bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of pregnancy on cardiac function and hemodynamics in women with Ebstein's anomaly
Authors: Kanoh Miki , Inai Kei , Shinohara Tokuko , Shimada Eriko , Shimizu Mikiko , Tomimatsu Hirofumi , Ogawa Masaki , Nakanishi Toshio 
Published: May 2018

AbstractIntroductionWe examined the perinatal outcomes and right ventricular function before pregnancy, during pregnancy, and after delivery in women with Ebstein's anomaly.Material and methodsWe retrospectively investigated the clinical course and mode of delivery and monitored hemodynamic parameters throughout pregnancy in 17 women with Ebstein's anomaly who delivered at our institution during the period of 1995–2015.ResultsEight women, including nine pregnancies, underwent elective cesarean section, and nine women, including 14 pregnancies, underwent vaginal delivery. Elective cesarean section was performed in cases with significant heart failure or arrhythmias and in the presence of more than two of the following: cardiothoracic ratio ≥60%, moderate or severe tricuspid valve regurgitation, tricuspid valve regurgitation pressure gradient ≥35 mmHg during pregnancy. The cardiothoracic ratio and tricuspid valve regurgitation pressure gradient significantly increased during pregnancy compared with prepregnancy values. The New York Heart Association classification deteriorated from class I to class II or III in five cases during pregnancy.ConclusionsAlthough pregnancy was relatively safe among women with Ebstein's anomaly, some women developed cyanosis, arrhythmia, and heart failure, leading to elective cesarean section. Monitoring clinical and hemodynamic changes throughout pregnancy is advised to minimize maternal cardiac risk and select the appropriate mode of delivery.
Final results from a defibrotide treatment‐IND study for patients with hepatic veno‐occlusive disease/sinusoidal obstruction syndrome
Authors: Kernan Nancy A. , Grupp Stephan , Smith Angela R. , Arai Sally , Triplett Brandon , Antin Joseph H. , Lehmann Leslie , Shore Tsiporah , Ho Vincent T. , Bunin Nancy , Iacobelli Massimo , Liang Wei , Hume Robin , Tappe William , Soiffer Robert , Richardson Paul 
Published: May 2018

SummaryHepatic veno‐occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is a potentially life‐threatening complication of haematopoietic stem cell transplant (HSCT) conditioning and chemotherapy. Defibrotide is approved for treatment of hepatic VOD/SOS with pulmonary or renal dysfunction [i.e., multi‐organ dysfunction (MOD)] after HSCT in the United States and severe VOD/SOS after HSCT in patients aged older than 1 month in the European Union. Defibrotide was available as an investigational drug by an expanded‐access treatment programme (T‐IND; NCT00628498). In the completed T‐IND, the Kaplan–Meier estimated Day +100 survival for 1000 patients with documented defibrotide treatment after HSCT was 58·9% [95% confidence interval (CI), 55·7–61·9%]. Day +100 survival was also analysed by age and MOD status, and post hoc analyses were performed to determine Day +100 survival by transplant type, timing of VOD/SOS onset (≤21 or >21 days) and timing of defibrotide treatment initiation after VOD/SOS diagnosis. Day +100 survival in paediatric patients was 67·9% (95% CI, 63·8–71·6%) and 47·1% (95% CI, 42·3–51·8%) in adults. All patient subgroups without MOD had higher Day +100 survival than those with MOD; earlier defibrotide initiation was also associated with higher Day +100 survival. The safety profile of defibrotide in the completed T‐IND study was similar to previous reports.
Comorbidities associated with higher von Willebrand factor (VWF) levels may explain the age‐related increase of VWF in von Willebrand disease
Authors: Atiq Ferdows , Meijer Karina , Eikenboom Jeroen , Fijnvandraat Karin , Mauser‐Bunschoten Eveline P. , van Galen Karin P. M. , Nijziel Marten R. , Ypma Paula F. , de Meris Joke , Laros‐van Gorkom Britta A. P. , van der Bom Johanna G. , de Maat Moniek P. , Cnossen Marjon H. , Leebeek Frank W. G. ,   the WiN study group
Published: May 2018

