Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 970
Filtrar
1.
J Natl Cancer Inst ; 2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33528007

RESUMO

BACKGROUND: Prior epidemiological and intervention studies have not been able to separate independent effects of dose, timing and duration of aspirin use in colorectal cancer (CRC) chemoprevention. We examined aspirin-based CRC chemoprevention according to timing in the Nurses' Health Study and Health Professionals Follow-Up Study. METHODS: The exposures include cumulative average dose and total duration of aspirin use in > 10 years before follow-up started (remote period), and in the immediate 10 years before follow-up started (recent period). Cox models were used to estimate hazard ratios (HR) and 95% confidence intervals for exposures and CRC risk. RESULTS: Aspirin use >10 years before follow-up started (HR = 0.88, 95% CI = 0.83 to 0.94) per 5 year increment) and immediate 10 years before follow-up started (HR = 0.90, 95% CI = 0.84 to 0.96) were similarly important in CRC chemoprevention, though a 5-year lag was required for a clear benefit in the recent period. In the remote period, the association was not dose-dependent; compared to < 0.5 standard (325 mg)-dose tablets/week; hazard ratios were HR = 0.78, 95% CI = 0.63 to 0.98, HR = 0.81, 95% CI = 0.72 to 0.91, and HR = 0.74, 95% CI = 0.64 to 0.86 for doses of 0.5 to < 1.5, 1.5 to < 5, ≥5 tablets/week, respectively. However, there was dose dependency in the recent period (with respective HR = 0.91, 95% CI = 0.79 to 1.06; HR = 0.87, 95% CI = 0.77 to 0.98; and HR = 0.76, 95% CI = 0.64 to 0.91). CONCLUSION: A suggestive benefit necessitates at least 6-10 years and most clearly after approximately 10 years since initiation of aspirin. Remote use and use within the previous 10 years both contribute independently to decreased risk, though a lower dose may be required for a benefit with longer term use.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33531435

RESUMO

BACKGROUND: Type 2 diabetes increases risk of developing colorectal cancer (CRC), but the association of pre-existing diabetes with CRC survival remains unclear. METHODS: We analyzed survival by diabetes status at cancer diagnosis among 4038 patients with CRC from two prospective U.S. cohorts. Cox proportional hazards regression was used to calculate HRs and 95% confidence intervals (CIs) for overall and cause-specific mortality, with adjustment for tumor characteristics and lifestyle factors. RESULTS: In the first 5 years after CRC diagnosis, diabetes was associated with a modest increase in overall mortality in women (HR, 1.22; 95% CI, 1.00-1.49), but not in men (HR, 0.83; 95% CI, 0.62-1.12; P heterogeneity by sex = 0.04). Beyond 5 years, diabetes was associated with substantially increased overall mortality with no evidence of sex heterogeneity; in women and men combined, the HRs were 1.45 (95% CI, 1.09-1.93) during >5 to 10 years and 2.58 (95% CI, 1.91-3.50) during >10 years. Compared with those without diabetes, CRC patients with diabetes had increased mortality from other malignancies (HR, 1.78; 95% CI, 1.18-2.67) and cardiovascular disease (HR, 1.93; 95% CI, 1.29-2.91). Only women with diabetes for more than 10 years had increased mortality from CRC (HR, 1.33; 95% CI, 1.01-1.76). CONCLUSIONS: Among patients with CRC, pre-existing diabetes was associated with increased risk of long-term mortality, particularly from other malignancies and cardiovascular disease. IMPACT: Our findings highlight the importance of cardioprotection and cancer prevention to CRC survivors with diabetes.

3.
Neurosurgery ; 2021 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-33575788

RESUMO

BACKGROUND: Posterior cervical decompression and fusion (PCF) is a common procedure used to treat various cervical spine pathologies, but the 90-d outcomes following PCF surgery continue to be incompletely defined. OBJECTIVE: To identify risk factors associated with 90-d readmission and reoperation following PCF surgery. METHODS: Adults undergoing PCF from 2012 to 2020 were identified. Demographic and radiographic data, surgical characteristics, and 90-d outcomes were collected. Univariate analysis was performed using Student's t-test, chi square, and Fisher exact tests as appropriate. Multivariable logistic regression models with lasso penalty were used to analyze various risk factors. RESULTS: A total of 259 patients were included. The 90-d readmission and reoperation rates were 9.3% and 4.6%, respectively. The most common reason for readmission was surgical site infection (SSI) (33.3%) followed by new neurological deficits (16.7%). Patients who smoked tobacco had 3-fold greater odds of readmission compared to nonsmokers (odds ratio [OR]: 3.48; 95% CI 1.87-6.67; P = .0001). Likewise, the most common reason for reoperation was SSI (33.3%) followed by seroma and implant failure (25.0% each). Smoking was also an independent risk factor for reoperation, associated with nearly 4-fold greater odds of return to the operating room (OR: 3.53; 95% CI 1.53-8.57; P = .003). CONCLUSION: Smoking is a significant predictor of 90-d readmission and reoperation in patients undergoing PCF surgery. Smoking cessation should be strongly considered preoperatively in elective PCF cases to minimize the risk of 90-d readmission and reoperation.

