3C Study Research Articles

Associations of physiologic subtypes based on HOMA2 indices of β-cell function and insulin sensitivity with the risk of kidney function decline, cardiovascular disease, and all-cause mortality from the 4C study

BackgroundPrevious studies have been limited by their inability to differentiate between the effects of insulin sensitivity and β-cell function on the risk of kidney function decline, cardiovascular disease (CVD), and all-cause mortality. To address this knowledge gap, we aimed to investigate whether the physiological subtypes based on homeostasis model assessment-2 (HOMA2) indices of β-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) could be used to identify individuals with subsequently high or low of clinical outcome risk.MethodsThis retrospective cohort study included 7,317 participants with a follow-up of up to 5 years. Based on HOMA2 indices, participants were categorized into four physiologic subtypes: the normal phenotype (high insulin sensitivity and high β-cell function), the insulinopenic phenotype (high insulin sensitivity and low β-cell function), the hyperinsulinaemic phenotype (low insulin sensitivity and high β-cell function), and the classical phenotype (low insulin sensitivity and low β-cell function). The outcomes included kidney function decline, CVD events (fatal and nonfatal), and all-cause mortality. Cox regression models were used to calculate hazard ratios (HRs) for outcomes, and spline models were used to examine the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ResultsA total of 1,488 (20.3%) were classified as normal, 2,179 (29.8%) as insulinopenic, 2,173 (29.7%) as hyperinsulinemic, and 1,477 (20.2%) as classical subtypes. Compared with other physiological subtypes, the classical subtype presented the highest risk of kidney function decline (classical vs. normal HR 11.50, 95% CI 4.31–30.67). The hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality (hyperinsulinemic vs. normal: fatal CVD, HR 6.56, 95% CI 3.09–13.92; all-cause mortality, HR 4.56, 95% CI 2.97–7.00). Spline analyses indicated the dose-dependent associations of HOMA2-B and HOMA2-S with outcomes.ConclusionsThe classical subtype had the strongest correlation with the risk of kidney function decline, and the hyperinsulinemic subtype had the highest risk of CVD and all-cause mortality, which should be considered for interventions with precision medicine.Graphical abstract

Associations of Diet and Lifestyle with Mortality and Stroke: The China Cardiometabolic Disease and Cancer Cohort (4C) Study.

This study aimed to examine the individual and combined associations between dietary habits and lifestyle factors concerning all-cause mortality and stroke in Chinese adults. We conducted a nationwide, multicenter, prospective cohort study involving 10,008 participants, gathering baseline data on lifestyle, metabolic status, dietary habits, and living behaviors. Subsequently, a 10-year follow-up was performed, resulting in the inclusion of 7,612 participants in this study. We employed Spearman correlation analysis, restricted cubic spline regression, and Cox regression analysis to evaluate the connections between outcome events, dietary habits, and lifestyle. For each additional serving of pulses consumed per week, there was a slight decrease in the risk of all-cause mortality (HR: 0.91, 95% CI: 0.83-0.99). The hazard ratios for stroke were 2.24 (1.48, 3.37) for current smokers, in comparison to individuals who had never smoked. Appropriate intake of specific dietary factors and certain lifestyle habits were associated with reduced stroke: fruit drinks at 0.51 (0.34, 0.87), and animal viscera at 0.58 (0.32, 1.04). Weekly consumption of at least 21 servings of vegetables (0.72, 0.53-0.98), 0-1 serving of fried food (0.58, 0.38-0.90), and at least 1 serving of carbonated beverages (0.51, 0.28-0.92) was associated with a reduced risk of stroke. Smoking was found to be linked to an increased risk of stroke. A higher intake of fruit drinks and animal viscera was associated with a reduced risk of stroke. In contrast, a higher intake of beans was associated with a decreased risk of overall mortality. Consuming an appropriate amount of vegetables, fried foods, and carbonated drinks was found to potentially lower the risk of stroke. Collectively, these findings underscore the importance of developing tailored dietary interventions conducive to the Chinese populace's health.

Association of social determinants, lifestyle, and metabolic factors with mortality in Chinese adults: A nationwide 10-year prospective cohort study

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5μm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Serum Medium-Chain Fatty Acids and the Risk of Incident Diabetes: Findings from the 4C Study.

Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies. To investigate associations and genetic susceptibility between serum MCFAs and diabetes risk. We investigated baseline serum MCFAs (n=5) in a nested case-control study comprising incident diabetes cases (n=1,707) and matched normoglycemic control subjects (n=1,707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants. In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% confidence intervals) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = 0.042, 0.034, and 0.037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = 0.003). These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

Timing and Modality of Kidney Replacement Therapy in Children and Adolescents

IntroductionThe choice and timing of kidney replacement therapy (KRT) is influenced by clinical factors, laboratory features, feasibility issues, family preferences and clinicians´ attitudes. We analyzed the factors associated with KRT modality and timing in a multicenter, multinational prospective pediatric cohort study. Methods695 pediatric chronic kidney disease patients enrolled into the 4C study at age 6 to 17 years with estimated glomerular filtration rate (eGFR) 10 to 60 ml/min/1.73 m2 were investigated. Competing risk regression was performed to identify factors associated with initiation of dialysis or pre-emptive transplantation (Tx), including primary renal diagnosis, demographics, anthropometrics and laboratory parameters. ResultsDuring the 8-year observation period, 342 patients (49%) started KRT. Of these, 200 patients started dialysis whereas 142 patients underwent pre-emptive Tx. A lower eGFR at enrolment (HR (hazard ratio) 0.76 [95% confidence interval 0.74-0.78], a steeper eGFR slope (HR 0.90 [0.85-0.95] and a higher systolic blood pressure standard deviation score (SDS) (HR 2.07 [1.49-2.87]) increased the likelihood of KRT initiation. Patients with glomerulopathies were more likely to start dialysis than children with CAKUT (HR 3.81 [2.52-5.76]). Lower BMI SDS (HR 0.73 [0.6-0.89]) and lower hemoglobin (HR 0.8 [0.72-0.9]) were associated with higher likelihood of dialysis. A significant center effect was observed, accounting for 6.8% (dialysis) to 8.7% (pre-emptive Tx) of explained variation. ConclusionThe timing and choice of KRT in pediatric patients is influenced by the rate of kidney function loss, the underlying kidney disease, nutritional status, blood pressure, anemia and center-specific factors.

Association of circulating long-chain free fatty acids and incident diabetes risk among normoglycemic Chinese adults: a prospective nested case–control study

BackgroundLong-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. ObjectivesOur study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. MethodsThis is a prospective nested case–control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score–matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. ResultsThe majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18–26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. ConclusionsThese findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

Dyslipidemia in children with chronic kidney disease—findings from the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study

BackgroundDyslipidemia is an important and modifiable risk factor for CVD in children with CKD.MethodsIn a cross-sectional study of baseline serum lipid levels in a large prospective cohort study of children with stage 3–5 (predialysis) CKD, frequencies of abnormal lipid levels and types of dyslipidemia were analyzed in the entire cohort and in subpopulations defined by fasting status or by the presence of nephrotic range proteinuria. Associated clinical and laboratory characteristics were determined by multivariable linear regression analysis.ResultsA total of 681 patients aged 12.2 ± 3.3 years with a mean eGFR of 26.9 ± 11.6 ml/min/1.73 m2 were included. Kidney diagnosis was classified as CAKUT in 69%, glomerulopathy in 8.4%, and other disorders in 22.6% of patients. Nephrotic range proteinuria (defined by a urinary albumin/creatinine ratio > 1.1 g/g) was present in 26.9%. Dyslipidemia was found in 71.8%, and high triglyceride (TG) levels were the most common abnormality (54.7%). Fasting status (38.9%) had no effect on dyslipidemia status. Except for a significant increase in TG in more advanced CKD, lipid levels and frequencies of dyslipidemia were not significantly different between CKD stages. Hypertriglyceridemia was associated with younger age, lower eGFR, shorter duration of CKD, higher body mass index (BMI-SDS), lower serum albumin, and higher diastolic blood pressure.ConclusionsDyslipidemia involving all lipid fractions, but mainly TG, is present in the majority of patients with CKD irrespective of CKD stage or fasting status and is significantly associated with other cardiovascular risk factors.Graphical abstract A higher resolution version of the Graphical abstract is available as Supplementary information

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Can FSRQ 3C 345 be a very high energy blazar candidate?

