Diabetes treatments were related with either an increased or reduced risk of cancer. There is ongoing debate about a potential protective action of metformin. To summarize evidence on the association ...between metformin and risk of cancer and cancer mortality in patients with diabetes.
MEDLINE and EMBASE (January 1966-April 2012). We selected randomized studies comparing metformin and other hypoglycaemic agents and observational studies exploring the association between exposure to metformin and cancer. Outcomes were cancer mortality, all malignancies and site-specific cancers.
Of 25307 citations identified, 12 randomized controlled trials (21,595 patients) and 41 observational studies (1,029,389 patients) met the inclusion criteria. In observational studies there was a significant association of exposure to metformin with the risk of cancer death 6 studies, 24,410 patients, OR:0.65, 95%CI: 0.53-0.80, all malignancies 18 studies, 561,836 patients, OR:0.73, 95%CI: 0.61-0.88, liver 8 studies, 312,742 patients, OR:0.34; 95%CI: 0.19-0.60 colorectal 12 studies, 871,365 patients, OR:0.83, 95%CI: 0.74-0.92, pancreas 9 studies, 847,248 patients, OR:0.56, 95%CI: 0.36-0.86, stomach 2 studies, 100701 patients, OR:0.83, 95%CI: 0.76-0.91, and esophagus cancer 2 studies, 100694 patients, OR:0.90, 95%CI: 0.83-0.98. No significant difference of risk was observed in randomized trials. Metformin was not associated with the risk of: breast cancer, lung cancer, ovarian cancer, uterus cancer, prostate cancer, bladder cancer, kidney cancer, and melanoma.
Results suggest that Metformin might be associated with a significant reduction in the risk of cancer and cancer-related mortality. Randomized trials specifically designed to evaluate the efficacy of metformin as an anticancer agent are warranted.
The natural history of benign thyroid nodules Durante, Cosimo; Costante, Giuseppe; Lucisano, Giuseppe ...
JAMA : the journal of the American Medical Association,
2015-Mar-03, Letnik:
313, Številka:
9
Journal Article
Recenzirano
Odprti dostop
Detection of asymptomatic thyroid nodules has increased. Consensus is lacking regarding the optimal follow-up of cytologically proven benign lesions and sonographically nonsuspicious nodules. Current ...guidelines recommend serial ultrasound examinations and reassessment of cytology if significant growth is observed.
To determine the frequency, magnitude, and factors associated with changes in thyroid nodule size.
Prospective, multicenter, observational study involving 992 consecutive patients with 1 to 4 asymptomatic, sonographically or cytologically benign thyroid nodules. Patients were recruited from 8 hospital-based thyroid-disease referral centers in Italy between 2006 and 2008. Data collected during the first 5 years of follow-up, through January 2013, were analyzed.
Baseline nodule growth (primary end point) was assessed with yearly thyroid ultrasound examinations. Size changes were considered significant for growth if an increase of 20% or more was recorded in at least 2 nodule diameters, with a minimum increase of 2 mm. Baseline factors associated with growth were identified. Secondary end points were the sonographic detection of new nodules and the diagnosis of thyroid cancer during follow-up.
Nodule growth occurred in 153 patients (15.4% 95% CI, 14.3%-16.5%). One hundred seventy-four of the 1567 original nodules (11.1% 95% CI, 10.3%-11.9%) increased in size, with a mean 5-year largest diameter increase of 4.9 mm (95% CI, 4.2-5.5 mm), from 13.2 mm (95% CI, 12.1-14.2 mm) to 18.1 mm (95% CI, 16.7-19.4 mm). Nodule growth was associated with presence of multiple nodules (OR, 2.2 95% CI 1.4-3.4 for 2 nodules; OR, 3.2 95% CI, 1.8-5.6 for 3 nodules; and OR, 8.9 95% CI, 4.4-18.0 for 4 nodules), main nodule volumes larger than 0.2 mL (OR, 2.9 95% CI, 1.7-4.9 for volumes >0.2 to <1 mL and OR, 3.0 95% CI, 1.8-5.1 for volumes ≥1 mL), and male sex (OR, 1.7 95% CI, 1.1-2.6), whereas an age of 60 years or older was associated with a lower risk of growth than age younger than 45 years (OR, 0.5 95% CI 0.3-0.9). In 184 individuals (18.5% 95% CI, 16.4%-20.9%), nodules shrank spontaneously. Thyroid cancer was diagnosed in 5 original nodules (0.3% 95% CI, 0.0%-0.6%). Only 2 had grown. An incidental cancer was found at thyroidectomy in a nonvisualized nodule. New nodules developed in 93 patients (9.3% 95% CI, 7.5%-11.1%), with detection of one cancer.
