Early hip arthroplasty in elderly hip-fracture patients: a perspective from HbA1c

Abstract

Background

To investigate whether stress-induced hyperglycemia influences postoperative outcomes in hip fracture patients with normal hemoglobin A1c (HbA1c) levels, and to determine if delaying surgery for blood glucose normalization is necessary.

Methods

This multicentre retrospective cohort (August 2017 – November 2022) included 212 patients (≥ 60 years) with femoral-neck or intertrochanteric fractures and admission random glucose ≥ 11.1 mmol/L. Patients were classified as early surgery (< 24 h from admission; median 18 h) or delayed surgery (≥ 24 h; median 38 h) after fasting glucose was reduced to 7.0–8.0 mmol/L. Primary outcomes were postoperative infection and delayed wound healing (failure to heal within 14 days). Secondary outcomes were Harris Hip Score (HHS) at 12 months and 24-h Visual Analogue Scale (VAS) pain. Multivariable logistic and linear regression adjusted for age, gender, body mass index (BMI), diabetes, hypertension, operative time, American Society of Anesthesiologists (ASA) classification and surgery type.

Results

Early surgery was not associated with higher infection risk (adjusted odds ratio [aOR] = 1.22, 95% CI 0.91–1.64) or delayed wound healing (aOR = 0.99, 95% CI 0.23–4.31). It had no significant impact on hip function (β = − 1.05, 95% CI − 1.99 to 0.12) or VAS pain (β = − 0.08, 95% CI − 0.42 to 0.27). BMI independently predicted outcomes: each 1 kg/m² increase raised infection risk by 16% (aOR = 1.16, 95% CI 1.07–1.26) but lowered the likelihood of delayed healing (aOR = 0.75, 95% CI 0.62–0.91).

Conclusion

In hip fracture patients with stress-induced hyperglycemia but normal HbA1c levels, delaying surgery for blood glucose normalization does not significantly impact postoperative outcomes. Therefore, surgery should not be postponed solely due to elevated blood glucose levels. Emphasizing the long-term optimization of nutritional status and weight maintenance may reduce postoperative infections and improve functional recovery.

Introduction

Hip fractures represent a significant and pressing medical issue, frequently associated with high disability rates, mortality, and considerable treatment costs [1]. Surgical intervention for hip fractures is generally considered essential, primarily due to complications related to pain, hemorrhage, and immobility, which can lead to inflammation, hypercoagulability, and other pathophysiological responses [2]. Studies have demonstrated that early surgical intervention is significantly correlated with reduced mortality risk, as well as lower incidences of postoperative pneumonia and pressure ulcers [3]. Stress-induced hyperglycemia following the fracture often results in the postponement of surgical procedures.

Stress-induced hyperglycemia is a physiological response to severe trauma or other stressors, wherein elevated levels of stress hormones lead to an increase in blood glucose [4]. This hyperglycemia may elevate the risk of postoperative complications, such as infections, thereby resulting in delays in surgical intervention [5]. Hemoglobin A1c (HbA1c) is a reliable biomarker reflecting the patient’s blood glucose control over the preceding 2–3 months and is also a well-established predictor of postoperative complications [6, 7]. A normal HbA1c value suggests adequate long-term glycemic control, and, in the context of acute stress, transient hyperglycemia may not accurately represent the patient’s underlying glucose metabolism [8, 9].

At present, there is no established consensus regarding the necessity of delaying hip fracture surgery in patients presenting with preoperative hyperglycemia. Some studies advocate postponing surgical intervention until random blood glucose levels are reduced to below 11.1 mmol/L, whereas others contend that hyperglycemia alone should not justify surgical delay [10]. Based on our previous clinical experience, we have observed that some patients may develop stress-induced hyperglycemia following hip fractures. When early surgical intervention is performed due to unavoidable circumstances, postoperative blood glucose is often effectively controlled, with no significant adverse effects on wound healing.

In previous investigations assessing the impact of blood glucose levels on surgical outcomes [11], the potential influence of HbA1c within the normal range has not been systematically explored [12], even in established perioperative management guidelines for diabetic patients, optimization of glycemic control is recommended only when HbA1c exceeds 8.5%. This study aims to investigate the impact of stress-induced hyperglycemia on the safety of emergency fracture surgery in patients with normal HbA1c levels, thereby providing evidence to inform clinical decision-making. This study hypothesised that performing hip-fracture surgery within 24 h of admission, despite persistent stress-induced hyperglycaemia, would not increase postoperative infection or delayed wound healing compared with surgery delayed beyond 24 h.

