Despite the clear association between remnant cholesterol (RC)and diabetes risk, no study to date has examined the relationship between RC and reversal of prediabetes to normoglycemia. This retrospective cohort study included a total of 15,023 patients with prediabetes who underwent a physical examination between 2010 and 2016. The link between initial RC levels and the reversion from prediabetes to normoglycemia was analyzed using the Cox proportional-hazards regression model. Additionally, the study explored the possible relationship between RC and the probability of returning normoglycemia by applying Cox proportional hazards regression models with cubic spline functions. To address competing risks, a multivariate Cox regression analysis was undertaken, treating the onset of diabetes as a competing risk event for reversing prediabetes to normoglycemia. Additionally, the study incorporated extensive subgroup analyses alongside multiple sensitivity analyses, enhancing the reliability and robustness of the results. After adjusting for covariates, the findings indicated that RC was inversely associated with the likelihood of reverting to normoglycemia (per 5 mg/dL increase, HR = 0.918, 95% CI 0.909-0.927). The analysis also revealed a nonlinear relationship between RC and normoglycemia reversion, with an inflection point at 51.08 mg/dL. For RC values below this inflection point (RC < 50.08 mg/dL), the HR for the probability of returning to normoglycemia was 0.907 (95% CI 0.897-0.917 per 5 mg/dL). Additionally, the competing risks model demonstrated a negative relationship between RC and the reversal of prediabetes to normoglycemia (SHR = 0.92, 95% CI 0.91-0.93). Sensitivity analyses confirmed the robustness and stability of these results. This study demonstrated a negative and non-linear association between RC and the probability of reversion to normoglycemia in Chinese adults with prediabetes. By actively intervening to reduce RC levels, at least to below 51.08 mg/dL, further reduction of RC may significantly increase the probability of returning to normoglycemia from prediabetes.

OBJECTIVE: Serum lactate and creatinine levels upon admission in cardiac arrest (CA) patients significantly correlate with acute kidney injury (AKI) post-restoration of autonomic circulation. However, the association between serum lactate/creatinine ratio (LCR) and AKI in this population remains unclear. This study aimed to explore the relationship between LCR at admission and cardiac arrest-associated acute kidney injury (CA-AKI).
METHODS: We conducted a secondary analysis of previously published data on CA patient resuscitation, categorizing them into tertiles based on LCR levels. Univariate and multivariate logistic regression models and subgroup analyses were employed to investigate the association between LCR and CA-AKI. Non-linear correlations were explored using restricted cubic splines, and a two-piece wise logistic proportional hazards model for both sides of the inflection point was constructed.
RESULTS: A total of 374 patients (72.19 % male) were included, with intensive care unit mortality, in-hospital mortality, and neurologic dysfunction rates of 51.87 %, 56.95 %, and 39.57 %, respectively. The overall CA-AKI incidence was 59.09 %. Multivariate logistic proportional hazards analysis revealed a negative association between LCR and CA-AKI incidence (adjusted odds ratio [OR] 0.85, 95 % confidence intervals [CI] = 0.78-0.93, P=0.001). Triple spline restriction analysis depicted an L-shaped correlation between baseline LCR and CA-AKI incidence. Particularly, a baseline LCR<0.051 was negatively associated with CA-AKI incidence (OR 0.494, 95 % CI=0.319-0.764, P=0.002). Beyond the LCR turning point, estimated dose-response curves remained consistent with a horizontal line.
CONCLUSIONS: Baseline LCR in CA patients exhibits an L-shaped correlation with AKI incidence following restoration of autonomic circulation. The threshold for CA-AKI is 0.051. This finding suggests that LCR may aid in identifying CA patients at high risk of AKI.

