Periodicals, Inc.
Decision making in pediatric oncology: Evaluation and incorporation of patient and parent preferences
Authors: Sung Lillian , Regier Dean A.
Published: January 2013

Decision making in pediatric cancer is particularly difficult. There may be uncertainty about prognosis, and long‐term survival estimates from trials may not be applicable to current patients. There are many motivations to conduct research into patient and provider decision making. This review discusses three approaches to understanding decision making, namely decision analysis, the threshold technique and discrete choice experiment. These techniques are applied to situations in pediatric oncology to illustrate how the results may be useful for patient care. Future work in pediatric oncology decision making should focus on methods to facilitate decision making and elicit preferences from children themselves. Pediatr Blood Cancer 2013; 60: 558–563. © 2012 Wiley Periodicals, Inc.
Long‐term follow‐up of children with high‐risk neuroblastoma: The ENSG5 trial experience
Authors: Moreno Lucas , Vaidya Sucheta J. , Pinkerton C. Ross , Lewis Ian J. , Imeson John , Machin David , Pearson Andrew D. J. ,   on behalf of the European Neuroblastoma Study Group and the Children's Cancer and Leukaemia Group (CCLG) (formerly UKCCSG)
Published: January 2013

Background

Therapy for high‐risk neuroblastoma is intensive and multimodal, and significant long‐term adverse effects have been described. The aim of this study was to identify the nature and severity of late complications of metastatic neuroblastoma survivors included in the ENSG5 clinical trial.

Procedure

The trial protocol included induction chemotherapy (randomized “Standard” OPEC/OJEC vs. “Rapid” COJEC), surgery of primary tumor and high‐dose melphalan with stem cell rescue. Two hundred and sixty‐two children were randomized, 69 survived >5 years, and 57 were analyzed. Data were obtained from the ENSG5 trial database and verified with questionnaires sent to participating centers.

Results

Median follow‐up was 12.9 (6.9–16.5) years. No differences were found in late toxicities between treatment arms. Twenty‐eight children (49.1%) developed hearing loss. Nine patients (15.8%) developed glomerular filtration rate <80 ml/min/1.73 m2, but no cases of chronic renal failure were documented. Endocrine complications (28.1% of children) included mainly hypogonadism and delayed growth. Four children developed second malignancies, three of them 5 years after diagnosis: one osteosarcoma, one carcinoma of the parotid gland and one ependymoma. There were no hematological malignancies or deaths in remission.

Conclusions

This study analyzed a wide cohort of high‐risk neuroblastoma survivors from a multi‐institutional randomized trial and established the profile of long‐term toxicity within the setting of an international clinical trial. Pediatr Blood Cancer 2013; 60: 1135–1140. © 2012 Wiley Periodicals, Inc.
Safety and efficacy of high‐dose tamoxifen and sulindac for desmoid tumor in children: Results of a Children's Oncology Group (COG) Phase II Study
Authors: Skapek Stephen X. , Anderson James R. , Hill D. Ashley , Henry David , Spunt Sheri L. , Meyer William , Kao Simon , Hoffer Fredric A. , Grier Holcombe E. , Hawkins Douglas S. , Raney R. Beverly
Published: January 2013

Background

Desmoid fibromatosis (desmoid tumor, DT) is a soft tissue neoplasm prone to recurrence despite complete surgical resection. Numerous small retrospective reports suggest that non‐cytotoxic chemotherapy using tamoxifen and sulindac may be effective for DT. We evaluated the safety and efficacy of tamoxifen and sulindac in a prospective phase II study within the Children's Oncology Group.

Procedures

Eligible patients were <19 years of age who had measurable DT that was recurrent or not amenable to surgery or radiation. The primary objective was to estimate progression‐free survival (PFS). Patients received tamoxifen and sulindac daily for 12 months or until disease progression or intolerable toxicity occurred. Response was assessed by magnetic resonance imaging.

Results

Fifty‐nine eligible patients were enrolled from 2004 to 2009; 78% were 10–18 years old. Twenty‐two (38%) were previously untreated; 15 (41%) of the remaining 37 enrolling with recurrent DT had prior systemic chemotherapy and six (16%) had prior radiation. No life‐threatening toxicity was reported. Twelve (40%) of 30 females developed ovarian cysts, which were asymptomatic in 11 cases. Ten patients completed therapy without disease progression or discontinuing treatment. Responses included four partial and one complete (5/59, 8%). The estimated 2‐year PFS and survival rates were 36% (95% confidence interval: 0.23–0.48) and 96%, respectively. All three deaths were due to progressive DT.

