Lower risk but high risk.
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ABSTRACT:
SUBMITTER: DeZern AE
PROVIDER: S-EPMC8791100 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundFollowing curative-intent neoadjuvant therapy in locally advanced rectal cancer, metastatic progression is still dominant. We investigated if patients' circulating 25-hydroxyvitamin D [25(OH)D] levels were associated with outcome.MethodsSerum 25(OH)D concentration was assessed by liquid chromatography-mass spectrometry in samples collected from 84 patients at baseline, completion of the neoadjuvant therapy, and treatment evaluation before surgery, and analyzed with respect to season, disease presentation, and treatment effects.ResultsIn the cohort of patients residing at latitude 58-62°N, baseline 25(OH)D differed significantly over the seasons, with highest measures (mean of 71.2 ± 5.6 nmol/L) in summer and lowest (48.7 ± 4.5 nmol/L) in spring, and changed over the three-month neoadjuvant period till response evaluation solely owing to season. The patient subgroup with slightly reduced performance status, anemia, and T4 disease that did not respond to the neoadjuvant therapy (ypT4 cases), had significantly lower baseline 25(OH)D (below 50 nmol/L) than T4 cases with response (ypT0-3) and T2-3 cases (above 60 nmol/L). Compared to the T4 patients with levels above 50 nmol/L, regarded as sufficient for a healthy bone status, those presenting levels below had significantly heightened risk of disease progression (mainly metastasis) and death, with hazard ratio of 3 and 17, respectively, on adjustment for age, sex, body mass index, and season.ConclusionRectal cancer T4 cases had high risk of metastatic progression and death if circulating 25(OH)D levels were insufficient but obtained short-term and long-term outcome to neoadjuvant treatment no worse than patients with T2-3 disease when 25(OH)D was sufficient.Trial registrationClinicalTrials.gov NCT00278694 ; registration date: 16 January 2006, retrospective to enrollment of the first 10 patients of the current report.
| S-EPMC6533753 | biostudies-literature
Project description:In 2004, Germany introduced a program based on voluntary contracting to strengthen the role of general practice care in the healthcare system. Key components include structured management of chronic diseases, coordinated access to secondary care, data-driven quality improvement, computerized clinical decision-support, and capitation-based reimbursement. Our aim was to determine the long-term effects of this program on the risk of hospitalization of specific categories of high-risk patients. Based on insurance claims data, we conducted a longitudinal observational study from 2011 to 2018 in Baden-Wuerttemberg, Germany. Patients were assigned to one or more of four open cohorts (in 2011, elderly, n = 575,363; diabetes mellitus, n = 163,709; chronic heart failure, n = 82,513; coronary heart disease, n = 125,758). Adjusted for key patient characteristics, logistic regression models were used to compare the hospitalization risk of the enrolled patients (intervention group) with patients receiving usual primary care (control group). At the start of the study and throughout long-term follow-up, enrolled patients in the four cohorts had a lower risk of all-cause hospitalization and ambulatory, care-sensitive hospitalization. Among patients with chronic heart failure and coronary heart disease, the program was associated with significantly reduced risk of cardiovascular-related hospitalizations across the eight observed years. The effect of the program also increased over time. Over the longer term, the results indicate that strengthening primary care could be associated with a substantial reduction in hospital utilization among high-risk patients.
| S-EPMC7902818 | biostudies-literature
Project description:The Spectrum-STI model, structured by sub-groups within a population, was used in a workshop in Yunnan, China, to estimate provincial trends in active syphilis in 15 to 49-year-old adults. Syphilis prevalence data from female sex workers (FSW), men who have sex with men (MSM), and lower-risk women and men in Yunnan were identified through literature searches and local experts. Sources included antenatal care clinic screening, blood donor screening, HIV/STI bio-behavioural surveys, sentinel surveillance, and epidemiology studies. The 2017 provincial syphilis prevalence estimates were 0.26% (95% confidence interval 0.17-0.34%) in women and 0.28% (0.20-0.36%) in men. Estimated prevalence was 6.8-fold higher in FSW (1.69% (0.68-3.97%) than in lower-risk women (0.25% (0.18-0.35%)), and 22.7-fold higher in MSM (5.35% (2.74-12.47%) than in lower-risk men (0.24% (0.17-0.31%). For all populations, the 2017 estimates were below the 2005 estimates, but differences were not significant. In 2017 FSW and MSM together accounted for 9.3% of prevalent cases. These estimates suggest Yunnan's STI programs have kept the overall prevalence of syphilis low, but prevalence remains high in FSW and MSM. Strengthening efforts targeting FSW and MSM, and identification of other risk populations e.g. among heterosexual men, are critical to reduce syphilis.
