bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intrahepatic Cholangiocarcinoma: An International Multi-Institutional Analysis of Prognostic Factors and Lymph Node Assessment
Authors: de Jong Mechteld C. , Nathan Hari , Sotiropoulos Georgios C. , Paul Andreas , Alexandrescu Sorin , Marques Hugo , Pulitano Carlo , Barroso Eduardo , Clary Bryan M. , Aldrighetti Luca , Ferrone Cristina R. , Zhu Andrew X. , Bauer Todd W. , Walters Dustin M. , Gamblin T. Clark , Nguyen Kevin T. , Turley Ryan , Popescu Irinel , Hubert Catherine , Meyer Stephanie , Schulick Richard D. , Choti Michael A. , Gigot Jean-Francois , Mentha Gilles , Pawlik Timothy M. 
Published: July 2011

Purpose To identify factors associated with outcome after surgical management of intrahepatic cholangiocarcinoma (ICC) and examine the impact of lymph node (LN) assessment on survival. Patients and Methods From an international multi-institutional database, 449 patients who underwent surgery for ICC between 1973 and 2010 were identified. Clinical and pathologic data were evaluated using uni- and multivariate analyses. Results Median tumor size was 6.5 cm. Most patients had a solitary tumor (73%) and no vascular invasion (69%). Median survival was 27 months, and 5-year survival was 31%. Factors associated with adverse prognosis included positive margin status (hazard ratio [HR], 2.20; P < .001), multiple lesions (HR, 1.80; P = .001), and vascular invasion (HR, 1.59; P = .015). Tumor size was not a prognostic factor (HR, 1.03; P = .23). Patients were stratified using the American Joint Committee on Cancer/International Union Against Cancer T1, T2a, and T2b categories (seventh edition) in a discrete step-wise fashion (P < .001). Lymphadenectomy was performed in 248 patients (55%); 74 of these (30%) had LN metastasis. LN metastasis was associated with worse outcome (median survival: N0, 30 months v N1, 24 months; P = .03). Although patients with no LN metastasis were able to be stratified by tumor number and vascular invasion (N0; P < .001), among patients with N1 disease, multiple tumors and vascular invasion, either alone or together, failed to discriminate patients into discrete prognostic groups (P = .34). Conclusion Although tumor size provides no prognostic information, tumor number, vascular invasion, and LN metastasis were associated with survival. N1 status adversely affected overall survival and also influenced the relative effect of tumor number and vascular invasion on prognosis. Lymphadenectomy should be strongly considered for ICC, because up to 30% of patients will have LN metastasis.
Approach to the Child with Fractures
Authors: Boyce Alison M. , Gafni Rachel I. 
Published: July 2011

Abstract
Evaluation of the child with fractures is challenging, as no clear guidelines exist to distinguish traumatic from pathological fractures. Although most fractures in childhood are benign, recurrent fractures may be associated with a wide variety of primary skeletal diseases as well as secondary causes, necessitating a careful history and physical exam to guide the evaluation. There is no “gold standard” for the evaluation and treatment of children with fractures and low bone mineral density (BMD); therefore, the diagnosis of osteoporosis in a pediatric patient should be made using a combination of clinical and radiographic features. Interpretation of bone densitometry in growing patients presents a unique set of challenges because areal BMD measured by dual-energy x-ray absorptiometry depends on multiple dynamic variables. Interpretation of pediatric dual-energy x-ray absorptiometry should be based on Z-scores (sd scores compared to age, sex, and ethnicity-matched controls), using normative databases specific to the brand of densitometer and the patient population. Given the skeleton's ability to recover from low BMD through modeling and remodeling, optimizing management of underlying conditions leading to bone fragility is the initial step. Conservative measures including calcium and vitamin D supplementation and weight-bearing physical activity are important interventions that should not be overlooked. The use of bisphosphonates in children and adolescents is controversial due to lack of long-term efficacy and safety data and should be limited to clinical trials and compassionate therapy in children with significantly compromised quality of life. Close monitoring is required, and further study is necessary to assess their long-term safety and efficacy in children.
The inflammatory bowel disease (IBD) susceptibility genes NOD1 and NOD2 have conserved anti-bacterial roles in zebrafish
Authors: Oehlers Stefan H. , Flores Maria Vega , Hall Chris J. , Swift Simon , Crosier Kathryn E. , Crosier Philip S. 
Published: July 2011

