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1.
JAMA Oncol ; 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33475710

RESUMO

Importance: Although aspirin is recommended for the prevention of colorectal cancer (CRC) among adults aged 50 to 59 years, recent data from a randomized clinical trial suggest a lack of benefit and even possible harm among older adults. Objective: To examine the association between aspirin use and the risk of incident CRC among older adults. Design, Setting, and Participants: A pooled analysis was conducted of 2 large US cohort studies, the Nurses' Health Study (June 1, 1980-June 30, 2014) and Health Professionals Follow-up Study (January 1, 1986-January 31, 2014). A total of 94 540 participants aged 70 years or older were included and followed up to June 30, 2014, for women or January 31, 2014, for men. Participants with a diagnosis of any cancer, except nonmelanoma skin cancer, or inflammatory bowel disease were excluded. Statistical analyses were conducted from December 2019 to October 2020. Main Outcomes and Measures: Cox proportional hazards models were used to calculate multivariable adjusted hazard ratios (HRs) and 95% CIs for incident CRC. Results: Among the 94 540 participants (mean [SD] age, 76.4 [4.9] years for women, 77.7 [5.6] years for men; 67 223 women [71.1%]; 65 259 White women [97.1%], 24 915 White men [96.0%]) aged 70 years or older, 1431 incident cases of CRC were documented over 996 463 person-years of follow-up. After adjustment for other risk factors, regular use of aspirin was associated with a significantly lower risk of CRC at or after age 70 years compared with nonregular use (HR, 0.80; 95% CI, 0.72-0.90). However, the inverse association was evident only among aspirin users who initiated aspirin use before age 70 years (HR, 0.80; 95% CI, 0.67-0.95). In contrast, initiating aspirin use at or after 70 years was not significantly associated with a lower risk of CRC (HR, 0.92; 95% CI, 0.76-1.11). Conclusions and Relevance: Initiating aspirin at an older age was not associated with a lower risk of CRC in this pooled analysis of 2 cohort studies. In contrast, those who used aspirin before age 70 years and continued into their 70s or later had a reduced risk of CRC.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33418133

RESUMO

OBJECTIVE: The etiology of diverticulitis is poorly understood. The long-held belief that constipation and low-fiber diet are risk factors for diverticulosis has recently been challenged by studies that suggest that more frequent bowel movements predispose to diverticulosis. We aim to prospectively explore the association between bowel movement frequency and incident diverticulitis. DESIGN: We studied participants of the Nurses' Health Study (NHS) and Health Professional Follow-up Study (HPFS). Participants' medical history, lifestyle factors and diet were used in Cox proportional hazards regression models to estimate multivariable-adjusted hazard ratios(HRs) and 95% confidence intervals(CI). RESULTS: In the NHS during over 24 years of follow-up encompassing 1,299,922 person-years, we documented 5,214 incident cases of diverticulitis, and in HPFS over 14 years encompassing 368,661 person-years of follow-up, we documented 390 incident cases of diverticulitis. We observed an inverse association between the frequency of bowel movements and risk of diverticulitis. In NHS, compared to women who had daily bowel movements, those with more than once daily bowel movements had a HR of 1.30 (95%CI 1.19, 1.42) and those with less frequent bowel movements had a HR of 0.89 (95%CI 0.82, 0.95; p-trend<0.0001). In HPFS, the corresponding HRs were 1.29 (95%CI 1.04, 1.59) and 0.61 (95%CI 0.36, 1.03; p-trend=0.003). The association between bowel movements and diverticulitis was not modified by categories of age, BMI, physical activity, laxative use or fiber intake. CONCLUSION: More frequent bowel movements appear to be a risk factor for subsequent diverticulitis both in men and women. Further studies are needed to understand the potential mechanisms that may underlie this association.

