Circulating long non-coding RNAs (lncRNAs) have been demonstrated to serve as diagnostic or prognosis biomarkers for various disease. We aimed to elucidate the diagnostic efficacy of serum lncRNA SCARNA10 for the hepatocellular carcinoma (HCC).In this study, a total of 182 patients with HCC, 105 patients with benign liver disease (BLD), and 149 healthy controls (HC) were enrolled. According to different classifications, the levels of serum SCARNA10 were assessed by quantitative real-time polymerase chain reaction (qPCR). The correlations between serum SCARNA10 and clinicopathological characteristics were further analyzed. The receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to estimate the diagnostic capacity of serum SCARNA10 and its combination with AFP for HCC.SCARNA10 + AFP = 0.92 vs AUCAFP = 0.83, p <  0.01). SCARNA10 retained significant diagnosis capabilities for AFP-negative HCC patients.The results demonstrated that the levels of serum SCARNA10 were significantly higher in HCC patients than in patients with BLD and healthy controls, and significantly increased in HCC patients with hepatitis B or C infection, or with liver cirrhosis. Furthermore, positive correlations were noted between serum SCARNA10 level and some clinicopathological characteristics, including tumor size, differentiation degrees, tumor stage, vascular invasion, tumor metastasis and complications. ROC analysis revealed that SCARNA10 had a significantly predictive value for HCC , the combination of SCARNA10 and AFP gained the higher sensitivity (AUCIn summary, lncRNA SCARNA10 may serve as a novel and non-invasive biomarker with relatively high sensitivity and specificity for HCC diagnosis.The online version contains supplementary material available at 10.1186/s12885-022-09530-3. Hepatocellular carcinoma (HCC) is one of the most common malignant tumors globally with relatively high morbidity and mortality , 2. AlthLong non-coding RNAs (lncRNAs) are a class of non-coding RNA, which is longer than 200 nucleotides in length . AccumulPreviously, we identified lncRNA Small Cajal body-specific RNA 10 (SCARNA10) is up-regulated in the serum and liver tissue samples from patients with advanced hepatic fibrosis, which promotes liver fibrosis both in vitro and in vivo through inducing HCs apoptosis and HSCs activation . It has Here, we initially found that serum SCARNA10 level is higher in HCC than in healthy controls, SCARNA10 level was correlated with tumor differentiation degrees, size, stage, vascular invasion, lymph node metastasis, distant metastasis and complications. Combined detection of SCARNA10 and AFP was more effective for the diagnosis of HCC. SCARNA10 may serve as a potential diagnostic biomarker for HCC.This study analyzed a total of 281 serum samples obtained from 127 patients diagnosed with HCC, 55 patients diagnosed with benign liver disease (BLD) and 99 healthy controls (HC) at Tianjin Medical University Cancer Institute and Hospital  between October 2019 and March 2021. In addition, we collected 50 patients diagnosed with HCC, 50 patients with BLD and 50 HCs at Tianjin Medical University General Hospital for external validation. Patients with hemorrhagic or thrombotic diseases and those who have taken anticoagulant agents such as warfarin and similar drugs or vitamin K within 6 months of enrollment were excluded. The baseline characteristics of HCC patients, BLD patients and HCs were summarized in Table Venous blood were collected from the participants before treatment, centrifuged at 3000 rpm for 20 min, transferred the supernatant to EP tube, and quickly frozen to − 80 °C for later use, avoiding freezing and thawing cycles. Clinicopathological feature data including age, sex, tumor size and number, stage, lymph node and distant metastasis, vascular invasion, differentiation degree and complicatons were collected.Total RNA was extracted from equal volume of serum samples with TRIzol LS reagent  as described in the manufacturer’s protocol. All RNAs were digested with DNase I . cDNA was generated using the First-strand cDNA synthesize kit  with random hexamer primers in accordance with the manufacturer’s instructions. The synthesized cDNA templates were further amplified by SYBR Green master kit , and the expression of β-actin was used as the internal control. We calculated the relative expression values by comparing the normalized cycle threshold (Ct). The sequences of primers were as follows: SCARNA10 (forward): 5′-GTTTGGCTAAGCCCAGGGAC-3′, (reverse): 5′-GTTGGTCTGCCCTTACAGTGA-3′; β-actin (forward): 5′-GCCGGGACCTGACTGACTAC-3′, (reverse): 5′-TTCTCCTTAATGTCACGCACGAT-3′.Serum AFP levels were measured using the Roche Cobas E601 electrochemical immune luminescence analyzer  equipped with Roche dedicated reagents following the instructions provided by the manufacturer.P-value < 0.05 was considered to indicate a significant difference. All statistical analyses were performed using SPSS 20.0 .The date was analyzed by the Mann-Whitney test to assess differences between groups. Spearman’s correlation test was used to determine the relationship between serum SCARNA10 levels and biochemical parameters. The ROC analysis was performed to obtain the area under the curve (AUC), cut-off values, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Z-test was used to compare the AUCs between two groups, and ANOVA with post hoc analysis was used for the comparison of three groups. p <  0.05, Fig. To determine the significance of lncRNA SCARNA10 in HCC, the expression levels of SCARNA10 in serum of 127 HCC patients, 55 benign liver disease (BLD) and 99 healthy controls (HC) were examined by qPCR analysis. The relative serum levels of SCARNA10 in HCC patients were significantly higher than that in patients diagnosed with BLD and HC . Moreover, serum SCARNA10 levels was positively correlated with the tumor stage (p <  0.01). Serum SCARNA10 