SummarySome comorbidities, such as hypertension, are associated with higher von Willebrand factor (VWF) levels in the general population. No studies have been conducted to assess this association in patients with von Willebrand disease (VWD). Therefore, we studied this association in patients with type 1 (n = 333) and type 2 (n = 203) VWD from the ‘WiN” study. VWF antigen (VWF:Ag) was higher in type 1 VWD patients with hypertension [difference: 0·23 iu/ml, 95% confidence interval (CI): 0·11–0·35], diabetes mellitus (0·11 iu/ml, 95% CI: −0·02 to 0·23), cancer (0·14 iu/ml, 95% CI: 0·03–0·25) and thyroid dysfunction (0·14 iu/ml, 95% CI: 0·03–0·26) than in patients without these comorbidities (all corrected for age, sex and blood group). Similar results were observed for VWF collagen binding capacity (VWF:CB), VWF activity as measured by the VWF monoclonal antibody assay (VWF:Ab) and factor VIII (FVIII) coagulant activity (FVIII:C). In type 1 VWD, age was associated with higher VWF:Ag (0·03 iu/ml; 95% CI: 0·01–0·04), VWF:CB (0·02 iu/ml; 95% CI: 0·00–0·04), VWF:Ab (0·04 iu/ml; 95% CI: 0·02–0·06) and FVIII:C (0·03 iu/ml; 95% CI: 0·01–0·06) per decade increase. After adjustment for relevant comorbidities, these associations were no longer significant. Despite the higher VWF and FVIII levels, type 1 VWD patients with comorbidities had more bleeding episodes, particularly during surgery. There was no association between comorbidities and VWF/FVIII levels or bleeding phenotype in type 2 VWD patients. In conclusion, comorbidities are associated with higher VWF and FVIII levels in type 1 VWD and may explain the age‐related increase of VWF and FVIII levels.
Mesenchymal stromal cells from Shwachman‐Diamond syndrome patients fail to recreate a bone marrow niche in vivo and exhibit impaired angiogenesis
Authors: Bardelli Donatella , Dander Erica , Bugarin Cristina , Cappuzzello Claudia , Pievani Alice , Fazio Grazia , Pierani Paolo , Corti Paola , Farruggia Piero , Dufour Carlo , Cesaro Simone , Cipolli Marco , Biondi Andrea , D'Amico Giovanna 
Published: May 2018

SummaryShwachman‐Diamond syndrome (SDS) is a rare multi‐organ recessive disease mainly characterised by pancreatic insufficiency, skeletal defects, short stature and bone marrow failure (BMF). As in many other BMF syndromes, SDS patients are predisposed to develop a number of haematopoietic malignancies, particularly myelodysplastic syndrome and acute myeloid leukaemia. However, the mechanism of cancer predisposition in SDS patients is only partially understood. In light of the emerging role of mesenchymal stromal cells (MSCs) in the regulation of bone marrow homeostasis, we assessed the ability of MSCs derived from SDS patients (SDS‐MSCs) to recreate a functional bone marrow niche, taking advantage of a murine heterotopic MSC transplant model. We show that the ability of semi‐cartilaginous pellets (SCPs) derived from SDS‐MSCs to generate complete heterotopic ossicles in vivo is severely impaired in comparison with HD‐MSC‐derived SCPs. Specifically, after in vitro angiogenic stimuli, SDS‐MSCs showed a defective ability to form correct networks, capillary tubes and vessels and displayed a marked decrease in VEGFA expression. Altogether, these findings unveil a novel mechanism of SDS‐mediated haematopoietic dysfunction based on hampered ability of SDS‐MSCs to support angiogenesis. Overall, MSCs could represent a new appealing therapeutic target to treat dysfunctional haematopoiesis in paediatric SDS patients.
Salt, inflammation, IL‐17 and hypertension
Authors: Wenzel Ulrich O , Bode Marlies , Kurts Christian , Ehmke Heimo 
Published: May 2018

