Patients with multiple serrated polyps are at an increased risk for developing colorectal cancer (CRC). Recent reports have linked cigarette smoking with the subset of CRC that develops from serrated ...polyps. The aim of this work therefore was to investigate the association between smoking and the risk of CRC in high-risk genetics clinic patients presenting with multiple serrated polyps.
We identified 151 Caucasian individuals with multiple serrated polyps including at least 5 outside the rectum, and classified patients into non-smokers, current or former smokers at the time of initial diagnosis of polyposis. Cases were individuals with multiple serrated polyps who presented with CRC. Controls were individuals with multiple serrated polyps and no CRC. Multivariate logistic regression was performed to estimate associations between smoking and CRC with adjustment for age at first presentation, sex and co-existing traditional adenomas, a feature that has been consistently linked with CRC risk in patients with multiple serrated polyps. CRC was present in 56 (37%) individuals at presentation. Patients with at least one adenoma were 4 times more likely to present with CRC compared with patients without adenomas (OR = 4.09; 95%CI 1.27 to 13.14; P = 0.02). For females, the odds of CRC decreased by 90% in current smokers as compared to never smokers (OR = 0.10; 95%CI 0.02 to 0.47; P = 0.004) after adjusting for age and adenomas. For males, there was no relationship between current smoking and CRC. There was no statistical evidence of an association between former smoking and CRC for both sexes.
A decreased odds for CRC was identified in females with multiple serrated polyps who currently smoke, independent of age and the presence of a traditional adenoma. Investigations into the biological basis for these observations could lead to non-smoking-related therapies being developed to decrease the risk of CRC and colectomy in these patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Serrated polyposis (hyperplastic polyposis) is characterized by multiple polyps with serrated architecture in the colorectum. Although patients with serrated polyposis are known to be at increased ...risk of colorectal cancer (CRC) and possibly extracolonic cancers, cancer risk for their relatives has not been widely explored. The aim of this study was to estimate the risks of CRC and extracolonic cancers for relatives of patients with serrated polyposis.
A cohort of the 1,639 first- and second-degree relatives of 100 index patients with serrated polyposis recruited regardless of a family history of polyps or cancer from genetic clinics in Australia, New Zealand, Canada, and the USA, were retrospectively analyzed to estimate the country-, age-, and sex-specific standardized incidence ratios (SIRs) for relatives compared with the general population.
A total of 102 CRCs were observed in first- and second-relatives (SIR 2.25, 95% confidence interval (CI) 1.75-2.93; P<0.001), with 54 in first-degree relatives (SIR 5.16, 95% CI 3.70-7.30; P<0.001) and 48 in second-degree relatives (SIR 1.38, 95% CI 1.01-1.91; P=0.04). Six pancreatic cancers were observed in first-degree relatives (SIR 3.64, 95% CI 1.70-9.21; P=0.003). There was no statistical evidence of increased risk for cancer of the stomach, brain, breast, or prostate.
Our finding that relatives of serrated polyposis patients are at significantly increased risk of colorectal and pancreatic cancer adds to the accumulating evidence that serrated polyposis has an inherited component.
The warm season (mid‐June through late August) partitioning between sensible (H) and latent (LE) heat flux, or the Bowen ratio (β = H/LE), was investigated at 27 sites over 66 site years within the ...international network of eddy covariance sites (FLUXNET). Variability in β across ecosystems and climates was analyzed by quantifying general climatic and surface characteristics that control flux partitioning. The climatic control on β was quantified using the climatological resistance (Ri), which is proportional to the ratio of vapor pressure deficit (difference between saturation vapor pressure and atmospheric vapor pressure) to net radiation (large values of Ri decrease β). The control of flux partitioning by the vegetation and underlying surface was quantified by computing the surface resistance to water vapor transport (Rc, with large values tending to increase β). There was a considerable range in flux partitioning characteristics (Rc, Ri and β) among sites, but it was possible to define some general differences between vegetation types and climates. Deciduous forest sites and the agricultural site had the lowest values of Rc and β (0.25–0.50). Coniferous forests typically had a larger Rc and higher β (typically between 0.50 and 1.00 but also much larger). However, there was notable variability in Rc and Ri between coniferous site years, most notably differences between oceanic and continental climates and sites with a distinct dry summer season (Mediterranean climate). Sites with Mediterranean climates generally had the highest net radiation, Rc, Ri, and β. There was considerable variability in β between grassland site years, primarily the result of interannual differences in soil water content and Rc.
