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- Chandanos, Evangelos, et al.
(författare)
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Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma
- 2008
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Ingår i: Gastric Cancer. - : Springer Science and Business Media LLC. - 1436-3291 .- 1436-3305. ; 11:3, s. 168-174
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Estrogen might protect women against gastric adenocarcinoma of the intestinal histological type. We addressed this hypothesis and proposed that gastric estrogen receptors (ERs) are involved. METHODS: A population-based cohort of patients with gastric adenocarcinoma diagnosed in 1958-2004 in the county of Stockholm was identified through the Swedish Cancer Register. The patients were categorized regarding their endogenous estrogen exposure at diagnosis into: women aged less than 50 years, labelled "exposed women" (n=364), men aged less than 50 years, labelled "unexposed men" (n=396), and women aged more than 70 years, labelled "unexposed women" (n=3008). Tumor specimens were reviewed, and 289 cases were classified into intestinal (n=101) or diffuse type (n=188). Cases of intestinal adenocarcinomas (n=45) were tested for presence of ERalpha, ERbeta, and ERbeta cx by immunohistochemistry. RESULTS: Compared to "exposed women", the intestinal type of gastric adenocarcinoma was more than four times more common among "unexposed men" (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.2-10.3) and nine times more common among "unexposed women" (OR, 9.1; 95% CI, 4.3-19.6). No differences in ER expression were found. A comparison of ERs in tissues taken from the tumors and adjacent gastric mucosa revealed a loss of ERbeta and a gain of ERalpha in the tumor cells. The presence of ERbeta cx was identified for the first time in gastric tumors. CONCLUSION: Gastric adenocarcinoma of the intestinal type is less common in women with high endogenous estrogen exposure, indicating a preventive effect of estrogen. No differences in the distribution of ERs was found between the three estrogen exposure groups. The presence of ERbeta cx in gastric cancer warrants further investigation.
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- Gedeborg, Rolf, et al.
(författare)
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Internationally comparable diagnosis-specific survival probabilities for calculation of the ICD-10-based Injury Severity Score
- 2014
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Ingår i: Journal of Trauma and Acute Care Surgery. - 2163-0755. ; 76:2, s. 358-365
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The International Statistical Classification of Diseases, 10th Revision (ICD-10) -based Injury Severity Score (ICISS) performs well but requires diagnosis-specific survival probabilities (DSPs), which are empirically derived, for its calculation. The objective was to examine if DSPs based on data pooled from several countries could increase accuracy, precision, utility, and international comparability of DSPs and ICISS. METHODS: Australia, Argentina, Austria, Canada, Denmark, New Zealand, and Sweden provided ICD-10-coded injury hospital discharge data, including in-hospital mortality status. Data from the seven countries were pooled using four different methods to create an international collaborative effort ICISS (ICE-ICISS). The ability of the ICISS to predict mortality using the country-specific DSPs and the pooled DSPs was estimated and compared. RESULTS: The pooled DSPs were based on a total of 3,966,550 observations of injury diagnoses from the seven countries. The proportion of injury diagnoses having at least 100 discharges to calculate the DSP varied from 12% to 48% in the country-specific data set and was 66% in the pooled data set. When compared with using a country's own DSPs for ICISS calculation, the pooled DSPs resulted in somewhat reduced discrimination in predicting mortality (difference in c statistic varied from 0.006 to 0.04). Calibration was generally good when the predicted mortality risk was less than 20%. When Danish and Swedish data were used, ICISS was combined with age and sex in a logistic regression model to predict in-hospital mortality. Including age and sex improved both discrimination and calibration substantially, and the differences from using country-specific or pooled DSPs were minor. CONCLUSION: Pooling data from seven countries generated empirically derived DSPs. These pooled DSPs facilitate international comparisons and enables the use of ICISS in all settings where ICD-10 hospital discharge diagnoses are available. The modest reduction in performance of the ICE-ICISS compared with the country-specific scores is unlikely to outweigh the benefit of internationally comparable Injury Severity Scores possible with pooled data.
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- Gedeborg, Rolf, et al.
(författare)
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Prehospital injury deaths-Strengthening the case for prevention : Nationwide cohort study
- 2012
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Ingår i: Journal of Trauma and Acute Care Surgery. - 2163-0755 .- 2163-0763. ; 72:3, s. 765-772
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To determine the frequency and characteristics of prehospital deaths compared with hospital deaths in different subpopulations with severe injuries.METHODS: Population-based cohort study using person-based linkage of the Swedish nationwide hospital discharge register with death certificate data. In all, 28,715 injury deaths were identified among 419,137 cases of severe injury during 1998 to 2004. Prehospital deaths were defined as autopsied out-of-hospital deaths with injury as the underlying cause. Their impact on mortality prediction was assessed using the International Classification of Disease Injury Severity Score with the C statistic as a measure of discrimination.RESULTS: The majority of all injury deaths occurred either at the scene or before hospitalization. Among persons younger than 65 years, for each hospital death there were nine prehospital deaths. A high proportion of deaths from drowning, suffocation, and firearm injuries were prehospital (85, 82, and 67% of all cases, respectively). More than 90% of hospital deaths resulted from unintentional injuries, while only 43% of prehospital deaths were unintentional. The largest increase in a cause-specific case fatality risk estimate was seen for poisoning, where inclusion of prehospital deaths increased the risk estimate from 1.6% to 22.8%. Injury mortality prediction based on International Classification of Disease Injury Severity Score improved when prehospital deaths were added to hospital data (C statistic increased from 0.86 to 0.93).CONCLUSIONS: Prehospital deaths constitute the majority of trauma deaths and differ in major characteristics from hospital deaths. The high proportion of prehospital deaths among young and middle aged people highlights the potential impact of preventive efforts.