4.
PLoS Med ; 18(2): e1003522, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33524029

RESUMO

BACKGROUND: Healthy lifestyle and screening represent 2 major approaches to colorectal cancer (CRC) prevention. It remains unknown whether the CRC-preventive benefit of healthy lifestyle differs by endoscopic screening status, and how the combination of healthy lifestyle with endoscopic screening can improve CRC prevention. METHODS AND FINDINGS: We assessed lifestyle and endoscopic screening biennially among 75,873 women (Nurses' Health Study, 1988 to 2014) and 42,875 men (Health Professionals Follow-up Study, 1988 to 2014). We defined a healthy lifestyle score based on body mass index, smoking, physical activity, alcohol consumption, and diet. We calculated hazard ratios (HRs) and population-attributable risks (PARs) for CRC incidence and mortality in relation to healthy lifestyle score according to endoscopic screening. Participants' mean age (standard deviation) at baseline was 54 (8) years. During a median of 26 years (2,827,088 person-years) follow-up, we documented 2,836 incident CRC cases and 1,013 CRC deaths. We found a similar association between healthy lifestyle score and lower CRC incidence among individuals with and without endoscopic screening, with the multivariable HR per one-unit increment of 0.85 (95% CI, 0.80 to 0.90) and 0.85 (95% CI, 0.81 to 0.88), respectively (P-interaction = 0.99). The fraction of CRC cases that might be prevented (PAR) by endoscopic screening alone was 32% (95% CI, 31% to 33%) and increased to 61% (95% CI, 42% to 75%) when combined with healthy lifestyle (score = 5). The corresponding PAR (95% CI) increased from 15% (13% to 16%) to 51% (17% to 74%) for proximal colon cancer and from 47% (45% to 50%) to 75% (61% to 84%) for distal CRC. Results were similar for CRC mortality. A limitation of our study is that our study participants are all health professionals and predominantly whites, which may not be representative of the general population. CONCLUSIONS: Our study suggests that healthy lifestyle is associated with lower CRC incidence and mortality independent of endoscopic screening. An integration of healthy lifestyle with endoscopic screening may substantially enhance prevention for CRC, particularly for proximal colon cancer, compared to endoscopic screening alone.

5.
Chem Rev ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33606500

RESUMO

The use of life-saving antibiotics has long been plagued by the ability of pathogenic bacteria to acquire and develop an array of antibiotic resistance mechanisms. The sum of these resistance mechanisms, the antibiotic resistome, is a formidable threat to antibiotic discovery, development, and use. The study and understanding of the molecular mechanisms in the resistome provide the basis for traditional approaches to combat resistance, including semisynthetic modification of naturally occurring antibiotic scaffolds, the development of adjuvant therapies that overcome resistance mechanisms, and the total synthesis of new antibiotics and their analogues. Using two major classes of antibiotics, the aminoglycosides and tetracyclines as case studies, we review the success and limitations of these strategies when used to combat the many forms of resistance that have emerged toward natural product-based antibiotics specifically. Furthermore, we discuss the use of the resistome as a guide for the genomics-driven discovery of novel antimicrobials, which are essential to combat the growing number of emerging pathogens that are resistant to even the newest approved therapies.

6.
Mult Scler ; : 1352458521996698, 2021 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-33620267

RESUMO

Severe prolonged lymphopenia as rare side-effect of dimethyl fumarate is mostly reversible. Caldito et al. report a case of persistent severe lymphopenia over 5 years after discontinuation of dimethyl fumarate. We discuss several clinical implications. Safe withdrawal of disease modifying therapies in terms of reoccurrence of disease activity and drug related adverse events need further attention as our treatment armamentarium continues to grow.

