Frequentist and Bayesian inferences were applied to compare HS and HU patients. The HS patients exhibited a significantly higher LFnu and lower HFnu. For MSE parameters, Scales 3–20 were significantly higher, as well as MSE1–5, MSE6–20, and MSE1–20 in HS, when compared to HU patients (p < 0.05). Regarding Bayesian inference, the spectral parameters demonstrated an anecdotal (65.9%) posterior probability favoring the alternative hypothesis, while MSE exhibited moderate to very strong probability (79.4 to 96.3%) at Scales 3–20, and MSE1–5, MSE6–20, and MSE1–20. HS patients exhibited a higher heart-rate complexity than HU patients. In addition, the MSE demonstrated a greater potential than spectral methods to differentiate variability patterns in successive RR intervals.Intradialytic hypotension is a common complication during hemodialysis sessions. The analysis of successive RR interval variability using nonlinear methods represents a promising tool for evaluating the cardiovascular response to acute volemic changes. Thus, the present study aims to compare the variability of successive RR intervals between hemodynamically stable (HS) and unstable (HU) patients during a hemodialysis session, through linear and nonlinear methods. Forty-six chronic kidney disease patients volunteered in this study. Successive RR intervals and blood pressures were recorded throughout the hemodialysis session. Hemodynamic stability was defined based on the delta of systolic blood pressure (higher SBP-lower SBP). The cutoff for hemodynamic stability was defined as 30 mm Hg, and patients were stratified as: HS ([n = 21]: ≤29.9 mm Hg) or HU ([n = 25]: ≥30 mm Hg). Linear methods (low-frequency [LFnu] and high-frequency [HFnu] spectra) and nonlinear methods  were applied. The area under the MSE curve at Scales 1–5 (MSE The low glomerular filtration rate, the main parameter used to diagnose chronic kidney disease (CKD) , was assIntradialytic hypotension (IH) is the most frequent and dangerous complication during the hemodialysis session, requiring immediate attention . In factIH is triggered by many factors, the intravascular volume depletion, associated with reduced osmolality, as occurs in patients undergoing a high rate of ultrafiltration, favors IH occurrence . PreviouHeart-rate variability (HRV) analysis stands out as a non-invasive and low-cost assessment approach to investigate the ANS influence over the cardiovascular system, which is performed by measuring changes  in successive RR intervals , supportAmong the nonlinear methods, entropy measurements have been pointed out as a promising way to deal with high-complexity biomedical data . In partCosta et al.  presenteAs biological systems with higher entropy exhibit a greater adaptive capacity , we hypoThe sample consisted of 46 patients (49.0 ± 18.4 years old) diagnosed with CKD, and undergoing hemodialysis treatment for at least 6 months. Uncontrolled hypertension (systolic blood pressure (SBP) ≥200 mm Hg and/or diastolic blood pressure (DBP) ≥120 mm Hg) and a previous diagnosis of cardiac arrhythmia were the exclusion criteria. Volunteers were invited to take part in the study and were informed about the study procedures; those who agreed signed their informed consent. The study was approved by the Research Ethics Committee of the Universidade Estadual do Sudoeste da Bahia (protocol: 09635912.3.0000.0055).® 742INT. The systolic (SBP) and diastolic (DBP) blood pressures were recorded during each hemodialysis session. During the sessions, the recordings were performed at the beginning and at every 30 min during the hemodialysis session as we had performed previously  and its 95% CI = 11.61 (0.90 to 22.33)); however, the Bayesian inference analysis indicated only a moderate posterior probability  of replicating this result. This fact may be related to the limitation of linear methods in extracting information from datasets with high complexity, such as the RR interval variability obtained from CKD patients during the hemodialysis session, as we have already indicated previously .Indeed, Silva et al.  demonstrNonlinear analysis methods are proposed as the better approach to describing the dynamics and complexity of biological phenomena ,43,44. MIt is important to emphasize that all frequentist inference was performed by adjusting the filtered volume during the hemodialysis session, since this variable is extremely important in defining the removed volume from the circulatory system; consequently, this is one of the main factors that predispose patients to IH.1–5, indicates a greater vagal modulation in HS patients, suggesting greater cardioprotection in conditions of cardiovascular stress.Recent studies have shown the usefulness of applying MSE to assess the variability of RR intervals ,45,46,47It is important to emphasize that Bayesian inference indicated a higher posterior probability of difference between HS vs. HU patients for the nonlinear parameters  than linear  parameters. This fact indicates that despite being proposed as an indirect measure of sympathovagal modulation, the spectral parameters may not be sensitive enough to detect small differences between HS and HU CKD patients; the nonlinear parameters used in our study were shown to be more sensitive for this purpose, corroborating previous studies that demonstrated the better adequacy of nonlinear methods in obtaining information from the cardiovascular system in different conditions and populations ,14,25,48The machine-learning approach applied in our study allowed for stratifying our sample into two clusters according to the features of selected variables. Based on the established criteria, MSE parameters were included in the machine-learning analysis and the generated Cluster 1 was composed of subjects with a greater heart-rate complexity, since Cluster 1 exhibited greater values of all of the included MSE parameters. In fact, 81.0% of HS patients were also assigned to Cluster 1, confirming the association between greater heart-rate complexity and hemodynamic stability during hemodialysis sessions. Additionally, subjects with Cluster 2 features exhibited a 2.94-times higher (relative risk = 2.94 [CI 95% = 1.14 to 7.58]) probability of being in the HU group during a hemodialysis session.Future studies should apply multivariate predictive models including the MSE parameters to predict the trend of hemodynamic instability during hemodialysis sessions, enabling the adoption of preventive strategies in relation to IH.The results of the present study indicate that HS CKD patients exhibit higher values of the LFnu spectral band and a higher entropy  of RR intervals when compared to HI patients. Additionally, MSE exhibited a greater posterior probability of identifying differences in the pattern of variability of RR intervals between HS and HU patients during hemodialysis sessions.


Gastrointestinal stromal tumor (GIST) makes up less than 1% of all gastrointestinal tumors, but it is the most common mesenchymal tumor of the digestive system. It is commonly found in the stomach and the small intestine and rarely seen in the colon and the esophagus. Additionally, sigmoid GIST is quite rare since colorectal GIST often occurs in the rectum. A total of 21 patients (including the study case) were looked at for this study, of which 14 (66.6%) were males and seven (33.3%) were females. We focused on GIST and conducted an online search and systematic analysis of all case presentations. KIT gene, which is responsible for the regulation of tyrosine kinase [Gastrointestinal stromal tumor (GIST) is one of the most prevalent mesenchymal tumors of the digestive tract despite constituting less than 1% of all gastrointestinal tumors. Historically, it was thought to originate from smooth muscle and misclassified as leiomyoma, leiomyoblastoma, and leiomyosarcoma . It was e kinase . Most GIe kinase .A 74-year-old male with a background of chronic obstructive pulmonary disease presented to the emergency department with a sudden onset of severe abdominal pain located in the lower abdomen. Moreover, despite normal laboratory results, the patient’s pain did not abate. An abdominal computed tomography (CT) scan was performed, and it illustrated a mid to lower intestinal perforation, suspected to be from either the sigmoid or the small bowl. Moreover, a diagnostic laparoscopy was done. The examination revealed diffuse peritonitis, fecal soiling of the entire abdomen, a 1.5 cm sigmoid colon perforation, and what appeared to be a small tumor close to the site, as can be seen in Figure Foremost, the removal of fecal material and the irrigation of the entire abdomen were initiated. Thereafter, laparoscopic partial sigmoid resection, i.e., Hartmann procedure, was done, and the tumor was then sent to for histological examination. The tumor is shown to express cluster of differentiation (CD) 117 and discovered on gastrointestinal stromal tumor protein 1 (DOG-1) confirming the diagnosis of a GIST, measuring at 0.7 cm with a low mitotic rate. There was no evidence of lymphatic or perineural sheath infiltration. The tumor’s tumor-node-metastasis (TNM) classification was pT1 L0 V0 Pn0 R0. Microscopically, the tumor had a spindle-like morphology with no necrosis nor high-grade atypia. It is also pertinent to note that the patient has experienced a myriad of complications following surgery including sigmoid stump insufficiency, multiple abscesses, urinary retention, postoperative ileus, intermittent tachycardic atrial fibrillation, and recurrent pleural effusion. The patient’s complications were treated over a period of several weeks, and he was later discharged. It was determined that the patient required follow-up examinations every 6-12 months. However, the patient refused chemotherapy, so annual CT scans are done regularly.Methodswww.pubmed.gov) and Embase (www.embase.com). The inclusion criteria were determined to be patients suffering from GIST, patients of both sexes, patients of various ages, patients of various body weights, and patients of various particular medically significant habits. Furthermore, the exclusion criteria were patients with comorbidities that could raise their risk for adverse events or affect the study’s findings, patients with terminal illnesses, patients with more than one tumor, or patients with a tumor other than the GIST, as well as patients who are likely to be lost to follow-up, missed data collection interviews, or gave inaccurate information. We looked at all studies applicable in English (or those having relevant English-language abstracts). The search results were as follows: There were 341 articles (not duplicates), of which 274 papers were disregarded because they did not primarily address GIST in their research title or abstract. Additionally, 47 publications were disregarded throughout the data extraction process after applying the inclusion and exclusion criteria. The other 20 papers were all then added to this study, and they were all carefully evaluated and assessed, as seen in Figure We searched the internet for data on GIST and systematically analyzed all case reports from September 16, 2022, to October 6, 2022. Using the search phrases “Gastrointestinal stromal tumour case report,” all studies were located on National Center for Biotechnology Information (NCBI)-PubMed  were investigated, of which 14 (66.6%) were males and seven (33.3%) were females. Their ages varied from 30 to 85 years, with a mean age of 64.05. The vast majority of patients (61.9%) were above the age of 60. The majority of cases demonstrate that the tumor had spindle cells with a high rate of mitosis. Additionally, immunocytochemistry shows that the majority of patients have a strong positivity to certain antibodies such as CD117, DOG-1, CD34, and vimentin being expressed, as seen in Table These individuals’ medical histories were examined, and it was discovered that the majority of them complained of vague symptoms that may have misled the diagnosis. Complaints vary from constipation, exhaustion, nausea, and vomiting and can even progress to acute severe pain, shock, or other emergencies. The average tumor size in these cases is 8.39 cm. The data that was collected also revealed the tumor’s site, as seen in Figure Despite GIST being the most common gastrointestinal mesenchymal tumor, its precise and exact global incidence is still under consideration due to the absence of a complete definition and classification. However, it is estimated that 10-20 million people are afflicted by it . In regaSymptoms that lead to the diagnosis of a GIST are often vague, such as abdominal pain and bloating . More spIn regard to anatomical location, there is no consensus if it is a reliable predictor of malignant behavior . GIST ofGIST is the most frequent gastrointestinal mesenchymal tumor; however, due to the lack of a comprehensive definition and classification, its true global incidence is still being debated. According to the literature, in our analysis of case reports, we have found that most GISTs are located in the stomach and are spindle-shaped. Moreover, most of these tumors were over 5 cm in size and have a high mitotic rate. GIST frequently exhibits symptoms, but the majority of these symptoms are vague and might mislead the diagnosis. This can result in sudden severe pain, shock, and other symptoms such as constipation, tiredness, nausea, and vomiting. Resection is the gold standard treatment for GIST and is typically followed by chemotherapy. Also, patients typically need lifelong follow-up.


