Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

Impact of suicidality on delayed-onset post-traumatic stress disorder is modified by age: A two-year longitudinal study.

OBJECTIVES: This study aimed to investigate the relationship between early suicidality and post-traumatic stress disorder (PTSD) onset in patients with physical injuries, focusing on age as a modifying factor. METHODS: At baseline, 1014 patients were evaluated for suicidality, age divided into younger (<60 years) vs. older (≥60 years) groups, and potential covariates. PTSD was diagnosed at follow-up at 3, 6, 12, and 24 months, and then were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models were used after adjusting for covariates. RESULTS: Presence of suicidality at baseline was significantly associated with delayed-onset PTSD in older but not younger patients with significant interaction terms, whereas it was significantly associated with early-onset PTSD across all age groups. CONCLUSION: Age-specific associations were found between suicidality and PTSD onset. The findings highlight the importance of early suicidality assessment, especially in older patients for ongoing monitoring and support, and underscore the critical need for early PTSD identification and intervention for all ages.

Serum lactate normalization time associated with prolonged postoperative ileus after surgical management of the small bowel and/or mesenteric injuries.

BACK GROUND: Determining the optimal timing of postoperative oral feeding in trauma patients who have undergone abdominal surgery with small bowel and/or mesenteric injuries is challenging. The aim of this study is to investigate serum lactate as a factor that can predict oral feeding tolerance and prolonged postoperative ileus (PPOI) in patients who underwent surgery for small bowel and/or mesenteric injury due to trauma. METHODS: The single center retrospective observational study was conducted on 367 patients who underwent surgery for small bowel and/or mesenteric injury between January 2013 and July 2021. The patient group was divided into two groups based on whether the peak serum lactate was over 2mmol/L (18 mg/dL). In the group of lactate > 2mmol/L, it was divided into prolonged postoperative ileus (PPOI) groups and groups rather than PPOI. RESULTS: Patients in the peak serum lactate > 2 group had tendency to use vasopressors, lower initial systolic blood pressure, larger number of packed red blood cells for 24 h, higher injury severity score, higher PPOI incidence, and a tendency for delayed oral intake tolerance. In peak serum lactate greater than 2 mmol/L group, the lactate normalization time (OR 1.699, p = 0.04), quantity of FFP transfusion for 24 h (OR 1.145, p = 0.012), and creatine kinase (OR 1.001, p = 0.023) were related to PPOI. The lactate normalization time had the highest correlation. CONCLUSION: In patients undergoing surgical management for small bowel and/or mesenteric injury after trauma, serum lactate normalization time affects oral intake tolerance and prolongs postoperative ileus.

Timing of Re-Laparotomy in Blunt Trauma Patients With Damage-Control Laparotomy.

INTRODUCTION: Damage-control laparotomy (DCL) was initially designed to treat patients with severe hemorrhage. There are various opinions on when to return to the operating room after DCL and there are no definitive data on the exact timing of re-laparotomy. METHODS: All patients at regional referral trauma center requiring a DCL due to blunt trauma between January 2012 and September 2021 (N = 160) were retrospectively reviewed from patients' electronic medical records. The primary fascial closure rate, lengths of intensive care unit stay and mechanical ventilation, mortality, and complications were compared in patients who underwent re-laparotomy before and after 48 h. RESULTS: One hundred one patients (70 in the ≤48 h group [early] and 31 in the >48 h group [late]) were included. Baseline patient characteristics of age, body mass index, injury severity score, and initial systolic blood pressure and laboratory finding such as hemoglobin, base excess, and lactate were similar between the two groups. Also, there were no differences in reason for DCL and operation time. The time interval from the DCL to the first re-laparotomy was 39 (29-43) h and 59 (55-66) h in the early and late groups, respectively. There were no significant differences in the rate of the primary fascial closure rate (91.4% versus 93.5%, P = 1.00), lengths of stay in the intensive care unit (10 [7-18] versus 12 [8-16], P = 0.553), ventilator days (6 [4-10] versus 7 [5-10], P = 0.173), mortality (20.0% versus 19.4%, P = 0.94), and complications between the two groups. CONCLUSIONS: The timing of re-laparotomy after DCL due to blunt abdominal trauma should be determined in consideration of various factors such as correction of coagulopathy, primary fascial closure, and complications. This study showed there was no significant difference in patient groups who underwent re-laparotomy before and after 48 h after DCL. Considering these results, it is better to determine the timing of re-laparotomy with a focus on physiologic recovery rather than setting a specific time.