An increasing evidence suggested that chronic kidney disease (CKD) is closely related to oxidative stress, and dietary antioxidant intake can serve as a primary preventive measure for CKD. However, the relationship between composite dietary antioxidant index (CDAI) and renal anemia is not well understood. We postulated that elevated CDAI levels would be inversely related to a higher likelihood of renal anemia. The standardized calculation of CDAI was performed to investigate the relationship between them by a binary regression model. A non-linear relationship was examined through restricted cubic spline curves, and then pinpointed the inflection point. Subgroup analysis was then used to assess the robustness of the model. Finally 5880 participants were included in the study and a notable correlation between CDAI and renal anemia was found (P < 0.0001). In the multivariate linear regression model with adjustment for all confounding variables, the odds ratio (OR) and 95% confidence interval (CI) was 0.96 (0.94, 0.98; P < 0.0001), A non-linear relationship between CDAI and renal anemia was explored through restricted cubic splines, with a inflection at 6.005. Before the inflection point, for each unit rise in CDAI, the prevalence of renal anemia decreased by 5.7%. Subgroup analysis showed no statistically significant differences in interactions between any subgroups (P > 0.05). Our findings indicated a non-linear negative correlation between CDAI and renal anemia. The causal relationship still needs to be further clarified through large-scale prospective studies.

UNASSIGNED: White blood cell (WBC) counts has been identified as a prognostic biomarker which frequently predict adverse outcomes and mortality risk in various conditions. However, evidence for the association between WBC counts and short-term outcomes after intracranial tumor resection remains limited. This study aimed to explore associations between preoperative WBC counts and thirty-day surgical mortality after craniotomy in adult intracranial tumor patients.
UNASSIGNED: This retrospective cohort study performed secondary analysis of 18,049 intracranial tumor craniotomy patients from the ACS NSQIP database (2012-2015). The major exposure and outcome were preoperative WBC counts and thirty-day surgical mortality, respectively. Cox regression modeling assessed the linear association between them. Non-linear associations between them were evaluated by conducting smooth curve fitting using an additive Cox proportional hazard model in conjunction with segmented linear regression modeling. Subgroup analysis and interaction testing assessed effect modification. Sensitivity analysis evaluated result robustness.
UNASSIGNED: The total thirty-day surgical mortality after craniotomy was 2.49% (450/18,049). The mean of preoperative WBC counts was 9.501 ± 4.402 × 10^9/L. Fully adjusted model shows that elevated preoperative WBC counts was independently associated with increased thirty-day surgical mortality (HR = 1.057, 95%CI: 1.040, 1.076). Further analysis revealed a non-linear association between them: below a WBC threshold of 13.6 × 10^9/L, higher WBC counts elevated thirty-day mortality (HR = 1.117; 95%CI: 1.077, 1.158), while risk plateaued and no significant mortality rise occurred above this level (HR = 1.015, 95%CI: 0.982, 1.050). Steroid usage status has a significant effect modification on the WBC-mortality association (P for interaction = 0.002). The non-linear WBC-mortality association was only present for non-steroid users (HR = 1.158, 95%CI: 1.108, 1.210) but not steroid users (HR = 1.009, 95%CI: 0.966, 1.055). The sensitivity analysis confirmed the result robustness.
UNASSIGNED: Elevated preoperative WBC counts were independently and non-linearly associated with an increased risk of thirty-day surgical mortality in adult non-steroid use patients undergoing craniotomy for intracranial tumors. As a convenient predictor, preoperative WBC data allows improved risk profiling and personalized management in adult intracranial tumor patients.

BACKGROUND: Obstructive sleep apnoea (OSA) is commonly associated with insulin resistance (IR) and dyslipidaemia. Apolipoprotein E (APOE) plays important roles in lipid metabolism. The study aimed to disentangle the multifactorial relationships between IR and APOE based on a large-scale population with OSA.
METHODS: A total of 5,591 participants who underwent polysomnography for OSA diagnosis were finally enrolled. We collected anthropometric, fasting biochemical and polysomnographic data for each participant. Linear regression analysis was performed to evaluate the relationships between APOE, IR, and sleep breathing-related parameters. Logistic regression, restricted cubic spline (RCS) and mediation analyses were used to explore relationships between APOE and IR in patients with OSA.
RESULTS: Increasing OSA severity was associated with greater obesity, more obvious dyslipidaemia, and higher levels of APOE and IR. APOE was positively correlated with the apnoea-hypopnoea index (AHI), oxygen desaturation index (ODI) and microarousal index (MAI) even after adjusting for age, sex, body mass index, and smoking and drinking levels (β = 0.107, β = 0.102, β = 0.075, respectively, all P < 0.001). The risks of IR increased from the first to fourth quartiles of APOE (odds ratio (OR) = 1.695, 95% CI: 1.425-2.017; OR = 2.371, 95% confidence interval (CI): 2.009-2.816; OR = 3.392, 95% CI: 2.853-4.032, all P < 0.001) after adjustments. RCS analysis indicated non-linear and dose response relationships between APOE, AHI, ODI, MAI and insulin resistance. Mediation analyses showed that HOMA-IR explained 9.1% and 10% of the association between AHI, ODI and APOE. The same trends were observed in men, but not in women.
CONCLUSIONS: This study showed that APOE is a risk factor for IR; moreover, IR acts as a mediator between OSA and APOE in men. APOE, IR, and OSA showed non-linear and multistage relationships. Taken together, these observations revealed the complex relationships of metabolic disorders in patients with OSA, which could lead to the development of new treatment modalities and a deeper understanding of the systemic impact of OSA.