Patients and methods

This study was obtained from The First Affiliated Hospital of Zhejiang Chinese Medical University (approval number: 2024-KL-644-01). A retrospective, randomly selected cohort of patients who underwent hip joint surgery and received 24 months of follow-up at multiple hospitals between August 2017 and November 2022 was analyzed.

Inclusion and exclusion criteria

Inclusion criteria: (1) Age ≥ 60 years; (2) Hospitalization due to femoral neck or intertrochanteric fractures; (3) Surgery performed at this institution after excluding relevant contraindications; (4) Total hip replacement or hemiarthroplasty, with a posterior-lateral approach being the selected surgical method; (5) Random blood glucose ≥ 11.1 mmol/L upon admission, fulfilling the criteria for stress hyperglycemia, and HbA1c ≤ 6.0%; (6) Complete and accurate documentation of required records. Exclusion criteria: (1) Open fracture; (2) Type 1 diabetes [13, 14]; (3) HbA1c > 6.0%; (4) Severe infections, malignancies, or heart, liver, or kidney dysfunction; (5) Patients with a history of multiple fractures in the same joint; (6) Currently receiving medications that could affect blood glucose control (e.g., corticosteroids); (7) Incomplete or missing data.

Data collection

Venous blood samples were obtained from each patient within 30 min of hospital admission and prior to the initiation of any intravenous infusion or oral intake. Given that all enrolled patients exhibited hyperglycemia, glucose-free crystalloid solutions—specifically 0.9% normal saline or lactated Ringer’s solution—were employed both as infusion fluids and as diluents throughout the hospitalization period. All surgical procedures were conducted by a consistent surgical team. Preoperative assessments were performed by anesthesiologists utilizing the ASA classification system. Surgical interventions were uniformly performed under combined spinal-epidural anesthesia.

All patients observed the ASA pre-operative fasting guideline: a minimum of 6 h without solid foods and 2 h without clear liquids before induction of anaesthesia. In the delayed-surgery cohort, fasting routinely began at 22:00 h on the night of admission, and procedures were scheduled on the first morning theatre list, yielding a median pre-incision fasting duration of 10 h. Patients in the early-surgery cohort adhered to the same ≥ 6 h/≥ 2 h rule; no individual proceeded to theatre within 2 h of ingesting any liquid.

Postoperative glycemic management was conducted in accordance with standardized protocols formulated by endocrinologists. Bedside capillary blood glucose monitoring was performed five times daily during hospitalization, including measurements at fasting (morning), 2 h postprandially after each main meal, and at 22:00 before sleep. Thereafter, monitoring was conducted at a minimum frequency of twice daily until discharge. In cases of clinical instability, supplementary venous glucose assessments were undertaken. The target blood glucose range was defined as 6.0–10.0 mmol/L. Therapeutic adjustments were initiated if blood glucose levels exceeded 10.0 mmol/L on two consecutive readings; if levels persisted at or above 16.7 mmol/L, temporary intravenous insulin infusion was administered, and the patient was transferred to an intensive care unit for intensive monitoring. Insulin therapy adhered to a basal–bolus regimen, comprising basal insulin (glargine) at a dose of 0.2–0.3 U/kg/day, supplemented by preprandial administration of rapid-acting insulin calculated based on body weight and individual insulin sensitivity, thereby avoiding exclusive reliance on sliding-scale protocols. Dextrose-containing infusions were withheld unless hypoglycaemia (< 3.9 mmol/L) occurred, in which case treatment comprised 15 g oral glucose or 20 mL of 50% dextrose intravenously, with retesting at 15-minute intervals per protocol. All insulin dose adjustments were performed daily by attending endocrinologists, and the same protocol was applied across both surgical timing groups.

HbA1c was determined using high-performance liquid chromatography (HPLC) in this study. Following blood collection, plasma was separated by centrifugation and subjected to analysis. The samples were separated using a C18 reverse-phase column, with the mobile phase composed of an appropriate buffer and organic solvents. HbA1c concentration in the samples was quantitatively assessed by comparison with a standard calibration curve.

