bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prevalence of Vitamin D Deficiency in Patients With Foot and Ankle Injuries
Authors: Smith Jeremy T. , Halim Kareem , Palms David A. , Okike Kanu , Bluman Eric M. , Chiodo Christopher P. 
Published: October 2013

Background: Vitamin D deficiency has been identified as one of the most common causes of fragility fractures and poor fracture healing. Although rates of vitamin D deficiency have been delineated in various orthopaedic populations, little is known about the prevalence of vitamin D deficiency in patients with foot and ankle disorders. The goal of this study was to identify the prevalence of vitamin D deficiency in patients with a low energy fracture of the foot or ankle. Methods: Over a 6-month period, a serum 25-OH vitamin D level was obtained from consecutive patients with a low energy ankle fracture, fifth metatarsal base fracture, or stress fracture of the foot or ankle. For comparative purposes, vitamin D levels in patients with an ankle sprain and no fracture were also examined. Results: The study cohort included 75 patients, of which 21 had an ankle fracture, 23 had a fifth metatarsal base fracture, and 31 had a stress fracture. The mean age was 52 (range, 16–80) years. Thirty-five of the fracture patients (47%) had an insufficient vitamin D level (below the recommended level of 30 ng/mL), and 10 of the patients (13%) had a level that was deficient (< 20 ng/mL). Vitamin D levels were significantly lower in those with a fracture than in those with an ankle sprain ( P = .02). In the fracture cohort, the factors significantly associated with vitamin D insufficiency in the multivariate analysis were smoking ( P = .03), obesity ( P = .003), and other medical risk factors for vitamin D deficiency ( P = .03). Conclusion: Hypovitaminosis D was common among patients with a foot or ankle injury seen at our institution. Patients with a low energy fracture of the foot or ankle were at particular risk for low vitamin D, especially if they smoked, were obese, or had other medical risk factors. Given that supplementation with vitamin D (± calcium) has been shown to reduce the risk of fragility fractures and improve fracture healing, monitoring of 25-OH vitamin D and supplementation should be considered in patients with fractures. Level of Evidence: Level III, prospective case control.
Application of methods for central statistical monitoring in clinical trials
Authors: Kirkwood Amy A , Cox Trevor , Hackshaw Allan 
Published: October 2013

Background On-site source data verification is a common and expensive activity, with little evidence that it is worthwhile. Central statistical monitoring (CSM) is a cheaper alternative, where data checks are performed by the coordinating centre, avoiding the need to visit all sites. Several publications have suggested methods for CSM; however, few have described their use in real trials. Methods R-programs were created to check data at either the subject level (7 tests within 3 programs) or site level (9 tests within 8 programs) using previously described methods or new ones we developed. These aimed to find possible data errors such as outliers, incorrect dates, or anomalous data patterns; digit preference, values too close or too far from the means, unusual correlation structures, extreme variances which may indicate fraud or procedural errors and under-reporting of adverse events. The methods were applied to three trials, one of which had closed and has been published, one in follow-up, and a third to which fabricated data were added. We examined how well the methods work, discussing their strengths and limitations. Results The R-programs produced simple tables or easy-to-read figures. Few data errors were found in the first two trials, and those added to the third were easily detected. The programs were able to identify patients with outliers based on single or multiple variables. They also detected (1) fabricated patients, generated to have values too close to the multivariate mean, or with too low variances in repeated measurements, and (2) sites which had unusual correlation structures or too few adverse events. Some methods were unreliable if applied to centres with few patients or if data were fabricated in a way which did not fit the assumptions used to create the programs. Outputs from the R-programs are interpreted using examples. Limitations Detecting data errors is relatively straightforward; however, there are several limitations in the detection of fraud: some programs cannot be applied to small trials or to centres with few patients (<10) and data falsified in a manner which does not fit the program’s assumptions may not be detected. In addition, many tests require a visual assessment of the output (showing flagged participants or sites), before data queries are made or on-site visits performed. Conclusions CSM is a worthwhile alternative to on-site data checking and may be used to limit the number of site visits by targeting only sites which are picked up by the programs. We summarise the methods, show how they are implemented and that they can be easy to interpret. The methods can identify incorrect or unusual data for a trial subject, or centres where the data considered together are too different to other centres and therefore should be reviewed, possibly through an on-site visit.
Inference from blinded data in randomized clinical trials
Authors: Zhou Kefei , Ganju Jitendra 
Published: October 2013