ABSTRACT The recent detection of very high energy (VHE) emissions from flat spectrum radio quasars (FSRQs) at high redshifts has revealed that the universe is more transparent to VHE γ-rays than it was expected. It has also questioned the plausible VHE emission mechanism responsible for these objects. Particularly for FSRQs, the γ-ray emission is attributed to the external Compton (EC) process. We perform a detailed spectral study of Fermi-detected FSRQ 3C 345 using synchrotron, synchrotron self-Compton, and EC emission mechanisms. The simultaneous data available in optical, ultraviolet, X-ray, and γ-ray energy bands is statistically fitted under these emission mechanisms using the χ2-minimization technique. Three high flux states and one low flux state are chosen for spectral fitting. The broad-band spectral energy distribution during these flux states is fitted under different target photon temperatures, and the model VHE flux is compared with the 50 h Cherenkov Telescope Array sensitivity. Our results indicate a significant VHE emission could be attained during the high flux state from MJD 59635−59715 when the target photon temperature is within 900–1200 K. Furthermore, our study shows a clear trend of variation in the bulk Lorentz factor of the emission region as the source transits through different flux states. We also note that during high γ-ray flux states, an increase in external photon temperature demands high bulk Lorentz factors, while this behaviour reverses in case of low γ-ray flux state.

Lifestyle for Brain Health Score, Genetic Risk and Incidence of Dementia

AbstractBackgroundAssessing whether modifiable factors are associated with dementia risk regardless of genetic risk for the disease is primordial for precision prevention. So far, studies on gene‐by‐environment interactions (GxE) in dementia have been controversial. We leveraged a large cohort of older persons to investigate the association between numerous modifiable factors, reflected by the lifestyle for brain‐health (LIBRA) score (defined in figure 1), and the incidence of dementia, evaluating effect modification by genetic risk.MethodWe included participants from the Three‐City (3C) study, free of dementia at baseline and followed for up to 17 years. The LIBRA score and a genetic risk score (GRS) based on the latest Alzheimer’s disease GWAS (excluding the apolipoprotein E {APOE} locus) were constructed. Illness‐death models for interval‐censored data were used to assess the relation of LIBRA, GRS and carriership of the e4 allele of the APOE gene (and their interactions) to the incidence of dementia, accounting for potential competing risk by death.ResultThe population included 5170 3C participants aged on average 73.8 years at baseline. Both genetic factors and LIBRA were significantly associated with dementia risk. In multivariable‐adjusted models, each one‐point increase in LIBRA was associated with a 10% higher risk of dementia (95% CI 1.07‐1.13). We found no evidence of GxE interaction (p≥0.2 for two‐order [LIBRA by each genetic variable] and three‐order interaction terms [LIBRA‐by‐GRS‐by‐APOE4]); a higher LIBRA was significantly associated with increased dementia risk in both APOE4 carriers and non‐carriers (figure 1) and in low, medium or high GRS level (figure 2), with similar magnitude of associations in all strata. Although power was limited to examine APOE4 carriers by GRS strata, the trend of association of LIBRA (continuous) to dementia risk was not meaningfully different from what found in other groups (figure 3).ConclusionIn this large cohort of older persons, increasing number of health and lifestyle risk factors for dementia was associated with higher dementia risk in all levels of genetic risk. These findings suggest prevention programs with targeted lifestyle modifications and health management may be efficient even in those with highest risk for dementia based on their genetic susceptibility.

Synthesis of novel coumarin-based thiosemicarbazones and their implications in diabetic management via in-vitro and in-silico approaches

