The objective of this study is to explore the risk factors of cardiovascular and cerebrovascular events (CCE) in patients with diabetic nephropathy (DN) receiving maintenance hemodialysis, and to establish a nomogram model on this basis.  144 patients with DN receiving maintenance hemodialysis from February 2020 to February 2021 were selected and followed up for 12 months. They were divided into the occurrence and nonoccurrence groups according to whether CCE occurred. The multivariate logistic regression analysis was used to analyze the influencing factors of CCE, and a predictive nomogram model was established. The receiver operating characteristic (ROC) curve was drawn to evaluate the predictive effect of the nomogram model. The Hosmer-Lemeshow method was used to test the calibration degree. μmol/L, and albumin (ALB) level <40 g/L were independent risk factors for CCE. Based on the above independent risk factors, a nomogram model of CCE was created. ROC curve analysis showed that the area under curve for predicting CCE was 0.881 (95% CI: 0.833~0.919), indicating that the nomogram model had great predictive effect. The Hosmer-Lemeshow method showed that the calibration curve was in good agreement with the standard curve.  Among the patients, 63 patients (43.75%) encountered CCE. Multivariate logistic regression analysis showed that age >60 years old, history of CCE, dialysis age >12 months, systolic blood pressure >140 mmHg, blood phosphorus level >1.5 mmol/L, triglyceride (TG) level >2.30 mmol/l, adiponectin (ADPN) level <5 mg/L, high-sensitivity-C-reactive protein (hs-CRP) level >10 mg/L, hemoglobin (Hb) level <120 g/L, serum creatinine (SCr) level >720  Age, history of CCE, dialysis age, systolic blood pressure and serum phosphorus, and TG, ADPN, hs-CRP, Hb, SCr, and ALB levels are all influencing factors for the occurrence of CCE in patients with DN receiving maintenance hemodialysis, and the nomogram model has a great predictive effect on CCE. Diabetic nephropathy (DN) is a common microvascular complication of diabetes, with its incidence increasing in recent years. It has various clinical manifestations, mainly including edema, proteinuria, and hypertension, and may result in renal failure in severe cases, which is one of the main causes of end-stage renal disease, seriously threatening the lives of patients , 2. At pA nomogram model is satisfactorily accurate, visual, and easy to understand and can be used to predict disease outcomes . A relatBased on the approval from the Ethics Committee of Huidong People's Hospital (2022-034), 144 patients with DN receiving maintenance hemodialysis, who have been admitted to the hospital during the period from February 2020 to February 2021, were selected.Diagnosis and Treatment of Diabetic Nephropathy [Inclusion criteria are as follows: patients who ① met the relevant criteria specified in hropathy , and werExclusion criteria are as follows: ① renal transplant recipients; ② patients with severe infection, peritoneal dialysis or malignant tumor, liver and lung and other serious chronic diseases; ③ complicated with respiratory failure or basic diseases of the nervous system; ④ pregnant or lactating; and ⑤ patients with infectious diseases and mental history.Elimination criteria are as follows: ① patients who lost to follow-up and ② patients who died due to other diseases or accidents.+ concentration of 2.00 mmol/L and a Ca2+ concentration of 1.50 mmol/L, and a speed of 500 ml/min, and low-molecular-weight heparin calcium injection and heparin sodium injection were used for anticoagulation. All patients were monitored in real time during treatment and given other basic treatments, such as correction of anemia, control of blood pressure, and correction of calcium-phosphorus metabolism disorder.All patients were treated with 4008 s dialysis machines  and disposable polysulfone membrane dialyzers for maintenance hemodialysis. They received dialysis three times a week, with a period of 4-4.5 h each time. An autologous arteriovenous fistula or a semi-permanent central venous catheter was used as vascular access. Dialysis was performed with standard bicarbonate dialysate (Sangon Biotech (Shanghai) Co., Ltd.) at a blood flow velocity of 200-250 ml/min, a dialysate KClinical data were collected on admission, including gender, age, body mass index (BMI), diabetes duration, diabetic nephropathy duration, smoking history, history of cardiovascular and cerebrovascular diseases, blood pressure, and dialysis age.When the patients were enrolled and every 3 months after enrollment, the laboratory indexes were examined. Fasting veins were collected from all patients before dialysis. After each patient got up in the morning and rested for 15 minutes, they continuously measured the upper limb arterial blood pressure three times with an electronic sphygmomanometer  Co., Ltd.). Systolic and diastolic blood pressure was recorded before dialysis, and peripheral venous blood was collected. Then, the blood samples were separated, and the levels of blood triglyceride (TG), serum phosphorus, serum adiponectin (ADPN), high-sensitivity C-reactive protein (hs-CRP), hemoglobin (HB), serum creatinine (SCR), and serum albumin (ALB) were detected by enzyme-linked immunosorbent assay  and automatic biochemical analyzer.We included cardiovascular and cerebrovascular events after hemodialysis as a result. Cardiovascular and cerebrovascular end points in DN patients included myocardial infarction, heart failure, malignant arrhythmia, ischemic heart disease, sudden death, and cerebral infarction. Patients with cardiovascular and cerebrovascular events were divided into occurrence groups, and other patients were divided into nonoccurrence groups.χ2 test. Multivariate logistic regression analysis was used to analyze the risk factors for cardiovascular and cerebrovascular events in DN patients receiving maintenance hemodialysis. A nomogram model was created based on the risk factors, and the receiver operating characteristic (ROC) curve was used to assess the effectiveness of the nomogram model in predicting cardiovascular and cerebrovascular events in diabetic nephropathy patients receiving maintenance hemodialysis. If P < 0.05, the difference was statistically significant. The Hosmer-Lemeshow method was used to test the predictive effect of the nomogram model; when P > 0.05, it indicated a great degree of calibration.The SPSS26.0 software was used for statistical analysis. The measurement data was described with mean ± standard deviation (SD) and tested with Student's t-test. And the count data was described with “%” and compared with 2, with an average of 23.27 ± 2.06 kg/m2; their courses of diabetes ranged from 1 year to 9 years, with an average of 60.41 ± 10.04 months; their courses of diabetic nephropathy ranged from 9 months to 6 years, with an average of 50.06 ± 8.35 months; and their dialysis ages ranged from 6 months to 4 years, with an average of 26.32 ± 4.34 months.Among the 144 patients with DN receiving maintenance hemodialysis enrolled in this study, these patients were aged 50-72, with an average age of 60.48 ± 10.06; their BMI was within a range of 18.45-28.12 kg/mP > 0.05). The constituent ratios of patients who had a history of cardiovascular and cerebrovascular diseases, a dialysis age >12 months, and a serum adiponectin (ADPN) level <5 mg/L in the occurrence group were higher than those in the nonoccurrence group (P < 0.05), and the ages and hs-CRP, systolic blood pressure, blood phosphorus, TG, and SCr levels of the patients in the occurrence group were higher than those in the nonoccurrence group (P < 0.05); the Hb and ALB levels of the patients in the occurrence group were lower than those in the non-occurrence group (P < 0.05) . There was no statistically significant difference in gender, BMI, course of diabetes, course of diabetic nephropathy, smoking history, and diastolic blood pressure between the occurrence group and the nonoccurrence group  , and it is found that the calibration curve was in good agreement with the standard curve, as shown in A nomogram model for predicting the risk of cardiovascular and cerebrovascular events in patients is created with the 11 independent risk factors screened by multivariate logistic regression analysis as predictors, as shown in DN is caused by long-term abnormal glucose metabolism, which results in decreased glomerular filtration rate and glomerular sclerosis, and thus leads to damage to renal functions, causing great harm to the health of patients . At presIn this study, it was found through logistic regression analysis that age, history of cardiovascular and cerebrovascular diseases, dialysis age, systolic blood pressure and serum phosphorus, and TG, ADPN, hs-CRP, Hb, SCr, and ALB levels are all influencing factors of the occurrence of cardiovascular and cerebrovascular events in diabetic nephropathy patients receiving maintenance hemodialysis. With the increase in age, patients experience a decline in bodily functions and a decrease in the elasticity of arterial vascular walls and often suffer from various underlying diseases, so their tolerance to maintenance hemodialysis decreases, and the probability of the occurrence of cardiovascular and cerebrovascular events increases. With the increase in dialysis age, the retention of toxins caused by the disease, the increase in volume load, and the hemodynamic changes during dialysis have adverse effects on the cardiac functions of the patients, leading to the gradual deterioration of their cardiac functions. As the dialysis age increases, the risk of developing dialysis-related amyloidosis increases, and the risk of the occurrence of cardiovascular and cerebrovascular events increases accordingly. When patients had a history of cardiovascular and cerebrovascular diseases, they might suffer cardiovascular and cerebrovascular damage, so the probability of cardiovascular and cerebrovascular adverse events was higher, which was consistent with relevant reports . HyperteA nomogram model draws multiple predictors on one plane based on multifactor regression analysis and can get the predicted probability of each individual's outcome according to the corresponding algorithm, which is highly operable and accurate . In thisTo sum up, age, history of cardiovascular and cerebrovascular diseases, dialysis age, systolic blood pressure and serum phosphorus, and TG, ADPN, hs-CRP, Hb, SCr, and ALB levels are all influencing factors of the occurrence of cardiovascular and cerebrovascular events in diabetic nephropathy patients receiving maintenance hemodialysis, and the nomogram model created on this basis has a great predictive effect on cardiovascular and cerebrovascular events in diabetic nephropathy patients receiving maintenance hemodialysis, which can provide significant guidance in clinical practice.


