bluuebunny/crossref_metadata_2025_split huggingface dataset:
Live cell evaluation of granzyme delivery and death receptor signaling in tumor cells targeted by human natural killer cells
Authors: Vrazo Alexandra C. , Hontz Adrianne E. , Figueira Sarah K. , Butler Braeden L. , Ferrell Julie M. , Binkowski Brock F. , Li Jinzhu , Risma Kimberly A. 
Published: June 2015

Key PointsNatural killer cell granzyme B, A, and K delivery and subsequent caspase activation is rapid after conjugation with tumor target cells. Natural killer cells also induce caspase activation through death receptor ligation that can be monitored in real time.
Correlation of mutation profile and response in patients with myelofibrosis treated with ruxolitinib
Authors: Patel Keyur P. , Newberry Kate J. , Luthra Rajyalakshmi , Jabbour Elias , Pierce Sherry , Cortes Jorge , Singh Rajesh , Mehrotra Meenakshi , Routbort Mark J. , Luthra Madan , Manshouri Taghi , Santos Fabio P. , Kantarjian Hagop , Verstovsek Srdan 
Published: June 2015

Key Points
In patients treated with ruxolitinib, harboring ≥3 mutations was inversely correlated with spleen response and time to treatment discontinuation. Multigene profiling may be useful for therapeutic planning.
New fixed point theorem under R-contractions
Authors: Roldán López de Hierro Antonio Francisco , Shahzad Naseer 
Published: June 2015

AbstractIn this manuscript we introduce the notions of R-function and R-contractions, and we show an ad hoc fixed point theorem. We prove that this new kind of contractions properly includes the family of all Meir-Keeler contractions and other well-known classes of contractions that have been given very recently (for instance, those using simulation functions and manageable functions). As a consequence, our approach turns out to be appropriate to unify the treatment of different kinds of contractive nonlinear operators.
The beta Marshall-Olkin family of distributions
Authors: Alizadeh Morad , Cordeiro Gauss M. , Brito Edleide de , B. Demétrio Clarice Garcia 
Published: June 2015

Abstract
We study general mathematical properties of a new generator of continuous distributions with three extra shape parameters called the beta Marshall-Olkin family. We present some special models and investigate the asymptotes and shapes. The new density function can be expressed as a mixture of exponentiated densities based on the same baseline distribution. We derive a power series for its quantile function. Explicit expressions for the ordinary and incomplete moments, quantile and generating functions, Bonferroni and Lorenz curves, Shannon and Rényi entropies and order statistics, which hold for any baseline model, are determined. We discuss the estimation of the model parameters by maximum likelihood and illustrate the flexibility of the family by means of two applications to real data. PACS 02.50.Ng, 02.50.Cw, 02.50.-r Mathematics Subject Classification (2010) 62E10, 60E05, 62P99
A randomized clinical trial of ascorbic acid in open abdominal aortic aneurysm repair
Authors: Duffy Martin J , O’Kane Cecilia M , Stevenson Michael , Young Ian S , Harkin Denis W , Mullan Brian A , McAuley Daniel F 
Published: June 2015

Abstract

Background
Open AAA repair is associated with ischaemia-reperfusion injury where systemic inflammation and endothelial dysfunction can lead to multiple organ injury including acute lung injury. Oxidative stress plays a role that may be inhibited by ascorbic acid.

Methods
A double blind, allocation concealed, randomized placebo-controlled trial was performed to test the hypothesis that a single bolus dose (2g) of intra-operative parenteral ascorbic acid would attenuate biomarkers of ischaemia-reperfusion injury in patients undergoing elective open AAA repair.

Results
Thirty one patients completed the study; 18 received placebo and 13 ascorbic acid. Groups were comparable demographically. Open AAA repair caused an increase in urinary Albumin:Creatinine Ratio (ACR) as well as plasma IL-6 and IL-8. There was a decrease in exhaled breath pH and oxygenation. Lipid hydroperoxides were significantly higher in the ascorbic acid group following open AAA repair. There were no other differences between the ascorbic acid or placebo groups up to 4 hours after removal of the aortic clamping.

Conclusions
Open AAA repair caused an increase in markers of systemic endothelial damage and systemic inflammation. Administration of 2g parenteral ascorbic acid did not attenuate this response and with higher levels of lipid hydroperoxides post-operatively a pro-oxidant effect could not be excluded.

