Search Results (45)

Background: Tourniquet release during total knee arthroplasty (TKA) can cause abrupt hypotension in elderly patients, but simple intraoperative predictors remain unclear. We evaluated whether blood pressure and the pleth variability index (PVi) predict tourniquet-release hypotension. Methods: In this prospective observational study, 90 elderly patients undergoing TKA with a thigh tourniquet were analyzed. Noninvasive blood pressure and PVi were recorded at predefined perioperative time points. The primary endpoint was hypotension after deflation, defined as mean blood pressure < 65 mmHg. Secondary exploratory endpoints were systolic blood pressure < 90 mmHg and a ≥20% decrease in systolic blood pressure from pre-release values. Results: The primary endpoint occurred in 28.9% of patients and was more common in those with lower pre-release blood pressure. In multivariable analysis, pre-release mean blood pressure and PVi measured immediately after intubation independently predicted hypotension, with odds ratios of 0.95 per 1 mmHg increase and 1.12 per 1-point increase, respectively. The combined model showed moderate discrimination (AUC = 0.71). Similar patterns were observed for systolic definitions, without clear associations with early postoperative complications or hospital length of stay. Conclusions: Lower pre-release mean blood pressure and higher intubation PVi may help identify elderly TKA patients at risk of tourniquet-release hypotension. Full article

Introduction: Intraoperative hypotension (IOH) is a frequent manifestation of haemodynamic instability during general anaesthesia. Advances in arterial waveform analysis have led to two distinct monitoring strategies: flow-derived platforms and predictive algorithms designed to anticipate hypotension. However, prospective comparisons and their associations with IOH and postoperative outcomes remain limited. The objective was to compare predictive haemodynamic monitoring using the Hypotension Prediction Index (HPI) with flow-derived monitoring using the Vigileo/FloTrac system and to evaluate their associations with IOH and postoperative outcomes. Methods: In this single-center prospective observational study, 101 adults undergoing elective major abdominal surgery under general anaesthesia were monitored using either the HPI system (n = 49) or the Vigileo/FloTrac system (n = 52). Primary outcomes were cumulative duration and frequency of IOH (mean arterial pressure < 65 mmHg). Secondary outcomes included postoperative complications, organ injury biomarkers (troponin, creatinine, eGFR), and hospital length of stay. Multivariable regression models adjusted for predefined confounders were used to estimate associations. Results: Vigileo/FloTrac monitoring, compared with HPI, was independently associated with a greater cumulative duration of IOH (adjusted β = 1.66; 95% CI, 0.63–2.72) and a higher number of hypotensive episodes (adjusted β = 0.53; 95% CI, 0.10–0.95). Monitoring strategy was not associated with surgical site, respiratory, or neurological complications. However, Vigileo/FloTrac monitoring was associated with higher odds of vascular complications (adjusted OR = 4.36; 95% CI, 1.13–20.41). No significant associations were observed between monitoring strategy and postoperative organ injury biomarkers or length of hospital stay. Conclusions: Predictive haemodynamic monitoring using the HPI system was associated with lower IOH burden compared with the Vigileo/FloTrac system. However, these differences were not consistently accompanied by improvements in postoperative outcomes. Haemodynamic optimisation should be considered as one component within a broader, integrated perioperative management strategy. Further large-scale, multicenter prospective studies are warranted to clarify its impact on patient-centered outcomes. Full article

Background: Hypotension is a common complication following spinal anesthesia, and it is particularly prevalent in older patients. The study aimed to develop and validate a nomogram integrating echocardiographic and clinical predictors for spinal anesthesia-induced hypotension (SAIH) in older patients. Methods: This was an observational cohort study conducted at Peking University People’s Hospital. A total of 865 older patients (age ≥ 65), enrolled from 1 January 2023 to 31 December 2024, were randomly split into a training set (70%) and an internal validation set (30%). For temporal external validation, 349 patients from January to March 2025 were enrolled. LASSO, univariable, and multivariate logistic regression analyses were used to identify predictive factors. A nomogram was subsequently developed based on the results of multivariate logistic regression, and its predictive efficacy was evaluated via both internal and temporal external validation. Results: SAIH occurred in 271 patients (44.8%) in the training set, 110 patients (42.3%) in the internal validation set, and 173 patients (49.6%) in the external validation set. Age, body mass index (BMI), bupivacaine dose, sensory block level, baseline systolic blood pressure (SBP), history of hypertension, interventricular septum thickness at end-diastole (IVSd), early diastolic mitral annular velocity (e’), and E/e’ ratio were significant predictors of SAIH on multivariate analysis. The diagnostic performance of the nomogram was favorable (AUC = 0.885, 95% CI: 0.859–0.911). The AUC values of the internal validation set and temporal external validation set were 0.856 (0.811–0.901) and 0.895 (0.863–0.927). Conclusions: This study identifies age, BMI, bupivacaine dose, sensory block level, baseline SBP, history of hypertension, and IVSd as predictors of SAIH with good discrimination and clinical utility. We present a predictive nomogram that accurately predicts SAIH in older patients. The external validation illustrates its generalizability. Full article