SUMMARY
Inflammatory bowel disease (IBD), in the form of Crohn’s disease (CD) or ulcerative colitis (UC), is a debilitating chronic immune disorder of the intestine. A complex etiology resulting from dysfunctional interactions between the intestinal immune system and its microflora, influenced by host genetic susceptibility, makes disease modeling challenging. Mutations in NOD2 have the highest disease-specific risk association for CD, and a related gene, NOD1, is associated with UC. NOD1 and NOD2 encode intracellular bacterial sensor proteins acting as innate immune triggers, and represent promising therapeutic targets. The zebrafish has the potential to aid in modeling genetic and environmental aspects of IBD pathogenesis. Here, we report the characterization of the Nod signaling components in the zebrafish larval intestine. The nod1 and nod2 genes are expressed in intestinal epithelial cells and neutrophils together with the Nod signaling pathway genes ripk2, a20, aamp, cd147, centaurin b1, erbin and grim-19. Using a zebrafish embryo Salmonella infection model, morpholino-mediated depletion of Nod1 or Nod2 reduced the ability of embryos to control systemic infection. Depletion of Nod1 or Nod2 decreased expression of dual oxidase in the intestinal epithelium and impaired the ability of larvae to reduce intracellular bacterial burden. This work highlights the potential use of zebrafish larvae in the study of components of IBD pathogenesis.
Fetal overgrowth in theCdkn1cmouse model of Beckwith-Wiedemann syndrome
Authors: Tunster Simon J. , Van de Pette Mathew , John Rosalind M. 
Published: July 2011

SUMMARYMutations in the imprinted CDKN1C gene are associated with the childhood developmental disorder Beckwith-Wiedemann syndrome (BWS). Multiple mouse models with deficiency of Cdkn1c recapitulate some aspects of BWS but do not exhibit overgrowth of the newborn, a cardinal feature of patients with BWS. In this study, we found that Cdkn1c mutants attained a 20% increase in weight during gestation but experienced a rapid reversal of this positive growth trajectory very late in gestation. We observed a marked effect on placental development concurrently with this loss of growth potential, with the appearance of large thrombotic lesions in the labyrinth zone. The trilaminar trophoblast layer that separates the maternal blood sinusoids from fetal capillaries was disordered with a loss of sinusoidal giant cells, suggesting a role for Cdkn1c in maintaining the integrity of the maternal-fetal interface. Furthermore, the overgrowth of mutant pups decreased in the face of increasing intrauterine competition, identifying a role for Cdkn1c in the allocation of the maternal resources via the placenta. This work explains one difficulty in precisely replicating BWS in this animal model: the differences in reproductive strategies between the multiparous mouse, in which intrauterine competition is high, and humans, in which singleton pregnancies are more common.
Thefeelgoodmutation in zebrafish dysregulates COPII-dependent secretion of select extracellular matrix proteins in skeletal morphogenesis
Authors: Melville David B. , Montero-Balaguer Mercedes , Levic Daniel S. , Bradley Kevin , Smith Jeffrey R. , Hatzopoulos Antonis K. , Knapik Ela W. 
Published: July 2011

