Predicting premature termination of exercise during Bruce protocol stress echocardiography.

AIMS: Clinical guidelines recommend that the exercise protocol of a stress echocardiogram is selected to induce volitional exhaustion after a target duration of at least 8 minutes. While the Bruce protocol is very commonly used for clinical stress tests, it is known to be "steep", and many patients therefore fail to reach 8 minutes. We studied predictors of failure and developed a method for identifying patients not suitable for Bruce protocol which was accurate and yet simple enough to be used as a point-of-care decision support tool. METHODS AND RESULTS: We studied data out-patients undergoing Bruce protocol stress echocardiograms (n = 11 086) and analyzed predictors of inappropriate early termination (defined as test duration < 8 min as per current practice guidelines) using logistic regression. A prediction model was constructed as follows: .5 points were given for each of hypertension, diabetes, smoking, and E/e' > 7.9 in the resting echocardiogram; .1 point was added for each 1-unit increment in body mass index; 1 point was added for patient age by decade; 2.0 points were subtracted for male sex (p for all < 0.001). In tests on held-out validation data, the model was well calibrated (in plots of predicted vs actual risk) and discriminated failure versus non-failure well (C-statistic .86 for a score of 6.0 points; p < 0.001). CONCLUSION: These data may help to standardize protocol selection in stress echocardiography, by identifying patients pre-hoc where Bruce protocol will be inappropriately steep.

Statin use after intracerebral hemorrhage: a 10-year nationwide cohort study.

INTRODUCTION: Although statin therapy is beneficial to patients with ischemic stroke, statin use, and intracerebral hemorrhage (ICH) remain a concern. ICH survivors commonly have comorbid cardiovascular risk factors that would otherwise warrant cholesterol-lowering medication, thus emphasizing the importance of assessing the characteristics of statin therapy in this population. METHODS: We performed a cohort study by using 10 years of data collected from the National Health Insurance Research Database in Taiwan. We enrolled 726 patients admitted for newly diagnosed ICH from January 1, 2001 to December 31, 2010. The patients were categorized into high- (92), moderate- (545), and low-intensity (89) statin groups, and into hydrophilic (295) and lipophilic (431) statin groups. The composite outcomes included all-cause mortality, recurrent ICH, ischemic stroke, transient ischemic attack, and acute coronary events. RESULTS: The patients in the low-intensity group did not differ significantly from the patients in the high-intensity group in risk of all-cause mortality (adjusted hazard ratio [aHR] = 0.65, 95% confidence interval [CI] = 0.28-1.55) and recurrent ICH (aHR = 0.66, 95% CI = 0.30-1.44). In contrast, the patients in the hydrophilic group had a significantly lower risk of recurrent ICH than did those in the lipophilic group (aHR = 0.69, 95% CI = 0.48-0.99). We determined no significant differences in other composite endpoints between hydrophilic and lipophilic statin use. CONCLUSION: Hydrophilic statin therapy is associated with a reduced risk of recurrent ICH in post-ICH patients. The intensity of statin use had no significant effect on recurrent ICH or other components of the composite outcome. Additional studies are required to clarify the biological mechanisms underlying these observations.

Symptom severity of patients with advanced cancer in palliative care unit: longitudinal assessments of symptoms improvement.