Background With blinded data, several authors have concluded that there is a negligible chance of inferring a non-null treatment effect. The recent Food and Drug Administration (FDA) draft guidance document on adaptive trials, by encouraging blinded sample size reestimation, implies the same. Purpose We derive methods to investigate whether the probability of inferring a treatment effect is much larger than previously thought, and whether that is of concern. Methods A statistic is developed that contributes to improving signal detection. Additionally, trials that are overpowered, for reasons external to powering the primary objective, further strengthen the chance of finding a signal. Results An example of data from a clinical trial shows how revealing a blinded analysis can be. The ability to infer a non-null effect while a blinded trial is ongoing is a serious matter. Limitations The methods apply to superiority trials and are of limited use for non-inferiority or equivalence trials. Conclusion It is important, therefore, that guidance documents include clear language to limit or prevent inference from blinded data to maintain trial integrity. Simple steps are proposed to make inference difficult.
Endoscopic submucosal dissection for early gastric cancer in cases preoperatively contraindicated for endoscopic treatment
Authors: Kakushima Naomi , Hagiwara Tomoko , Tanaka Masaki , Sawai Hiroaki , Kawata Noboru , Takizawa Kohei , Imai Kenichiro , Takao Toshitatsu , Hotta Kinichi , Yamaguchi Yuichiro , Matsubayashi Hiroyuki , Ono Hiroyuki 
Published: October 2013

Background and study aimsEndoscopic submucosal dissection (ESD) is an optimal treatment for early gastric cancer (EGC) with negligible risk of lymph node metastasis; however, ESD is sometimes performed to treat lesions preoperatively contraindicated for the procedure due to various reasons. Here we aim to evaluate the treatment outcomes of ESD for lesions that were preoperatively contraindicated for ESD.Patients and methodsClinicopathological data of 104 EGC lesions in 104 patients were reviewed retrospectively. The demographic characteristics of patients, reasons for ESD, treatment results, complications, and outcomes were assessed.ResultsThe major reasons for undergoing ESD included advanced age, desire to undergo ESD, and the existence of comorbidities. En‐bloc and complete resection rates were 97 and 71%, respectively. Perforation and postoperative bleeding rates were 13 and 9%, respectively. Resection was beyond the expanded Japanese criteria for endoscopic treatment of EGC in 87 patients (84%), 41 (47%) of whom underwent additional therapy, including subsequent gastrectomy (29 patients) and photodynamic therapy (12 patients). The median follow‐up period was 47 months, during which seven patients died from recurrent disease. The 5‐year overall and disease‐specific survival rates were 70 and 91.5%, respectively.ConclusionsESD is a technically demanding procedure for lesions preoperatively contraindicated for endoscopic resection. The curative resection rate was low, but the 5‐year disease‐specific survival rate of 91.5% was favourable. In experienced hands, ESD may be a treatment option for patients not suitable for radical surgery, and the relevant risk of complications must be considered before treatment.
Molecular analysis of subtilase cytotoxin genes of food-borne Shiga toxin-producing Escherichia coli reveals a new allelic subAB variant
Authors: Funk Joschua , Stoeber Helen , Hauser Elisabeth , Schmidt Herbert 
Published: October 2013

AbstractBackgroundThe open reading frames ofsubABgenes and their flanking regions of 18 food-borne Shiga toxin-producingE. coli(STEC) strains were analyzed.ResultsAll but onesubABopen reading frames (ORF) were complete in all STEC strains. ThesubAB1genes of nine STEC strains were located on large plasmids. ThesubAB2allele (here designatedsubAB2-1), which was recently described by others to be present in the Subtilase-Encoding PAI (SE-PAI) was found in 6 STEC strains. A new chromosomalsubAB2variant, designatedsubAB2-2was detected in 6 strains and was linked to a chromosomal gene hypothetically encoding an outer membrane efflux protein (OEP). Three STEC strains contained bothsubAB2variants. DNA analysis indicated sequence conservation in the plasmid-located alleles and sequence heterogeneity among the chromosomalsubAB2genes.ConclusionsThe results of this study have shown that 18subAB-PCR positive STEC strains contain completesubABopen reading frames. Furthermore, the new allelic variantsubAB2-2was described, which can occur in addition tosubAB2-1on a new chromosomal locus.
Brachial plexus palsy after a left-side modified radical mastectomy with immediate latissimusdorsi flap reconstruction: report of a case
Authors: Wu Jun-Dong , Huang Wen-He , Huang Zi-Yi , Chen Ming , Zhang Guo-Jun 
Published: October 2013