Engineering Hydroxylase Activity, Selectivity, and Stability for a Scalable Concise Synthesis of a Key Intermediate to Belzutifan.

Biocatalytic oxidations are an emerging technology for selective C-H bond activation. While promising for a range of selective oxidations, practical use of enzymes catalyzing aerobic hydroxylation is presently limited by their substrate scope and stability under industrially relevant conditions. Here, we report the engineering and practical application of a non-heme iron and α-ketoglutarate-dependent dioxygenase for the direct stereo- and regio-selective hydroxylation of a non-native fluoroindanone en route to the oncology treatment belzutifan, replacing a five-step chemical synthesis with a direct enantioselective hydroxylation. Mechanistic studies indicated that formation of the desired product was limited by enzyme stability and product overoxidation, with these properties subsequently improved by directed evolution, yielding a biocatalyst capable of >15,000 total turnovers. Highlighting the industrial utility of this biocatalyst, the high-yielding, green, and efficient oxidation was demonstrated at kilogram scale for the synthesis of belzutifan.

Abdominal compartment syndrome in critically ill patients.

Intra-abdominal hypertension can have severe consequences, including abdominal compartment syndrome, which can contribute to multi-organ failure. An increase in intra-abdominal hypertension is influenced by factors such as diminished abdominal wall compliance, increased intraluminal content, and certain systemic conditions. Regular measurement of intra-abdominal pressure is essential, and particular attention must be paid to patient positioning. Nonsurgical treatments, such as decompression of intraluminal content using a nasogastric tube, percutaneous drainage, and fluid balance optimization, play crucial roles. Additionally, point-of-care ultrasonography aids in the diagnosis and treatment of intra-abdominal hypertension. Emphasizing the importance of regular measurements, timely decompressive laparotomy is a definitive, but complex, treatment option. Balancing the urgency of surgical intervention against potential postoperative complications is challenging.

Possible Link between Serotonin and Interleukin 18 on Suicidality in Patients with Acute Coronary Syndrome.

Objective: We investigated effects of serum serotonin and interleukin 18 levels on suicidal ideation (SI) at acute and chronic phases of acute coronary syndrome (ACS). Methods: Recent-onset 969 ACS patients were evaluated for serum serotonin and interleukin 18 levels; and SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale. After 1-year, 711 patients were re-evaluated for SI. Logistic regression models were used adjustment for potential covariates. Results: Associations between serum interleukin 18 and SI at both phases were significant only in the lower serotonin group. Conclusion: By evaluating serum serotonin and interleukin 18 levels, the clinical prediction of SI of ACS may be improved.

Ghrelin Modifies the Impact of Life Stress on Suicidality in Patients With Acute Coronary Syndrome.

OBJECTIVE: This study investigated associations of life stressors and serum ghrelin levels with suicidal ideation (SI), and evaluated the potential mediating effect of ghrelin on associations between life stressors and SI in patients with acute coronary syndrome (ACS). METHODS: In total, 969 ACS patients recruited from a tertiary university hospital in Korea within 2 weeks of disease onset were evaluated in terms of life stressors (using the List of Threatening Events Questionnaire), serum ghrelin levels, and SI (using the "suicidal thoughts" item of the Montgomery-Asberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of SI; logistic regression was performed with adjustment for covariates. RESULTS: Life stressors were significantly associated with SI at baseline and follow-up. Serum ghrelin showed no such associations, but high levels thereof mediated associations of life stressors with SI; significant interaction terms were also observed after adjustment for covariates. CONCLUSION: By evaluating life stressors and serum ghrelin levels, clinical prediction of SI in the acute and chronic phases of ACS could be improved.