Summary Background & aims This study assessed the effects of administering a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid before and after open-heart surgery on cytokine ...production and length of hospital stay in infants. Methods Thirty-two infants (40 ± 2.3 weeks gestational age; 10.6 days at time of surgery) undergoing open-heart surgery with cardiopulmonary bypass were randomized to receive an intravenous lipid emulsion with (treatment) or without (control) eicosapentaenoic and docosahexaenoic acid in this prospective, randomized, double-blind, controlled trial. Results Mean plasma TNF-α concentration was significantly ( p = 0.003) lower in the treatment (5.9 pg/mL) compared to the control group (14.8 pg/mL). In infants without sepsis, plasma TNF-α did not differ according to treatment, however when sepsis developed, mean plasma TNF-α was 21.1 pg/mL and 1.5 pg/mL ( p = 0.0007) in control and treatment groups, respectively. Plasma TNF-α was positively correlated with length of hospital stay in the control group ( p = 0.01), and negatively correlated with length of stay in the treatment group ( p = 0.004), with a significant time by treatment interaction ( p = 0.02). Conclusions Providing a lipid emulsion containing eicosapentaenoic and docosahexaenoic acid reduces TNF-α concentrations in infants undergoing open-heart surgery. Lipid emulsions containing eicosapentaenoic and docosahexaenoic acid may ameliorate the inflammatory response among critically ill infants. This trial was registered at clinicaltrials.gov as NCT00336908.
Faculties of 1 Medicine, 2 Physical Education, and 3 Agricultural, Food, and Nutritional Sciences, University of Alberta, Edmonton, Canada
Submitted 2 June 2004
; accepted in final form 19 November ...2004
ABSTRACT
The objective was to determine the effects of exercise training on changes in blood immune function in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise ( n = 25) or control group ( n = 28). The exercise group trained on cycle ergometers three times per week for 15 wk. The control group did not train. The primary end point was change in natural killer cell cytotoxic activity in isolated peripheral blood mononuclear cells. Secondary end points were changes in standard hematological variables, whole blood neutrophil function, the phenotypes of isolated mononuclear cells, estimations of unstimulated and phytohemaglutinin-stimulated mononuclear cell function (rate of 3 Hthymidine uptake), and the production of proinflammatory interleukin (IL)-1 , tumor necrosis factor- , IL-6 and anti-inflammatory cytokines (IL-4, IL-10, transforming growth factor- 1 ). Statistical tests were two-sided ( < 0.05). Fifty-two participants completed the trial. Intention-to-treat analyses, which included the baseline value as a covariate, showed significant differences between groups for change in percent specific lysis of a target natural killer cell at all five effector-to-target ratios (adjusted mean between-group change over all 5 effector-to-target ratios = +6.34%; P < 0.05 for all comparisons), the lytic activity per cell (adjusted mean between-group change = 2.72 lytic units; P = 0.035), and unstimulated 3 Hthymidine uptake by peripheral blood lymphocytes (adjusted mean between-group change = +218 per dpm x 10 6 cells; P = 0.007). There were no significant differences between groups for change in any other end point. Exercise training increased natural killer cell cytotoxic activity and unstimulated 3 Hthymidine uptake by peripheral blood lymphocytes in postmenopausal breast cancer survivors.
clinical exercise physiology; natural killer cell cytotoxic activity; unstimulated 3 Hthymidine uptake
Address for reprint requests and other correspondence: K. S. Courneya, Faculty of Physical Education, Univ. of Alberta, E-424 Van Vliet Center, Edmonton, Alberta, Canada T6G 2H9 (E-mail: kerry.courneya{at}ualberta.ca )
Objective We sought to evaluate whether the presence of condition-specific obstetric protocols within a hospital was associated with better maternal and neonatal outcomes. Study Design This was a ...cohort study of a random sample of deliveries performed at 25 hospitals over 3 years. Condition-specific protocols were collected from all hospitals and categorized independently by 2 authors. Data on maternal and neonatal outcomes, as well as data necessary for risk adjustment were collected. Risk-adjusted outcomes were compared according to whether the patient delivered in a hospital with condition-specific obstetric protocols at the time of delivery. Results Hemorrhage-specific protocols were not associated with a lower rate of postpartum hemorrhage or with fewer cases of estimated blood loss >1000 mL. Similarly, in the presence of a shoulder dystocia protocol, there were no differences in the frequency of shoulder dystocia or number of shoulder dystocia maneuvers used. Conversely, preeclampsia-specific protocols were associated with fewer intensive care unit admissions (odds ratio, 0.28; 95% confidence interval, 0.18–0.44) and fewer cases of severe maternal hypertension (odds ratio, 0.86; 95% confidence interval, 0.77–0.96). Conclusion The presence of condition-specific obstetric protocols was not consistently shown to be associated with improved risk-adjusted outcomes. Our study would suggest that the presence or absence of a protocol does not matter and regulations to require protocols are not fruitful.
