Challenges of implementing complexity in healthcare.

Complexity is a form of system that is relevant in virtually all aspects and levels of healthcare. The importance and relevance of the science of complexity for healthcare has been written about extensively for over two decades. The problem this article addresses is that complex systems and how to manage them still appear to be relatively unknown nor well understood by most stakeholders of healthcare.

Exploring the glycosylation of mucins by use of O-glycodomain reporters recombinantly expressed in glycoengineered HEK293 cells.

Mucins and glycoproteins with mucin-like regions contain densely O-glycosylated domains often found in tandem repeat (TR) sequences. These O-glycodomains have traditionally been difficult to characterize because of their resistance to proteolytic digestion, and knowledge of the precise positions of O-glycans is particularly limited for these regions. Here, we took advantage of a recently developed glycoengineered cell-based platform for the display and production of mucin TR reporters with custom-designed O-glycosylation to characterize O-glycodomains derived from mucins and mucin-like glycoproteins.

Installation of O-glycan sulfation capacities in human HEK293 cells for display of sulfated mucins.

The human genome contains at least 35 genes that encode Golgi sulfotransferases that function in the secretory pathway, where they are involved in decorating glycosaminoglycans, glycolipids, and glycoproteins with sulfate groups. Although a number of important interactions by proteins such as selectins, galectins, and sialic acid-binding immunoglobulin-like lectins are thought to mainly rely on sulfated O-glycans, our insight into the sulfotransferases that modify these glycoproteins, and in particular GalNAc-type O-glycoproteins, is limited. Moreover, sulfated mucins appear to accumulate in respiratory diseases, arthritis, and cancer.

Validity and reliability of the Interagency Integrated Triage Tool in a regional emergency department in Papua New Guinea.

Objective: The Interagency Integrated Triage Tool (IITT) is a novel, three-tier triage system recommended by the World Health Organization. The present study sought to assess the validity and reliability of a pilot version of the tool in a resource-limited ED in regional Papua New Guinea.

Methods: This pragmatic prospective observational study, conducted at Mount Hagen Provincial Hospital, commenced 1 month after IITT implementation.

Display of the human mucinome with defined O-glycans by gene engineered cells.

Mucins are a large family of heavily O-glycosylated proteins that cover all mucosal surfaces and constitute the major macromolecules in most body fluids. Mucins are primarily defined by their variable tandem repeat (TR) domains that are densely decorated with different O-glycan structures in distinct patterns, and these arguably convey much of the informational content of mucins. Here, we develop a cell-based platform for the display and production of human TR O-glycodomains (~200 amino acids) with tunable structures and patterns of O-glycans using membrane-bound and secreted reporters expressed in glycoengineered HEK293 cells.

An Atlas of Human Glycosylation Pathways Enables Display of the Human Glycome by Gene Engineered Cells.

The structural diversity of glycans on cells-the glycome-is vast and complex to decipher. Glycan arrays display oligosaccharides and are used to report glycan hapten binding epitopes. Glycan arrays are limited resources and present saccharides without the context of other glycans and glycoconjugates.

Exploring Regulation of Protein O-Glycosylation in Isogenic Human HEK293 Cells by Differential O-Glycoproteomics.

Most proteins trafficking the secretory pathway of metazoan cells will acquire GalNAc-type O-glycosylation. GalNAc-type O-glycosylation is differentially regulated in cells by the expression of a repertoire of up to twenty genes encoding polypeptide GalNAc-transferase isoforms (GalNAc-Ts) that initiate O-glycosylation. These GalNAc-Ts orchestrate the positions and patterns of O-glycans on proteins in coordinated, but poorly understood ways - guided partly by the kinetic properties and substrate specificities of their catalytic domains, as well as by modulatory effects of their unique GalNAc-binding lectin domains.

A prospective cohort study to assess the role of FDG-PET in differentiating benign and malignant follicular neoplasms.

Background: Follicular and Hürthle cell neoplasms are diagnostic challenges. This prospective study was designed to evaluate the efficacy of [18F]-2-fluoro-2-deoxy--glucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the risk of malignancy in follicular/Hürthle cell neoplasms.

Materials And Methods: Fifty thyroid nodules showing follicular/Hürthle cell neoplasm on prior ultrasonography guided fine needle aspiration cytology (FNAC) were recruited into this study.

Comparing a thyroid prognostic nomogram to the existing staging systems for prediction risk of death from thyroid cancers.

Objective: Thyroid prognostic nomogram can be applied across different histological types for predicting the individualized risk of death from thyroid cancer. The objective of this study was to compare the strength of our recently published thyroid prognostic nomogram with 12 existing staging systems to predict the risk of death from thyroid cancer.

Method: This study included 1900 thyroid cancer patients, from a population based cohort of 2296 patients, on whom adequate staging information was available.

FDG-PET characteristics of Hürthle cell and follicular adenomas.

Objective: Follicular (FN) and Hürthle cell neoplasms (HCN) are considered indeterminate on thyroid fine needle aspiration cytology and are preoperative diagnostic challenges. The role of [(18)F]-2-fluoro-2-deoxy-D-glucose (FDG) in characterizing indeterminate thyroid nodules remains equivocal, because of the increased FDG uptake by some benign thyroid nodules. The objective of this study was to compare the FDG positron emission tomography/computerized tomography (PET/CT) characteristics of follicular (FA) and Hürthle cell adenomas (HCA).