Trial registration

ISRCTN27369400
Early Relapse of Follicular Lymphoma After Rituximab Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Defines Patients at High Risk for Death: An Analysis From the National LymphoCare Study
Authors: Casulo Carla , Byrtek Michelle , Dawson Keith L. , Zhou Xiaolei , Farber Charles M. , Flowers Christopher R. , Hainsworth John D. , Maurer Matthew J. , Cerhan James R. , Link Brian K. , Zelenetz Andrew D. , Friedberg Jonathan W. 
Published: June 2015

Purpose Twenty percent of patients with follicular lymphoma (FL) experience progression of disease (POD) within 2 years of initial chemoimmunotherapy. We analyzed data from the National LymphoCare Study to identify whether prognostic FL factors are associated with early POD and whether patients with early POD are at high risk for death. Patients and Methods In total, 588 patients with stage 2 to 4 FL received first-line rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Two groups were defined: patients with early POD 2 years or less after diagnosis and those without POD within 2 years, the reference group. An independent validation set, 147 patients with FL who received first-line R-CHOP, was analyzed for reproducibility. Results Of 588 patients, 19% (n = 110) had early POD, 71% (n = 420) were in the reference group, 8% (n = 46) were lost to follow-up, and 2% (n = 12) died without POD less than 2 years after diagnosis. Five-year overall survival was lower in the early-POD group than in the reference group (50% v 90%). This trend was maintained after we adjusted for FL International Prognostic Index (hazard ratio, 6.44; 95% CI, 4.33 to 9.58). Results were similar for the validation set (FL International Prognostic Index–adjusted hazard ratio, 19.8). Conclusion In patients with FL who received first-line R-CHOP, POD within 2 years after diagnosis was associated with poor outcomes and should be further validated as a standard end point of chemoimmunotherapy trials of untreated FL. This high-risk FL population warrants further study in directed prospective clinical trials.
Mapisal Versus Urea Cream as Prophylaxis for Capecitabine-Associated Hand-Foot Syndrome: A Randomized Phase III Trial of the AIO Quality of Life Working Group
Authors: Hofheinz Ralf-Dieter , Gencer Deniz , Schulz Holger , Stahl Michael , Hegewisch-Becker Susanna , Loeffler Luisa Mantovani , Kronawitter Ursula , Bolz Georg , Potenberg Jochem , Tauchert Felix , Al-Batran Salah-Eddin , Schneeweiss Andreas 
Published: June 2015

Purpose Hand-foot syndrome (HFS) is a frequently occurring adverse event associated with anticancer drugs. This study compares a newly introduced ointment containing several antioxidants and exhibiting high radical protection factor, which has been available on the German market since 2011, with urea cream for prevention of HFS in patients treated with capecitabine. Patients and Methods Patients with GI tumors or breast cancer treated with capecitabine were included in this randomized phase III study. The primary end point was prevention of HFS of any grade within 6 weeks of treatment as indicated by a standardized patient diary. The study had 80% power to show a 20% reduction of the incidence of HFS with the new ointment. Secondary end points included time to development of HFS greater than grade 1, evaluation of capecitabine dose intensity, and quality of life analyses. Results A total of 152 patients were evaluable. In total, 47 of 152 patients experienced HFS (30.9%), 39.5% with the new ointment and 22.4% in the urea arm (stratified odds ratio, 2.37; P = .02). Time to HFS greater than grade 1 was comparable, but time to any-grade HFS was significantly longer in the urea group (P = .03). Capecitabine dose intensity, time under study, and percentage of days with correct administration of study medication were identical, as were adverse events except for HFS. Skin-related quality of life was significantly worse in the group treated with the new ointment at the end of study treatment. Conclusion This trial demonstrated that 10% urea cream was superior to the new ointment at preventing HFS over the first 6 weeks of treatment with capecitabine.
Addressing Pricing Power in Integrated Delivery: The Limits of Antitrust
Authors: Berenson Robert 
Published: June 2015