The discovery of an effective airway inflammation marker which correctly identifies the condition and phenotype of asthma still constitutes a significant challenge. The determination of NLR, that is, the ratio of neutrophils to lymphocytes, would overcome this challenge. The role of the neutrophil–lymphocytic index in the diagnosis of specific types of asthma is investigated in the present study. The results of laboratory tests of 482 pediatric patients were used for the analysis. The results of 107 children without allergic disease symptoms were selected for the control group. The mean NLR in patients with asthma was 3.42 ± 4.05, and in the control group it was 1.94 ± 1.91. The difference between the NLR in allergic and non-allergic asthma was statistically significant in the allergic asthma and control groups. There was no statistically significant difference between NLR and body temperature, BMI, and gender. The value of NLR was significantly higher in the blood of patients suffering from asthma compared to the control group. The NLR was the highest among patients with allergic asthma. The use of this blood test in daily practice may facilitate the diagnosis of asthma and differentiation between asthma types, especially when the results of other tests are inconclusive. Asthma is one of the most common chronic diseases among children, and in recent years there has been a sharp increase in its prevalence. It is estimated that approximately 300 million people worldwide suffer from asthma, and by 2025 this number may increase by another 100 million . This diAsthma is characterized by bronchial hyperreactivity and airway obstruction. It is defined by a number of respiratory symptoms, such as wheezing, shortness of breath, chest tightness and cough, and may have a sudden onset and a varying severity, depending on the condition of the respiratory tract, asthma control, medication intake, and exposure to allergens or infection . ClinicaThe immunohistopathological picture of the condition includes infiltrates of inflammatory cells such as: neutrophils, eosinophils, lymphocytes, active mast cells and damaged epithelial cells. In people suffering from asthma, apart from inflammation of the airways, there is also a systemic activation of immune mechanisms . CirculaAn important asthma diagnostic problem, especially in pediatric patients, lies in the lack of identification of an airway inflammation marker. This would correctly identify the disease and its phenotype and significantly facilitate further prognosis. The guidelines of The American Thoracic Society, The European Respiratory Society (ATS/ERS) and The Global Initiative for Asthma (GINA) recommend that lung function tests, such as, and primarily, spirometry, should be performed to confirm the diagnosis. Unfortunately, the reliability and accuracy of this test significantly decreases in children under the age of 6, who may have difficulty following the necessary instructions . AlternaThe solution may be to determine the neutrophil–lymphocytic index (NLR), which could be a useful marker and could support existing methods. This indicator is the quotient of the number of neutrophils and lymphocytes. It has already been used in many branches of medicine, e.g., in the diagnosis of cardiovascular diseases or in the assessment of postoperative complications, in which it is an important predictor of worse prognosis, shorter survival time and the occurrence of life-threatening arrhythmias ,13. It it test to analyze parametric values and Kruskal–Wallis Test to analyze non-parametric data. A receiver operating characteristic (ROC) analysis was performed. We use the area under the ROC curve (AUC) ≥ 0.5 to confirm predictive capacity.The study analyzed the results of 482 pediatric patients admitted to the Department of Paediatric Pulmonology and Rheumatology of the University Children’s Hospital in Lublin. We conducted a retrospective study of the blood results of the patients admitted to hospital between January 2017 and December 2020. The values of laboratory parameters were obtained from the blood count taken on the first day after the patient’s admission to hospital ward. The research group consisted of 375 children. Based on the International Classification of Diseases ICD-10, the asthma patients were divided into three categories: allergic patients , non-allergic  and unspecified . The doctors classified the subjects as allergic or non-allergic according to positive or negative skin prick tests or serum-specific IgE. The control group consisted of 107 hospitalized patients diagnosed with other conditions, without a history of asthma, allergic diseases or chronic diseases. The data analysis was carried out using the Statistica 13.3 StaSoft Software. We used Student’s p > 0.05). The comparison of the mean value of the NLR coefficient between the entire study group and the control group showed that this indicator reached the value of 3.42 in the study group, which is almost twice as high as the control group (1.94). The NLR in the control group reached a clearly lower value than in each of the other examined groups, and the values of the indicator in the examined groups differed from each other. In the group of patients diagnosed with allergic asthma, the index was more than twice as high as that of the control group (4.09 vs. 1.94). It was almost twice as high (3.48) in patients with unspecified asthma (J45.9), and among children with non-allergic asthma (J45.1) the index was 50% higher than in the control group (2.72 vs. 1.07). The difference between the index in the study group and the control group was statistically significant. This difference was also statistically significant between NLR in allergic and non-allergic asthma , with a sensitivity of 93% and specificity of 24% . The proIn relation to the results obtained in other publications, the present study also indicated that the value of the NLR index is significantly higher in patients suffering from asthma compared to the control group, which may indicate the usefulness of the marker in the diagnosis of bronchial asthma. This indicator was almost twice as high in the study group compared to the control group. Moreover the results of this marker present different values for different types of asthma, and the highest values were found in the group of allergic asthma patients; therefore, the NLR index in this group of patients may have the greatest significance. Their results were twice as high as those of the control group and patients with unspecified and non-allergic asthma. As in the studies of other authors, the statistically significant difference between NLR and body temperature, BMI, and gender has not been shown here. A ROC analysis indicated that the NRL cut-off point should be about 0.53 to distinguish asthmatic children from others, with a sensitivity of about 93% and specificity of only 27%, and 2.30 for allergic asthma with a specificity of 68% and sensitivity of 51%. Compared to the results of studies by M. Dogru et al.  conducteRuilin Pan et al., in their study at Wuxi Children’s Hospital, tested the ability of NLR to distinguish pediatric patients with asthma exacerbations from healthy children. The study group, consisting of 89 patients, showed significantly higher values of white blood cells, neutrophils, C-reactive protein and NLR compared to the control group. Additionally, parameters such as NAR  and NBR  were researched in the study. The use of a combination of these three parameters significantly influenced the selection of children with asthma exacerbation from healthy patients . This stThe neutrophil-to-lymphocyte ratio can be readily and easily calculated using basic laboratory tests, eliminating the need for additional visits to the doctor or extended hospital stays for the youngest patients. The conducted research provides an opportunity to expand the current diagnostic tools for asthma by incorporating the NLR index. This would enable the accurate differentiation of the type of condition in pediatric patients, thereby allowing the appropriate therapy to be initiated at the very onset of the disease. In the case of the suspicion of asthma in young children, a significant difficulty is limited diagnostic possibilities, especially the performance of additional tests, including spirometry with a bronchial reversibility test and non-specific bronchial provocation tests . Spirometry testing is recommended from the age of 6 due to the need for the patient’s cooperation. The test is not possible in infants, and is not always possible in younger children. In most cases, the diagnosis is based only on the clinical picture and the use of trial pharmacotherapy with glucocorticosteroids, which in some cases could be avoided and is a cause of parental fear and apprehension. Therefore other markers of asthma available in GP practice are needed in this group of patients. A blood test (a complete blood count test) is one of the most popular tests, and it may be performed in a GP practice and a hospital ward. It is the basis for the diagnosis of many diseases, and is important in patients with recurrent respiratory infections. Checking the NLR may help doctors decide the treatment for the subsequent episode of wheezing. This especially applies to the youngest group of patients, whose symptoms are not very specific and therefore often underestimated. Before asthma is diagnosed, patients often are ineffectively treated with antibiotics for bronchitis, pneumonia, colds or viral diseases common in the pediatric population. During this time, the disease develops, which brings more consequences.There are several potential limitations to this study. Other inflammatory parameters, such as CRP or ESR, were not specified. Our study was conducted retrospectively, which is why we were unable to conduct further additional tests. Secondly, patients were not divided based on the severity of their asthma. However, the ROC analysis showed quite a good specificity and sensitivity, PPV was about 0.62 and NPV was about 0.58, so we strongly believe that despite these limitations, our study may prove useful in the diagnostic assessment of asthma in the pediatric population, which could be a reason for future studies on this.The presented results reveal the prospect of including the NLR marker in everyday medical practice, which would facilitate the correct diagnosis of asthma and its phenotype, as well as the implementation of appropriately selected therapy at an early stage of the disease, especially in the presence of the ambiguous results of other tests or the inability to perform these these tests on children. The ease of performance and low cost of the test may also ensure the widespread use of this method in many medical units in the future.It is worth pointing that the calculation of this indicator may contribute to the patient’s assignment to group with a high risk of asthma development. The objective diagnosis in this age group is difficult due to the child’s lack of cooperation, and simple blood tests may allow for a quicker diagnosis. The tests, which are minimally invasive to perform, help reduce the stress and anxiety of parents, children and medical staff.Due to the paucity of publications on the correlation between NLR and asthma, further research is needed to assess airway inflammation, systemic inflammation and the correlation between spirometry results and NLR in patients with asthma, especially in the pediatric population. Introducing this index into everyday practice may facilitate the differentiation of asthma types and risk assessment, improve prognosis, and determine the effectiveness of different therapeutic approaches. Long-term studies may be more precise and reliable in this respect.