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- Muñoz, Nubia, et al.
(författare)
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Impact of Human Papillomavirus (HPV)-6/11/16/18 Vaccine on All HPV-Associated Genital Diseases in Young Women.
- 2010
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 102, s. 325-339
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Tidskriftsartikel (refereegranskat)abstract
- Background The impact of the prophylactic vaccine against human papillomavirus (HPV) types 6, 11, 16, and 18 (HPV6/11/16/18) on all HPV-associated genital disease was investigated in a population that approximates sexually naive women in that they were "negative to 14 HPV types" and in a mixed population of HPV-exposed and -unexposed women (intention-to-treat group). Methods This analysis studied 17 622 women aged 15-26 years who were enrolled in one of two randomized, placebo-controlled, efficacy trials for the HPV6/11/16/18 vaccine (first patient on December 28, 2001, and studies completed July 31, 2007). Vaccine or placebo was given at day 1, month 2, and month 6. All women underwent cervicovaginal sampling and Papanicolaou (Pap) testing at day 1 and every 6-12 months thereafter. Outcomes were any cervical intraepithelial neoplasia; any external anogenital and vaginal lesions; Pap test abnormalities; and procedures such as colposcopy and definitive therapy. Absolute rates are expressed as women with endpoint per 100 person-years at risk. Results The average follow-up was 3.6 years (maximum of 4.9 years). In the population that was negative to 14 HPV types, vaccination was up to 100% effective in reducing the risk of HPV16/18-related high-grade cervical, vulvar, and vaginal lesions and of HPV6/11-related genital warts. In the intention-to-treat group, vaccination also statistically significantly reduced the risk of any high-grade cervical lesions (19.0% reduction; rate vaccine = 1.43, rate placebo = 1.76, difference = 0.33, 95% confidence interval [CI] = 0.13 to 0.54), vulvar and vaginal lesions (50.7% reduction; rate vaccine = 0.10, rate placebo = 0.20, difference = 0.10, 95% CI = 0.04 to 0.16), genital warts (62.0% reduction; rate vaccine = 0.44, rate placebo = 1.17, difference = 0.72, 95% CI = 0.58 to 0.87), Pap abnormalities (11.3% reduction; rate vaccine = 10.36, rate placebo = 11.68, difference = 1.32, 95% CI = 0.74 to 1.90), and cervical definitive therapy (23.0% reduction; rate vaccine = 1.97, rate placebo = 2.56, difference = 0.59, 95% CI = 0.35 to 0.83), irrespective of causal HPV type. Conclusions High-coverage HPV vaccination programs among adolescents and young women may result in a rapid reduction of genital warts, cervical cytological abnormalities, and diagnostic and therapeutic procedures. In the longer term, substantial reductions in the rates of cervical, vulvar, and vaginal cancers may follow.
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- Yakimchuk, Konstantin, et al.
(författare)
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Up-regulated estrogen receptor β2 in chronic lymphocytic leukemia
- 2012
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Ingår i: Leukemia and Lymphoma. - : Informa UK Limited. - 1042-8194 .- 1029-2403. ; 53:1, s. 139-144
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Tidskriftsartikel (refereegranskat)abstract
- The estrogen receptors alpha (ERα) and beta (ERβ) have been demonstrated in mouse models to be important for immune system regulation, and are differentially expressed in lymphoid organs. One ERβ splice variant, ERβ2, inhibits the ERα-mediated estrogen effect, and expression might predict response to selective estrogen receptor modulators. We studied the expression of ERα, ERβ1 and ERβ2 in peripheral blood mononuclear cells from 26 patients with chronic lymphocytic leukemia (CLL) and 30 normal controls using immunocytochemistry. ERα expression was generally low, while ERβ1 was expressed in 65% of patients with CLL and in 83% of controls (NS). In contrast, nuclear staining for ERβ2 was positive in 69% of patients with CLL, but in only 17% of controls (p < 0.001). In CLL, ERβ2 was found in B- but not in T-lymphocytes. Our data show the expression of ERβ1 and ERβ2 in the majority of patients with CLL, suggesting that the ERs are important in CLL and might be used as therapeutic targets.
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