N-acetyl-d-glucosamine. Our kidney biopsy-based study showed that the liver fibrosis markers fibrosis-4 index and non-alcoholic fatty liver disease score were negatively correlated with the estimated glomerular filtration rate in nephrosclerosis and IgA nephropathy.Non-alcoholic fatty liver disease is the most common chronic liver disease and is associated with chronic kidney disease. The fibrosis-4 index and non-alcoholic fatty liver disease score are widely used as non-invasive diagnostic methods for non-alcoholic fatty liver disease. However, the relationship between these markers and specific renal histopathologies in chronic kidney disease remain unclear. This study included 179 patients aged between 16 and 80 years who underwent renal biopsy. We examined the association between the fibrosis-4 index or non-alcoholic fatty liver disease score and change in estimated glomerular filtration rate 12 months after kidney biopsy for each renal histopathology. Renal histopathologies were determined by renal biopsy. Our results showed that there was a significant negative correlation between the fibrosis-4 index and estimated glomerular filtration rate. In nephrosclerosis, the non-alcoholic fatty liver disease score and estimated glomerular filtration rate tended to have a negative correlation, albeit without significance. In IgA nephropathy, both the fibrosis-4 index and non-alcoholic fatty liver disease score were significantly negatively correlated with estimated glomerular filtration rate. Furthermore, the fibrosis-4 index was not associated with urinary protein-to-creatinine ratio or renal function markers such as urinary b2 microglobulin and urinary  Obesity and insulin resistance are the most common causes of CKD3. It has been reported that non-alcoholic fatty liver disease (NAFLD) is a clinicopathological condition that encompasses a variety of chronic liver diseases ranging from asymptomatic hepatic fat accumulation to progressive liver disease, with clinical symptoms resembling alcoholic liver disease despite the absence of excessive alcohol consumption5. A recent study revealed that the prevalence of NAFLD diagnosed by ultrasound was estimated to be about 25%6. It is estimated that either NAFLD or non-alcoholic steatohepatitis (NASH) will be the most common indication for liver transplantation by 20307. NAFLD is a multisystem disease that is associated with various diseases such as diabetes mellitus, obesity, metabolic syndrome, cardiovascular diseases, and CKD8. The fibrosis-4 (FIB-4) index and NAFLD fibrosis score (NFS) are simple and validated diagnostic markers used to stratify the degree of liver fibrosis according to risk in patients with suspected NAFLD9. Moreover, these non-invasive fibrosis markers have been shown to be associated with the prevalence of CKD in recent studies10. However, there have been no reports on the association between these fibrosis markers and decreased estimated glomerular filtration rate (eGFR) by renal histopathology classification as determined by kidney biopsy. Thus, we performed this renal pathology-based study to elucidate whether the FIB-4 index and NFS can predict eGFR decline in CKD patients.Chronic kidney disease is associated with increased risks of mortality and morbidity. Furthermore, CKD is also associated with diabetes mellitus, including diabetic kidney disease (DKD)2; urine protein-to-creatinine ratio, 0.538; N-acetyl-β-d-glucosaminidase (urinary NAG), 8.9 IU/L; and urinary β2 microglobulin (urinary β2 MG), 198 mg/L  were female. The median body mass index was 22.7, and the median FIB-4 index was 0.96. The other median values are as follows: systolic blood pressure (SBP), 129 mmHg; diastolic blood pressure (DBP), 78 mmHg; serum creatinine (Cr), 76.02 mmol/L; blood urea nitrogen (BUN), 5 mmol/L; estimated glomerular filtration rate (eGFR), 64 mL/min/1.73 m2 = 0.1458, P < 0.01, Fig. 2 = 0.0164, P = 0.08, Fig. 2 = 0.0819, P = 0.08, Fig. 2 = 0.0483, P < 0.01, Fig. We calculated the FIB-4 index and eGFR before renal biopsy for all diseases. The results showed that there was a weak but negative correlation between the FIB-4 index and eGFR . In nephrosclerosis, we found that the FIB-4 index was more significantly negatively correlated with the rate of change in eGFR when examined in all cases including the low FIB-4 index (< 1.3) , resulting in greater variability.Our results showed that there was an association, albeit very weak, between the FIB-4 index and changes in eGFR. This may be due to the wide range of eGFR  acts via inflammation and protein kinase C to activate the expression of cytokines; NF-kB is transferred to the nucleus, promptly activating the subsequent transcription of tumor necrosis factor-α, vascular cell adhesion molecule 1, or interleukin-6 in the kidneys of CKD patients17.Recent studies have indicated that NAFLD could affect CKD, including DKD18. We reported that Smad1 signaling plays a significant role in increasing the extracellular matrix, such as type 4 collagen and α-smooth muscle actin, in mesangial cells19. Inflammatory processes inevitably cause damage; as part of the healing process, glomerulosclerosis increases the mesangial extracellular matrix, leading to a decreased glomerular filtration rate20. Our results showed that the FIB-4 index and NFS were negatively correlated with eGFR in nephrosclerosis and IgA nephropathy, which are both characterized by an increase in mesangial extracellular matrix.Previous reports have indicated that the activation of the TGF-β/Smad pathway is associated with the FIB-4 index and NFS21. Furthermore, we have reported the mechanisms of developing obesity-related CKD22. NAFLD is one of the most common causes of chronic liver disease in clinical practice in its entire spectrum of conditions, ranging from simple lipidosis to steatohepatitis and cirrhosis25. It has been reported that liver fibrosis and fatty liver are crucial in the development of DKD26. In contrast, another study using multivariate analysis showed that the presence of NAFLD was not a significant predictor of the development of DKD11. In this regard, the association between NAFLD and DKD remains inconsistent. Although patients in our study tended to be obese , we could not find any correlation between the FIB-4 index and eGFR in patients with type 2 diabetes.Obesity is the most common risk factor for NAFLD and an independent risk for developing CKD27, which is a mechanism of glomerulosclerosis caused by glomerular endothelial dysfunction17. Thus, the FIB-4 index may be more reflective of glomerulosclerotic lesions. In contrast, proteinuria, which is mainly caused by podocyte dysfunction, may not be associated with the FIB-4 index, which is associated with glomerular endothelial cells29.Unlike eGFR, there was no clear correlation between urinary protein or tubulointerstitial markers and FIB-4 index. It has been reported that the FIB-4 index may be associated with vascular endothelial functionThis study has several limitations. First, liver diseases, such as NASH or NAFLD, were not evaluated by imaging and liver biopsy. Second, we conducted a retrospective analysis of a cohort from a single center. Finally, some diseases, especially nephrosclerosis, had a small number of cases.The FIB-4 index and NFS, which are non-invasive fibrosis markers, could be predictive markers of reduced eGFR, especially in nephrosclerosis and IgA nephropathy.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The ethics committee of Osaka Medical and Pharmaceutical University approved this study . Written informed consent was obtained from all subjects. This study included a retrospective cohort of 179 cases who underwent kidney biopsy at Osaka Medical and Pharmaceutical University Hospital between April 2015 and July 2020. Data were collected and analyzed retrospectively by using electronic medical records maintained by the Department of Nephrology at Osaka Medical and Pharmaceutical University Hospital. Cr, BUN, eGFR, urine protein-to-creatinine ratio, urinary NAG, urinary β2 MG, and patient characteristics  were searched from the electronic medical records and kidney biopsy database. No diagnosis of fatty liver was diagnosed by liver biopsy or ultrasonography.Kidney specimens were obtained with a 16-gauge biopsy needle . Specimens were fixed in 10% formalin, and the prepared sections were stained with hematoxylin–eosin, Masson trichrome, periodic acid silver methenamine, or periodic acid-Schiff. At least three pathologists evaluated each specimen.30. NFS was calculated using the following formula: − 1.675 + 0.037 × age (years) + 0.094 × body mass index (kg/m2) + 1.13 × impaired fasting glucose/diabetes  + 0.99 × AST (IU/L) / ALT (IU/L)—0.013 × platelet (109/L)—0.66 × albumin (g/dL).The degree of liver fibrosis was evaluated by the FIB-4 index and NFS. FIB-4 was calculated using the following formula: age (years) × aspartate aminotransferase  / platelet (109/L) × √ alanine aminotransferase . High FIB-4 index group was defined as 1.3 or higherLevels of serum creatinine were measured in all samples using an enzymatic method in laboratories, and the values are represented using two decimal places. The eGFR of each patient was calculated using the following formula: 194 × serum creatinine − 1.094 × age − 0.287 × 0.739 . The rate of change in eGFR was used to evaluate renal function in each period and was calculated using the following formula: ((eGFR 12 months after kidney biopsy—eGFR before kidney biopsy))/eGFR before kidney biopsy) × 100.P < 0.05.Continuous variables are presented as medians. Comparisons were made between groups using the Mann–Whitney U test; categorical variables were presented as numbers (percentage) and compared using Pearson’s Chi-squared test and Fisher’s exact test, as appropriate. All analyses were performed using StatView  and Excel software. Statistical significance was defined as


BackgroundAcute kidney injury (AKI) is a syndrome that has been receiving considerable attention as a common risk in cardiac surgeries, which has consequences for short- and long-term survival implications, even for those who do not progress to renal failure. There have been limited studies in the Middle East, and specifically in the Kingdom of Saudi Arabia (KSA). Therefore, our study aimed to identify the prevalence of and risk factors for AKIs following adult cardiac interventions during 2010-2020 at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia.MethodsSetting and Design: A retrospective medical record review was conducted among all the adult patients who underwent cardiac interventions and developed AKIs between 2010 and 2020. Google forms were used to extract the data from the hospital records. About statistical analysis binary logistic regression analyses, relative risks (RRs), and confidence intervals (CI) were used to determine the associations among the variables.ResultsP < 0.012, RR = 2.280, CI = 1.198-4.339). Hypertension showed a strong effect in the development of AKIs . Moreover, patients who suffered from chronic heart failure were more prone to the development of AKIs . Furthermore, anemia with significant P-values (<0.002), and CIs of 1.509-6.822, indicated that these patients were more likely to develop AKIs (3.209 times).After applying the inclusion and exclusion criteria, 564 patients were included. Their baseline demographic, clinical, biological, and operative characteristics were analyzed. AKIs developed in 110 (19.5%) patients and patients with diabetes were more likely to develop AKIs (ConclusionWe demonstrated that AKIs are frequent complications in adults after cardiac interventions and were associated with poor outcomes. Risk factors for the development of AKIs were identified to be diabetes mellitus, hypertension, chronic heart failure, and anemia. Further investigation of this cohort is necessary to better understand the problem of kidney injuries. Acute kidney injury (AKI) is a syndrome that has been receiving considerable attention as a common risk in cardiac surgeries, which has consequences for short- and long-term survival implications, even for those who do not progress to renal failure . Additio2O, mechanical ventilation ≥9 hours, use of angiotensin converting enzyme inhibitors (ACEIs)/angiotensin-receptor blockers (ARBs), postoperative CVP <6 cmH2O, and hypotension [Nevertheless, AKI is reported to