BACKGROUND: This study assessed the symptom severity of patients with advanced cancer in a palliative care unit and explored the factors associated with symptom improvement. METHODS: This study was conducted in a palliative care unit in Taiwan between October 2004 and December 2009. Symptom intensity was measured by the "Symptom Reporting Form", and graded on a scale of 0 to 4 (0 = none, and 4 = extreme). These measures were assessed on the 1(st), 3(rd), 5(th), and 7(th) Day in the palliative care unit. The study data comprised routine clinical records and patients' demographic data. Generalized estimating equation (GEE) was used to assess the symptom improvement, and investigate the factors associated with the symptom reporting form scores. RESULTS: Among the 824 recruited patients with advanced cancer, pain (78.4%), anorexia (64.4%) and constipation (63.5%) were the most common and severe symptom. After controlling for other factors in the multivariate GEE model, the day of palliative care administration was a significant factor associated with all of the scales, except Days 7 on the dyspnoea and oedema scales and Day 5 on the anxiety scale. In addition, patients aged ≥ 65 years exhibited significantly lower scores on the pain, sleep disturbance, depression, and anxiety scales than did those aged < 65 years. Moreover, female patients exhibited higher scores on the vomiting, anorexia, oedema, depression, and anxiety scales than did male patients. Furthermore, patients with gastrointestinal tract cancer exhibited higher scores on the constipation, vomiting, anorexia, oedema, depression, and anxiety scales and lower scores on the dyspnoea scale than did those with lung cancer. Patients with breast cancer exhibited higher scores on the oedema scale and lower scores on the anxiety scale. Patients with genitourinary cancer exhibited higher scores on the vomiting and oedema scales and lower scores on the dyspnoea scale. Patients with head, neck, and oral cancer exhibited lower scores on the oedema scale alone. CONCLUSION: The symptom severity declined during the first week in the palliative care unit. In addition, differences in sex and primary cancer sites may contribute to varying degrees of symptom improvement.

Clinical risk factors of prediabetes in Taiwanese women without substance uses (tobacco, alcohol, or areca nut).

BACKGROUND/PURPOSE: Individuals with prediabetes (100-125 mg/dL) and diabetes mellitus (DM) increase the risk of all-cause and cardiovascular disease (CVD) mortality. Since personal substance use such as cigarette smoking, alcohol drinking, and areca nut chewing may confound the true effect of clinical biochemistries on the risk of prediabetes, this study aims to examine the relationship between clinical biochemical parameters and the risk of prediabetes among Taiwanese without the habits of consuming tobacco, alcohol drinking, or areca nut. METHODS: Women aged between 40 years and 64 years who came to one community teaching hospital between January 1, 2001 and December 31, 2008 for general health screening for the first time were studied. The general health screening is provided every 3 years gratis. The package of this health screening includes personal history, physical examination, and biochemical tests in serum and urine. RESULTS: In total, 8580 nonsmoking, nondrinking, and nonareca nut chewing women who did not have a history of DM were eligible for this study. Of these, 1861 (21.7%) out of 8580 women were prediabetic. Compared to women with normal fasting glucose (NFG), we found a dose-response relationship of the risk of prediabetes with age and body mass index (BMI) and total cholesterol, triglyceride, glutamic-pyruvic transaminase (GPT), and uric acid in serum. Women with hypertension or proteinuria (≥30 mg/dL) had also an increased risk to have prediabetes. CONCLUSION: Besides age, the factors of BMI, hypertension, dyslipidemia, GPT, hyperuricemia, and proteinuria are the main risk factors for prediabetes in Taiwanese women without substance uses. A follow-up study is necessary to clarify the causality of these important biochemical parameters and prediabetes.

Effects of marital status and shift work on family function among registered nurses.

This study aims to assess the interactive effect of marital status and shift work on family function. A population-based sample of 1,438 nurses between the ages of 20-45 yr was recruited from Taiwan during the period from July 2005 to April 2006 using a mailed questionnaire. The self-administered questionnaire contained information about demographic data, work status, shift work schedule, and the Family APGAR (Adaptation, Partnership, Growth, Affection, and Resolve) Scale, to evaluate family function. Compared to day shift nurses, non-night and rotation shift nurses had 1.53- and 1.38-fold (95% CI=1.09-2.14 and 1.01-1.88) risk to have poor family function after adjusting for other covariates. Married nurses, by contrast, had a 0.44-fold (95% CI=0.29-0.66) risk to have poor family function compared to single nurses. In addition, married nurses who worked non-night or rotation shifts had a significantly higher percent of poor family function than those married nurses working day shifts; however, similar results were not replicated in single nurses. We concluded that shift work and marital status could influence family function.