UNASSIGNED: Previous studies on the liner associations between serum 25-hydroxyvitamin D [25(OH)D] levels and lipid profiles revealed ambiguous findings. The current study therefore tried to elucidate the possible non-linear associations between 25(OH)D and lipid profiles.
UNASSIGNED: This study involved 8,516 adult participants (aged 18-74 years, males N = 3,750, females N = 4,766) recruited from the Dalian health management cohort (DHMC). The risk (OR) for specific dyslipidemias was estimated across the serum 25(OH)D levels and the cut-off value for serum 25(OH)D were determined by using logistic regression, restricted cubic spline, and piecewise linear regression methods, adjusted for age, sex, season, and ultraviolet index.
UNASSIGNED: In this study, a high prevalence of 25(OH)D deficiency was observed in the participants (65.05%). The level of 25(OH)D showed the inverse U-shaped correlations with the risks (ORs) of abnormal lipid profile, with inflection points observed at 23.7 ng/ml for hypercholesterolemia, 24.3 ng/ml for hypertriglyceridemia, 18.5 ng/ml for hyper-low-density lipoprotein cholesterolemia, 23.3 ng/ml for hypo-high-density lipoprotein cholesterolemia, 23.3 ng/ml for hyper-non-high-density lipoprotein cholesterol, and 24.3 ng/ml for high remnant cholesterol. The stratified analyses showed that the risk for most dyslipidemias related to deficiency of 25(OH)D was particularly increased among females aged 50-74 (except for hypertriglyceridemia, where the highest risk was among men aged 50-74 years), during winter/spring or under low/middle ultraviolet index environments.
UNASSIGNED: Nonlinear inverse U-shaped associations were observed between 25(OH)D levels and abnormal lipid profile. The risk was particularly increased among females aged 50-74, during winter/spring period or under lower ultraviolet index environments. In vitamin D deficient subjects [25(OH)D <20 ng/ml], a positive association of serum vitamin D levels with the risk for dyslipidemia was observed, which needs a further.

Over the years, obesity has become more commonplace and has had a substantial impact on several medical specialties, including reproductive medicine. The potential correlation between the visceral adiposity index (VAI) and infertility has yet to be determined. Women between the ages of 18 and 45 were included in this cross-sectional study, which was conducted as part of the National Health and Nutrition Examination Survey (NHANES) between 2015 and 2020. Three tertiles were used to group VAI levels. Subgroup analysis and weighted binary logistic regression were employed to investigate the independent relationship between VAI and infertility. Smooth curve fitting was used to explore nonlinear relationships. This cross-sectional study followed the criteria of the STROBE guidelines. Of the 1231 participants, 127 were infertile women aged 18-45 years. A higher VAI was associated with a higher prevalence of infertility (OR = 1.22, 95% CI:1.03-1.45), which remained consistent across all subgroups (p > 0.05 for all interactions). We demonstrated a positive nonlinear association between VAI and infertility using a smooth curve fit. A higher visceral adiposity index level is positively correlated with a higher incidence of infertility among women in the United States. Women who are infertile can be identified using the visceral obesity index, and controlling visceral obesity may help lower the chances of becoming infertile.