Traditionally, arterial hypertension and subsequent end‐organ damage have been attributed to haemodynamic factors, but increasing evidence indicates that inflammation also contributes to the deleterious consequences of this disease. The immune system has evolved to prevent invasion of foreign microorganisms and to promote tissue healing after injury. However, this beneficial activity comes at a cost of collateral damage when the immune system overreacts to internal injury, such as prehypertension. Over the past few years, important findings have revolutionized hypertension research. Firstly, in 2007, a seminal paper showed that adaptive immunity is involved in the pathogenesis of hypertension. Secondly, salt storage in the skin and its consequences for cardiovascular physiology were discovered. Thirdly, after the discovery that salt promotes the differentiation of CD4+ T cells into TH17 cells, it was demonstrated that salt directly changes several cells of the innate and adaptive immune system and aggravates autoimmune disease but may improve antimicrobial defence. Herein, we will review pathways of activation of immune cells by salt in hypertension as the framework for understanding the multiple roles of salt and immunity in arterial hypertension and autoimmune disease.Linked ArticlesThis article is part of a themed section on Immune Targets in Hypertension. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.12/issuetoc
Pyrimidine‐based pyrazoles as cyclin‐dependent kinase 2 inhibitors: Design, synthesis, and biological evaluation
Authors: Vekariya Mayur K. , Vekariya Rajesh H. , Brahmkshatriya Pathik S. , Shah Nisha K. 
Published: May 2018

A series of new pyrimidine‐pyrazole hybrid molecules were designed as inhibitors of cyclin‐dependent kinase 2. Designed compounds were docked using Glide and the compounds showing good score values and encouraging interactions with the residues were selected for synthesis. They were then evaluated using CDK2‐CyclinA2 enzyme inhibition by a luminescent ADP detection assay. We show that of the 26 compounds synthesized and evaluated, at least 5 compounds were found to be highly potent (IC50 < 20 nm); which can be further optimized to have selectivity over other kinase isoforms.
Cyberbullying prevention: Insight and recommendations from youths, parents, and paediatricians
Authors: Mehari K. R. , Moore W. , Waasdorp T. E. , Varney O. , Berg K. , Leff S. S. 
Published: May 2018

AbstractBackgroundThe purpose of this study was to identify injunctive norms for cyberbullying prevention among youths, parents, and primary care providers, as well as barriers to preventive behaviours.MethodsSemi‐structured interviews on the topic of cyberbullying were conducted with 29 adolescents, 13 paediatricians, and 15 parents recruited from 3 primary care sites. Transcripts were coded for themes related to various stakeholders' perceived roles in cyberbullying prevention and barriers to preventive behaviours.ResultsParticipants reported perceptions that youths should intervene in the moment and get outside help for others. Fear of repercussions emerged as a significant barrier to these behaviours. Participants believed that parents should communicate with their children and monitor and supervise youths' online activities. Barriers included perception of priority and low parental efficacy or naiveté. Participants believed that providers should provide education and resources and ask screening questions; the most frequently identified barrier to those behaviours was the perception of providers' role.ConclusionsYouths and providers may not be aware of their potential to prevent cyberbullying before it occurs. Educating youths, parents, and providers about cyberbullying prevention is warranted.
Children's experiences with an intervention aimed to prevent further physical abuse
Authors: Thulin Johanna , Kjellgren Cecilia , Nilsson Doris 
Published: May 2018

AbstractAlthough many children across cultures are victims of physical abuse, few treatment models target these children and their parents. In Sweden, Combined Parent–Child Cognitive Behavioural Therapy for families at risk for child physical abuse has been successfully used according to pretreatment and posttreatment studies. However, few studies have explored how physically abused children experience treatment. This study includes 20 physically abused children aged 9–17 who completed Combined Parent–Child Cognitive Behavioural Therapy. Children had a positive overall impression of the treatment and highlighted addressing the abuse, as well as processing their experiences as particularly essential. Children described a positive transformation in their family life as a result of treatment, including violence cessation and bonding among family members. Children experienced the intervention as inclusive and child‐friendly. The implications of the promising findings are discussed.
Challenges of operationalizing trauma‐informed practice in child protection services in New Zealand
Authors: Atwool Nicola 
Published: May 2018

AbstractNew Zealand is undergoing major change in service delivery to children and families. A new Ministry for Children Oranga Tamariki has been established to oversee 5 work streams, one of which provides intensive intervention with families requiring a statutory response to child protection concerns. The government minister responsible promised that the service would be child‐centred and trauma‐informed. To date, these terms remain undefined, and there is no shared understanding of their meaning. Practice frameworks to support the work of the new ministry are still being developed, creating something of a vacuum in the meantime. The focus of this paper is the challenge of implementing trauma‐informed practice in the child protection service provided by the Intensive Intervention work stream. Limited research or commentary on trauma‐informed practice in this context currently exists. Drawing on the relevant available literature, the concept and its application in child protection social work is explored. An ecological framework is used to discuss the changes needed to achieve this. Particular attention is paid to the impact of historical trauma for indigenous people due to New Zealand's colonial history and their over‐representation in care and protection services.
Organic psychosis: The pathobiology and treatment of delusions
Authors: Joyce Eileen Maria 
Published: May 2018