Iliofemoral anatomy among Asians: implications for transcatheter aortic valve implantation.

BACKGROUND/OBJECTIVES: This study aims to examine iliofemoral anatomy and predictors of vessel size and tortuosity in Asian patients as transfemoral transcatheter aortic valve implantation (TAVI) may be limited by the smaller Asian physique. METHODS: Characteristics and vessel dimensions of 549 patients undergoing ultrasonography were reviewed. The minimal luminal diameter (MLD) along the iliofemoral vasculature of each side was identified and the larger of the two sides was used to determine suitability for transfemoral TAVI. RESULTS: The mean age was 66 ± 11 years (68% males). Mean iliac MLD was 7.6 ± 1.7 mm, females smaller than males (7.2 ± 1.7 vs 7.8 ± 1.7, p<0.001). Mean iliac MLD decreased with age: 7.9 ± 1.7 mm, 7.4 ± 1.9 mm and 7.3 ± 1.6mm for ages <70 years, 70-79 years and ≥ 80 years respectively (p=0.038). Mean femoral MLD was 7.0 ± 1.7 mm, females smaller than males (6.3 ± 1.5mm vs 7.3 ± 1.8mm, p<0.001). Females were more likely than males to have iliac and femoral MLD <6mm (20% vs 12%, p=0.019 and 34% vs 21%, p=0.001). Independent predictors of smaller iliofemoral dimensions were female gender, lower body surface area, diabetes mellitus, dyslipidemia and smoking history. Significant iliac tortuosity was present in 11.8%, more frequent in males than females (15% vs 6%, p=0.005), and in those with logistic EuroSCORE ≥ 15 than <15 (27% vs 10%, p=0.001). CONCLUSIONS: This study establishes the mean iliac and femoral artery diameters in a cohort of relatively young Asian patients. Age and female gender were associated with smaller vessel dimension and several independent predictors of smaller vasculature and tortuosity were identified. These results have implications for TF TAVI in Asia.

The ailing gut: a therapeutic role for bone marrow cells?

It is obvious that the BM does more than simply supply the GIT with cells of the innate and adaptive immune system. A growing number of studies suggest that BMCs can differentiate into ISEMFs (Lee et al., PLOS ONE 2011;6:e26082) and in the setting of inflammation can be contributors to all lineages of the neovasculature. The role of BMCs in epithelial turnover is more problematic; their contribution after transient mucosal injury seems negligible, but a number of studies in both rodents and man suggest that small numbers of BMCs can be incorporated into the epithelial compartment with more chronic injury (e.g., GvHD in man and chemically induced colitis in rodents); commonly cell fusion seems to be responsible for this. Significantly, this engraftment does not seem to occur in the stem-cell compartment, with the notable single report of the chronically infected murine gastric mucosa, where the BM origin of the stem cells can be the only rational explanation for the complete colonization of the mucosa by BMDCs. In the clinical setting, a role for MSCs in ameliorating colitis seems promising, though the mechanisms by which this is achieved remain somewhat unclear, though both immunomodulatory and regenerative effects of BMCs are likely to be important.

Bone marrow cells in murine colitis: multi-signal analysis confirms pericryptal myofibroblast engraftment without epithelial involvement.