3.
Br J Cancer ; 2021 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-33398066

RESUMO

BACKGROUND: Higher dairy intake during adulthood has been associated with lower colorectal cancer risk. As colorectal carcinogenesis spans several decades, we hypothesised that higher dairy intake during adolescence is associated with lower risk of colorectal adenoma, a colorectal cancer precursor. METHODS: In 27,196 females from the Nurses' Health Study 2, aged 25-42 years at recruitment (1989), who had completed a validated high school diet questionnaire in 1998 and undergone at least one lower bowel endoscopy between 1998 and 2011, logistic regression for clustered data was used to calculate odds ratios (ORs) and 95% confidence intervals (CI). RESULTS: Colorectal adenomas were diagnosed in 2239 women. Dairy consumption during adolescence was not associated with colorectal adenoma risk (OR highest vs. lowest [≥4 vs. ≤1.42 servings/day] quintile [95% CI] 0.94 [0.80, 1.11]). By anatomical site, higher adolescent dairy intake was associated with lower rectal (0.63 [0.42, 0.95]), but not proximal (1.01 [0.80, 1.28]) or distal (0.97 [0.76, 1.24]) colon adenoma risk. An inverse association was observed with histologically advanced (0.72 [0.51, 1.00]) but not non-advanced (1.07 [0.86, 1.33]) adenoma. CONCLUSIONS: In this large cohort of younger women, higher adolescent dairy intake was associated with lower rectal and advanced adenoma risk later in life.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33290138

RESUMO

Objectives: Glucosamine and chondroitin supplements have been associated with reduced inflammation, as measured by C-reactive protein (CRP). It is unclear if associations vary by formulation (glucosamine alone vs. glucosamine+chondroitin), form (glucosamine hydrochloride vs. glucosamine sulfate), or dose. Design, Subjects, Setting, Location: The authors evaluated these questions using cross-sectional data collected between 1999 and 2010 on 21,917 US adults, surveyed as part of the National Health and Nutrition Examination Survey (NHANES). Exposures: Glucosamine and chondroitin use was assessed during an in-home interview; exposures include supplement formulation, form, and dose. Outcome/Analysis: CRP was measured using blood collected at interview. Survey-weighted linear regression was used to evaluate the multivariable-adjusted association between exposures and log-transformed CRP. Results: In early years (1999-2004), use of glucosamine (ratio = 0.87; 95% confidence interval [CI] = 0.79-0.96) and chondroitin (ratio = 0.83; 95% CI = 0.72-0.95) was associated with reduced CRP. However, associations significantly varied by calendar time (p-interaction = 0.04 and p-interaction = 0.01, respectively), with associations nonsignificant in later years (ratio = 1.09; 95% CI = 0.94-1.28 and ratio = 1.16; 95% CI = 0.99-1.35, respectively). Consequently, all analyses have been stratified by calendar time. Associations did not significantly differ by formulation in either set of years; however, significant associations were observed for combined use of glucosamine+chondroitin (ratioearly = 0.82; 95% CI = 0.72-0.95; ratiolate = 1.16; 1.00-1.35), but not glucosamine alone. Associations also did not significantly differ by supplement form. Even so, a significant inverse association was observed only for glucosamine sulfate in the early years (ratio = 0.78; 95% CI = 0.64-0.95); no significant association was observed for glucosamine hydrochloride. No significant trends were observed by dose. Conclusions: Although a significant inverse association was observed for glucosamine and chondroitin and CRP in early years, this association did not hold in later years. This pattern held for combined use of glucosamine+chondroitin as well as glucosamine sulfate, although associations did not significantly vary by supplement form, formulation, or dose. Further study is needed to better understand these associations in the context of calendar time.

5.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 37(6): 1037-1044, 2020 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-33369343

RESUMO

To enhance the accuracy of computer-aided diagnosis of adolescent depression based on electroencephalogram signals, this study collected signals of 32 female adolescents (16 depressed and 16 healthy, age: 16.3 ± 1.3) with eyes colsed for 4 min in a resting state. First, based on the phase synchronization between the signals, the phase-locked value (PLV) method was used to calculate brain functional connectivity in the θ and α frequency bands, respectively. Then based on the graph theory method, the network parameters, such as strength of the weighted network, average characteristic path length, and average clustering coefficient, were calculated separately ( P < 0.05). Next, using the relationship between multiple thresholds and network parameters, the area under the curve (AUC) of each network parameter was extracted as new features ( P < 0.05). Finally, support vector machine (SVM) was used to classify the two groups with the network parameters and their AUC as features. The study results show that with strength, average characteristic path length, and average clustering coefficient as features, the classification accuracy in the θ band is increased from 69% to 71%, 66% to 77%, and 50% to 68%, respectively. In the α band, the accuracy is increased from 72% to 79%, 69% to 82%, and 65% to 75%, respectively. And from overall view, when AUC of network parameters was used as a feature in the α band, the classification accuracy is improved compared to the network parameter feature. In the θ band, only the AUC of average clustering coefficient was applied to classification, and the accuracy is improved by 17.6%. The study proved that based on graph theory, the method of feature optimization of brain function network could provide some theoretical support for the computer-aided diagnosis of adolescent depression.