levels in HCC patients with vascular invasion, lymph node metastasis and distant metastasis were significantly increased . Simultaneously, serum SCARNA10 levels in patients experiencing complications were significantly higher than the levels observed in patients without complications (p < 0.01). However, there was no significant correlation between the SCARNA10 levels and age, sex, or tumor numbers.To investigate the clinical significance of SCARNA10 expression in HCC, the relationship between serum SCARNA10 levels and clinicopathological features in HCC patients were summarized in Table To further explore the utility of SCARNA10 as a promising diagnostic molecular marker for HCC, ROC curves of SCARNA10 and AFP were plotted in participants. As shown in Fig. To further estimate the complementary role of SCARNA10 for AFP in the diagnosis of HCC, the diagnostic value of SCARNA10 were assessed in HCC patients that were missed by AFP, based on the cut-off values obtained in this study (12.40 ng/ml and 31.20 ng/ml). As shown in Fig. Currently, the identification of novel potential serum biomarkers for the detection of HCC remains a vital goal, particularly for the diagnosis of early-stage HCC. Nevertheless, only a few biomarker candidates have been translated to clinical applications due to the limited study cohorts or diagnostic performance. For instance, so far, there is still only AFP as the most commonly used biomarker for HCC patients, despite its unsatisfactory sensitivity and specificity . SeveralAs previously researches, a large number of lncRNAs are aberrantly expressed in HCC compared with normal liver tissue, which is useful to distinguish HCC patients from healthy cohorts . HoweverHBV infection is the major risk factor for HCC development. Worldwide, > 50% of HCC cases are associated with HBV infection , 27. SevIn conclusion, we found the serum SCARNA10 level was increased in HCC patients, and associated with some clinicopathological features, including tumor size, differentiation degrees, stage, vascular invasion, metastasis and complications. The combined detection of SCARNA10 and AFP significantly improved the diagnostic sensitivity of HCC. However, the roles of SCARNA10 in HCC need to be elucidated in more detail. In future study, we will further research the definite function and mechanism of SCARNA10 in liver carcinogenesis.Additional file 1: Supplementary figure 1. Serum SCARNA10 levels in participants of external validation. (A-B) The relative levels of SCARNA10 in patients with HCC, benign liver diseases (BLD) and healthy controls (HC) were performed by qPCR. Scatter plot (A) and bar plot (B) are shown for SCARNA10 in HCC, BLD and HC. *p < 0.05. Supplementary figure 2. SCARNA10 and AFP complementation in the diagnosis of HCC. ROC of SCARNA10, AFP, SCARNA10 + AFP to distinguish HCC from HC (A), and BLD (B). Supplementary Table 1. Characteristics of participants in external validation. Supplementary Table 2. Performances of SCARNA10 and AFP for the diagnosis of HCC patients in external validation.


This trial was conducted to compare effects of continuing versus withholding single-pill combination tablets consisting of angiotensin receptor blockers (ARBs) and calcium channel blockers (CCBs) on perioperative hemodynamics and clinical outcomes.n = 106) were randomly assigned to Group C, in which ARB/CCB combination tablets were continued until surgery, or Group W, in which they were withheld within 24 h of surgery. Perioperative hemodynamics and clinical outcomes were compared between the Groups.Patients undergoing minor abdominal or urological surgery (p = 0.0052). Blood pressure during anesthesia was generally lower in Group C than Group W (p < 0.05) despite significantly more doses of ephedrine and phenylephrine administrated in Group C . The incidence of postoperative hypertension did not differ between Groups (p = 0.3793). Estimated glomerular filtration rate (eGFR) on the preoperative day did not differ between Groups (p = 0.7045), while eGFR was slightly lower in Group C than Group W on the first and third postoperative days , although clinically relevant acute kidney injury did not develop.The incidence of hypotension during anesthesia requiring repeated treatment with vasoconstrictors was higher in Group C than Group W  at Japanese Ministry of Health, Labour, and Welfare . Hypertension is a common condition affecting a significant percentage of populations. Current guidelines for the management of hypertension recommend a target blood pressure (BP) of < 140/90 or < 130/80 mmHg . AlthougIn patients with hypertension undergoing elective surgery, it is considered reasonable to continue medical therapy for hypertension until surgery . EspeciaAs mentioned above, CCBs are generally continued throughout the perioperative period while ARBs recently tend to be withheld preoperatively. However, it remains to be known whether ARB/CCB combination tablets should be continued or withheld preoperatively. The present study was conducted to compare effects of continuing versus withholding ARB/CCB combination tablets preoperatively on perioperative hemodynamics and clinical outcomes.The present single-blinded randomized controlled trial (RCT) was approved by the Institutional Review Board (IRB) of Juntendo University Hospital (JUH) and Juntendo Tokyo Koto Geriatric Medical Center (KGMC) , and registered with the Japan Registry of Clinical Trials (jRCT) at Japanese Ministry of Health, Labour, and Welfare . Written informed consent was obtained from each patient.2.Enrolled were ASA-PS II patients aged 20–80 years with primary hypertension treated with ARB/CCB combination tablets, who were scheduled to undergo minor abdominal surgery or minor urological surgery under general anesthesia between May, 2019 and March, 2020. Minor surgery was arbitrarily defined as surgery of which scheduled surgical time was 3 h or shorter and in which significant perioperative bleeding was unexpected. Excluded were patients with severe systemic disease corresponding to ASA-PS III or more, and patients with severe renal insufficiency defined as estimated glomerular filtration rate (eGFR) less than 30 mL/min/1.73 m® Combination Tablets  , REZALTAS® Combination Tablets LD and HD  , UNISIA® Combination Tablets LD and HD  , Micamlo® Combination Tablets AP and BP  , AIMIX® LD and HD  , ZACRAS® Combination Tablets LD and HD  , ATEDIO® Combination Tab.  , and generic products of these combination tablets. Consequently, these tablets included 12 different ARB/CCB combination tablets with different components and/or doses.ARB/CCB combination tablets under evaluation included 12 originator products—EXFORGEPatients were registered in the order of patients’ consent. Patients were randomly assigned to either continuing drug group (Group C), in which ARB/CCB combination tablets were continued until the evening before surgery or the morning of surgery, or withholding drug group (Group W), in which ARB/CCB combination tablets were withheld within 24 h of surgery, using the envelope method applied separately to patients scheduled for abdominal surgery and those scheduled for urological surgery.Patients were allowed to eat freely on the day before surgery. They were allowed to drink clear liquids freely until 2 or 3 h before scheduled operation room entry time. Patients not allocated to the first case of the day received i.v. infusion of Ringer’s solution, starting on the morning.Attending anesthesiologists were blinded to patients’ Groups. They were just instructed to anesthetize patients with general anesthesia alone, by inducing general anesthesia with opioids (fentanyl and/or remifentanil) and propofol and by maintaining anesthesia with inhalational anesthetics (sevoflurane or desflurane) and opioids. Otherwise, methods of the anesthesia management were left to the discretion of attending anesthesiologists depending on each patient’s condition and each surgical procedure, considering patient safety to be the first priority. At the end of surgery, i.v. fentanyl and/or i.v. acetaminophen were given for immediate postoperative analgesia. After anesthesia, patients were transferred from the operation room (OR) to the post-anesthesia care unit (PACU), and then to the ward.In the OR and PACU, significant hypotension defined as systolic BP (SBP) < 80 mmHg was treated with i.v. injections of vasopressors—i.v. ephedrine (4 or 5 mg/bolus) or i.v. phenylephrine (0.1 mg/bolus). If required, continuous infusion of phenylephrine was used. Significant hypertension defined as SBP > 160 mmHg persisting for 15 min was treated with vasodilators—i.v. nicardipine (0.5 mg/bolus) and/or transdermal isosorbide dinitrate (40 mg). If required, continuous infusion of nicardipine was used.2), a pulse rate (as a surrogate of the heart rate [HR]), a respiratory rate, and body temperature (BT) were measured and recorded on the medical record at least three times—after hospitalization, on the evening before surgery, and on the morning of surgery. In the OR, BP was measured and recorded on the electronical anesthesia record every 2.5 min. HR, SpO2, end-tidal carbon dioxide tension (ETCO2) and BT were monitored continuously and recorded every one minute. In the PACU, BP, BT, and pain scores and nausea scores rated on an 11-point numerical rating scale (NRS) were measured and recorded every 5 min. HR and SpO2 were monitored continuously and recorded every minute. Patients stayed in the PACU at least for 20 min until stable vital signs and adequate pain control were achieved. Postoperatively in the ward, the five above-mentioned vital signs and NRS pain and nausea scores were recorded every 2 h during the first 6 h, and thereafter every 6 h until the next morning. Afterwards, these variables were measured at least three times a day until discharge.Preoperatively in the ward, BP, percutaneous oxygen saturation  BP after hospitalization, (2) BP on the morning of surgery before drug administration, (3) BP after entering the OR before anesthesia, (4) the lowest BP after induction of anesthesia and before tracheal intubation, (5) the highest BP after tracheal intubation, (6) the lowest BP before surgery, (7) BP at the start of surgery, (8) the highest BP during surgery, (9) the lowest BP during surgery, (10) BP at the end of surgery, (11) the highest BP after extubation, (12) BP at the end of anesthesia, (13) BP after entering the PACU, (14) the highest BP in the PACU, (15) the lowest BP in the PACU, (16) BP at the end of PACU stay, (17) BP after return to the ward, (18) the highest BP in the ward, (19) the lowest BP in the ward, and (20) BP on the morning of the first postoperative day before drug administration. Likewise, HRs at the 20 perioperative time points were noticed.Routine blood tests were performed at least three times—on the day before surgery (PreOD), and on the first and third postoperative days (POD 1 and POD 3). Thereafter, they were performed repeatedly, as required.The primary endpoint was to investigate the effect of continuing versus withholding ARB/CCB combination tablets on the incidence of significant hypotension during anesthesia, defined as SBP < 80 mmHg requiring treatment with vasoconstrictors. Secondary endpoints included effects of continuing versus withholding drugs on (1) perioperative BPs and HRs, (2) vasoactive agents required during the perioperative period, and (3) clinical outcomes, such as postoperative complications, including abnormal blood test data, and postoperative hospital stay.Many RCTs investing the effect of continuing versus withdrawing ARBs or ACEIs, cited in a recent meta-analysis , were cot test and within each Group with the paired t test or repeated measures ANOVA followed by the Scheffe test. Nonparametric data were compared between Groups