Although fasting blood-glucose (FBG) provides a more stable indicator of glycaemic status than random blood-glucose (RBG) [15], the 8-h fast required for an accurate FBG is often unattainable in emergency settings. Accordingly, all patients were initially screened with an admission RBG. Stratification was then based exclusively on the time from admission to skin incision. The early surgery group comprised patients taken to theatre within 24 h (median 18 h, IQR 14–22 h) because immediate fixation was clinically indicated; the compressed timeline rendered an 8-h fast not feasible, so pre-incision FBG was unobtainable. The delayed surgery group consisted of patients whose operations were deferred for ≥ 24 h (median 38 h, IQR 30–47 h) to allow targeted insulin therapy until FBG fell to 7.0–8.0 mmol/L before incision.

The following variables were incorporated as covariates in the statistical analysis: BMI, age, gender, diabetes status, hypertension status, operative time, ASA classification, and the type of surgical procedure performed (total hip arthroplasty or hemiarthroplasty). These covariates were adjusted for to control potential confounding effects and to isolate the relationship between the primary variables and postoperative outcomes.

The primary outcomes of this study were postoperative infection and delayed wound healing. Postoperative infection was defined as any superficial incisional, deep incisional or organ/space infection involving the operative hip (including periprosthetic joint infection) that occurred within 24 months after surgery and required systemic antimicrobial therapy and/or re-operation. Delayed wound healing was defined as the failure to achieve adequate wound closure or healing within 14 days postoperatively, necessitating further medical or surgical management.

Secondary outcomes included VAS pain scores and HHS [16]. VAS pain scores was assessed at 24 h postoperatively to quantify pain intensity, while HHS was used to assess postoperative hip joint function, including pain, function, mobility, and deformity, with evaluations conducted at 12 months postoperatively.

Statistical analysis

Descriptive statistics were employed to summarize the baseline characteristics of the study population, including age, gender, BMI, history of diabetes, hypertension status, surgery type, operative time, and ASA classification. Continuous variables were first tested for normality using the Shapiro–Wilk test. Variables conforming to normality were reported as mean ± SD and compared using independent-samples t-tests or one-way ANOVA; non-normal variables were presented as median (interquartile range) and compared using Mann–Whitney U or Kruskal–Wallis tests, as appropriate. Categorical and ordinal variables were expressed as n (%) and compared using chi-square tests or Fisher’s exact tests when expected cell counts were < 5.

To assess the relationship between early surgery and postoperative complications, such as wound infection and delayed wound healing, univariate analysis was initially conducted. Independent impact of early surgery on postoperative outcomes was evaluated using multivariate logistic regression, adjusting for potential confounders. In the presence of significant covariate effects, additional stratified analyses were conducted. Statistical analysis was performed using SPSS version 26.0. A p-value of < 0.05 was considered statistically significant.

Result

A total of 212 participants were included. Table 1 presents the results of Shapiro–Wilk normality testing. Based on these results, age, BMI and surgical time were non-normally distributed. Group comparisons of baseline characteristics are shown in Table 2: none of the variables—age, BMI, surgical time, gender, diabetes, hypertension, ASA classification, or surgery type—differed significantly between the early and delayed surgery groups. Univariate analysis revealed no significant differences between the early and delayed surgery groups in terms of postoperative infection, wound healing delay, VAS pain scores and HHS. These findings suggest that surgical timing does not have a significant impact on the primary postoperative outcomes (Table 3).

Table 1.

Normality test results for continuous variables

Variable	Group	Shapiro–Wilk test	P-value	Normality
Age	Total	0.9592	≤ 0.05	Non-normal
Age	Early	0.9513	≤ 0.05	Non-normal
Age	Delayed	0.9595	≤ 0.05	Non-normal
BMI	Total	0.9444	≤ 0.05	Non-normal
BMI	Early	0.9455	≤ 0.05	Non-normal
BMI	Delayed	0.9366	≤ 0.05	Non-normal
Surgery time	Total	0.9603	≤ 0.05	Non-normal
Surgery time	Early	0.9525	≤ 0.05	Non-normal
Surgery time	Delayed	0.9599	≤ 0.05	Non-normal

Normality was assessed using the Shapiro–Wilk test. P-values are presented categorically as P > 0.05 or P ≤ 0.05

Table 2.