Machine Learning has been increasingly used in the medical field, including managing patients undergoing hemodialysis. The random forest classifier is a Machine Learning method that can generate high accuracy and interpretability in the data analysis of various diseases. We attempted to apply Machine Learning to adjust dry weight, the appropriate volume status of patients undergoing hemodialysis, which requires a complex decision-making process considering multiple indicators and the patient’s physical conditions.All medical data and 69,375 dialysis records of 314 Asian patients undergoing hemodialysis at a single dialysis center in Japan between July 2018 and April 2020 were collected from the electronic medical record system. Using the random forest classifier, we developed models to predict the probabilities of adjusting the dry weight at each dialysis session.The areas under the receiver-operating-characteristic curves of the models for adjusting the dry weight upward and downward were 0.70 and 0.74, respectively. The average probability of upward adjustment of the dry weight had sharp a peak around the actual change over time, while the average probability of downward adjustment of the dry weight formed a gradual peak. Feature importance analysis revealed that median blood pressure decline was a strong predictor for adjusting the dry weight upward. In contrast, elevated serum levels of C-reactive protein and hypoalbuminemia were important indicators for adjusting the dry weight downward.The random forest classifier should provide a helpful guide to predict the optimal changes to the dry weight with relative accuracy and may be useful in clinical practice.The online version contains supplementary material available at 10.1186/s12882-023-03248-5. Machine learning (ML) has been increasingly used in the medical field for diagnosing and predicting illnesses based on multiple parameters and background characteristics of patients . ML has Heart failure is a major cause of mortality among patients undergoing hemodialysis . Many laClinically, physicians determine DW by considering multiple indicators, such as blood pressure, increased body weight between dialysis sessions, cardiothoracic ratio, pleural effusion, edema, brain natriuretic peptide (BNP), and other blood tests . RevisinThe random forest (RF) classifier is a ML method that generates high accuracy in the data analysis of various diseases, such as cardiovascular disease , stroke Previous studies using ML have shown that there are significant errors in the predictions of DW , 27. TheWe conducted a retrospective observational study at the Seirei Sakura Citizen Hospital in Chiba, Japan. Figure The clinical parameters, backgrounds, and medications of the eligible patients were collected from the electronic medical record system and anonymized. Laboratory tests were routinely performed twice a month at the beginning of the week. Table Generally, patients undergo hemodialysis twice or thrice a week for 240 min per session. In every session, nephrologists are attending near the hemodialysis patients and checking the hemodialysis procedure being correctly done. Hemodialysis patients usually have regular laboratory tests twice a month, meaning they are tested every two or three weeks. The DW of each patient was assessed and adjusted by several nephrologists periodically and when clinically indicated, by referring to multiple indicators such as blood pressure, clinical findings, chest x-ray findings, laboratory test results, sonographic measurement of the inferior vena cava diameter, and blood volume monitor, as recommended by the Japanese Society for Dialysis Therapy guidelines  and K/DOThe default dialysate sodium concentration was 140 mmol/L, and the dialysate calcium concentration was 2.75 mmol/L. The dialysate flow rate was 500 ml/min, and the dialysate temperature was 36.0 °C for almost all patients.Table up” and “Pdown” scores, respectively, with both scores ranging between 0 and 1. The probabilities of the classified predictions were rescaled using the probability calibration [There are many machine learning algorithms that can be applied to this task. In our initial examination, we have found that RF produces better results than other algorithms such as XGBoost and ANN, since the number of explanatory variables in our data is not very large and the task is a simple binary prediction of Dry Weight change. Our previous study also showed that RF performs reproducibly better than other algorithms in a binary classification task based on the similar clinical parameters as in this study . For theibration –32. The We retrospectively collected 69,375 dialysis records from 314 Asian patients during the observation period. The average observation period was 17.5 months. 73% of the patients were men. The mean age of the patients was 66.4 years old, and the median dialysis vintage was 4.0 years. The most common primary disease for dialysis induction was diabetic nephropathy 42.4%), followed by chronic glomerulonephritis (19.4%), nephrosclerosis (16.6%), and others (17.8%)  for DW up model, and  for DW down model. After the calibration of the models, the optimal probability thresholds with the highest Youden were 0.204 for the DW up model, and 0.114 for the DW down model. The AUC, accuracy, precision, recall, and F1 score of the two models for the test data set were  for DW up model, and  for DW down model, respectively (Fig. up had a sharp peak at the time of the actual upward change in DW and then declined immediately (Fig. down was slow and remained high for a while after the actual downward change in DW occurred (Fig. Thereafter, we examined the changes in the prediction probabilities of ML in the 30 hemodialysis sessions before and after the actual DW change for all cases included in the test dataset. The average Pely Fig. a. Howevered Fig. b.To clarify the parameters on which the determination of DW changes in the ML process is based, we calculated the variable importance of the two ML models. Figure For the model to predict upward DW changes, variables related to blood pressure are of great importance Fig. a. The toSystolic blood pressure was also an essential factor in predicting downward DW changes Fig. b. HoweveNext, the transition of the most important features was examined in 30 hemodialysis sessions before and after the actual DW change. Blood pressure, an important predictor of the upward DW change, showed a marked decrease at the time of the actual upward DW change, followed by rapid recovery Fig. c. HoweveCRP, an important indicator of the downward DW change, showed a sharp increase just before the actual DW change, but its peak occurred a little later than the actual DW change Fig. d. The chIn this study, we developed novel methods to predict whether DW should be adjusted at each dialysis session using an RF classifier. The AUCs of the models were 0.70 or more, indicating high reliability. By analyzing approximately 150 variables, our approach revealed the most important input factors for each decision-making. These models may enable medical staff to determine the correct timing for adjusting DW more efficiently.Several studies have used machine learning to predict DW in patients undergoing dialysis. Guo et al. predicted DW using a neural network model and compared it to the DW predicted by a body composition monitor; their model’s root mean square error was 1.316 . Kim et DW could be acceptable in a particular range for stable maintenance hemodialysis patients with few cardiac problems. Usually, DW is not immediately determined as a constant value but is probed and adjusted gradually based on various information gathered . Thus, wWe have also shown how the predicted scores varied over time, another point that has yet to be addressed. Our models can capture even small changes in the input variables that reflect the patient’s condition.up score showed a quick rise, precisely detecting the timing at which the DW should be adjusted upward. However, the average Pdown score gradually changed. A possible reason is that the model could not catch up with real-time changes in medical conditions because the frequency of laboratory tests was only twice a month. Furthermore, a gradual reduction of DW is recommended in clinical settings [down score.The average Psettings , correspImportance analysis revealed that serum levels of CRP and albumin, rather than blood pressure, showed the highest importance in predicting DW reduction. In addition to the elevation of CRP, hypoalbuminemia also indicates an inflammatory status , 35, whiImportance analysis also showed that declining blood pressure was related to predicting upward changes in DW. Several studies have shown that hypotension during dialysis is a significant poor prognostic factor , 46. DecIn our data, there were only small changes in the average levels of CRP, albumin, and blood pressure in the sessions where DW was actually adjusted, compared to 30 previous sessions. Even if these changes are gradual and difficult for medical staff to recognize, our ML models can detect slight changes and inform them by raising their scores. Using our models, DW can be adjusted to prevent adverse events and improve a patient’s quality of life and prognosis.BNP has been used to indicate fluid volume status, cardiac function, and cardiovascular disease. Many reports have shown an association between the biomarker and heart failure and prognosis in hemodialysis patients, but the threshold for this association is not consistent . In the up and Pdown scores were elevated simultaneously. Most of them were as follows: the elevation of a Pdown score caused the reduction of DW and was immediately followed by a drop in blood pressure and hence an increasing Pup score, as well as elevated inflammatory states and low blood pressure in critical conditions. Our models can detect these unstable situations.For each patient, the predicted scores were elevated around the time of the actual DW changes in most cases; however, in some instances, both the PIn a real clinical setting, based on inputs such as vital signs, clinical findings and blood test results of each patient, our model could calculate the probabilities that DW should be raised and lowered respectively. If the probability exceeds thresholds, alerts will be issued, prompting the doctor to consider changing the DW. The alerts are also helpful for non-specialist doctors, other medical staff, and trainees. Furthermore, our model can be presented to patients as a rationale for changing their DW.Our study has several limitations. Due to the retrospective nature of this study, the description of some findings, such as edema and pleural effusion, seemed inadequate in some cases. In addition, because of the low frequency of laboratory tests, the models do not reflect real-time changes. Therefore, we plan to start collecting data prospectively, using templates to enter findings and devices to monitor blood concentration during dialysis to improve the accuracy of our models. Furthermore, the findings of this work are not immediately generalizable because it was a single-center study. In the future, we plan to collect data from other dialysis facilities and apply transfer learning to them.In summary, we developed novel models to predict whether the DW of hemodialysis patients should be adjusted using an RF classifier. Our analysis showed the importance of declining blood pressure during dialysis for predicting an upward change in the DW and the impact of elevated CRP levels and hypoalbuminemia on predicting a downward change in the DW. Further studies are required to evaluate the clinical effectiveness of our models.Below is the link to the electronic supplementary material.Supplementary Material 1