Among patients with asymptomatic, sonographically or cytologically benign thyroid nodules, the majority of nodules exhibited no significant size increase during 5 years of follow-up and thyroid cancer was rare. These findings support consideration of revision of current guideline recommendations for follow-up of asymptomatic thyroid nodules.
Background:
The optimal timing of treatment starts for achieving the best control on the long-term disability accumulation in multiple sclerosis (MS) is still to be defined.
Objective:
The aim of ...this study was to estimate the optimal time to start disease-modifying therapies (DMTs) to prevent the long-term disability accumulation in MS, using a pooled dataset from the Big Multiple Sclerosis Data (BMSD) network.
Methods:
Multivariable Cox regression models adjusted for the time to first treatment start from disease onset (in quintiles) were used. To mitigate the impact of potential biases, a set of pairwise propensity score (PS)-matched analyses were performed. The first quintile, including patients treated within 1.2 years from onset, was used as reference.
Results:
A cohort of 11,871 patients (median follow-up after treatment start: 13.2 years) was analyzed. A 3- and 12-month confirmed disability worsening event and irreversible Expanded Disability Status Scale (EDSS) 4.0 and 6.0 scores were reached by 7062 (59.5%), 4138 (34.9%), 3209 (31.1%), and 1909 (16.5%) patients, respectively. The risk of reaching all the disability outcomes was significantly lower (p < 0.0004) for the first quintile patients’ group.
Conclusion:
Real-world data from the BMSD demonstrate that DMTs should be commenced within 1.2 years from the disease onset to reduce the risk of disability accumulation over the long term.
Background and aims:
No consensus exists on how aggressively to treat relapsing–remitting multiple sclerosis (RRMS) nor on the timing of the treatment. The objective of this study was to evaluate ...disability trajectories in RRMS patients treated with an early intensive treatment (EIT) or with a moderate-efficacy treatment followed by escalation to higher-efficacy disease modifying therapy (ESC).
Methods:
RRMS patients with ⩾5-year follow-up and ⩾3 visits after disease modifying therapy (DMT) start were selected from the Italian MS Registry. EIT group included patients who received as first DMT fingolimod, natalizumab, mitoxantrone, alemtuzumab, ocrelizumab, cladribine. ESC group patients received the high efficacy DMT after ⩾1 year of glatiramer acetate, interferons, azathioprine, teriflunomide or dimethylfumarate treatment. Patients were 1:1 propensity score (PS) matched for characteristics at the first DMT. The disability trajectories were evaluated by applying a longitudinal model for repeated measures. The effect of early versus late start of high-efficacy DMT was assessed by the mean annual Expanded Disability Status Scale (EDSS) changes compared with baseline values (delta-EDSS) in EIT and ESC groups.
Results:
The study cohort included 2702 RRMS patients. The PS matching procedure produced 363 pairs, followed for a median (interquartile range) of 8.5 (6.5–11.7) years. Mean annual delta-EDSS values were all significantly (p < 0.02) higher in the ESC group compared with the EIT group. In particular, the mean delta-EDSS differences between the two groups tended to increase from 0.1 (0.01–0.19, p = 0.03) at 1 year to 0.30 (0.07–0.53, p = 0.009) at 5 years and to 0.67 (0.31–1.03, p = 0.0003) at 10 years.
Conclusion:
Our results indicate that EIT strategy is more effective than ESC strategy in controlling disability progression over time.
Aim
Variability in HbA1c and blood pressure is associated with the risk of diabetic kidney disease (DKD). No evidence exists on the role of variability in lipids or serum uric acid (UA), or the ...interplay between the variability of different parameters, in renal outcomes.