SUMMARYCraniofacial and skeletal dysmorphologies account for the majority of birth defects. A number of the disease phenotypes have been attributed to abnormal synthesis, maintenance and composition of extracellular matrix (ECM), yet the molecular and cellular mechanisms causing these ECM defects remain poorly understood. The zebrafish feelgood mutant manifests a severely malformed head skeleton and shortened body length due to defects in the maturation stage of chondrocyte development. In vivo analyses reveal a backlog of type II and type IV collagens in rough endoplasmic reticulum (ER) similar to those found in coat protein II complex (COPII)-deficient cells. The feelgood mutation hinders collagen deposition in the ECM, but trafficking of small cargos and other large ECM proteins such as laminin to the extracellular space is unaffected. We demonstrate that the zebrafish feelgood mutation causes a single amino acid substitution within the DNA-binding domain of transcription factor Creb3l2. We show that Creb3l2 selectively regulates the expression of genes encoding distinct COPII proteins (sec23a, sec23b and sec24d) but find no evidence for its regulation of sec24c expression. Moreover, we did not detect activation of ER stress response genes despite intracellular accumulation of collagen and prominent skeletal defects. Promoter trans-activation assays show that the Creb3l2 feelgood variant is a hypomorphic allele that retains approximately 50% of its transcriptional activity. Transgenic rescue experiments of the feelgood phenotype restore craniofacial development, illustrating that a precise level of Creb3l2 transcriptional activity is essential for skeletogenesis. Our results indicate that Creb3l2 modulates the availability of COPII machinery in a tissue- and cargo-specific manner. These findings could lead to a better understanding of the etiology of human craniofacial and skeletal birth defects as well as adult-onset diseases that are linked to dysregulated ECM deposition, such as arthritis, fibrosis or osteoporosis.
Comparison of total and intact aminoterminal propeptide of type I procollagen assays in patients with breast cancer with or without bone metastases
Authors: Marin Lauri , Koivula Marja-Kaisa , Jukkola-Vuorinen Arja , Leino Aila , Risteli Juha 
Published: July 2011

Background Aminoterminal propeptide of type I procollagen (PINP) reflects bone formation. Two different antigens exist in human serum: intact PINP and a monomeric form. The intact PINP assay measures trimeric form and the total assay measures both forms. The structure and origin of the monomeric form is still unclear. Methods Automated intact and total PINP assays were compared in breast cancer patients with ( n = 60) or without bone metastases ( n = 226). In addition, cross-linked carboxyterminal telopeptide of type I collagen (ICTP) was measured from the same patients and compared with the concentration of PINP monomer (difference between intact and total PINP). Monomeric PINP was purified from human ascitic fluid and characterized by sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Results The correlations were good ( r > 0.948) between intact PINP and total P1NP in all patient groups. The correlation between the monomeric form and ICTP was lower in patients without bone metastases ( r = 0.507) than in patients with bone metastases ( r = 0.894). This indicates that the monomeric form reflects the degradation of type I collagen because bone metastases are osteolytic in nature. After several steps in the purification of the monomer form there was a single peak. Only the single band was visible in the SDS-PAGE gel. The alpha1-chain of intact PINP consists of 161 amino acids with a molecular weight of 14224.02. The purified monomer peptide in MALDI-TOF MS was smaller, 10576.41, and most likely cleaved after the arginine residue (amino acid number 120) with a trypsin-like protease. Conclusions Intact and total PINP assays give similar results in many conditions, but there are differences, for example in breast carcinoma, which should be recognized.
Tech-Check-Tech Pilot in a Regional Public Psychiatric Inpatient Facility
Authors: McKee Jerry , Zimmerman Melinda 
Published: July 2011

Purpose A pilot project assessing the impact of utilizing well-trained, competency-assessed, certified pharmacy technicians (referred to as advanced practice pharmacy technicians or APPTs) to check unit dose medications prepared by other technicians is described. The pilot site, a regional inpatient public mental health facility, petitioned the North Carolina Board of Pharmacy for a waiver pursuant to Board Rule .2510 to conduct this pilot to compare the accuracy of APPTs to pharmacists in similar roles. Further, the pilot assessed clinical pharmacist time savings generated by improved personnel utilization and the subsequent redeployment by use of this time. Summary Four pharmacy technicians were trained and their competency assessed per the approved protocol. The project entailed 3 distinct components: (1) submitting the petition to the Board of Pharmacy and obtaining approval, (2) training pharmacy technicians and assessing their competency, and (3) incrementally implementing new work processes and project assessment. Clinical pharmacist time saved, in excess of 50 hours per month at full pilot implementation, was utilized in deploying increased patient-focused clinical services. The full pilot implementation was in place for 13 months, with a reported variance rate of 0.31 per month (95% CI, 0-0.77). Two variances were detected by nursing and corrected prior to reaching the patient (near misses). In 2 cases, the medication reached the patient; neither case led to patient harm. The mean number of pharmacist variances (near misses and reaching the patient) for the 12-month period immediately preceding the pilot implementation was 1.42 per month (95% CI, 0.95-1.88), while performing similar functions. Conclusion For this public inpatient psychiatric facility, the APPT variance rate was substantially lower than that for pharmacists in routine checking functions. This superior accuracy is consistent with other documented studies, however it is the first in a non-acute care setting, further demonstrating the potential for the utility of expanded technician roles.
Implementation of a Medication Therapy Management Program in a Hospital-Based Outpatient Pharmacy
Authors: Hall Deanne L. , Pater Karen S. 
Published: July 2011