Renal artery Doppler sonography with resistive index (RI) determination is a noninvasive, fast, and reliable diagnostic tool increasingly used in the intensive care unit (ICU) to predict and assess the reversibility of acute kidney injury (AKI). However, interpreting the RI can be challenging due to numerous influencing factors. While some studies have explored various confounding factors, arterial blood gases have received limited attention. Therefore, our study aims to evaluate the impact of arterial blood gases on the RI in the ICU setting.This prospective observational study enrolled ICU patients who required blood gas analysis and had not experienced significant hemodynamic changes recently. The RI was measured using standardized Doppler ultrasound within an hour of the arterial blood gases sampling and analysis.2 , age , diastolic arterial pressure (DAP) , and SaO2 . Multivariate analysis confirmed that age > 58 years and PaCO2 were significant factors influencing the RI, with respective odds ratios of 18.67 (p = 0.0003) and 1.132 (p = 0.0267).A total of sixty-four patients were included in the analysis. Univariate analysis revealed a correlation between the RI and several variables, including PaCO2, age, and diastolic arterial pressure. Further studies are needed to develop a comprehensive scoring system that incorporates all these cofactors for a reliable analysis of RI levels.The interpretation of renal arterial RI should take into account thresholds for PaCOTrial registration This observational study, registered under number 70–0914, received approval from local Ethical Committee of Toulouse University Hospital. Acute kidney injury (AKI) is a significant complication that affects approximately 30–40% of patients in the intensive care unit (ICU) and 1% of patients undergoing major postoperative surgery . It servThe renal interlobar arterial resistive index (RI), initially introduced by Pourcelot for the study of renal perfusion, is increasingly utilized in various renal disorders, including graft dysfunction and obstructive nephropathies , 6. ThisThe relationship between renal macro hemodynamics and renal function is not linear. Multiple independent factors can influence the resistive index, including vascular resistance, vascular compliance, and mean arterial pressure . ConsequTherefore, the primary objective of this study was to evaluate the influence of arterial blood gases on the RI in ICU patients.This prospective, observational study included adult patients admitted to the ICU. Patients who required arterial blood gas analysis and had not experienced changes in catecholamine administration within the past hour were eligible for inclusion. The inclusion process commenced at the time of blood gas analysis.Exclusion criteria encompassed the following: individuals under 18 years of age, pregnant women, incapacitated adults, patients with a history of chronic kidney failure, kidney malformation, a single kidney, renal artery stenosis, or diabetic nephropathy. Patients who were undergoing dialysis or had received diuretic treatment within the past 4 h were also excluded. Furthermore, patients with hemodynamic failure necessitating an increased dosage of catecholamines in the hour before measurements, as well as those with therapeutic limitations, were not included in the study.This observational study, registered under number 70–0914, received approval from local Ethical Committee of Toulouse University Hospitals. The study was performed according to the declaration of Helsinki. No change in our current clinical practice  and no randomization was performed. As it was an observational study, in accordance with French law, oral informed consent was required.2, tidal volume, expiratory volume, respiratory rate, heart rate and blood pressure). The blood gas and ultrasound data were collected over a period of less than one hour . The other laboratory data were from daily assessments of the patient.At inclusion we collected the demographic data , and the ventilator and hemodynamic clinical data  and 160 mL/min/1.73 m2 (men)) [After a first descriptive statistical step and verification of the normal distribution of values (Kolmogorov–Smirnov test), the studied population was separated into three groups according to the glomerular filtration rate (decreased GFR for CrCl measured < 60 mL/min/1.73 m2 (men)) .The patient characteristics between the different groups were compared using non-parametric tests  due to the non-homogeneity of the group sizes. The results are expressed as median and 95% confidence intervals (95% CI).Then, we analyzed the relationship between the RI and the quantitative variables, including age, GFR, the hemodynamic parameters and those characterizing arterial blood gases (linear regression through Pearson’s r coefficient and/or Spearman’s rank correlation coefficient). Next, we integrated the significant variables in multiple regressions to describe a model that included the only factors of interest.As the limited population of patients with an alteration in renal function did not enable calculation of a statistically valid RI threshold, a RI threshold > 0.7 was chosen since it is found in most published studies to date , 19. TheA multi-dimensional analysis through logistic regression evaluated the association between the covariates for which the p value was < 0.2 and the dependent variable (RI > 0.7) through measurement of the odds ratio. We tested several models by choosing that for which the observed data was best adjusted to the model .To highlight patients at risk of having an RI > 0.7, a partitioning of the population was represented using a Classification and Regression Trees (CART) analysis. The advantage of this approach is to describe the means of distribution of the population in homogeneous groups according to RI level and the covariates selected from the multidimensional analysis.Statistical analysis was conducted using MedCalc® statistical software, version 15  for the majority of the analyses except for the CART method, which was carried out on SPSS® for Window version 24 . A p value < 0.05 was considered statistically significant.Among the 64 patients included in the study, the median interval between ICU admission and inclusion was 5 (3–7) days. 53% of the patients were under controlled mode ventilation, 30% were on non-invasive mode during the procedure, and 16% were on spontaneous ventilation. Table 2. Conversely, a significant negative correlation was found between the RI and measured creatinine clearance, diastolic arterial pressure (DAP), and SaO2 , and PaCOMultivariate analysis using multiple regressions was conducted, considering the integration or non-integration of measured creatinine clearance (CrCl) depending on whether the RI was regarded as a consequence or an indicator of glomerular filtration rate (GFR). In both models, it was found that the only significant factors influencing the RI level were age (p < 0.0001), PaCO2 (p = 0.0056), and DAP (p = 0.0416).Table Figure The ROC curve analysis determined an RI threshold of 0.77 (gray zone: 0.66–0.77) for detecting kidney function impairment. Notably, the discrimination ability was relatively low, with an AUC = 0.73) below the threshold of 0.8. Considering the limited sample size of patients with kidney failure and the wide “gray zone” of RI values within this population, we selected an RI threshold of 0.7 (previously used in the literature with a larger patient cohort for screening kidney function impairment). This threshold falls within the predefined gray zone. The results are presented in Table  below thThe most discriminatory variable appears to be age, with a threshold of > 58 years, demonstrating a sensitivity of 77%, specificity of 85%, positive predictive value (PPV) of 82%, negative predictive value (NPV) of 81%, and an area under the receiver operating characteristic (AUROC) curve of 0.82. However, for the other variables, the ROC curve analysis did not yield a statistically significant threshold (AUC not different from 0.5).Furthermore, the RI exhibits variations based on the underlying condition necessitating admission to the intensive care unit, as depicted in Fig. The RI values differ among patient groups, with a measurement of 0.62 (0.59–0.66) in multiple trauma patients, 0.72 (0.69–0.75) in postoperative patients, and 0.71 (0.65–0.74) in medical patients (p = 0.00504). The significant difference observed is primarily attributed to the multiple trauma group.The multivariate analysis of factors associated with an RI > 0.7, incorporating both continuous and categorical variables, is presented in Table However, multiple trauma was not included in the model due to its strong correlation with age. It was observed that 96% of multiple trauma patients were under the age of 58, and this variable lost significance when age was included in the analysis.2, although a specific threshold for PaCO2 could not be determined.The influence of age and PaCO2 on the RI level was confirmed. The RI tends to increase after the age of 58, and it also increases with higher levels of PaCO2 thresholds within different subgroups, along with a threshold for diastolic arterial pressure (DAP) for patients under the age of 58.The Classification and Regression Tree (CART) analysis was employed to define several thresholds based on the data. Figure 2 > 37.75 mmHg has a 100% likelihood of having an RI > 0.7. On the other hand, a patient under the age of 58 with a DAP > 56.5 mmHg and a PCO2 < 34.6 mmHg has a 100% chance of having an RI < 0.7.In summary, a patient above the age of 58 with a PaCO2 thresholds. The RI serves as a reproducible and user-friendly tool for early screening and prognostication of AKI in the ICU [Our study highlights that in the ICU setting, the interpretation of the RI should be based on age and PaCO the ICU . However the ICU , 24. Add the ICU , 25–29.2, on the RI in ICU patients under routine care conditions. Previous studies have suggested that severe hypoxemia in rats or patients on mechanical ventilation leads to renal vasodilation, while significant increases in PaCO2 result in vasoconstriction [2 (or SaO2) and variation in RI, which contradicts findings from other studies conducted on patients undergoing postoperative cardiac surgery or those with acute lung injury (ALI) [Our study stands out due to its focus on examining the influence of arterial blood gases, particularly PaCOtriction , 30. Howtriction , 17. Thery (ALI) .We selected an RI threshold of 0.7 based on relevant literature, as it has been demonstrated to be associated with the occurrence of organic acute kidney failure , 32. An 2 significantly influenced the RI (p = 0.0416) across patients with augmented renal clearance (ARC), normal GFR, or glomerular hypofiltration. In each of these groups, both PaCO2 and RI increased concurrently. The multivariate analysis further confirmed the impact of PaCO2 on the RI . Through multivariate analysis using classification and regression tree, we found that ICU patients aged over 58 years with a PaCO2 level exceeding 37.75 had a 100% risk of having an RI above 0.7. In certain conditions such as acute respiratory distress syndrome (ARDS), higher thresholds of PaCO2 are generally tolerated. Nevertheless, based on the results of our study, the actual effects of hypercapnia on renal parenchyma and its function still require further evaluation.Previous studies have not been able to establish a direct correlation between the resistive index (RI) and renal blood flow or glomerular filtration rate (GFR) , 33, 34.As evidenced in existing literature, age has a direct influence on the glomerular filtration rate (GFR), which was reduced in approximately 20% of the patients in our study . Additionally, there is a corresponding increase in the resistive index (RI) with age . This riWe also identified a correlation between diastolic arterial pressure (DAP) and the resistive index (RI). Previous studies have explored the relationship between global hemodynamics and the RI, indicating that an increase in mean arterial pressure (MAP) due to noradrenaline administration leads to an elevated RI with a threshold effect . This suThe resistive index (RI) has demonstrated its predictive value in determining the reversibility of acute kidney failure and its potential for guiding hemodynamic optimization, especially in cases of septic shock. However, its diagnostic performance cannot be utilized as a screening tool for augmented renal clearance (ARC) . AlthougOur study has several limitations. One key limitation is the complexity of interpreting the resistive index (RI) due to the influence of multiple factors, including mean arterial pressure, pulse pressure, vascular compliance, oxygenation levels, and intra-abdominal pressure –29, 38. 2 on the RI, particularly in hypercapnic patients. It highlights the importance of analyzing the RI alongside normalized PaCO2 levels and age and diastolic arterial pressure (DAP) thresholds. Further research is warranted to develop a scoring system that integrates these cofactors, enabling more reliable interpretation of the RI results.The resistive index (RI) serves as a noninvasive, fast, and reliable diagnostic tool that can help predict the reversibility of acute kidney injury (AKI) and tailor individualized hemodynamic management for patients. Our study demonstrates the positive influence of PaCO


The relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and atherosclerosis has been controversial, which has become a hit of recent research. The study aimed to explore the association between MASLD, cardiovascular and cerebrovascular diseases (CCVD), and the thickness of carotid plaque which was assessed by ultrasound.From September 2018 to June 2019, 3543 patients were enrolled. We asked participants to complete questionnaires to obtain information. All patients underwent liver ultrasound and bilateral carotid ultrasound to obtain carotid intima-media thickness (IMT) and maximum carotid plaque thickness (CPT). Hepatic steatosis was quantified during examination according to Hamaguchi’s ultrasonographic score, from 0 to 6 points. A score < 2 was defined as without fatty liver, and a score ≥ 2 was defined as fatty liver. Information about blood lipids was collected based on the medical records.We found common risk factors for CCVD events, MASLD, and atherosclerosis. There was a significant correlation between MASLD and carotid plaque, but not with CPT. No association was found between MASLD and CCVD events. CPT and IMT were thicker in CCVD patients than in non-CCVD patients. No significant difference was found between IMT and CPT in MASLD patients and non-MASLD patients. CCVD was independently and consistently associated with higher IMT, and free fatty acid (FFA).According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Due to the distribution of CPT of both CCVD and MASLD patients in the CPT 2-4 mm group, contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events. Overweight is a global epidemic, affecting an increasing number of the world population . In ChinThe most common cause of death in patients with MASLD is cardiovascular and cerebrovascular diseases (CCVD) events. CCVD has high morbidity, high disability rate, and high mortality rate. This has become grown up to be a global public health and livelihood issue. Several previous studies –12 have Accordingly, the purpose of this study was to explore the association between MASLD, CCVD, and the thickness of carotid plaque which was assessed by ultrasound.n = 471), (b) patients with poor ultrasound image quality (n = 117), and (c) patients who did not receive a carotid ultrasound examination and a liver ultrasound examination within one week (n = 122). Finally, 3543 patients were enrolled  and written informed consent was issued from all participants. Seven hundred and ten patients were excluded with exclusion criteria including (a) patients who refused to accept questionnaires and provide personal medical history , who was blinded to participant history, using a 6–10 MHz linear probe . The image parameters were set to show the plaque and surrounding tissue as clearly as possible. Before the formal study, the ultrasound physician selected 100 images for review.. After completing the first IMT and CPT measurement, the measurement was repeated one week later. And the consistency was obtained before proceeding to the next step.All patients were examined in a supine position. The carotid artery was scanned from the clavicle, upwards to the bifurcation of the carotid artery, and finally towards the internal and external carotid arteries. Each segment of carotid artery was examined and the thickest IMT was recorded . The IMTFig. . After cAll patients underwent liver ultrasound examination when they underwent carotid ultrasound in 1 week without excessive alcohol abuse  and other liver diseases. The subjects were all in the supine position, scanning the liver under the ribs and between the ribs to observe its size and shape, the echo of the liver parenchyma, and whether the blood vessels in the liver were positive. At the same time, the echoes of the liver and right kidney parenchyma were compared. Hepatic steatosis was quantified during examination according to Hamaguchi’s ultrasonographic score , 19, froThe database with liver ultrasound images was collected by three ultrasound physicians with at least five years of experience in abdomen ultrasound. We randomly selected 200 liver images from the database. These images were sent respectively to the three ultrasound physicians, who were blinded to the clinical information of patients. These images were evaluated according to the standard of Hamaguchi’s ultrasonographic score by physicians A, B, and C. The consistency of the 200 images assessed by three physicians was evaluated. A satisfactory agreement was obtained before the formal collection of patient images began.Trained investigators interviewed participants face-to-face, using a standard questionnaire to obtain their demographics, lifestyle, disease history, and the potential risk factors related to CCVD.Smoke (Regular consumption of cigarettes in the past 6 months was defined as a current smoker).Alcohol consumption .Hypertension .Diabetes Dyslipidemia  .Exercise status .Obstructive sleep apnea hypoventilation (Previously diagnosed).History of atrial fibrillation (AF) (Previously diagnosed as AF).Family history of CCVD .Physical examination was performed before the ultrasound examination, including the measurements of BMI and blood pressure. Participants' body weight and height were obtained in light clothes and bare feet to the nearest 0.1 kg and 0.1 cm, respectively. BMI was calculated as the weight (kg) divided by the square of the height (m). Overweight was defined as BMI ≥ 26 , 22. BloHypertension and DM were determined according to the 2013 Hypertension Clinical Practice Guidelines  and the The medical records of all subjects were reviewed for information about blood lipids and CCVD events. CCVD events were defined as stroke, transient ischemic attack, stroke death, and myocardial infarction. Stroke was defined as a neurological deficit lasting at least 24 h or until death and accompanied by a brain imaging finding associated with stroke. A transient ischemic attack was defined as a neurological deficit lasting between the 30 s and 24 h but not accompanied by a brain imaging finding associated with stroke . MyocardContinuous data were presented as mean ± standard deviation or as median.P < 0.05 was considered to indicate statistical significance.(interquartile range), as appropriate (skewed distribution). Continuous normally distributed variables were compared using the student’s test for independent samples and analysis of variance. Alternatively, the Mann–Whitney U test was used for independent samples and the Wilcoxon test for repeated measurements. The proportion of categorical variables was compared using a Chi-square test or the Fisher exact test. The consistency assessment of the three ultrasound physicians on the diagnosis of MASLD was completed by Kendall's W test and the kappa test. The consistency of carotid plaque measurement was completed by intra-class correlation (ICC) estimates. Interobserver variations were investigated by using the Kappa statistics. ICC estimates and their 95% confidence intervals were calculated based on a mean-rating, absolute-agreement, 2-way mixed-effects model.Strong agreement was observed for the inter-observer assessment of MASLD by three ultrasound physicians , the Kendall's W test was 0.950 , indicating good reliability and rated as "mostly perfect". For the intra-observer reproducibility of CPT and IMT, the ICC value was 0.994 (95% CI 0.991–0.996) and 0.937(95% CI 0.917–0.953), Kendall's W test was 0.996 and 0.970, indicating excellent reliability and rated as "mostly perfect" (Table P < 0.05). CPs were present in 60.5% of MASLD patients. Compared with those with non-MASLD, subjects with MASLD were younger. Participants with MASLD had a higher elevated blood lipid level and a higher BMI in comparison with those with non-MASLD. There seemed to be no association between fatty liver disease and cardio-cerebrovascular events.Study participants included 3543 men and women, aged from 20 to 88 years old. The mean age of patients was 64.12 ± 11.47 years, and 45.1% of them were male. Overall, 26.3% of the patients were overweight, 16.7% of the patients were current smokers, 57.4% of the patients had hypertension, 21.1% of the patients had DM, 25.9% of the patients had a family history of CCVD, 12.6% of the patients had a personal history of CCVD, 45.1% of the patients had dyslipidemia, 76.9% of the patients were lack of exercise, and 4.2% of the patients had obstructive sleep apnea. The potential risk factors associated with MASLD, CP, and CCVD were shown in Table P = 0.000). The mean IMT with non-CCVD patients was 1.022 ± 0.225 mm, and with CCVD patients was 1.110 ± 0.217 mm (P = 0.000). 816 patients suffered from MASLD among 2052 patients with CP. The mean CPT with non-MASLD patients was 2.458 ± 1.051 mm, and with MASLD patients was 2.374 ± 0.945 mm (P > 0.05). The mean IMT with non-MASLD patients was 1.031 ± 0.221 mm, and with MASLD patients was 1.069 ± 0.234 mm (P > 0.05). CPT and IMT had no significant correlation between non-MASLD and MASLD . Participants with CCVD had a thicker CP thickness in comparison with those with non-CCVD. In both CCVD and MASLD patient groups, carotid plaque thickness was mostly distributed in the CPT 2-4 mm group.There were 2052 patients with CP in our study cohort. Among them, 352 patients suffered from CCVD. The mean CPT with non-CCVD patients was 2.328 ± 0.935 mm, and with CCVD patients was 2.887 ± 1.214 mm (P = 0.249) .The univariate logistic regression analysis revealed a significantly increased risk of major access site complications for Male in gender, age , DM , AF , IMT , CPT , Glucose ,TC , HDL and FFA . These parameters were included in multivariate logistic regression analysis and the result was shown in Table The population in our study came from Changning District, one of the most prosperous communities among the 16 districts of Shanghai. In 2020, The GDP of Changning District was 156.117 billion yuan, and the resident population was 693,051. Residents of the Changning district were relatively affluent. In this study, the prevalence of MASLD was 38.1%, and the prevalence of DM was 21.1%. CCVD occurred in 12.6% of the patients. CP was present in 57.9% of all patients and 60.5% of MASLD patients. Although this data showed that atherosclerosis burden increased in the presence of MASLD, this association may be due to the fact that the samples in this study were from inpatients and outpatients of our hospital, which led to the high proportion of CCVD and CP. The high prevalence of DM may be the cause of the high prevalence of MASLD . Our resP = 0.016). In the carotid plaque group population of this study, there was no significant difference in the distribution of CPT and IMT between MASLD and non-MASLD patients. Interestingly, we found that in both CCVD and MASLD patient groups, carotid plaque thickness was mostly distributed in the CPT 2-4 mm group. This may be similar to plaque characteristics distribution in patients in the real world. Our multivariate logistic regression analysis was shown that CCVD was independently and consistently associated with higher IMT and FFA. Regarding the CPT, statistically significant relationships with CCVD were observed less frequently and were less robust. After adjustment, CPT was no significant relationship with CCVD. This may be due to the lack of information on plaque characteristics in this study, which included only the thickness of the plaque. We should probably pay more attention to the characteristics of plaques and use various imaging techniques to observe the vulnerability of the plaques, not just the degree of stenosis. In our previous study on carotid plaque assessment with contrast-enhanced ultrasound [We found common risk factors for CCVD events, fatty liver, and atherosclerosis, which included smoke, age, male, DM, and hypertension. Risk factors for CCVD and CP were similar. Many studies justify this association. Our restrasound , we fountrasound . MASLD mtrasound . MASLD itrasound . It is rtrasound , 43, butPrevious studies reported that the pathogenesis of MASLD can be partially explained by a metabolic component and partially explained by a genetic component , 45, theThere were some limitations in our study. Firstly, this was a cross-section study, with all its inherent limitations. In particular, as the carotid plaque images were only obtained at a single time point, we could not determine how the carotid artery measurements and fatty livers change over time, nor can we prove a causal relationship. Although our study lacks follow-up data, we will continue to supplement it. Secondly, liver biopsy remains the gold standard for diagnosing MASLD and grading hepatic steatosis. However, the biopsy is costly, invasive, inappropriate for screening and follow up and it is not acceptable to most patients . A meta-According to our results, we recommend carotid ultrasound examination of the patients when FFA is increased, regardless of the presence of risk factors and MASLD. Contrast-enhanced ultrasound is necessary to assess the vulnerability of the plaque when CPT ≥ 2 mm. Timely treatment of vulnerable plaques may reduce the incidence of future CCVD events.


