bluuebunny/crossref_metadata_2025_split huggingface dataset:
Predicting survival in patients with advanced cancer in the last weeks of life: How accurate are prognostic models compared to clinicians’ estimates?
Authors: Hui David , Ross Jeremy , Park Minjeong , Dev Rony , Vidal Marieberta , Liu Diane , Paiva Carlos Eduardo , Bruera Eduardo 
Published: September 2019

Background: It is unclear if validated prognostic scores such as the Palliative Performance Scale, Palliative Prognostic Index, and Palliative Prognostic Score are more accurate than clinician prediction of survival in patients admitted to an acute palliative care unit with only days of survival. Aim: We compared the prognostic accuracy of Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival in this setting. Design: This is a pre-planned secondary analysis of a prospective study. Setting/participants: We assessed Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival at baseline. We computed their prognostic accuracy using the Concordance index and area under the receiver operating characteristics curve for 7-, 14-, and 30-day survival. Results: A total of 204 patients were included with a median overall survival of 10 days (95% confidence interval: 8–11 days). The Concordance index for Palliative Performance Scale, Palliative Prognostic Index, Palliative Prognostic Score, and clinician prediction of survival were 0.74, 0.71, 0.70, and 0.75, respectively. The areas under the curve for these approaches were 0.82–0.87 for 30-day survival, 0.75–0.80 for 14-day survival, and 0.74–0.81 for 7-day survival. The four prognostic approaches had similar accuracies, with the exception of 7-day survival in which clinician prediction of survival was significantly more accurate than Palliative Prognostic Score (difference: 7%) and Palliative Prognostic Index (difference: 8%). Conclusion: In patients with advanced cancer with days of survival, clinician prediction of survival and Palliative Performance Scale alone were as accurate as Palliative Prognostic Score and Palliative Prognostic Index. These four approaches may be useful for prognostication in acute palliative care units. Our findings highlight how patient population may impact the accuracy of prognostic scores.
Specialist palliative care services for older people in primary care: A systematic review using narrative synthesis
Authors: de Nooijer Kim , Penders Yolanda WH , Pivodic Lara , Van Den Noortgate Nele J , Pype Peter , Van den Block Lieve 
Published: September 2019

Background: There is recognition that older people with incurable conditions should have access to specialist palliative care services. However, it remains unclear which activities and outcomes these services entail for older people in primary care and to which patients they are provided. Aim: The aim of this review was to identify the criteria for referral to specialist services; who provides specialist palliative care; through which activities and with which frequency; which outcomes are reported; and which suggestions are made to improve services. Design: Systematic review of the literature and narrative synthesis. Quality appraisal and selection of studies were performed independently by two researchers. Participant characteristics, intervention features, outcome data and suggestions for improvement were retrieved. Data sources: Embase, Medline, Web of Science, Cochrane, Google Scholar, PsycINFO and CINAHL EBSCO databases (until June 2019). Results: Ten eligible articles, three qualitative, three quantitative, three mixed-method and one narrative review, were identified. Referral criteria were mainly based on patient characteristics such as diagnosis. The specialist services involved a variety of activities and outcomes and descriptions were often lacking. Services could be improved regarding the information flow between healthcare professionals, greater in-depth palliative care knowledge for case managers and social workers, identification of a key worker and support for family carers. Conclusion: The limited evidence available shows areas for improvement of the quality of and access to specialist services for older people, such as support for family carers. In addition, this review underscores the need for comprehensive reporting of interventions and the use of consensus-based outcome measures.
Exosomes Isolated From Adipose-Derived Stem Cells: A New Cell-Free Approach to Prevent the Muscle Degeneration Associated With Torn Rotator Cuffs
Authors: Wang Chongyang , Song Wei , Chen Bi , Liu Xudong , He Yaohua 
Published: September 2019