BACKGROUND: The contribution of bone marrow-derived cells to epithelial tissues in the inflamed gut remains controversial. Recent reports have suggested that cell fusion between bone marrow-derived cells and the intestinal epithelium takes place in inflammatory conditions. METHODS: In attempts to confirm this, we have undertaken gender mis-matched bone marrow (BM) transplants from male Swiss Webster (SWR) mice to B and T cell-deficient female Rag2 KO mice which, 4 weeks later, were given 5% dextran sodium sulphate in drinking water to induce acute colitis. A further BM-treated group of animals with a graft versus host-like condition was also studied. We developed a new method to combine up to three brightfield or fluorescent lectin- or immuno-histochemical signals with fluorescent in situ hybridisation for the Y and X chromosomes to enable us unequivocally to identify BM-derived male cells which presented as different cell types in the gastrointestinal tract. PRINCIPAL FINDINGS: In rolled preparations of whole intestines we scanned around 1.5 million crypts at many tissue levels. In no instance did we see a Y chromosome-positive cell in the epithelial compartment, which was not also CD45-positive. We saw no evidence of cell fusion, based on combined X and Y chromosome analysis. Levels of CD45-positive stromal and lymphoid cells and pericryptal myfibroblasts (positive for α-smooth muscle actin) increased with time up to a plateau, which resembled the level seen in untreated control grafted animals. We saw very few Y chromosome-positive endothelial cells in intestinal stromal vessels. CONCLUSIONS: We conclude that whole BM transplantation does not result in intestinal epithelial engraftment in this model. Our new methods can usefully assist in multi-signal analyses of cell phenotypes following BM transplant and in models of chimaerism and regenerative medicine.

Mechanisms of field cancerization in the human stomach: the expansion and spread of mutated gastric stem cells.

BACKGROUND & AIMS: How mutations are established and spread through the human stomach is unclear because the clonal structure of gastric mucosal units is unknown. Here we investigate, using mitochondrial DNA (mtDNA) mutations as a marker of clonal expansion, the clonality of the gastric unit and show how mutations expand in normal mucosa and gastric mucosa showing intestinal metaplasia. This has important implications in gastric carcinogenesis. METHODS: Mutated units were identified by a histochemical method to detect activity of cytochrome c oxidase. Negative units were laser-capture microdissected, and mutations were identified by polymerase chain reaction sequencing. Differentiated epithelial cells were identified by immunohistochemistry for lineage markers. RESULTS: We show that mtDNA mutations establish themselves in stem cells within normal human gastric body units, and are passed on to all their differentiated progeny, thereby providing evidence for clonal conversion to a new stem cell-derived unit-monoclonal conversion, encompassing all gastric epithelial lineages. The presence of partially mutated units indicates that more than one stem cell is present in each unit. Mutated units can divide by fission to form patches, with each unit sharing an indentical, mutant mtDNA genotype. Furthermore, we show that intestinal metaplastic crypts are clonal, possess multiple stem cells, and that fission is a mechanism by which intestinal metaplasia spreads. CONCLUSIONS: These data show that human gastric body units are clonal, contain multiple multipotential stem cells, and provide definitive evidence for how mutations spread within the human stomach, and show how field cancerization develops.

Identification of blottin: a novel gastric trefoil factor family-2 binding protein.

The trefoil factor family (TFF) peptides are important in gastro-intestinal mucosal protection and repair. Their mechanism of action remains unclear and receptors are sought. We aimed to identify and characterise proteins binding to TFF2. A fusion protein of mouse TFF2 with alkaline phosphatase was generated and used to probe 2-D protein blots of mouse stomach. The resulting spots were analysed by MS. The protein identified was characterised by bioinformatics, rapid amplification of cDNA ends, in situ hybridisation (ISH) and immunohistochemistry (IHC). Functional assays were performed in gastrointestinal cell lines. A single major murine protein was identified and named blottin. It was previously unknown as a translated product. Blottin is also present in rat and human; the latter gene is also known as GDDR. The predicted full-length proteins are 184 amino acids long (20 kDa), reducing to 164 amino acids (18 kDa) after signal peptide cleavage. ISH of gastrointestinal tissues shows abundant blottin mRNA in gastric surface and foveolar epithelium. IHC shows cytoplasmic staining for blottin protein, and by immunoelectron microscopy in mucus granules and Golgi stacks. Previous work showed that blottin is down-regulated in gastric cancers. Blottin contains a BRICHOS domain, and has 56% similarity with gastrokine-1. Cultured HT-29 cells express blottin and show increased DNA synthesis with antiblottin antibody; however, this effect is reversed by the immunising peptide. We have identified and characterised a TFF2-binding protein produced by gastric epithelium. Blottin may play a role in gastrointestinal mucosal protection and modulate gut epithelial cell proliferation.