6.
Nat Rev Clin Oncol ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33219329

RESUMO

The incidence of early-onset colorectal cancer (CRC), which occurs in individuals <50 years of age, has been increasing worldwide and particularly in high-income countries. The reasons for this increase remain unknown but plausible hypotheses include greater exposure to potential risk factors, such as a Western-style diet, obesity, physical inactivity and antibiotic use, especially during the early prenatal to adolescent periods of life. These exposures can not only cause genetic and epigenetic alterations in colorectal epithelial cells but also affect the gut microbiota and host immunity. Early-onset CRCs have differential clinical, pathological and molecular features compared with later-onset CRCs. Certain existing resources can be utilized to elucidate the aetiology of early-onset CRC and inform the development of effective prevention, early detection and therapeutic strategies; however, additional life-course cohort studies spanning childhood and young adulthood, integrated with prospective biospecimen collections, omics biomarker analyses and a molecular pathological epidemiology approach, are needed to better understand and manage this disease entity. In this Perspective, we summarize our current understanding of early-onset CRC and discuss how we should strategize future research to improve its prevention and clinical management.

7.
Anticancer Drugs ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33229902

RESUMO

BACKGROUND: Brusatol is a butyrolactone compound isolated from traditional Chinese medicine Brucea javanica. It has been reported to possess strong cytotoxicity against various cancer cells, thus showing its potential as an anticancer drug. Besides, lipopolysaccharide (LPS) plays a central role in the tumor microenvironment, while epithelial-mesenchymal transformation (EMT), a biological process by which epithelial cells are transformed into mesenchymal phenotypic cells through specific procedures, participates in chronic inflammation and tumor metastasis. OBJECTIVE: This study aimed to investigate the inhibition of LPS-induced tumor cell invasion and metastasis and the molecular mechanism of apoptosis induced by brusatol in human gastric cancer SGC-7901 cells. METHODS: Cell viability, cell migration and invasion ability, inflammatory factor release, and protein expression were detected using methyl thiazolyl tetrazolium assays, transwell assays, ELISA kit, and Western blot analysis, respectively. The change of EMT marker protein vimentin was assessed using immunofluorescence, while the apoptosis rate was measured using flow cytometry. CONCLUSION: In summary, brusatol inhibited LPS-induced EMT via the deactivation of the PI3K/Akt/NF-кB signaling pathway. This provides a useful new theoretical basis for the treatment of gastric cancer in the future.

8.
J Natl Cancer Inst ; 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33136160

RESUMO

BACKGROUND: The role of poor diet quality in the rising incidence of colorectal cancer (CRC) diagnosed under age 50 has not been explored. Based on molecular features of early-onset CRC, early-onset adenomas are emerging surrogate endpoints. METHODS: In a prospective cohort study (Nurses' Health Study II), we evaluated two empirical dietary patterns (Western and prudent) and three recommendation-based indexes (Dietary Approaches to Stop Hypertension [DASH], Alternative Mediterranean Diet [AMED], and Alternative Healthy Eating Index [AHEI]-2010) with risk of early-onset adenoma overall and by malignant potential (high-risk: ≥1 cm, tubulovillous/villous histology, high-grade dysplasia, or ≥ 3 adenomas), among 29474 women with ≥1 lower endoscopy before age 50 (1991-2011). Multivariable logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: We documented 1157 early-onset adenomas with 375 of high-risk. Western diet was positively, whereas prudent diet, DASH, AMED, and AHEI-2010 were inversely associated with risk of early-onset adenoma. The associations were largely confined to high-risk adenomas (OR [95% CI] for the highest versus lowest quintile: Western = 1.67 [1.18 to 2.37]; prudent = 0.69 [0.48 to 0.98]; DASH = 0.65 [0.45 to 0.93]; AMED = 0.55 [0.38 to 0.79]; AHEI-2010 = 0.71 [0.51 to 1.01]; all P  trend≤.03), driven by those identified in the distal colon and rectum (all P  trend≤.04 except AMED: Ptrend=.14). CONCLUSION: Poor diet quality was associated with an increased risk of early-onset distal and rectal adenomas of high malignant potential. These findings provide preliminary but strong support to the role of diet in early-onset CRC.