Altered levels of cerebrospinal fluid (CSF) glucose and lactate concentrations are associated with poor outcomes in acute brain injury patients. However, no data on changes in such metabolites consequently to therapeutic interventions are available. The aim of the study was to assess CSF glucose-to-lactate ratio (CGLR) changes related to therapies aimed at reducing intracranial pressure (ICP).A multicentric prospective cohort study was conducted in 12 intensive care units (ICUs) from September 2017 to March 2022. Adult (> 18 years) patients admitted after an acute brain injury were included if an external ventricular drain (EVD) for intracranial pressure (ICP) monitoring was inserted within 24 h of admission. During the first 48–72 h from admission, CGLR was measured before and 2 h after any intervention aiming to reduce ICP (“intervention”). Patients with normal ICP were also sampled at the same time points and served as the “control” group.n = 115, 53%), ICP significantly decreased and CPP increased. After 2 h from the intervention, CGLR rose in both the intervention and control groups, although the magnitude was higher in the intervention than in the control group . In a linear regression model adjusted for several confounders, therapies to manage ICP were independently associated with changes in CGLR. There was a weak inverse correlation between changes in ICP and CGRL in the intervention group.A total of 219 patients were included. In the intervention group (In this study, CGLR significantly changed over time, regardless of the study group. However, these effects were more significant in those patients receiving interventions to reduce ICP.The online version contains supplementary material available at 10.1186/s13054-023-04409-6. Acute brain injury (ABI), such as traumatic brain injury (TBI), intracranial hemorrhage (ICH) and subarachnoid hemorrhage (SAH), is a significant cause of morbidity and mortality worldwide –3. The cIn this setting, energetic metabolism is also often disturbed . The injIn this setting, high cerebral extracellular lactate concentrations can be observed. Although initially considered a sign of anaerobic metabolism and tissue hypoxia, this phenomenon could also happen because of enhanced lactate uptake from the circulation or increased lactate production in the astrocytes –19, withHowever, CMD and PET scans are not widely available and not feasible in many critically ill patients, while analyses of glucose and lactate concentrations in the cerebrospinal fluid (CSF) are more easily performed. A reduced cerebral spinal fluid glucose-to-lactate ratio (CGLR) has been associated with an increased risk of mortality and poor neurological recovery after ABI , 22. HowAs such, the objective of this study was to determine whether therapeutic interventions aiming to reduce intracranial pressure (ICP) would also result in CGLR changes in severe ABI patients.This prospective multicentric observational study includes all patients admitted over 3 years following an aneurysmal SAH, TBI, ICH or other forms of ABI in 12 European Intensive Care Units (ICU). Patients were eligible for the study if they met the following criteria: (a) age > 18 years; (b) presence of an external ventricular drain (EVD) for intracranial pressure monitoring inserted within 24 h from admission. The local Ethics Committees approved this study in each participating center. According to local legislation, written informed consent for study participation was obtained from a patient family member or a legal representative. This study followed the recommendations of the Strengthening the reporting of observational studies in epidemiology (STROBE) guidelines .Patients' management followed the current guidelines for the management of TBI , SAH 2525 and ICPatients’ demographics and pre-injury comorbid diseases were recorded. Clinical status on admission was evaluated using the Glasgow Coma Scale (GCS) . The tomA CSF sample of 5 mL was collected from the proximal port of the EVD catheter using a sterile technique and analyzed within 60 min from the collection for biochemistry and cytology. CSF total counts of red and white blood cells, as well as protein concentrations, were obtained whenever possible before the start of any intervention; the first CSF lactate, CSF glucose, and CGLR assessment  occurred within the first 72 h from ICU admission . In patients with ICP values requiring a specific therapy (“intervention” group), baseline measurement occurred just before the intervention and the second CSF sample was collected 2 h thereafter. In patients with relatively normal ICP values (“control” group), the baseline sample was also collected within 72 h from admission, according to the decision of local investigators, and the second sample 2 h thereafter, as in the intervention group. CSF glucose was measured using the hexokinase method; CSF lactate was measured using the enzymatic method in which L-lactate is oxidized to pyruvate and hydrogen peroxidase by lactate oxidase. However, each center had its own analyzer, reference values and internal validation procedures.2, PaO2, blood lactate and blood glucose levels were collected. Physiological variables, such as ICP, mean arterial pressure (MAP) and body temperature, were measured in real time and collected prospectively at the same time points. CPP was calculated as the difference between MAP and ICP. Vasopressors and insulin use, but not drug doses, were also recorded concomitantly with CSF samples.Blood gas analyses were performed at the same points, and arterial pH, PaCO2 < 35 mmHg; barbiturate therapy, decompressive craniectomy, hypothermia or a combination of these strategies).Therapeutic interventions used to reduce ICP were then classified as “tier 1”  or “tier 2/3” . An “increase” in CGLR was defined as ΔCGLR > 0.The primary outcome of the study was the difference in ΔCGLR between the two groups. Secondary outcomes included: (a) the effects of the type of therapy  on ΔCGLR; (b) the association of ICU mortality and unfavorable neurological outcome (UO) at 3 months on CGLR and ΔCGLR.This was an exploratory study. An initial cohort of 21 patients was studied as a pilot phase to assess the feasibility of the two measurements, which showed that the CGLR was reduced by 15% among patients receiving an intervention, remaining almost unchanged in control patients. As such, to obtain a significant difference in ΔCGLR between the two groups, a total of 60 patients would be needed . However, considering that interventions might provide different effects on ΔCGLR and to avoid bias in recruiting control patients, a cohort of at least 150 patients was considered adequate to evaluate the study hypothesis.th–75th percentiles], as appropriate. Differences between the two groups  were assessed using a chi-square or Fisher’s exact test for categorical variables and a t test  or a Mann–Whitney U test (independent nonparametric data) or Wilcoxon signed-rank test (nonparametric related data) for continuous variables. To account for repeated measures, ΔCGLR in the two groups were assessed using a mixed linear model, which considered the time (baseline vs. 2 h) and group (intervention vs. control) in the final analysis, both as categorical variables. A similar model was applied for other physiological and CSF variables. Univariable and multivariable linear models were constructed to assess the association of baseline variables and the percentage of ΔCGLR.Descriptive statistics were computed for all study variables. A Kolmogorov–Smirnov test was used, and histograms and normal-quartile plots were examined to verify the normality of the distribution of continuous variables. Data were presented as count (percentage), mean (± standard deviation) or median  vs. 2 h: 1.55 (1.11–2.02), p = 0.005] and the intervention  groups. The trend of CGLR over time was similar between groups in TBI, ICH and SAH patients, as shown in Additional file 1In TBI patients . The administration of osmotic agents and tier 2/3 therapies significantly increased CGLR, while CSF drainage and sedation resulted in marginal CGLR changes. Finally, a lower CGLR at baseline was independently associated with ICU mortality and unfavorable neurological outcome at 3 months.CSF analysis has an important role in the management of several infectious and non-infectious neurological conditions, as it provides information on the presence of blood, inflammation, infection as well as degenerative diseases , 32–35. To the best of our knowledge, this is the first study to address the impact of ICP-directed therapies on CGLR, although different studies have shown a decrease in the lactate-to-pyruvate ratio (LPR) measured by CMD when specific therapies to reduce ICP were given , 39. We We believe that our findings have important clinical relevance. First CGLR assessment can identify patients with a more relevant brain injury, as suggested by the prognostic value of CGLR , 39. ThiRegarding CSF analysis, Fujishima et al. demonstrated an increase in CSF lactate and LPR immediately after the injury, followed by a gradual reduction in the following weeks, especially in patients with unfavorable outcomes ; CSF lacThe present study has several limitations. First, we did not concomitantly collect data from CMD catheters and, therefore, could not compare the predictive value of glucose and lactate sampled using the two different techniques. Moreover, we did not measure pyruvate in the CSF, which can also be an interesting marker to be assessed. Secondly, we collected paired CSF glucose and lactate only once per patient; although the study did not focus on this issue, repeated CSF measurements could increase the risk of infections and it would be difficult to propose such daily strategy in ABI patients. Third, we did not evaluate the potential causes of low CGLR  in our study cohort. Fourth, the delay between admission and CGLR assessment was not the same for all patients, which could have also impacted our results. Fifth, we included different acute brain injury etiologies with different pathophysiology which can have influenced our results. Sixth, we did not account for differences in the intensity of treatment throughout the ICU stay and specially in the first 72 h. Finally, CSF glucose and lactate measurements were not performed using the same analyzers; although this might potentially influence the absolute values, CGLR (as a ratio) and relative changes over time (as glucose and lactate would be measured on the same device) should be unaffected.In this study, CGLR increased over time in the two groups. These effects were more significant in those patients receiving ICP-directed therapies, in particular osmotics or tier 2/3 therapies. These findings also confirmed that low CGLR measured in the first 72 h after ABI was a marker of poor prognosis.Additional file 1. Supplemental electronic material of STAR-TRIP study.