Abstract
Brachial plexus injury is a rare complication during operation and anesthesia; it can occur as a result of various mechanisms such as inappropriate positioning, over-abduction and stretching the upper limbs. Brachial plexus injury can cause the poor function of the upper limb before recovery, and sometimes serious injury is unable to completely recovered the function permanently. Here, we report a female breast cancer patient who sustained a left brachial plexus palsy after modified radical mastectomy with immediate breast reconstruction with latissimusdorsi flap (LDF). The patient had fully recovered with normal function of her left upper limb six months postoperation after conservative treatment.
Mesenchymal stem cells from umbilical cord matrix, adipose tissue and bone marrow exhibit different capability to suppress peripheral blood B, natural killer and T cells
Authors: Ribeiro Andreia , Laranjeira Paula , Mendes Sandrine , Velada Isabel , Leite Cristiana , Andrade Pedro , Santos Francisco , Henriques Ana , Grãos Mário , Cardoso Carla M P , Martinho António , Pais M Luísa , da Silva Cláudia Lobato , Cabral Joaquim , Trindade Hélder , Paiva Artur 
Published: October 2013

Abstract
Introduction
The ability to self-renew, be easily expanded in vitro and differentiate into different mesenchymal tissues, render mesenchymal stem cells (MSCs) an attractive therapeutic method for degenerative diseases. The subsequent discovery of their immunosuppressive ability encouraged clinical trials in graft-versus-host disease and auto-immune diseases. Despite sharing several immunophenotypic characteristics and functional capabilities, the differences between MSCs arising from different tissues are still unclear and the published data are conflicting.

Methods
Here, we evaluate the influence of human MSCs derived from umbilical cord matrix (UCM), bone marrow (BM) and adipose tissue (AT), co-cultured with phytohemagglutinin (PHA)-stimulated peripheral blood mononuclear cells (MNC), on T, B and natural killer (NK) cell activation; T and B cells’ ability to acquire lymphoblast characteristics; mRNA expression of interleukin-2 (IL-2), forkhead box P3 (FoxP3), T-bet and GATA binding protein 3 (GATA3), on purified T cells, and tumor necrosis factor-alpha (TNF-α), perforin and granzyme B on purified NK cells.

Results
MSCs derived from all three tissues were able to prevent CD4+ and CD8+ T cell activation and acquisition of lymphoblast characteristics and CD56dim NK cell activation, wherein AT-MSCs showed a stronger inhibitory effect. Moreover, AT-MSCs blocked the T cell activation process in an earlier phase than BM- or UCM-MSCs, yielding a greater proportion of T cells in the non-activated state. Concerning B cells and CD56bright NK cells, UCM-MSCs did not influence either their activation kinetics or PHA-induced lymphoblast characteristics, conversely to BM- and AT-MSCs which displayed an inhibitory effect. Besides, when co-cultured with PHA-stimulated MNC, MSCs seem to promote Treg and Th1 polarization, estimated by the increased expression of FoxP3 and T-bet mRNA within purified activated T cells, and to reduce TNF-α and perforin production by activated NK cells.

Conclusions
Overall, UCM-, BM- and AT-derived MSCs hamper T cell, B cell and NK cell-mediated immune response by preventing their acquisition of lymphoblast characteristics, activation and changing the expression profile of proteins with an important role in immune function, except UCM-MSCs showed no inhibitory effect on B cells under these experimental conditions. Despite the similarities between the three types of MSCs evaluated, we detect important differences that should be taken into account when choosing the MSC source for research or therapeutic purposes.
Disabling Immune Tolerance by Programmed Death-1 Blockade With Pidilizumab After Autologous Hematopoietic Stem-Cell Transplantation for Diffuse Large B-Cell Lymphoma: Results of an International Phase II Trial
Authors: Armand Philippe , Nagler Arnon , Weller Edie A. , Devine Steven M. , Avigan David E. , Chen Yi-Bin , Kaminski Mark S. , Holland H. Kent , Winter Jane N. , Mason James R. , Fay Joseph W. , Rizzieri David A. , Hosing Chitra M. , Ball Edward D. , Uberti Joseph P. , Lazarus Hillard M. , Mapara Markus Y. , Gregory Stephanie A. , Timmerman John M. , Andorsky David , Or Reuven , Waller Edmund K. , Rotem-Yehudar Rinat , Gordon Leo I. 
Published: October 2013

