Cardiac arrest is the leading cause of natural death in the United States, and most surviving patients suffer from neurological dysfunction. Although this is recognized as a problem, there have been very few changes to the cardiopulmonary resuscitation (CPR) procedure. Tourniquets have been recognized for their ability to increase truncal blood pressure and have been shown to improve CPR outcomes in animal models. However, the relationship between tourniquet application and blood pressure elevation has not been adequately explored in healthy human adults.The objective of this study is to demonstrate that bilateral, non-invasive, peripheral vascular occlusion in the thighs results in an increased proximal systolic blood pressure ≥ 10 mmHg.This is a single-center, non-blinded clinical trial. Volunteers will be screened for eligibility at least 24 hours before the day of the trial. On the day of the trial, volunteers will undergo an informed consent process. If they choose to participate in the trial after informed consent, their baseline blood pressure will be measured. Volunteers will then have a Combat Application Tourniquet (CAT) applied to each thigh, and the windlasses will be tightened by IRB-approved personnel. Once no pulse can be felt in the lower extremity, blood pressure will be measured in the arm. This will be replicated three times, and the tourniquets will be loosened between trials to allow the volunteers to rest. Any complications that arise during the trial will be handled by the physician that is present.Changes in systolic blood pressure and diastolic blood pressure will be analyzed using a Shapiro-Wilk test. Then, a one-way repeated measures analysis of variance (ANOVA) will be performed with a Holm-Sidak post-hoc test to determine the mean differences. The significance level will be set to 5% for statistical significance.NCT05324306.Clinicaltrials.gov,  For decades, the fields of trauma, orthopedics, and cardiology have utilized vascular occlusion devices for either hemorrhage control or to increase central pressure –3. Due tQ = ΔPπr4) gives the volumetric flow rate (Q) in a cylindrical tube as it relates to the viscosity of the fluid (v), length of the system (L), radius of the tube (r), and pressure gradient across the tubing (ΔP). Tourniquets placed on the legs would decrease the length of the system (L), thereby increasing the flow (Q) as these variables are inversely proportional. While this equation is an obvious oversimplification, we find it models our expectant results and confirms what we intuitively and anecdotally have noted in our patients. Beyond theory, studies in large animal models and clinical trials offer additional proof of concept [The fluid dynamics Hagen-Poiseuille Equation demonstrates in physical law why peripheral vasoconstriction increases the flow in conserved vascular networks. The Hagen-Poiseuille Equation Q = ΔPπr gives th concept , 15–19.  concept . Increas concept . Increas concept .To our knowledge, blood flow or pressure to vascular beds supplying vital organs  has not been measured in healthy adult subjects following administration of a non-invasive peripheral vascular occlusion device. This proof-of-concept data is necessary for future development and hypothesis testing for novel CPR adjuncts, which could improve survival and neurologic recovery following cardiac arrest.Our goal is to acquire proof of concept data demonstrating increased blood pressure in the upper extremities as a read-out for perfusion of the heart and brain following tourniquet administration on the lower extremities. This data will be critical in the development of novel CPR adjuncts. To complete our hypothesis testing safely, we plan to deploy well-studied and FDA-approved combat application tourniquets (CAT) on volunteer healthy adult subjects while measuring blood pressure and heart rate in the upper extremities. CAT tourniquets were developed in 2005 by Mark Esposito et al.  and soon after obtained FDA approval. CAT tourniquets have been indicated for use in emergency situations revolving around a wounded limb, such as hemorrhage control , 23. CATWe intend to demonstrate that non-invasive, peripheral vascular occlusion increases blood pressure in the conserved vasculature in healthy humans while maintaining a baseline heart rate. Data from this study will provide proof of concept for the development of a novel device to improve cardiopulmonary resuscitation (CPR) outcomes during non-traumatic cardiac arrest. We hypothesize that peripheral vascular occlusion of non-vital vascular beds (the lower extremities) will increase blood flow to the more vital organs, the heart and the brain, leading to an improvement in survival and neurologic recovery after cardiac arrest as these outcomes are dependent on heart and brain ischemic injury. By using commercially available, FDA-approved tourniquets on healthy humans to measure blood pressure and heart rate with peripheral vascular occlusion, we will be testing our hypothesis in the safest way.Study participants will meet in a specified conference room at the Medical University of South Carolina where the research protocol will be completed.Healthy adults with no known chronic medical conditions between the ages of 18 and 60 years old willing and able to consent themselves.Subjects who are native English speakers or self-report as fluent in English.Subjects who have a history of or are a current smoker, have a history of or current illicit drug use, have a history of or current alcohol abuse.Subjects who self-report as pregnant.Subjects who self-report diabetes, cardiac disease (including hypertension) requiring medication, or a history of compartment syndrome or peripheral vascular disease.Subjects with known chronic diseases not listed above, including but not limited to Rheumatoid Arthritis, McArdle’s disease, etc.Subjects with elevated blood pressure (>130/80mmHg) on the day of the study.Each participant’s height and weight will be recorded, and they will have their blood pressure and heart rate measured in each arm by an automated sphygmomanometer while lying down on a medical bench (baseline must not be >130/80 mmHg). This will allow each research participant to act as their own control for the experimental procedure. The measurements will be recorded by IRB-approved personnel. Then, one CAT will be placed around each thigh and tightened until no pulse can be felt in the lower extremity. Blood pressure and heart rate measurements will be repeated in each arm once the tourniquets are secured. Once these measurements are documented, the tourniquets will be removed. The maximum time the tourniquets will be applied is 5 minutes to ensure ample time for blood pressure recording. If the measurement cannot be taken within the time frame, the tourniquets will be released. The participants will rest 3–5 minutes between each repetition of the tourniquet application. The whole process will be repeated three times for data validity. CATs have been extensively studied for safety, and no long-term consequences or complications have been noted for up to two hours of continuous use.The research team will prioritize the safety and comfort of the participant and will limit the tourniquet application time to a maximum of 5 minutes. Participant data and personal information will be kept in a secure database with a password-protected server. The data will be coded and a linking document containing any identifiers will be kept separate from the research data. Only IRB-approved personnel will have access to the final trial dataset. Upon completion, the deidentified data will be available in a separate manuscript.After the data is collected, a debrief session will be conducted, allowing for additional subject monitoring after removal of the tourniquets. During the debrief session, the participant will be asked to lay down or sit in a relaxed position for 5 minutes or until they feel that their leg function is back to baseline. If there is any concern from the participant, the PI or IRB-approved personnel who are medical doctors, will conduct an evaluation. If any of the safety endpoints are noted, it will be recorded, and the participant will be taken to the emergency room for full examination and work-up. The PI or IRB-approved personnel will follow-up with the participant remotely until the safety concern is resolved.Research subjects may refuse to participate or stop participating in the study at any time by notifying the principal investigator or approved IRB personnel. If research participants would like to have their data removed from the study, they must notify the principal investigator in writing within a week of completing the study. If the principal investigator or approved IRB personnel determine that participation in the study is not in the best interest of the research subject, they may remove the research participant from the study.A cardiac arrest porcine model that utilized an intra-aortic balloon catheter for occlusion of the aorta at the level of the diaphragm demonstrated a mean increase in systolic pressure of 17mmHg . ExtrapoVolunteers identified as potential study participants will be informed of the study protocol and guidelines by a phone call at least 24 hours prior to the start of the study. Immediately following the phone call, volunteers will be emailed a copy of the consent form to review. On the day of the study, participants will be seen in the order that they arrive, and they will be consented in a private room by IRB-approved personnel. After being consented, they will have their baseline measurements taken. Then, they will undergo the three tourniquet trials with appropriate breaks between each trial. The informed consent, baseline measurements, and tourniquet trials will be done on the same day. No follow-up is needed .A total of 30 healthy volunteered adults will be used for our study. A power analysis was conducted to determine appropriate sample size based on previous data examining hemodynamics following tourniquet application on the lower extremities . Based oFlyers will be displayed around the University campus in order to recruit subjects voluntarily. Volunteers will be screened to determine their ASA Class and will be asked questions regarding known chronic diseases and the exclusion criteria to identify potential subjects.Data will be collected by IRB-approved personnel only. Blood pressure and heart rate will be measured using the OMRON 3 Series upper arm home blood pressure monitor BP7100. IRB-approved personnel will be trained on how to deploy the CAT tourniquets properly and safely on the lower extremities  and the automated sphygmomanometers on the upper extremities prior to the start of the study. Prior to deployment of either the CAT tourniquet or the automated sphygmomanometer, IRB-approved personnel will inspect the devices for any defects and sterilize the devices with 70% isopropyl alcohol or 70% ethanol. Following removal of the devices from the study participants, they will be sterilized with 70% isopropyl alcohol or 70% ethanol.All data associated with the research participants will be kept in a secure database with a password-protected server. The data will be coded, and a linking document containing any identifiers will be kept separate from the research data. Hard copies of the consent forms and any recorded data will be kept in a locked file cabinet with the key stored separately. Data may be used in future studies following IRB approval without additional informed consent from research participants.Changes in systolic blood pressure, diastolic blood pressure, and heart rate will be analyzed using a Shapiro-Wilk test. Then, a one-way repeated measures analysis of variance (ANOVA) will be performed as well as a Holm-Sidak post-hoc test to determine the mean differences. The significance level will be set to 5% for statistical significance.The most common complications following application of a CAT are nerve injury, as a result of compression, and pain at the site of tourniquet application. Nerve injury usually occurs at the edges of the tourniquet due to the increased pressure gradient. Symptoms are typically transient resulting in mild to moderate pain. To increase the safety of the study and reduce the likelihood of complications, the tourniquet will be tightened to the minimum pressure needed to occlude blood flow to the lower extremities and will be removed after 5 minutes, since injury usually occurs 30–60 minutes following tourniquet application . If 25% Auditing of the trial conduct will be conducted by the Institutional Representatives. The investigators and trial sponsor will have no role in the auditing process.The Institutional Review Board-II–Medical University of South Carolina has reviewed and approved this protocol  as well Modifications made to the trial methods, site selection, informed consent documents, recruitment methods, safety assessments, risk factors, or any other aspects of the protocol will be reviewed and approved by the Institutional Review Board-II–Medical University of South Carolina as well as the trial sponsor.If a research subject is injured as a result of participation in the study, they will be advised to immediately go to the emergency room of the nearest hospital. The participant should tell the physician on call that they were part of a research study and may call the study doctor for details. If the study sponsor does not pay for the treatment, the healthcare facility who administered treatment will bill the research participant’s insurance company. If the insurance company denies coverage or the participant is uninsured, the research participant will be responsible for payment for all services administered. The research participants will be notified of these guidelines during voluntary informed consent.Results or data collected in the study will not be disclosed to study participants. Results will only become available to non-IRB-approved personnel after they are published in a peer-reviewed journal.Eligibility for authorship requires IRB approval, participation in data collection, participation in data analysis, and participation in writing and/or reviewing the manuscript. There will be no professional writers employed.This study is currently recruiting participants.S1 Checklist(DOC)Click here for additional data file.S1 Appendix(DOCX)Click here for additional data file.S2 Appendix(DOCX)Click here for additional data file.