Conclusions

Tamoxifen and sulindac caused few serious side effects in children with DT, although ovarian cysts were common. However, the combination showed relatively little activity as measured by response and PFS rates. Pediatr Blood Cancer 2013; 60: 1108–1112. © 2012 Wiley Periodicals, Inc.
Improvement of toughness in polypropylene nanocomposite with the addition of organoclay/silicone copolymer masterbatch
Authors: Kaneko Manuela L.Q.A. , Romero Rafaelle B. , de Paiva Raphael E.F. , Felisberti Maria I. , Gonçalves Maria C. , Yoshida Inez V.P.
Published: January 2013

Polypropylene nanocomposites were prepared with organic‐modified montmorillonite, by blending the polymer and the organoclay (direct addition), or by blending the polymer with an organoclay/silicone copolymer masterbatch. The effect of the organoclay/silicone copolymer masterbatch on the morphology and properties of polypropylene was compared with that nanocomposite obtained with the direct organoclay addition. The results showed that the morphology of both polypropylene nanocomposites is constituted by clay tactoids together with some few individual platelets and clay aggregates. Smaller tactoids were observed for the nanocomposite prepared with the masterbatch, in which the silicone copolymer remained intercalated in the clay or adjacent to tactoids. The introduction of the organoclay in the polymer matrix resulted only in an increase in the Young's modulus (28%), while yielding stress, elongation at break and Izod impact strength remained practically unchanged. On the other hand, the incorporation of organoclay by using the masterbatch resulted in a marked improvement (111%) in the elongation at break and in Izod impact strength (85%). The improvement in the elongation at break came with the reduction of the modulus and the yielding stress, by 25 and 15%, respectively. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers
Role of calcium stearate as a dispersion promoter for new generation carbon black‐organoclay based rubber nanocomposites for tyre application
Authors: Mohanty Tapas R , Bhandari Vivek , Chandra Arup K. , Chattopadhyay Pijush K. , Chattopadhyay Santanu
Published: January 2013

A novel carbon black (CB) and nanoclay (NC) dual phase‐filled system in SBR matrix has been developed to be employed as a tyre tread compound with optimized performance properties. The nanocomposite has shown improved dynamic properties i.e. rolling resistance (tan δ at 60°C) and wet skid resistance (tan δ at 0°C), for relatively lower loading of NC (3 phr). However, the mechanical properties and wear resistance combined with above mentioned dynamic properties have been further improved by direct substitution of stearic acid with calcium stearate. This has been argued to be due to enhanced filler‐rubber interaction by the strong ionic interactions between the calcium ion (Ca++) and layered silicates (NC) having anionic surface. Transmission electron microscopy and low angle X‐ray diffraction studies have revealed the role of calcium stearate as a dispersion promoter for organoclay. Fourier transform infra‐red spectroscopy study has shown a shift in the SiOSi bond towards lower wave number indicating better polymer‐clay interaction. A detailed investigation on the dynamic rheological behavior of SBR‐CB‐NC nanocomposites has been carried out using rubber process analyzer to invoke an insight into the processing behavior of these composites. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers
Adsorption of cadmium (II) and copper (II) ions from aqueous solution using chitosan composite
Authors: Ramya R. , Sudha P.N.
Published: January 2013

The binary chitosan/silk fibroin composite synthesized by reinforcement of silk fibroin fiber into the homogenous solution of chitosan in formic acid was used to investigate the adsorption of two metals of Cu(II) and Cd(II) ions in an aqueous solution. The binary composite was characterized by Fourier transform infrared and scanning electron microscopy. The optimum conditions for adsorption by using a batch method were evaluated by changing various parameters such as contact time, adsorbent dose, and pH of the solution. The experimental isotherm data were analyzed using the Freundlich and Langmuir equations, indicated to be well fitted to the Langmuir isotherm equation under the concentration range studied, by comparing the correlation co‐efficient. Adsorption kinetics data were tested using pseudo‐first‐order and pseudo‐second‐order models. Kinetics studies showed that the adsorption followed a pseudo‐second‐order reaction. Due to good performance and low cost, this binary chitosan/silk fibroin composite can be used as an adsorbent for removal of Cu(II) and Cd(II) from aqueous solutions. POLYM. COMPOS., 2013. © 2013 Society of Plastics Engineers
Evaluation of FDA safety‐related drug label changes in 2010
Authors: Lester Jean , Neyarapally George A. , Lipowski Earlene , Graham Cheryl Fossum , Hall Marni , Dal Pan Gerald
Published: January 2013

Purpose

This study characterizes drug safety‐related label changes by evidence source contribution, time from drug approval to label change, initiator (FDA or sponsor), and drug class.

Methods

A retrospective review of the FDA's internal files was used to obtain regulatory documentation on drugs undergoing a 2010 label change. Contribution of evidence sources were identified and label change initiator and drug class were determined for each drug.

Results

A total of 371 drugs were analyzed. Spontaneous reports contributed to 52% and 55% of label changes when analyzed by unique safety issue and drug, respectively. The median time from approval to 2010 safety‐related label change was 11 years. The sponsor was more likely than the FDA to initiate a label change (58% and 42%). Label changes were most common among nervous system drugs (23%), antiinfectives for systemic use (17%), and cardiovascular system drugs (14%).