Purpose To describe the integration of a medication therapy management (MTM) service in a hospital-based outpatient pharmacy, including adapting Medicare-based screening criteria to target a primarily non-Medicare population, integrating data into the medical center's electronic medical record, and designing a method to track identified drug-related problems (DRPs). Methods The hospital-based outpatient pharmacy at the University of Pittsburgh Medical Center (UPMC) established an MTM service to enhance patient medication safety. Identification criteria were developed in accordance with the Medicare Modernization Act of 2003 and institutional practices: older than 65 years, more than 5 chronic medications, more than 3 chronic disease states, presence of diabetes, tobacco use, or possible adverse drug event (ADE). As this was a proof of concept pilot, both Medicare and non-Medicare patients were included. Additionally, an intervention tracking form was developed to use in conjunction with the medical center's electronic medical record. Results During an 18-month period, 319 patients met the criteria upon random screening. Sixty-eight patients enrolled in the MTM program, resulting in 234 patient visits. One hundred and seventy DRPs were identified, with 2.5 DRP per patient. The most common problems found were the need for additional drug therapy and nonadherence. The overall physician acceptance rate for recommendations was 69%. Conclusion MTM programs are adaptable to a hospital-based outpatient pharmacy utilizing Medicare-based screening criteria in a primarily non-Medicare population resulting in identification of DRPs.
Belimumab
Authors: Cada Dennis J. , Levien Terri L. , Baker Danial E. 
Published: July 2011

Each month, subscribers to The Formulary Monograph Service receive 5 to 6 well-documented monographs on drugs that are newly released or are in late phase 3 trials. The monographs are targeted to Pharmacy & Therapeutics Committees. Subscribers also receive monthly 1-page summary monographs on agents that are useful for agendas and pharmacy/nursing in-services. A comprehensive target drug utilization evaluation/medication use evaluation (DUE/MUE) is also provided each month. With a subscription, the monographs are sent in print and are also available on-line. Monographs can be customized to meet the needs of a facility. Subscribers to The Formulary Monograph Service also receive access to a pharmacy bulletin board, The Formulary Information Exchange (The F.I.X.). All topics pertinent to clinical and hospital pharmacy are discussed on The F.I.X. Through the cooperation of The Formulary, Hospital Pharmacy publishes selected reviews in this column. For more information about The Formulary Monograph Service or The F.I.X., call The Formulary at 800-322-4349. The July 2011 monograph topics are on linagliptin, peginterferon alfa-2b, abiraterone acetate, vandetanib, and ibuprofen/famotidine. The DUE/MUE is on linagliptin.
Efficacy and Safety of Long-Acting Glucagon-Like Peptide-1 Receptor Agonists Compared with Exenatide Twice Daily and Sitagliptin in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
Authors: Pinelli Nicole R , Hurren Kathryn M 
Published: July 2011