occur in up to 30% of patients who have undergone heart surgery, and 1% to 2% of those with heart surgery require renal replacement treatment (RRT) -21. Howeotension .Nonetheless, there have been limited studies in the Middle East, and specifically in the Kingdom of Saudi Arabia (KSA). Therefore, our study aimed to identify the prevalence and risk factors of AKIs following adult cardiac interventions during 2010-2020 at the King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia.Setting and designThis 10-year retrospective record review was conducted during May-June 2021 after receiving approval from the Research Ethical Committee at the College of Medicine, KAUH, Jeddah, KSA (Reference: 228-21). KAUH is a government tertiary healthcare center that serves all strata of society. The focus of our study was to first to identify the most significant risk factors that led to AKIs after cardiac interventions and then to determine its prevalence.Inclusion and exclusion criteriaWe included all the adult (>18 years) patients who underwent cardiac interventions and developed AKIs during the period of 2010-2020 at KAUH.Method and materialThe data were collected manually from our hospital information system, Phoenix , using Google Forms. After excluding patients with end-stage renal disease on regular dialysis, we extracted the following variables from 564 patients: medical record number, nationality, gender, age at the time of surgery, developed AKI after cardiac intervention (Yes-No), any associated comorbidities (diabetes mellitus (DM), hypertension (HTN), ischemic heart disease (IHD), chronic heart failure (CHF); malignancies: chronic kidney disease (CKD), cardiovascular disease (CVD), thyroid disease, autoimmune disease, peripheral vascular disease (PVD), chronic liver disease, liver cirrhosis, respiratory disease, anemia, hyperlipidemia, obesity, smoking), type of cardiac intervention (coronary artery bypass graft (CABG) or percutaneous transluminal coronary angioplasty (PTCA)), priority of surgery (elective or emergency), date and time of surgery, length of hospitalization, surgery duration, LVEF, patient BMI, and preoperative and postoperative lab assessment , preoperative Hb, preoperative hematocrit (HCT)).Statistical analysis usedMicrosoft Excel v16.0 was used to organize the data, which were then analyzed statistically using IBM SPSS Statistics for Windows . For the descriptive statistics, the continuous variables were summarized using means and associated standard deviations (SDs), while the categorical variables were presented using numbers and associated frequencies. The differences in the clinical characteristics and outcomes between patients with or without AKIs were tested using the student’s t-test for the continuous variables and a chi-square test or Fisher’s exact test for the categorical variables. Preoperative and intraoperative risk factors for kidney injuries were identified using univariable and multivariable logistic regressions, and the results were presented as relative risks (RR) with 95% CIs. P-values <0.05 were deemed significant.Patient population and sample attritionAfter applying the inclusion and exclusion criteria, 74 patients  were excluded and 564 patients were included. Their baseline demographic, clinical, biological, and operative characteristics were analyzed in this retrospective cohort study. We targeted those who developed AKIs after cardiac interventions in KAUH in Jeddah, Saudi Arabia, between 2010 to 2020.Demographic and descriptive characteristic of patientsIn the overall sample, the mean age was 61.6± 9.9 years, males were predominant 481 (85.3%) comparatively. Female patients accounted for 83 (14.7%) of the total number of patients, with 34.9% of them having AKIs  . Furthermore, HTN had a strong effect on the occurrence of AKIs . Moreover, patients who suffered from CHF were susceptible to AKIs . In addition, anemia showed a significant P-value (0.002), and these patients were more likely to progress to AKIs (3.2 times) with CIs between 1.509 and 6.822  to time 2; postoperative  = 12.595, P <0.000). On the other hand, using binary logistic analyses, we found no relationships between the preoperative hemoglobin (P = 0.779), BUN (P = 0.648), HCT (P = 0.979), and the development of AKIs, as shown in Table Prevalence of AKIsOne of the most important findings in our study was that the prevalence of AKIs after cardiac interventions was 19.5%. Studies that were conducted in other countries such as China , MalaysiHypertension and AKIIn our study, HTN was the most common comorbidity that the patient had before the intervention. The RR of HT was found to be very significant in our study and similar to two other studies that were conducted in Shanghai Renji Hospital, China  and the Diabetes mellitus and AKIIn our study, diabetes was the second most common comorbidity that the patients presented with significant P-values and results for its RR. While other studies that were conducted in China , the USAAnemia and AKIAnemia is one of the major comorbidities that contributed to the development of AKIs following the interventions. Additionally, studies conducted in the USA , MalaysiChronic heart failure and AKIPatients with CHF are in greater danger of AKIs. A previous study conducted at the University Hospital Vienna, Austria  and at tCABG surgeries and AKICABG surgery was the most common intervention that was performed in our study with the findings suggesting a relationship between CABG surgeries and AKIs. Furthermore, a study that was conducted in China showed a higher likelihood of the development of AKIs after CABG surgeries . AdditioAge and AKIIn this study, the mean age of the patients who developed AKIs was 63.05±10.03. Studies conducted in Sweden  and the Priority of surgery and AKIFrom the SPSS data analysis, emergency surgeries showed a significant correlation with elective surgeries. The Cleveland Clinic Foundation identified urgent surgery as an important factor in the development of AKIs . We consAKI and surgery durationWith respect to the surgery duration, this study did not show a relationship with AKIs. Furthermore, a study that was conducted in the USA  did not LimitationsThis study had a number of limitations, which should be taken into account when interpreting the findings. First, the study was retrospective in nature and was conducted at a single organization. This made the findings of the study prone to bias and it also limited its generalizability. Second, since the Phoenix system was established in 2013 at KAUH, we faced difficulties in obtaining patients’ information and laboratory tests from the period between 2010 and 2013. Third, we did not have an accurate measurement of the preoperative glomerular filtration rate, which indicated that some patients with preexisting mild renal disease may have been included. Fourth, the type of acute renal failures , as well as the stages of the AKI, could not be determined precisely due to poor documentation. Finally, due to the lack of urine output values, only the creatinine values were used to determine whether or not a patient met the criteria for AKIs.In summary, this study explored the relationship between cardiac interventions and AKIs in adults, between 2010 and 2020, at KAUH in Jeddah, Saudi Arabia. Acute kidney injuries are common complications in adults after cardiac interventions, especially after CABG surgeries, and they are linked to poor outcomes. According to our findings, DM, HTN, CHF, CKD, and anemia are risk factors associated significantly with the development AKIs in patients. Other studies have also indicated that patients who underwent cardiac surgeries with these risk factors had the potential to develop AKIs compared with healthy individuals. Moreover, we need to identify these risk factors and manage them appropriately to avoid the complication of cardiac interventions. Furthermore, we recommend being more aware of these comorbidities and not ignore them, to better understand the burden of kidney injuries.


We also administered the NIH cognitive toolbox (cognitive function), measured carotid‐femoral pulse‐wave velocity , and assessed ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human brain endothelial cells incubated with serum obtained from study participants. MCA PI was higher in patients with CKD vs. controls; however, normalized MCA blood velocity response to hypercapnia did not differ between groups. Similar results were observed in a validation cohort of midlife and older adults divided by the median estimated glomerular filtration rate (eGFR). MCA PI was associated with greater large‐elastic artery stiffness , worse executive function (trails B time), lower eGFR, and higher ex vivo ROS production. These data suggest that impaired kidney function is associated with greater cerebrovascular stiffness, which may contribute to the known increased risk for cognitive impairment in patients with CKD.Patients with chronic kidney disease (CKD) are more likely to die of cardiovascular diseases, including cerebrovascular disease, than to progress to end‐stage kidney disease. Cerebrovascular dysfunction, characterized by reduced cerebrovascular reactivity, cerebral hypoperfusion, and increased pulsatile flow within the brain, precedes the onset of dementia and is linked to cognitive dysfunction. However, whether impaired cerebrovascular function is present in non‐dialysis dependent CKD is largely unknown. Using transcranial Doppler, we compared middle cerebral artery (MCA) blood velocity response to hypercapnia  pulsatility index (PI) was higher, but cerebrovascular reactivity to hypercapnia was preserved in patients with non‐dialysis dependent CKD as compared to matched controls. MCA PI was positively associated with pulse‐wave velocity and ex vivo reactive oxygen species production from human brain endotheial cells incubated with serum from study participants and inversely associated with executive function. Further research is needed to confirm these results in larger cohorts and to delineate the mechanisms linking arterial stiffness, cerebrovascular function, and cognitive impairment in patients with CKD. Additionally, we assessed cognitive function, as well as large‐artery vascular function , circulating markers, and ex vivo nitric oxide (NO) and reactive oxygen species (ROS) production from human cerebrovascular endothelial cells treated with serum obtained from participants, as well as their association with measures of cerebrovascular function. We also sought to extend and confirm our findings to a validation cohort of midlife and older adults with varied kidney function. We hypothesized that participants with CKD would exhibit cerebrovascular dysfunction that associated with large‐artery stiffness, cognitive dysfunction, and differences in circulating markers, as well as ex vivo NO and ROS production from serum incubated brain endothelial cells.The primary goal of this study was to assess cerebrovascular function  in the assessment of all outcomes.2 using the Chronic Kidney Disease Epidemiology Collaboration (CKD‐EPI) equation , as well as kidney disease , cardiovascular disease, diabetes, and other chronic diseases, as assessed by self‐report, medical history and physical exam (including a resting 12‐lead electrocardiogram), and screening laboratories. Additional exclusion criteria in both groups were dementia, history of stroke, diagnosis of a major psychiatric disorder , medications likely to affect central nervous system functions , current diagnosis and treatment of major depression (based on DSM‐IV‐TR criteria for Major Depressive Episode), alcohol or other substance abuse (self‐report or undergoing treatment), significant sensory or motor deficits that would interfere with cognitive testing, active infection or antibiotic therapy, hospitalization in the last month, immunosuppressive therapy within the last year, body mass index (BMI) >40 kg/m2, current tobacco or nicotine use or history of use in the last 12 months, oral hormone therapy, cannabis use within 2 weeks prior to testing, and antioxidant and/or omega‐3 fatty acid use within 2 weeks prior to testing.Inclusion criteria for both the CKD and control group were: 50–80 years of age , confirmation of a suitable temporal window for cerebrovascular assessments, and the ability to provide informed consent. Participants