Baseline characteristics of the study population

Variable		Total group	Early surgery group	Delayed surgery group	P_Value
Age		63 (55, 72)	63 (55, 73)	62 (55, 70)	0.569
BMI		25.3 (20, 30.5)	24.2 (19.8, 30.1)	26.1 (20.6, 31.1)	0.364
Gender					0.522
Male		124 (58.49%)	68 (56.20%)	56 (61.54%)
Female		88 (41.51%)	53 (43.80%)	35 (38.46%)
Surgery time		78 (72, 90)	78 (72, 90)	78 (72, 90)	0.586
Surgery type					0.692
THA		112 ( 52.83 %)	62 ( 51.24 %)	50 ( 54.95 %)
HA		100 ( 47.17 %)	59 ( 48.76 %)	41 ( 45.05 %)
ASA					0.079
I		19 ( 8.96 %)	8 ( 6.61 %)	11 ( 12.09 %)
II		144 ( 67.92 %)	79 ( 65.29 %)	65 ( 71.43 %)
III		49 ( 23.11 %)	34 ( 28.1 %)	15 ( 16.48 %)
Diabetes					0.87
Yes		19 (8.96%)	10 (8.26%)	9 (9.89%)
No		193 (91.04%)	111 (91.74%)	82 (90.11%)
Hypertension					0.336
Yes		76 (35.85%)	47 (38.84%)	29 (31.87%)
No		136 (64.15%)	74 (61.16%)	62 (68.13%)
Postoperative infection					0.936
Yes		13 (6.13%)	8 (6.61%)	5 (5.49%)
No		199 (93.87%)	113 (93.39%)	86 (94.51%)
Delayed wound healing					0.997
Yes		11 (5.19%)	6 (4.96%)	5 (5.49%)
No		201 (94.81%)	115 (95.04%)	86 (94.51%)

Table 3.

Univariate analysis results for postoperative outcomes

Outcomes	Variable	Test_Type	Statistic	P_Value
Primary outcomes	Postoperative Infection	Chi-squared test	X² = 0.002	0.96300
	Delayed Wound Healing	Chi-squared test	X² = 7.318e-30	0.98710
Secondary outcomes	VAS Score	t-test	t = 0.562	0.57430
	HHS Score	t-test	t = 1.703	0.09016

After adjusting for age, gender, BMI, diabetes, hypertension, surgery type, operative time, and ASA classification, early surgery did not significantly increase the risk of postoperative infection (aOR = 1.22, 95% CI 0.91–1.64) or delayed wound healing (aOR = 0.99, 95% CI 0.23–4.31) compared to delayed surgery (Fig. 1). It also showed no significant impact on postoperative HHS (β = −1.05, 95% CI − 1.99 to 0.12) or VAS pain scores (β = −0.08, 95% CI − 0.42 to 0.27). BMI had a dual effect: each 1 kg/m² increase was associated with a 16% higher risk of infection (aOR = 1.16, 95% CI 1.07–1.26, P = 0.009) but a reduced risk of delayed healing (aOR = 0.75, 95% CI 0.62–0.91, P = 0.004). Other covariates, including age, gender, diabetes, hypertension, operative time, surgery type, and ASA classification, showed no significant associations with any outcomes (P > 0.05). Overall, after adjusting for these factors, surgical timing did not negatively influence outcomes, while BMI consistently emerged as a key predictor, highlighting its importance in perioperative management.

Fig. 1.

Stacked forest plots summarise four multivariable models examining the impact of surgical timing on (top to bottom) postoperative infection, delayed wound healing, Visual Analogue Scale pain, and Harris Hip Score. Points show adjusted odds ratios (infection, healing) or β-coefficients (VAS, HHS) with 95% confidence intervals; the vertical line marks OR = 1 or β = 0. Models adjust for age, gender, BMI, diabetes, hypertension, surgical procedure, operative time, and ASA class

Given that BMI exhibited a significant effect in the preceding multivariate regression analysis, further examination of its relationship with postoperative infection and delayed wound healing was conducted. After stratifying body-mass index into underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 24.9) and overweight (BMI ≥ 25), multivariable logistic regression—adjusted for age, gender, diabetes, hypertension, operative time, ASA and surgery type—showed no association between BMI category and postoperative infection (normal weight: P = 0.992; overweight: P = 0.991, each versus the underweight reference), whereas both normal-weight (P = 0.028) and overweight (P = 0.005) status were independently associated with a significantly lower likelihood of delayed wound healing relative to underweight patients, indicating that a higher BMI within the non-obese range confers protection against wound-healing complications without influencing infectious risk (Table 4).