Background: Fatty infiltration, inflammation, and apoptosis are common degenerative changes in patients with chronic rotator cuff tears that can lead to muscle atrophy and can even result in massive irreparable rotator cuff tears. Some data have demonstrated the proregenerative, anti-inflammatory, and anti-apoptotic properties of stem cell–derived exosomes in some orthopaedic disorders, but their effect on torn rotator cuff muscles has never been investigated. Purpose: To study the effect of exosomes isolated from human adipose-derived stem cells (ASCs-Exos) on muscle degeneration, regeneration, and biomechanical properties in a rat model of a massive rotator cuff tear (MRCT). Study Design: Controlled laboratory study. Methods: A bilateral supraspinatus and infraspinatus tenotomy was performed on rats to create an MRCT model. Forty-two rats were randomly assigned to 3 groups: the sham surgery group, the saline group (lesions treated with a saline injection), and the ASCs-Exos group (lesions treated with an ASCs-Exos injection). Wet muscle weight, fatty infiltration, inflammation, vascularization, regeneration, and biomechanical properties were evaluated at 8 and 16 weeks after surgery. Results: The results revealed that the ASCs-Exos treatment could prevent the atrophy, fatty infiltration, inflammation, and vascularization of muscles in the MRCT model ( P < .001). Additionally, the myofiber regeneration and biomechanical properties of ASCs-Exos-treated rotator cuffs were significantly elevated compared with those in the saline-treated group ( P < .001). Conclusion: This study demonstrates that ASCs-Exos can effectively decrease atrophy and degeneration and improve muscle regeneration and biomechanical properties in torn rotator cuff muscles. Clinical Relevance: ASCs-Exos can be used as a new cell-free approach to prevent the muscle degeneration associated with torn rotator cuffs and may be helpful to repair torn rotator cuffs. Nevertheless, further work needs to be done in a large animal model owing to the inherent regenerative potential possessed by rodents.
Blended collaborative care in the secondary prevention of coronary heart disease improves risk factor control: Results of a randomised feasibility study
Authors: Bosselmann Lena , Fangauf Stella V , Herbeck Belnap Birgit , Chavanon Mira-Lynn , Nagel Jonas , Neitzel Claudia , Schertz Anna , Hummers Eva , Wachter Rolf , Herrmann-Lingen Christoph 
Published: September 2019

Background: Risk factor control is essential in limiting the progression of coronary heart disease, but the necessary active patient involvement is often difficult to realise, especially in patients suffering psychosocial risk factors (e.g. distress). Blended collaborative care has been shown as an effective treatment addition, in which a (non-physician) care manager supports patients in implementing and sustaining lifestyle changes, follows-up on patients, and integrates care across providers, targeting both, somatic and psychosocial risk factors. Aims: The aim of this study was to test the feasibility, acceptance and effect of a six-month blended collaborative care intervention in Germany. Methods: For our randomised controlled pilot study with a crossover design we recruited coronary heart disease patients with ⩾1 insufficiently controlled cardiac risk factors and randomised them to either immediate blended collaborative care intervention (immediate intervention group, n=20) or waiting control (waiting control group, n=20). Results: Participation rate in the intervention phase was 67% ( n=40), and participants reported high satisfaction ( M=1.63, standard deviation=0.69; scale 1 (very high) to 5 (very low)). The number of risk factors decreased significantly from baseline to six months in the immediate intervention group ( t(60)=3.07, p=0.003), but not in the waiting control group t(60)=−0.29, p=0.77). Similarly, at the end of their intervention following the six-month waiting period, the waiting control group also showed a significant reduction of risk factors ( t(60)=3.88, p<0.001). Conclusion: This study shows that blended collaborative care can be a feasible, accepted and effective addition to standard medical care in the secondary prevention of coronary heart disease in the German healthcare system.
Reduced serum immunoglobulin G concentrations in multiple sclerosis: prevalence and association with disease-modifying therapy and disease course
Authors: Zoehner Greta , Miclea Andrei , Salmen Anke , Kamber Nicole , Diem Lara , Friedli Christoph , Bagnoud Maud , Ahmadi Farhad , Briner Myriam , Sédille-Mostafaie Nazanin , Kilidireas Constantinos , Stefanis Leonidas , Chan Andrew , Hoepner Robert , Evangelopoulos Maria Eleftheria 
Published: September 2019