Haemoglobin A1c (HbA1c) was measured both at baseline and follow-up. At baseline, 52 patients had NAFLD (hepatic steatosis) alone, and 9 had NAFLD with coexisting clinically significant fibrosis (defined as LSM ≥ 7 kPa on Fibroscan®). At follow-up, 16 patients had a worsening of glycaemic control (arbitrarily defined as HbA1c increase ≥ 0.5% from baseline). The prevalence of NAFLD and coexisting clinically significant fibrosis at baseline was at least three times greater among patients who developed worse glycaemic control at follow-up, compared with those who did not . In logistic regression analysis, the presence of NAFLD and clinically significant fibrosis was associated with an approximately 4.5-fold increased likelihood of developing worse glycaemic control at follow-up , even after adjustment for baseline confounding factors, such as age, body mass index, haemoglobin A1c (or HOMA-estimated insulin resistance) and use of some glucose-lowering agents that may positively affect NAFLD and liver fibrosis. In conclusion, our results suggest that the presence of Fibroscan®-assessed significant fibrosis was associated with a higher risk of developing worse glycaemic control in postmenopausal women with T2DM and NAFLD.Currently, there are limited data regarding the long-term effect of liver stiffness on glycaemic control in patients with type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD). We prospectively followed an outpatient sample of 61 consecutive postmenopausal women with T2DM and NAFLD who had baseline data on liver ultrasonography and Fibroscan Nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver diseases worldwide, affecting up to ~30% of adults in the general population . NAFLD aOn this background of evidence, in 2022, the American Diabetes Association (ADA) guidelines recommended that individuals with T2DM and elevated serum liver enzyme levels or NAFLD on ultrasonography should be evaluated for the presence of liver fibrosis . This alThus, the main aim of this observational longitudinal pilot study was to examine whether T2DM patients with NAFLD and coexisting clinically significant fibrosis (as noninvasively assessed by liver ultrasonography and vibration-controlled transient elastography (VCTE)) had a worsening of glycaemic control over time, compared with their counterparts with NAFLD alone.®) at baseline; 7 of these 9 patients with NAFLD and coexisting significant fibrosis had a LSM ≥ 8.2 kPa .Of the 61 postmenopausal women with T2DM included in the study, 52 (85%) patients had NAFLD (hepatic steatosis) alone, and 9 (15%) patients had NAFLD and coexisting clinically significant fibrosis  ≥ 7 kPa on Fibroscan® were significantly higher in patients who developed worse glycaemic control at follow-up compared with those who did not (median LSM: 6.6 (IQR 5.4–8.6) vs. 4.4 (3.6–5.6) kPa; p = 0.005). Similarly, the proportion of patients with NAFLD and clinically significant fibrosis  at baseline was greater among those who developed worse glycaemic control at follow-up compared with those who did not . Again, the proportion of those with NAFLD and LSM ≥ 8.2 kPa at baseline was greater among those who developed worse glycaemic control at follow-up compared with those who did not . Conversely, the two patient groups did not significantly differ for other clinical and biochemical characteristics at baseline, such as age; BMI; smoking history; blood pressure; HbA1c; proportion of those with HbA1c from 7% to 8% or those with HbA1c > 8%; plasma lipid profile; HOMA-IR score; serum liver enzymes; kidney function parameters; prevalence of ischaemic heart disease or stroke; and use of glucose-lowering, antihypertensive, lipid-lowering or antiplatelet agents.p < 0.001). Moreover, the proportion of those with HbA1c >8% at follow-up was also significantly greater in patients with NAFLD and clinically significant fibrosis than in those with NAFLD alone . All other clinical and biochemical characteristics recorded at follow-up were not significantly different between the two groups of patients, including the use of glucose-lowering, antihypertensive, lipid-lowering or antiplatelet agents.p = 0.041). The adjustment for age and BMI (model 1) or for the baseline use of some specific glucose-lowering agents, such as glucagon-like peptide 1 (GLP-1) receptor agonists (model 2), sodium-glucose cotransporter-2 (SGLT2) inhibitors (model 3) or pioglitazone (model 4) that might favourably affect NAFLD and liver fibrosis did not weaken the strength of this association. Almost identical results were found even when we used LSM ≥ 8.2 kPa instead of ≥7 kPa  for defining the presence of clinically significant fibrosis Further adjustment for baseline HbA1c levels did not change the strength of the association between the severity of NAFLD at baseline and risk of developing worsening of glycaemic control at follow-up  compared with NAFLD alone, the presence of NAFLD and clinically significant fibrosis at baseline (as noninvasively assessed by liver ultrasound and VCTE examinations) was significantly associated with an approximately 4.5-fold increased risk of glycaemic worsening at follow-up (5 years later); and (b) this significant association persisted even after adjusting for baseline confounding factors such as age, BMI, HbA1c (or HOMA-IR score) and use of some glucose-lowering agents  that may positively affect hepatic steatosis and fibrosis. In this study, we used an increase in HbA1c of at least 0.5% from baseline to define glycaemic worsening. This HbA1c increase has been used as a marker of worsening of glycaemic control in patients with T2DM in other published studies ,18.In 2022, the ADA scientific guidelines recommended that patients with T2DM and elevated serum liver enzymes or NAFLD on ultrasonography should be evaluated for presence of liver fibrosis , therebyTo date, there is evidence showing that poor glycaemic control is associated with a higher likelihood of having NASH or advanced fibrosis ,10. For ®, Patel et al. showed that patients with NAFLD were more likely to have HbA1c levels ≥7% (≥53 mmol/mol) and to be treated with insulin [Little information is available to date about the long-term effects of NAFLD and its more advanced forms on long-term glycaemic control in people with T2DM. In this context, in a small cross-sectional study of 230 individuals who underwent Fibroscan insulin . Prelimi insulin .Collectively, therefore, the results of our study corroborate and expand the aforementioned findings, showing that the baseline presence of NAFLD and coexisting significant fibrosis (as assessed by ultrasonography and VCTE) were strongly associated with a worsening of glycaemic control at follow-up, irrespective of age, BMI, HbA1c, HOMA-IR score and baseline use of certain glucose-lowering agents.The most obvious explanation for our findings is that the association between advanced NAFLD and worsening of glycaemic control at follow-up might arise from shared metabolic risk factors. However, it is important to note that in our study, the association of NAFLD and clinically significant fibrosis with worsening of glycaemic control remained statistically significant even after adjusting for some important confounding factors at baseline, including the use of GLP-1 receptor agonists, SGLT-2 inhibitors or pioglitazone that may positively affect NAFLD (steatosis) and liver fibrosis. Notably, as reported in Although further research is certainly needed, our findings may have some important clinical implications, as they further support the need for a multidisciplinary and holistic approach to patients with T2DM and advanced NAFLD, as well as the need for a tailored drug treatment of NAFLD in this specific patient population ,23,24. I®) are two noninvasive methods that are widely used for diagnosing and staging NAFLD in clinical practice [®-assessed LSMs may be affected not only by hepatic fibrosis but also by severe hepatic steatosis and inflammation [Our study has some important limitations that should be mentioned. First, the observational design of the study precludes making any causal inferences. Second, the number of participants was small, and the study included only Caucasian postmenopausal women with T2DM and NAFLD. Hence, our results cannot be necessarily generalizable to other patient groups, including, for example, men with T2DM (the investigation of possible sex-related differences is now becoming a priority in NAFLD research ). Third,practice , althougpractice ,33 and Fammation . FinallyDespite these limitations, our study has some important strengths, including the consecutive enrolment of the study population and the completeness of our database. Additionally, both liver ultrasound and VCTE examinations were performed by a single expert physician, who was blinded to participants’ clinical and biochemical details, thereby eliminating possible assessment bias and interobserver variability. However, we cannot exclude a certain degree of intraobserver variability in the diagnosis of hepatic steatosis on ultrasonography ,33. FinaIn conclusion, the results of our longitudinal pilot study suggest that the presence of NAFLD and clinically significant fibrosis at baseline was associated with a markedly higher risk of worsening of glycaemic control at follow-up (5 years later) in postmenopausal women with T2DM and NAFLD. The strength of this association was not weakened by adjustment for important baseline confounding factors such as age, BMI, HbA1c, HOMA-IR score and use of some specific glucose-lowering agents  that might favourably affect NAFLD and liver fibrosis. Further studies are certainly needed to confirm these data in other patient cohorts and to better understand whether the prescription of certain glucose-lowering drugs with potential hepatoprotective effects may increase the probability of achieving good glycaemic control in patients with T2DM and advanced NAFLD.We studied 61 Caucasian postmenopausal women with T2DM and NAFLD consecutively attending our diabetes outpatient service who had data on liver ultrasonography and VCTE that were performed in the year 2017 (baseline) and who subsequently underwent a diabetic visit in the first 6 months of 2022 (follow-up). The exclusion criteria of the study were as follows: (a) history of significant alcohol consumption  and other competing causes of hepatic steatosis ; (b) cirrhosis, cancer and end-stage kidney disease; and (c) chronic use of potentially hepatotoxic drugs. Considering the technical limitations of VCTE methodology, patients with congestive heart failure or free abdominal fluid were also excluded from the study. Most patients enrolled in this study have also been included in our previous studies ,35.The local Ethics Committee approved the study protocol. All patients gave their written informed consent for participation in this research.Body mass index (BMI) was measured as kilograms divided by the square of height in meters. Blood pressure was measured with a standard sphygmomanometer after the patient had been seated quietly for at least 5 min. Patients were considered to have hypertension if their blood pressure was ≥140/90 mmHg or if they were taking any antihypertensive drugs.Venous blood samples were collected in the morning after an overnight fast. Complete blood count, glucose, lipids, creatinine, liver enzymes and other biochemical blood parameters were measured using standard laboratory procedures  at the central laboratory of our hospital. Haemoglobin A1c (HbA1c) was measured using the high-performance liquid chromatography analyser Tosoh-G7 . The Homeostasis model assessment—insulin resistance (HOMA-IR) score was used for estimating insulin resistance. Glomerular filtration rate (GFR) was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) study equation .Presence of ischaemic heart disease was defined as a documented history of myocardial infarction, angina or coronary revascularizations. Presence of ischaemic stroke was based on medical history and examination and was confirmed by reviewing hospital medical records of patients, including radiology imaging results. Presence of diabetic retinopathy, diagnosed with fundoscopy after pupillary dilation, was also recorded in all patients. All these data were collected both at baseline and at follow-up, except for the HOMA-IR score, which was available only at baseline.A single expert physician, who was blinded to participants’ clinical and biochemical details, performed both liver ultrasonography and VCTE examinations at baseline. Hepatic steatosis was diagnosed by using ultrasonography , according to specific ultrasonographic characteristics, such as diffuse hyperechogenicity of the liver relative to kidneys, ultrasound beam attenuation and poor visualization of intrahepatic vessel borders and the diaphragm ,35. Semi®  and an M probe [® XL probe for patients with severe obesity. The accuracy of the Fibroscan® M probe to identify significant liver fibrosis is excellent in those with overweight or grade 1 obesity (BMI ≤ 35 kg/m2). In our study, only four patients had a BMI > 35 kg/m2. Our Fibroscan® system was not equipped with the controlled attenuation parameter (CAP) technology for measuring hepatic steatosis [Liver stiffness measurement (LSM) was performed by VCTE using Fibroscan M probe ,35. We dteatosis . Brieflyteatosis .a priori sample size calculation. Continuous variables were expressed as means ± SD or medians and inter-quartile ranges (IQR) when indicated, while categorical variables were expressed as proportions. The Fischer’s exact test for categorical variables, the unpaired Student’s t test for normally distributed continuous variables and the Mann–Whitney test for non-normally distributed continuous variables  were used to examine the intergroup differences in main clinical and biochemical characteristics of the study participants, who were stratified either by severity of NAFLD at baseline  or by an overall worsening of glycaemic control at follow-up (arbitrarily defined as HbA1c increase ≥ 0.5% from baseline).Given the exploratory design of the study, we did not perform an We tested the independent association between the severity of NAFLD at baseline and worsening of glycaemic control at follow-up  by using logistic regression analyses. We performed four adjusted logistic regression models. Model 1 was adjusted for age and BMI at baseline; model 2 was adjusted for age, BMI and baseline use of GLP-1 receptor agonists; model 3 was adjusted for age, BMI and baseline use of SGLT2 inhibitors; and, finally, model 4 was adjusted for age, BMI and baseline use of pioglitazone. We also repeated the same multivariable logistic regression models after further adjustment for HbA1c or HOMA-IR score at baseline. Additionally, we performed an ordered logistic regression analysis  using four increasing categories of worsening of glycaemic control  that was included as the ordinal dependent variable in all ordered logistic regression models. The ordered logistic regression models were adjusted for the same list of covariates that were included in the four aforementioned logistic regression models. Covariates included in logistic regression models were selected as potential confounding factors based on their significance in univariable analyses or based on their biological plausibility.p-value of < 0.05 (two-tailed) was considered to be statistically significant. Statistical analyses were performed using STATA software, version 16.1 .All statistical tests were two-sided, and a


The effectiveness of the multidisciplinary nursing model in the nursing of chronic kidney disease (CKD) by using meta-analysis is explored. Relevant literatures that are in line with the multidisciplinary nursing model for CKD intervention are searched and screened from domestic and foreign literature databases such as Wanfang Medical Center, CNKNET, VIP, and PubMed, and Meta-analysis is conducted with RevMan 5.2 software. A total of 6 literatures are included, and the publication bias of the included literatures is low. Meta-analysis shows that the multidisciplinary group had a better Hb compliance rate, Hb level, Scr, eGFR, SBP, and DBP than the traditional group. The experimental results show that multidisciplinary nursing intervention can improve the nursing effect of patients with CKD and help to improve Hb, Scr, blood pressure, and glomerular filtration function of patients. The incidence of Chronic Kidney Disease (CKD) increases with a change of people's living habits. According to an epidemiological survey, the incidence of CKD in China is more than 10%. This disease is a lifelong disease, and bad living habits will increase the risk of disease and deterioration . The priThe rest of this paper is organized as follows. The disease was CKD induced by a variety of risk factors for CKD, patients may suffer kidney structure changes and kidney function decline, the symptom of kidney function can appear serious but his entire condition does not deteriorate, so reasonable control of high glomerular filtration and albuminuria in patients with symptoms was the effective measure to alleviate illness development . In keepEGFR and SCr were sensitive indicators that can directly reflect patients' renal function. The abnormal decrease of eGFR and the abnormal increase of SCr and Hb can both reflect patients' renal function decline and indicate that patients may have kidney injury . Chen foHypertension was a common clinical manifestation of renal disease, and active control of hypertension level was the first choice of treatment for renal disease control. Some studies have pointed out that professional nurses and clinical pharmacists, after systematic training, can effectively control the blood pressure level of CKD patients to a certain extent, help the blood pressure level of patients reach the normal standard, and delay the progression of patients' disease . In thisThe literature types are clinical controlled trials and dissertations. The effect of the multidisciplinary nursing mode on CKD intervention is in the direction of retrieval, which is searched according to the Chinese and English keys in accordance with the research direction in Wanfang Medical Science, CNKI, VIP, and foreign PubMed. Including Scr, eGFR, CKD, multidisciplinary nursing, blood pressure, renal function, creatinine, glomerular filtration rate, systolic and diastolic blood pressure, chronic kidney disease, nursing, hemoglobin, blood pressure, renal function, and so on, the literature retrieval time is nearly 6 years, and a meta-analysis is conducted based on the selected literature.The selected literature treatments are assessed using a modified Jadad score scale with an overall score of 1–7, with ≤ 3 being low quality and ≥ 4 being high quality.P < 0.1 and I2 ≥ 50%, subgroup or sensitivity is used to analyze the source of this property. When the heterogeneity between studies met the conditions of P > 0.1 and I2 < 50%, the heterogeneity had no statistical significance, and the fixed effect model is used for meta-analysis. When the source of heterogeneity is not clear, the random effect model and descriptive analysis of obvious clinical and methodological heterogeneity are used in the analysis.RevMan5.2 statistical software is used to analyze the study data, and the counting data are expressed as risk ratio (RR). The weighted mean difference is selected as analysis statistics, weighted mean difference (WMD), or standard mean difference (SMD). All effect sizes are expressed with a 95% confidence interval (CI). The heterogeneity between the results of each study is tested by the Chi-square test. When the heterogeneity between studies is statistically significant After searching and screening in terms of keywords and research directions in the Chinese-English donation database, a total of 6 literatures are included, including 5 Chinese literatures and 1 English literature. The specific retrieval process is shown in I2 = 20.0%, P=0.23). According to the fixed-effect model analysis, the Hb compliance rate of the multidisciplinary group is higher than that of the traditional group, and there is no statistically significant difference between the combined studies , P=0.07) [Two literatures are included, and the heterogeneity test shows that there is heterogeneity among literatures ( P=0.07) , 19.  FiI2 = 93.0%, P < 0.0001). Random-effects model analysis shows that Hb in the multidisciplinary group significantly is lower than that in the traditional group, and the differences are statistically significant after all studies are combined , P < 0.0001). Four references are included, and the heterogeneity test shows that there is heterogeneity among the references . eGFR in the multidisciplinary group significantly increased than that in the traditional group, with statistically significant differences between the combined studies , P < 0.00001). Five references are included, and the heterogeneity test shows that there is heterogeneity among the references . After random-effects model analysis, the multidisciplinary group has significantly decreased creatinine than the traditional group, with statistically significant differences between the combined studies , P < 0.00001). Three references are included, and the heterogeneity test shows that there is heterogeneity among the references . The SBP of the multidisciplinary group significantly is decreased than that of the traditional group, with statistically significant differences between the combined studies , P < 0.00001). Three references are included, and the heterogeneity test shows that there is heterogeneity among the references . According to the random-effects model analysis, the DBP of the multidisciplinary group significantly decreased than that of the traditional group, with statistically significant differences between the combined studies , P < 0.00001). Three references are included, and the heterogeneity test showed that there is heterogeneity among the references (There are still some deficiencies in this study. For example, the literature screening scope is small, resulting in a relatively small number of included literature compared with previous studies of the same type, which may increase the risk of research results error and further literature heterogeneity. In addition, CKD has multiple disease types, and its clinical symptoms are relatively complex and diverse. As a validation of multidisciplinary care intervention in quality of care for patients with CKD and the improvement of symptoms of one of the research ideas, such as the quality of life for patients with CKD, and survival condition such as prognostic indicators can be as a new research direction for further analysis, the design idea of this study has further improved space. The follow-up study should further expand the scope of searching literature in order to ensure that sufficient literature samples are obtained, and meta-analysis conducted based on them is of great guiding significance for obtaining higher quality information data, and it can improve the reference value of meta-analysis results.In conclusion, the application of multidisciplinary nursing intervention in patients with CKD can effectively improve the nursing effect and meanwhile can improve the patients' blood pressure, renal function indicators, and hemoglobin level. The multidisciplinary nursing mode has the value of promotion and implementation in the nursing work of CKD.


Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3,  Mepolizumab SB-240563) is a fully humanized IgG1/k-class monoclonal antibody that selectively binds to interleukin-5 (IL-5), preventing its engagement with IL-5 receptor alpha (IL-5Rα) and finally inhibiting its downstream activities. Because of its high-affinity interaction, mepolizumab does not appear to interfere with other cytokines and exhibits a good safety and tolerability profile [40563 is A regimen of 100 mg of subcutaneous mepolizumab, administered once every 4 weeks, has been approved since 2015 for the add-on maintenance treatment of patients over 6 years old affected by moderate-to-severe eosinophilic asthma (SEA), being uncontrolled despite maximal standard therapy according to the Global Initiative for Asthma (GINA) guidelines . In addiFrom previous trials, mepolizumab proved to be highly effective in treating SEA. The benefits on the lower airways included a reduction in exacerbations’ rates and in asthma control questionnaires scores   and an iOn the other hand, knowledge on the effects of mepolizumab on CRSwNP in patients with SEA is not yet conclusive. The SYNAPSE trial reported how mepolizumab is effective at multiple levels, in decreasing the occurrence of nasal surgeries and the use of oral corticosteroids (OCS) and in improving nasal symptoms . In addiConsidering these premises, the aim of this study was to verify the efficacy of mepolizumab on sinonasal aspects in a specific subset of patients affected by SEA and concomitant CRSwNP in real life. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test 22 (SNOT-22), NP score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab’s effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients.A retrospective no-profit observational multicentric study was conducted revising clinical data from adult patients affected by SEA and concomitant CRSwNP who started mepolizumab treatment according to GINA guidelines ,13,14,153 and/or peripheral total IgE ≥ 100 kU/L, which are EPOS indicators of a “type 2 inflammation” profile of the airways [Existing diagnosis of CRSwNP was verified in accordance with the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) criteria . Patient airways .The study was conducted in compliance with the Helsinki Declaration and with policies approved by the Insubria Board of Ethics. Informed consent was obtained from all participants included in the study.Baseline data were collected, concerning demographic features, smoking habits, chronic rhinosinusitis (CRS) and asthma onset, non-steroidal anti-inflammatory drug (NSAID) intolerance, sensitization to common inhalants, type of ongoing nasal therapies, need for OCS, history of previous biological treatment, history, type, and timing of sinonasal surgeries.improvement, respectively, for asthma and CRSwNP.A set of five clinical parameters, acquired at baseline (t0) and at 12 months of treatment (t12), was examined to accomplish the study endpoints: SNOT-22 score, approximated overall CRS symptoms, and CRS-related QoL; scores defined by the first 12 items of SNOT-22 (SNOT 1-12) and by some individual symptoms  were also evaluated; NP score expressed the endoscopic extension of NP; blood eosinophil count was assumed as a surrogate of eosinophilic inflammation of the airways; the ACT score and EPOS assessment scale were employed to evaluate, respectively, asthma and CRS control of disease over 12 months of observation. The EPOS scale for CRS control is a multimodal scale coupled with standard subjective and objective outcomes of CRS  to items such as sleep disturbance or fatigue and need of rescue (steroid or antibiotic) treatment for disease control. The advancement of at least one step on the clinical control scale  was classified as The magnitude of mepolizumab effect was first defined based on the size of changes  of the clinical assessment parameters  between t0 and t12.Clinical improvement was defined on achieving at least 1 MCID  in SNOT-22 score. The MCID is the lowest degree of change that a patient will notice, which, for SNOT-22 score, has previously been defined as 8.9 points [Endoscopic improvement was defined on achieving at least a 1-point reduction in NP score. Patients who achieved an improvement both in SNOT-22 score and NP score were classified as overall responder; those who obtained benefits either on clinical or endoscopic scores were considered as partly responder and those who did not improve in any aspect as nonresponder.9 points . EndoscoAll adverse events potentially related to the use of the drug during the observation period were collected.p > 0.1), whereas the distributions of the other variables were not normal. Analyses were performed with parametric tests for normally distributed variables (Student’s t-test and One-way ANOVA) and nonparametric tests for nonnormally distributed variables, and ordinal and nominal variables . Results are reported as mean ± standard deviation (SD) for normally distributed variables and median with interquartile range (IQR) for nonnormally distributed variables.The distribution of continuous variables was verified using the Kolmogorov–Smirnov test. The distributions of age, SNOT-22, and blood eosinophils values were found normal  and A total of 45 severe asthmatic patients with comorbid CRSwNP treated with mepolizumab were identified. Two subjects did not conclude the 12-month observation period, due to early discontinuation of treatment (4 months) because of disabling adverse events (AEs). As a result, subsequent analyses were performed on the remaining 43 patients.The final population included 18 males and 25 females, with an average age of 52.2 ± 10.9 years. Demographic and clinical data are reported in At baseline, 19 patients (44%) and 24 patients (56%) presented, respectively, with partly controlled asthma and with uncontrolled asthma, based on ACT score. None of the patients had clinically controlled asthma. Regarding CRSwNP, 1 patient (2%) presented with controlled disease, 9 patients (21%) with partly controlled disease, and 33 patients (77%) with uncontrolled disease, according to the EPOS assessment scale. As a result, 17 patients (40%) presented with a concordant uncontrolled clinical status of asthma and CRSwNP, whereas 16 patients (37%) presented with a clinically partly controlled asthma and uncontrolled CRSwNP. These were the two most frequently observed combinations of clinical airway control.Mean baseline (t0) SNOT-22 score was 54.8 ± 25.9 and mean t0 SNOT 1–12 score was 34.9 ± 13.7. Median t0 scores of SNOT-22-specific symptoms were: nasal obstruction 4 (IQR 2), nasal discharge 4 (IQR 3), loss of smell 5 (IQR 2), facial pain 2 (IQR 0), and ear fullness 3 (IQR 3). Median t0 NP score was 3 (IQR 3) and mean t0 blood eosinophil count was 804.7 ± 461.5 cell/µL.Mean t12 SNOT-22 score was 31.5 ± 21.3 and mean t12 SNOT 1–12 score was 20.4 ± 12.5. Median t12 scores of SNOT-22 individual symptoms were: nasal obstruction 2 (IQR 3), nasal discharge 2 (IQR 4), loss of smell 2 (IQR 5), facial pain 0 (IQR 2.5), and ear fullness 1 (IQR 2). Median t12 NP score was 2 (IQR 4) and mean t12 blood eosinophil count was 107.5 ± 104.6 cell/µL.p < 0.0001), SNOT 1-12 score (p < 0.0001), NP score (p < 0.0001), and blood eosinophil count (p < 0.0001) .A statistically significant difference was observed for all clinical parameters examined at t0 and t12 and, therefore, attributable to the effect of mepolizumab treatment: SNOT-22 score ( 0.0001) . The samAs in-treatment nasal surgery could have represented a bias for the measurement of mepolizumab effect, the same analysis was conducted in the subgroup of the population excluding patients operated during treatment, and the above-mentioned statistically significant differences were fully confirmed.improvement, 28 patients (64%) improved their asthma status, and 22 patients (51%) their CRSwNP status, suggesting that mepolizumab positively impacts on asthma and the CRSwNP clinical control in more than half the population.Concerning delta (Δ) SNOT-22 score was −22 (IQR 31), median delta (Δ) NP score was −1 (IQR 2.5), and mean delta (Δ) blood eosinophils were −699.9 ± 464.5 cell/mm3.Median p = 0.0022), whereas the greatest improvement in NP score was gained by allergic patients (p = 0.0412) and patients operated during treatment (p = 0.0012). Lastly, the greatest reduction in blood eosinophil count was observed in patients presenting with a t0 ACT uncontrolled asthma (p = 0.0374).The greatest improvement in SNOT-22 score was obtained by patients with t0 SNOT-22 score ≥40  had unchanged (13/17) or worsened (4/17) their clinical status. Among clinical responders, the median number of achieved MCID was 3 (IQR 3) and the percentage of relative improvement was −61.2 ± 24.6. There were no statistically significant differences in the distribution of several t0 clinical variables  between clinical responders and nonresponders, except for baseline SNOT-22 score; mepolizumab clinical responder presented a t0 SNOT-22 significantly higher than that of nonresponders (p = 0.0015).Twenty-six patients (60%) were classified as endoscopic responders, having experienced a reduction of at least 1 point in NP score; the remaining 16 patients (37%) had unchanged (13/16) or worsened (3/16) their endoscopic status. Among endoscopic responders, the median of NP score reduction was 2 (IQR 1). There were no statistically significant differences in the distribution of several t0 clinical variables  between endoscopic responders and nonresponders, except for atopic status; allergic patients are, indeed, significantly more represented among mepolizumab endoscopic responder than nonresponders (p = 0.0293).Twenty-seven patients (63%) were classified as overall responder and 23 patients (53%) as partly (13/23) or nonresponder (10/23). There were no statistically significant differences in the distribution of several t0 clinical variables  between overall responders and nonresponders, except for baseline SNOT-22 score; mepolizumab overall responders presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011).Combining both clinical and endoscopic effects, 20 patients (47%) were classified as Apart from the 2 patients (4.4%) whose biologic treatment was discontinued due to AEs (arthritis in one case and gastroenteritis in the other), no other serious AEs were reported in the remaining 43 patients. However, 11 patients (25.6%) reported one or more minor AEs, including nasopharyngitis (4), pharyngodynia (4), arthralgia (3), flu (3), back pain (1), stomachache (1), pyrexia (1), and headache (1).Patients affected by SEA frequently present with comorbid CRSwNP . It is eAs anti-IL-5 biological agents were introduced as a new-line treatment for patients affected by SEA, the finding of a concomitant sinonasal therapeutic effect in patients with comorbid CRSwNP has sparked interest in the application of such drugs as a possible breakthrough treatment in patients with type 2 eosinophilic difficult-to-treat nasal polyposis.The effect of mepolizumab on CRSwNP has been evaluated in two phase II randomized clinical trials (RCT), which showed a reduction in NP score from baseline (mean change −1.30 ± 1.72)  and, accThe encouraging results obtained in RCTs prompted several authors to evaluate the effect of mepolizumab on CRSwNP in severe asthmatic patients in the real-life setting. A limited number of dissimilar real-life studies (RLS) have been published so far .p < 0.0001). The delta NP score was −1 points (IQR 2.5) and substantially overlapped with that from the SYNAPSE study (−0.8 points) [In line with RLSs results ,11,30,31 points) . To date points) ) for NP  points) , whereasIn addition, it is crucial to recognize the impact of sinonasal surgery on NP score. Indeed, on the one hand, it influences the baseline value in patients operated shortly before the biological treatment, thus covering the possible effect of mepolizumab on NP shrinking ; on the p < 0.0001). However, due to the limited data available, it was not possible to compare the magnitude of the clinical improvement among the identified RLSs. Interestingly, the delta SNOT-22 score in the present study was −22 points (IQR 31), which is almost double that obtained from the SYNAPSE study (−13.7 points) [A reduction in nasal symptoms has been described by all RLSs, except for a small case-series in which a disconnection between the effect of mepolizumab on upper and lower airways was observed . Among t points) , to indip < 0.0001). Indeed, in accordance with existing literature, the present study proved that 64% of patients benefited from asthma clinical control, demonstrated by an advancement of at least one step in the ACT scale. Furthermore, patients with clinically uncontrolled asthma showed at baseline both a median NP score and mean blood eosinophil count significantly higher than patients with partly controlled asthma (unpublished data). These data suggest that the baseline degree of asthma clinical control, in addition to running parallel to the extent of sinus disease (in terms of NP volume), is the only variable, among those examined, that significantly affects the baseline blood eosinophil count.The clear and reproducible therapeutic effect of mepolizumab both on the clinical control of asthma, assessed by ACQ or ACT, and on the reduction in circulating blood eosinophils has been widely reported by previous studies ,5,6,28. The paradox that the depletion of blood eosinophils may not proceed in parallel with the reduction in clinical and endoscopic impact of sinonasal disease has long been a subject of debate ,10,34. Hresponder and nonresponder patients based on clinical outcomes of upper and lower airways [overall responder patients (47%) were those with a higher SNOT-22 score at baseline. Curiously, this parameter appeared to be the only positive indicator of overall response to mepolizumab, just as it is for the response to surgical therapy in CRS [The response to mepolizumab treatment can be evaluated by applying different scores and PROMs (Patient Reported Outcome Measures) in both rhinological and pneumological fields. The definition of response is arbitrarily established by the authors. As an example, one study classified  airways . The prey in CRS ,35.endoscopic responders than nonresponders (p = 0.0293) is unclear. The reduction trend observed also for SNOT-22 score and blood eosinophils in this subset of patients, though not statistically significant (unpublished data), seems to indicate that allergic patients may be more responsive to mepolizumab treatment, possibly due to either an unclear effect of the drug itself or an intrinsic feature of allergic patients.The reason allergic patients are significantly more represented among In conclusion, studies on the efficacy of mepolizumab treatment in patients with severe asthma and CRSwNP in the real-life setting are in line with the results obtained in RCTs for symptom control and blood eosinophil count reduction. Data on NP score reduction remain controversial. More extensive and uniform outcomes in RLSs are necessary to increase the accuracy of results.AEs in mepolizumab treatment are cited. An overall prevalence of treatment-related AEs is reported in 15% of patients; any serious events, reported in the SYNAPSE trial, occurred in 6% of treated patients even though they were not considered treatment-related . In our The present study shows several limitations. It is a retrospective analysis on a small and diverse sample size. Larger and more uniform series are needed to verify these results. Secondly, all patients were treated with mepolizumab and, therefore, a control group is lacking. We have shortcomings regarding biological parameters. Indeed, other biomarkers of type 2 inflammation  were not available. Furthermore, we were unable to assess the radiological changes after treatment. In fact, sinus-computed tomography (CT) scans are repeated in daily practice only in refractory cases awaiting surgery or in case of a clinical need. We also did not extensively evaluate the impact of surgery on outcomes, because the variability in the type of surgical procedure did not allow for comparisons between patients. Lastly, asthma improvement could not be verified through respiratory functional data, because these were not available for all patients.Treatment of CRSwNP is currently undergoing a rapid evolution since the introduction of biological therapies targeting type 2 inflammatory pathways. After observing the promising results obtained in the management of SEA, studies focusing on the effect of these therapies in CRSwNP are in the spotlight of the scientific community. There are still many open questions on how to properly and timely integrate biologics in CRSwNP care and to conveniently select suitable patients based on a much more comprehensive phenotyping and a focused endotyping.In this study, mepolizumab was found to significantly improve the CRSwNP outcome parameters in a population of severe asthmatic patients. An overall benefit on clinical and endoscopic aspects has been demonstrated with a reduction in symptoms severity, nasal polyps’ volume, and blood eosinophils. No clinical feature emerged to outline the profile of a “typical” responder patient, except for baseline SNOT-22 score, which seems to affect the response to treatment .Further studies would be necessary to supplement these preliminary evaluations both with a more complete clinical scoring set and with other biomolecular parameters that may better reflect an inflammatory profile dominated by IL-5 and eosinophils.


Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity. Age-related macular degeneration (AMD) is a leading cause of central vision loss among people over age 55 years in developed countries .Two main subtypes of AMD have been clinically recognized: neovascular or wet AMD, and non-neovascular or dry AMD . The latIn its early stages, dry AMD is characterized by the presence of drusen  and pigmentary abnormalities resulting from alterations in the retinal pigment epithelium (RPE) and Bruch’s membrane (BM). In late stages, dry AMD usually can progress to geographic atrophy (GA) associated to outer retinal degeneration and loss of photoreceptors and choriocapillaris . Several3 vitamin (Astazin 10®) for a period of at least 6 months.We retrospectively reviewed the electronic charts of 15 consecutive patients affected by intermediate AMD treated with daily oral nutritional supplement with AXT, antioxidants, lutein, bromelain, folic acid and DAll patients who consecutively presented to the Ophthalmology Department of the University “G. d’Annunzio” Chieti-Pescara Italy were recruited.The study adhered to the tenets of the Declaration of Helsinki. Informed consent was obtained before the enrollment. The staging of AMD was based on the clinical AMD classification proposed by Ferris et al. . BrieflyIf both eyes met requirement criteria, one randomly selected eye of each subject was imaged.3 vitamin) for a mean period of 180 ± 21 days. A control group (n = 13) homogenous for age and sex was also included in the analysis .SD-OCT and OCTA evaluation were performed in each patient at a time included between nine and eleven a.m.Outcome measures included in this study were: choroidal thickness (CHT) and choriocapillaris vessel density (CCVD) after six months.The MC retinal imaging was obtained using a commercially device , which uses a confocal scanning laser ophthalmoscope to capture simultaneous reflectance images of the retina with three different wavelengths: blue (488 nm), green (515 nm), and infrared (828 nm) reflectances, respectively . The MC The SD-OCT images were obtained with the high-speed resolution mode and Eye Tracking Automatic Real-Time System with a scan protocol covering a 30 × 30 degree macular cube area centered on the fovea. The CHT was manually measured in the sub-foveal location from the outer portion of the hyper-reflective band of the RPE to the inner surface of the sclera, and its value was calculated as the average of two manual measurement each taken by a single retinal specialist (L.D.A.). The OCTA assessment was performed by means of a commercially available device  that uses a scan speed of 70,000 A-scans per second and a light source centered on 840 nm, with a bandwidth of 45 nm. The OCTA images were processed using a split-spectrum amplitude decorrelation angiography (SSADA) algorithm (version 2018.1.0.24), providing axial and transverse resolutions of 15 microns in tissue for OCTA images. This algorithm identifies blood flow by calculating the decorrelation of signal amplitude from consecutive B-scans performed at the same retinal acquisition plane by splitting the spectrum, improving the signal-to-noise-ratio, and enhancing flow detection . Study pData were reported as mean and standard deviation (SD). Differences between groups at baseline were tested with linear models for continuous variables, whereas chi-square test was used to test differences in categorical variables. To assess the variation in CHT and CCVD between baseline and follow-up, linear mixed models were applied only in the cases group, adjusted for age and sex.p-value ≤ 0.05 was considered statistically significant.Linear regression analysis with robust option was applied to evaluate correlations between variables of interest. Analyses were performed with the SAS statistical software, version 9.4. A two-sided p = 0.70) (Fifteen eyes (cases) from 15 patients  with intermediate AMD and thirteen eyes (controls) from 13 healthy age-matched subjects  were included in this study. The mean age was 70.20 ± 8.13 years in cases and 68.92 ± 8.62 years in controls ( = 0.70) .p = 0.34)  . The comp < 0.001) and in the cases during follow-up after oral therapy  and in the cases during follow-up (p < 0.001)  B.p < 0.001) was found between CCVD and CHT at baseline considering both cases and controls , followed by dysfunction and death of photoreceptors and choriocapillaris atrophy . It is aPrevious studies have reported a significant reduction in CC perfusion density in eyes suffering from intermediate AMD, especially in concurrence with nascent geographic atrophy or neovascularization in the fellow eye . In wet It has been widely stated that AXT is a form of carotenoid spread in nature with a large variety of physiological and biological activities including antioxidant, anti-tumor, anti-inflammatory, and anti-arteriosclerosis functions ,23,24,25A preliminary human blood rheology study showed a decrease of blood transit time in healthy subjects after AXT ingestion for a ten-day period by collecting blood samples compared with the placebo group . The bloOur work aimed at investigating blood flow choroidal changes by means of multimodal imaging analysis in patients with intermediate AMD after AXT supplement intake combined with bromelain, vitamin D3, folic acid, lutein, and antioxidants for at least 6 months. In our sample, we excluded eyes with refractive error greater than three diopters because it is known that high myopia affects choroidal thickness and choriocapillaris vessel density ,28,29.A previous randomized, double-blind, placebo-controlled study was the first to describe the impact of oral administration of 12 mg AXT on choroidal blood perfusion using Laser speckle flowgraphy in healthy subjects .Conversely, we used both SD-OCT and OCTA imaging for assessing choroidal blood flow changes after AXT supplement intake combined with bromelain, vitamin D3, folic acid, lutein and antioxidants. In particular, we reported the variation of subfoveal choroidal thickness and choriocapillaris vessel density values at baseline and after six months of such combined treatment. Using OCTA, a qualitative and quantitative analysis of retinal and choroidal microvasculature and its changes in ocular diseases are of great interest for both research purpose and clinical practice .3 (Astazin 10®) on choroidal and choriocapillaris flow improvement.In our cohort of patients with AMD, vascular parameters changed significantly during follow-up, likely due to action of oral treatment on choroidal circulation. In detail, a significant increase of both CCVD and CHT was observed, suggesting a potential role of the synergy between AXT, antioxidants, lutein, bromelain, folic acid, and vitamin DAs reported in the literature, there is a relationship between choriocapillary dysfunction, drusen formation, and AMD progression. Several clinical human studies demonstrated a relationship between CC flow impairment and drusen onset . MoreoveIn our sample of eyes, a significant correlation between CCVD and CHT at baseline was found in both cases and controls, suggesting a strong connection between these two vascular structures in AMD pathophysiology. To date, choroidal thinning and CC dropout in AMD patients are known, particularly in GA condition.Oxidative stress and apoptosis of RPE cells leading to their death are key processes in AMD pathogenesis with an evident dysregulation of nutrient exchange pathway between photoreceptors and choriocapillaris . TherefoOtherwise, no functional changes in terms of visual acuity were assessed in cases after therapy, although previous studies reported visual acuity and accommodation improvement ,28.The main limitation of the study concerns the sample of the study. Our study is a retrospective case series; therefore, it was not possible to assess the sample size and the power of the study. We enrolled all subjects that were available in our dataset. Obviously, the interpretation of the results of the study must be evaluated with caution, keeping in mind that external validity could be questionable, but internal validity was conversely robust.Other limitations of this study are the following: (i) patients with only intermediate AMD; (ii) the retrospective nature; (iii) structural and functional parameters assessment by a single trained retinal specialist; (iv) scan protocol performed at different daily times, affecting final results of CHT and CCVD measurements due to their circadian fluctuations; (v) the CHT measured only in the subfoveal region.A sub-analysis of different stages of AMD could be appropriate to validate these results.A strength of this study was the detailed analysis of such vasculature structures (choroid and CC), whose quantification remains challenging and questionable.Further studies with a longer follow-up should be conducted to strengthen these findings and to understand the actual role of AXT assumption, alone or in combination with antioxidants and protective agents, in AMD condition. The accurate segmentation of choriocapillaris is still demanding in patients with different stages of AMD for large drusen or geographic atrophy, confounding flow signal and final analysis.Moreover, future studies using SS OCTA could help with better visualization of CC with deeper light penetration through RPE.This study could be considered as a pilot study, useful as a starting point for further perspectives and randomized clinical trials assessing the role of astaxanthin in the treatment of intermediate AMD.


Successful management of bilateral Wilm's tumor (BWT) involves a radical resection while preserving enough normal kidney tissue. Nephron-sparing surgery often results in an R1/R2 resection with a high recurrence rate in children with huge or multiple tumors, or tumors proximity to the renal hilum. In contrast, kidney autotransplantation can completely resect the tumor while maintaining homeostasis and preserving the patient's healthy kidney tissues.Ex vivo tumor resection and kidney autotransplantions were performed on 11 kidneys. The baseline characteristics, perioperative management, and survival status were reported.We summarized the clinical data of 8 synchronous BWT patients who underwent kidney autotransplantation at the First Affiliated Hospital of Sun Yat-sen University from 2018 to 2020. in vivo. Among all the 8 patients, six of them (75%) received staged operation and the other 2 patients (25%) received single-stage operation. No residual tumors were found on the postoperative imaging in all the 8 patients. In total, 6 (75%) patients occurred complications after the autotransplantation, among which, 2 (33.3%) patients had complication of Clavien-Dindo grade IIIa, and 4 (66.7%) patients had complication of grade < 3. During the 38 months of follow-up, 87.5% (7/8) of patients were tumor-free survival with normal renal function. One patient died from renal failure without tumor recurrence.Nephron-sparing surgeries were performed on 5 kidneys Therefore, our study indicated that autologous kidney transplantation can be an option for patients with complex BWT if the hospital's surgical technique and perioperative management conditions are feasible. Wilms tumor (WT) is the most common malignant pediatric renal tumor, with an incidence rate of about 1 in 10,000 . The chaCurrently, bilateral nephron-sparing surgery (NSS) is commonly used for the surgical management of BWT. However, in complex cases  we can only perform an R1/R2 resection, resulting in a high recurrence rate . The 5-yex vivo. The organ is then retransplanted. Autologous kidney transplantation can completely resect the tumor while maintaining homeostasis and preserving the patient's normal kidney tissues. Previous literatures had described the technique in BWT two decades before with small sample size  and perioperative data  were retrospectively collected.All the patients and their parents gave informed consent. This study was approved by the Clinical Research and Experimental Animal Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University [Approval number: (2021)129].According to the 2016 Wilms tumor guidelines of the International Society of Pediatric Oncology (SIOP) , childrein vivo completely. 