Table 4.

Logistic regression for postoperative outcomes by BMI

Variable	Postoperative infection (P_value)	Delayed wound healing (P_value)
BMI (18.5 ≤ BMI < 24.9)	0.992	0.028
BMI (BMI ≥ 25)	0.991	0.005
Age	0.142	0.254
Gender	0.919	0.148
Diabetes	0.910	0.994
Hypertension	0.659	0.293
Surgical time (hours)	0.985	0.829
ASA II	0.913	0.794
ASA III	0.131	0.813
Hip Replacement (Partial)	0.539	0.517

The analysis employs logistic regression to examine the relationship between BMI categories and postoperative outcomes (infection and delayed wound healing), adjusting for age, gender, diabetes, hypertension, surgical timing, ASA classification, and hip replacement type

Discussion

Early surgery for hip fractures is widely considered to offer greater benefits. A retrospective cohort study by Pincus et al. demonstrated that a surgical delay exceeding 24 h was significantly associated with an increased 30-day mortality risk (6.5% vs. 5.8%). Reducing the surgical wait time to less than 24 h may help reduce mortality and postoperative complications [17]. An international randomized controlled trial conducted by the HIP ATTACK research group found no significant difference in mortality or major complications between the accelerated surgery group (median surgical time of 6 h) and the standard care group (median surgical time of 24 h) [18]. These findings suggest that early surgery does not appear to have detrimental effects on patient outcomes. In the present study, early surgery did not result in differences in postoperative complications related to elevated blood glucose. Nevertheless, early preoperative intervention remains essential [19].

Diabetes is a chronic condition caused by dysregulation of blood glucose, and prolonged hyperglycemia can lead to vascular damage, neuropathy, and impaired wound healing [20]. Hyperglycemia not only contributes to postoperative complications following fracture surgery but also influences the incidence of fractures themselves. Emanuelsson et al., through a large-scale observational study and Mendelian randomization (MR) analysis, found that elevated fasting and non-fasting blood glucose levels, along with HbA1c concentrations, were significantly associated with an increased risk of any fragility fracture. In comparison to individuals without diabetes, the risk of fragility fractures was 1.5 times higher in patients with type 1 diabetes and 1.22 times higher in those with type 2 diabetes [21]. Fluctuations in HbA1c concentrations exhibit smaller variation than blood glucose levels, thereby demonstrating greater reliability [22]. Lee et al., in a cohort study involving 480,539 individuals, observed that, after adjusting for confounding factors, patients with greater fluctuations in weight (HR 1.36, 95% CI 1.24–1.50) and blood glucose levels (HR 1.29, 95% CI 1.16–1.43) had a significantly higher risk of hip fractures [23]. The results of this study suggest that hyperglycemia occurring in the short term following a fracture, in the absence of an increase in HbA1c concentrations, may be stress-induced. Early surgical intervention may be considered without concern for adverse outcomes associated with hyperglycemia.

Studies have been conducted to evaluate HbA1c as a marker of glycemic control in predicting adverse outcomes. Thörling et al. conducted a single-center prospective observational cohort study to examine the relationship between poor preoperative diabetes control, indicated by elevated HbA1c levels, and adverse events following hip fracture surgery. The results showed no significant differences between the two groups in terms of complication rates within 30 days (P = 0.55) or 1-year mortality rates (P = 0.35), suggesting that elevated preoperative HbA1c is not associated with an increased risk of postoperative complications or mortality. The findings of this study are relevant to our research, which indicates that when HbA1c is within the normal range, blood glucose levels should not limit the consideration of surgical timing [24].

In the multivariate regression analysis, we identified BMI as a significant predictive factor that should be given due consideration. BMI is commonly recognized as a surrogate marker for obesity [25], and elevated BMI is associated with a range of adverse outcomes [26, 27]. Brahmbhatt et al. indicated that obesity is an independent risk factor for both morbidity and mortality following trauma. Numerous studies and reviews have consistently demonstrated that obesity is associated with an increased risk of postoperative complications and mortality. Obesity is frequently accompanied by a pro-inflammatory state, which can adversely affect multiple systems, including the respiratory, cardiovascular, coagulation, and renal systems, and can impair the healing process [28]. In our study, we similarly observed that higher BMI is associated with an increased risk of postoperative infection; lower BMI, likely due to malnutrition, may lead to delayed wound healing. Maintaining a balanced BMI is therefore critical in minimizing postoperative complications [29].