with CKD had an estimated glomerular filtration rate (eGFR) of 20–59 ml/min/1.73 m2.1.22 and no recent changes in medications or health status. Participants in this validation cohort were divided in half based upon the median CKD‐EPI eGFR (86 ml/min/1.73 m2). While a slightly higher eGFR than the primary cohort, inclusion of the goal of the validation cohort provided some initial evidence that changes in cerebrovascular function occur early in the process of kidney function decline.To confirm our findings in the primary cohort, we assessed a validation cohort of participants in research studies at the University of Colorado Boulder Integrative Physiology of Aging Laboratory. The validation cohort was comprised of all individuals aged 50 years and older studied in the laboratory between June 2021 (when the current cerebrovascular measurements were established) and May 2022 . Participants were recruited through a recruitment database and community advertisement. These individuals were generally healthy midlife and older adults  and free from overt cardiovascular diseases and dementia, with a BMI <40 mg/m2.22.2.1A metabolic panel, complete blood count, and lipid panel were performed. Demographic data and medical history were collected by self‐report. Arterial blood pressure was measured in triplicate while seated at rest using an automated oscillometric machine.2.2.2MCA in response to a vasodilatory hypercapnic challenge  using transcranial Doppler  as described previously  to induce mild hypercapnia. For the primary cohort, each condition was recorded for 5 min in the seated position to achieve a steady‐state velocity with paced breathing using a metronome. For the validation cohort, assessments were made in the supine position, the duration of hypercapnia was 4 min, and breathing was self‐paced. MVMCA was determined for each condition by calculating the average MCAv over each cardiac cycle for the last minute of each condition. Percent ΔMVMCA was calculated as: [(hypercapnic MVMCA−normocapnic MVMCA)/(normocapnic MVMCA)] × 100 and used to compare cerebrovascular reactivity between groups.All measurements were made following standard recommendations including an overnight fast  calibrated to brachial artery blood pressure was used. Relative cerebrovascular reactivity was calculated as %ΔMVMCA/(hypercapnia ETCO2–resting ETCO2). Vascular conductance was calculated as MVMCA/mean arterial pressure for each condition. Percent Δ in MCA vascular conductance (VCMCA) was calculated as [(hypercapnic VCMCA–normocapnic VCMCA)/(normocapnic VCMCA)] × 100. Relative VCMCA reactivity was calculated as % ΔVCMCA/(hypercapnia ETCO2 – resting ETCO2).Breath‐by‐breath end‐tidal partial pressure of CO2 (ETCO2) was continuously monitored (Vacumed) and was used to normalize the MV(systolic) − MCAv(diastolic))/MVMCA as described previously 2, as described previously  was assessed in the semi‐seated position (45‐degree angle at the hips) using extracranial high‐resolution duplex ultrasound  to capture both diameter and time‐averaged mean blood velocity (MV) of the right internal carotid artery (ICA) and vertebral artery (VA) . ICA and VA diameter were measured over 30 s each during the diastolic phase of the cardiac cycle and averaged. CBF was calculated for each artery as follows: CBF = MFV × 2.2.3Carotid‐femoral PWV was measured as described in detail previously , interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor‐α (TNF‐α) (pro‐inflammatory cytokines), and monocyte chemoattractant protein  were measured using fasting plasma samples . Soluble CD14  was measured by ELISA using fasting serum samples . Enolase 2  was measured in fasting serum samples by ELISA . Superoxide dismutase  activity was measured in fasting serum samples .2.2.62) for 2 h in basal media supplemented with 10% subject serum. After serum exposure, cells were co‐incubated with the fluorescent probes CellROX Deep Red  to detect ROS production and DAR‐4 M‐AM  to detect NO production  were treated with serum from the primary cohort. HBECs  were plated in 96‐well culture plates and incubated under standard conditions . All data are reported as means ± SD or medians (interquartile range). ANCOVA was used to adjust for covariates when comparing outcomes between groups. Pearson's bivariate correlations and multiple linear regression were used to evaluate associations between variables and sex differences (group × sex interaction). Analyses were performed using SPSS 27 and statistical significance was set at p < 0.05 with a two‐sided alpha. As the data were considered hypothesis‐generating, adjustment was not made for multiple comparisons.Differences in variables between groups were assessed using independent samples t‐test. Based on a value of 5.26 ± 0.82 in the control group and 2.6 ± 1.18 in the kidney failure group, with an effect size of 2.20, 10 participants would be needed per group with 80% power and an α‐level of 0.05. As we anticipated that the effect size may not be as large for the difference between patients with non‐dialysis dependent CKD and controls, we increased the number of participants needed by 50% (to 15 per group).An effect size was estimated for a primary outcome of cerebrovascular reactivity based on a previous cross‐sectional study comparing patients with anemia secondary to kidney failure and healthy controls  were treated with antihypertensive agents not used by controls and were more likely to be treated with a statin.In the primary cohort, 20 participants with stage 3–4 CKD were assessed for eligibility and five were excluded from enrollment , for a total CKD cohort of 15. Twenty‐one control participants were assessed for eligibility and six were excluded from enrollment , for a total control cohort of 15. Healthy control participants had a lower BMI , or BMI (p = 0.0160), but not for hypertension (p = 0.250). However, resting MVMCA did not differ between groups . There was no difference in cerebrovascular reactivity between participants with CKD and healthy controls, whether expressed as %ΔMVMCA , relative cerebrovascular reactivity , %Δ VCMCA , or relative MCA VC reactivity . Peak ETCO2 also did not differ between groups . Total CBF was not significantly different in the CKD group as compared to the control group .Participants with CKD had a 32% higher MCA PI as compared to healthy controls  for PI. The group difference in MCA PI was significant in males , but not in females , albeit sample size was greater in males. Estimated GFR was inversely correlated with MCA PI .There was a significant group × sex interaction (3.1.3p = 0.0330). Carotid‐femoral PWV was positively correlated with MCA PI .Consistent with previous reports, carotid‐femoral PWV was greater in participants with CKD as compared to healthy controls . Hemoglobin was correlated with uncorrected processing speed , which also persisted after correction for age, sex, eGFR, and education .Participants with CKD had a slower time on the trail making part B test but did not significantly differ in NIH toolbox cognitive test scores as compared to healthy controls Table . MCA PI 3.1.5p = 0.956), BDNF (p = 0.171), IL‐1β (p = 0.980), IL‐6 (p = 0.0561), MCP‐1 (p = 0.135), or TNF‐α (p = 0.0757). Greater (log‐transformed) sCD14, adjusted for age, sex, and eGFR was associated with higher MCA PI .Soluble CD14 and SOD levels were higher in CKD as compared to control participants Table . There w3.1.6p = 0.894; ROS: control: 750.4 ± 34.8, CKD: 773.0 ± 34.0, p = 0.0837). However, greater ROS production was positively correlated with higher MCA PI .HBEC production of NO  but did not significantly differ in other characteristics or in cognitive function . Also similar to the primary cohort, eGFR was inversely associated with MCA PI, and MCA PI was positively associated with carotid‐femoral PWV and trail making time part B .Participant characteristics of the validation cohort are provided in Table on Table . Similary Figure . Resting4In this cross‐sectional study, MCA PI was significantly greater in patients with non‐dialysis dependent CKD as compared to healthy controls, and MCA PI was associated with greater large‐elastic artery stiffness (CFPWV), worse executive function (trails B time), lower eGFR, and greater ex vivo ROS production. In contrast, MCA cerebrovascular reactivity and total CBF did not differ between groups. Importantly, similar results were observed in a validation cohort of midlife and older adults divided by the median eGFR.Patients with CKD exhibited significantly greater MCA PI, an index of cerebrovascular stiffness, as compared to healthy controls, consistent with a recent observation in patients with lacunar infarction with and without CKD . Prior research on the influence of kidney function on CBF is unclear, with population‐based studies observing an association of lower eGFR with both reduced  vs. those with eGFR ≥86 ml/min/1.73 m2. Furthermore, higher MCA PI was associated with lower eGFR, higher CFPWV, and slower performance on the Trails B test. Combined, these observations strengthen the primary findings that impaired kidney function, as defined by eGFR, is associated with greater cerebrovascular and aortic stiffness. That similar results were obtained in both cohorts despite slight variations in data collection  between the two institutions further validates the primary findings and provides confidence in the results.To extend our findings to individuals with mildly impaired renal function and validate our findings from the primary cohort, we utilized a secondary cohort with cerebrovascular function measurements performed at a separate institution. Of note, this validation cohort consisted of generally healthy midlife and older adults with eGFR in the mildly decreased to normal range that were otherwise well matched for confounding variables . In accordance with results from our primary cohort, MCA PI was higher, but cerebrovascular reactivity to hypercapnia was not different, in adults with eGFR <86 ml/min/1.73mThere are several limitations to this study. Most notably, our sample size was small. However, we performed comprehensive physiological assessments and cognitive testing, and we were appropriately powered for our a priori primary outcome of cerebrovascular reactivity. An additional limitation is that group differences between the CKD and healthy control group other than the primary disease process, such as differences in BMI or the presence of diabetes and/or hypertension may have accounted for the observed results rather than CKD per se. However, such comorbidities are very common in patients with CKD, thus may contribute to phenotypic changes observed in patients with CKD, and even if beyond reductions in eGFR alone, are critical to the clinical presentation of this patient population. Hypertension and CKD (decline in kidney function) have a bidirectional and complex relationship  stimulus, but ETCO2 was the best noninvasive index of PaCO2 available to us, particularly given that arterial sampling is contraindicated in CKD patients who need to preserve the vasculature for potential vascular access for dialysis. The major strength of our study is that to our knowledge, this is the first study to assess MCA PI in patients with non‐dialysis dependent CKD, as well as assess cerebrovascular reactivity in early‐stage patients with CKD. Moreover, we also confirmed our main results in a validation cohort of generally healthy midlife and older adults with varied eGFR, further supporting the validity of our findings.Furthermore, due to budgetary constraints for necessary equipment, we were unable to assess beat‐to‐beat blood pressure in the primary cohort. Last, providing fixed inspired COIn conclusion, we have provided evidence that MCA PI is higher, but cerebrovascular reactivity is preserved in non‐dialysis dependent CKD. Further research is needed to confirm these results in larger cohorts and to delineate the mechanisms linking arterial stiffness, cerebrovascular function, and cognitive impairment in patients with CKD.E.O., K.A.F., D.H.C., and K.L.N were involved in conceptualization and writing—original draft. D.H.C. and K.L.N were involved in methodology. M.E.C. and K.L.N. were involved in validation and data curation. K.L.N. was involved in formal analysis and visualization. E.S.O., K.A.F., C.N.S., W.W., H.F‐B., M.J.R., D.H.C., and K.L.N were involved in investigation. D.R.S. and M.C. were involved in resources. C.N.S., W.W., H.F‐B., M.E.C., D.R.S., M.C., and M.J.R. were involved in writing—review and editing. D.R.S., M.C., D.H.C., and K.L.N. were involved in supervision. D.R.S., M.C., M.J.R., D.H.C., and K.L.N were involved in funding acquisition.None.Declaration of Helsinki. The nature, benefits and risks of the study were explained to the volunteers and their written informed consent was obtained prior to participation.All procedures were approved by the Institutional Review Board of the University of Colorado Anschutz Medical Campus and the University of Colorado Boulder campus and adhere to the