Factors associated with enteral nutrition tolerance after trauma laparotomy of the small bowel and mesenteric injuries by blunt trauma.

BACKGROUND: In patients with blunt injury due to abdominal trauma, the common cause for laparotomy is damage to the small bowel and mesentery. Recently, postoperative early enteral nutrition (EEN) has been recommended for abdominal surgery. However, EEN in patients with blunt bowel and/or mesenteric injury (BBMI) has not been established. Therefore, this study aimed to identify the factors that affect early postoperative small bowel obstruction (EPSBO) and the date of tolerance to solid food and defecation (SF + D) after surgery in patients with BBMI. METHODS: We retrospectively reviewed patients who underwent laparotomy for BBMI at a single regional trauma center between January 2013 and July 2021. A total of 257 patients were included to analyze the factors associated with enteral nutrition tolerance in patients with EPSBO and the postoperative day of tolerance to SF + D. RESULTS: The incidence of EPSBO in patients with BBMI was affected by male sex, small bowel organ injury scale (OIS) score, mesentery OIS score, amount of crystalloid, blood transfusion, and postoperative drain removal date. The higher the mesentery OIS score, the higher was the EPSBO incidence, whereas the small bowel OIS did not increase the incidence of EPSBO. The amount of crystalloid infused within 24 h; the amount of packed red blood cells, fresh frozen plasma, and platelet concentrate transfused; the time of drain removal; Injury Severity Score; and extremity abbreviated injury scale (AIS) score were correlated with the day of tolerance to SF + D. Multivariate analysis between the EPSBO and non-EPSBO groups identified mesentery and small bowel OIS scores as the factors related to EPSBO. CONCLUSION: Mesenteric injury has a greater impact on EPSBO than small bowel injury. Further research is needed to determine whether the mesentery OIS score should be considered during EEN in patients with BBMI. The amount of crystalloid infused and transfused blood components within 24 h, time of drain removal, injury severity score, and extremity AIS score are related to the postoperative day on which patients can tolerate SF + D.

Nickel-Catalyzed Sulfonylation of Aryl Bromides Enabled by Potassium Metabisulfite as a Uniquely Effective SO2 Surrogate.

The development and mechanistic investigation of a nickel-catalyzed sulfonylation of aryl bromides is disclosed. The reaction proceeds in good yields for a variety of substrates and utilizes an inexpensive, stench-free, inorganic sulfur salt (K2 S2 O5 ) as a uniquely effective SO2 surrogate. The active oxidative addition complex was synthesized, isolated, and fully characterized by a combination of NMR spectroscopy and X-ray crystallography analysis. The use of the isolated oxidative addition complex in both stoichiometric and catalytic reactions revealed that SO2 insertion occurs via dissolved SO2 , likely released upon thermal decomposition of K2 S2 O5 . Key to the success of the reaction is the role of K2 S2 O5 as a reservoir of SO2 that is slowly released, thus preventing catalyst poisoning.

Addressing diffusion behavior and impact in an epoxy-amine cure system using molecular dynamics simulations.

To deepen understanding of diffusion-controlled crosslinking, molecular dynamics (MD) simulations are carried out by taking the diffusion image of 3,3'-diamino diphenyl sulfone (3,3'-DDS) and polyethersulfone (PES) with epoxy resin varying temperatures from 393.15 to 473.15 K over crosslinking conversion of 0-85%. The diffusion of PES and 3,3'-DDS into the bulk increased with increasing the temperature as a result of enhanced mobility of the molecules when the difference between the glass-transition temperature (Tg) and the curing temperature. Beyond the onset points of the converged crosslinking conversion ratio of 3,3'-DDS and PES, their diffusion properties are obviously restricted with crosslinking conversion ratio. At low crosslinking conversion ratios (> 10%), the diffusion coefficients of triglycidyl p-aminophenol (TGAP) were 1.1 times higher than those of diglycidyl ether of bisphenol F (DGEBF) because of the lower molecular weight of TGAP. On the other hand, the diffusion coefficients of TGAP decreased when the crosslinking ratio was up to ~ 60% because, compared with DGEBF, it had more functional groups available to react with the curing agent. At higher crosslinking ratios, the diffusion coefficients of both resins converged to zero as a result of their highly crosslinked structures.