Abstract
Prices are the major driver of why the United States spends so much more on health care than other countries do. The pricing power that hospitals have garnered recently has resulted from consolidated delivery systems and concentrated markets, leading to enhanced negotiating leverage. But consolidation may be the wrong frame for viewing the problem of high and highly variable prices; many “must-have” hospitals achieve their pricing power from sources other than consolidation, for example, reputation. Further, the frame of consolidation leads to unrealistic expectations for what antitrust's role in addressing pricing power should be, especially because in the wake of two periods of merger “manias” and “frenzies” many markets already lack effective competition. It is particularly challenging for antitrust to address extant monopolies lawfully attained. New payment and delivery models being pioneered in Medicare, especially those built around accountable care organizations (ACOs), offer an opportunity to reduce pricing power, but only if they are implemented with a clear eye on the impact on prices in commercial insurance markets. This article proposes approaches that public and private payers should consider to complement the role of antitrust to assure that ACOs will actually help control costs in commercial markets as well as in Medicare and Medicaid.
Antitrust and Provider Collaborations: Where We've Been and What Should Be Done Now
Authors: Leibenluft Robert F. 
Published: June 2015

Abstract
Antitrust enforcement has a crucial role to play in consolidated health care markets as providers undertake mergers, acquisitions, and other types of collaborations to integrate care and achieve greater size and scale. But antitrust enforcers and policy makers need to refine their approach in two fundamental ways. First, in addition to focusing on whether particular transactions or conduct will increase prices above competitive levels, a more pressing concern should be on assuring that health care markets are conducive to fundamental changes in how care is reimbursed and delivered — that is, the impact on payment and health care delivery innovation. Second, it is important to recognize the practical limits that apply to antitrust enforcement, both in terms of existing law and precedent and the constrained resources available to government enforcers. Government resources can be leveraged substantially through greater collaboration among federal and state antitrust enforcers, government payers, health care regulators, and economists and other policy makers. This can result in not only better-targeted antitrust enforcement actions but also payment and regulatory initiatives that can produce better-functioning and more competitive health care markets.
Case Report: Stevens-Johnson syndrome following a single double dosing of nevirapine-containing regimen once in an HIV-infected woman on long-term antiretroviral therapy.
Authors: Kakande Betty , Isaacs Thuraya , Muloiwa Rudzani , Dlamini Sipho , Lehloenya Rannakoe 
Published: June 2015

A 31-year old HIV-infected African woman on nevirapine, tenofovir and lamivudine for more than 4 years presented with an 8-day history of symptoms and signs of Stevens-Johnson syndrome. She was on no other medication. Her viral load was undetectable and she had maintained a CD4 count of between 356 and 387cells/mm3 in the preceding 2½ years. She missed her antiretrovirals 10 days before the onset of her symptoms and subsequently doubled her daily dose the following day. She had been on no other medication in the preceding 8 weeks.Her ARVs were stopped and she fully re-epithelialized with the exception of the lips, over the following 10 days. She was started on a daily single tablet of Odimune® (a fixed drug combination antiretroviral containing tenofovir, emtricitabine and efavirenz).Nevirapine is the most common offender in cases of antiretroviral-associated SJS in published literature. Lamivudine is very rarely implicated while there are no similar reports with tenofovir. We concluded that nevirapine was by far the most likely offender in this case. Nevirapine toxicity is associated with high CD4 counts, undetectable viral load and high drug plasma level. We postulate that the sudden increase of the plasma levels of nevirapine in a patient with a high CD4 count and undetectable viral load created a perfect storm for the development of SJS in our patient, who had been on the NVP-containing regimen for many years.Clinicians should be aware that severe adverse drug reactions are dynamic and can occur even when the drug has been in use for a long time.
Impingement-free range of movement, acetabular component cover and early clinical results comparing ‘femur-first’ navigation and ‘conventional’ minimally invasive total hip arthroplasty
Authors: Renkawitz T. , Weber M. , Springorum H-R. , Sendtner E. , Woerner M. , Ulm K. , Weber T. , Grifka J. 
Published: June 2015