with the Mann–Whitney U test and within each Group with the Friedman test and the Wilcoxon signed-rank test. Categorical data were compared between Groups with the Chi-square test. Since BPs and HRs in the ward and PACU were mostly normally distributed, although occasionally, they were non-normally distributed in the OR, they were treated as parametric data. Conversely, most blood tests data were non-normally distributed, and they were treated as nonparametric data. However, most of percent changes in blood laboratory tests data investigated were normally distributed, they were treated as parametric data. Statistical analysis was performed with SPSS 25.0  and StatFlex ver. 7 . A p value < 0.05 was considered statistically significant.Continuous data are presented as Mean ± SD (Range) or Median (Interquartile range) (10th percentile–90th percentile or Range), according to data types indicated by the Kolmogorov–Smirnov test. Categorical data are presented as Number (%). Parametric data were compared between Groups with the unpaired A hundred and ten patients were registered. However, four patients (one in Group C and three in Group W) were excluded because the exclusion criterion was met by two patients, and the method of anesthesia was changed from general anesthesia alone to other anesthesia methods in two patients. As a result, a total of 106 patients (54 in Group C and 52 in Group W) were investigated.p = 0.5738 by the Chi-square test). Further, there were no significant differences between the Groups in patients’ demographic, surgical, and anesthetic characteristics (except for requirements of vasoconstrictors), albeit on the condition that amounts of bleeding and urine during transurethral procedures were assumed to be zero , while in Group C, the mean values increased from 126.4/70.1 mmHg to 148.4/85.3 mmHg (p < 0.0001). These mean values in the OR were lower in Group C than in Group W, as described below  changed significantly in both Groups during the perioperative period (p < 0.0001 for each by the ANOVA). Briefly, BP after entering the OR before anesthesia was higher; BPs during anesthesia were lower (except for the highest BP after intubation and the highest BP during surgery); BPs after extubation in the OR and PACU were higher; compared with BP on the morning of surgery in both Groups , including SBP/MBP/DBP after entering the OR before anesthesia, the highest MBP/DBP after tracheal intubation, the lowest SBP/MBP/DBP after tracheal intubation before surgery, the lowest intraoperative SBP/MBP, the highest DBP after extubation, and MBP/DBP at the end of anesthesia . Perioperative HRs mostly did not differ between the Groups, except for HR at the start of surgery and the lowest HR during surgery, which were higher in Group C than in Group W (p < 0.05 for each by the unpaired t test).HR changed significantly during the perioperative period in both the Groups (p > 0.05 by the Mann–Whitney U test) , including hemoglobin (Hb), total protein (TP), albumin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), creatinine, and estimated glomerular filtration rate (eGFR) (st) Fig. .Fig. 2Blp < 0.05 for each by the Friedman test). Hb, TP, albumin, and BUN were lower on POD 1 and POD 3 than on PreOD , while eGFR was higher on POD 1 and POD 3 than on PreOD . In the total cohort, percent decreases in TP, albumin, and BUN from PreOD to POD 1  were more than a percent decrease in Hb . Likewise, percent decreases in TP, albumin, and BUN from PreOD to POD 3  were more than a percent decrease in Hb .In the total cohort, these variables, other than AST and ALT, changed significantly . Creatinine was lower while eGFR was higher on POD 1 and POD 3 than on PreOD  .In both Groups, Hb, TP, albumin, and BUN were lower on POD 1 and POD 3 than on PreOD Fig. , and theeOD Fig. . In Grouts) Fig. . As a rets) Fig. . Follow-p > 0.05 for each by the Mann–Whitney U test).AST or ALT did not change significantly in Group C or Group W (p > 0.05 for each by the Friedman test), although AST and/or ALT increased to extremely high levels (> 100 IU/L) on POD 1 and/or POD 3 in two patients (one in Group W and one in Group C). AST or ALT on PreOD, POD 1 or POD 3 did not differ between the Groups . Hospital stay after surgery was not different between the Groups Table .In the present study, the incidence of hypotension during anesthesia defined as SBP < 80 mmHg requiring treatment with vasoconstrictors at least once did not differ between the Groups. However, the incidence of hypotension requiring repeated treatment with vasoconstrictors was higher in Group C than in Group W. BP during anesthesia was mostly significantly lower in Group C despite significantly more doses of vasoconstrictors administrated in Group C. The incidence of postoperative hypertension treated with vasodilators did not differ between the Groups. Although eGFR was not different between the Groups preoperatively, eGFR was lower in Group C than in Group W postoperatively.In both patients receiving and not receiving ARB/CCB combination tablets, BP after entering the OR before anesthesia significantly increased, compared with BP on the morning of surgery. BP after entering the OR was lower in patients receiving than not receiving ARB/CCB combination tablets. These results suggested that continuing ARB/CCB combination tablets helps to ameliorate hypertension in the OR before anesthesia. However, because it is unknown whether abnormal hypertension before surgery is associated with worse postoperative outcomes , clinicaClinically relevant AKI according to its definition  developeTherefore, creatinine might decrease normally and eGFR might increase normally postoperatively, thereby resulting in apparent improvement in postoperative renal function. In our patients, however, such changes were observed only in patients not receiving ARB/CCB combination tablets, and not in those