3. Renal tumor ex vivo resection and autologous kidney in-situ transplantation was selected for huge or multiple tumors adjacent to the renal hilum; or located in the deep middle of kidney, or proximal to renal vessels.If deemed resectable, one of the 3 following operation methods was chosen: 1. Radical nephrectomy was performed for huge tumors when the kidney could not be preserved at all. 2. NSS surgery was performed for small tumors that could be removed in vitro and processing the renal pelvis and blood vessels, another group of surgeons removed the retroperitoneal lymph nodes.Intraoperatively, the patient was placed in a supine position, the lumbar region was elevated, and a transverse incision was made on the upper abdomen. Intraoperatively, the renal hilar vessels and ureters were freed, and sufficient lengths of the ureters and renal hilar vessels were reserved. The proximal renal artery and vein were clamped with blood vessel clamps. The distal ureter was also handled, and the kidney (including the tumor) was removed. While removing the renal tumor in vitro to keep the kidney in a bloodless state. After incising the renal capsule, tumors were peeled from the normal tissue carefully with complete tumor capsule. Hemostasis and ligation were given to blood vessels at the cutting edge, and renal arteries and veins were trimmed for anastomosis. Then, we repaired the damaged renal system, and sutured the renal capsule. The excised and processed tumor-free kidney was orthotopically implanted into the body  cryopreservation solution was simultaneously injected. The preservation solution was perfused in the kidney to completely replace the residual blood. This perfusion was continued during the whole process of removing tumors and kidney repairing the body . The renPostoperative renal function and blood supply were assessed by monitoring the hourly urine output, and the occurrence of any hematuria. An ultrasound examination assessing the blood supply of the kidneys was performed on postoperative day 1. The urinary catheter was routinely indwelled for 3–5 days and was removed after the urine volume and color became normal. During the perioperative period, the patient's blood pressure was dynamically monitored and controlled. Indicators such as serum creatinine, the volume of the abdominal drainage, and urine volume were monitored. The severity of complications was evaluated according to Clavien-Dindo classification system . Post-opFrom 2018 to 2020, 88 patients diagnosed as WT in our center. Among them, 16 patients were BWT and a total of 8 children with BWT met the inclusion criteria and were enrolled in this study. The average age of onset of the 8 patients was 14 months (7–40 months). Among them, 2 cases were genetically diagnosed as Denys-Drash syndrome, and 2 cases were complicated with hydronephrosis. 37.5% (3//8) of them had multiple tumors. After 2–12 courses of neoadjuvant chemotherapy, all the tumors were stable without significant size reduction. The baseline characteristics of the patients were shown in in vivo. The blood loss during unilateral autologous kidney transplantation was less than 50 ml. 2 cases of children undergoing surgery had major intraoperative blood loss and required a blood transfusion to replenish the blood volume. The kidney on the autologous kidney transplant side was reimplanted in situ, and the blood flowed smoothly in the blood vessels, without any thrombus or stenosis. Imaging examination of all 8 children, 1 month post-operatively showed no residual tumor. The postoperative pathological diagnosis of all 8 children was nephroblastoma. All of the 11 kidneys who underwent ex vivo tumor dissection and kidney autotransplantation had no residual tumor cell on microscopic surgical margins. Immunohistochemistry (IHC) indicated WT1 positive in 6 patients. Six patients performed IHC tests of Ki67 with varied positive ratio (2%–50%). According to the mid-term results of a stage III randomized clinical trial conducted in our center (ChiCTR-PRRC-12002525), adjuvant radiotherapy combined with chemotherapy didn't show significant efficacy in patients with WT at stage IIIA  received staged operation and the other 2 patients (25%) received single-stage operation. In details, 4 patients underwent bilateral autologous kidney transplantation, 2 patients underwent unilateral renal autologous transplantation and contralateral radical nephrectomy, and 2 patients underwent unilateral renal autologous transplantation and contralateral NSS resection. One patient underwent intraoperative inferior vena cava tumor thrombus extraction. Ex vivo tumor resection and kidney autotransplantions were performed on 11 kidneys. Nephron-sparing surgeries were performed on 5 kidneys age IIIA . Thus, a2 in three days after surgery. Two cases were complicated with Denys-Drash syndrome and therefore suffered from postoperative renal insufficiency. Case 2 had severe proteinuria on admission. After neoadjuvant chemotherapy and staged surgery, her renal function was maintained for 28 months. Then, she underwent allogeneic kidney implantation with both autologous nephrectomies at the same time and kept tumor-free survival for 19 months till now. Case 1 with nephrotic syndrome and WT had a right hydrocele, left cryptorchidism, and hypospadias; consistent with complete Denys-Drash syndrome. He had decreasing eGFR in four months after surgery and then underwent dialysis for a short period (8 months), but died from treatment interruption. So far, 7 children are still tumor-free survival with a median follow-up time of 38 months (range: 24–42 months).Complications of different severity occurred in 6 children post-operatively, among which, 2 (33.3%) patients had complication of Clavien-Dindo grade IIIa, and 4 (66.7%) patients had complication of grade <3 . There wCurrently, the diagnosis and treatment strategies for BWT are relatively uniform. They all start with neoadjuvant chemotherapy and then undergo surgical treatment. Intra-operatively, to preserve normal renal function, it is necessary to preserve the nephron as much as possible. Adjuvant chemotherapy should be given according to the highest unilateral stage. The application of neoadjuvant chemotherapy regimens also gives children with BWT the opportunity to undergo NSS , therebyAt present, NSS mainly refers to the resection or stripping of kidney tumors. For small tumors located at the two poles of the kidney, the tumor and surrounding normal kidneys can be resected to ensure negative margins. However, an R0 resection cannot be guaranteed in few cases, namely when the tumor is in the middle of the kidney or close to the collecting system and hilum . PerformThe bilateral renal tumors in the 8 children with BWT reported in this study were either all quite large, or were located in the middle of the kidney or close to the renal hilum. Performing a traditional NSS would result in a residual tumor, inability to preserve sufficient normal residual renal tissue, and major intra-operative bleeding, which could further affect the judgment of the resection margin, and lead to damage of the renal vessels and pelvis. Intra-operatively, there can also be tumor rupture and dissemination, which increases the risk of postoperative recurrence and metastasis. In contrast, in kidney autotransplantation, resection of both the kidney and the tumor is performed in an isolated bloodless state. In this state, one can easily identify the tumor boundary, resect the tumors completely, reduce marginal tumor residues, retain more nephrons, reduce bleeding, and avoid complications such as high blood pressure and renal ischemia caused by damage to renal blood vessels. Thus, kidney autotransplantation with ex vivo resection of the renal tumor and reconstruction of the organ can be considered the best approach for this kind of complex case and can prevent permanent loss of renal function .Previous reports of the technique mostly focused on benign kidney diseases or adult patients. Up-to-date case reports on pediatric Wilm's tumor were limited. In our study, the duration from kidney resection to HCA cryopreservation solution injection was all within 2 min. This action shortened the renal warm ischemia time, which was significantly shorter when compared to the traditional NSS operation. Perfusion with cryopreservative solution and local cooling of the kidney with ice can preserve more renal function than conventional NSS surgery . FurtherThe most common postoperative complications in the 8 patients included urinary fistula, renal insufficiency, and hypertension. If there is a post-operative long-term urinary fistula, ultrasound-guided renal puncture with catheter drainage should be considered, according to the patient's situation. Perinephric drainage tubes and ureteral stent could be considered during the operation to reduce the morbidity and outcome of urinary fistula. Due to the huge size of the tumor, hyperperfusion nephropathy caused by the remaining normal kidney after removal can result in postoperative hypertension. Relative stenosis caused by intraoperative renal vascular anastomosis may also cause postoperative renal insufficiency or high blood pressure. We suggest paying particular attention to the risk of high blood pressure and using anti-hypertensive drugs early in management. Post-operative urinary tract ultrasonography should be performed regularly to check the patency of renal vessels. This kind of hypertension was often temporary and could be relieved by early diagnosis and treatment.In this study, 2 children had Denys-Drash syndrome, which is an extremely rare congenital genetic disease. The complete form of Denys-Drash syndrome manifests as diffuse mesangial sclerosing nephrotic syndrome, male pseudohermaphroditism, and Wilms tumor. Incomplete Denys-Drash syndrome has nephrotic syndrome as the main symptom and may be accompanied by male pseudohermaphroditism or Wilms tumor. Treatment with neoadjuvant chemotherapy and surgery should not be delayed even in children with bilateral nephroblastoma who have severe nephrotic syndrome and little normal renal tissue on preoperative evaluation. Such patients should be followed up regularly for the first 2 years after surgery to confirm the absence of tumor recurrence. Subsequently, the need for allogeneic kidney transplantation can be decided based on renal function. Patients with this syndrome may suffer from proteinuria, which can result in a loss of plasma albumin. Meanwhile, residual kidney has the possibility of tumor recurrence. For this situation, we suggest the resection of autologous residual kidney, with simultaneous transplantation of an allogeneic kidney.The median follow-up time in this study is 38 months and so far, none of the patients had a tumor recurrence. There is a need to further follow up on the long-term efficacy and the recovery of renal function. Furthermore, due to the small sample size, our experience is limited. SIOP-renal tumor study group from Europe and COG from America have conducted several international multi-center clinical trials, which may provide more evidences. In summary, we suggest that if the hospital's surgical technology and perioperative management conditions are feasible, kidney autotransplantation can be a choice for complicated BWT patients with a lower risk of perioperative complications and good prognosis.