Background: Long-acting glucagon-like peptide-1 receptor agonists (LA-GLP-1RAs) may deliver additional therapeutic benefits over other available incretin-based therapies. Objective: To pool results of randomized controlled trials comparing the efficacy and safely of maximum dose LA-GLP-1RAs (liraglutide, exenatide once weekly) with exenatide twice daily and dipeptidyl-peptidase-IV inhibitors in patients with type 2 diabetes. Methods: We searched PubMed, Cochrane Central Register of Controlled Trials and Database of Systematic Reviews, EMBASE (all from inception-December 2010), and abstracts presented at the American Diabetes Association Scientific Sessions in 2009 and 2010 to identify English-language reports of studies of at least 24 weeks' duration. The primary endpoint was mean change in hemoglobin A1c (A1C) from baseline to study endpoint. Weighted mean differences or odds ratios and their 95% confidence intervals for each outcome relative to control were calculated as appropriate. Results: A1C was reduced favoring LA-GLP-1RAs compared with exenatide twice daily and sitagliptin (weighted mean difference [WMD] –0.47% [95% CI –0.69 to –0.25] and WMD –0.60% [95% CI –0.75 to –0.45], respectively). Odds ratios greater than 1 favored LA-GLP-1RAs for reaching the A1C target goal of less than 7%. Fasting plasma glucose (FPG) was reduced and favored the LA-GLP-1RA–based regimens. Exenatide demonstrated significantly greater reductions in postprandial glucose (PPG) after the morning and evening meals, compared with LA-GLP-1RAs. Body weight was reduced similarly between LA-GLP-1RAs and exenatide, but favored LA-GLP-1RAs in the sitagliptin comparator trials. LA-GLP-1RA therapy was not associated with severe hypoglycemia or acute pancreatitis. Compared with exenatide twice daily, vomiting was reduced significantly with LA-GLP-1RAs (OR 0.55; 95% CI 0.34 to 0.89); there was a trend toward decreased nausea (OR 0.58; 95% CI 0.32 to 1.06) and no difference in the incidence of diarrhea (OR 1.03; 95% CI 0.67 to 1.58). Conclusions: Compared with other incretin-based therapies, LA-GLP-1RAs produce greater improvement in A1C and FPG. They provide lesser effect on PPG, similar reduction in body weight, and result in a potentially favorable adverse event profile compared with exenatide twice daily.
Influence of Intravenous Opioid Dose on Postoperative Ileus
Authors: Barletta Jeffrey F , Asgeirsson Theodor , Senagore Anthony J 
Published: July 2011

Background: Intravenous opioids represent a major component in the pathophysiology of postoperative ileus (POI). However, the most appropriate measure and threshold to quantify the association between opioid dose (eg, average daily, cumulative, maximum daily) and POI remains unknown. Objective: To evaluate the relationship between opioid dose, POI, and length of stay (LOS) and identify the opioid measure that was most strongly associated with POI, Methods: Consecutive patients admitted to a community teaching hospital who underwent elective colorectal surgery by any technique with an enhanced-recovery protocol postoperatively were retrospectively identified. Patients were excluded if they received epidural analgesia, developed a major intraabdominal complication or medical complication, or had a prolonged workup prior to surgery. Intravenous opioid doses were quantified and converted to hydromorphone equivalents. Classification and regression tree (CART) analysis was used to determine the dosing threshold for the opioid measure most associated with POI and define high versus low use of opioids. Risk factors for POI and prolonged LOS were determined through multivariate analysis. Results: The incidence of POI in 279 patients was 8.6%. CART analysis identified a maximum daily intravenous hydromorphone dose of 2 mg or more as the opioid measure most associated with POI. Multivariate analysis revealed maximum daily hydromorphone dose of 2 mg or more (p = 0.034), open surgical technique (p = 0.045), and days of intravenous narcotic therapy (p = 0.003) as significant risk factors for POI. Variables associated with increased LOS were POI (p < 0.001), maximum daily hydromorphone dose of 2 mg or more (p < 0.001), and age (p = 0.005); laparoscopy (p < 0.001) was associated with a decreased LOS. Conclusions: Intravenous opioid therapy is significantly associated with POI and prolonged LOS, particularly when the maximum hydromorphone dose per day exceeds 2 mg. Clinicians should consider alternative, nonopioid-based pain management options when this occurs.