Artificial intelligence (AI) is rapidly reshaping adult cardiac surgery, enabling more accurate diagnostics, personalized risk assessment, advanced surgical planning, and proactive postoperative care. Preoperatively, deep-learning interpretation of ECGs, automated CT/MRI segmentation, and video-based echocardiography improve early disease detection and refine risk stratification beyond conventional tools such as EuroSCORE II and the STS calculator. AI-driven 3D reconstruction, virtual simulation, and augmented-reality platforms enhance planning for structural heart and aortic procedures by optimizing device selection and anticipating complications. Intraoperatively, AI augments robotic precision, stabilizes instrument motion, identifies anatomy through computer vision, and predicts hemodynamic instability via real-time waveform analytics. Integration of the Hypotension Prediction Index into perioperative pathways has already demonstrated reductions in ventilation duration and improved hemodynamic control. Postoperatively, machine-learning early-warning systems and physiologic waveform models predict acute kidney injury, low-cardiac-output syndrome, respiratory failure, and sepsis hours before clinical deterioration, while emerging closed-loop control and remote monitoring tools extend individualized management into the recovery phase. Despite these advances, current evidence is limited by retrospective study designs, heterogeneous datasets, variable transparency, and regulatory and workflow barriers. Nonetheless, rapid progress in multimodal foundation models, digital twins, hybrid OR ecosystems, and semi-autonomous robotics signals a transition toward increasingly precise, predictive, and personalized cardiac surgical care. With rigorous validation and thoughtful implementation, AI has the potential to substantially improve safety, decision-making, and outcomes across the entire cardiac surgical continuum. Full article

Background/Objectives: Intraoperative hypotension (IOH) is related to the occurrence of postoperative complications and may be a frequent event during major vascular surgery. The Hypotension Prediction Index (HPI) is a technology applied to predict hypotension and enable preventive interventions. This study aimed to compare intraoperative haemodynamic stability between patients monitored with the HPI algorithm and those monitored with arterial pressure cardiac output (APCO) monitoring. Methods: We performed a retrospective study including 100 adult patients undergoing elective major aortic surgery between January 2023 and June 2025. Fifty patients were managed with APCO monitoring and 50 with the HPI algorithm. The primary endpoint was time-weighted average mean arterial pressure below 65 mmHg (TWA-MAP < 65 mmHg). Secondary endpoints included total hypotension time, number and duration of hypotensive episodes, and time spent with MAP > 90 and > 100 mmHg. Multiple comparison correction (Holm–Bonferroni) was applied separately for hypotension and hypertension outcomes. Results: The primary outcome, TWA-MAP < 65 mmHg, did not differ significantly between groups (0.22 vs. 0.26 mmHg; $p=0.27$). After correction for multiple comparisons, no hypotension-related outcomes reached statistical significance, although clinically relevant trends were observed: the HPI group showed 50% shorter total hypotension time (5 vs. 10 min; $p_{\mathrm{uncorrected}}=0.03$, $p_{\mathrm{adjusted}}=0.18$) and 33% shorter episode duration. In contrast, patients in the HPI group spent significantly more time with elevated MAP: 38% vs. 25% of monitored time with MAP > 90 mmHg ($p_{\mathrm{adjusted}}=0.036$) and 18% vs. 9% with MAP > 100 mmHg ($p_{\mathrm{adjusted}}=0.036$). Conclusions: In patients undergoing major vascular aortic surgery, HPI monitoring did not significantly reduce the burden of hypotension after accounting for multiple comparisons, though clinically meaningful trends were noted. However, HPI use was associated with significantly increased hypertensive exposure, suggesting overly aggressive correction. These findings highlight the need for careful titration of interventions when using predictive algorithms and warrant further prospective randomised studies. Full article