THE INITIAL ION SHIFT INDEX AS A PROGNOSTIC INDICATOR TO PREDICT PATIENT SURVIVAL IN TRAUMATIC DAMAGE CONTROL LAPAROTOMY PATIENTS.

ABSTRACT: Objective: The ion shift index (ISI), which considers extracellular fluid ions such as phosphate, calcium, and magnesium, represents the ion shift following ischemia; concentrations of these ions are maintained within narrow normal ranges by adenosine triphosphate-dependent homeostasis. The ISI is defined as follows: {potassium (mmol/L-1) + phosphate (mmol/L-1) + Mg (mmol/L-1)}/calcium (mmol/L-1). This study investigated the possibility of predicting the 30-day survival rate of patients who underwent traumatic damage control laparotomy by comparing ISI and other laboratory findings, as well as the initial Trauma and Injury Severity Score (TRISS) and shock indices. Methods: Among the 134 patients who underwent damage control surgery between November 2012 and December 2021, 115 patients were enrolled in this study. Data regarding injury mechanism, age, sex, laboratory findings, vital signs, Glasgow Coma Scale score, Injury Severity Score, Abbreviated Injury Scale score, blood component transfusion, type of surgery, postoperative laboratory outcomes, morbidity, mortality rates, fluids administered, and volume of transfusions were collected and analyzed. Results: In univariate analysis, the odds ratio of the initial ISI was 2.875 (95% confidence interval, 1.52-5.43; P = 0.04), which showed a higher correlation with mortality compared with other indices. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were derived from different multivariable logistic regression models. The initial ISI had high sensitivity and specificity in predicting patient mortality (AUC, 0.7378). In addition, in the model combining the initial ISI, crystalloids, and TRISS, the AUC showed a high value (AUC, 0.8227). Conclusion: The ISI evaluated using electrolytes immediately after admission in patients undergoing traumatic damage control surgery may be a predictor of patient mortality.

Differential effects of anxiety on long-term outcomes of acute coronary syndrome and stroke according to their disease severities.

This study investigated associations of anxiety at the acute phase with long-term outcomes of acute coronary syndrome (ACS) and stroke, and potential modifying effects of cardiovascular/cerebrovascular severity at onset. In 1152 ACS and 423 stroke patients with recent onset, long-term follow-up for cardio-cerebro-vascular outcomes was conducted. Acute-phase anxiety predicted long-term outcomes, but these associations were significant only in patients with great initial disease severities with significant interaction terms in both diseases after adjustment for relevant covariates. Clinical prediction of cardio-cerebro-vascular prognosis might be improved by screening for anxiety and disease severities in the acute phase of ACS and stroke.

Associations of systemic inflammation and social support with suicidal ideation in patients with acute coronary syndrome and stroke.

BACKGROUND: This study aimed to investigate associations of serum high-sensitivity C-reactive protein (hsCRP) and social support (SS) levels with suicidal ideation (SI), and to evaluate potential modifying effects of SS on the associations between serum hsCRP levels and SI in two longitudinal cohorts with cardio-/cerebrovascular diseases. METHODS: 1152 acute coronary syndrome (ACS) and 423 stroke patients were recruited at baseline within 2 weeks of disease onset, and evaluated for: i) serum hsCRP levels; ii) SS by the Social Support Scale and Social Undermining Scale; iii) SI by the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale; and iv) covariates including socio-demographics, depression, vascular risk factors, and index disease severity. At 12-month follow-up, SI was re-evaluated. Logistic regression models were used to adjust for potential covariates. RESULTS: In the ACS cohort, higher serum hsCRP and lower SS levels were significantly associated with SI at baseline; and only lower SS levels were significantly associated with SI at follow-up. In the stroke cohort, lower SS levels were significantly associated with SI at baseline; but no other association was found. Associations of serum hsCRP levels with SI at both baseline and follow-up were only significant at higher SS levels with significant interaction terms in both cohorts. LIMITATIONS: This study evaluated SI, but not suicide attempts or death; it also used a single-center design. CONCLUSIONS: By considering SS evaluations with routine serum hsCRP levels in cardio-/cerebrovascular disease, clinical prediction of SI both at acute and chronic phases of the diseases might be improved.