In recent years, solid organ transplantations, such as kidney or lung grafts, have been performed worldwide with an improvement of quality of life under immunosuppressive therapy and an increase in life expectancy, allowing young women to consider childbearing. In the current study, we conduct a retrospective study in two French centers for kidney and lung transplantations to evaluate the rate and outcomes of pregnancies, contraception and gynecological monitoring for women under 40 years old who underwent solid organ transplantation. Among 210 women, progestin was the most widely used contraceptive method. Of the 210 women, 24 (11.4%) conceived 33 pregnancies of which 25 (75.8%) were planned with an immunosuppressant therapy switch. Of the 33 pregnancies, 7 miscarried (21.2%) and 21 (63.7%) resulted in a live birth with a high rate of pre-eclampsia (50%). No graft rejections were observed during pregnancies. Among the deliveries, 19 were premature  and the C-section rate was high (52.4%). No particular pathology was identified among newborns. We conclude that pregnancies following solid organ transplantation are feasible, and while they are at an increased risk of pre-eclampsia and prematurity, they should still be permitted with close surveillance by a multidisciplinary care team. Solid organ transplantation (SOT) is routinely used to treat organ failure. For example, kidney transplantation (KT) is the most cost-effective treatment for end-stage renal failure  and lungAmong the numerous issues a transplant recipient faces, childbearing is a major one for these women. For many women, having children is a lifelong goal, yet there are several obstacles to overcome in this context, which are compounded by apprehensiveness regarding the life-long morbidity of one parent. Thus, preconception counseling must be personalized to each patient , particuIn addition to preconception counseling, a gynecological work-up is required  to screeThe aim of the present study is to describe the mode of contraception used, the incidence of pregnancies, maternal and fetal outcomes and gynecological cancers in recipients who underwent SOT transplantations in two centers in France spanning a decade. In these centers, only lung and kidney transplantations were performed.This study was approved by the Foch Hospital ethical committee (IRB00012437).We performed a retrospective analysis of all female patients under 40 years of age who underwent kidney transplantations (Department of Nephrology) between 1 January 2010 and 31 December 2019 or lung transplantations (Department of Thoracic Surgery & Lung Transplantation) between 1 January 2010 and 31 December 2018 at Foch Hospital ; or kidney transplantations (Department of Nephrology) between 1 January 2010 and 31 December 2019 at Bicêtre Hospital .Women aged 15 to 40 years at organ transplantation.At least one year after kidney transplantations and two years after lung transplantations, in line with recommendations to reduce possible complications.No objection recorded for inclusion in medical research.Data were collected from each of the hospital’s databases. The following inclusion criteria were applied to identify study patients:We excluded female patients who died or underwent a transplantectomy during the first year for kidney recipients and the first two years for lung recipients after the initial surgery, as well as those patients with missing data. The sole patient who underwent a combined lung and kidney transplantation was included in the LT group because she underwent a lung transplantation before the kidney transplantation.The following data were collected: demographic variables ; medical history ; data regarding the SOT  and occurrence of transplant rejection . Rejection was recorded when there was a decrease function of the grafted organ. Cellular rejection was confirmed by a CD8+ T-cell-significant interstitial infiltration, commonly diagnosed on biopsy. Humoral rejection was defined by the association between histological lesion, positive c4d immunolabelling and/or positive donor-specific antibodies in blood circulation.3, liver transaminase levels increased two fold above the upper normal limit, severe persistent epigastric and/or right upper quadrant pain, thoracic pain or dyspnea and acute pulmonary edema or neurologic symptoms . HELLP syndrome was defined by hemolysis (LDH > 600 UI/L), liver transaminase levels two times the upper limit of normal and low platelet count .Other data collected were the use of contraception ; occurrence of pregnancy and related data , planned/unplanned pregnancy, pregnancy outcome, hypertensive disorders of pregnancy  eclampsia, chronic hypertension and chronic hypertension with superimposed pre-eclampsia), infections, diabetes, fetal outcome, such as birth weight, prematurity, physical abnormalities, week of delivery, mode of and reason for delivery). Pregnancy outcomes investigated were: birth, early miscarriage (before 12 weeks of gestation (WG)), late loss (after 12 WG), medical termination, ectopic pregnancy, molar pregnancy or medical abortion. Pre-eclampsia was defined as the association between hypertension (systolic blood pressure [SBP] ≥ 140 mmHg and/or diastolic blood pressure [DBP] ≥ 90 mmHg) and proteinuria ≥ 0.3 g/24 h after 20 WG. Severe pre-eclampsia was defined by at least one of the following criteria: severe hypertension (SBP ≥ 160 mmHg and/or DBP ≥ 110 mmHg), uncontrollable hypertension, proteinuria ≥ 3 g/24 h, serum creatinine ≥ 90 µmol/L, oliguria ≤ 500 mL/24 h or anuria, thrombocytopenia < 100,000/mm2) for kidney recipients and for which the normal GFR for a young woman is ≥90 mL/min/1.73 m2 with the lower limit of the normal FEV1 being 80% in the general population. Pregnancies were usually contra-indicated for women with a respiratory disorder if the FEV1 was under 40%. We reported these indicators at one and two years after the graft transplant for both SOT types, as well as the occurrence of proteinuria just before and during pregnancy and, for pregnant patients, when there was a significant decrease in GFR or FEV1.Graft functionality was described using timed, forced expiratory volume  for lung recipients and the glomerular filtration rate . Of the lung recipients, 48.2% also had a history of diabetes, which was explained by the high majority of patients having cystic fibrosis (91.2%). The remaining LT patients had other respiratory diseases, including primary ciliary dyskinesia (PCD), bronchiectasis and interstitial pulmonary fibrosis (IPF). One had a borderline ovarian tumor treated with ovariectomy before transplantation and most were nulligravid (75.4%) and nulliparous (82.5%).The demographic and medical histories of the two transplantations are shown in Kidney recipients were presented with a different profile, compared to LT recipients. Not surprisingly 70.8% had a history of high blood pressure. The major cause of end-stage renal disease was glomerulopathy (26.0%) followed by undetermined nephropathy (19.8%), microvascular condition, diabetes mellitus (13.5%) and hypertension (5.0%), and polycystic kidney disease (5.0%).The average duration of dialysis before transplantation was 2.34 ± 2.2 years. A small majority (51.0%) of these women had been pregnant at least once before transplantation and 44.8% had children. Twelve of the 20 patients (60%) with a known history and who had previously given birth had experienced pre-eclampsia (PE).p < 0.001), which, in most cases, was either pancreas and kidney, or liver and kidney, which was statistically significant.Of the lung recipients, 2.6% (3 patients) had a combined transplantation . By comparison, a higher number of the kidney recipients underwent a combined transplantation  who experienced cell-mediated rejection , tacrolimus and corticosteroids (CTSs) . After tejection . The valOne lung and one kidney recipient developed gynecological cancers in the years following the procedure: a vulval epidermoid carcinoma and a breast invasive lobular carcinoma, respectively. Six patients (three in each group) developed cervical precancerous lesions that required conization. After the transplantation, close to 60% of all patients, whether LT or KT recipients, used progestin as their contraceptive method. Approximately 18% used a combined oral contraceptive (COC) with estrogen + progestin, and 16% and 22% of LT and KT patients, respectively, used barrier contraception.p = 0.07).We identified 33 pregnancies in 24 women ; 9/114 (7.9%) in lung recipients and 15/96 (15.6%) in kidney recipients. Of the 24 women, 17 were pregnant once, 5 were pregnant twice and 2 were pregnant three times . There wn = 24) versus those who did not (n = 186) revealed no statistically significant differences for any of the maternal characteristics assessed, except for the incidence of diabetes, which was higher in the patients with no pregnancy  for kidney recipients or timed forced expiratory volume (FEV1) for lung recipients . Howeverp = 0.43; p < 0.001), the remainder being medically assisted with ART plus ovulation induction. Most pregnancies were carefully planned for both SOT groups  and underwent a switch of immunosuppressive medication mostly from MMF to azathioprine. Only four pregnancies began under MMF, none of which resulted in delivery: one ectopic pregnancy, one abortion, one medical termination and one ended in early miscarriage. In one pregnancy, MMF was switched to azathioprine shortly after the diagnosis.The interval between transplantation and conception was similar for the two groups . There were two cases of threatened preterm births in the LT group (29th week for both). There was one case of threatened preterm birth, three cases of gestational diabetes, one preterm rupture of the membrane (36th week) and one anomaly of fetal heart rate (35th week) in the KT group.Two patients in each group developed a severe infection during pregnancy. Three patients had chorioamnionitis at 15, 26 and 33 WG (the 2nd newborn died 15 days after birth) and one patient in the LT group had pyelonephritis, which required an intravenous antibiotic. Furthermore, one of the lung recipients had a significative decrease in FEV1 during pregnancy, which led to premature delivery at 34 WG. Likewise, two kidney recipients had kidney failure during pregnancy, both of whom had induced labor, one at 37 WG because of acute renal failure and the other at 35 WG . The average birth weight of all neonates was 2049 g and the caesarian-section rate among all patients was 52.4% with no significant differences observed for either between the two SOT groups.This dicentric study was performed to provide a descriptive analysis of a cohort of patients under 40 years of age to determine the incidence and course of pregnancies after SOT. The principal findings were that slightly more than 10% of these women (11.4%) had at least one pregnancy after transplantation (9 of the 114 (7.9%) lung recipients and 15 (15.6%) of the 96 kidney recipients) with a high incidence of hypertensive disorders during pregnancy (50%). The mean term of delivery was 34 WG and C-section was performed in 52% of the cases.The overall low rate of pregnancy in this transplant patient population may be related to their complex medical history. However, the medical characteristics and graft function were similar for women who conceived versus those who did not. This strongly suggests that in this population, a fear of pregnancy is greater than the desire for pregnancy, whether arising from the woman’s or the transplant physician’s perspective.The high frequency of a previous history of pre-eclampsia in kidney recipients ,18,19 anLung transplantation is often a necessary step in the current care