9.
Front Pharmacol ; 11: 562084, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33123008

RESUMO

The aim of this study was to assess the underlying impact of Tetramethylpyrazine (TMP), which is the main activity compound of Ligusticum chuanxiong Hort, on the blood-brain barrier, inflammatory and nitrous oxide systems in a rat model of lipopolysaccharide (LPS)-induced sepsis. The SD rats were divided into control group, LPS treatment group, and LPS + TMP treatment group. TMP administered by tail vein injection. The mortality of experimental rats was recorded during the experiment. Rats were sacrificed after 14 days. Peripheral blood was collected and the expression levels of inflammatory factors TNF-α, IL-1ß, and IL-6 were detected by ELISA. The integrity of blood-brain barrier was detected by sodium fluorescein staining. Lung and brain tissues were taken to detect the infiltration of immune cells. Immunohistochemistry was performed to detect the expression of tight junctions related proteins and oxidative stress-related proteins. The results showed that TMP treatment for 14 days significantly decreased the weight loss and increased the survival rate of the septic rats significantly. TMP decreased the infiltration of inflammatory cells and alleviated the sepsis-induced damage in both the lung and brain tissues. The inflammatory cytokines TNF-α, IL-1ß, and IL-6, were significantly decreased post-TMP treatment. Histopathological analysis with sodium fluorescein staining density showed that TMP had a protective effect on the basal lamina and cerebral cortex. Also, TMP significantly increased expression of the tight junction-related proteins claudin-5 and occludin in the brain tissue and increased the expression of the ZO-1, Occludin, and Claudin-5 genes, indicating alleviated the degree of blood-brain barrier destruction. Furthermore, immunohistochemistry (IHC) and immunoblotting confirmed that TMP could inhibit the indicators of the nitrous oxide system, iNOS and eNOS; in addition, TMP significantly decreased the levels of MDA and NO. The findings showed that TMP treatment during sepsis was associated with the protection of the blood-brain barrier and the suppression of inflammatory reactions and the nitrous oxide system. This study reveals a promising protective role of TMP in septic encephalopathy and may suggest a therapeutic approach for fighting the deadly disease of sepsis in the clinic.

10.
Gut ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037055

RESUMO

OBJECTIVE: Factors that lead to metabolic dysregulation are associated with increased risk of early-onset colorectal cancer (CRC diagnosed under age 50). However, the association between metabolic syndrome (MetS) and early-onset CRC remains unexamined. DESIGN: We conducted a nested case-control study among participants aged 18-64 in the IBM MarketScan Commercial Database (2006-2015). Incident CRC was identified using pathologist-coded International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, and controls were frequency matched. MetS was defined as presence of ≥3 conditions among obesity, hypertension, hyperlipidaemia and hyperglycaemia/type 2 diabetes, based on ICD-9-CM and use of medications. Multivariable logistic regressions were used to estimate ORs and 95% CIs. RESULTS: MetS was associated with increased risk of early-onset CRC (n=4673; multivariable adjusted OR 1.25; 95% CI 1.09 to 1.43), similar to CRC diagnosed at age 50-64 (n=14 928; OR 1.21; 95% CI 1.15 to 1.27). Compared with individuals without a metabolic comorbid condition, those with 1, 2 or ≥3 conditions had a 9% (1.09; 95% CI 1.00 to 1.17), 12% (1.12; 95% CI 1.01 to 1.24) and 31% (1.31; 95% CI 1.13 to 1.51) higher risk of early-onset CRC (ptrend <0.001). No associations were observed for one or two metabolic comorbid conditions and CRC diagnosed at age 50-64. These positive associations were driven by proximal (OR per condition 1.14; 95% CI 1.06 to 1.23) and distal colon cancer (OR 1.09; 95% CI 1.00 to 1.18), but not rectal cancer (OR 1.03; 95% CI 0.97 to 1.09). CONCLUSIONS: Metabolic dysregulation was associated with increased risk of early-onset CRC, driven by proximal and distal colon cancer, thus at least in part contribute to the rising incidence of early-onset CRC.