Conclusions

Drug label changes involve contributions from multiple evidence sources. The findings from this comprehensive review are consistent with previous findings and demonstrate (i) the continued importance of the spontaneous reporting system and complementary evidence sources and (ii) safety‐related label changes take place years after postmarket approval, emphasizing the importance of continued drug safety surveillance throughout a product's lifecycle. Copyright © 2013 John Wiley & Sons, Ltd.
Titanium(IV) nonmetallocene complex catalyzed aqueous homopolymerization and copolymerization of styrene and methyl methacrylate: An Environmentally friendly approach to ultrahigh molecular weight polymer nanoparticles
Authors: De Sudip K. , Bhattacharjee Manish
Published: January 2013

A new titanium(IV) complex bearing [ONO] type ligand has been synthesized, characterized, and employed as catalyst in homopolymerization and copolymerization of styrene and methyl methacrylate. In the presence of sodium tetraphenyl borate and sodium n‐dodecyl sulfate (SDS), it exhibits moderate to high activity and afford ultrahigh molecular weight polymers. © 2013 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013
MicroRNAs and lung development
Authors: Khoshgoo Naghmeh , Kholdebarin Ramin , Iwasiow Barbara Maria , Keijzer Richard
Published: January 2013

MicroRNAs (miRNAs) constitute a large group of small (∼22 nucleotides), non‐coding RNA sequences that are highly conserved among animals, plants and microorganisms, suggesting that microRNAs represent a highly conserved and important regulatory mechanism. They have been demonstrated to play an important role in gene regulation. Recently, miRNAs have become a major focus of interest for research in organ development. Research focusing on the potential role of microRNAs during lung development is slowly starting to emerge. A number of miRNAs have been demonstrated to play important roles during early and late lung development. Several studies have begun to profile miRNA expression at various stages of lung development and this article provides an overview of the various miRNAs that have been implicated in lung organogenesis. Pediatr Pulmonol. 2013; 48:317–323. © 2012 Wiley Periodicals, Inc.
Endobronchial nocardiosis in an 11‐year‐old child
Authors: Cakir Erkan , Buyukpinarbasili Nur , Ziyade Sedat , Selcuk‐Duru Hatice N. , Bilgin Mehmet , Topuz Ufuk
Published: January 2013

Pulmonary nocardiosis is a rare infection and overwhelmingly limited to immunocompromised individuals. Endobronchial nocardiosis is even more rare. Nocardiosis is rarely seen in immunocompetent hosts mostly as cutaneous infection. Here we report an immunocompetent child with endobronchial nocardiosis presenting as nonresolving pneumonia and lung abscess. To our knowledge, this is the first case reported in the literature of endobronchial nocardiosis in a child. Pediatr Pulmonol. 2013; 48:1144–1147. © 2012 Wiley Periodicals, Inc.
The lung is involved in juvenile dermatomyositis
Authors: Pouessel Guillaume , Deschildre Antoine , Le Bourgeois Muriel , Cuisset Jean‐Marie , Catteau Benoit , Karila Chantal , Nève Véronique , Thumerelle Caroline , Quartier Pierre , Tillie‐Leblond Isabelle
Published: January 2013

Background

Juvenile dermatomyositis (JDM) is the main cause of chronic idiopathic inflammatory myopathy of autoimmune origin in children. The aim of this multicenter prospective study was to describe respiratory status and treatment of children followed for JDM.

Methods and patients

Clinical manifestations, pulmonary function tests (PFT), chest high‐resolution computed tomography (HRCT) scan results, and treatments and their adverse effects were analyzed in children followed for JDM.

Results

Twenty‐one patients (median age: 9.9 years; range: 20 months–18 years) were included. The median of disease duration at the time of the analysis was 3 years (range: 6 months–9 years 4 months). Overall 16 (76%) of 21 children presented with a respiratory involvement related to JDM including interstitial lung disease (n = 3) and/or respiratory muscle involvement (n = 7). Seven patients presented with other nonspecific manifestations. Three children had aspiration pneumonia. A chest HRCT was performed in 15 children, and abnormalities were observed in 12. PFT were performed in 20 of 21 patients. Seven showed functional abnormalities: restrictive ventilatory defect (n = 3) or obstructive ventilatory defect (n = 4). Six patients had abnormal respiratory muscle tests, including three with a restrictive ventilatory defect and one with an obstructive ventilatory defect. One other child with an acute aspiration pneumonia had a clearly muscle respiratory involvement but was too young to perform respiratory muscle tests and confirm this diagnosis. Treatment comprised systemic corticosteroid for all patients and adjuvant immunosuppressive therapy for 11. Adverse effects linked to treatment were reported in eight patients.