of patients with cystic fibrosis, although the development of new therapies, such as CFTR (cystic fibrosis transmembrane conductance regulator) modulators, seem consistent with pregnancy ,23 and mFollowing the transplantation and under immunosuppressive medications, the majority of our patients used progestin as the contraceptive method of choice. There is no evidence regarding the contraceptive method that should be used among SOT recipients ,26,27, aGynecological follow-up is essential in SOT patients as immunosuppressive medications after SOT are often associated with cervical dysplasia and carcinoma ,31. It iRegarding the optimal timing for pregnancy following SOT, a consensus conference held by the American Society of Transplantation in 2003 established that pregnancy is usually safe after the first year, providing that there is stable graft function and no rejection episode in the year before conception . There aIn the setting of pregnant SOT patients, the health and safety of offspring are clearly of paramount importance. MMF is one of the major immunosuppressants used after SOT, but it is associated with an increased risk of spontaneous abortion and facial malformation as others mycophenolic acid products ,35. TherAll pregnancies in our KT recipients were spontaneous, whereas more than half of the lung recipients were conceived using assisted reproductive technologies (ARTs). Minimal data are available on medically assisted pregnancies among lung disease patients. Edenborough et al. suggested that patients with cystic fibrosis may have reduced fertility due to increased cervical mucus plugging and ovulation disorders , which mWe observed an early miscarriage rate of 18,2% for LT recipients, which is consistent with the available data . HoweverThe hypertensive disorders during pregnancy incidence of 42.9% in our LT recipients was slightly lower than the 50% hypertension rate previously reported ,40. HoweSevere infections are common triggers of severe prematurity in solid organ recipients ,40 due tNone of our patients had a diagnosed rejection episode during their pregnancies. This is consistent with the absence of SOT rejections during pregnancy reported in the previous studies ,40. The Deliveries were mostly premature due to induction for maternal reasons , as previously described in SOT patients ,15,16. OWe observed a high C-section rate in our study: 42.9% among the lung recipients and 57.3% in the KT group compared to the mean C-section rate in the two institutions (22%). Mastrobattista et al. reported C-section rates of 30% and 49–59% in the same groups . HoweverAchieving pregnancy and delivering a child after SOT raises several ethical questions . Having The strength of our study was the analysis of a large cohort of women of a childbearing age who underwent SOT during a ten-year period. The study was designed not only to investigate maternal and fetal outcomes in this vulnerable patient population, but also to determine the incidence of pregnancy in this cohort. This study was dicentric with data extraction performed from two major transplantation centers in France. Foch Hospital is the first French center to perform lung transplantations , with 82Pregnancies following a kidney or lung transplantation are feasible with loss rates comparable to those in non-transplanted women, although the risks of pre-eclampsia and prematurity are high. Physicians caring for women of a childbearing age who are SOT recipients should take into account their desire to conceive. When in good health and in the absence of recent rejection, planning a pregnancy for this population is reasonable. The risks of maternal complications  and fetal outcomes (preterm birth) should be carefully evaluated and considered to provide complete information for thorough counseling before proceeding with pregnancy. Multidisciplinary care, which includes the transplant surgery team and perinatologists, should be provided during the pregnancy, delivery and post-natal period.


Introduction: There is currently a lack of published data on kidney elasticity and viscosity. Non-invasive techniques, such as two-dimensional shear-wave elastography (2D-SWE PLUS) and viscosity plane-wave ultrasound (Vi PLUS), have surfaced as new detection methods, which, thanks to efficient processing software, are expected to improve renal stiffness and viscosity measurements. This study aims to be the first one to assess the normal range values in normal renal function subjects and to investigate the factors that impact them. Methods: We conducted a cross-sectional study employing 50 participants (29 women and 21 men) with a mean age of 42.22 ± 13.17, a mean estimated glomerular filtration rate (eGFR) of 97.12 ± 11 mL/min/1.73 m2, a mean kidney length of 10.16 ± 0.66 cm, and a mean body mass index (BMI) of 24.24 ± 3.98. With a C6-1X convex transducer and the Ultra-FastTM software available on the Hologic Aixplorer Mach 30 ultrasound system, we acquired five measurements of renal cortical stiffness and viscosity (achieved from five distinct images in the middle part of the subcapsular cortex) from each kidney. The ten measurements’ median values correlated with the participant’s demographical, biological, and clinical parameters. Results: The mean kidney elasticity was 31.88 ± 2.89 kiloPascal (kPa), and the mean viscosity was 2.44 ± 0.57 Pascal.second (Pa.s) for a mean measurement depth 4.58 ± 1.02 cm. Renal stiffness seemed to be influenced by age , the measurement depth , and eGFR  but not by BMI , while viscosity appeared to be impacted by age , eGFR , the measurement depth , and BMI . The results of the one-way ANOVA used to test the differences in the variables among the three age sub-groups are statistically significant for both 2D-SWE PLUS (p < 0.001) and Vi PLUS (p = 0.015). The method found good intra-operator reproducibility for the 2D-SWE PLUS measurements, with an ICC of 0.8365 and a 95% CI of 0.7512 to 0.8990, and for the Vi PLUS measurements, with an ICC of 0.9 and a 95% CI of 0.8515 to 0.9397. Conclusions: Renal stiffness and viscosity screening may become an efficacious, low-cost way to gather supplemental diagnostic data from patients with chronic kidney disease (CKD). The findings demonstrate that these non-invasive methods are highly feasible and not influenced by gender and that their values correlate with renal function and decrease with age progression. Nevertheless, more research is required to ascertain their place in clinical practice. CKD is becoming more common, and its development is linked to a rise in death rates and healthcare costs.  ThereforClassic sonography is utilized to analyze the kidneys, although it only offers a few quantifiable metrics of renal length and parenchyma width, which both reduce as the CKD stage advances. Even though it has been found to have limited diagnostic value in the assessment of CKD, it does provide several pieces of non-quantifiable information regarding the echogenicity of the renal cortex as it improves with fibrosis progression in the later stages of CKD . Even afElasticity is described as a property of tissues that enables them to change shape after a load and then regain their original form, with Ophir et al. 1991  being thThe first and most commonly used technique for evaluating renal stiffness was transient elastography (TE) ,7,8,9, fRecently, US manufacturers provided better imaging methods that claim to be capable of measuring more specific shear-wave displacement curves in the kidney while at the same time measuring the dispersion of shear-wave characteristics, which can be utilized to estimate viscosity (a metric for shearing motion resistance). Instead of rapid deformation, slow deformation causes tissues to migrate, and necro-inflammation-related alterations are thought to affect how shear waves propagate (viscosity) . SupersoThe purpose of this study was to assess the feasibility and performance of these new ultrasound-based techniques embedded in the new Hologic SuperSonic Mach 30 system . To distinguish between normal and pathological cases, it is first necessary to establish the normal kidney elasticity and viscosity values in order to differentiate the factors that influence them, as well as their variability in healthy subjects.In a tertiary department of nephrology over a seven-month period (March 2022 to September 2022), a monocentric, cross-sectional study was conducted. Using 2D-SWE PLUS and Vi PLUS from the new Hologic Aixplorer Mach 30 ultrasound system, elastography-based measurements were carried out on all subjects during the same session by a single operator with three years of experience in kidney elastography (F.-M.M). The study was carried out in accordance with the World Medical Association Declaration of Helsinki, amended in 2000, Edinburgh, and it was authorized by our university’s ethics committee for research and institutional review board (number 41/4 March 2022). Before enrolling in the trial, each patient gave their written informed consent.2), no illness that might affect the findings , and regular kidneys on conventional ultrasonography. We measured the renal parenchyma thickness in all participants, and those with a renal parenchyma thickness under 10 mm were eliminated. The exclusion criteria were hydronephrosis, autosomal dominant polycystic disease, pregnancy, clinical signs of upper urinary tract infection, and refusal to provide informed consent.Fifty healthy subjects consisting of hospital employees  took part in the study following the confirmation of informed consent. We collected the following information from each participant: age, sex, height, weight, BMI, and serum creatinine. Prior to the elastography measurements, we performed a urine dipstick test on each participant. The eligible participants for the control group were those who were aged over 18, well-hydrated , and without obesity (BMI lower than 30) and who had normal renal function , using the equation E = ρ*cs2, where E represents the elasticity of the tissue expressed in kPa, ρ represents the tissue density measured in kg/md in m/s . A quantd in m/s .After the subject emptied their bladder, measurements were taken in the central section of the kidney right under the subcapsular cortex, while they were in the lateral decubitus position. The equipment software produced data for each measurement (the ROI is pre-established at 10mm by the kidney software program and is displayed on the screen as a Q-box). The “Depth” parameter represents the distance from the skin to the ROI, which is used for measuring the 2D-SWE PLUS and Vi PLUS values .Operations were carried out with the participant in neutral respiratory apnea. We collected 5 valid readings of renal stiffness and viscosity from each participant’s kidney (5 different images in the middle portion of the subcapsular cortex), blinded to the clinical and biological data , with a mean time of examination of approximately 10 min. The subjects’ demographic and clinical parameters were correlated with the mean values of the ten non-invasive imaging measurements.The shear-wave measuring box was positioned in the center of the renal parenchyma, immediately underneath the renal cortex, after choosing the most appropriate window using a traditional ultrasound scan and achieving a favorable image .The success rate of performing elastography in native healthy kidneys was 100%; however, it is true that, in patients with CKD (excluded from this pilot study), who sometimes have a thinner renal parenchyma, it is quite difficult to differentiate between the cortex and medulla and to perform the measurements exclusively in the cortex. Vi PLUS can now be utilized to display information about tissue shear-wave dispersion by performing an examination of shear-wave propagation velocity at varying wavelengths. In a color-coded chart, the degree of the shear-wave speed shift between frequencies is qualitatively shown, and it is provided mathematically in Pa.s across a value range. Vi PLUS was utilized in tandem with the 2D-SWE PLUS mode, and both followed the same technique.For the statistical analysis, MedCalc software Version 19.4 and Excel from Microsoft Office 2020 for Windows were utilized. Descriptive statistics were used to analyze the demographic and anthropometric findings. The Kolmogorov–Smirnov test was used to assess the distribution of the