11.
Cancer Epidemiol Biomarkers Prev ; 29(12): 2693-2701, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33055203

RESUMO

BACKGROUND: Studies have shown an inverse association between use of glucosamine and chondroitin supplements and colorectal cancer risk. However, the association with the precursor lesion, colorectal adenoma and serrated polyp, has not been examined. METHODS: Analyses include 43,163 persons from the Nurses' Health Study (NHS), Health Professionals Follow-up Study (HPFS), and NHS2 who reported on glucosamine/chondroitin use in 2002 and who subsequently underwent ≥1 lower gastrointestinal endoscopy. By 2012, 5,715 conventional (2,016 high-risk) adenomas were detected, as were 4,954 serrated polyps. Multivariable logistic regression for clustered data was used to calculate OR and 95% confidence intervals (CI). RESULTS: Glucosamine/chondroitin use was inversely associated with high risk and any conventional adenoma in NHS and HPFS: in the pooled multivariable-adjusted model, glucosamine + chondroitin use at baseline was associated with a 26% (OR = 0.74; 95% CI, 0.60-0.90; P heterogeneity = 0.23) and a 10% (OR = 0.90; 95% CI, 0.81-0.99; P heterogeneity = 0.36) lower risk of high-risk adenoma and overall conventional adenoma, respectively. However, no association was observed in NHS2, a study of younger women (high-risk adenoma: OR = 1.09; 95% CI, 0.82-1.45; overall conventional adenoma: OR = 1.00; 95% CI, 0.86-1.17), and effect estimates pooled across all three studies were not significant (high-risk: OR = 0.83; 95% CI, 0.63-1.10; P heterogeneity = 0.03; overall conventional adenoma: OR = 0.93; 95% CI, 0.85-1.02; P heterogeneity = 0.31). No associations were observed for serrated polyps. CONCLUSIONS: Glucosamine/chondroitin use was associated with lower risks of high-risk and overall conventional adenoma in older adults; however, this association did not hold in younger women, or for serrated polyps. IMPACT: Our study suggests that glucosamine and chondroitin may act on early colorectal carcinogenesis in older adults.

12.
JNCI Cancer Spectr ; 4(5): pkaa042, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32923935

RESUMO

Background: Postmenopausal hormone therapy (HT) is associated with a decreased colorectal cancer (CRC) risk. As CRC is a heterogeneous disease, we evaluated whether the association of HT and CRC differs across etiologically relevant, molecularly defined tumor subtypes and tumor location. Methods: We pooled data on tumor subtypes (microsatellite instability status, CpG island methylator phenotype status, BRAF and KRAS mutations, pathway: adenoma-carcinoma, alternate, serrated), tumor location (proximal colon, distal colon, rectum), and HT use among 8220 postmenopausal women (3898 CRC cases and 4322 controls) from 8 observational studies. We used multinomial logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of ever vs never HT use with each tumor subtype compared with controls. Models were adjusted for study, age, body mass index, smoking status, and CRC family history. All statistical tests were 2-sided. Results: Among postmenopausal women, ever HT use was associated with a 38% reduction in overall CRC risk (OR =0.62, 95% CI = 0.56 to 0.69). This association was similar according to microsatellite instability, CpG island methylator phenotype and BRAF or KRAS status. However, the association was attenuated for tumors arising through the serrated pathway (OR = 0.81, 95% CI = 0.66 to 1.01) compared with the adenoma-carcinoma pathway (OR = 0.63, 95% CI = 0.55 to 0.73; P het =.04) and alternate pathway (OR = 0.61, 95% CI = 0.51 to 0.72). Additionally, proximal colon tumors had a weaker association (OR = 0.71, 95% CI = 0.62 to 0.80) compared with rectal (OR = 0.54, 95% CI = 0.46 to 0.63) and distal colon (OR = 0.57, 95% CI = 0.49 to 0.66; P het =.01) tumors. Conclusions: We observed a strong inverse association between HT use and overall CRC risk, which may predominantly reflect a benefit of HT use for tumors arising through the adenoma-carcinoma and alternate pathways as well as distal colon and rectal tumors.