Purpose The Programmed Death-1 (PD-1) immune checkpoint pathway may be usurped by tumors, including diffuse large B-cell lymphoma (DLBCL), to evade immune surveillance. The reconstituting immune landscape after autologous hematopoietic stem-cell transplantation (AHSCT) may be particularly favorable for breaking immune tolerance through PD-1 blockade. Patients and Methods We conducted an international phase II study of pidilizumab, an anti–PD-1 monoclonal antibody, in patients with DLBCL undergoing AHSCT, with correlative studies of lymphocyte subsets. Patients received three doses of pidilizumab beginning 1 to 3 months after AHSCT. Results Sixty-six eligible patients were treated. Toxicity was mild. At 16 months after the first treatment, progression-free survival (PFS) was 0.72 (90% CI, 0.60 to 0.82), meeting the primary end point. Among the 24 high-risk patients who remained positive on positron emission tomography after salvage chemotherapy, the 16-month PFS was 0.70 (90% CI, 0.51 to 0.82). Among the 35 patients with measurable disease after AHSCT, the overall response rate after pidilizumab treatment was 51%. Treatment was associated with increases in circulating lymphocyte subsets including PD-L1E–bearing lymphocytes, suggesting an on-target in vivo effect of pidilizumab. Conclusion This is the first demonstration of clinical activity of PD-1 blockade in DLBCL. Given these results, PD-1 blockade after AHSCT using pidilizumab may represent a promising therapeutic strategy in this disease.
Trastuzumab-Related Cardiotoxicity Among Older Patients With Breast Cancer
Authors: Chavez-MacGregor Mariana , Zhang Ning , Buchholz Thomas A. , Zhang Yufeng , Niu Jiangong , Elting Linda , Smith Benjamin D. , Hortobagyi Gabriel N. , Giordano Sharon H. 
Published: October 2013

Purpose The use of trastuzumab in the adjuvant setting improves outcomes but is associated with cardiotoxicity manifested as congestive heart failure (CHF). The rates and risk factors associated with trastuzumab-related CHF among older patients are unknown. Patients and Methods Breast cancer patients at least 66 years old with full Medicare coverage, diagnosed with stage I-III breast cancer between 2005 and 2009, and treated with chemotherapy were identified in the SEER-Medicare and in the Texas Cancer Registry–Medicare databases. The rates and risk factors associated with CHF were evaluated. Chemotherapy, trastuzumab use, comorbidities, and CHF were identified using International Classification of Diseases, version 9, and Healthcare Common Procedure Coding System codes. Analyses included descriptive statistics and Cox proportional hazards models. Results In total, 9,535 patients were included, of whom 2,203 (23.1%) received trastuzumab. Median age of the entire cohort was 71 years old. Among trastuzumab users, the rate of CHF was 29.4% compared with 18.9% in nontrastuzumab users (P < .001). Trastuzumab users were more likely to develop CHF than nontrastuzumab users (hazard ratio [HR], 1.95; 95% CI, 1.75 to 2.17). Among trastuzumab-treated patients, older age (age > 80 years; HR, 1.53; 95% CI, 1.16 to 2.10), coronary artery disease (HR, 1.82; 95% CI, 1.34 to 2.48), hypertension (HR, 1.24; 95% CI, 1.02 to 1.50), and weekly trastuzumab administration (HR, 1.33; 95% CI, 1.05 to 1.68) increased the risk of CHF. Conclusion In this large cohort of older breast cancer patients, the rates of trastuzumb-related CHF are higher than those reported in clinical trials. Among patients treated with trastuzumab, those with cardiac comorbidities and older age may be at higher risk. Further studies need to confirm the role that the frequency of administration plays in the development of trastuzumab-related CHF.
Oral Tetra-Arsenic Tetra-Sulfide Formula Versus Intravenous Arsenic Trioxide As First-Line Treatment of Acute Promyelocytic Leukemia: A Multicenter Randomized Controlled Trial
Authors: Zhu Hong-Hu , Wu De-Pei , Jin Jie , Li Jian-Yong , Ma Jun , Wang Jian-Xiang , Jiang Hao , Chen Sai-Juan , Huang Xiao-Jun 
Published: October 2013