numeric values. Correlations between variables are expressed using the Pearson or Spearman correlation coefficients, with a “p“ of under 0.05 being considered statistically significant. Univariate and multivariate regression models were used in order to determine which factors influence 2D-SWE PLUS and Vi PLUS values. One-way ANOVA was used to test the difference in variables among three age sub-groups, and box-and-whisker plots were provided afterward to better understand the distinctions between them.2, a mean kidney length of 10.16 ± 0.66 cm, and a mean BMI of 24.24 ± 3.98 kg/m2 were included in our analysis  of 97.12 ± 11 mL/min/1.73 manalysis .p < 0.0001) and Vi Plus  values. We also found a negative correlation between age and eGFR  and a positive correlation between the median measurements of the 2D-SWE PLUS and Vi PLUS values with an r = 0.2892, p = 0.0417. No statistically significant differences between genders were noticed: the mean kidney stiffness values in men were 32.03 ± 2.84 kPa, slightly higher than the mean stiffness values in women at 31.08 ± 2.5 kPa (p = 0.2185) (p = 0.8964)  , while t 0.8964) .p < 0.0001) (p = 0.0021) (p = 0.1338), only with viscosity . The results of the one-way ANOVA used to test the differences in variables among the three age sub-groups are statistically significant for both 2D-SWE PLUS (p < 0.001) and Vi PLUS (p = 0.015).Age seemed to influence both renal stiffness   and visc 0.0021) , but, rep = 0.0075), as well as with the Vi PLUS measurements . The method found good intra-operator reproducibility for the 2D-SWE PLUS measurements, with an ICC of 0.8365 and a 95% CI of 0.7512 to 0.8990, and for Vi PLUS, with an ICC of 0.9 and a 95% CI of 0.8515 to 0.9397. We also found a positive correlation between the mean measurement depths and the 2D-SWE PLUS values (r = −0.3776, We discovered that eGFR, the median measurement depths, the median viscosity, and age influenced the 2D-SWE PLUS and Vi PLUS values in the univariate regression, but when they were included in the multivariate analysis, no statistically significant model was found.In reality, determining tissue mechanical properties is impossible, but to fully comprehend these new US-based parameters, it is crucial to assess the baseline data from healthy kidney subjects of various ages and sexes and to further investigate the variables that affect them. Nonetheless, to the best of our knowledge, no other clinical study has concentrated on identifying the reference values of kidney stiffness and viscosity in healthy kidney subjects by employing these new, non-invasive methods. 2, and this also indicated that, when the disease advances, renal stiffness declines [The mean kidney stiffness value was 31.88 ± 2.89 kPa, and the mean viscosity value was 2.44 ± 0.57 Pa.s. As a result, a 2D-SWE PLUS measurement of around 31.88 kPa and a Vi PLUS value of around 2.44 Pa.s are indicative of a healthy kidney free of fibrosis or inflammation. Age appears to have an effect on renal stiffness; deterioration is a physiological process of cellular and organ senescence, and, therefore, it is linked with structural changes in the kidneys. A potential explanation for the decrease in stiffness with advanced age could be the fact that renal blood flow decreases with age due to these structural changes. The mean 2D-SWE PLUS and Vi PLUS measurements decreased with age but were unaffected by the participant’s sex. In addition, we also published a study on kidney transplant recipients evaluated using the same elastography measurements in which we obtained a cut-off value of 27.3 kPa for estimating an eGFR of under 60 mL/min/1.73 mdeclines .A decrease in renal stiffness with the progression of CKD has also been shown in other kidney elastography studies ,31,32,33The depth of the kidneys was another issue related to renal elastography until now. The placing of the measurement box in native kidneys is a massive obstacle in the non-invasive evaluation of renal stiffness and viscosity, and previous methods have been limited in their capacity to analyze deep tissues. The target anatomical depth of acoustic radiation force impulse-based approaches is reported to be 7 cm . The sofThe inflammatory process is essential in the advancement of fibrosis . Vi PLUSThe performance capability of acoustic radiation force impulse for measuring renal parenchymal stiffness was assessed in a meta-analysis by Hwang et al., 2021 . The proHowever, more research on patients with CKD using a kidney biopsy as a reference method is required to learn more about the various factors that actually influence kidney elasticity and viscosity. Nonetheless, the current study included volunteers who had never had kidney disease, and obtaining a biopsy would be inappropriate. Non-invasive evaluations are unlikely to be able to rival the gold standard’s diagnostic power, but their capacity to monitor variations in the parenchymal structure as time passes may be the most plausible and attractive reasons for their use.The limitations of the current research are the study’s small number of participants, the examination of a small proportion of variables that may influence cortical stiffness and viscosity (lack of the urinary albumin-to-creatinine ratio  or not cRenal stiffness and viscosity screening may become an efficacious, low-cost way to gather supplemental diagnostic data from patients with CKD. The findings demonstrate that these non-invasive methods are highly feasible and not influenced by gender and that their values correlate with renal function and decrease with age progression. Nevertheless, more research is required to ascertain their place in clinical practice.


Current guidelines recommended patent foramen ovale (PFO) occlusion as the preferred treatment for PFO-related cryptogenic stroke (CS); however, finding the causative foramen ovale remains challenging. This study aimed to identify predictors and establish a scoring system by assessing PFO morphology and stroke-related factors.Based on a prospective multicenter registered clinical trial, we compared data mainly derived from transesophageal echocardiography (TEE) and clinical history in patients with PFO-related CS and those without CS (non-CS) with incidental PFO. Subsequently, we explored independent predictors using logistic analysis, established a scoring system based on the results, and finally evaluated the scoring system using receiver operating characteristic (ROC) analysis and internal validation.75 patients with PFO-related CS and 147 non-CS patients were enrolled. Multivariate logistic analysis showed that the change in PFO height, large PFO, atrial septal aneurysm (ASA), and sustained right-to-left shunt (RLS) had independent relationships with CS. Based on the odds ratio value of each independent factor, a scoring system was built: change in PFO height ≥ 1.85 mm (3 points), large PFO (2 points), ASA (5 points), sustained RLS (2 points). 0–2 points correspond to low-risk PFO, 3–5 points medium-risk PFO, and 7–12 points high-risk PFO. ROC analysis showed an area under the curve of 0.80 to predict CS. The proportion of patients with CS is increasing based on these points.Our study screened out the change in PFO height as an independent predictor of CS. A simple and convenient scoring system can provide constructive guidance for identifying whether the PFO is causal and consequently selecting patients more likely to benefit from closure. It is well known that patent foramen ovale (PFO) is involved in the pathogenesis of many diseases including cryptogenic stroke (CS), migraine, decompression sickness, and arterial deoxygenation syndromes. Randomized controlled trials (RCTs) and long-term follow-up analyses have demonstrated that PFO occlusion could reduce stroke recurrence compared to drug therapy alone –4. Howevhttp://www.chictr.org.cn/; ChiCTR-ONRC-13003436). This study was approved by the Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University, and all patients provided signed informed consent. Between September 2018 and September 2021, a total of 75 patients admitted to our department for PFO-related CS were included. CS was defined as an episode without a major cause, including atherosclerotic stenosis of the large arteries, small artery (lacunar) disease, or cardioembolism , contrast transthoracic echocardiography (cTTE), and TEE were performed by an experienced echocardiographer, and the results were assessed by two investigators who were unaware of whether the patient had a stroke. We utilized TTE to measure the dimensions of the left atrium and aorta. Right-to-left shunt (RLS) grading was defined by microbubbles in the left heart at rest: negative was considered if no microbubbles were observed and sustained shunt if any microbubbles were present. We evaluated the length and height of the PFO channel both at rest and during the Valsalva maneuver, the presence of atrial septal aneurysm (ASA), and hypermobile interatrial septum by TEE, GE-Vivid-E9. The PFO channel length was defined as the maximal visible overlap between the septum primum and secundum. The height of the PFO was measured as the maximum separation between the septum primum and secundum on the left atrial side. Changes in length and height were defined as the value difference between rest and the Valsalva maneuver. The percentage change in length and height were defined as the change in length and height/value at rest *100% . ASA was*100% . Large P*100% , 16.t-test or Mann-Whitney U-test, and categorical variables using the chi-squared test or Fisher's exact test. The independent risk factors were screened using univariate and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curves were used to transform continuous variables into dichotomous variables using cut-off values that depended on the Youden index and to assess the predictive power of the scoring system.Statistical analyses were conducted using SPSS25.0 . We presented continuous variables as mean ± standard deviation or median (quartile), and categorical variables as numbers and proportions. We compared continuous variables using the P < 0.001). The two groups were compared based on sex, history of hypertension, diabetes, atrial fibrillation, coronary heart disease, and hyperlipidemia. P < 0.05). The PFO channel height in the CS group during the Valsalva maneuver was significantly greater . The same trends were shown in height change  and in percentage change of height . The PFO channel length at rest and during the Valsalva maneuver was significantly greater in the CS group . Large PFO, long-tunnel PFO, ASA, hypermobile interatrial septum, and sustained RLS were more prevalent in the CS group .A total of 222 patients were enrolled, including 75 with PFO-related CS and 147 non-CS. Baseline characteristics were showed in Univariate logistic analysis revealed that the dimensions of the aortic sinus and ascending aorta, PFO height during the Valsalva maneuver, change in PFO height, the percentage change in PFO height, PFO length during the Valsalva maneuver, ASA, hypermobile interatrial septum, and sustained RLS were associated with CS. Multivariate logistic analysis showed that changes in PFO height, ASA, and sustained RLS had an independent relationship with CS .We defined 1.85 mm of change in PFO height as the optimal cut-off value with an area under the curve (AUC) of 0.73 to predict PFO-related CS see . When diWe built a scoring system based on the odds ratio (OR) value of each independent factor related to the CS as shown in Based on assessing the characteristics of PFO in patients with CS and non-CS, we obtained the following findings: (1) change in PFO height, large PFO, ASA, and sustained RLS had independent relationships with CS; (2) a scoring system was proposed to evaluate the extent of the pathogenic relationship between PFO and CS. This study emphasized the understanding that PFO anatomical features are associated with CS, and the scoring system could help identify optimal patients who can benefit from PFO occlusion.TEE, a semi-invasive examination, is considered the gold standard for diagnosing PFO. Clinical settings and scientific research have focused on the height and length of the PFO at rest and after Valsalva maneuvers under TEE, however, the situation between these two states is rarely studied. A larger PFO channel diameter promotes more RLS, along with greater risk and severity of stroke , 17, 18.The presence of ASA was more common in CS patients , and thoBased on the selected factors, we built a scoring system with a satisfying AUC to predict PFO-related CS, and it also had excellent internal validation ability. Several scoring models have been proposed in the literature. The Risk of Paradoxical Embolism (RoPE) score was the first model built for the purpose of selecting optimal patients who could benefit from occlusion therapy; however, RoPE is based on the medical history and neuroimaging findings, ignoring the morphological characteristics of PFO . To reduThe study still had limitations. Although this was a prospective study, it had a relatively small sample size, which may have negatively affected the results. We missed external validation of the score which will schedule in the future. To avoid errors induced by the number of counts on cTTE, our study adopted a more direct classification method, positive or negative, ignoring the effect of different degrees of shunting on the results. Additionally, all TEE was performed without sedation, which may have affected the predictive power of the scoring system in the anesthesia population.Changes in PFO height, large PFO, ASA, and sustained RLS were independently related to CS. The scoring system based on the four independent anatomical factors built here can be used to confirm the pathogenicity of PFO and is beneficial to screen patients for occlusion.