Serotonin modifies the impact of sleep disturbance on suicidality in patients with acute coronary syndrome.

Background: This study investigated the associations of sleep disturbance and serum serotonin levels with suicidal ideation, and evaluated the potential modifying effects of serotonin on these associations in patients with the acute coronary syndrome (ACS). Methods: In total, 969 ACS patients were recruited from a tertiary university hospital in Korea within 2 weeks of disease onset and evaluated in terms of sleep disturbance (using the Leeds Sleep Evaluation Questionnaire), serum serotonin levels, and suicidal ideation (using the "suicidal thoughts" item of the Montgomery-Åsberg Depression Rating Scale). Covariates included sociodemographics, depression, vascular risk factors, and disease severity. After 1 year, 711 patients were re-evaluated in terms of suicidal ideation. Logistic regression analysis was performed with adjustment for covariates. Results: Sleep disturbance was significantly associated with suicidal ideation at baseline and follow-up. Serum serotonin showed no such association but modified the association of sleep disturbance with suicidal ideation such that it was significant only in the lower serum serotonin group, with significant interaction terms obtained after adjustment for relevant covariates. Conclusion: Evaluating sleep disturbance and serum serotonin levels could improve the accuracy of clinical predictions of suicidal ideation in the acute and chronic phases of ACS.

Modifying Effect of the Interleukin-18 Level on the Association between BDNF Methylation and Long-Term Cardiovascular Outcomes in Patients with Acute Coronary Syndrome.

This study investigated the potential modifying effects of the level of the serum interleukin-18 (IL-18) on the association between BDNF methylation status and long-term cardiovascular outcomes in patients with acute coronary syndrome (ACS). Hospitalized ACS patients were recruited sequentially from 2006 to 2012. At baseline, the IL-18 level and BDNF methylation status were evaluated in 969 patients who were followed for major adverse cardiac events (MACEs) for 5-12 years, until 2017 or death. The time to first composite or individual MACE was compared between individuals with lower and higher average BDNF methylation levels (in the low- and high-IL-18 groups, respectively) using a Cox proportional hazards model. After adjusting for potential covariates, the modifying effects of IL-18 and average BDNF methylation levels on the initial composite and individual MACEs were examined. In the high-IL-18 group, but not in the low-IL-18 group, a higher average BDNF methylation level was associated with increases in composite MACEs (HR (95% CI) = 2.15 (1.42-3.26)), all-cause mortality (HR (95% CI) = 1.89 (1.11-3.22)), myocardial infarction (HR (95% CI) = 1.98 (1.07-3.67)), and percutaneous coronary intervention (HR (95% CI) = 1.81 (1.01-3.23)), independent of confounding variables. The interaction effect between the IL-18 and average BDNF methylation levels on composite MACEs (p = 0.019) and myocardial infarction (p = 0.027) was significant after adjusting for covariates. Analysis of BDNF methylation status and IL-18 levels may help identify ACS patients who are most likely to have adverse clinical outcomes.

Impact of the establishment of a trauma center on blunt traumatic spleen injury treatment: Comparison between pre-traumatic center and trauma center periods.