receiving these drugs. As a result of apparently unchanged postoperative renal function in patients receiving these drugs in contrast to apparently improved renal function in patients not receiving them, creatinine was higher or tended to be higher and eGFR was lower postoperatively in patients receiving than not receiving ARB/CCB combination tablets, despite that both patients had comparable renal function preoperatively. Such small inter-group differences in indicators of renal function that appeared postoperatively might indicate that clinically latent, but not clinically relevant, deterioration of renal function developed postoperatively in patients receiving ARB/CCB combination tablets, relative to those not receiving these drugs. While ARBs and CCBs exert renoprotective effects in patients with hypertension and chronic kidney disease , intraopThere are some limitations of the study. First, we did not follow-up all the patients after discharge especially regarding their renal function primarily because we had not expected a possible unfavorable effect of continuing ARB/CCB combination tablets on renal function until we analyzed data. However, there were no patients who developed evident AKI as far as we searched. Second, our study evaluated effects of 12 different ARB/CCB combination tablets with different components and/or doses and thus with different vasodilatory potencies because it was quite difficult to recruit a sufficient number of patients receiving a single ARB/CCB combination tablet. Therefore, it may not be practical to standardize medication protocols of ARB/CCB combination tablets based on our results. Third, the sample size might be too small to perform multiple comparisons and to analyze multiple endpoints. Therefore, we could not obtain a definite conclusion from our data except for that intraoperative hypotension requiring repeated treatment with vasoconstrictors occur more frequently when ARB/CCB combination tablets are continued than withheld. However, we do not intend to conduct a further large-scale study to verify the present results especially in patients undergoing major surgery because from our results, the possibility can not be excluded that continuing ARB/CCB combination tablets perioperatively may cause AKI in some sensitive patients.In conclusion, continuing ARB/CCB combination tablets preoperatively in patients undergoing minor surgery increased the incidence of hypotension requiring repeated treatment with vasoconstrictors during anesthesia, increased requirements of vasoconstrictors to treat hypotension, and might deteriorate postoperative renal function, albeit only slightly. Further, continuing ARB/CCB combination tablets preoperatively did not help to prevent postoperative hypertension. Therefore, withholding ARB/CCB combination tablets within 24 h of surgery seemed to be a more acceptable clinical practice than continuing these drugs until surgery.


In 2014, Ontario’s Point-of-Care (POC) test providers were advised to focus efforts on provincially defined priority populations who experience a greater risk of HIV. Our objective was to describe the POC program before, during and after this change, including tester characteristics, follow-up testing results, positive predictive value (PPV) over time, and trends and characteristics of those with reactive test results without a confirmatory serological specimen.Test-level data of POC screening and confirmatory results were extracted from the Public Health Ontario HIV Datamart. Final test results were defined based on results of the confirmatory blood sample, or the POC test for “non-reactive” tests. Testing volumes, percent of total tests, percent positivity and PPV were calculated overall, annually, and by exposure group.P < .001), MSM , HIV-endemic , heterosexual – partner with identified risk  , and people who use injection drugs (PWID) . A total of 13.5% of reactive POC results did not have a serological sample submitted.Overall testing volumes decreased by 39.8% between 2014 and 2018. The majority of confirmed positive tests were in the men who have sex with men (MSM) exposure category, followed by HIV-endemic and heterosexual – no identified risk . Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 , increasing to 0.69% in 2018 . Increases in percent positivity corresponded with a decrease in the overall proportion of tests conducted in low-risk populations. When compared to the heterosexual-NIR category, PPV was significantly higher for men who have sex with men – people who use injection drugs (MSM-PWID) (52.7% compared to 100%, Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario’s POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations. The INSTI HIV-1/HIV-2 Rapid Antibody Test  provides rapid point-of-care (POC) testing for HIV and has been approved and available in Canada since 2005 . AdditioDespite the known benefits of POC testing, an ongoing concern of POC testing in Canada is the test performance characteristics compared to conventional serological testing for low-prevalence populations . For exaIn Ontario, Canada, a publicly-funded program for HIV POC testing has been available since 2007 . The majBeginning in 2014, POC test providers in Ontario were advised to focus POC testing efforts towards provincially defined priority populations who experience a greater risk of HIV . These iTest-level POC data were extracted from the Public Health Ontario HIV Datamart, for the POC test requisition data and the clinical laboratory data of confirmatory samples linked to reactive or window period POC tests. Test requisition data includes age, sex, reason for testing, and testing provider . Data was restricted to 2011 to 2018 due to data quality issues that affected the reliability of POC data capture prior to 2011 and extracted on September 18, 2019. Results for patients younger than 15 years of age were