Diabetes mellitus has a high prevalence rate and it has been deemed a severe chronic metabolic disorder with long-term complications. This research aimed to identify compounds that could potentially inhibit the vital metabolic enzyme α-glucosidase and thereby exert an anti-hyperglycemic effect. The main goal was to establish an effective approach to control diabetes. To proceed with this study, a series of novel coumarin-derived thiosemicarbazones 3a–3m was synthesized and examined using a variety of spectroscopic methods. Moreover, all the compounds were subjected to α-glucosidase inhibition bioassay to evaluate their antidiabetic potential. Fortunately, all the compounds exhibited several folds potent α-glucosidase inhibitory activities with IC50 values ranging from 2.33 to 22.11 µM, in comparison to the standard drug acarbose (IC50 = 873.34 ± 1.67 µM). The kinetic studies of compound 3c displayed concentration-dependent inhibition. Furthermore, the binding modes of these molecules were elucidated through a molecular docking strategy which depicted that the thiosemicarbazide moiety of these molecules plays a significant role in the interaction with different residues of the α-glucosidase enzyme. However, their conformational difference is responsible for their varied inhibitory potential. The molecular dynamics simulations suggested that the top-ranked compounds (3c, 3g and 3i) have a substantial effect on the protein dynamics which alter the protein function and have stable attachment in the protein active pocket. The findings suggest that these molecules have the potential to be investigated further as novel antidiabetic medications.

The Impact of Sedentary Behavior on Renal Function Decline in 132,123 Middle Aged and Older Adults: A Nationwide Cohort Study.

BACKGROUND Prior studies suggest that sedentary behavior is a well-known risk factor for cardiometabolic diseases. However, the longitudinal association between overall siting time and kidney function decline is not known. MATERIAL AND METHODS We performed a nationwide prospective cohort study in individuals aged more than 40 years enrolled in the China Cardiometabolic Disease and Cancer Cohort (4C) study. A total of 132 123 individuals were included in this study. Sitting time was measured with the short version of the International Physical Activity Questionnaire (IPAQ). Kidney function decline was defined as an eGFR <60 mL/min/1.73 m² or more than a 30% decrease in eGFR from baseline. Multivariate Cox proportional hazards regression analyses were conducted to estimate the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of the relation between kidney function decline and sitting time. RESULTS During a mean follow-up of 3.8 years, 3890 (2.9%) participants experienced kidney function decline. Longer sitting time was significantly associated with the risk of kidney function decline (aHR, 1.136; 95% CI, 1.036-1.247, P=0.007, comparing participants with baseline sitting time in the lowest quartile with those in the highest quartile) after adjustment for potential confounders. CONCLUSIONS Longer sitting time was independently and prospectively associated with a higher risk of kidney function decline. Sedentary behavior might represent a modifiable risk factor for chronic kidney disease (CKD) prevention.

A Nomogram for Predicting the Risk of CKD Based on Cardiometabolic Risk Factors.

In China, the spectrum of causes for CKD has been changing in recent years, and the proportion of CKD caused by cardiometabolic diseases, such as diabetes and hypertension continues to increase. Thus, predicting CKD based on cardiometabolic risk factors can to a large extent help identify those at increased risk and facilitate the prevention of CKD. In this study, we aimed to develop a nomogram for predicting CKD risk based on cardiometabolic risk factors. We developed a nomogram for predicting CKD risk by using a subcohort population of the 4C study, which was located in central China. The prediction model was designed by using a logistic regression model, and a backwards procedure based on the Akaike information criterion was applied for variable selection. The performance of the model was evaluated by the concordance index (C-index), and Hosmer‒Lemeshow goodness-of-fit test. The bootstrapping method was applied for internal validation. During the 3-years follow-up, 167 cases of CKD developed. By using univariate and multivariate logistic regression models, the following factors were identified as predictors in the nomogram: age, sex, HbA1c, baseline eGFR, low HDL-C levels, high TC levels and SBP. The bootstrap-corrected C-index for the model was 0.84, which indicated good discrimination ability. The Hosmer‒Lemeshow goodness-of-fit tests yielded chi-square of 13.61 (P=0.192), and the calibration curves demonstrated good consistency between the predicted and observed probabilities, which indicated satisfactory calibration ability. We developed a convenient and practicable nomogram for the 3‑year risk of incident CKD among a population in central China, which may help to identify high-risk individuals for CKD and contribute to the prevention of CKD.