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Ethics Committee of the First Affiliated Hospital of Xi'an Jiaotong University. The patients/participants provided their written informed consent to participate in this study.XL and YusZ were the principal investigators, conducted the statistical analysis, and drafted the manuscript. JS, LS, BL, and XX performed data collection. XL, HX, HZ, and YusZ edited and revised the manuscript. All authors approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


This study aimed to identify potential biomarkers associated with the occurrence of minor ischaemic stroke.Four hundred patients hospitalized with minor ischaemic stroke were enrolled in the department of neurological internal medicine in Taiyuan Central Hospital, and 210 healthy subjects examined at the Taiyuan Central Hospital Medical Center during the same period were selected. We collected information on the general demographic characteristics and fasting blood samples of the subjects. We then used untargeted metabolomic assay to measure blood glucose, blood lipids, homocysteine, and high-sensitivity C-reactive protein.There were statistically significant differences between the mild ischemic stroke group and the healthy control group in smoking, hypertension, and physical activity (P< 0.05). Compared with the healthy group, the minor ischaemic stroke group showed increased lactate, pyruvate, trimetlylamine oxide levels, and lactic acid, pyruvic acid, and trimethylamine N-oxidation (TMAO) levels were statistically significant (P< 0.001). In the minor ischaemic stroke risk model, hypertension, physical activity, smoking, and elevated TMAO levels influenced the occurrence of minor stroke.Increased levels of lactic acid, pyruvate, and TMAO may be related to the pathophysiological changes in the minor ischaemic stroke population. High blood pressure, a lack of physical activity, smoking, and increased TMAO level were the influencing factors for the occurrence of minor ischaemic stroke. The serum metabolite TMAO may be associated with MS occurrence Stroke is the second major cause of death worldwide. The results of a worldwide meta-analysis in 2010 revealed that 169 and 59 million patients respectively developed stroke and died of stroke-related causes (Minor ischaemic stroke (MIS) refers to mild neurological deficit or lacunar cerebral infarction. Clear diagnostic criteria have not yet been established for MIS, and cerebral infarction is usually defined as MIS with a National Institutes of Health Stroke Scale (NIHSS) score of 0–3 points . MIS cauMetabolomics refers to changes in the concentrations of endogenous small molecular metabolites with a molecular weight [(MW)<1 kDa] due to internal and external stimuli. The number of metabolites in humans ranges from 2,000–20,000. Metabolic spectrum can be generated from blood, urine, and other biological samples using magnetic resonance imaging, chromatography, mass spectrometry, and other techniques. The height or area of the peak represents the relative levels of chemical components and can be used to detect and reflect changes among metabolites during various pathological or biological metabolic stages. Untargeted metabolomics is used to test relationships among metabolites in multiple interconnected pathways. Wang et al. used protWe screened and followed up 400 patients with MIS over a period of 3 years using nuclear magnetic resonance (NMR) and untargeted metabolomics to generate new strategies with which to prevent and treat MIS.We selected 400 patients with clinically confirmed MIS who were hospitalized at Taiyuan Central Hospital between January 2013 and December 2015 and 210 healthy persons (controls) who were assessed at the same hospital during the same period. All of them provided written, informed consent to participate in this study, which was approved by Shanxi Medical University Science Research Ethics Committee.All participants were aged ≥ 18 years and had resided in Taiyuan City for > 2 years.The inclusion criteria for patients were as follows: acute cerebral infarction confirmed by diffusion-weighted cranial magnetic resonance imaging (MRI), degree of neurological deficits due to MIS assessed by NIHSS  scores aThe inclusion criteria for controls comprised people who were deemed healthy after a physical examination.A history of stroke, severe infection, severe liver and kidney impairment, immune system diseases, malignant tumors, neurological diseases not associated with MIS, mental illness, and severe hematologic diseases.We collected the following information using a structured questionnaire: demographic , lifestyle habits , a medical history of diabetes, hypertension, coronary atherosclerotic heart disease [coronary heart disease], and atrial fibrillation.The patients with MIS were assessed using cranial NMR imaging. Acute cerebral infarction was confirmed when hyperintense signals on diffusion-weighted images corresponded to hypointense signals on analogue-to-digital conversion (ADC) maps.We assessed the consciousness level, sensory neglect, and visual, motor, and cerebellar functions of the patients using the NIHSS scale based on a confirmed diagnosis of acute cerebral infarction by MRI. Scores for individual parameters were obtained using a corresponding scale. The total NIHSS score for each patient comprised the sum of each component.The following were purchased from the respective suppliers: a 1.5-T superconducting magnetic resonance imaging system , a −80°C freezer , a Bruker 600-MHz Avance III NMR Spectrometer with a proton frequency of 600.13-MHz , a TGL-16 high-speed refrigerated centrifuge , NMR heavy water , 3-(Trimethylsilyl) propionic acid sodium salt , a 7180 fully automated biochemical analyzer , blood glucose and lipid quantitation reagents , a homocysteine quantitation reagent , and high-sensitivity C-reactive protein quantitation reagent .Venous blood from participants within 24 h of enrolment was collected in the morning after fasting and stored with anticoagulants. Blood glucose, blood lipids, homocysteine, and high-sensitivity C-reactive protein were quantified and serum metabolomics was assessed in 5 mL samples.Blood samples for quantifying blood glucose, blood lipids, homocysteine, and high-sensitivity C-reactive protein were left at room temperature for 1 h before centrifugation at 3,500 rpm for 10 min to collect serum which was immediately analyzed or stored at -20°C and analyzed within 24 h.Blood samples for serum metabolomics analysis were immediately centrifuged at 3,500 rpm for 10 min, then serum was separated and transferred to 1.5-mL Eppendorf (EP centrifuge) tube, sealed, and stored at -80°C.Blood glucose, total cholesterol, triglycerides, and high-density lipoprotein (HDL) were measured using oxidase as described by the manufacturer of the fully automated analyzer. Levels of low-density lipoprotein (LDL) were determined using a homogeneous enzymatic assay. Homocysteine and high-sensitivity C-reactive protein levels were measured using enzymatic cycling and enzyme-linked immunosorbent assays, respectively.2O for 30 seconds and centrifuged at 13,000 rpm for 10 min at 4°C and 600 μL of the supernatant in 5-mm NMR tubes were then analyzed as follows:Untargeted metabolomics was quantified using NMR imaging. Serum samples were thawed in ice water, then 450 μL samples were vortex-mixed with 350-μL D(1) Broad peaks of proteins and lipoproteins were attenuated using the 600-MHz NMR scanner  with the Carr–Purcell–Meiboom–Gill (CPMG) pulse sequence.(2) MestReNova v. 8.0.1 software  was used to process spectral NMR maps in which the phase and baseline were manually adjusted. The chemical shift of creatinine (δ3.04) was the standard for chemical shift correction, and segments were integrated at δ0.80–8.50 chemical shift regions using δ0.01. Segments were not integrated at δ4.67–4.96 . The integration data were normalized and performed the multivariate statistical analysis.(3) SIMCA-P+ software  was used for multivariate and principal component analysis (PCA). PCA analysis converts a large number of correlated variables into a small set of uncorrelated variables, while preserving as much information as possible about the original variables. It can be used to replace the original large number of correlated variables, thereby simplifying the analysis process. We further applied orthogonal signal correction (OSC) followed by orthogonal partial least squares discrimination analysis (OPLS-DA) to eliminate the effects of relevant factors such as individual differences on grouping and to strengthen intergroup differences. OPLS-DA establishes the relationship model between metabolite expression and sample category by using partial least squares regression, and the sample relationship can be better established by reducing the dimensionality of the data.t test was used for comparison between the two groups. Data from multiple groups were compared using One-way analysis of variance (ANOVA), intra-group pairwise comparisons were assessed using the least significant difference method. The quantity and ratios (%) of discrete data were analyzed using the chi-square test, and Fisher exact probability test on rows × columns. P value of<0.05 was considered statistically significant. The inclusion and exclusion criteria were 0.05 and 0.10, respectively, for multivariate analysis with logistic regression.Structural questionnaire, NIHSS scores, imaging, serum biochemistry, and metabolomics were statistically analyzed using SPSS 17.0 . Continuous data were described as mean and standard error, and a In this study, we enrolled 400 patients with MIS and 210 healthy controls. A comparison of general status revealed that smoking, hypertension, and physical activity significantly differed between the two groups (P< 0.05), whereas age, alcohol consumption, sex, and diabetes did not. These findings indicated that the two populations are generally similar and comparable, while smoking, hypertension, and physical activity might influence MIS Table 1.The results of univariate analysis of blood glucose, blood lipids, homocysteine, and high-sensitivity C-reactive protein revealed significant differences in triglyceride, HDL, and high-sensitivity C-reactive protein levels between the two groups P< 0.05, Table 2.http://www.hmdb.ca) and Biological Magnetic Resonance Data Bank  databases, and a comparison with the literature , physical activity , smoking , and TMAO  affected the occurrence of MIS. Hypertension, smoking, and TMAO levels were risk factors for MIS, while physical activity was a protective factor  and Four “Batches” Innovation Project of Invigorating Medical through Science and Technology of Shanxi Province (2022XM07).The reviewer RY declared a shared affiliation with the authors to the handling editor at the time of review.The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.