Background/Objectives: We aimed to construct a nomogram model for predicting arteriovenous fistula dysfunction risk and to conduct internal validation. Methods: The clinical data of 335 patients from the 8th Affiliated Hospital of Sun Yat-Sen University, collected from January 2019 to January 2024, were retrospectively analyzed. Among these patients, 103 were assigned to the arteriovenous fistula (AVF) dysfunction group, while 232 were in the non-dysfunction group. In this study, we first identified risk factors for AVF dysfunction using univariate and logistic regression analyses, and then constructed a prediction model by resampling the data. The model’s performance was evaluated using the C-index, ROC curve, calibration plot, and decision curve analysis, confirming its strong predictive ability and clinical value. Results: The results indicated that post-dialysis hypotension, abnormal fibrinogen levels, platelet abnormalities, total cholesterol levels, and diabetes mellitus emerged as independent risk factors for AVF dysfunction in MHD patients; however, total protein levels were a protective factor for AVF dysfunction. The model’s performance was assessed using the receiver operating characteristic (ROC) curve, the Hosmer–Lemeshow test, and the calibration curve. The ROC curve results demonstrated that the area under the curve (AUC) for the training set was 0.852 (0.799–0.904), while that for the validation set was 0.810 (0.715–0.906), indicating good calibration. The decision curve analysis revealed that the predictive nomogram was clinically useful when the threshold for intervention was set between a 15% and 78% probability of dysfunction. Conclusions: The nomogram prediction model constructed in this study can be used to predict the risk of autogenous arteriovenous fistula dysfunction in hemodialysis patients. Full article

Background: Locoregional anesthesia (LRA) during cesarean section (CS) is effective but frequently causes hypotension, affecting maternal hemodynamics and fetal outcomes. We investigated whether baseline hemodynamic characteristics predict post-LRA changes, vasopressor needs, and neonatal outcomes. Methods: Women undergoing elective CS with LRA were monitored with USCOM^® (Ultrasonic Cardiac Output Monitor), recording cardiac output (CO), cardiac index (CI), stroke volume (SV), stroke volume index (SVI), and systemic vascular resistance (SVR) every five minutes. Maternal demographics, vasopressor use, and neonatal outcomes were analyzed using multilevel linear regression. Results: LRA caused significant reductions in blood pressure and heart rate (p < 0.001). SV initially declined but recovered, while SVR showed minimal variation. Vasopressors were required in 63%, with choice guided by heart rate. Lower baseline SVI predicted greater vasopressor need (37.9 ± 6.7 vs. 34.5 ± 6.6, p = 0.050). Lower CO and CI before fetal extraction correlated with reduced neonatal pH, with CI significantly associated with pH < 7.20 (p = 0.043). Conclusions: USCOM^® enables real-time, non-invasive monitoring, supporting individualized management during CS. Full article

This pilot study aims to compare advanced and standard haemodynamic monitoring during TAVI in terms of predicting and avoiding hypotension. Intraoperative hypotension influences postoperative outcomes by increasing mortality, renal failure, and cardiac complications. In TAVI (transaortic valve implantation), haemodynamic stability is essential because the patients are usually old and vulnerable. Fifty patients underwent transfemoral TAVI under standard anaesthetic care. Blood pressure was measured invasively, using Edwards Acumen sensors connected to a HemoSphere monitor. The signal was simultaneously fed to anaesthesia monitors. Patients were randomly divided into two groups: in the test group, the Edwards monitor with the HPI (hypotension prediction index) values was available to the anaesthetist, whereas in the control group, the HemoSphere monitor was covered. The primary endpoint of the study was the time-weighted average of intraoperative hypotension, which is calculated from the intensity and duration of hypotension, adjusted for the duration of surgery (TWA₆₅). Secondary endpoints were the cumulative time of hypotensive episodes adjusted for the duration of the procedure (TWA_total). No difference in intraoperative hypotension in terms of TWA₆₅ between control and intervention group could be detected, the overall duration of intraoperative hypotension was reduced in the intervention group, and the administration of intraoperative volume was higher in the intervention group when compared to controls. The use of HPI during TAVI leads to improved haemodynamic stability, and this is particularly important in these extremely vulnerable patients. Not only is it possible to reduce overall intraoperative hypotension with HPI, but postoperative complications associated with intraoperative hypotension that might occur will also be diminished. Full article