Background: In multiple sclerosis (MS), the frequency of hypogammaglobulinemia is unknown. We aimed to evaluate the frequency of reduced immunoglobulin (Ig) concentrations and its association with immunotherapy and disease course in two independent MS cohorts. Methods: In our retrospective cross-sectional study, MS patients and control patients with head or neck pain from Bern University Hospital (Bern, Switzerland) and Eginition University Hospital (Athens, Greece) were included. The lower limits of normal (LLN) for serum Ig concentration were IgG < 700 mg/dl, IgM < 40 mg/dl, and IgA < 70 mg/dl. Mann–Whitney U test, analysis of variance test, and multiple linear regression analysis were employed. Results: In total, 327 MS patients were retrospectively identified (Bern/Athens: n = 226/101). Serum IgG concentrations were frequently under LLN in both MS cohorts (Bern/Athens: 15.5%/14.9%), even when considering only untreated patients (Bern/Athens: 7.9%/8.6%). MS patients ( n = 327) were significantly more likely to have IgG concentrations below LLN and below 600 mg/dl in comparison with controls ( n = 58) ( p = 0.015 and 0.047, respectively). Between both patient groups, no significant differences were found in frequencies of IgA and IgM concentrations under LLN [ n (MS patients/controls): IgA 203/30, IgM 224/24]. Independently of age, secondary progressive MS patients had lower IgG concentrations than relapsing–remitting and primary progressive patients (both: p ⩽ 0.01). After adjusting for sex, age, and disease course, IgG concentrations were lower in patients treated with rituximab ( p = 0.001; n = 42/327), intravenous corticosteroids ( p < 0.001; n = 16/327), natalizumab ( p < 0.001; n = 48/327), and fingolimod ( p = 0.003; n = 6/327). Conclusion: Our study demonstrated high prevalence rates of reduced serum IgG concentrations in MS patients with and without disease-modifying treatments. The significance of lower IgG concentrations at the levels noted is unclear considering that infections or interference with antibody production generally occur when IgG levels are much lower, at or below 400 mg/dl. However, the information is useful to monitor IgG levels especially with anti-B-cell therapies and consider IgG substitution when levels drop below 400 mg/dl.
Syndrome of inappropriate anti-diuretic hormone secretion in cancer patients: results of the first multicenter Italian study
Authors: Berardi Rossana , Mastroianni Candida , Lo Russo Giuseppe , Buosi Roberta , Santini Daniele , Montanino Agnese , Carnaghi Carlo , Tiseo Marcello , Chiari Rita , Camerini Andrea , Barni Sandro , De Marino Valeria , Ferrari Daris , Cristofano Antonella , Doni Laura , Freddari Federica , Fumagalli Daniele , Portalone Luigi , Sarmiento Roberta , Schinzari Giovanni , Sperandi Francesca , Tucci Marcello , Inno Alessandro , Ciuffreda Libero , Mariotti Marita , Mariani Cinzia , Caramanti Miriam , Torniai Mariangela , Gallucci Rosaria , Bennati Chiara , Bordi Paola , Buffoni Lucio , Galeassi Achille , Ghidini Michele , Grossi Emidio , Morabito Alessandro , Vincenzi Bruno , Arvat Emanuela 
Published: September 2019