Importantly, NSPT significantly reduced the blood level of CRP (p < 0.02). However, no significant reduction in BP parameters was noted in the evaluated follow-up periods. NSPT, despite the benefits in periodontal clinical parameters, reduced the plasma level of CRP but not the BP in patients with combined RAH and periodontitis.We sought to evaluate the effects of non-surgical periodontal treatment (NSPT) on periodontal clinical parameters, systemic blood pressure (BP), and plasma levels of systemic inflammation markers in patients with combined refractory arterial hypertension (RAH) and stage III grade B periodontitis. Twenty-seven participants with RAH and periodontitis received NSPT. The analyzed clinical parameters were probing depth (PD), clinical attachment level (CAL), bleeding on probing (BOP), and plaque index (PI). An assessment was performed for systemic BP, complete blood count, coagulogram, creatinine measurement, C-reactive protein (CRP), glycated hemoglobin, cholesterol, glutamic oxaloacetic transaminase, glutamate pyruvic transaminase, waist–hip ratio, and body mass index. In the follow-up period, twenty-two patients were evaluated at baseline and after 90 and 180 days. The data were submitted for statistical analysis (α = 0.05%). As expected, the clinical results showed a significant improvement in the percentages of PI, BOP, PD, and CAL, which were statistically significant at 90 and 180 days ( Arterial hypertension (AH), a complex multifactorial clinical condition, is characterized by an elevation of blood pressure at levels ≥ 140 and 90 mmHg . CardiovPeriodontitis is a multifactorial chronic inflammatory disease associated with a dysbiotic biofilm and characterized by the progressive destruction of supporting periodontal tissues . DysbiosP. gingivalis, from the ulcerated epithelium through the bloodstream has been found in circulating leukocytes and was also found in atherosclerotic plaques acting as a pro-atherogenic stimuli  [Participants underwent analysis of the waist–hip relationship (WHR = waist [cm] ÷ hip [cm]) using a tape measure, considering limit values for men and women at 0.85 and 0.90, respectively . Further2 [m2] .A specialized clinical analysis laboratory collected peripheral blood samples 7 days before the clinical evaluations. The requested tests were complete blood count, coagulogram, CRP, fasting and estimated blood glucose, glycated hemoglobin (HbA1c), total cholesterol, oxalacetic glutamic transaminase (OGT), pyruvic glutamic transaminase (PGT) and creatinine. The determination of positive CRP was characterized by levels equal to or above 6 mg/l, with indices below that threshold considered negative . The aboFifteen days before treatment, the clinical periodontal examinations were performed (baseline) using a millimeter periodontal probe . Immediately after this procedure, participants received detailed information about the etiology of periodontal disease and oral hygiene instructions (OHI), including toothbrushes, dental floss, and interproximal brushes as needed. This instruction was repeated at each visit.The initial treatment of periodontitis consists of the NSPT of subgingival instrumentation (SI) in combination with OHI . SI refeOne week after SI, all participants were visually inspected to assess possible undesirable signs and symptoms. Subsequently, follow-ups took place after 90 and 180 days, during which clinical exams were performed and laboratory tests requested, following the same parameters as in the initial exams. In these reassessments, supragingival plaque control and OHI were given according to each participant’s needs ,32.Based on previous studies ,32, sampThe demographic data, periodontal clinical parameters, complementary exams obtained from blood tests, physical exams, and BP were submitted to descriptive and analytical statistical analysis using software package . The data showed a normal distribution after the normality test (Shapiro–Wilk). Periodontal clinical variables, blood tests, and physical and BP data were compared between periods  and presented as means and standard deviation (SD). The data were then submitted to the ANOVA test, followed by Tukey’s post hoc test. The categorical variable CRP was compared using the chi-square test. All analyses were performed at a significance level of 5%.A linear regression analysis was performed with the help of STATA 12.0 for Windows  to evaluate the effects of the different periods on the periodontal clinical parameters, biochemical and physical exams, and BP parameters. Logistic regression analysis was then performed to evaluate the effect of different periods on periodontal clinical parameters  and SBP and DBP. The results were binary (presence or not): (i) severity of the periodontal disease, with a predominance of deep pockets  ; or (ii)In the pre-experimental period, the examiner’s calibration procedures were performed through a clinical periodontal evaluation of six participants. PD and CAL parameters were obtained on two separate occasions . Data were tabulated and submitted to the Kappa agreement test . The obtFollowing the initial screening, 129 participants were recruited . Of thesThirteen men and fourteen women aged 45 to 71 years underwent NSPT and were individually informed about the nature of the study and signed an informed consent form. During the follow-up visit, five participants were excluded due to antibiotic use (2) and non-attendance at follow-ups (3). Thus, the final assessment in 90 and 180 days consisted of 22 participants .The antihypertensive drugs most used by the participants were losartan (63.3%) and atenolol (15.40%). Regarding diuretics, 45.45% of the participants used hydrochlorothiazide, and 22.72% used furosemide. Regarding anticoagulants, 18.18% used the drug acetyl salicylic acid. To reduce blood cholesterol levels, 45.45% of the participants used simvastatin, and for glycemic control, 18.18% used metformin.p = 0.11) and CAL ≥ 6 mm (p = 0.59), no significant difference between the evaluated periods was found . Regarding CAL ≥ 6 mm, no significant differences were found at 90 days , or 180 days .p > 0.05). No significant reductions were observed at 90 and 180 days, when compared to baseline, in the data of SBP (p = 0.28), DBP (p = 0.39), mean arterial pressure , and differential pressure  and 180 days , or in the DBP at 90 days  and 180 days  and BMI (p = 0.98) between the evaluation periods . Thus, residual confounders can affect the degree of these associations. Importantly, this connection may also be driven by an association between BP changes and other undetected sources or chronic infections . PeriodoGood periodontal health may be associated with better BP control during antihypertensive treatment . The effp = 0.00). These finds indicate that NSPT decreases the chances of generalized gingival inflammation in all experimental periods.In the logistic regression analysis, aimed at the categorization of periodontal disease according to its severity, it can be observed that at both assessment points, patients had lower chances of ≥30% sites with BOP (OR 0.02, 95%CI 0.002–0.29, Porphyromonas gingivalis can cause elevated blood pressure, vascular inflammation, and endothelial dysfunction [The identification of periodontitis as a possible risk factor for hypertension can be explained by some mechanisms . Periodofunction . CRP is elevated in hypertensive patients, being one of the determinants of systemic inflammation caused by AH . FurtherThe effects of periodontal treatment on the plasma levels of inflammatory markers are described in the literature. Some studies have shown that plasma and/or serum levels of IL-6, fibrinogen, CRP, other proteins, and interleukins decrease after NSPT in individuals with CVDs , coronarRegarding the biochemical tests for total cholesterol, creatinine, OGT, and PGT after NSPT, it was observed that NSPT did not result in any beneficial effect. Furthermore, NSPT did not influence the levels of HbA1c, estimated glycemia, and fasting glycemia in individuals with RAH. Some studies have demonstrated an improvement in the control of HbA1c levels in diabetic patients following NSPT ,55. TherOur study did not show statistically significant reductions in the physical examinations of WHR and BMI after NSPT in individuals with RAH. The literature has indicated that obesity plays a role in developing AH and CVDs . Some stSubgingival periodontal bacteria levels were directly correlated with SBP and DBP and the prevalence of hypertension . AnotherRecent meta-analyses have shown that regular aerobic and aquatic exercises can significantly reduce SBP . PietropThis prospective interventional clinical study possesses some important caveats. One is the impossibility of controlling variables that can affect the control of systemic AH, such as changes in the use of antihypertensive drugs, diet, or the individual’s emotional state. The present study was carried out during the Covid-19 pandemic, which may have significantly influenced the control of patients’ systemic BP due to the effects of stress, changes in eating and dietary habits, use of medication, a lack of medical control, and a decrease in physical activity . FinallyWithin the limits of this study, it can be concluded that NSPT effectively improved periodontal clinical parameters and reduced the plasma level of CRP but did not interfere with systemic BP parameters in individuals with combined stage III periodontitis and RAH.