Conclusion

The frequency of lung involvement in children with JDM justifies systematic respiratory assessment with PFT including measures of respiratory muscle strength. We suggest that a chest HRCT scan is indicated in cases of respiratory symptoms and/or PFT abnormalities. Longitudinal studies are needed to assess pediatric characteristics, long‐term outcomes, and responses to treatment taking into account the risk–benefit ratio. Pediatr Pulmonol. 2013; 48:1016–1025. © 2012 Wiley Periodicals, Inc.
Feasibility and reproducibility of spirometry and inductance plethysmography in healthy Brazilian preschoolers
Authors: França Danielle C. , Camargos Paulo A.M. , Martins Jocimar A. , Abreu Mercês C.S. , e Araújo Gilda Helena Avelar , Parreira Verônica F.
Published: January 2013

Rationale

Preschoolers show peculiarities that reinforce the importance of assessing their pulmonary function. However, there are few data on the success rate and between‐occasions reproducibility of pulmonary function tests in preschoolers, particularly in the Brazilian population.

Objective

To assess the success rate and between‐occasions reproducibility of the variables obtained by spirometry and respiratory inductive plethysmography in healthy children aged 4–6 years.

Methods

Breathing pattern was assessed by plethysmography (tidal volume‐VT, respiratory rate‐f, inspiratory duty cycle‐Ti/Ttot, mean respiratory flow‐VT/Ti, displacement of the rib cage‐RC and phase relation during the total breath‐PhRTB) and spirometry (forced vital capacity‐FVC, forced expiratory volume in 0.5 sec‐FEV0.5 and forced expiratory volume in first second‐FEV1) in 47 healthy children, aged 4–6 years. To evaluate between‐occasions reproducibility, 10 children (according to the sample size calculation) were reassessed after 3 weeks. Between‐occasions reproducibility was evaluated by paired t‐test, considering significant P < 0.05, Intraclass Correlation Coefficient (ICC) and coefficient of variation of method error (CVME).

Results

The results showed an 83% success rate for spirometry and a 98% success rate for plethysmography. Regarding reproducibility, there were no significant differences between the variables of any test. Spirometry ICC was above 0.80 and the CVME was lower than 10%. The plethysmography ICC was between 0.61 and 0.95, and the CVME was between 2% and 31%.

Conclusions

These results suggest a high success rate in performing the pulmonary function tests and good between‐occasions reproducibility for spirometry and plethysmography in healthy preschoolers. Pediatr Pulmonol. 2013; 48:716–724. © 2012 Wiley Periodicals, Inc.
Bronchoscopic assessment of airway involvement in children presenting with clinically significant airway obstruction due to tuberculosis
Authors: Goussard Pierre , Gie Robert P. , Kling Sharon , Andronikou Savvas , Lucas Susan , Janson Jacques , Roussouw Gawie
Published: January 2013

Introduction

The incidence of complicated lymph node disease in tuberculosis (TB) in children less than 15 years of age varies from 8% to 38%. There are few published studies on the bronchoscopic appearance and severity of airway obstruction caused by lymph node involvement of the airways resulting from Mycobacterium tuberculosis (MTB). The primary aim of the study was to describe the flexible bronchoscopic findings of lymph node involvement of the airways caused by MTB in children with severe airway obstruction. The secondary aim was to compare the degree of airway involvement in HIV negative to HIV positive children as well the airway involvement caused by drug susceptible and drug resistant MTB.

Patients and Methods

All children between 1 month and 13 years of age presenting with clinical and radiological signs of significant airway obstruction suspected of being the result of MTB infection were studied. In addition to routine examination for MTB disease a flexible bronchoscope and bronchoalveolar lavage (BAL) for MTB culture were performed on all the children.

Results

Two hundred fifty children (16% HIV positive) were studied. Median age was 14 months and the median weight 8.5 kg. MTB was cultured from 78% (n = 194) of children with the BAL positive in 44%. The BAL culture yield was significantly higher in children with radiological evidence of pneumonia when compared to children with airway involvement alone (P = 0.004). The bronchial tree was obstructed on the right in 85% (n = 212), the left in 66% (n = 164), and both sides in 53% (n = 132) of cases. The commonest sites of obstruction were bronchus intermedius (72%) and left main bronchus (62%). Drug resistance was present in 16% (n = 28). There was no difference in the site or severity of obstruction when comparing drug susceptible to drug resistant cases or HIV positive to HIV negative children.