13.
Mol Biol Evol ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32941615

RESUMO

How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here we conducted a comprehensive genomic analysis of diversity, interspecies introgression and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600k and 50k genome-wide SNP data from 3447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248302667-248306614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.

14.
Front Oncol ; 10: 909, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850304

RESUMO

Objective: The stage, size, grade, and necrosis (SSIGN) score can facilitate the assessment of tumor aggressiveness and the personal management for patients with clear cell renal cell carcinoma (ccRCC). However, this score is only available after the postoperative pathological evaluation. The aim of this study was to develop and validate a CT radiomic signature for the preoperative prediction of SSIGN risk groups in patients with ccRCC in multicenters. Methods: In total, 330 patients with ccRCC from three centers were classified into the training, external validation 1, and external validation 2 cohorts. Through consistent analysis and the least absolute shrinkage and selection operator, a radiomic signature was developed to predict the SSIGN low-risk group (scores 0-3) and intermediate- to high-risk group (score ≥ 4). An image feature model was developed according to the independent image features, and a fusion model was constructed integrating the radiomic signature and the independent image features. Furthermore, the predictive performance of the above models for the SSIGN risk groups was evaluated with regard to their discrimination, calibration, and clinical usefulness. Results: A radiomic signature consisting of sixteen relevant features from the nephrographic phase CT images achieved a good calibration (all Hosmer-Lemeshow p > 0.05) and favorable prediction efficacy in the training cohort [area under the curve (AUC): 0.940, 95% confidence interval (CI): 0.884-0.973] and in the external validation cohorts (AUC: 0.876, 95% CI: 0.811-0.942; AUC: 0.928, 95% CI: 0.844-0.975, respectively). The radiomic signature performed better than the image feature model constructed by intra-tumoral vessels (all p < 0.05) and showed similar performance with the fusion model integrating radiomic signature and intra-tumoral vessels (all p > 0.05) in terms of the discrimination in all cohorts. Moreover, the decision curve analysis verified the clinical utility of the radiomic signature in both external cohorts. Conclusion: Radiomic signature could be used as a promising non-invasive tool to predict SSIGN risk groups and to facilitate preoperative clinical decision-making for patients with ccRCC.

15.
Lancet Gastroenterol Hepatol ; 5(11): 986-995, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818437

RESUMO

BACKGROUND: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. METHODS: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. FINDINGS: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls. INTERPRETATION: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. FUNDING: National Institutes of Health. Crohn's and Colitis Foundation.


Assuntos
Antibacterianos , Disbiose , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idade de Início , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Sistemas de Informação em Farmácia Clínica/estatística & dados numéricos , Disbiose/induzido quimicamente , Disbiose/prevenção & controle , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Irmãos , Suécia/epidemiologia
16.
J Natl Cancer Inst ; 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32778876

RESUMO

BACKGROUND: ASPirin in Reducing Events in the Elderly (ASPREE), a randomized double-blind placebo-controlled trial (RCT) of daily low-dose aspirin (100 mg) in older adults, showed an increase in all-cause mortality, primarily due to cancer. In contrast prior RCTs, mainly involving younger individuals, demonstrated a delayed cancer benefit with aspirin. We now report a detailed analysis of cancer incidence and mortality. METHODS: 19,114 Australian and U.S. community-dwelling participants aged 70+ years (U.S. minorities 65+ years) without cardiovascular disease, dementia or physical disability were randomized and followed for a median of 4.7 years. Fatal and non-fatal cancer events, a prespecified secondary endpoint, were adjudicated based on clinical records. RESULTS: 981 cancer events occurred in the aspirin and 952 in the placebo groups. There was no statistically significant difference between groups for all incident cancers (HR = 1.04, 95% CI = 0.95 to 1.14), hematological cancer (HR = 0.98, 95% CI = 0.73 to 1.30), or all solid cancers (HR = 1.05, 95% CI = 0.95 to 1.15), including by specific tumor type. However, aspirin was associated with an increased risk of incident cancer that had metastasized (HR = 1.19, 95% CI = 1.00 to 1.43) or was stage 4 at diagnosis (HR = 1.22, 95% CI = 1.02 to 1.45), and with higher risk of death for cancers that presented at stages 3 (HR = 2.11, 95% CI = 1.03 to 4.33) or 4 (HR = 1.31, 95% CI = 1.04 to 1.64). CONCLUSIONS: In older adults, aspirin treatment had an adverse effect on later stages of cancer evolution. These findings suggest that in older persons, aspirin may accelerate the progression of cancer and thus, suggest caution with its use in this age group.