Background and Objectives: Spinal anesthesia is a common anesthetic method for cesarean delivery. However, it is associated with spinal hypotension, which can negatively impact both the mother and the fetus. We hypothesized that parturients with preoperatively prolonged corrected QT interval (QTc) would have a lower incidence of developing spinal hypotension. Materials and Methods: This prospective observational study analyzed eighty-five parturients undergoing cesarean delivery. The participants were divided into two groups based on their baseline QTc, which was measured automatically using a patient monitor in the operating room rather than using a standardized 12-lead electrocardiogram: <440 ms (n = 42) or ≥440 ms (n = 43). Following combined spinal-epidural anesthesia, the incidence of spinal hypotension until delivery was analyzed and the vasopressor requirements within 30 min were compared between the QTc groups. The area under the receiver operating characteristic curve was measured to identify the optimal QTc cut-off for predicting spinal hypotension. Results: Spinal hypotension was observed in 37/43 parturients (86.0%) with QTc < 440 ms, compared to 17/42 (40.5%) with QTc ≥ 440 ms (p < 0.001). The total amount of phenylephrine significantly differed between groups (300 μg [100–400] vs. 100 μg [0–300], p = 0.009). The area under the ROC curve for spinal hypotension prediction was 0.75 (95% confidence interval [CI] 0.64–0.86). The optimal QTc cut-off interval, determined using the maximum Youden index (J = 0.510), which corresponded to the best combination of sensitivity and specificity, was 441 ms. Conclusions: These preliminary patient-monitor-based findings indicate an association between preoperative QTc and spinal hypotension, which should be validated using standardized electrocardiographic methods. Full article

Background: Intensive Care Units (ICUs) provide critical support for patients after major surgery or acute abdominal conditions. Despite medical advances, mortality remains high in surgical ICU patients. This study aimed to identify clinical and biochemical predictors of mortality in surgical patients admitted to a tertiary ICU. Methods: We conducted a retrospective case–control study on 231 adult general surgery patients admitted to a tertiary anesthesia ICU between January 2018 and December 2023. Patients under 18 years or who underwent solid organ transplantation were excluded. Data collected included demographic, clinical, and laboratory parameters such as the Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) score, neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein (CRP)/albumin ratio. Patients were divided into mortality and survival groups, with subgroup analyses performed for malignancy, sepsis, and trauma. Receiver operating characteristic (ROC) curve and Cox regression analyses were used to identify mortality predictors. Results: The ICU mortality rate was 64.9%. Significant predictors included age ≥ 58 years (odds ratio [OR] 4.56), body mass index (BMI) > 30 kg/m² (OR 7.62), mean arterial pressure < 70 mmHg (OR 1.66), serum albumin < 21.3 g/L (OR 1.5), APACHE II > 18.5 (OR 2.42), and SOFA > 9.5 (OR 2.68). Mortality was also associated with lower GCS scores, prolonged mechanical ventilation, and inotropic support. The CRP/albumin ratio was significantly elevated in the mortality group (p = 0.024). Other inflammatory markers showed no significant differences. Predictive factors varied among subgroups. Conclusions: Older age, obesity, hypotension, hypoalbuminemia, and high severity scores independently predict mortality in surgical ICU patients. Early risk identification may enhance management and improve outcomes in this population. Full article