The retinoblastoma protein regulates hypoxia-inducible genetic programs, tumor cell invasiveness and neuroendocrine differentiation in prostate cancer cells.

Loss of tumor suppressor proteins, such as the retinoblastoma protein (Rb), results in tumor progression and metastasis. Metastasis is facilitated by low oxygen availability within the tumor that is detected by hypoxia inducible factors (HIFs). The HIF1 complex, HIF1α and dimerization partner the aryl hydrocarbon receptor nuclear translocator (ARNT), is the master regulator of the hypoxic response.

An International Multi-Institutional Validation of Age 55 Years as a Cutoff for Risk Stratification in the AJCC/UICC Staging System for Well-Differentiated Thyroid Cancer.

Background: Age is a critical factor in outcome for patients with well-differentiated thyroid cancer. Currently, age 45 years is used as a cutoff in staging, although there is increasing evidence to suggest this may be too low. The aim of this study was to assess the potential for changing the cut point for the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) staging system from 45 years to 55 years based on a combined international patient cohort supplied by individual institutions.

What is the most appropriate intraoperative baseline parathormone? A prospective cohort study.

Introduction: The time of drawing pre-incision intraoperative parathyroid hormone (ioPTH) is crucial to provide the right baseline for post-excision PTH measurement. The objective of this study was to identify the optimal time and the numbers of baseline PTH samples that best predict excision of all hypercellular parathyroid tissue when compared with 10-min post-excision PTH level.

Materials And Methods: In this prospective study, two pre-incision (pre-induction and 10-min post-induction) baseline ioPTH samples along with pre- and post-excision ioPTH were collected and analyzed for 352 parathyroidectomies in 341 patients for sporadic primary hyperparathyroidism at a University hospital.

Stage II differentiated thyroid cancer: A mixed bag.

Background And Objectives: AJCC-TNM Stage II well-differentiated thyroid cancer (WDTC) comprises T2N0M0 tumors in patients ≥45 years of age or metastatic WDTC in patients younger than 45 years. The objectives of this study were to assess the oncological outcome of stage II WDTC and to compare the oncological outcome of metastatic WDTC in patient younger (stage II) and older (stage IVC) than 45 years.

Methods: This study involved review of clinical presentation and oncological outcome of population cohort of 2,128 consecutive WDTC, diagnosed during 1970-2010 that includes 215 Stage II WDTC and 61 metastatic WDTC.

Identifying the most appropriate age threshold for TNM stage grouping of well-differentiated thyroid cancer.

Objective: Age is integrated in most risk stratification systems for well-differentiated thyroid cancer (WDTC). The most appropriate age threshold for stage grouping of WDTC is debatable. The objective of this study was to evaluate the best age threshold for stage grouping by comparing multivariable models designed to evaluate the independent impact of various prognostic factors, including age based stage grouping, on the disease specific survival (DSS) of our population-based cohort.

The changing face of thyroid cancer in a population-based cohort.

In North America, the incidence of thyroid cancer is increasing by over 6% per year. We studied the trends and factors influencing thyroid cancer incidence, its clinical presentation, and treatment outcome during 1970-2010 in a population-based cohort of 2306 consecutive thyroid cancers in Canada, that was followed up for a median period of 10.5 years.

Prognostic nomograms to predict oncological outcome of thyroid cancers.

Context: Thyroid cancers represent a conglomerate of diverse histological types with equally variable prognosis. There is no reliable prognostic model to predict the risks of relapse and death for different types of thyroid cancers.

Objective: The purpose of this study was to build prognostic nomograms to predict individualized risks of relapse and death of thyroid cancer within 10 years of diagnosis based on patients' prognostic factors.

Impact of a regional acute care surgery model on patient access and outcomes.

Background: The consolidation of acute care surgery (ACS) services at 3 of 6 hospitals in a Canadian health region sought to alleviate a relative shortage of surgeons able to take emergency call. We examined how this affected patient access and outcomes.

Methods: Using the generalized linear model and statistical process control, we analyzed ACS-related episodes that occurred between 39 months prior to and 17 months after the model's implementation (n = 14,713).

The age factor in survival of a population cohort of well-differentiated thyroid cancer.

Well-differentiated thyroid carcinoma (WDTC) represents a group of thyroid cancers with excellent prognosis. Age, a well-recognized risk factor for WDTC, has been consistently included in various prognostic scoring systems. An age threshold of 45 years is currently used by the American Joint Cancer Committee-TNM staging system for the risk stratification of patients.

Head and neck soft tissue sarcoma.

Sarcomas are malignant neoplasms originating from mesodermal tissues and constitute less than 1% of body's tumors, including those of the head and neck region. 5-15% of adult sarcomas are in the head and neck region (20% from bones and cartilages and 80% in soft tissues). Commonly encountered sarcomas in the head and neck region are - osteosarcoma, rhabdomyosarcoma, malignant fibrous histiocytoma, fibrosarcoma and angiosarcoma.

P. aeruginosa infection increases morbidity in experimental cholesteatomas.

Objectives: Clinicians have long noted that infected cholesteatomas are more aggressive than uninfected ones without data to support these observations. The purpose of this study is to determine the etiological role of biofilm forming P. aeruginosa (PA) and the virulence factor, type IV pili (TFP), in the pathogenesis of experimental cholesteatomas.