17.
Diabetes ; 69(11): 2423-2439, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32801139

RESUMO

Metagenome sequencing has not been used in infected bone specimens. This prospective observational study explored the microbiome and its function in patients with diabetic foot osteomyelitis (DFO) and posttraumatic foot osteomyelitis (PFO) based on 16S rRNA sequencing and metagenome sequencing technologies. Spearman analysis was used to explore the correlation between dominant species and clinical indicators of patients with DFO. High-throughput sequencing showed that all the specimens were polymicrobial. The microbial diversity was significantly higher in the DFO group than in the PFO group. Firmicutes, Prevotellaceae, and Prevotella were the most abundant microbes in the DFO group. The most abundant microbes in the PFO group were Proteobacteria, Halomonadaceae, and Halomonas Prevotella denticola, Prevotella jejuni, and Prevotella fusca had positive correlation with the duration of diabetic foot infection (DFI_d). Proteus vulgaris was positively correlated with the infection index, while Bacteroides fragilis was negatively correlated. The microbial functional genes were more abundant in the DFO group than in the PFO group. Metagenome sequencing is feasible for the analysis of the microbiome in infected bone specimens. Gram-negative bacteria and anaerobes are dominant in DFO.

18.
Cancer Res ; 80(20): 4578-4590, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32816852

RESUMO

Protective associations of fruits, vegetables, and fiber intake with colorectal cancer risk have been shown in many, but not all epidemiologic studies. One possible reason for study heterogeneity is that dietary factors may have distinct effects by colorectal cancer molecular subtypes. Here, we investigate the association of fruit, vegetables, and fiber intake with four well-established colorectal cancer molecular subtypes separately and in combination. Nine observational studies including 9,592 cases with molecular subtypes for microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and somatic mutations in BRAF and KRAS genes, and 7,869 controls were analyzed. Both case-only logistic regression analyses and polytomous logistic regression analyses (with one control set and multiple case groups) were used. Higher fruit intake was associated with a trend toward decreased risk of BRAF-mutated tumors [OR 4th vs. 1st quartile = 0.82 (95% confidence interval, 0.65-1.04)] but not BRAF-wildtype tumors [1.09 (0.97-1.22); P difference as shown in case-only analysis = 0.02]. This difference was observed in case-control studies and not in cohort studies. Compared with controls, higher fiber intake showed negative association with colorectal cancer risk for cases with microsatellite stable/MSI-low, CIMP-negative, BRAF-wildtype, and KRAS-wildtype tumors (P trend range from 0.03 to 3.4e-03), which is consistent with the traditional adenoma-colorectal cancer pathway. These negative associations were stronger compared with MSI-high, CIMP-positive, BRAF-mutated, or KRAS-mutated tumors, but the differences were not statistically significant. These inverse associations for fruit and fiber intake may explain, in part, inconsistent findings between fruit or fiber intake and colorectal cancer risk that have previously been reported. SIGNIFICANCE: These analyses by colorectal cancer molecular subtypes potentially explain the inconsistent findings between dietary fruit or fiber intake and overall colorectal cancer risk that have previously been reported.