We report the kinematic and early clinical results of a patient- and observer-blinded randomised controlled trial in which CT scans were used to compare potential impingement-free range of movement (ROM) and acetabular component cover between patients treated with either the navigated ‘femur-first’ total hip arthroplasty (THA) method (n = 66; male/female 29/37, mean age 62.5 years; 50 to 74) or conventional THA (n = 69; male/female 35/34, mean age 62.9 years; 50 to 75). The Hip Osteoarthritis Outcome Score, the Harris hip score, the Euro-Qol-5D and the Mancuso THA patient expectations score were assessed at six weeks, six months and one year after surgery. A total of 48 of the patients (84%) in the navigated ‘femur-first’ group and 43 (65%) in the conventional group reached all the desirable potential ROM boundaries without prosthetic impingement for activities of daily living (ADL) in flexion, extension, abduction, adduction and rotation (p = 0.016). Acetabular component cover and surface contact with the host bone were > 87% in both groups. There was a significant difference between the navigated and the conventional groups’ Harris hip scores six weeks after surgery (p = 0.010). There were no significant differences with respect to any clinical outcome at six months and one year of follow-up. The navigated ‘femur-first’ technique improves the potential ROM for ADL without prosthetic impingement, although there was no observed clinical difference between the two treatment groups.Cite this article: Bone Joint J 2015; 97-B:890–8.
A new classification of peri-articular heterotopic ossification of the hip associated with neurological injury
Authors: Arduini M. , Mancini F. , Farsetti P. , Piperno A. , Ippolito E. 
Published: June 2015

In this paper we propose a new classification of neurogenic peri-articular heterotopic ossification (HO) of the hip based on three-dimensional (3D) CT, with the aim of improving pre-operative planning for its excision. A total of 55 patients (73 hips) with clinically significant HO after either traumatic brain or spinal cord injury were assessed by 3D-CT scanning, and the results compared with the intra-operative findings. At operation, the gross pathological anatomy of the HO as identified by 3D-CT imaging was confirmed as affecting the peri-articular hip muscles to a greater or lesser extent. We identified seven patterns of involvement: four basic (anterior, medial, posterior and lateral) and three mixed (anteromedial, posterolateral and circumferential). Excellent intra- and inter-observer agreement, with kappa values > 0.8, confirmed the reproducibility of the classification system. We describe the different surgical approaches used to excise the HO which were guided by the 3D-CT findings. Resection was always successful. 3D-CT imaging, complemented in some cases by angiography, allows the surgeon to define the 3D anatomy of the HO accurately and to plan its surgical excision with precision. Cite this article: Bone Joint J 2015; 97-B:899–904.
RhBMP-7 for the treatment of nonunion of fractures of long bones
Authors: Papanagiotou M. , Dailiana Z. H. , Karachalios T. , Varitimidis S. , Vlychou M. , Hantes M. , Malizos K. N. 
Published: June 2015

We report the outcome of 84 nonunions involving long bones which were treated with rhBMP-7, in 84 patients (60 men: 24 women) with a mean age 46 years (18 to 81) between 2003 and 2011. The patients had undergone a mean of three previous operations (one to 11) for nonunion which had been present for a mean of 17 months (4 months to 20 years). The nonunions involved the lower limb in 71 patients and the remainder involved the upper limb. A total of 30 nonunions were septic. Treatment was considered successful when the nonunion healed without additional procedures. The relationship between successful union and the time to union was investigated and various factors including age and gender, the nature of the nonunion (location, size, type, chronicity, previous procedures, infection, the condition of the soft tissues) and type of index procedure (revision of fixation, type of graft, amount of rhBMP-7) were analysed. The improvement of the patients’ quality of life was estimated using the Short Form (SF) 12 score.A total of 68 nonunions (80.9%) healed with no need for further procedures at a mean of 5.4 months (3 to 10) post-operatively. Multivariate logistic regression analysis of the factors affecting union suggested that only infection significantly affected the rate of union (p = 0.004).Time to union was only affected by the number of previous failed procedures (p = 0.006). An improvement of 79% and 32.2% in SF-12 physical and mental score, respectively, was noted within the first post-operative year.Rh-BMP-7 combined with bone grafts, enabled healing of the nonunion and improved quality of life in about 80% of patients. Aseptic nonunions were much more likely to unite than septic ones. The number of previous failed operations significantly delayed the time to union.Cite this article: Bone Joint J 2015;97-B:997–1003.
An alternative to a randomised control design for assessing the efficacy and effectiveness of bracing in adolescent idiopathic scoliosis
Authors: Fong D. Y. T. , Cheung K. M. C. , Wong Y. W. , Cheung W. Y. , Fu I. C. Y. , Kuong E. E. , Mak K. C. , To M. , Samartzis D. , Luk K. D. K. 
Published: June 2015