excluded from the analysis.Clinician entered risk factor information from the HIV test requisition was used to create hierarchical and mutually exclusive exposure categories for each patient, representing their most likely source of HIV risk . These en = 13) were excluded from this analysis.Table POC provider entered POC test results on the test requisition were extracted from the datamart: “reactive” , “non-reactive” , or “non-reactive—window period”. Tests were considered to be in the “window period” if the test was performed within 90 days of possible exposure to HIV . “ReactiWe defined the final test result based on results of the confirmatory blood sample for “reactive” and “non-reactive – window period” tests, and the POC test for “non-reactive” tests. Tests with no confirmatory sample sent were classified as having a negative final result, as per Ontario surveillance guidelines .Testing volumes, percent of total tests, and percent positivity were calculated overall, annually, and by exposure group using all test results as the denominator, and all first-time positive test results as the numerator. Tests that were identified in the HIV Datamart as repeat positives, based on patient data linkage, were excluded from the calculation of percent positivity.Positive predictive value (PPV) was calculated overall, annually, and by exposure group, using all POC reactive samples with a blood sample sent. PPV was calculated as the percent of POC reactive tests that were confirmed positive by laboratory testing. As the primary focus of this analysis was on the performance of the INSTI test as delivered by the Ontario POC program, both first time and repeat positive test results were included in the analysis.Changes over time for percent positivity and PPV were assessed for statistical significance by calculating confidence intervals using the standard error of the difference in percentage between the time frame. Statistically significant difference in PPV between exposure groups was calculated using Fisher’s exact test with Bonferroni correction. All statistical analyses were performed using Stata 15.1.POC testing numbers in Ontario increased from 25,901 in 2011, to a peak of 30,103 in 2014, and subsequently declined each year to a low of 18,128 in 2018. The majority of POC tests were conducted in males , the 20–29 year age group , and anonymously . Tester proportions by exposure category shifted over time, with testers in the MSM exposure category increasing from 29.0% of tests in 2011 to 55.7% of tests in 2018, and testers in the heterosexual—NIR category declining from 58.8% of tests in 2011 to 29.9% of tests in 2018.Overall testing volumes decreased by 39.8% between 2014 and 2018, with larger decreases for females (59.6%), testers ages 15–19 (64.5%), testers ages 20–29 (47.3%), as well as for coded tests (69.8%) and tests conducted at local public health unit clinics (64.6%)  were confirmed positive after an initial POC reactive or window period test, averaging 135 tests per year. The majority of confirmed positive tests were in the MSM exposure category (79.6%), followed by HIV-endemic (6.6%), heterosexual—NIR (4.2%), PWID (3.3%), MSM-PWID (3.0%), and heterosexual—PIR (2.8%).Overall percent positivity decreased from 0.59% in 2011 to 0.42% in 2015 , increasing to 0.69% in 2018 . Increases in positivity rates corresponded with a decrease in the overall proportion of tests conducted in low-risk populations (defined as testers indicating no identified risk (NIR) and testers indicating heterosexual sex with partners with no identified risk  – see Table P < 0.001), MSM , HIV-endemic , heterosexual – PIR , and PWID . While PPV remained consistently high over time in the MSM-PWID exposure categories and increased in the MSM and HIV-endemic exposure group after 2015, PPV fluctuated in other exposure categories and showed no consistent trend over time  of reactive POC results did not have a serological sample submitted. The number of reactive tests without a serological sample submitted fluctuated over time and did not show a consistent trend. Those with unknown or missing risk factors (35.3%), heterosexual – NIR (30.4%), PWID (25.0%) and NIR (25.0%) had the largest proportion of reactive tests where no confirmatory sample was submitted , that does not allow duplicate tests or prior positive results to be linked and accounted for at patient-level. Exposure information was missing for approximately 5% of tests; and entered exposure information may be misclassified due to inaccurate data collection or entry, or transcription error by the individual completing the requisition. Some of the exposure groups have a low number of reactive results due to either low testing numbers or very low prevalence of infection. Results for these populations, particularly trends over time, should be interpreted with caution due to low numbers. Additionally, test performance of individual POC sites were not assessed, and there is the potential for confounding to occur if false-positive test results were caused by testing errors at specific sites that also had larger patient populations of low-risk clients. Finally, as non-reactive tests that are not in the window period for potential infection were not subjected to confirmatory testing, other test performance characteristics  could not be assessed.Targeted testing towards populations at higher risk of HIV improved the overall test performance characteristics of Ontario’s POC testing program. While not unexpected, the large discrepancies between PPV in higher-risk, compared to lower-risk populations, suggests the need for greater awareness and messaging of the likelihood of false positive test results in different populations. This may be particularly important as POC testing expands to different modalities and settings , in order to prevent unnecessary concern or misinterpretation of HIV status.