Multi-frequency study of large size radio galaxies 3C 35 and 3C 284

We report multi-frequency observations of two large radio galaxies, 3C 35 and 3C 284. The low-frequency observations were done with Giant Metrewave Radio Telescope starting from ∼150 MHz, and the high-frequency observations were done with the Very Large Array. We have studied the radio morphology of these two sources at different frequencies. We present the spectral ageing map using two of the most widely used models, the Kardashev-Pacholczyk and Jaffe-Perola models. Another more realistic and complex Tribble model is also used. We also calculate the jet power and the speed of the radio lobes of these galaxies. We check whether any episodic jet activity is present in these galaxies and found no sign of such activity.

Double SSA spectrum and magnetic field strength of the FSRQ 3C 454.3

ABSTRACT We present the results of a radio multifrequency ($\rm 3{-}340~GHz$) study of the blazar 3C 454.3. After subtracting the quiescent spectrum corresponding to optically thin emission, we found two individual synchrotron self-absorption (SSA) features in the wide-band spectrum. The one SSA had a relatively low turnover frequency (νm) in the range of $\rm 3{-}37~GHz$ (lower νm SSA spectrum, LSS), and the other one had a relatively high νm of $\rm 55{-}124~GHz$ (higher νm SSA spectrum, HSS). Using the SSA parameters, we estimated B-field strengths at the surface where optical depth τ = 1. The estimated B-field strengths were $\rm \gt 7$ and $\rm \gt 0.2~mG$ for the LSS and HSS, respectively. The LSS-emitting region was magnetically dominated before the 2014 June γ-ray flare. The quasi-stationary component (C), ∼0.6 mas apart from the 43 -GHz radio core, became brighter than the core with decreasing observing frequency, and we found that component C was related to the LSS. A decrease in jet width was found near component C. As a moving component, K14 approached component C, and the flux density of the component was enhanced while the angular size decreased. The high intrinsic brightness temperature in the fluid frame was obtained as TB, int ≈ (7.0 ± 1.0) × 1011 K from the jet component after the 2015 August γ-ray flare, suggesting that component C is a high-energy emitting region. The observed local minimum of jet width and re-brightening behaviour suggest a possible recollimation shock in component C.

Surgical margin status in relation to surgical approach in the management of early-stage cervical Cancer: A Canadian cervical Cancer collaborative (4C) study

ObjectiveSurgical margin status in women undergoing surgery for early-stage cervical cancer is an important prognostic factor. We sought to determine whether close (<3 mm) and positive surgical margins are associated with surgical approach and survival. MethodsThis is a national retrospective cohort study of cervical cancer patients treated with radical hysterectomy. Patients with stage IA1/LVSI-Ib2(FIGO 2018) with lesions up to 4 cm at 11 Canadian institutions from 2007 to 2019 were included. Surgical approach included robotic/laparoscopic (LRH), abdominal (ARH) or combined laparoscopic-assisted vaginal/vaginal (LVRH) radical hysterectomy. Recurrence free survival(RFS) and overall survival (OS) were estimated using Kaplan-Meier analysis. Chi-square and log-rank tests were used to compare groups. Results956 patients met inclusion criteria. Surgical margins were as follows: negative (87.0%), positive (0.4%) or close <3 mm (6.8%), missing (5.8%). Most patients had squamous histology (46.9%); 34.6% had adenocarcinomas and 11.3% adenosquamous. Most were stage IB (75.1%) and 24.9% were IA. Mode of surgery included: LRH(51.8%), ARH (39.2%), LVRH (8.9%).Predictive factors for close/positive margins included stage, tumour diameter, vaginal involvement and parametrial extension. Surgical approach was not associated with margin status (p = 0.27). Close/positive margins were associated with a higher risk of death on univariate analysis (HR = non calculable for positive and HR = 1.83 for close margins, p = 0.017), but not significant for OS when adjusted for stage, histology, surgical approach and adjuvant treatment. There were 7 recurrences in patients with close margins (10.3%, p = 0.25). 71.5% with positive/close margins received adjuvant treatment. In addition, MIS was associated with a higher risk of death (OR = 2.39, p = 0.029). ConclusionSurgical approach was not associated to close or positive margins. Close surgical margins were associated with a higher risk of death. MIS was associated with worse survival, suggesting that margin status may not be the driver of worse survival in these cases.