Mendelian randomisation (MR) is an established technique in epidemiological investigation, using the principle of random allocation of genetic variants at conception to estimate the causal linear effect of an exposure on an outcome. Extensions to this technique include non-linear approaches that allow for differential effects of the exposure on the outcome depending on the level of the exposure. A widely used non-linear method is the residual approach, which estimates the causal effect within different strata of the non-genetically predicted exposure (i.e. the \"residual\" exposure). These \"local\" causal estimates are then used to make inferences about non-linear effects. Recent work has identified that this method can lead to estimates that are seriously biased, and a new method-the doubly-ranked method-has been introduced as a possibly more robust approach. In this paper, we perform negative control outcome analyses in the MR context. These are analyses with outcomes onto which the exposure should have no predicted causal effect. Using both methods we find clearly biased estimates in certain situations. We additionally examined a situation for which there are robust randomised controlled trial estimates of effects-that of low-density lipoprotein cholesterol (LDL-C) reduction onto myocardial infarction, where randomised trials have provided strong evidence of the shape of the relationship. The doubly-ranked method did not identify the same shape as the trial data, and for LDL-C and other lipids they generated some highly implausible findings. Therefore, we suggest there should be extensive simulation and empirical methodological examination of performance of both methods for NLMR under different conditions before further use of these methods. In the interim, use of NLMR methods needs justification, and a number of sanity checks (such as analysis of negative and positive control outcomes, sensitivity analyses excluding removal of strata at the extremes of the distribution, examination of biological plausibility and triangulation of results) should be performed.

Non-linear and dynamic systems analysis of human movement has recently become increasingly widespread with the intention of better reflecting how complexity affects the adaptability of motor systems, especially after a stroke. The main objective of this scoping review was to summarize the non-linear measures used in the analysis of kinetic, kinematic, and EMG data of human movement after stroke. PRISMA-ScR guidelines were followed, establishing the eligibility criteria, the population, the concept, and the contextual framework. The examined studies were published between 1 January 2013 and 12 April 2023, in English or Portuguese, and were indexed in the databases selected for this research: PubMed®, Web of Science®, Institute of Electrical and Electronics Engineers®, Science Direct® and Google Scholar®. In total, 14 of the 763 articles met the inclusion criteria. The non-linear measures identified included entropy (n = 11), fractal analysis (n = 1), the short-term local divergence exponent (n = 1), the maximum Floquet multiplier (n = 1), and the Lyapunov exponent (n = 1). These studies focused on different motor tasks: reaching to grasp (n = 2), reaching to point (n = 1), arm tracking (n = 2), elbow flexion (n = 5), elbow extension (n = 1), wrist and finger extension upward (lifting) (n = 1), knee extension (n = 1), and walking (n = 4). When studying the complexity of human movement in chronic post-stroke adults, entropy measures, particularly sample entropy, were preferred. Kinematic assessment was mainly performed using motion capture systems, with a focus on joint angles of the upper limbs.

UNASSIGNED: Diabetic kidney disease (DKD) patients with anemia face an elevated risk of glomerular filtration rate decline. However, the association between hemoglobin and estimated Glomerular Filtration Rate (eGFR) progression remains to be elucidated.
UNASSIGNED: A retrospective cohort of 815 subjects with DKD was followed from January 2010 to January 2023. A Cox proportional hazard regression model was utilized to explore the predictive role of hemoglobin in renal outcomes. Renal outcomes were defined as a composite endpoint, including a 50% decline in eGFR from baseline or progression to End-Stage Renal Disease (ESRD). To unveil any nonlinear relationship between hemoglobin and renal outcomes, Cox proportional hazard regression with cubic spline functions and smooth curve fitting was conducted. Additionally, subgroup analyses were performed to identify specific patient populations that might derive greater benefits from higher hemoglobin.
UNASSIGNED: Among the 815 DKD subjects, the mean age was 56.482 ± 9.924 years old, and 533 (65.4%) were male. The mean hemoglobin was 121.521±22.960 g/L. The median follow-up time was 21.103±18.335 months. A total of 182 (22.33%) individuals reached the renal composite endpoint during the study period. After adjusting for covariates, hemoglobin was found to exert a negative impact on the renal composite endpoint in patients with DKD (HR 0.975, 95% CI [0.966, 0.984]). A nonlinear relationship between hemoglobin and the renal composite endpoint was identified with an inflection point at 109 g/L. Subgroup analysis unveiled a more pronounced association between hemoglobin and renal prognosis in males.
UNASSIGNED: Hemoglobin emerges as a predictive indicator for the renal prognosis of diabetic kidney disease in China. This study reveals a negative and non-linear relationship between hemoglobin levels and the renal composite endpoint. A substantial association is noted when hemoglobin surpasses 109 g/L in relation to the renal composite endpoint.