Randomised controlled trials (RCTs) that assessed the efficacy of bracing for adolescent idiopathic scoliosis have suffered from small sample sizes, low compliance and lack of willingness to participate. The aim of this study was to assess the feasibility of a comprehensive cohort study for evaluating both the efficacy and the effectiveness of bracing in patients with adolescent idiopathic scoliosis. Patients with curves at greater risk of progression were invited to join a randomised controlled trial. Those who declined were given the option to remain in the study and to choose whether they wished to be braced or observed. Of 87 eligible patients (5 boys and 63 girls) identified over one year, 68 (78%) with mean age of 12.5 years (10 to 15) consented to participate, with a mean follow-up of 168 weeks (0 to 290). Of these, 19 (28%) accepted randomisation. Of those who declined randomisation, 18 (37%) chose a brace. Patients who were more satisfied with their image were more likely to choose bracing (Odds Ratio 4.1; 95% confidence interval 1.1 to 15.0; p = 0.035). This comprehensive cohort study design facilitates the assessment of both efficacy and effectiveness of bracing in patients with adolescent idiopathic scoliosis, which is not feasible in a conventional randomised controlled trial. Cite this article: Bone Joint J 2015; 97-B:973–81
Frozen shoulder after simple arthroscopic shoulder procedures
Authors: Evans J. P. , Guyver P. M. , Smith C. D. 
Published: June 2015

Frozen shoulder is a recognised complication following simple arthroscopic shoulder procedures, but its exact incidence has not been reported. Our aim was to analyse a single-surgeon series of patients undergoing arthroscopic subacromial decompression (ASD; group 1) or ASD in combination with arthroscopic acromioclavicular joint (ACJ) excision (group 2), to establish the incidence of frozen shoulder post-operatively. Our secondary aim was to identify associated risk factors and to compare this cohort with a group of patients with primary frozen shoulder. We undertook a retrospective analysis of 200 consecutive procedures performed between August 2011 and November 2013. Group 1 included 96 procedures and group 2 104 procedures. Frozen shoulder was diagnosed post-operatively using the British Elbow and Shoulder Society criteria. A comparative group from the same institution involved 136 patients undergoing arthroscopic capsular release for primary idiopathic frozen shoulder. The incidence of frozen shoulder was 5.21% in group 1 and 5.71% in group 2. Age between 46 and 60 years (p = 0.002) and a previous idiopathic contralateral frozen shoulder (p < 0.001) were statistically significant risk factors for the development of secondary frozen shoulder. Comparison of baseline characteristics against the comparator groups showed no statistically significant differences for age, gender, diabetes and previous contralateral frozen shoulder. These results suggest that the risk of frozen shoulder following simple arthroscopic procedures is just over 5%, with no increased risk if the ACJ is also excised. Patients aged between 46 and 60 years and a previous history of frozen shoulder increase the relative risk of secondary frozen shoulder by 7.8 (95% confidence interval (CI) 2.1 to 28.3)and 18.5 (95% CI 7.4 to 46.3) respectively. Cite this article: Bone Joint J 2015; 97-B:963–6.
Hip fracture surgery
Authors: Fernandez M. A. , Griffin X. L. , Costa M. L. 
Published: June 2015

Hip fracture is a common injury associated with high mortality, long-term disability and huge socio-economic burden. Yet there has been relatively little research into best treatment, and evidence that has been generated has often been criticised for its poor quality. Here, we discuss the advances made towards overcoming these criticisms and the future directions for hip fracture research: how co-ordinating existing national infrastructures and use of now established clinical research networks will likely go some way towards overcoming the practical and financial challenges of conducting large trials. We highlight the importance of large collaborative pragmatic trials to inform decision/policy makers and the progress made towards reaching a consensus on a core outcome set to facilitate data pooling for evidence synthesis and meta-analysis. These advances and future directions are a priority in order to establish the high-quality evidence base required for this important group of patients. Cite this article: Bone Joint J 2015;97-B:875–9.