Conclusions

Bronchus intermedius and left main bronchus were the commonest sites of airway obstruction. The MTB culture yield from BAL was higher in children with pneumonia when compared to those with airway involvement alone. HIV positive or children with drug resistant TB did not have more severe airway obstruction. Pediatr Pulmonol. 2013; 48:1000–1007. © 2012 Wiley Periodicals, Inc.
Single‐cell analysis of circulating tumor cells identifies cumulative expression patterns of EMT‐related genes in metastatic prostate cancer
Authors: Chen Chun‐Liang , Mahalingam Devalingam , Osmulski Pawel , Jadhav Rohit R. , Wang Chiou‐Miin , Leach Robin J. , Chang Tien‐Cheng , Weitman Steven D. , Kumar Addanki Pratap , Sun LuZhe , Gaczynska Maria E. , Thompson Ian M. , Huang Tim Hui‐Ming
Published: January 2013

BACKGROUND

Prostate tumors shed circulating tumor cells (CTCs) into the blood stream. Increased evidence shows that CTCs are often present in metastatic prostate cancer and can be alternative sources for disease profiling and prognostication. Here we postulate that CTCs expressing genes related to epithelial–mesenchymal transition (EMT) are strong predictors of metastatic prostate cancer.

METHODS

A microfiltration system was used to trap CTCs from peripheral blood based on size selection of large epithelial‐like cells without CD45 leukocyte marker. These cells individually retrieved with a micromanipulator device were assessed for cell membrane physical properties using atomic force microscopy. Additionally, 38 CTCs from eight prostate cancer patients were used to determine expression profiles of 84 EMT‐related and reference genes using a microfluidics‐based PCR system.

RESULTS

Increased cell elasticity and membrane smoothness were found in CTCs compared to noncancerous cells, highlighting their potential invasiveness and mobility in the peripheral circulation. Despite heterogeneous expression patterns of individual CTCs, genes that promote mesenchymal transitioning into a more malignant state, including IGF1, IGF2, EGFR, FOXP3, and TGFB3, were commonly observed in these cells. An additional subset of EMT‐related genes (e.g., PTPRN2, ALDH1, ESR2, and WNT5A) were expressed in CTCs of castration‐resistant cancer, but less frequently in castration‐sensitive cancer.

CONCLUSIONS

The study suggests that an incremental expression of EMT‐related genes in CTCs is associated with metastatic castration‐resistant cancer. Although CTCs represent a group of highly heterogeneous cells, their unique EMT‐related gene signatures provide a new opportunity for personalized treatments with targeted inhibitors in advanced prostate cancer patients. Prostate 73: 813–826, 2013. © 2012 Wiley Periodicals, Inc.
Near‐infrared fluorescence imaging of gastrin releasing peptide receptor targeting in prostate cancer lymph node metastases
Authors: Cai Quan‐Yu , Yu Ping , Besch‐Williford Cynthia , Smith Charles J. , Sieckman Gary L. , Hoffman Timothy J. , Ma Lixin
Published: January 2013

BACKGROUND

Development of high affinity and specificity molecular imaging probes that increase accuracy for early detection of lymph node (LN) metastases is important for improving survivorship in prostate cancer. We evaluated the specificity, sensitivity, and accuracy of fluorescence‐labeled bombesin (BBN) peptides to detect LN and systematic metastases in orthotopic mouse models bearing gastrin releasing peptide receptor (GRPR)‐positive human prostate cancer.

METHODS

PC‐3 cells were orthotopically implanted in severe combined immunedeficient or thymic nude (nu/nu) male mice. Tumor growth was monitored using magnetic resonance imaging. Alexa Fluor 680 conjugated BBN[7‐14]NH2 (AF680‐BBN) peptides were administered intravenously at 4–7 weeks post‐tumor‐implantation. Near‐infrared fluorescence (NIRF) imaging was performed for up to 6 hr post‐injection. The imaging sensitivity and specificity were assessed by co‐registration of AF680‐BBN NIRF imaging and luciferase bioluminescence imaging of the PC‐3/Luc+ orthotopic mouse model.

RESULTS

AF680‐BBN showed a high binding affinity and selectivity to GRPR‐positive cancer in vitro and in vivo. LN and peritoneal metastases were detected by NIRF imaging, and confirmed by histopathology. Tumor‐to‐muscle (T/M) ratio was the highest at 2‐hr post‐injection (4.12 ± 1.77). Blocking experiments, using unlabeled BBN as the inhibiting agent, significantly reduced the T/M ratio (1.64 ± 0.21, P = 0.02). AF680‐BBN NIRF imaging had a sensitivity of 89.4%, specificity of 92.9%, and accuracy of 90.2% for the detection of metastases in mice.

CONCULSIONS

The studies suggest the potential of use and development of NIR‐fluorescent BBN probes as site‐directed agents to help improve the current detection and LN staging accuracy in prostate cancer. Prostate 73: 842–854, 2013. © 2012 Wiley Periodicals, Inc.
The association between calcium channel blocker use and prostate cancer outcome
Authors: Poch Michael A. , Mehedint Diana , Green Dawn J. , Payne‐Ondracek Rochelle , Fontham Elizabeth T.H. , Bensen Jeannette T. , Attwood Kristopher , Wilding Gregory E. , Guru Khurshid A. , Underwood Willie , Mohler James L. , Heemers Hannelore V.
Published: January 2013

BACKGROUND

Epidemiological studies indicate that calcium channel blocker (CCB) use is inversely related to prostate cancer (PCa) incidence. The association between CCB use and PCa aggressiveness at the time of radical prostatectomy (RP) and outcome after RP was examined.