Background: Hyponatremia in cancer patients is often caused by the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The aim of this observational multicenter study was to analyze the medical and economic implications of SIADH in this setting. Methods: This study included 90 oncological patients from 28 Italian institutions that developed SIADH between January 2010 and September 2015. Data on clinical–pathological characteristics, anticancer therapies, hyponatremia, and related treatments were statistically analyzed. Results: The majority were lung cancer patients (73%) with metastatic disease at the onset of hyponatremia (83%). A total of 76 patients (84%) were hospitalized because of SIADH and less than half (41%) received tolvaptan for SIADH treatment. The duration of hospitalization was significantly longer in patients who did not receive tolvaptan and in those who do not reach sodium normalization during hospitalization. Patients who experienced a second episode of hyponatremia following tolvaptan dose modification/discontinuation presented a significantly lower serum sodium value at the time of hospitalization and minimum sodium value during hospitalization compared with patients who had not experienced another episode. The severity of hyponatremia, defined as minimum sodium value during hospitalization with a cut-off value of 110 mmol/l, and not obtaining sodium correction during hospitalization significantly correlated with overall survival rate. Conclusions: Hyponatremia due to SIADH could result in longer hospitalization and in a decreased overall survival when not adequately treated, and tolvaptan represents an effective treatment with a potential effect of both improving overall survival and decreasing duration of hospitalization.
BZD9L1 sirtuin inhibitor as a potential adjuvant for sensitization of colorectal cancer cells to 5-fluorouracil
Authors: Tan Yi Jer , Lee Yeuan Ting , Petersen Sven H. , Kaur Gurjeet , Kono Koji , Tan Soo Choon , Majid Amin M. S. Abdul , Oon Chern Ein 
Published: September 2019

Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC). Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry. Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC. Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.
Capacity of Infusion Lines for Insulin Adsorption: Effect of Flow Rate on Total Adsorption
Authors: Knopp Jennifer L. , Bishop Kaia , Lerios Theodore , Chase J. Geoffrey 
Published: September 2019

Background: Insulin adsorption to clinical materials has been well observed, but not well quantified. Insulin adsorption reduces expected and actual insulin delivery and is unaccounted for in insulin therapy or glycemic control. It may thus contribute to poor control and high glycemic variability. This research quantifies the problem in the context of clinical use. Method: Experimental insulin adsorption data from literature is used to calculate insulin delivery and total insulin adsorption capacities for polyethylene (PE) and polyvinal chloride (PVC) lines at clinically relevant flow rates and concentrations. Results: Insulin adsorption capacity decreased hyperbolically with flow rate for both PE and PVC, where low flow scenarios result in greater insulin adherence to infusion lines. When the infusion flow rate was halved from 1 to 0.5 mL/h, twice as much insulin adsorbed to the line. Insulin loss to adsorption resulted in up to ~50% of intended insulin not delivered over 24 hours in a low flow and low concentration context. Conclusion: Material capacity for insulin adsorption is not constant, but increases with decreasing flow. Different materials have different adsorption capacities. In low flow and low concentration contexts, such as in neonatal or pediatric intensive care, insulin loss to adsorption represents a significant proportion of daily insulin delivery, which needs to be accounted for.
Is e-cigarette use associated with coronary heart disease and myocardial infarction? Insights from the 2016 and 2017 National Health Interview Surveys
Authors: Farsalinos Konstantinos E , Polosa Riccardo , Cibella Fabio , Niaura Raymond 
Published: September 2019

Background: This study analyzed the National Health Interview Surveys (NHIS) of 2016 ( n = 33,028) and 2017 ( n = 26,742) to examine whether e-cigarette use is consistently associated with myocardial infarction (MI) and coronary heart disease (CHD). Methods: Surveys were examined separately and pooled. Logistic regression analysis was used, with demographics, e-cigarette use, smoking and risk factors for CHD (hypertension, hypercholesterolemia, and diabetes) being independent variables. Former smokers were subclassified according to quit duration (⩽ 6 and > 6 years). Results: For MI, an association was observed with some days e-cigarette (but not daily) use in the 2017 survey (OR: 2.11, 95% CI: 1.14–3.88, p = 0.017). No statistically significant association was observed in the pooled analysis (daily e-cigarette use: OR: 1.35, 95% CI: 0.80–2.27, p = 0.267). For CHD, an association was observed with daily e-cigarette use in the 2016 survey (OR: 1.89, 95% CI: 1.01–3.53, p = 0.047). From the pooled analysis, no association was found between any pattern of e-cigarette use and CHD. In single-year and pooled analysis, both MI and CHD were strongly associated with all patterns of smoking, hypertension, hypercholesterolemia, diabetes, and age. Conclusions: The pooled analysis of the 2016 and 2017 NHIS showed no association between e-cigarette use and MI or CHD. The associations between established risk factors, including smoking, and both conditions were remarkably consistent. The inconsistent associations observed in single-year surveys and the cross-sectional design of the NHIS cannot substantiate any link between e-cigarette use and an elevated risk for MI or CHD. Longitudinal studies are needed to explore the effects of e-cigarette use on cardiovascular disease.
The effect of guideline revisions on vascular complications of type 2 diabetes
Authors: Heijmans Ralph , Singh Sunny S. , Lieverse Aloysius G. , Sijbrands Eric J.G. , van Hoek Mandy 
Published: September 2019