This study indicates in patients with hip fractures who present with stress-induced hyperglycemia but normal HbA1c levels, the timing of surgery should not be deferred solely due to elevated blood glucose levels. Long-term emphasis should be placed on the management of physical function and nutritional status, as optimization of these factors could effectively reduce the incidence of postoperative infections and enhance functional recovery. Additionally, postoperative glycemic control warrants equal attention. Future studies should aim to identify more precise and reliable biomarkers, such as hemoglobin levels, to accurately predict postoperative complications [30].

Although adjusted analyses revealed no statistically significant effect of surgical timing on postoperative infection (aOR = 1.22, 95% CI 0.91–1.64) or delayed wound healing (aOR = 0.99, 95% CI 0.23–4.31), these null results must be interpreted in light of event scarcity—only 13 infections and 11 delayed-healing events—which yielded a post-hoc power of roughly 55% to detect an odds ratio ≤ 0.70. Point estimates for functional outcomes were likewise small: early surgery was associated with a − 1.05-point difference in HHS, well below the minimal clinically important difference (MCID) of ≈ 4 points, and a negligible − 0.08 change in VAS pain. The narrow absolute effect sizes, coupled with wide confidence intervals, suggest that any true impact of operating < 24 h is clinically modest at best. Furthermore, BMI functioned as a dominant covariate, with each 1 kg/m² increment increasing infection risk by 16% yet decreasing delayed-healing risk—an effect that may have diluted the marginal contribution of surgical timing. Residual confounding (e.g., corticosteroid exposure) and the mitigating influence of a uniform insulin protocol could also mask subtle differences. Collectively, the data support proceeding to theatre without delay when stress-induced hyperglycaemia occurs in the context of normal HbA1c, while underscoring BMI as a key modifiable risk factor.

This study was limited by its retrospective design, potential misclassification of surgical timing in transferred patients, and unmeasured covariates such as corticosteroid exposure and detailed nutritional indices beyond BMI. Although the study was designed as a multicenter investigation, all participating hospitals were located within southern provinces of China, which may impose limitations on the generalizability of the findings to other geographic regions. Given that the emergency nature of early surgery precluded adherence to the standard 8-hour preoperative fasting protocol, FBG were not obtainable in the majority of patients in the early surgery group. This limitation may compromise the direct intergroup comparability of pre-incisional glycemic status. Finally, a 24-month follow-up duration may be inadequate to comprehensively identify late-onset infections or to accurately capture the trajectory of functional deterioration.

Conclusion

In patients with hip fractures who exhibit stress-induced hyperglycemia but have normal HbA1c levels, the surgical timing (early versus delayed) did not have a significant impact on postoperative infection, wound healing delay, VAS pain scores, or HHS. In such cases, surgery should not be postponed solely due to elevated blood glucose levels. Long-term optimization of nutritional status and weight maintenance remains an important strategy for reducing postoperative complications and supporting functional recovery.

Abbreviations

HbA1c

Hemoglobin A1c

BMI

Body mass index

VAS

Visual analog scale

HHS

Harris hip score

HPLC

High-performance liquid chromatography

OR

Odds ratio

CI

Confidence interval

MCID

Minimal clinically important difference

Author contributions

Rong-Zhen Xie: Designed the study, wrote the manuscript, and performed software analysis. Xu-Song Li: Collected and gathered case information. Guo-Qing Li: Collected and gathered case information. Long-Chao Liu: performed software analysis. Wei-Qiang Zhao: Conducted the literature search. Yu-Feng Liang: Assisted with the literature search. Jie-Feng Huang: Supervised the study design and manuscript preparation, collected cases, and provided critical revisions.

Funding

This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Data availability

The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.

Declarations

Ethical approval

Ethical approval for this study was obtained from The First Affiliated Hospital of Zhejiang Chinese Medical University (approval number: 2024-KS-HbA001). All methods were performed in accordance with the relevant guidelines and regulations, including the Declaration of Helsinki. Written informed consent was obtained from all participants prior to their inclusion in the study.

Consent for publication

All authors agree to publication.

Competing interests

The authors declare no competing interests.