METHODS

Medication use, PCa aggressiveness and post‐RP outcome were retrieved from a prospectively populated database that contains clinical and outcome for RP patients at Roswell Park Cancer Institute (RPCI) from 1993 to 2010. The database was queried for anti‐hypertensive medication use at diagnosis for patients with ≥1 year follow‐up. Recurrence was defined using NCCN guidelines. Chi‐Square tests assessed the relationship between CCB use and PCa aggressiveness. Cox regression models compared the distribution of progression‐free survival (PFS) and overall survival (OS) with adjustment for covariates. Results for association between CCB usage and PCa aggressiveness were validated using data from the population‐based North Carolina‐Louisiana Prostate Cancer Project (PCaP).

RESULTS

48%, 37%, and 15% of RPCI's RP patients (n = 875) had low, intermediate, and high aggressive PCa, respectively. 104 (11%) had a history of CCB use. Patients taking CCBs were more likely to be older, have a higher BMI and use additional anti‐hypertensive medications. Diagnostic PSA levels, PCa aggressiveness, and margin status were similar for CCB users and non‐users. PFS and OS did not differ between the two groups. Tumor aggressiveness was associated with PFS. CCB use in the PCaP study population was not associated with PCa aggressiveness.

CONCLUSIONS

CCB use is not associated with PCa aggressiveness at diagnosis, PFS or OS. Prostate 73: 865–872, 2013. © 2012 Wiley Periodicals, Inc.
Mechanisms of synergism between antagonists of growth hormone‐releasing hormone and antagonists of luteinizing hormone‐releasing hormone in shrinking experimental benign prostatic hyperplasia
Authors: Rick Ferenc G. , Schally Andrew V. , Block Norman L. , Abi‐Chaker Andrew , Krishan Awtar , Szalontay Luca
Published: January 2013

BACKGROUND

Benign prostatic hyperplasia (BPH) affects aging men. Combined therapy with antagonists of growth hormone‐releasing hormone (GHRH) and of luteinizing hormone‐releasing hormone (LHRH or GnRH) induces prostate shrinkage in rat models. We investigated the mechanisms of action of this combination on cell cycle traverse and expression of prostatic genes.

METHODS

Effects of GHRH antagonist, JMR‐132 (40 µg/day), the LHRH antagonist, cetrorelix (0.625 mg/kg), and their combination were evaluated on testosterone‐induced benign prostatic hyperplasia in male Wistar rats. Influence of JMR‐132, cetrorelix, and their combinations on cell viability was assessed by MTS assay in BPH‐1 human prostate epithelial cells and WPMY‐1 normal prostate stromal cells. Cell cycle was analyzed by laser flow cytometry. Real‐time PCR arrays were performed.

RESULTS

The combination of antagonists caused marked shrinkage of rat prostate (29.5%). In vitro, JMR‐132 plus cetrorelix (both 5µM) produced synergistic (57.4%) inhibition of growth of BPH‐1 cells, but a lesser inhibition (46%) of WPMY‐1 cells. Co‐treatment of with JMR‐132 plus cetrorelix induced a significant increase of BPH‐1 cells blocked in S‐phase plus cells with lower G0/G1 and G2/M DNA content. Significant changes in expression of >40 gene transcripts related to growth factors, inflammatory cytokines, and signal transduction were identified.

CONCLUSIONS

GHRH antagonist and LHRH antagonist combination potentiates rat prostate weight reduction and synergistically inhibits of growth of BPH‐1 leading to cell cycle arrest in S‐phase. These effects were lesser in normal stromal prostate cell line, WPMY‐1. Our findings suggest that GHRH antagonists could be useful for BPH therapy, possibly in combination with LHRH antagonists. Prostate 73: 873–883, 2013. © 2012 Wiley Periodicals, Inc.
Endothelial‐rich microenvironment supports growth and branching morphogenesis of prostate epithelial cells
Authors: Bergthorsson Jon Thor , Magnusson Magnus Karl , Gudjonsson Thorarinn
Published: January 2013

BACKGROUND

Development of epithelial organs depends on interaction between the epithelium and the underlying mesenchyme including the vasculature. The aim of this study was to explore the morphogenic effect of endothelial cells on prostate epithelial cell lines in 3D culture and to establish an in vitro model for prostate branching morphogenesis.

METHODS

A panel of eleven cell lines originating in normal or malignant prostate and primary prostate epithelial cells were cultured in reconstituted basement membrane (rBM) matrix with or without non‐proliferating but metabolically active endothelial cells. Morphogenesis was evaluated by phase contrast microscopy and further characterized by immunocyto/histocemistry and confocal microscopy.