Methods
Within the AMD Annals database, we identified patients with ≥5 measurements of HbA1c, systolic blood pressure (SBP) and diastolic blood pressure (DBP), total‐, high‐density lipoprotein (HDL)‐ and low‐density lipoprotein (LDL)‐cholesterol, triglycerides, and UA. Patients were followed‐up for up to 5 years. The impact of measures of variability on the risk of DKD was investigated by Cox regression analysis and recursive partitioning techniques.
Results
Four‐thousand, two‐hundred and thirty‐one patients were evaluated for development of albuminuria, and 7560 for decreased estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2). A significantly higher risk of developing albuminuria was associated with variability in HbA1c upper quartile hazard ratio (HR) = 1.3; 95% confidence interval (CI) 1.1‐1.6. Variability in SBP, DBP, HDL‐C, LDL‐C and UA predicted the decline in eGFR, the association with UA variability being particularly strong (upper quartile HR = 1.8; 95% CI 1.3‐2.4). The concomitance of high variability in HbA1c and HDL‐C conferred the highest risk of developing albuminuria (HR = 1.47; 95% CI 1.17‐1.84), while a high variability in UA (HR = 1.54; 95% CI 1.19‐1.99) or DBP (HR = 1.47; 95% CI 1.11‐1.94) conferred the highest risk of decline in eGFR.
Conclusion
The variability of several parameters influences the development of DKD, having a different impact on albuminuria development and on the decline in GFR.
HbA1c variability has emerged as risk factor for cardiovascular diseases in diabetes. However, the impact of HbA1c variability on cardiovascular diseases in subjects within the recommended HbA1c ...target has been relatively unexplored.
Using data from a large database, we studied 101,533 people with type 2 diabetes without cardiovascular diseases. HbA1c variability was expressed as quartiles of the standard deviation of HbA1c during three years (exposure phase). The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, all-cause mortality and was assessed during five years following the first three years of exposure to HbA1c variability (longitudinal phase). An expanded composite outcome including non-fatal myocardial infarction, non-fatal stroke, coronary revascularization/reperfusion procedures, peripheral revascularization procedures, and all-cause mortality was also considered, as well as a series of specific cardiovascular complications. Cox models were adjusted for a large range of risk factors and results were expressed as adjusted hazard ratios.
An association between HbA1c variability and all the outcomes considered was found. The correlation between HbA1c variability and cardiovascular complications development was confirmed in both the subgroups of subjects with a mean HbA1c ≤ 53 mmol/mol (recommended HbA1c target) or > 53 mmol/mol during the exposure phase. The risk related to HbA1c variability was higher in people with mean HbA1c ≤ 53 mmol/mol for the primary outcome (p for interaction 0.004), for the expanded secondary outcome (p for interaction 0.001) and for the stroke (p for interaction 0.001), even though HbA1c remained at the target during the follow-up.
These findings suggest that HbA1c variability may provide additional information for an optimized management of diabetes, particularly in people within the target of HbA1c.
: Arsenic is a toxic metalloid element widely distributed throughout the environment. Arsenic contaminated water has become an ongoing public health issue affecting hundred million people worldwide. ...The aim of this paper was to summarize the evidence in the association between arsenic metabolites and urinary tract cancer risk.
: A systematic review was conducted searching for observational studies that evaluated the association of arsenic metabolites and urinary tract cancer. Risk estimates from individual studies were pooled by using random effects models.
: All the metabolites considered in this study resulted to be significantly associated to urothelial cancer, respectively: IA% 3.51 (1.21-5.82) (
= 0.003), MMA with WMD = 2.77 (1.67-3.87) (
< 0.001) and DMA with WMD = -4.56 (-7.91-1.22) (
= 0.008).
: Arsenic metabolites are significantly associated to urothelial cancer. Future studies will help to verify the independent association(s) between arsenic metabolites and urothelial cancer.