P=0.016) between serum IL-6 levels and the synovitis grading suggests a direct correlation between IL-6 production and disease severity. An additional trial of 20 male BALB/c mice  showed no clinical nor histopathological evidence of adverse effects. According to histopathological and blood test results, we conclude that neutral electrolyzed saline minimizes mechanical and inflammatory damage to the joint and may be helpful as an alternative to rheumatoid arthritis therapy.Rheumatoid arthritis is globally present in about 1% of the population. This autoinflammatory disease modifies the connective tissue, causing pain and inflammation of the joints. Over time, it causes the loss of joint cartilage and bone mass, decreasing the patient's quality of life. Treatment options now available either give symptomatic alleviation or alter the disease process. Nonetheless, adherence to chronic treatment is typically limited due to adverse effects. As a result, new therapy approaches, such as systemic administration of neutral electrolyzed saline to improve patients' quality of life, are being investigated. The study is a randomized prospective preclinical trial with a single-blind and a 4-arm parallel group using a collagen-induced mice model to generate rheumatoid arthritis. It was carried out on 36 male BALB/c mice, with the primary outcome measure being a scoring system for histopathologic assessment. When all groups are compared, there are significant differences. In addition, the animal model was validated by the healthy group. The animals treated with neutral electrolyzed saline had much less cartilage degradation, bone erosion, pannus development, and inflammation than the placebo-treated mice. Serum IL-6 levels were evaluated in parallel with disease severity expressed as synovitis grading of the affected joints. Spearman's rank correlation coefficient (Rs) = 0.399 ( Rheumatoid arthritis (RA) is an autoimmune disorder that targets the connective tissue , ultimatApproved RA treatments include NSAIDs, DMARDs, corticosteroids, methotrexate, TNF-blocking, interleukin blocking, B-cell depletion, and CTLA4-Ig –9; they Therefore, there is an opportunity to explore new treatment options, which is the objective of this study by evaluating histopathological and functional changes in a murine RA model, treated or not with neutral electrolyzed saline. This solution has been activated by a controlled electrochemical process that leads to reactive chlorine and oxygen species (ROS) formation from a sodium chloride saline solution .Evidence about ROS intervention during RA is controversial. On the one hand, it leads to tissue damage, while on the other hand, it mediates disease severity by reducing tissue damage , 13. In Murine arthritis models are highly accepted, particularly the collagen-induced arthritis (CIA) mouse model . It is rThe study consisted of two stages. First, the safety and toxicity of parenteral administration  of neutral electrolyzed saline in mice fed a high-fat diet were analyzed. In a second stage, the therapeutic effect of the neutral electrolyzed saline  was evaluated in an animal model of rheumatoid arthritis.Neutral electrolyzed saline is an aqueous saline solution of sodium chloride, activated by a controlled electrolysis process (patent no. MX330845 B), and thus resembles activated saline, electrolyzed saline, or electrolyzed water. It had a neutral pH (6.0–7.5), and its active ingredient was 0.002% of active species of chlorine and oxygen . The parThis experimental procedure was approved by the Research and Ethics Committee of the Instituto Estatal de Cancerologia, Secretaria de Salud del Estado de Colima . The experimental subjects were handled in accordance with institutional procedures and satisfied the Mexican legislation related to laboratory animal practice (NOM-062-ZOO-1999) and the National Academy of Sciences Guide for the Care and Use of Laboratory Animals (2011). In addition, all animals were sacrificed following the American Veterinary Medical Association's 2013 criteria for animal sacrifice.Male BALB/c mice between 8 and 12 weeks of age with an average weight of 24–30 g  were included, and they were fed a high-fat diet (Western diet) as previously described . All anin = 10) was injected parenterally  with physiological saline solution (0.9% of NaCl) (placebo group) at a dose of 40 µL/d for 30 consecutive days. Group 2 (n = 10) was injected intraperitoneally with neutral electrolyzed saline (NES group) at a dose of 40 µL/d for 30 consecutive days.For this assay, two groups were formed. Group 1  were considered: autonomic evaluation , neuromuscular evaluation , and behavioral evaluation  . After tAccording to the “ARRIVE Essential 10” guidelines for Animal Research , the stuThe model includes two phases: induction and development of the disease. The induction starts with the immunization and lasts until the development phase is observed, detecting any visible sign of the disease. In this case, the development phase started on day 33, from the first immunization, when mechanical allodynia was observed. Then, immunization emulsion and boost emulsion were prepared as previously described by Raza et al. .The sample size was calculated by the resource equation  and resuMale BALB/c mice between 8 and 10 weeks of age were included and weighed 25–28g . For the animals selected to develop collagen-induced arthritis, the first sign of clinical disease  occurred on day 33 from the first immunization; a whole sample of 27 mice was randomized into three parallel groups of nine animals each, using a random allocation software package . The fouμL/d or 40 μL/d of neutral electrolyzed saline intraperitoneally.According to their corresponding group, all the animals  began the treatment in the development phase. The healthy group (not induced into AR) received no treatment, and the placebo group received an intraperitoneally physiological saline solution. According to their group, the two remaining groups received 20 All animals were euthanized by decapitation following the protocols outlined above and after the treatment period. Blood samples were obtained afterward, and the serum was separated and analyzed for inflammatory mediator interleukin-6 (IL-6) levels. According to the manufacturer's instructions, the analysis was made using the mouse IL-6 ELISA Kit RAB0308  and performed in triplicate. Simultaneously, a dissection of the left knee was conducted for histological processing.