Health trajectories of elderly living in French senior housing: a longitudinal perspective

Senior housing for older adults could be an alternative or a transitional care model between home care and nursing home care. Using two longitudinal cohorts of community dwellers aged 65 years or older, we compared risks of mortality and of nursing homes admission between older adults who did or did not move to senior housing over time. In the 3C study (n = 2104, 17 years of follow-up), 143 (6.8%) participants moved into a senior housing during the follow-up. This move was associated with a lower risk of mortality (hazard ratio (HR): 0.64; 95% confidence interval (CI) 0.46–0.77) and a higher risk of nursing home admissions (HR: 1.54 (1.10–2.15)). The risks of hospitalizations (HR: 0.54 (0.40–0.73)) and falls (HR: 0.63 (0.50–0.79)) were lower. In the PAQUID study (n = 3777, 27 years of follow-up), 161 (4.3%) participants moved into a senior housing. This move was also associated with a lower mortality risk (HR: 0.72 (0.58–0.88)) and a higher risk of nursing home admissions (HR: 1.39 (1.05–1.86)). Our results showing lower risks of mortality suggest that senior housing may be a relevant model for vulnerable older adults.

Urinary DKK3 Predicts Short-Term eGFR Decline and Nephroprotec-tive Efficacy of Antihypertensive Therapy in Children With CKD: Findings From the 4C Study and ESCAPE Trial

Urinary DKK3 Predicts Short-Term eGFR Decline and Nephroprotec-tive Efficacy of Antihypertensive Therapy in Children With CKD: Findings From the 4C Study and ESCAPE Trial

Arterial Stiffness and Chronic Kidney Disease Progression in Children.

CKD has been linked to increased arterial stiffness in adults, but data in children with CKD remain conflicting. We aimed to investigate the longitudinal dynamics and determinants of pulse wave velocity in children with CKD and its association with CKD progression. We performed an analysis of the Cardiovascular Comorbidity in Children with Chronic Kidney Disease (4C) study, which prospectively followed children aged 6-17 years with CKD stages 3-5. Follow-up was censored at the time of KRT initiation. Two separate analyses were performed: with absolute pulse wave velocity (primary outcome) and with pulse wave velocity standardized to height (z score; restricted to participants ≤17 years) as a sensitivity analysis. In total, 667 patients with a mean baseline eGFR of 27 ml/min per 1.73 m2 were included. Pulse wave velocity above the 95th percentile was observed in 124 (20%) patients at baseline. Absolute pulse wave velocity increased gradually over the median follow-up of 2.7 (interquartile range, 0.7-4.4) years, whereas pulse wave velocity z score remained relatively stable. Absolute pulse wave velocity over time associated with time; older age; higher mean arterial pressure, LDL cholesterol, and albuminuria; and lower ferritin. Pulse wave velocity z score (n=628) was associated with the same variables and additionally, with higher diastolic BP z score, lower height z score, younger age, and girls. Of 628 patients, 369 reached the composite end point of CKD progression (50% eGFR loss, eGFR <10 ml/min per 1.73 m2, or the start of KRT) during a median follow-up of 2.4 (interquartile range, 0.9-4.6) years. Pulse wave velocity z score did not associate with CKD progression by univariable or multivariable proportional hazard analysis correcting for the established predictors eGFR, proteinuria, and BP. Pulse wave velocity is increased in children with CKD but does not associate with eGFR or CKD progression.

Examining the Linear Association Between Blood Pressure Levels and Cardiovascular Diseases in the Absence of Major Risk Factors in China.

Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association. In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, <110 mg/dL; 2-hour post-load glucose, <140 mg/dL) and lipid profile (total cholesterol, <200 mg/dL; LDL [low-density lipoprotein] cholesterol, <130 mg/dL) were selected. The total person-years of follow-up for CVRF-free subjects and CVRF-preferable subjects were 130 147 and 63 573 person-years, respectively. Information on the development of major CVDs was collected during 2014 to 2016. Cox proportional hazard models were performed to estimate the risks for incident CVD by SBP and DBP groups, respectively. We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19-2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36-3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40-3.28]) compared with SBP <110 mm Hg. Significant increases were also observed for DBP level of 80 to 89 mm Hg (hazard ratio, 1.43 [95% CI, 1.03-1.97]) compared with DBP <70 mm Hg. Similar results were observed in CVRF-preferable participants. SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.