| S-EPMC7096386 | biostudies-literature
Project description:BackgroundObesity, a known risk factor for chronic kidney disease (CKD), is generally assessed using body mass index (BMI). However, BMI may not effectively reflect body composition, and the impact of muscle-to-fat (MF) mass balance on kidney function has not been elucidated. This study evaluated the association between body muscle and fat mass balance, represented as the MF ratio, and incident CKD development.MethodsData were retrieved from a prospective community-based cohort study (Korean Genome and Epidemiology Study). Muscle and fat mass were measured using multifrequency bioelectrical impedance analysis. The study endpoint was incident CKD (estimated glomerular filtration rate <60 mL/min/1.73 m2 in at least two or more consecutive measurements during the follow-up period).ResultsTotally, 7682 participants were evaluated. Their mean age was 51.7 ± 8.7 years, and 48% of the subjects were men. During a median follow-up of 140.0 (70.0-143.0) months, 633 (8.2%) subjects developed incident CKD. When the association between body composition and incident CKD was investigated, multivariable Cox proportional hazard analysis revealed that increase in MF ratio was related with a decreased risk of CKD development [per 1 increase in MF ratio: hazard ratio (HR), 0.86; 95% confidence interval (CI), 0.77-0.96; P = 0.008]. This association was also maintained when MF ratio was dichotomized according to sex-specific median values (high vs. low: HR, 0.83; 95% CI, 0.70-0.98; P = 0.031). Analyses preformed in a propensity score matched group also revealed a similar decreased risk of incident CKD in high MF ratio participants (high vs. low: HR, 0.84; 95% CI, 0.71-0.98; P = 0.037). This relationship between MF ratio and incident CKD risk was consistently significant across subgroups stratified by age, sex, hypertension, estimated glomerular filtration rate categories, and proteinuria. Among different BMI groups (normal, overweight, and obese), the relationship between high MF ratio and lower incident CKD risk was significant only in overweight and obese subjects.ConclusionsLower fat mass relative to muscle mass may lower the risk of CKD development in individuals with normal renal function. This relationship seems more prominent in overweight and obese subjects than in normal weight subjects.
| S-EPMC7296269 | biostudies-literature
Project description:Mouse skin carcinogenesis experiments suggest upon carcinogen treatment and promotion on mouse skin there arise at least two populations of tumors. One population has a higher incidence of progression from benign papilloma to a squamous cell carcinoma. Further studies have shown that a certain carcinogenesis protocol can select for these high risk tumors. These microarray experiments aim to reveal the genetic signatures of the low risk and high risk papilloma. Keywords: Genetic Signatures
2007-08-01 | GSE5576 | GEO
Project description:CD34+ transriptome analysis of lower-risk MDS at risk of rapid progression
| PRJEB66515 | ENA
Project description:ObjectiveTo determine whether strict blood pressure (BP) control is the best medical management for patients with symptomatic carotid artery occlusion and hemodynamic cerebral ischemia.MethodsIn this prospective observational cohort study, we analyzed data from 91 participants in the nonsurgical group of the Carotid Occlusion Surgery Study (COSS) who had recent symptomatic internal carotid artery occlusion and hemodynamic cerebral ischemia manifested by ipsilateral increased oxygen extraction fraction. The target BP goal in COSS was ≤130/85 mm Hg. We compared the occurrence of ipsilateral ischemic stroke during follow-up in the 41 participants with mean BP ≤130/85 mm Hg to the remaining 50 with higher BP.ResultsOf 16 total ipsilateral ischemic strokes that occurred during follow-up, 3 occurred in the 41 participants with mean follow-up BP of ≤130/85 mm Hg, compared to 13 in the remaining 50 participants with mean follow-up BP >130/85 mm Hg (hazard ratio 3.742, 95% confidence interval 1.065-13.152, log-rank p = 0.027).ConclusionBPs ≤130/85 mm Hg were associated with lower subsequent stroke risk in these patients.Classification of evidenceThis study provides Class III evidence that control of hypertension ≤130/85 mm Hg is associated with a reduced risk of subsequent ipsilateral ischemic stroke in patients with recently symptomatic carotid occlusion and hemodynamic cerebral ischemia (increased oxygen extraction fraction).