19.
Front Oncol ; 10: 694, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32670862

RESUMO

Background: Regorafenib is a second-line therapy drug used for advanced hepatocellular carcinoma (HCC). Unfortunately, the survival benefit of the patients receiving this treatment is modest, which may be attributed to drug resistance. In the present study, sphingosine kinase 2 (SphK2) was targeted to reverse regorafenib resistance in HCC. Methods: The functions of SphK2 and sphingosine-1-phosphate (S1P), the catalytic product of SphK2 in regorafenib resistance of HCC cells, were evaluated by cell counting kit-8 assay, colony formation, cell cycle evaluation, and annexin V-fluorescein isothiocyanate/propidium iodide double-staining assay. The antitumor activity of combined treatment of regorafenib and the SphK2-specific inhibitor ABC294640 was examined in HCC cells in vitro and xenograft model in vivo. The molecular mechanisms of SphK2/S1P-mediating regorafenib resistance were investigated using cell line establishment and Western blot analysis. Results: Well-developed regorafenib-resistant HCC cells indicated high expression levels of SphK2. The sensitivity to regorafenib of regorafenib-resistant HCC cells was restored following SphK2 knockdown or pharmacological inhibition by ABC294640. In addition, ectopic expression of SphK2 and exogenous addition of S1P decreased the sensitivity of HCC cells to regorafenib. Furthermore, the combination treatment with ABC294640 sensitized resistant tumor to regorafenib in xenograft model of HCC. The phosphorylation levels of nuclear factor κB (NF-κB), as well as those of signal transducer and activator of transcription 3 (STAT3), were positively associated with SphK2 and S1P. Conclusions: SphK2/S1P mediates regorafenib resistance of HCC through NF-κB and STAT3 activation. Targeting SphK2 by ABC294640 potently reduces regorafenib resistance of HCC cells both in vitro and in vivo. The combination of ABC294640 and regorafenib could be developed as a novel potential treatment strategy for advanced HCC.

20.
Chin J Traumatol ; 23(4): 233-237, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32680703

RESUMO

PURPOSE: To evaluate the efficacy of closed reduction on the humeroradial joint in the treatment of Bado type Ⅰ, Ⅱ and Ⅲ fresh Monteggia fractures in children and investigate the effect of clinical factors, including Bado classification, age and time of treatment on the success rate of closed reduction. METHODS: We retrospectively studied the data of children ≤10 years old with fresh Monteggia fractures (injury within two weeks) treated by manual reduction with plaster immobilization from January 2014 to April 2019. All patients were followed up in the outpatient department every two weeks for 4-6 weeks until plaster removal and then 3, 6 and 12 months. Online or telephone interview was provided for some inconvenient patients after 6 months. Mackay criteria were used to evaluate the clinical effect. Radiographic data were collected and reviewed to assess the reduction of the humeroradial joint. Function of the elbow joint and forearm was evaluated and risk factors related to the failure of reduction were assessed. The successful manual reduction was analyzed from three aspects, respectively Bado fracture type (Ⅰ, Ⅱ, Ⅲ), patient age (<3 year, 3-6 years, >6 years) and time interval from injury to treatment (group A, <1 day; group B, 1-3 days; group C, >3 days). RESULTS: Altogether 88 patients were employed in this study, including 58 males (65.9%) and 30 females (34.1%) aged from 1 to 10 years. There were 29 cases (33.0%) of Bado type Ⅰ Monteggia fractures, 16 (18.2%) type Ⅱ and 43 (48.7%) type Ⅲ. Successful manual reduction was achieved in 79 children (89.8%) at the last follow-up. The failed 9 patients received open surgery. Mackay criteria showed 100% good-excellent rate for all the patients. The success rate of manual reduction was 89.7%, 87.5% and 90.7% in Bado type Ⅰ, Ⅱ and Ⅲ cases, respectively, revealing no significant differences among different Bado types (χ2 = 0.131, p = 0.937). Successful closed reduction was achieved in 13 toddlers (13/13, 100%), 38 preschool children (28/42, 90.5%) and 28 school-age children (28/33, 84.8%), suggesting no significant difference either (χ2 = 2.375, p = 0.305). However time interval from injury to treatment showed that patients treated within 3 days had a much higher rate of successful manual reduction: 67 cases (67/71, 94.4%) in group A, 10 cases (10/11, 90.9%) in group B, and 2 cases (2/6, 33.3%) in group C (χ2 = 22.464, p < 0.001). Fisher's test further showed significant differences between groups A and C (p = 0.001) and groups B and C (p = 0.028). CONCLUSION: Closed reduction is a safe and effective method for treating fresh Monteggia fractures in children. The reduction should be conducted as soon as possible once the diagnosis has been made.


Assuntos
Redução Fechada/métodos , Fratura de Monteggia/cirurgia , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Lactente , Masculino , Fratura de Monteggia/classificação , Fratura de Monteggia/terapia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento
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