SummaryOrganic or secondary psychosis can be seen in diverse conditions such as toxic/metabolic disorders, neurodegenerative disease, and stroke. Poststroke psychosis is a rare phenomenon, but its study has significantly contributed to the understanding of delusion formation. The evidence from case studies of patients with focal strokes shows that delusions develop following unilateral damage of the right hemisphere. The majority of patients with right hemisphere stroke do not develop delusions however, and advanced neuroimaging analysis has elucidated why this symptom develops in only a small proportion. Lesions of the right lateral prefrontal cortex or lesions with connectivity to this area correlate with delusional beliefs in this subgroup. Studies of patients with primary psychosis, for example schizophrenia, or under the influence of the psychotogenic drug ketamine, also show abnormal function of this area in relation to the severity of their abnormal beliefs. The conclusion of these studies is that the right lateral prefrontal cortex is 1 hub in a neural network which includes the basal ganglia and limbic system and receives inputs from midbrain dopamine neurones. In patients with schizophrenia, or at risk of psychosis, dopamine is dysregulated and evidence suggests that faulty dopamine signaling is the precursor of delusion formation. It is therefore likely that the mechanism of delusion formation is the same in both primary and secondary psychosis. This is consistent with the mainstay of treatment of both conditions being antipsychotic medication. However, antipsychotic medication in people with cerebrovascular disease should be avoided if at all possible. This is because epidemiological studies have found that antipsychotic use is associated with an increased risk of stroke and will thus compound the possibility of a further cerebrovascular accident.
Change of signs, symptoms and voice quality evaluations throughout a 3‐ to 6‐month empirical treatment for laryngopharyngeal reflux disease
Authors: Lechien J.R. , Finck C. , Khalife M. , Huet K. , Delvaux V. , Picalugga M. , Harmegnies B. , Saussez S. 
Published: May 2018

ObjectiveTo assess the usefulness of voice quality measurements as a treatment outcome in patients with laryngopharyngeal reflux (LPR)‐related symptoms.DesignProspective uncontrolled multi‐centre study.Material and methodsA total of 80 clinically diagnosed LPR patients with a reflux finding score (RFS)>7 and a reflux symptom index (RSI)>13 were treated with pantoprazole and diet recommendations during 3 or 6 months, according to their evolution. RSI; RFS; blinded Grade, Roughness, Breathiness, Asthenia, Strain and Instability (GRBASI) and aerodynamic and acoustic measurements were evaluated at baseline, 3 months (n = 80), and 6 months (n = 41) post‐treatment. We conducted a correlation analysis between the adherence to the diet, and the evolution of both signs and symptoms and between videolaryngostroboscopic signs and acoustic measurements.ResultsReflux symptom index, RFS, perceptual voice quality evaluations (dysphonia, roughness, strain and instability), and aerodynamic and acoustic measurements (ie, percent jitter and percent shimmer) were significantly improved at 3 months post‐treatment but not at 6 months. Percent jitter was the most useful outcome for evaluating the clinical evolution of patients throughout the treatment course. A significant relationship between globus sensation and posterior commissure hypertrophy was documented; both seemed to significantly improve from 3 to 6 months. The correlation analysis revealed correlations between adherence to diet recommendations and the improvement of symptoms and between posterior commissure granulation severity and acoustic measurement impairments.ConclusionVoice quality improved in a manner similar to both signs and symptoms throughout a 6‐month empirical treatment with better improvement the 3 first months. Voice quality assessments can be used as indicators of treatment effectiveness in patients with LPR‐related symptoms.
Cochlear implant performance in children deafened by congenital cytomegalovirus—A systematic review
Authors: Kraaijenga V.J.C. , Van Houwelingen F. , Van der Horst S.F. , Visscher J. , Huisman J.M.L. , Hollman E.J. , Stegeman I. , Smit A.L. 
Published: May 2018