Background: Hypotensive events may occur during surgical interventions and are associated with major postoperative complications, depending on their duration and severity. Intraoperative hemodynamic goal-directed therapy can reduce postoperative complications and mortality in high-risk surgeries and high-risk patients. The study hypothesis was that a proactive approach by hypotension predictive index (HPI) is more effective than a reactive goal-directed therapy (GDT) in reducing the number of hypotensive events during radical cystectomy and that this is associated with improved postoperative outcomes. Methods: The study was a single-center prospective observational study conducted at Galliera Hospital, from November 2019 to February 2025, with a before-after population of sixty-seven patients with reactive approach (GDT group) and sixty-five patients with a proactive approach (HPI group) undergoing radical cystectomy, managed with a standardized ERAS protocol and invasive or non-invasive hemodynamic monitoring. The aim of the study was to compare the incidence, duration, and severity of intraoperative hypotensive episodes between a proactive approach guided by the Hypotension Prediction Index (HPI) and a reactive goal-directed therapy (GDT) strategy guided by an advanced hemodynamic monitoring system. Results: The HPI group had a 65% reduction in hypotensive events (225 vs. 633, p < 0.001), with a 72% reduction in their duration (14 vs. 49 min, p < 0.001) and an 85% reduction in their severity (time-weighted average MAP < 65 mmHg 0.11 vs. 0.76, p < 0.001) compared to the GDT group. The HPI-guided group showed a reduction in postoperative infectious complications (10 vs. 26) and in-hospital length of stay (8 ± 4 versus 13 ± 8 days). Conclusions: A proactive approach may allow attenuating the occurrence and severity of hypotensive events more than a reactive goal-directed approach during radical cystectomy. Full article

Background: Hypotension following epidural labor analgesia (ELA) is its most common complication, affecting approximately 20% of patients and posing risks to both maternal and fetal health. As digital tools and predictive analytics increasingly shape perioperative and obstetric anesthesia practices, real-world implementation data are needed to guide their integration into clinical care. Current monitoring practices rely on intermittent non-invasive blood pressure (NIBP) measurements, which may delay recognition and treatment of hypotension. The Hypotension Prediction Index (HPI) algorithm uses continuous arterial waveform monitoring to predict hypotension for potentially earlier intervention. This clinical trial evaluated the feasibility, acceptability, and efficacy of continuous HPI-guided treatment in reducing time-to-treatment for ELA-associated hypotension and improving maternal hemodynamics. Methods: This was a prospective randomized controlled trial design involving healthy pregnant individuals receiving ELA. Participants were randomized into two groups: Group CM (conventional monitoring with NIBP) and Group HPI (continuous noninvasive blood pressure monitoring). In Group HPI, hypotension treatment was guided by HPI output; in Group CM, treatment was based on NIBP readings. Feasibility, appropriateness, and acceptability outcomes were assessed among subjects and their bedside nurse using the Acceptability of Intervention Measure (AIM), Intervention Appropriateness Measure (IAM), and Feasibility of Intervention Measure (FIM) instruments. The primary efficacy outcome was time-to-treatment of hypotension, defined as the duration between onset of hypotension and administration of a vasopressor or fluid therapy. This outcome was chosen to evaluate the clinical responsiveness enabled by HPI monitoring. Hypotension is defined as a mean arterial pressure (MAP) < 65 mmHg for more than 1 min in Group CM and an HPI threshold < 75 for more than 1 min in Group HPI. Secondary outcomes included total time in hypotension, vasopressor doses, and hemodynamic parameters. Results: There were 30 patients (Group HPI, n = 16; Group CM, n = 14) included in the final analysis. Subjects and clinicians alike rated the acceptability, appropriateness, and feasibility of the continuous monitoring device highly, with median scores ≥ 4 across all domains, indicating favorable perceptions of the intervention. The cumulative probability of time-to-treatment of hypotension was lower by 75 min after ELA initiation in Group HPI (65%) than Group CM (71%), although this difference was not statistically significant (log-rank p = 0.66). Mixed models indicated trends that Group HPI had higher cardiac output (β = 0.58, 95% confidence interval −0.18 to 1.34, p = 0.13) and lower systemic vascular resistance (β = −97.22, 95% confidence interval −200.84 to 6.40, p = 0.07) throughout the monitoring period. No differences were found in total vasopressor use or intravenous fluid administration. Conclusions: Continuous monitoring and precision hypotension treatment is feasible, appropriate, and acceptable to both patients and clinicians in a labor and delivery setting. These hypothesis-generating results support that HPI-guided treatment may be associated with hemodynamic trends that warrant further investigation to determine definitive efficacy in labor analgesia contexts. Full article