Missense variants are a major source of human genetic variation. Here we analyze a new mouse missense variant, Rasgrp1(Anaef), with an ENU-mutated EF hand in the Rasgrp1 Ras guanine nucleotide ...exchange factor. Rasgrp1(Anaef) mice exhibit anti-nuclear autoantibodies and gradually accumulate a CD44(hi) Helios(+) PD-1(+) CD4(+) T cell population that is dependent on B cells. Despite reduced Rasgrp1-Ras-ERK activation in vitro, thymocyte selection in Rasgrp1(Anaef) is mostly normal in vivo, although CD44 is overexpressed on naïve thymocytes and T cells in a T-cell-autonomous manner. We identify CD44 expression as a sensitive reporter of tonic mTOR-S6 kinase signaling through a novel mouse strain, chino, with a reduction-of-function mutation in Mtor. Elevated tonic mTOR-S6 signaling occurs in Rasgrp1(Anaef) naïve CD4(+) T cells. CD44 expression, CD4(+) T cell subset ratios and serum autoantibodies all returned to normal in Rasgrp1(Anaef)Mtor(chino) double-mutant mice, demonstrating that increased mTOR activity is essential for the Rasgrp1(Anaef) T cell dysregulation. DOI: http://dx.doi.org/10.7554/eLife.01020.001.
This overview will demonstrate that cough is a common and potentially expensive health-care problem. Improvement in the quality of care of those with cough has been the focus of study for a variety ...of disciplines in medicine. The purpose of the Cough Guideline and Expert Panel is to synthesize current knowledge in a form that will aid clinical decision-making for the diagnosis and management of cough across disciplines and also identify gaps in knowledge and treatment options.
IMPORTANCE: The time-benefit association of endovascular thrombectomy (EVT) in ischemic stroke with patient-reported outcomes is unknown. OBJECTIVE: To assess the time-dependent association of EVT ...with self-reported quality of life in patients with acute ischemic stroke. DESIGN, SETTING, AND PARTICIPANTS: Data were used from the Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke (ESCAPE-NA1) trial, which tested the effect of nerinetide on functional outcomes in patients with large vessel occlusion undergoing EVT and enrolled patients from March 1, 2017, to August 12, 2019. The ESCAPE-NA1 trial was an international randomized clinical trial that recruited patients from 7 countries. Patients with EuroQol 5-dimension 5-level (EQ-5D-5L) index values at 90 days and survivors with complete domain scores were included in the current study. Data were analyzed from July to September 2023. EXPOSURE: Hospital arrival to arterial puncture time and other time metrics. MAIN OUTCOMES AND MEASURES: EQ-5D-5L index scores were calculated at 90 days using country-specific value sets. The association between time from hospital arrival to EVT arterial-access (door-to-puncture) and EQ-5D-5L index score, quality-adjusted life years, and visual analog scale (EQ-VAS) were evaluated using quantile regression, adjusting for age, sex, stroke severity, stroke imaging, wake-up stroke, alteplase, and nerinetide treatment and accounting for clustering by site. Using logistic regression, the association between door-to-puncture time and reporting no or slight symptoms (compared with moderate, severe, or extreme problems) was determined in each domain (mobility, self-care, usual activities, pain or discomfort, and anxiety or depression) or across all domains. Time from stroke onset was also evaluated, and missing data were imputed in sensitivity analyses. RESULTS: Among 1105 patients in the ESCAPE-NA1 trial, there were 1043 patients with EQ-5D-5L index values at 90 days, among whom 147 had died and were given a score of 0, and 1039 patients (mean SD age, 69.0 13.7 years; 527 male 50.7%) in the final analysis as 4 did not receive EVT. There were 896 survivors with complete domain scores at 90 days. There was a strong association between door-to-puncture time and EQ-5D-5L index score (increase of 0.03; 95% CI, 0.02-0.04 per 15 minutes of earlier treatment), quality-adjusted life years (increase of 0.29; 95% CI, 0.08-0.49 per 15 minutes of earlier treatment), and EQ-VAS (increase of 1.65; 95% CI, 0.56-2.72 per 15 minutes of earlier treatment). Each 15 minutes of faster door-to-puncture time was associated with higher probability of no or slight problems in each of 5 domains and all domains concurrently (range from 1.86%; 95% CI, 1.14-2.58 for pain or discomfort to 3.55%; 95% CI, 2.06-5.04 for all domains concurrently). Door-to-puncture time less than 60 minutes was associated higher odds of no or slight problems in each domain, ranging from odds ratios of 1.49 (95% CI, 1.13-1.95) for pain or discomfort to 2.59 (95% CI, 1.83-3.68) for mobility, with numbers needed to treat ranging from 7 to 17. Results were similar after multiple imputation of missing data and attenuated when evaluating time from stroke onset. CONCLUSIONS AND RELEVANCE: Results suggest that faster door-to-puncture EVT time was strongly associated with better health-related quality of life across all domains. These results support the beneficial impact of door-to-treatment speed on patient-reported outcomes and should encourage efforts to improve patient-centered care in acute stroke by optimizing in-hospital processes and workflows.
PDF