RESULTS

Endothelial cells induced clonogenic potential of most prostate cell lines and formation of branching and mesenchymal‐like colonies. One of the normal‐derived cell lines in the panel (PZ‐HPV‐7) displayed unique properties in rBM culture by forming large and complex branching structures resembling the ductal architecture of the prostate. This ability was highly dependent on epithelial seeding density and soluble factors derived from the endothelial cells. High seeding density suppressed branching of PZ‐HPV‐7 but survival was compromised at low density in the absence of endothelium.

CONCLUSIONS

We have generated an endothelial‐based clonogenic assay to study prostate epithelial morphogenesis in three‐dimensional context. This assay will be important tool to study prostate epithelial–endothelial interactions in 3D context and open up possibilities to study molecular regulation of prostate morphogenesis and cancer progression. Prostate 73: 884–896, 2013. © 2012 Wiley Periodicals, Inc.
Prostate cancer patients older than 70 years treated by radical prostatectomy have higher biochemical recurrence rate than their matched younger counterpart
Authors: Ko Jennifer , Falzarano Sara M. , Walker Esteban , Streator Smith Karen , Stephenson Andrew J. , Klein Eric A. , Magi‐Galluzzi Cristina
Published: January 2013

BACKGROUND

Consensus on prostate cancer (PCA) treatment in older men is currently lacking. We evaluated clinicopathological and oncological outcomes in patients >70‐year‐old treated with radical prostatectomy (RP).

METHODS

Clinicopathological and follow‐up (FU) data for >70‐year‐old RP men (2000–2011) were recorded. Association between preoperative features, extraprostatic extension (EPE) and biochemical failure (bF), and postoperative features and bF, was explored. Patients >70‐year‐old were matched with younger (50‐ to 70‐year‐old) men with similar RP features to analyze the effect of age on bF.

RESULTS

Two hundred eighteen RP patients were >70‐year‐old. Clinical stage (cT) was T1 in 74.1%. Biopsy (Bx) Gleason score (GS) was 6 (35.8%), 7 (45.9%), and ≥8 (18.3%); RP GS was 6 (10.1%), 7 (63.3%), and ≥8 (26.6%). Median PSAD was 0.14 (range: 0.01–1.12). Pathologic stage (pT) was pT3 in 45.9%. bF occurred in 14.0%. Best preoperative predictive model for pT3 disease included D'Amico risk, number of Bx positive cores, PSAD, maximum % of PCA per core (P < 0.0001); cT, PSAD and primary Bx Gleason pattern best predicted bF preoperatively (P = 0.0031). Among postoperative features, high RP GS, positive margins, and pT3 were significantly associated with bF. Margin status and pT best predicted bF. Patients >70‐year‐old had 85% higher odds of bF compared to younger men (P = 0.036).

CONCLUSIONS

PCA detected in >70‐year‐old men shows adverse pathologic features. Failure rate is significantly higher in older than in matched younger patients. Prostate 73: 897–903, 2013. © 2012 Wiley Periodicals, Inc.
Ocean memory effect on the dynamics of coastal heavy precipitation preceded by a mistral event in the northwestern Mediterranean
Authors: Lebeaupin Brossier Cindy , Drobinski Philippe , Béranger Karine , Bastin Sophie , Orain Francoise
Published: January 2013

In this study, we examine the possible role of 3D oceanic circulation in ‘connecting’ a strong mistral windstorm in the northwestern Mediterranean with a heavy precipitating event in southern France in November 1999. These two events are both governed by intense air–sea exchanges and are only separated by a week. From an atmospheric point of view, these two events may be considered as fully uncorrelated and independent.

However, using the MORCE regional coupled system with WRF atmospheric model and NEMO‐MED12 ocean model, we show that the oceanic cyclonic circulation is a key feature, which can trap strong modifications of the ocean mixed layer over few days. In our specific situation, the mistral (5–9 November 1999) induces a rapid mixed‐layer cooling. This cold anomaly is trapped in the cyclonic gyre in the Gulf of Lions and maintained over a week. This directly affects the following heavy precipitating event (12–13 November 1999) with less energy supplied where the cold anomaly is maintained and larger evaporation near the coast. This modulates the rainfall amounts over land, with an increase in the eastern part and a decrease in the western part compared to an uncoupled simulation. These simulations highlight the key role of the general ocean circulation, and especially of the dynamic of the cyclonic gyre in the Gulf of Lions on the ocean memory in the area. The ocean maintains the temperature anomaly over typical periods of a few days, which thus enables some indirect links between two weather systems in which air–sea interactions are significant.
Evaluation of the ECMWF ocean reanalysis system ORAS4
Authors: Balmaseda Magdalena Alonso , Mogensen Kristian , Weaver Anthony T.
Published: January 2013

A new operational ocean reanalysis system (ORAS4) has been implemented at ECMWF. It spans the period 1958 to the present. This article describes its main components and evaluates its quality. The adequacy of ORAS4 for the initialization of seasonal forecasts is discussed, along with the robustness of some prominent climate signals.