The guidelines of the Surviving Sepsis Campaign suggest using invasive blood pressure (IBP) measurement in septic shock patients, without specifying for a preferred arterial site for accuracy in relation to the severity of septic shock. The objective of this study was to determine the mean arterial pressure (MAP) gradient between the femoral and radial artery sites in septic shock patients.This prospective study was carried out at a 20-bed ICU in a university hospital. Simultaneous MAP measurements at femoral and radial arterial sites were obtained in septic shock patients receiving norepinephrine (≥0.1 μg/kg/min), with a pre-planned subgroup analysis for those receiving a high dose of norepinephrine (≥0.3 μg/kg/min).p < 0.001. In Bland–Altman analysis of MAP measurements, the detected effect sizes were 1.14 and 1.04 for the overall and high-dose cohorts, respectively, which indicates a significant difference between the measurements taken at each of the two arterial sites. The Pearson correlation coefficient indicated a weak but statistically significant correlation between MAP gradient and norepinephrine dose among patients receiving a high dose of norepinephrine .The median norepinephrine dose across all 80 patients studied, including 59 patients on a high dose, was 0.4 (0.28–0.7) μg/kg/min. Overall, simultaneous measurement of MAP (mmHg) at the femoral and radial arterial sites produced mean (95% CI) MAP values of 81 (79–83) and 78 (76–80), respectively, with a mean difference of 3.3 (2.67–3.93), In septic shock patients, MAP readings were higher at the femoral site than at the radial site, particularly in those receiving a high dose of norepinephrine.ClinicalTrials.gov], identifier [NCT03475667].[ Invasive blood pressure (IBP) monitoring is a common procedure carried out in critically ill patients admitted to the intensive care unit (ICU) to optimize their hemodynamics. The international guidelines of the Surviving Sepsis Campaign (SSC) for the management of sepsis also suggest the placement of an arterial catheter as soon as practical in all patients requiring vasopressors . The accGenerally, in physiological conditions, systolic blood pressure (SBP) is higher and diastolic blood pressure (DBP) is lower, while mean arterial pressure (MAP) is unchanged, when measurements are taken at a peripheral arterial site  in comparison to a central arterial site  . HoweverAmong extant studies in the septic population, many have reported observing higher MAP values at the femoral artery site –23, whilOur study aimed to determine the MAP gradient between the femoral and radial artery sites in septic shock patients receiving norepinephrine (≥0.1 μg/kg/min), with pre-planned subgroup analysis for those receiving a high dose of norepinephrine (≥0.3 μg/kg/min).ClinicalTrials.gov website .This prospective observational study was conducted at a tertiary care center, specifically the 20-bed ICU of a university hospital in India, from Apr 2018–Jan 2020. The primary objective of this study was to compare femoral and radial arterial invasive blood pressure measurements in patients receiving norepinephrine (≥0.1 μg/kg/min) for septic shock and to correlate the pressure gradient with the dose of norepinephrine. The study protocol was approved by the Institutional Ethics Committee (IEC code: 2018-27-DM-EXP). A waiver of consent was granted by the Ethics Committee. The study was recorded on the Critically ill adult septic shock patients (as per Sepsis-3 definition) requiring norepinephrine infusion (≥0.1 μg/kg/min) and in whom the site of arterial invasive blood pressure monitoring was changed from radial to femoral, due to the current practice in our ICU as per the existing literature, were considered for inclusion in this study. All consecutively presenting eligible patients were included if they received a static dose of norepinephrine for at least 30 min with a functional radial artery monitoring system in place. Patients below the age of 18 years, pregnant women, patients with abdominal compartment syndrome, patients in whom a supine position was not feasible due to their clinical condition, and patients with a history of peripheral artery disease were all excluded from the study.All relevant demographic details, clinical characteristics, all vasopressor doses, and each patient’s need for mechanical ventilation were recorded, along with scores on two measures of ICU severity, namely the Sequential Organ Failure Assessment (SOFA) and the Acute Physiology and Chronic Health Evaluation II (APACHE II). In addition to IBP  readings, we also noted the number of patients in whom an absolute pressure gradient of ≥5 and ≥10 mm Hg was observed.via the spirit level technique  was used for femoral artery cannulation, while a 20-gauge catheter (BD Venflon™ Pro IV Cannula) was used for the radial artery. The arterial lines (pressure monitoring lines) used at both sites were similar. Blood pressure measurements were recorded in a supine position in cases in which both procedures were carried out on the same side (left or right), with the radial arterial line transducer at the level of the 5th rib in the mid-axillary line (phlebostatic axis), and the femoral line transducer placed at the same level as the radial line transducer. The equality of the levels of both the transducers was confirmed echnique . The adeAll pressure values  were recorded simultaneously three times within a 5-minute period, by freezing or taking a snapshot of the monitor, after placement of the femoral arterial catheter and before removal of the radial arterial line. The three readings for each value were averaged for analysis purposes.In a previous observational study, the minimum average paired difference in MAP (mean ± SD) between radial (86.7 ± 10.7) and femoral (91.1 ± 11.5) site blood pressure recordings was 4.4 ± 11.1 mmHg (effect size = 0.396) . Based ot-test was used to test the significance level of the mean differences observed. A Bland–Altman analysis was conducted, in which the bias (mean difference between two paired measurements) and corresponding 95% limits of agreement (reported in the form of mean ± 1.96 SD for the paired differences) were calculated for both the overall group and the high-dose group. To evaluate the absolute change in mean values in paired observations with respect to the corresponding pooled standard deviation, the effect size of the mean difference was calculated. The Pearson correlation coefficient (r) was used as an index of the relationship between norepinephrine dose and blood pressure gradient. All statistical analyses were performed using SPSS for Windows, version 23.0 , and a two-tailed P-value < 0.05 was considered to represent statistical significance.The normality of the continuous variables were assessed; variable was considered to be normally distributed when the Z score of the skewness was within a range of ±3.29 . NormallDuring the study period, a total of 520 patients were admitted to the ICU, and 422 of these received vasopressor therapy for septic shock. Among septic shock patients, 314 (74%) received a norepinephrine dose of at least 0.1 μg/kg/min at any point during their ICU stay . In accon = 80), invasive blood pressure readings (mmHg) taken simultaneously at the femoral and radial arterial sites revealed that the mean (95% CI) SBP values were 122 (118–126) mmHg and 119 (115–123) mmHg, respectively, with a statistically significant difference between the means of 2.9 (1.1–4.7), p = 0.002; additionally, the mean (95% CI) MAP values were 81 (79–83) mmHg and 78 (76–80) mmHg, respectively, with a statistically significant difference between the means of 3.3 (2.7–3.9), p < 0.001. In the subgroup of patients receiving a high dose of norepinephrine (n = 59), the mean (95% CI) MAP values (mmHg) at the femoral and radial arterial sites were 80 (78–83) and 78 (75–80), with a statistically significant difference between the means of 2.9 (0.6–5.2), p < 0.001  was observed for SBP in 21 patients (26%) and for MAP in 17 patients (21%). Among the subgroup of patients receiving high-dose norepinephrine, an SBP gradient of ≥5 mmHg was observed in 13 patients (22%), and a MAP gradient of ≥5 mmHg was observed in 11 patients (19%), with the radial site frequently underestimating the central blood pressure .Bland–Altman analysis indicated the presence of marked discrepancies or uncertainty in the measurement between the two methods, as the 95% limits of agreement indicated no specific direction for the change in mean difference . To quanr = 0.105; p = 0.805; 95% CI: −0.118 to 0.317). However, there was a statistically significant weak positive correlation between MAP gradient and norepinephrine dose among patients receiving a high dose of norepinephrine   and norepinephrine dose was not found to be significant across the entire sample, i.e., among patients receiving a norepinephrine dose ≥0.1 μg/kg/min (o 0.508) .Our study found that MAP measurements taken at the radial artery site are frequently underestimates in comparison to those taken at the femoral artery site in septic shock patients requiring norepinephrine (≥0.1 μg/kg/min). In previous studies comparing MAP measurements between the femoral and radial arterial sites in septic shock patients, findings have been inconsistent . Studiesn = 14) receiving a mean norepinephrine dose of 86 mcg/min, and the mean femoral site MAP observed was 15 mmHg higher than that observed at the radial artery site. Kim  at the femoral site, while no patients had a higher MAP (gradient ≥ 5 mmHg) at the radial artery site. This higher MAP (gradient ≥ 5 mmHg) at the femoral site was also observed in 58% of patients in the Kim study  and in 5r = 0.289; p = 0.026) between MAP gradient and vasopressor dose, which is a similar finding to that of the study by Kim    dose: 0.5 (0.35–1) μg/kg/min], the Pearson correlation coefficient indicated a weak correlation (< 0.001) . In anot 0.0001) . This co 0.0001) ; this coOur study has certain limitations. First, we did not include patients who were receiving a norepinephrine dose <0.1 μg/kg/min. Second, we did not investigate the effects of age, radial artery diameter, intra-thoracic pressure, or intra-abdominal pressure on the MAP gradient between the femoral and radial arterial sites. Additionally, we did not analyze the effect of concurrent use of vasopressin on the MAP gradient observed in patients who were receiving this. The long-term adverse effects of femoral artery site cannulation, such as digital ischemia, thrombosis, or other complications, were not followed up in our study. On the other hand, the primary strength of our study is that we included only septic shock patients receiving a norepinephrine dose of at least 0.1 μg/kg/min, including a pre-planned analysis with an adequate sample size of patients receiving a norepinephrine dose of at least 0.3 μg/kg/min.In comparison to the femoral artery site, invasive pressure monitoring at the radial artery site frequently underestimates SBP and MAP in septic shock patients receiving norepinephrine therapy. Hence, the findings of our study suggest that the femoral artery could be considered over the radial artery for accurate MAP measurement in septic shock patients, particularly in those who are receiving a high dose of norepinephrine, in order to minimize possible side effects arising from unnecessary exposure to higher doses of vasopressor agents for a prolonged period of time. However, the risk–benefit ratio of giving preference to the femoral arterial site in these patients is still not clear and needs to be investigated further.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by the Institutional Ethics Committee, SGPGIMS, Lucknow, India. Written informed consent for participation was not required for this study in accordance with the national legislation and the institutional requirements.BB: data curation, investigation, and original draft preparation. MG: conceptualization, methodology, project administration, supervision, validation, and writing – review and editing. PM: methodology, formal analysis, and software. AA: supervision and writing – review and editing. BP: methodology, and writing – review and editing. AB: project administration and writing – review and editing. All authors contributed to the article and approved the submitted version.