Autism spectrum disorder (ASD) is one of the most common neurodevelopment disorders, characterized by a multifactorial etiology based on the interaction of genetic and environmental factors. Recent ...evidence supports the neurobiological hypothesis based on neuroinflammation theory. To date, there are no sufficiently validated diagnostic and prognostic biomarkers for ASD. Therefore, we decided to investigate the potential diagnostic role for ASD of two biomarkers well known for other neurological inflammatory conditions: the glial fibrillary acidic protein (GFAP) and the neurofilament (Nfl). Nfl and GFAP serum levels were analyzed using SiMoA technology in a group of ASD patients and in a healthy control group (CTRS), age- and gender-matched. Then we investigated the distribution, frequency, and correlation between serum Nfl and GFAP levels and clinical data among the ASD group. The comparison of Nfl and GFAP serum levels between ASD children and the control group showed a mean value of these two markers significantly higher in the ASD group (sNfL mean value ASD pt 6.86 pg/mL median value ASD pt 5.7 pg/mL; mean value CTRS 3.55 pg/mL; median value CTRS 3.1 pg; GFAP mean value ASD pt 205.7 pg/mL median value ASD pt 155.4 pg/mL; mean value CTRS 77.12 pg/mL; median value CTRS 63.94 pg/mL). Interestingly, we also found a statistically significant positive correlation between GFAP levels and hyperactivity symptoms (
-value <0.001). Further investigations using larger groups are necessary to confirm our data and to verify in more depth the potential correlation between these biomarkers and ASD clinical features, such as the severity of the core symptoms, the presence of associated symptoms, and/or the evaluation of a therapeutic intervention. However, these data not only might shed a light on the neurobiology of ASD, supporting the neuroinflammation and neurodegeneration hypothesis, but they also might support the use of these biomarkers in the early diagnosis of ASD, to longitudinally monitor the disease activity, and even more as future prognostic biomarkers.
There is a high incidence of cardiovascular disease in diabetes. Weight variability has been reported as independent risk factor for cardiovascular disease in the general population and preliminarily ...also in people with type 2 diabetes.
Using data from the Swedish National Diabetes Register the possible link between visit-to-visit body weight variability and the risk of cardiovascular complications among people with type 2 diabetes and without prevalent cardiovascular diseases at baseline has been evaluated. Overall, 100,576 people with type 2 diabetes, with at least five measurements of body weight taken over three consecutive years, were included. Variability was expressed as quartiles of the standard deviation of the measures during the three years. The primary composite outcome included non-fatal myocardial infarction, non-fatal stroke, and all-cause mortality and was assessed during five years following the first 3 years of exposure to weight variability.
After adjusting for known cardiovascular risk factors, the risk of the primary composite outcome significantly increased with increasing body weight variability upper quartile HR = 1.45; 95% confidence interval 1.39-1.52. Furthermore, elevated body weight variability was associated with almost all the other cardiovascular complications considered (non-fatal myocardial infarction, non-fatal stroke, all-cause mortality, peripheral arterial disease, peripheral vascular angioplasty, hospitalization for heart failure, foot ulcer, and all-cause mortality).
High body weight variability predicts the development of cardiovascular complications in type 2 diabetes. These data suggest that any strategy to reduce the body weight in these subjects should be aimed at maintaining the reduction in the long-term, avoiding oscillations.
Background:
No uniform criteria for a sensitive identification of the transition from relapsing–remitting multiple sclerosis (MS) to secondary-progressive multiple sclerosis (SPMS) are available.
...Objective:
To compare risk factors of SPMS using two definitions: one based on the neurologist judgment (ND) and an objective data-driven algorithm (DDA).
Methods:
Relapsing-onset MS patients (n = 19,318) were extracted from the Italian MS Registry. Risk factors for SPMS and for reaching irreversible Expanded Disability Status Scale (EDSS) 6.0, after SP transition, were estimated using multivariable Cox regression models.
Results:
SPMS identified by the DDA (n = 2343, 12.1%) were older, more disabled and with a faster progression to severe disability (p < 0.0001), than those identified by the ND (n = 3868, 20.0%). In both groups, the most consistent risk factors (p < 0.05) for SPMS were a multifocal onset, an age at onset >40 years, higher baseline EDSS score and a higher number of relapses; the most consistent protective factor was the disease-modifying therapy (DMT) exposure. DMT exposure during SP did not impact the risk of reaching irreversible EDSS 6.0.
Conclusion:
A DDA definition of SPMS identifies more aggressive progressive patients. DMT exposure reduces the risk of SPMS conversion, but it does not prevent the disability accumulation after the SP transition.
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