Purpose This randomized, multicenter, phase III noninferiority trial was designed to test the efficacy and safety of an oral tetra-arsenic tetra-sulfide (As4S4) –containing formula named the Realgar-Indigo naturalis formula (RIF) compared with intravenous arsenic trioxide (ATO) as both induction and maintenance therapies for newly diagnosed acute promyelocytic leukemia (APL). Patients and Methods In all, 242 patients with APL were randomly assigned (1:1) to oral RIF (60 mg/kg) or ATO (0.16 mg/kg) combined with all-trans retinoic acid (ATRA; 25 mg/m2) during induction therapy. After achieving complete remission (CR), all patients received three courses of consolidation chemotherapy and maintenance treatment with sequential ATRA followed by either RIF or ATO for 2 years. The primary end point was the rate of disease-free survival (DFS) at 2 years, which was assessed for noninferiority with a 10% noninferiority margin. Results The median follow-up time was 39 months. DFS at 2 years was 98.1% (106 of 108) in the RIF group and 95.5% (107 of 112) in the ATO group. The DFS difference was 2.6% (95% CI, −3.0% to 8.0%). The lower limit of the 95% CI of DFS difference was greater than the −10% noninferiority margin, confirming noninferiority (P < .001). No significant differences were noted between the RIF and ATO groups with regard to the CR rate (99.1% v 97.2%; P = .62) or the overall survival at 3 years (99.1% v 96.6%; P = .18). The rates of adverse events were similar in the two groups. Conclusion Oral RIF plus ATRA is not inferior to intravenous ATO plus ATRA as first-line treatment of APL and may be considered as a routine treatment option for appropriate patients.
Tumor-Infiltrating Lymphocyte Grade in Primary Melanomas Is Independently Associated With Melanoma-Specific Survival in the Population-Based Genes, Environment and Melanoma Study
Authors: Thomas Nancy E. , Busam Klaus J. , From Lynn , Kricker Anne , Armstrong Bruce K. , Anton-Culver Hoda , Gruber Stephen B. , Gallagher Richard P. , Zanetti Roberto , Rosso Stefano , Dwyer Terence , Venn Alison , Kanetsky Peter A. , Groben Pamela A. , Hao Honglin , Orlow Irene , Reiner Anne S. , Luo Li , Paine Susan , Ollila David W. , Wilcox Homer , Begg Colin B. , Berwick Marianne 
Published: October 2013

Purpose Although most hospital-based studies suggest more favorable survival with tumor-infiltrating lymphocytes (TILs) present in primary melanomas, it is uncertain whether TILs provide prognostic information beyond existing melanoma staging definitions. We addressed the issue in an international population-based study of patients with single and multiple primary melanomas. Patients and Methods On the basis of the Genes, Environment and Melanoma (GEM) study, we conducted follow-up of 2,845 patients diagnosed from 1998 to 2003 with 3,330 invasive primary melanomas centrally reviewed for TIL grade (absent, nonbrisk, or brisk). The odds of TIL grades associated with clinicopathologic features and survival by TIL grade were examined. Results Independent predictors (P < .05) for nonbrisk TIL grade were site, histologic subtype, and Breslow thickness, and for brisk TIL grade, they were age, site, Breslow thickness, and radial growth phase. Nonbrisk and brisk TIL grades were each associated with lower American Joint Committee on Cancer (AJCC) tumor stage compared with TIL absence (Ptrend < .001). Death as a result of melanoma was 30% less with nonbrisk TIL grade (hazard ratio [HR], 0.7; 95% CI, 0.5 to 1.0) and 50% less with brisk TIL grade (HR, 0.5; 95% CI, 0.3 to 0.9) relative to TIL absence, adjusted for age, sex, site, and AJCC tumor stage. Conclusion At the population level, higher TIL grade of primary melanoma is associated with a lower risk of death as a result of melanoma independently of tumor characteristics currently used for AJCC tumor stage. We conclude that TIL grade deserves further prospective investigation to determine whether it should be included in future AJCC staging revisions.