Background: The aim of this study was to investigate the impact of implementation and revision of the ‘Diabetes Mellitus type II’ guideline by the Dutch College of General Practitioners (DCGP) on the prevalence and incidence of macrovascular and microvascular complications. Methods: The DiaGene study is a case-control study ( n = 1886 patients of type 2 diabetes) with extensive, retrospectively collected complication data, as well as prospective follow up of complications. The study incorporates all lines of diabetes care. Cases were divided into categories according to the date of onset of diabetes and publication dates of the DCGP. Logistic regression models were used to investigate the associations between guideline version and complications. To investigate a possible trend between guideline version and complications, the ‘guideline category’ was also used as a continuous variable. All models were adjusted for clinical covariables. Results: The 1999 and 2006 guidelines versions were associated with significantly lower risk of retinopathy than the group that started without a guideline [OR 0.32 (95% CI 0.14–0.72, p = 0.006) and 0.31 (95% CI 0.11–0.91, p = 0.034), respectively]. A significant trend in reduction of peripheral artery disease (PAD) over the guideline versions was found, adjusted for age, sex and diabetes duration (odds ratio (OR) 0.70, 95% CI 0.51-0.97, p trend = 0.029) and for retinopathy in all models (OR = 0.52, 95% CI 0.37-0.73, p trend < 0.001). Conclusions: The introduction of the first diabetes guideline and subsequent revisions have reduced the risk of macrovascular and microvascular complications of type 2 diabetes, most strongly in diabetic retinopathy. This indicates that real-time diabetes care has improved over time.
Catalytic dysregulation of SHP2 leading to Noonan syndromes affects platelet signaling and functions
Authors: Bellio Marie , Garcia Cédric , Edouard Thomas , Voisin Sophie , Neel Benjamin G. , Cabou Cendrine , Valet Philippe , Mori Jun , Mazharian Alexandra , Senis Yotis A. , Yart Armelle , Payrastre Bernard , Severin Sonia 
Published: September 2019

Abstract
Src homology 2 domain–containing phosphatase 2 (SHP2), encoded by the PTPN11 gene, is a ubiquitous protein tyrosine phosphatase that is a critical regulator of signal transduction. Germ line mutations in the PTPN11 gene responsible for catalytic gain or loss of function of SHP2 cause 2 disorders with multiple organ defects: Noonan syndrome (NS) and NS with multiple lentigines (NSML), respectively. Bleeding anomalies have been frequently reported in NS, but causes remain unclear. This study investigates platelet activation in patients with NS and NSML and in 2 mouse models carrying PTPN11 mutations responsible for these 2 syndromes. Platelets from NS mice and patients displayed a significant reduction in aggregation induced by low concentrations of GPVI and CLEC-2 agonists and a decrease in thrombus growth on a collagen surface under arterial shear stress. This was associated with deficiencies in GPVI and αIIbβ3 integrin signaling, platelet secretion, and thromboxane A2 generation. Similarly, arterial thrombus formation was significantly reduced in response to a local carotid injury in NS mice, associated with a significant increase in tail bleeding time. In contrast, NSML mouse platelets exhibited increased platelet activation after GPVI and CLEC-2 stimulation and enhanced platelet thrombotic phenotype on collagen matrix under shear stress. Blood samples from NSML patients also showed a shear stress–dependent elevation of platelet responses on collagen matrix. This study brings new insights into the understanding of SHP2 function in platelets, points to new thrombopathies linked to platelet signaling defects, and provides important information for the medical care of patients with NS in situations involving risk of bleeding.