BACKGROUND: The spleen is a commonly injured intra-abdominal organ from blunt trauma. In cases of traumatic blunt spleen injury, immediate treatment is often required. This study aimed to investigate the prognostic impact of the establishment of a trauma center on the treatment of patients with blunt trauma injury to the spleen. METHODS: We retrospectively reviewed 235 patients who visited our center from 2012 to 2019 for blunt trauma injury to the spleen. The study period was divided into two groups: January 2012 to September 2015 was the pre-center period (PCP), and September 2015 to December 2019 was the trauma center period (TCP). In each period, there were three treatment groups: Surgical group, embolization group, and conservative treatment group. The primary outcome was mortality, and the secondary outcomes were patient characteristics, such as injury severity score and abbreviated injury scale score, time from admission to intervention (both surgery and angiography embolization), and rate of spleen-preserving surgery. RESULTS: In the conservative treatment group, the Hb and hct values were relatively low in the TCP than in the PCP (p=0.007, p=0.008, respectively). The intensive care unit admission rate was relatively high in the TCP (72.9% vs. 90.6%, p=0.031). The ISS was relatively low in the TCP (18 vs. 17, p=0.001). In the surgical group, the time taken to transfer patients to the operating room after admission was greatly reduced in the TCP (151 min vs. 107 min, p=0.028). In the embolization group, the patient's age and SBP were lower in the PCP than in the TCP (p=0.003, p=0.049, respectively); three patients had undergone embolization with CPR in the PCP, and no patient underwent CPR in the TCP. There were three deaths in PCP and none in the TCP (p=0.05). CONCLUSION: The establishment of a trauma center has led to improvements in the treatment quality and prognosis of patients with blunt trauma injury to the spleen receiving either of the three treatments.

Antiphospholipid syndrome with renal and splenic infarction after blunt trauma: A case report.

BACKGROUND: In trauma patients, bleeding is an immediate major concern. At the same time, there are few cases of acute vascular occlusion after blunt trauma, and it is unclear what assessment and diagnosis should be considered for these cases. Herein, we describe a patient diagnosed with antiphospholipid syndrome after a hypercoagulable workup for acute renal and splenic vascular occlusion due to blunt trauma. CASE SUMMARY: A 20-year-old man was admitted to the emergency department with abdominal pain after hitting a tree while riding a sled 10 h ago. He had no medical history. Radiological investigations revealed occlusion of the left renal artery with global infarction of the left kidney and occlusion of branches of the splenic artery with infarction of the central portion of the spleen. Attempted revascularization of the left renal artery occlusion through percutaneous transluminal angioplasty failed due to difficulty in passing the wire through the total occlusion. Considering the presence of acute multivascular occlusions in a young man with low cardiovascular risk, additional laboratory tests were performed to evaluate hypercoagulability. The results suggested a high possibility of antiphospholipid syndrome. Treatment with a subcutaneous injection of enoxaparin was started and changed to oral warfarin after two weeks. The diagnosis was confirmed, and he continued to visit the rheumatology outpatient clinic while taking warfarin. CONCLUSION: A hypercoagulable workup can be considered in trauma patients with acute multivascular occlusion, especially in young patients with low cardiovascular risk.

Modifying effect of the serum level of brain-derived neurotrophic factor (BDNF) on the association between BDNF methylation and long-term cardiovascular outcomes in patients with acute coronary syndrome.

Introduction: This study investigated the potential modifying effects of the serum brain-derived neurotrophic factor (sBDNF) level on the association between BDNF methylation status and long-term cardiovascular outcomes in acute coronary syndrome (ACS) patients. Methods: From 2006 to 2012, hospitalized ACS patients were consecutively recruited. The sBDNF level and BDNF methylation status were assessed at baseline in 969 patients who were followed up for major adverse cardiac events (MACEs) over 5-12 years, until 2017 or death. Cox proportional hazards models were utilized to compare the time to first composite or individual MACEs between individuals with lower and those with higher average BDNF methylation levels in the low and high sBDNF groups, respectively. The modifying effects of the sBDNF and average BDNF methylation levels on first composite and individual MACEs were analyzed using Cox proportional hazards models after adjusting for potential covariates. Results: In the low sBDNF group, a higher average BDNF methylation level was linked to an increase in composite MACEs independent of confounding variables, but not in the high sBDNF group [HR (95 percent CI) = 1.04 (0.76-1.44)]. The interaction effect between the sBDNF and average BDNF methylation levels on composite MACEs was significant after adjusting for covariates (P = 0.008). Conclusion: Combining the BDNF methylation status and sBDNF levels may help identify ACS patients who are likely to have unfavorable clinical outcomes.