Background and Objectives: Assessing risk is essential for optimal care in acute pulmonary embolism (PE). The present research seeks to evaluate the value of admission blood cellular indices as predictors of in-hospital outcome in acute PE and their utility in conjunction with validated risk tools such as the Pulmonary Embolism Severity Index (PESI) score and the European Society of Cardiology (ESC) risk stratification. Materials and Methods: A total of 1058 individuals hospitalized at Bihor County Emergency Hospital, Oradea, Romania, with a diagnosis of acute PE confirmed by contrast-enhanced computed tomographic pulmonary angiography were retrospectively evaluated. Results: A total of 165 patients (18.2%) experienced adverse outcomes, including in-hospital mortality, cardiac arrest, cardiogenic shock, or persistent hypotension, and required rescue thrombolytic therapy. The neutrophil-to-lymphocyte ratio (NLR) was an independent predictor for in-hospital adverse outcome OR = 1.071 (95% CI 1.01–1.137), p < 0.001. NLR as a predictor of adverse outcome had an AUC of 0.712 (95% CI 0.661–0.742), p < 0.001, sensitivity of 72.56%, and specificity of 64.19% for a cutoff value of >5.493. In a combined model with PESI or with ESC risk classification, NLR is leading to a significant improvement in their AUC (p < 0.001). Conclusions: Among hematological markers, NLR holds the greatest relevance for stratifying risk in acute pulmonary embolism and serves as an independent indicator of unfavorable in-hospital prognosis. NLR had an acceptable discriminative power to predict short-term complications and can increase the predictive value of the PESI score and of ESC risk classification. Full article

Background and Objectives: Postoperative delirium (PODil) is a cognitive condition characterized by sudden fluctuations in consciousness and orientation after surgery. PODil following total knee arthroplasty (TKA) is associated with prolonged hospital stays and increased morbidity. Therefore, prevention of PODil is particularly important. Life’s Simple 7 score, published by the American Heart Association, is a new measure of cardiovascular health (CVH). Better CVH is associated with a lower risk of cognitive impairment. Hence, this study aimed to determine whether Life’s Simple 7 score is associated with PODil following TKA. Materials and Methods: This retrospective study included 973 patients who underwent TKA between January 2015 and January 2020. Patients were divided into two groups (group I: delirium group, n = 60; group II: non-delirium group, n = 913). Demographic data, use of analgesics, surgical factors, underlying diseases, laboratory results, and Life’s Simple 7 score were evaluated. Results: Significant differences were observed between the two groups for Parkinson’s disease, intraoperative hypotension, preoperative duloxetine administration, and Life’s Simple 7 score. In the receiver operating characteristic (ROC) curve analysis, the optimal cut-off value for Life’s Simple 7 score was determined to be 8 at the maximal Youden index, with an area under the curve (AUC) of 0.82, a sensitivity of 0.92, and a specificity of 0.58. Conclusions: Lower Life’s Simple 7 score is an independent risk factor for the incidence of PODil after TKA. Given its ease of measurement, Life’s Simple 7 score may be a useful measure for predicting PODil and will aid in preoperative risk assessment and post-operative patient management. Full article

Introduction: Microvascular free flap surgery is a treatment method for patients with head and neck cancer requiring reconstruction surgery. Patients undergoing this complex, long-lasting surgery are prone to prolonged episodes of intraoperative hypotension, which is associated with increased incidence of postoperative mortality, morbidity, and free flap failure. A new technology recently approved, named the Hypotension Prediction Index (HPI), allows precise hemodynamic monitoring of patients under general anesthesia, with a significant reduction of intraoperative hypotension events. This study aims to assess the impact of the Hypotension Prediction Index (HPI) on the incidence and severity of intraoperative hypotension in patients undergoing free flap surgery. Methods and analysis: Eligible patients will be randomly assigned to one of two groups: Group A, receiving invasive blood pressure monitoring with standard medical therapy, or Group B, undergoing hemodynamic monitoring using the Hypotension Prediction Index (HPI) software. The primary outcome is the time-weighted average (TWA) of mean arterial pressure (MAP) < 65 mmHg. Secondary outcomes include free flap viability and perioperative complications. Ethics and dissemination: Ethics approval was obtained from the Poznan University of Medical Sciences Ethics Committee (KB-560/22; date 1 July 2022). Results will be submitted for publication in a peer-reviewed journal. Trial registration number: NCT 05738603. Full article