ORAS4 has been evaluated using different metrics, including comparison with observed ocean currents, RAPID‐derived transports, sea‐level gauges, and GRACE‐derived bottom pressure. Compared to a control ocean model simulation, ORAS4 improves the fit to observations, the interannual variability, and seasonal forecast skill. Some problems have been identified, such as the underestimation of meridional overturning at 26°N, the magnitude of which is shown to be sensitive to the treatment of the coastal observations.

ORAS4 shows a clear and robust shallowing trend of the Pacific Equatorial thermocline. It also shows a clear and robust nonlinear trend in the 0–700 m ocean heat content, consistent with other observational estimates. Some aspects of these climate signals are sensitive to the choice of sea‐surface temperature product and the specification of the observation‐error variances. The global sea‐level trend is consistent with the altimeter estimate, but the partition into volume and mass variations is more debatable, as inferred by discrepancies in the trend between ORAS4‐ and GRACE‐derived bottom pressure.
Comments on ‘Sensitivity of tropical‐cyclone models to the surface drag coefficient’
Authors: Bryan George H.
Published: January 2013

Some conclusions from a recent numerical modeling study regarding the potential intensity of tropical cyclones are shown to be attributable to a relatively short model integration time. Three‐dimensional simulations that are long enough to allow for a quasi‐steady state of maximum intensity show a result consistent with theory, i.e., that maximum intensity is inversely proportional to surface drag coefficient. An alternative hypothesis for how tropical cyclones can intensify in numerical models in the absence of surface drag is also offered.
A two‐step variational method for analyzing severely aliased radar velocity observations with small Nyquist velocities
Authors: Xu Qin , Nai Kang
Published: January 2013

By formulating the effect of radar velocity aliasing and the resulting zigzag discontinuities into the cost function for the velocity azimuth display (VAD) analysis, the previously developed alias‐robust VAD analysis, called AR‐VAD, can estimate the horizontal mean wind by directly fitting the VAD uniform‐wind model to raw aliased radial‐velocity observations. In this article, the AR‐VAD analysis is further developed into a two‐step alias‐robust variational analysis, called AR‐Var, to estimate the radial‐velocity field beyond the VAD uniform‐wind model from raw aliased radial‐velocity observations on each range circle. In the first step, the original AR‐VAD analysis is modified to fit the raw aliased radial‐velocity observations around each of the two zero radial‐velocity points on the selected range circle. The two analyzed radial‐velocity fields are then combined into a single radial‐velocity field not rigidly constrained by the VAD uniform‐wind assumption. This combined radial‐velocity field represents an improved fit to the observations over the entire range circle and thus can be used as the first‐guess background to refine and perform the AR‐Var analysis in the second step. The two‐step AR‐Var analysis can provide a reliable reference radial‐velocity field for the reference check in radar velocity de‐aliasing even when the Nyquist velocity is reduced below 12 m s−1, and this is illustrated by both idealized and real examples.
Nerve sparing technique in robotic‐assisted radical hysterectomy: results
Authors: Gil‐Ibáñez Blanca , Díaz‐Feijoo Berta , Pérez‐Benavente Asunción , Puig‐Puig Oriol , Franco‐Camps Silvia , Centeno Cristina , Xercavins Jordi , Gil‐Moreno Antonio
Published: January 2013

Background

This work assessed the role of robotic‐assisted lapararoscopic radical hysterectomy in the treatment of early invasive cervical cancer with special regard to nerve sparing technique.

Methods

Between October 2009 and June 2011, a total of 14 non‐consecutive patients underwent early cervical cancer surgery at the authors' institution. Patients with FIGO stage IA2 or IB1 with a tumor size less than or equal to 2 cm underwent radical hysterectomy type B1 and patients with FIGO stage IB1 with a tumor mass bigger than 2 cm underwent a radical hysterectomy using a C1 type technique.

Results

Three type B1 and 11 type C1 radical hysterectomies with robotic‐assisted laparoscopy were performed using Da Vinci®. The median operation time was 260 min (range 150–300 min). The median follow‐up after surgery was 13.7 months (range 1–23 months). During this time, three patients reported anorectal dysfunction while none reported sexual or bladder dysfunction. All patients remain without evidence of disease except one with high risk factors for recurrence. They all are alive.

Conclusions

Laparoscopic robotic‐assisted radical hysterectomy with nerve sparing technique is an attractive surgical approach for early invasive cervical cancer. Robotic technology allows a stereoscopic visualization of blood vessels and autonomic nerve supplies (sympathetic and parasympathetic branches) to the bladder and rectum making nerve sparing a safe and feasible procedure. Copyright © 2013 John Wiley & Sons, Ltd.