7.
Nat Med ; 27(2): 333-343, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33574608

RESUMO

To address how the microbiome might modify the interaction between diet and cardiometabolic health, we analyzed longitudinal microbiome data from 307 male participants in the Health Professionals Follow-Up Study, together with long-term dietary information and measurements of biomarkers of glucose homeostasis, lipid metabolism and inflammation from blood samples. Here, we demonstrate that a healthy Mediterranean-style dietary pattern is associated with specific functional and taxonomic components of the gut microbiome, and that its protective associations with cardiometabolic health vary depending on microbial composition. In particular, the protective association between adherence to the Mediterranean diet and cardiometabolic disease risk was significantly stronger among participants with decreased abundance of Prevotella copri. Our findings advance the concept of precision nutrition and have the potential to inform more effective and precise dietary approaches for the prevention of cardiometabolic disease mediated through alterations in the gut microbiome.

8.
Sci Rep ; 11(1): 1087, 2021 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-33441684

RESUMO

Segmentation of white matter lesions and deep grey matter structures is an important task in the quantification of magnetic resonance imaging in multiple sclerosis. In this paper we explore segmentation solutions based on convolutional neural networks (CNNs) for providing fast, reliable segmentations of lesions and grey-matter structures in multi-modal MR imaging, and the performance of these methods when applied to out-of-centre data. We trained two state-of-the-art fully convolutional CNN architectures on the 2016 MSSEG training dataset, which was annotated by seven independent human raters: a reference implementation of a 3D Unet, and a more recently proposed 3D-to-2D architecture (DeepSCAN). We then retrained those methods on a larger dataset from a single centre, with and without labels for other brain structures. We quantified changes in performance owing to dataset shift, and changes in performance by adding the additional brain-structure labels. We also compared performance with freely available reference methods. Both fully-convolutional CNN methods substantially outperform other approaches in the literature when trained and evaluated in cross-validation on the MSSEG dataset, showing agreement with human raters in the range of human inter-rater variability. Both architectures showed drops in performance when trained on single-centre data and tested on the MSSEG dataset. When trained with the addition of weak anatomical labels derived from Freesurfer, the performance of the 3D Unet degraded, while the performance of the DeepSCAN net improved. Overall, the DeepSCAN network predicting both lesion and anatomical labels was the best-performing network examined.

10.
Spine (Phila Pa 1976) ; 46(4): E222-E233, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33475275

RESUMO

STUDY DESIGN: An experimental animal study. OBJECTIVE: The aim of this study was to investigate the effect of pulsed electromagnetic fields (PEMF) on recovery of sensorimotor function in a rodent model of disc herniation (DH). SUMMARY OF BACKGROUND DATA: Radiculopathy associated with DH is mediated by proinflammatory cytokines. Although we have demonstrated the anti-inflammatory effects of PEMF on various tissues, we have not investigated the potential therapeutic effect of PEMF on radiculopathy resulting from DH. METHODS: Nineteen rats were divided into three groups: positive control (PC; left L4 nerve ligation) (n = 6), DH alone (DH; exposure of left L4 dorsal root ganglion [DRG] to harvested nucleus pulposus and DRG displacement) (n = 6), and DH + PEMF (n = 7). Rodents from the DH + PEMF group were exposed to PEMF immediately postoperatively and for 3 hours/day until the end of the study. Sensory function was assessed via paw withdrawal thresholds to non-noxious stimuli preoperatively and 1 and 3 days postoperatively, and every 7 days thereafter until 7 weeks after surgery. Motor function was assessed via DigiGait treadmill analysis preoperatively and weekly starting 7 days following surgery until 7 weeks following surgery. RESULTS: All groups demonstrated marked increases in the left hindlimb response threshold postoperatively. However, 1 week following surgery, there was a significant effect of condition on left hindlimb withdrawal thresholds (one-way analysis of variance: F = 3.82, df = 2, P = 0.044) where a more rapid recovery to baseline threshold was evident for DH + PEMF compared to PC and DH alone. All groups demonstrated gait disturbance postoperatively. However, DH + PEMF rodents were able to regain baseline gait speeds before DH and PC rodents. When comparing gait parameters, DH + PEMF showed consistently less impairment postoperatively suggesting that PEMF treatment was associated with less severe gait disturbance. CONCLUSION: These data demonstrate that PEMF accelerates sensorimotor recovery in a rodent model of DH, suggesting that PEMF may be reasonable to evaluate for the clinical management of patients with herniation-associated radiculopathy.Level of Evidence: N/A.