μm slices were stained with hematoxylin and eosin. Only the kidney sections were stained with Masson's trichrome. Images were taken with an Axiocam MRC-5 model digital camera  mounted on an AxioPlan 2M model bright-field optical microscope (Zeiss GmbH) with a motorized stage, and A-plan x4, x10, x20, and x40 objectives were used to grade the slices. All the photographs were acquired under the same lighting and exposure conditions. AxioVision software version 4.0 was used to conduct the analyses .All tissues initially analyzed were preserved in 10% buffered formalin and embedded in paraffin. For histopathologic evaluation, 5 Toxicity animal model: for kidney damage detection, the main parameters evaluated were acute tubular necrosis, tubular atrophy, tubulointerstitial fibrosis, and interstitial infiltrate of inflammatory cells. In addition, all renal histological findings were evaluated and quantified as a percentage of the cortical area affected by each defined parameter. x20 and x40 objectives were used to evaluate kidney slices.For liver damage detection, the main parameters evaluated were the number of hepatocytes, inflammatory cells, hepatic ballooning, and cell binucleation; all findings were evaluated under 400x magnification field, as the percentages of steatohepatitis and necrosis, previously reported.Rheumatoid arthritis animal model: mice's knee joints were evaluated microscopically using a modified scoring method for inflammation, cartilage injury, pannus development, bone resorption, and ectopic chondrocytes on a scale of 0 to 3. This score was determined by two blinded observers using a modified version of the previously published mouse scoring method of Tseng et al. , where 0p < 0.05. Since the Shapiro–Wilk test indicated nonnormal data distribution, all variables are shown with medians and the 25th and 75th percentiles (Q1 and Q3). The Kruskal–Wallis test was used to compare groups, with the Mann–Whitney U-test used as a post hoc analysis. Finally, Spearman's test was used to calculate correlations.Statistical tests were conducted with IBM SPSS version 20 software  with a statistical significance level of During the study, there was no evidence of toxic effects clinically detected in mice, according to FOB analysis. The mice did not present autonomic alterations , neuromuscular alterations , or behavioral alterations  (data not shown). In addition, no animal mortality was reported during the administration of NES. The weight of the mice did not show any differences when comparing the two groups .Kidney and liver weight did not differ between groups . The aniIt is essential to mention that the mice were fed a high-fat diet, simulating individuals on a Western diet. This is relevant to consider when analyzing the liver histological data mentioned in All the mice included in the treatment and follow-up concluded the study and were analyzed . Significant differences were found when comparing all groups. The healthy group had significantly less joint damage than all other groups, confirming the animal model . TreatmeAll histopathological scored variables have a high positive correlation, showing a direct relationship between the studied morphological alterations .Q1 = 4.9 to Q3 = 7.8), 13.9 pg/mL (Q1 = 6.0 to Q3 = 20.1), and 6.4 pg/mL (Q1 = 5.5 to Q3 = 10.1) in the healthy, NES20, and NES40 groups, respectively. The Kruskal–Wallis test shows a significant difference between the groups (P < 0.001). The post hoc analysis (Mann–Whitney U-test) shows that the NES20 group has elevated IL-6 levels in comparison with the healthy (P < 0.001) and NES40 (P=0.026) groups, while the IL-6 levels from the NES40 and healthy groups were not significantly different (P=0.116). To establish possible correlations between IL-6 levels and the severity of arthritis, serum IL-6 levels were evaluated in parallel with disease severity expressed as synovitis grading of the affected joints. The Spearman correlation coefficient (Rs) = 0.399 (P=0.016) between serum IL-6 levels and the synovitis grading suggested a direct correlation between IL-6 production and disease severity.Serum level values of the inflammatory mediator IL-6 were 5.1 pg/mL (μL vs. 20 μL per day), suggesting a dose-response relationship.Parenteral administration of neutral electrolyzed saline (NES) was safe and reduced inflammation and other joint degenerative changes caused by induced rheumatoid arthritis in a mouse model. In addition, the administration of NES at the highest dose prevented the elevation of IL-6 levels. Most benefits were linked to administering the highest dose  showed no difference in their IL-6 levels compared with the healthy group, while the values of the group that only received 20 μL/day were significantly elevated compared with the healthy or NES40 groups. Besides, a significant correlation was found between serum IL-6 levels and the synovitis grading, suggesting a direct correlation between IL-6 production and disease severity. Interleukin-6 (IL-6) is overproduced in the joints of patients with rheumatoid arthritis, suggesting that IL-6 production is a crucial factor in the pathogenesis of the disease [In addition, the beneficial effects of NES administration are reflected in the modulation of the IL-6 levels in the animal model of RA. The group that received the highest dose of NES  were normal throughout the follow-up. In addition, no adverse alterations were found in the liver or kidney tissues . The aniThe current study has certain flaws. The trial did not include current therapy, such as NSAIDs or DMARDs. In this regard, the aim of this study was just to determine the efficacy of the neutral electrolyzed saline on RA and not to make a comparison of efficacy among treatments. A gold standard therapy must be included once the efficacy of NES is evaluated in clinical models .Rheumatoid arthritis treatment with neutral electrolyzed saline reduces the joint's mechanical and inflammatory damage, which is correlated with a reduction in IL-6 serum levels.


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.