| S-EPMC3962994 | biostudies-literature
Project description:The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant hematopoietic stem cell disorders characterized by ineffective growth and differentiation of hematopoietic progenitors leading to peripheral blood cytopenias, dysplasia, and a variable risk of transformation to acute myelogenous leukemia. As most patients present with lower-risk disease, understanding the pathogenesis of ineffective hematopoiesis is important for developing therapies that will increase blood counts in patients with MDS. Various inflammatory cytokines are elevated in MDS and contribute to dysplastic differentiation. Inflammatory pathways mediated by interleukin (IL) 1b, IL-6, IL-1RAP, IL-8, and others lead to growth of aberrant MDS stem and progenitors while inhibiting healthy hematopoiesis. Spliceosome mutations can lead to missplicing of genes such as IRAK4, CASP8, and MAP3K, which lead to activation of proinflammatory nuclear factor κB-driven pathways. Therapeutically, targeting of ligands of the transforming growth factor β (TGF-β) pathway has led to approval of luspatercept in transfusion-dependent patients with MDS. Presently, various clinical trials are evaluating inhibitors of cytokines and their receptors in low-risk MDS. Taken together, an inflammatory microenvironment can support the pathogenesis of clonal hematopoiesis and low-risk MDS, and clinical trials are evaluating anti-inflammatory strategies in these diseases.
| S-EPMC9821551 | biostudies-literature
Project description:AimsCardiac troponin T (cTnT) is suggested as a predictor of amputation in patients with peripheral artery disease (PAD). However, cTnT-PAD association has not been systematically studied in a large study. This study evaluated the association of high-sensitivity cTnT (hs-cTnT) with PAD incidence and also explored whether natriuretic peptide (NT-proBNP), another representative cardiac marker, predicts PAD risk.Methods and resultsAmong 12 288 middle-aged adults, the associations of hs-cTnT and NT-proBNP with incident PAD (hospitalizations with PAD diagnosis or leg revascularization [cases with rest pain or tissue loss considered as critical limb ischaemia (CLI)]) were quantified with multivariable Cox regression models. The risk discrimination was assessed by c-statistic. During a follow-up over 22 years, 454 participants developed PAD (164 CLI cases). In demographically adjusted models, the highest category of hs-cTnT (≥14 vs. <3 ng/L) and NT-proBNP (≥258.3 vs. <51.5 pg/mL) showed ∼8- and 10-20-fold higher risk of PAD and CLI, respectively. Even after adjusting for potential confounders and each other, hazard ratios were greater for CLI than for PAD (7.74 95% confidence interval [95% CI 4.43-13.55] vs. 2.84 [2.02-4.00] for the highest vs. reference hs-cTnT category and 4.63 [2.61-8.23] vs. 3.16 [2.23-4.49] for the highest vs. reference NT-proBNP category). The addition of these cardiac markers improved c-statistics for CLI.ConclusionHigh-sensitivity cTnT and NT-proBNP were independently associated with incident PAD, particularly its severe form, CLI. Although future studies are warranted to investigate pathophysiological mechanisms behind these associations, our study suggests the usefulness of cardiac markers to identify individuals at high risk of CLI.
| S-EPMC6031056 | biostudies-literature
Project description:After initially successful treatment of infantile spasms, the long-term cumulative risk of relapse approaches 50%, and there is no established protocol to mitigate this risk. Although vigabatrin may be an effective means to prevent relapse, there is little guidance as to ideal duration and dosage. Using a cohort of children with infantile spasms and tuberous sclerosis complex (TSC), we evaluated the potential association of post-response VGB treatment and the rate of infantile spasms relapse. Patients with infantile spasms and clinical response to vigabatrin were identified among a multicenter prospective observational cohort of children with TSC. For each patient we recorded dates of infantile spasms onset, response to vigabatrin, relapse (if any), and quantified duration and dosage of vigabatrin after response. Time to relapse as a function of vigabatrin exposure was evaluated using survival analyses. We identified 50 children who responded to VGB. During a median follow-up of 16.6 months (IQR 10.3-22.9), 12 (24%) patients subsequently relapsed after a median of 7.8 months (IQR 3.1-9.6). Relapse occurred after VGB discontinuation in four patients, and during continued VGB treatment in the remaining eight cases. In survival analyses, risk of relapse was unaffected by the presence or absence of VGB treatment (HR 0.31, 95%CI 0.01-28.4, P = 0.61), but weighted-average dosage was associated with marked reduction in relapse risk: Each 50 mg/kg/d increment in dosage was associated with 61% reduction in risk (HR 0.39, 95%CI 0.17 - 0.90, P = 0.026). This study suggests that the risk of infantile spasms relapse in TSC may be reduced by high-dose vigabatrin treatment.
| S-EPMC6347124 | biostudies-literature