Multiple tissue perfusion markers are described to guide therapy in critically ill pediatric patients undergoing congenital heart surgery. Given the advantages of capillary refill time, our goal is to determine its predictive capacity for mortality and postoperative extracorporeal oxygenation requirements in congenital heart surgery and compare it to serum lactate. We conducted a prospective cohort observational study in a single high-complexity university hospital. Serum lactate and capillary refill time were measured at five predetermined time points: preoperative, immediate postoperative, 6, 12, and 24 h after the surgery. Prolonged immediate postoperative, 6 h, and 12 h capillary refill time measurements turned out to be independent risk factors for both outcomes. The capillary refill time area under the curve ranged between 0.70 and 0.80, while the serum lactate resulted between 0.79 and 0.92 for both outcomes. Both tissue perfusion markers resulted in mortality and extracorporeal oxygenation requirement predictors. Given the advantages of capillary refill time over serum lactate, a monitoring strategy including these two perfusion markers should be considered for congenital heart surgeries. The assessment and monitoring of tissue perfusion is mandatory in congenital heart surgeries (CHS) . MultiplCentral venous oxygen saturation, another widely used biomarker, requires serial measurements with invasive devices and is unreliable in residual intracardiac shunts ,8. CapilThe use of CRT has been mainly studied in adult patients ,13,14,15A prospective observational study was conducted in la Fundación Valle Del Lili in Cali, Colombia. All pediatric patients (under 5 years of age) undergoing CHS between November 2020 and May 2022 were included. Patients with any oncoproliferative disease or low-complexity heart surgeries with no perioperative extracorporeal circulation requirement were excluded.Initially, the medical history was queried for patient demographics and pre-operative clinical status. We identified the age, sex, weight, height, surgery condition, medical history, preoperative laboratories, and risk adjustment for CHS (RACHS-1). SL and CRT were measured at predetermined time points; preoperative (PO), immediate postoperative (IPO) (on admission to the pediatric ICU), at 6, 12, and 24 h after the surgery. Each patient was assigned a study ID to ensure anonymity. The data corresponding to the outcomes in the first 24 h were collected by the critical care physician on duty in the case report forms (CRF) of the study. The outcomes after 30 days were obtained by reviewing the clinical history of the subjects who remained hospitalized. The collected CRF were transcribed in a clinical database management system of the institution by the researchers, a platform for protected data collection.All CRT measurements were performed by 2 individuals  after standardizing the measurement technique. Twenty-five percent of the measurements were corroborated by a researcher, obtaining a 100% concordance. The measurement was performed by applying firm pressure to the right heel with a glass see . If not For induction of anesthesia, a combination of sevoflurane  and either dexmedetomidine (0.3–0.8 mcg/kg/h) or fentanyl (1–3 mcg/kg/h) was used. For neuromuscular blockage, rocuronium was administered in a dose range of 0.6–1.2 mg/kg. Mechanical ventilation was performed with a tidal volume of 6–8 mL/kg and a ventilatory frequency aimed at achieving an end-tidal carbon dioxide level between 35 and 45 mmHg.Blood reservation included one unit of fresh frozen plasma plus one unit of packed red blood cells (RBC) or fresh whole blood for purging the extracorporeal circulation machine (approximately 150 mL). From this blood, before the start of ECMO, one or two 60 mL syringes were provided for exclusive use by the cardiovascular anesthesiologist. In RACHS-1 ≥ 4 surgeries one unit of plateletpheresis (approximately 150 mL) and 4 units of cryoprecipitate were requested. Platelets were administered to all children under 8 kg (kg) undergoing RACHS-1 ≥ 4 surgeries (10 cc/kg). Cryoprecipitate was given to all children under 6 months undergoing RACHS-1 ≥ 4 surgeries (10 cc/kg) to achieve a fibrinogen level greater than 200 mg/dL. To avoid fluid overload, platelets and cryoprecipitate were administered while ultrafiltration was performed (approximately 15 min). Prothrombin Complex Concentrate (octaplex and blood clotting factors II-VII-IX-X) was available for massive bleeding, aorta surgeries, or at the discretion of the anesthesiologist.In RACHS-1 ≥ 4 surgeries cell saver was performed. The recovered cells were taken to the ICU but expired 4 h after being processed. The cell salvage removed 92% of the heparin and potassium and had an average hematocrit of 60%.The administration of inotropes and vasoactive medications was based on hemodynamic variables, echocardiographic monitoring, and perfusion monitoring . For surgeries with RACHS-1 ≥ 3, milrinone was administered at a dose of 0.4–1.2 mcg/kg/min. The vasoactive medications we used were epinephrine at a dose of 0.03–0.2 mcg/kg/min, vasopressin at a dose of 0.002 UI/kg/min (preferred in patients with pulmonary hypertension), and norepinephrine at a dose of 0.05–0.2 mcg/kg/min.p < 0.05 for all tests. Analyzes were carried out in R V.4.1.1  through RStudio V.1.4.1717.A descriptive analysis was made. The normality of continuous variables was analyzed using the Shapiro–Wilk test and a box plot. If the assumption of normality was rejected, data were reported as median (interquartile range (IQR)). Categorical variables were expressed in number and percentage. The receiver operating characteristic (ROC) curve was used to assess the ability of different SL levels and CRT to predict 30-day mortality and the postoperative requirement of ECMO. To identify the cut-off points (COP), which refers to the value closest to the point of maximum sensitivity and specificity, the Youden J index was calculated as J = sensitivity + (specificity − 1). Sensitivity (S), specificity (Sp), and predictive values  were calculated for each measurement time. A problem that appears frequently when applying logistic regression to small data sets is a partial or total separation, which results in the non-existence of maximum likelihood estimators . LogistiEthical considerations: This study was approved by the Institutional Ethics Committee  following national and international recommendations for human research. In accordance with resolution 8430 of 1993, this study was considered risk-free, and the waiver of informed consent was requested and obtained.Six hundred measurements of SL and CRT of 120 pediatric patients undergoing CHS were analyzed. The median age of the participants was 4.5 months  and 50% were male. The most common age group was infants (54.2%), followed by newborns (25%) and toddlers (20.8%). Thirty-five percent of the patients had low weight-for-height and 22.5% were preterm (birth < 37 weeks). Regarding the outcomes evaluated, 12 (10%) patients died and 16 (13.3%) required ECMO after surgery . Mortalip = 0.001) and at 12 h . The OR of SL ranged between 1.30 and 1.51, being more significant at 6 h . For the ECMO requirement, the CRT obtained an OR between 1.63 and 3.03 with a greater predictive capacity at 6 h  and at 12 h . The OR of lactate ranged between 1.22 and 2.04, being more significant at 24 h . Both perfusion markers at the different measurement times were statistically significant   between 1.57 and 4.31 with a greater predictive capacity at 6 h  1.54–6.27,  < 0.05) .In the multivariate analysis for mortality, PO, 6 h and 24 h SL, and IPO, 6 h and 12 h CRT maintained statistical significance . RegardiOverall, SL obtained a higher area under the curve (AUC) than CRT for both outcomes . The AUCThis observational study in pediatric patients undergoing CHS showed that both CRT and SL were associated with 30-day mortality and the need for postoperative ECMO. IPO, 6 h, and 12 h CRT turned out to be independent risk factors for both outcomes, and at 24 h for postoperative ECMO requirement. In addition, the AUC of CRT showed an acceptable discriminative capacity for the two outcomes, with better performance at IPO and 12 h for mortality. Similarly, Shaker et al. found better predictive values of CRT at 6 and 12 h than in other measurement times in patients with abdominal sepsis  and Moron = 34) conducted by Shaker et al. in adult patients with abdominal sepsis [We used the Youden index to identify the optimal COP point at the different measurement times. Other studies have reported similar optimal COP found in our study . Morochol sepsis .SL turned out to be an independent risk factor for both outcomes except at IPO and 12 h measurements for 30-day mortality and ECMO requirement. We found an inversely proportional relationship between the measurement time and the COP. Likewise, Fuernau et al. reported an initial SL COP of 5 mmol and a COP of 3.1 mmol/L at 8 h in cardiogenic shock . ScolariThe normal SL clearance is one of the possible reasons that explain why both tissue perfusion markers are not abnormal at the same time point and differ in the significance timing. Other possible causes include the factors that can influence SL such as muscle activity, medications, or medical conditions, especially in type B lactic acidosis, which is caused by an impairment of the body’s ability to clear lactate production . In addiEven though the SL AUC showed a better discriminative capacity for both outcomes, the multivariate analysis suggests that the CRT has a better independent predictive capacity at IPO and 12 h, which has also been reported in some studies ,12. LikeOur study is a starting point, in which the utility of the CRT is proven, and it may have the potential to suggest a different approach regarding the use of perfusion markers for monitoring pediatric CHS. Serum lactate remains the main marker of tissue perfusion in CHS; however, phlebotomy blood losses play a key role in anemia and the need for RBC transfusions , especiaThe subjective measure of CRT is controversial, and it can be unreliable . HoweverAmong the strengths, this is the first study in which the predictive capacity of SL and CRT was measured for mortality and the ECMO requirement in patients undergoing pediatric CHS. Moreover, a strict and reproducible method was used for the measurement of the CRT. The research team was trained to apply the same measurement technique, using a specific instrument to apply pressure  and a stBoth CRT and SL were related to 30-day mortality and the need for postoperative ECMO in pediatric patients undergoing CHS. CRT is a reliable perfusion clinical marker and, given its advantages over other biomarkers that require blood samples, it should be included as a monitoring tool. A combined SL and CRT monitoring strategy will likely decrease the serial blood sample complication risks without negatively impacting the outcomes.