11.
J Orthop Sci ; 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33441260

RESUMO

BACKGROUND: Randomized controlled trials (RCTs) are the gold standard for study design and are considered to have the highest level of evidence. The purpose of this study is to evaluate quality of evidence of prospective RCTs that investigated the clinical efficacy of platelet-rich plasma (PRP) treatments for knee osteoarthritis. We hypothesized that a high level of clinical evidence does not correlate with a high-quality scientific study. MATERIAL AND METHODS: A systematic literature search to identified RCTs that evaluated the efficacy of PRP treatments for knee osteoarthritis. Inclusion criteria included studies that contained key terms "Platelet-rich plasma," "PRP", "knee", and "osteoarthritis". Exclusion criteria excluded studies that were not prospective RCTs. Ten RCTs were evaluated by four independent reviewers. The studies were assessed according to the Oxford Levels of Evidence, a modified Coleman Methodology Score, and the revised Consolidated Standards of Reporting Trials (CONSORT) score. RESULTS: Three of the four Observers rated all 10 studies as Level I, while one Observer rated 80% of the studies as Level I. Using the Coleman Methodology Score, the average score for all studies was 58.0 out of 100 points, designating the studies as "fair." Areas of deficiency included clinical effect measurement and intent-to-treat analysis. Using the CONSORT checklist, the average score was 16.9 out of 22 points, designating the studies as "good". Areas of deficiency included inadequate implementation of randomization and interpretation of results. DISCUSSION: Clinicians should critically evaluate research studies regardless of study design. A sophisticated study design and high level of evidence designation does not guarantee quality research. We determined that RCTs for PRP treatment of knee osteoarthritis were not as robust in quality despite their Level I Oxford Level of Evidence rating.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33468560

RESUMO

OBJECTIVE: To test the hypothesis that dimethyl fumarate (DMF, Tecfidera) elicits different biological changes from DMF combined with monoethyl fumarate (MEF) (Fumaderm, a psoriasis therapy), we investigated DMF and MEF in rodents and cynomolgus monkeys. Possible translatability of findings was explored with lymphocyte counts from a retrospective cohort of patients with MS. METHODS: In rodents, we evaluated pharmacokinetic and pharmacodynamic effects induced by DMF and MEF monotherapies or in combination (DMF/MEF). Clinical implications were investigated in a retrospective, observational analysis of patients with MS treated with DMF/MEF (n = 36). RESULTS: In rodents and cynomolgus monkeys, monomethyl fumarate (MMF, the primary metabolite of DMF) exhibited higher brain penetration, whereas MEF was preferentially partitioned into the kidney. In mice, transcriptional profiling for DMF and MEF alone identified both common and distinct pharmacodynamic responses, with almost no overlap between DMF- and MEF-induced differentially expressed gene profiles in immune tissues. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated oxidative stress response pathway was exclusively regulated by DMF, whereas apoptosis pathways were activated by MEF. DMF/MEF treatment demonstrated that DMF and MEF functionally interact to modify DMF- and MEF-specific responses in unpredictable ways. In patients with MS, DMF/MEF treatment led to early and pronounced suppression of lymphocytes, predominantly CD8+ T cells. In a multivariate regression analysis, the absolute lymphocyte count (ALC) was associated with age at therapy start, baseline ALC, and DMF/MEF dosage but not with previous immunosuppressive medication and sex. Furthermore, the ALC increased in a small cohort of patients with MS (n = 6/7) after switching from DMF/MEF to DMF monotherapy. CONCLUSIONS: Fumaric acid esters exhibit different biodistribution and may elicit different biological responses; furthermore, pharmacodynamic effects of combinations differ unpredictably from monotherapy. The strong potential to induce lymphopenia in patients with MS may be a result of activation of apoptosis pathways by MEF compared with DMF.