BackgroundCongenital cytomegalovirus (cCMV) infection is a major cause of sensorineural hearing loss in children.Objective of reviewThe objective of this systematic review was to compare performance in paediatric cochlear implant users with SNHL caused by cCMV compared to non‐cCMV implantees.Type of reviewSystematic reviewSearch strategyPubMed, EMBASE and the Cochrane databases were searched from inception up to 15 May 2017 for children, cochlear implant, performance and their synonyms.Evaluation methodsTitles, abstracts and full texts were screened for eligibility. Directness of evidence and risk of bias were assessed. From the included studies, study characteristics and outcome data (speech perception, speech production, receptive language and auditory performance of cCMV groups and non‐cCMV groups) were extracted.ResultsA total of 5280 unique articles were screened of which 28 were eligible for critical appraisal. After critical appraisal, 12 studies remained for data extraction. Seven of 12 studies showed worse performance after cochlear implantation in cCMV children compared to non‐cCMV children. Worse performance in cCMV children was attributed to cCMV‐related comorbidities in six of these studies. Available data on asymptomatic cCMV children compared to non‐cCMV children did not reveal an unfavourable effect on cochlear implant performance.ConclusionsThe available evidence reveals that cCMV children often have worse cochlear implant performance compared to non‐cCMV children, which can be attributed to cCMV related comorbidities. We urge physicians to take into account the cCMV related comorbidities in the counselling of paediatric CI users deafened by cCMV.
Management of early pouch‐related septic complications in ulcerative colitis: a systematic review
Authors: Worley G. H. T. , Segal J. P. , Warusavitarne J. , Clark S. K. , Faiz O. D. 
Published: May 2018

AbstractAimIt is well established that ileo‐anal pouch‐related septic complications (PRSC) increase the risk of pouch failure. There are a number of publications that describe the management of earlyPRSCin ulcerative colitis (UC) in small series. This article aims to systematically review and summarize the relevant current data on this subject and provide an algorithm for the management of earlyPRSC.MethodA systematic review was undertaken in accordance withPRISMAguidelines. Studies published between 2000 and 2017 describing the clinical management ofPRSCin patients withUCwithin 30 days of primary ileo‐anal pouch surgery were included. A qualitative analysis was undertaken due to the heterogeneity and quality of studies included.ResultsA total of 1157 abstracts and 266 full text articles were screened. Twelve studies were included for analysis involving a total of 207 patients. The studies described a range of techniques including image‐guided, endoscopic, surgical and endocavitational vacuum methods. Based on the evidence from these studies, an algorithm was created to guide the management of earlyPRSC.ConclusionThe results of this review suggest that although successful salvage of earlyPRSCis improving there is little information available relating to methods of salvage and outcomes. Novel techniques may offer an increased chance of salvage but comparative studies with longer follow‐up are required.
Further options for treating lipids in people with diabetes: targeting LDL‐cholesterol and beyond
Authors: Wierzbicki A. S. 
Published: May 2018

AbstractDiabetes is associated with increased cardiovascular disease (CVD) risk. Previous studies with statins have established that a 1 mmol/l reduction in LDL‐cholesterol reduces CVD events by 21% over 5 years in people with diabetes. More recently, trials in people with acute coronary syndromes showed that ezetimibe reduced CVD events by 6% at 5 years and achieved a LDL‐cholesterol of 1.6 mmol/l with better results in people with Type 2 diabetes. Several novel lipid‐lowering therapies have recently been developed. Most data have been accumulated with proprotein convertase subtilisin kexin‐9 (PCSK‐9) inhibitors, which reduce LDL‐cholesterol by 50–55%. A large CVD outcome trial with evolocumab, in which 40% of participants had diabetes, achieved a LDL‐cholesterol of 0.8 mmol/l and showed a consistent 20% relative risk reduction within 2 years, including in people with diabetes. Trials to increase HDL‐cholesterol using cholesterol ester transfer protein (CETP) inhibitors have generally underwhelmed. Although anacetrapib reduced coronary ischaemic events by 7% in a population with chronic CVD, more expansive CVD endpoints were not improved. The complex nature of CETP inhibitor trial outcomes means that these compounds are not being developed further. Trials targeting inflammation‐associated lipids have been generally unsuccessful but recent data on the interleukin‐1B receptor antagonist canakinumab have shown a reduction in acute coronary intervention, validating this target although at the cost of increased infections. The ability to achieve low LDL‐cholesterol with off‐patent medications and the costs of novel therapies will confine the use of novel agents to subgroups of people at highest risk of CVD.