15.
EMBO Mol Med ; 13(2): e12632, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33428810

RESUMO

Glycine transporters (GlyT1 and GlyT2) that regulate levels of brain glycine, an inhibitory neurotransmitter with co-agonist activity for NMDA receptors (NMDARs), have been considered to be important targets for the treatment of brain disorders with suppressed NMDAR function such as schizophrenia. However, it remains unclear whether other amino acid transporters expressed in the brain can also regulate brain glycine levels and NMDAR function. Here, we report that SLC6A20A, an amino acid transporter known to transport proline based on in vitro data but is understudied in the brain, regulates proline and glycine levels and NMDAR function in the mouse brain. SLC6A20A transcript and protein levels were abnormally increased in mice carrying a mutant PTEN protein lacking the C terminus through enhanced ß-catenin binding to the Slc6a20a gene. These mice displayed reduced extracellular levels of brain proline and glycine and decreased NMDAR currents. Elevating glycine levels back to normal ranges by antisense oligonucleotide-induced SLC6A20 knockdown, or the competitive GlyT1 antagonist sarcosine, normalized NMDAR currents and repetitive climbing behavior observed in these mice. Conversely, mice lacking SLC6A20A displayed increased extracellular glycine levels and NMDAR currents. Lastly, both mouse and human SLC6A20 proteins mediated proline and glycine transports, and SLC6A20 proteins could be detected in human neurons. These results suggest that SLC6A20 regulates proline and glycine homeostasis in the brain and that SLC6A20 inhibition has therapeutic potential for brain disorders involving NMDAR hypofunction.

16.
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.

17.
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 the 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 the NHS, compared with 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 the 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.

18.
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.

19.
Artigo em Inglês | MEDLINE | ID: mdl-33514605

RESUMO

BACKGROUND: We prospectively examined the extent to which greater inflammatory and insulinemic potential of diet and lifestyle are associated with the risk of developing hepatocellular carcinoma (HCC) in two nationwide cohorts. METHODS: Five kinds of pattern scores including the empirical dietary inflammatory pattern (EDIP), empirical dietary index for hyperinsulinemia (EDIH) and insulin resistance (EDIR), empirical lifestyle pattern score for hyperinsulinemia (ELIH) and insulin resistance (ELIR) were calculated. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression. RESULTS: After an average follow-up of 25.6 years among 119,316 participants, 142 incident HCC cases were documented. Higher adherence to EDIP (HR by comparing extreme tertiles: 2.03, 95% CI: 1.31-3.16, Ptrend= 0.001), EDIH (HR=1.61, 95% CI: 1.06-2.43, Ptrend= 0.02), and EDIR (HR=1.62, 95% CI: 1.08-2.42, Ptrend= 0.02) were associated with increased risk of HCC. Likewise, participants with higher scores of ELIH (HR=1.89, 95% CI: 1.25-2.87, Ptrend= 0.001) and ELIR (HR=2.05, 95% CI: 1.34-3.14, Ptrend= 0.0004) had higher risk of developing HCC. Additional adjustment for diabetes mellitus and/or body mass index attenuated the magnitude of the associations, indicating that diabetes and/or adiposity may partly mediate the association of these patterns with HCC risk. CONCLUSIONS: Our findings suggest that inflammation and insulin resistance/hyperinsulinemia are potential mechanisms linking dietary or lifestyle factors and HCC development. IMPACT: Inflammation and insulin resistance/hyperinsulinemia may partly mediate the association of diet and other lifestyles with HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyperinsulinemic diet and lifestyle may reduce HCC risk.

20.
BMC Med ; 19(1): 18, 2021 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-33504335

RESUMO

BACKGROUND: Sex hormones have been suggested to play a role in colorectal cancer (CRC), but their influence on early initiation of CRC remains unknown. METHODS: We retrospectively examined the associations with risk of CRC precursors, including conventional adenomas and serrated polyps, for plasma estrone, estradiol, free estradiol, testosterone, free testosterone, sex hormone-binding globulin (SHBG), and the ratio of estradiol to testosterone among 5404 postmenopausal women from the Nurses' Health Study I and II. Multivariable logistic regression was used to calculate the odds ratio (OR) and 95% confidence intervals (CI). Given multiple testing, P < 0.005 was considered statistically significant. RESULTS: During 20 years of follow-up, we documented 535 conventional adenoma cases and 402 serrated polyp cases. Higher concentrations of SHBG were associated with lower risk of conventional adenomas, particularly advanced adenomas (multivariable OR comparing the highest to the lowest quartile, 0.40, 95% CI 0.24-0.67, P for trend < 0.0001). A nominally significant association was found for SHBG with lower risk of large serrated polyps (≥ 10 mm) (OR, 0.47, 95% CI 0.17-1.35, P for trend = 0.02) as well as free estradiol and free testosterone with higher risk of conventional adenomas (OR, 1.54, 95% CI 1.02-2.31, P for trend = 0.03 and OR, 1.33, 95% CI 0.99-1.78, P for trend = 0.03, respectively). CONCLUSIONS: The findings suggest a potential role of sex hormones, particularly SHBG, in early colorectal carcinogenesis.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA