To evaluate whether a model of a daily fitness checklist for spontaneousbreathing tests is able to identify predictive variables of extubationfailure in pediatric patients admitted to a Brazilian intensive careunit.This was a single-center, cross-sectional study with prospective datacollection. The checklist model comprised 20 items and was applied to assessthe ability to perform spontaneous breathing tests.The sample consisted of 126 pediatric patients ) on invasivemechanical ventilation, for whom 1,217 daily assessments were applied at thebedside. The weighted total score of the prediction model showed the highestdiscriminatory power for the spontaneous breathing test, with sensitivityand specificity indices for fitness failure of 89.7% or success of 84.6%.The cutoff point suggested by the checklist was 8, with a probability ofextubation failure less than 5%. Failure increased progressively withincreasing score, with a maximum probability of predicting extubationfailure of 85%.The extubation failure rate with the use of this model was within what isacceptable in the literature. The daily checklist model for the spontaneousbreathing test was able to identify predictive variables of failure in theextubation process in pediatric patients. Thus, it isextremely important to establish protocols for the safe application of IMV,including the assessment of readiness for elective extubation, with the objective ofminimizing the morbidity associated with extubation failure and prolongedIMV.Weaning from invasive mechanical ventilation (IMV) is a critical period of transitionfrom mechanical respiratory support to spontaneous respiratory control by thepatient himself or herself.For this purpose, the child is placed on minimum IMV settings for a certain time,when signs of respiratory distress and blood gas changes are evaluated.,6 Some studies conducted in the pediatric population attempted toidentify predictors of successful extubation but were unable to determine the exactset of parameters sufficient for this discrimination.,6,7 Thus, there are no data in theliterature pointing to the superiority between the types of SBT performancemethods; therefore, thecombined factors that may predict test failure or success remainuncertain.,10,11The spontaneous breathing test (SBT) is used to assess whether patients are fit forextubation and thus minimize the duration of IMV and decrease complicationsassociated with hospitalization. because they facilitate the interaction andintegration of the professionals involved in their implementation. While some checklists have beenpublished to monitor ventilatory weaning in the adult population,,15,16 in the pediatricpopulation, there is a lack of research on the subject.Checklists are usually used in the hospital environment as tools for systematicapproaches to ensure the quality of care processesThus, the objective of this study was to evaluate whether a daily checklist model offitness for SBT can identify predictive variables of failure in the extubationprocess in pediatric patients admitted to the pediatric ICU.This study was approved by the Ethics Committee for Research on Human Beings of theinstitution (CAAE 91370818.0.0000.0096), and the results were presented according tothe STrengthening the Reporting of OBservational studies in Epidemiology (STROBE)protocol.Complexo do Hospital de Clínicas da Universidade Federal doParaná (UFPR) from August 2018 to August 2019, with theobjective of internally validating a daily fitness checklist model for SBT.This was a cross-sectional study conducted through the Graduate Program in Child andAdolescent Health, with data collection performed in the pediatric ICU ofPatients aged between 28 days and 14 years, with more than 24 hours and less than 30days of IMV, with parental and/or guardian consent, and who signed the informedconsent form were included in the study. Patients with tracheostomy, those who diedprior to extubation, as well as those who withdrew informed consent wereexcluded.During the study period, 388 patients were hospitalized and underwent IMV, of whom126 met the inclusion criteria .The researchers developed a daily fitness checklist model for SBT that consisted of20 variables, scored as one when present in the daily assessment at the bedside andzero when absent, with the final score ranging from zero to 20 .The 20 variables include in the daily SBT fitness checklist were studied usingmultivariate logistic regression to identify those variables with the greatestdiscriminatory power to better predict extubation failure and the risk of trachealextubation failure, estimated by adding the scores for the variables, multiplied bytheir weights, divided by the sum of the weights[math]The discriminatory power and the predictive power for extubation failure of thegenerated scores were evaluated using receiver operating characteristic (ROC) curvesand univariate logistic regression, respectively.The checklist was applied in the morning by the physical therapy team to all patientsuntil the decision of tracheal extubation. This decision was always made on thebasis of institutional practice, through laboratory and imaging tests, withoutinterference from the authors.Patients were considered eligible for tracheal extubation and SBT on the basis of theunit’s routine: stable clinical data, chest X-ray and previous arterial blood gasanalysis, with diet and sedoanalgesia suspended 3 hours before the procedure andprophylactic use of corticosteroids at least 30 minutes before the procedure toprevent upper airway obstruction.2O above thepositive end-expiratory pressure (PEEP), with a PEEP of 5cmH2O andinspired oxygen fraction (FiO2) ≤ 40%. The level of consciousnesswas assessed every 10 minutes using the Glasgow coma scale; tidal volume wasassessed using the mechanical ventilator; and heart, respiratory and blood pressurerates were monitored to ensure that they were within normal limits for eachpatient’s age group. When values were within the normal range, tracheal extubationwas performed, recording posttracheal conditions such as the need for inhalationwith adrenaline, respiratory support (oxygen therapy or noninvasive ventilation) orchange in the state of consciousness and vital data. In the presence of any changeduring the 30-minute SBT, the previous IMV parameters were reinstated, withreassessment at 24 hours.All patients submitted to the SBT protocol were placed in pressure supportventilation mode for 30 minutes, with a value of 7cmHThe primary outcome measure evaluated in the study was extubation failure, which canbe defined as the inability to maintain spontaneous breathing in the first 48 hoursafter removal of the tracheal tube.For data analysis, the Mann-Whitney test and the Pearson/Yates chi-square test wereapplied. A multivariate logistic regression model was applied to identify thevariables with the highest prediction and their respective odds ratios (ORs). ROCcurves were constructed to estimate the discriminant power of the independentvariables for the indication of SBT and planned extubation and to establish theweights of the variables. A univariate logistic regression model was applied toidentify the probability of SBT and planned extubation based on different scores andto establish the sensitivity, specificity and cutoff point. For all analyses, p <0.05 was considered the minimum level of significance .The sample size to evaluate the accuracy of the daily fitness checklist for SBT wasestimated with a sensitivity of 90%, type I error of 5% and margin of error of 5%,resulting in a suggested sample size of 126 participants.The study sample comprised 126 patients who followed the proposed protocol ofclinical evaluation, SBT and extubation. For these patients, the indication for IMVwas mainly lung disease; among the 17 patients with other causes of indication forintubation, 11 (8.7%) were patients with neurological diseases, 3 (2.3%) werepatients with some hematological disease, and 3 (2.3%) were patients with endocrinedisease complications .versus 9.0 (7.0 - 11.0), p < 0.001] < 0.001] .2O, ratio betweenpartial pressure of oxygen (Pa02) and FiO2 ≤ 200 and absence ofcough. These variables generated the so-called weighted total score (WTS),calculated using the weighted average equation, with attribution of the weightsindicated by the OR  ≥ 20mmHg, PEEP ≥ 6cm/Hy the OR .Using the total score, the checklist model for SBT predicted tracheal extubationfailure with a sensitivity of 83.3% and specificity of 86.7%, with a cutoff point of5 points. However, with WTS, higher sensitivity (89.7%) was obtained, with asignificantly lower number of variables and a cutoff of eight points .The cutoff of eight points indicated by the ROC curve was the same as that indicatedby the univariate logistic regression; when the probability of extubation failurewas less than 5%, the score obtained progressively increased, with a maximumprobability of predicting extubation failure of 85% with a score of 26 .The nine patients in whom extubation failed after SBT were reintubated (7.1%) due toaltered level of consciousness (2), upper airway obstruction (3) and postextubationrespiratory distress (4). Six patients received noninvasive ventilation (NIV), andthree received oxygen therapy prior to reintubation. The median number of days inthe ICU for patients who were reintubated was 11.0 (interquartile range - IQR 8.5 -24.0).2O, PaO2/FiO2 ≤ 200 and absence ofcough, with a good predictive power for extubation failure and a cutoff point of 8points.The checklist model for SBT, composed of 20 variables, was able to predict trachealextubation failure with a sensitivity of 83.3% and specificity of 86.7%, with acutoff point of 5 points. However, with WTS, a sensitivity of 89.7% was obtained fora weighted model with only six variables - indication of unresolved trachealintubation, chest X-ray abnormalities, PIP ≥ 20 mmHg, PEEP ≥6cm/H,18 and strongly recommended inpediatric ventilator weaning.Daily evaluations for extubation are considered an important practice for safeextubation in ICUs Thus, to wean from a ventilator, the patient must behemodynamically stable, and the cause that led to tracheal intubation must haveresolved to ensure safe and successful extubation. An association between chest X-ray abnormalitiesand extubation failure has also been reported. Thus, it is inferred that ventilatory parameters mayindicate the persistence of respiratory disease and, consequently, failure in theextubation process, justifyingthe use of parameters such as PIP, PEEP, and PaO2/FiO2≤ 200 as well as abnormalities on chest radiography.The transition from IMV to spontaneous breathing is complex and tests thefunctionality of multiple organs.Evidence suggests a strong association between a weak or absent cough reflex andextubation failure in pediatric patients. ,25,26Other authors have also highlighted the importance of evaluating cough during weaningand tracheal extubation.,27 The percentage of extubation failure within the normalrange can be explained by the protocol used, as standardization provides importantinformation for the team to manage the extubation process, supporting the idea thatSBT can be applied safely in a pediatric ICU. Another possible explanation is that SBT was conducted by aphysiotherapist, confirming the idea that respiratory weaning therapists add anadditional level of safety for pediatric patients without increasing IMV duration,length of hospital stay or extubation failure rate.,29Extubation failure occurred in nine patients (7.1%) of the sample, a percentagesimilar to that found in the literature, i.e., between 5 and 12%.,30 Therefore, even with prophylactic corticosteroids, threepatients presented with upper airway obstruction. This condition is the major causeof reintubation in the pediatric population, so much so that airway evaluations suchas the cuffleak test and the airway patency test are indicated. However, a negative test, whichsuggests the absence of leakage, should not delay an extubation attempt; therefore, this procedure was notconsidered in the checklist model proposed herein, although some researchers claimthat it is a safe method for evaluating and preventing postextubationstridor.,32,33There is no concensus on the prophylactic administration of corticosteroids prior totracheal extubation, and its efficacy is still under debate.The creation of daily assessment protocols for pediatric ventilator weaning thatidentify the ideal time to perform SBT is essential to ensure extubation safety inthese patients. However, the identification of risk factors associated withextubation failure still represents a challenge in pediatric ICUs. There is noconsensus that indicates precisely which variables are important during theextubation process and which of those factors should receive more attention fromevaluators. In this context, it is important for new daily assessment tools to beimplemented, both in digital media and free platforms, to facilitatemultiprofessional teams in the identification of patients able to be weaned fromventilation.The model developed herein for predicting the risk of extubation failure wasinternally validated, meaning that it was developed and tested with the same sample,and ORs and regression coefficients were used to assign weights to variables withlower or higher predictive power, with a reduction in variables when using WTS. Theresults obtained should, therefore, be interpreted considering this limitation, andexternal validation studies, with the application of the daily fitness checklist forSBT in other samples, should be conducted to confirm its applicability Otherlimitations include the noninclusion of an airway patency test prior to extubationfor patients at high risk of stridor and the unicentric nature of the study;therefore, the model should be applied with caution in other institutions due toinstitutional peculiarities.2O, positive end-expiratory effort ≥6cmH2O, arterial partial pressure/fractional inspired oxygen ratio≤ 200 and absence of cough being the variables most associated with failure.Thus, the weighted total score showed good discriminatory and predictive power forpredicting failure in planned extubation.The checklist model analyzed for the spontaneous breathing test was able to predicttracheal extubation failure with good sensitivity and specificity, with unresolvedtracheal intubation, chest X-ray abnormalities, positive inspiratory pressure≥ 20cmH


The efficacy and safety of endovascular treatment (EVT) in acute basilar artery occlusion (ABAO) has been confirmed by four randomized clinical trials. Nevertheless, the predictors of a 90-day favorable outcome after EVT have not been elucidated. We attempted to establish a nomogram for the prediction of a 90-day favorable outcome in ABAO patients with EVT.Clinical data of ABAO patients with EVT were obtained from two nationwide clinical trial registries in China. Factors associated with a 90-day favorable outcome were screened by multivariable step-wise regression on the basis of univariable analysis. A nomogram was established to predict 90-day favorable outcome after EVT.P-value < 0.0001], posterior circulation Alberta Stroke Program Early CT (pc-ASPECT) score ≥7 , Pons-Midbrain Index (PMI) score < 2 , Posterior Circulation Collateral Score (PC-CS) ≥5 , local anesthesia , time from onset to recanalization (OTR) <330 min , and no occurrence of early neurological deterioration  were included into the nomogram, with C-index values of 0.8730 and 0.8857 in the training and the internal validation set, respectively.The proportion of ABAO patients with a favorable outcome was 41.53% (157/378). Seven variables, including baseline National Institutes of Health Stroke Scale (NIHSS) <20 [odds ratio (OR): 8.330; The proposed nomogram provided a reliable prognostic scale, which can be employed in clinical settings for the selection and clinical management of ABAO patients.https://www.clinicaltrials.gov, identifier: NCT03370939. The clinical benefits of endovascular treatment (EVT) for acute ischemic stroke (AIS) patients with intracranial large artery occlusions (LVOs) in the anterior circulation, whether within or beyond the time window, have been confirmed in seven randomized clinical trials (RCTs) –7. The pIn this study, we established a nomogram to identify the preprocedural and peri-procedural factors for EVT outcome in ABAO patients that enable the prediction of functional outcome and assist clinicians in patient selection and clinical management.For purposes of replicating the procedure or reproducing the results, data are available to researchers upon request, by directly contacting the corresponding author.n = 2,071), vertebral artery occlusion (n = 174), or posterior cerebral artery occlusion (n = 54). The remaining 411 ABAO patients were further excluded if they have not undergone angiographic collateral assessment (n = 25), or a 90-day follow-up stage (n = 8). In total, 378 patients were retained in the cohort for subsequent analyses.This study is a retrospective analysis of the prospective data from the Acute Ischemic Stroke Cooperation Group of Endovascular Treatment (ANGEL)  and the The prospectively collected variables included age, sex, baseline modified Rankin Scale (mRS) score, baseline National Institutes of Health Stroke Scale (NIHSS) score, intravenous thrombolysis, mechanical thrombectomy (MT) procedure details, and follow-up outcomes. Neuroimaging variables included the posterior circulation Alberta Stroke Program Early CT Score [pc-ASPECTS] , the posFunctional outcomes in this study included a favorable outcome [modified Rankin Scale (mRS) of 0–2] and patient mortality within 90 days. Early neurological deterioration (END) was defined as an increase of the NIHSS score of ≥4 points compared to the baseline NIHSS, or if the patient died within 24 h after EVT. Successful recanalization was defined as a modified thrombolysis in a cerebral infarction grade (mTICI) score of 2b or 3, while futile recanalization was defined as 90-day mRS score of 3–6, despite a technically successful recanalization (mTICI score of 2b or 3). Symptomatic intracranial hemorrhage (sICH) was defined as a hemorrhage detected by CT/MRI, with an increase of ≥4 points or an increase of ≥2 points of the NIHSS score in any NIHSS domain compared with the immediate prehemorrhage neurological status, or the need for surgical treatment according to Heidelberg Bleeding Classification criteria . Trainedhttp://www.R-project.org, foundation for statistical computing, Vienna, Austria). For continuous variables, data are presented as the median and interquartile ranges (IQRs). For categorical variables, data are presented as frequency and percentage. The optimal cutoff value for each continuous variable in predicting the probability of favorable outcome after EVT in ABAO patients was calculated by a receiver operating characteristics (ROC) curve, in which all continuous variables were converted into categorical variables. Univariable logistic regression analysis was performed to compare variables in the framework of demographic, medical history, etiology, imaging parameters, procedural parameters, times and incidence of complication, between the favorable outcome and the unfavorable outcome groups. To test for collinearity between predictors of the multivariable logistic model, the variance inflation factor (VIF) of each predictor was calculated. No predictors with a VIF >5 were included in the final regression model . The discriminative performance of the nomogram model was assessed by a concordance index value, with values ranging between 0.5 (for a noninformative model) and 1 (for a perfectly discriminating model). The calibration plot was used to evaluate the degree of fit between the actual and the nomogram-predicted favorable outcomes. Decision curve analysis was used to discriminate the net benefit and the probability of a favorable outcome at 90 days, for ABAO patients undergoing EVT.All statistical analyses were performed using SAS version 9.4  and R version 4.2.1 software (on model . All stan = 25), or due to the absence of follow-up information (n = 8). Finally, 378 basilar artery occlusion patients who underwent EVT were included in the final analyses . After screening by step-wise logistic regression method, a baseline NIHSS < 20 , PC-ASPECT score ≥7 , PMI score < 2 , PC-CS score ≥5 , local anesthesia method , time from symptom onset to puncture < 330 min , and no occurrence of END  were associated with the 90-day favorable outcome in ABAO patients with EVT , are listed in with EVT .n = 302). The results of the corresponding univariable and step-wise multivariable logistic regression analysis of the internal validation set are listed in Based on the multivariable logistic regression model, a nomogram was developed to predict the probability of a 90-day favorable outcome, by assigning each independent predictor with a score ranging from 0 to 100 points. The cumulative sum of the assigned points for each factor in the nomogram represented the probability of a 90-day favorable outcome and ranged from 0 to 350 points. The probability of a 90-day favorable outcome ranged between 0.1 and 0.9 . In ordeFinally, we translated the predictive model into practice, by assigning the corresponding scores to each indicator, according to their contributions to the nomogram model, with 62 points for Baseline NIHSS scores < 20, 20 points for PC-ASPECT scores ≥7, 22.68 points for PMI scores < 2, 34.28 points for PC-CS scores ≥5, 52.57 points for the local anesthesia method and 25.97 points for OTP < 330 min, and 100 points for no-END. And the total scores of each patient were calculated as follows: total scores = (0 for NIHSS ≥20 or 1 for NIHSS < 20) × 62 + (0 for PC-ASPECT scores < 7 or 1 for PC-ASPECT scores ≥7) × 20 + (0 for PMI scores ≥2 or 1 for PMI scores < 2) × 22.68 + (0 for PC-CS scores < 5 or 1 for PC-CS scores ≥5) × 34.28 +  × 52.57 + (0 for OTP ≥330 min or 1 for OTP < 330 min) × 25.97 + (0 for END or 1 for no-END) × 100. The thresholds were 188.05 (in the training set) and 186.5 . Their sensitivities were 0.78344 (training set) and 0.82456 , and specificities were 0.82805 (training set) and 0.79389 . The probability of achieving functional independence was about 48%. The receiver operating curve and the scatter plot of the total scores of each patient in the training and in the internal validation sets are shown in The present study introduces a nomogram model, which incorporated with both pre- and peri-procedural parameters, including baseline NIHSS, PC-ASPECT, PMI, PC-CS, the anesthesia method, OTP, and END, and with a good performance of C-index of 0.873, to predict a favorable outcome at 90 days after EVT in patients with ABAO.In this study, the successful reperfusion rate was 87.04% 329/378), which was slightly higher than the 71% rate in the HERMES   clinical9/378, whThe scoring system , 35 for The limitations of this study are as follows. Although an internal validation of the nomogram has been conducted in this study, a future external verification would be required to determine the generalizability of the model. In addition, the high proportion of intracranial atherosclerotic disease (ICAD) due to the different ethnicity of the population in this study and the low proportion of intravenous thrombolysis might affect the extrapolation of the study's findings. Nevertheless, there might be additional unknown factors that were not included in the model, which would require further extension studies.Taken together, the proposed nomogram demonstrated a good discriminative performance in evaluating the probability of a 90-day favorable outcome for ABAO patients after EVT. This nomogram can be easily translated into practice, providing a reliable prognostic scale that can be employed in clinical settings, for the selection and clinical management of acute BAO patients.The original contributions presented in the study are included in the article/This study was approved by the Institutional Review Boards at Beijing Tiantan Hospital and at each trial site (KY2014-51-01 and 2017-048-01). The studies were conducted in accordance with the local legislation and institutional requirements. The participants provided their written informed consent to participate in this study.LL: Writing—original draft, Data curation, Investigation. JL: Writing—original draft, Conceptualization, Methodology, Writing—review and editing. J-jH: Conceptualization, Investigation, Writing—original draft. YG: Methodology, Writing—review and editing. Z-xY: Methodology, Writing—review and editing. QW: Investigation, Writing—review and editing. X-lZ: Data curation, Formal analysis, Methodology, Software, Writing—review and editing. FG: Conceptualization, Funding acquisition, Project administration, Resources, Writing—original draft, Writing—review and editing.


BackgroundRenalase gene polymorphisms are associated with an increased risk of essential hypertension, chronic kidney disease (CKD), heart disease, diabetes, and stroke. One of these polymorphisms is a common missense (rs2296545) polymorphism, which was reported to be related to hypertension. The aim of this work was to investigate the possible relation between renalase gene polymorphism (rs2296545) and hypertension in patients with CKD patients.Subjects and methodsNinety patients were included in this case-control study: 30 normotensive CKD patients, 30 hypertensive CKD patients, and 30 apparently healthy controls. Genomic deoxyribonucleic acid (DNA) was extracted from peripheral whole blood, and renalase gene (rs2296545) polymorphism was genotyped in all patients and controls by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios (OR) and their 95% CIs were calculated.ResultsWe found that the CC genotype and the C allele renalase (rs2296545) were statistically associated with the risk of CKD  and , respectively. There was a statistically significant difference between the hypertensive CKD patients and the controls regarding the CC genotypes and the C allele,  and  for the CC genotype and the C allele, respectively. The mean values of systolic and diastolic blood pressure were higher in the normotensive CKD patients with the CC genotype compared to other genotypes  and also were higher in hypertensive CKD patients with the CC genotype when compared to other genotypes (P= 0.001 for both).ConclusionThis study demonstrated a statistically significant increase in the renalase gene (rs2296545) CC genotype and the C allele in CKD patients, especially hypertensive CKD. Chronic kidney disease (CKD) is a global disorder with many etiologies. Genetic etiology is an important predictor of CKD, especially for those who end up with end-stage renal disease (ESRD) . Also, hRenalaseis is a 342-amino-acid flavoprotein enzyme that regulates cardiac function and blood pressure ,6. WhileOne of the renalase polymorphisms is a common missense rs2296545, in that there is a substitution from glutamic acid to aspartic acid Glu 37 Asp) at codon 37  Asp at c. Also, iThis study aimed to assess the genetic association of renalase gene (rs2296545) polymorphism and HTN among Egyptian CKD patients.Setting and populationA total of 90 participants were included in this case-control study; of these, 60 were CKD patients and 30 were age- and gender-matched healthy control participants. The included CKD patients were further divided into two groups: the first included 30 hypertensive patients, and the other included 30 normotensive patients. The included patients were recruited from the Nephrology Department and Renal Dialysis Unit of the Internal Medicine Department at Benha University Hospital, Benha, Egypt, between March 2017 and May 2018. All participants provided written informed consent before participating in this study. The Research Ethics Committee of Benha University Faculty of Medicine approved the protocol of the study . A full history and clinical examination were applied to all participants.CKD diagnosis was based on the Kidney Disease Outcomes Quality Initiative (KlDOQI) clinical practice guidelines for CKD, which provided evidence-based guidelines for all stages of CKD . Glomeru2 for three months or more; (iii) Non-diabetic; (iv) No evidence of hereditary kidney disease as solitary kidney; (v) Free from immune complex disease; (vi) Able to understand the information about all study procedures and to give free written approval consent prior enrollment in the study, and (vii) BP > 140/90 mmHg or patient on antihypertensive drugs in hypertensive CKD group and BP < 140/90 mmHg without treatment in normotensive CKD group.We included patients of both sexes who fulfill the following criteria: (i) Aged between 40 and 60 years; (ii) CKD patients with estimated GFR (eGFR) < 60 ml/min/1.73 mMolecular assessmentDNA ExtractionGenomic DNA was extracted from peripheral whole blood on EDTA by spin column method in concordance with blood genome DNA extraction kits protocol  . The extDetection of Renalase Gene Polymorphism (rs2296545)Using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP), renalase gene single nucleotide polymorphism (SNP) genotypes (rs2296545) were detected . Then, aPCR was done according to the manufacturer structure . Initial denaturation was at 95°C for five minutes for one cycle, denaturation at 94°C for 30 seconds, annealing at 58°C for 30 seconds, extension at 72°C for one minute for 35 cycles, and final extension at 72°C for five minutes.PCR products were added to the loading dye and then separated by gel electrophoresis 2% agarose gel and ethidium bromide was used for band staining. Then, it was visualized by ultraviolet light . The amplified products were analyzed with restriction enzyme (Eco 81I) that is unique for the target polymorphism renalase (rs2296545)with incubation for 16 hours with (Eco 81I).Statistical analysisOur data were analyzed by IBM SPSS Statistics for Windows, Version 20.0 . Shapiro-Wilks test was used to test normality. Mean ± standard deviation and range were used to describe the normally distributed quantitative data, and median and interquartile range were used to describe the not-normally distributed quantitative data, while numbers and percentages were used to show the categorical data. OR and 95%CIs were calculated. ANOVA test was used to statistically analyze the mean difference between the groups and the chi-square test was applied to compare qualitative categorical variables between groups. P <0.05 was considered significant.In the present study, after digestion of rs2296545 with corresponding restriction endonuclease Eco 81I), three genotypes were found: CC (139 and 70 bp), GG (209 bp), and CG  . The frequency of the C allele showed a statistically highly significant increase in the hypertensive CKD group compared to the control group (P<0.001).Renalase CC genotype and C allele carriers had a considerably higher risk of developing hypertensive CKD  and , respectively. CG genotype frequency between the hypertensive CKD group and the control group did not differ in a statistically significant way from the control group (P=0.12).The mean SBP and DBP showed a statistically significant increase in normotensive CKD patients with renalase CC genotype compared to other renalase genotypes (P= 0.014 and 0.002. respectively) Table .AdditionThe study focused on analyzing the rs2296545 polymorphism within the renalase gene, aiming to determine its potential association with CKD and HTN. After enzymatic digestion, three genotypes, CC, GG, and CG, were identified. Comparisons between CKD patients and controls revealed a significant increase in the frequency of the CC genotype and the C allele in the CKD group. The C allele was found to be an independent risk factor for CKD development.Further analysis of the genotypes and allele frequencies in normotensive and hypertensive CKD patients compared to controls showed that the frequency of the CC genotype and the C allele was significantly higher in hypertensive CKD patients. These carriers were at a notably higher risk of developing hypertensive CKD. The findings highlight the potential role of the rs2296545 polymorphism in the renalase gene as a risk factor for CKD, particularly in the presence of HTN. These results suggest that this genetic variation may be a potential marker for assessing susceptibility to CKD, emphasizing the importance of genetic factors in the development of this condition.CKD and HTN are often in a firmly merged relationship as either a cause or a result of one another. Many CKD patients have HTN, and the rate rises when CKD progresses in stages . HTN is Many genetic variants increase the risk of kidney disease and kidney failure in non-diabetic, hypertensive adults with African progenitors . RenalasIn the present study, we assessed Egyptian CKD patients (hypertensive and normotensive) to show the relation between renalase gene rs2296545) polymorphism and HTN in these patients. Renalase gene (rs2296545) polymorphism is related to the development of CKD and hypertensive CKD. A previous study proved that recombinant renalase has powerful hypotensive effects through cardiac contractility decreasing and slowing heart rate. Renalase supplementation can prevent the development of renal impairment and further organ injury [96545 polCC genotypes and C allele carriers had a significant risk of having CKD in comparison to a control group  and  respectively and also more likely to have hypertensive CKD , . George et al. revealed that renalase polymorphism was associated with CKD and its progression to ESRD in Africans in their systematic review .Malyszko et al. demonstrated the association between renalase and HTN in hemodialysis patients because of an overactive sympathetic nervous system . Lv et aIn renalase rs2296545) SNP, at codon 37, glutamic acid is replaced by aspartic acid; this substitution is critical as it affects the affinity of the enzyme for NADH (nicotinamide adenine dinucleotide + hydrogen) 6545 SNP,.In our study, we unearthed a striking correlation between the CC genotype of renalase rs2296545) and blood pressure readings in both CKD patients and those with hypertensive CKD. On the contrary, Shi and Wang concluded that renalase polymorphism was not associated with risk of HTN in all genetic models in their meta-analysis and confirmed that pooling data through meta-analysis increases the statistical power and the strength of their result . Fava et6545 and These conflicting results have sparked much debate among the scientific community, hinting at the possibility of divergent outcomes stemming from the differences in the populations under study. This intriguing discovery underscores the complexity involved in unraveling the genetic underpinnings of blood pressure regulation and the development of HTN. It challenges us to delve deeper into the intricacies of these genetic variants and their interplay with diverse physiological contexts, paving the way for a more nuanced understanding of this intricate puzzle.There are some limitations to the present study. The small sample size and collection from a single location do not reflect the whole Egyptian population. In addition, using regression analysis in studying the genetic association of renalase gene (rs2296545) polymorphism and HTN was a better statistical choice.From the results of this study and due to the statistically significant increase of C allele and CC genotypes in CKD and hypertensive CKD groups more than in the control group, the C allele is considered an independent risk factor for CKD and hypertensive CKD compared to G allele, which is a protective allele. Also, this study concluded that renalase gene polymorphism (rs2296545) was found to be significantly associated with increased risk of CKD and hypertensive CKD in Egyptian patients and can be used to predict the susceptibility of such diseases among Egyptian populations.


It is not known whether withdrawal of angiotensin-converting enzyme inhibitors (ACEIs) in children with advanced chronic kidney disease (CKD) is beneficial similar to adults. We report a case series of children with advanced CKD whose ACEIs were stopped.2 (range 8.8–19.9).In the last 5 years, we stopped ACEIs in seven consecutive children on ACEI therapy with rapidly declining CKD stage 4–5. The median age was 12.5 years (range 6.8–17.6); the median estimated glomerular filtration rate (eGFR) at stopping ACEIs was 12.5 ml/min/1.73 m2 (range −2.3 to +20.0) and relative increase of eGFR was 30% (range −34 to +99). The median follow-up after stopping ACEIs was 2.7 (range 0.5–5.0) years, either until the start of dialysis (n = 5) or until the last follow-up without dialysis (n = 2).Six to twelve months after stopping ACEIs, the eGFR increased in five children (71%). The median absolute increase of eGFR was 5.0 ml/min/1.73 mThis case series showed that withdrawal of ACEIs in children with CKD stage 4–5 and rapidly declining kidney function may lead to an increase in eGFR. Treatment of children with chronic kidney disease (CKD) with renin–angiotensin–aldosterone system inhibitors (RAASi) is the cornerstone of conservative therapy due to their antihypertensive, antiproteinuric, and renoprotective effects. Recently, van den Belt et al.  publisheWe aimed to present a case series of seven children from our tertiary pediatric nephrology center with CKD stage 4–5 (CKD5) and rapidly declining GFR with stopping angiotensin-converting enzyme inhibitors (ACEIs). Our case series is unique as no pediatric study has yet shown that, in contrary to adults, withdrawal of ACEIs in children with CKD5 can be beneficial in terms of kidney function.In the last 5 years, we stopped ACEIs in all seven consecutive children on therapy with RAASi who had rapidly declining GFR toward CKD stage 5 and have been not yet indicated for KRT with the aim to win time for preparation of KRT. We did it after reading the positive results of stopping ACEI in adults with advanced CKD –4 in hop2/day) and two received enalapril (0.1 and 0.2 mg/kg/day). The indication for ACEI was hypertension (n = 5) and hypertension with proteinuria (n = 2). The median eGFR [Schwartz formula (2 (range 8.8–19.9), and six children were already in CKD stage 5. The median eGFR slope 6–12 months before stopping ACEI was −9.8 ml/min/1.73 m2/year (range from −4.0 to −19.5). All children had declining eGFR at least in the last two assessments before stopping ACEI and had no acute infection or dehydration. The blood pressure index was calculated as patients’ blood pressure (BP) divided by the 95th percentile. Formal statistical analysis was not performed due to the low number of cases.The median age of the patients was 12.5 years (range 6.8–17.6); the primary kidney diseases were mainly congenital anomalies of kidneys and urinary tract. Five children received ramipril (median dose 2.3 mg/m2 (range −2.3 to +20.0) and relative increase of eGFR was 30% (range from −34 to +99). Improvement of eGFR >25% from baseline value [a parameter used by Ahmed et al. in their study (n = 5) or until the last follow-up without KRT (n = 2). The prognosis of these children improved as the time without the need for KRT  was prolonged.Six to twelve months after stopping ACEIs, the eGFR increased in five of seven children (71%). The median absolute increase of eGFR was 5.0 ml/min/1.73 mThe median BP and proteinuria at the time of stopping ACEI were 107/68 mmHg (BP index 0.93) and 28 mg/mmol creatinine (range 13–41), respectively, and they increased to 121/80 mmHg (BP index 0.97) and 138 mg/mmol creatinine (range 43–209) after stopping, respectively. The median serum potassium was 5.3 mmol/L (range 4.9–6.7) at the time of stopping ACEI and 4.8 mmol/L (range 4.4–5.2) after stopping. Patient and laboratory characteristic in all individual patients is given in In this small case series from our center, we compare the kidney function before and after withdrawal of ACEI in children with rapidly declining CKD stages 4–5. We could demonstrate that kidney function, similarly to the adults, improved also in children by approximately 70%.There are at least three adult studies showing that the withdrawal of ACEI in CKD patients leads to improved GFR –4. AhmedOn the contrary to the three adult studies that stopped ACEIs, the only pediatric study published recently by van den Belt et al.  showed i2) (2/year) (2) very slowly and as late as in 8 years.The reasons for discrepant results in the study by van den Belt et al.  and othe2) , 2. More(2/year) , 2. The 2/year  than in our case series (12 ml/min/1.73 m2), and the reasons for RAASi discontinuation were not specified. Furthermore the authors stated that “our results suggest that clinicians choose to maintain residual kidney function by discontinuing ACEi/ARBs.”In another pediatric study, Abraham et al.  showed i2) being prepared for the start of KRT with a rapid declining GFR slope might potentially profit from stopping ACEI with subsequent improvement of GFR as it has been shown in adults and in our pediatric cases.We speculate that the different results between our case series, adult studies, and those by van den Belt et al. and Abraham et al. are mainly due to different GFR at ACEI stopping (lower in the adult studies and our patients) and GFR slope before stopping (faster in the adult studies and our patients). We hypothesize, that highly selected patients with very low GFR at CKD stage 5 (10–15 ml/min/1.73 mOur case series has strengths and limitations. The main strength is the fact that it is only the second pediatric study dealing with kidney effects of withdrawal of ACEIs in patients with advanced CKD. There are several limitations, especially very small number of cases, the retrospective design, and the lack of a control group of patients without ACEI withdrawal.In a most recent article on the topic of stopping ACEIs in advanced CKD, Chan et al. recommended cessation of RAASi if patients develop rapidly declining kidney function progressing to CKD stage 5 . NeverthOur case series suggests that in some children with advanced CKD stage 5 and rapidly deteriorating kidney function, stopping ACEIs may lead to an increase in eGFR in some patients.


Mobile health  interventions are effective in improving chronic disease management, mainly in high-income countries. However, less is known about the efficacy of mHealth interventions for the reduction of cardiovascular risk factors, including for hypertension and diabetes, which are rapidly increasing in low- and middle-income countries.This study aimed to assess the efficacy of mHealth interventions for diabetes and hypertension management in Africa.1c (HbA1c), systolic blood pressure, and diastolic blood pressure. The random or fixed effect model was used for the meta-analysis, and the I2 statistic was used to gauge study heterogeneity. Z tests and P values were used to evaluate the effect of mHealth interventions on HbA1c and blood pressure levels.We searched PubMed, Cochrane Library, Google Scholar, African Journals Online, and Web of Science for relevant studies published from inception to July 2022. The main outcomes of interest were changes in hemoglobin A1c levels  among patients with diabetes and systolic blood pressure  and diastolic blood pressure  among patients with hypertension. After conducting sensitivity analyses using the leave-one-out method, the Kingue et al study had an impact on the intervention, resulting in a 2 mm Hg reduction in systolic blood pressure  but was nonsignificant for diastolic blood pressure and HbA1c levels after omitting the study.This review included 7 studies  with a total of 2249 participants. Two studies assessed the effect of mHealth on glycemic control, and 5 studies assessed the effect of mHealth on blood pressure control. The use of mHealth interventions was not associated with significant reductions in HbAOur review provided no conclusive evidence for the effectiveness of mHealth interventions in reducing blood pressure and glycemic control in Africa among persons with diabetes and hypertension. To confirm these findings, larger randomized controlled trials are required.https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=230642PROSPERO CRD42021230642;  Managing chronic diseases often calls for a long-term care strategy . DiabeteDisease management programs using mobile health  are promising emerging strategies to help patients self-manage their conditions . mHePrevious studies in some low- and middle-income countries have assessed the application of mHealth as a tool to increase drug compliance in patients with a range of long-term illnesses, including diabetes, chronic obstructive pulmonary disease, and HIV infection ,16. AlthMost individuals now possess mobile phones, and there are over 5.3 billion subscribers to mobile services worldwide, 67% of the world’s population ,20. TherThis systematic review was conducted following the PRISMA  guidelines  Multime. The proPubMed, Cochrane Library, Google Scholar, African Journals Online, and Web of Science were searched for relevant studies published from inception to July 2022, with assistance from a clinical librarian. The full search strategies, common Medical Subject Headings (MeSH), and search terms used across databases are available in Table S1 in Two independent authors (PA and KA) manually assessed and screened studies for both the titles and abstracts as well as full-text articles using an Excel sheet (Microsoft Corporation). Disagreements were resolved by consensus with a third author (CA) as necessary. This was performed in three stages as follows. First, PA screened the titles of all papers to determine their relevance. KA performed a cross-check by screening 20% of the titles excluded by the first reviewer, and it was confirmed that none of the titles screened by the second reviewer met the inclusion criteria. Second, abstracts of the papers selected after the title screening stage were again screened by PA and KA following the same procedure as described in step one. Finally, the full texts of potentially relevant papers were retrieved and evaluated by PA and KA independently to ascertain their relevance and usefulness to the review. Disagreements were settled through dialogue with CA to reach an agreement. Duplicates were also identified using EndNote reference manager .1c (HbA1c), systolic blood pressure, or diastolic blood pressure; the studies were randomized controlled trials (RCTs); the articles were written in English; and the studies were conducted in hospitals and primary health centers.We included studies that met the following criteria: the patients had hypertension or diabetes and were 18 years or older; the patients had received treatment at a selected health care setting; the intervention included an mHealth component; the results included target values of hemoglobin AWe excluded studies in which the full text was not available after attempts to contact the author, the research participants were pregnant women or a specific patient population , the results did not describe primary outcomes, the primary intervention did not use mHealth devices, or the articles were unpublished manuscripts or conference abstracts.The quality of each study was assessed using a 28-point scoring system as adopted from the Downs and Black checklist . The incTwo authors (PA and KA) independently extracted the following study characteristics from each included article using a tested extraction form: first author, year of publication, mean age, the country where the study was conducted, the participant (patient with diabetes or hypertension), mHealth location , condition (diabetes/hypertension), sample size, mHealth intervention, study design, and outcome of the intervention.1c, systolic blood pressure, and diastolic blood pressure) were analyzed separately using random or fixed effects models with a weighted mean difference (WMD) in ReviewManager  [I2 statistic was calculated to measure the percentage of variation across trials due to heterogeneity, with values of <50% and ≥50% indicating low and high levels of heterogeneity, respectively. The WMD for blood pressure and HbA1c between the intervention and control and Z tests were used to compare groups, and P<.05 was regarded as statistically significant. We checked publication bias subjectively by funnel plots and objectively by Begg and Egger tests using Stata version 16 (StataCorp). Begg and Egger tests with P<.05 were considered to have signiﬁcant publication bias.The data for the primary outcomes (HbAoration) . The I2We identified 2908 records from our search; authors screened 2880 titles and abstracts after duplicates were removed. In total, 7 studies (RCTs) -29,31 we1c levels in patients with diabetes . No significant publication bias was detected visually by the funnel plot (P=.30) and Egger (P=.10) tests.As shown in nel plot  or statiP=.69; I2=47%) between the intervention and control groups (P=.65) and Egger (P=.81) tests.There was no statistically significant difference in diastolic blood pressure . No significant publication bias was detected visually by the funnel plot (P=.96) and Egger (P=.10) tests.Additionally, as shown in nel plot  or statiP=.01; 1c, the exclusion of each of the studies rendered the WMD nonsignificant (Sensitivity analyses were conducted using the leave-one-out method. For systolic blood pressure, the Kingue et al  study hanificant  and 10.This systematic review and meta-analysis identified 7 RCT studies that assessed the effectiveness of mHealth interventions on blood pressure and glycemic control among patients with hypertension and diabetes in Africa. In this review, the effectiveness of mHealth interventions on blood pressure and glycemic control among patients with hypertension and diabetes in Africa did not show conclusive evidence.For systolic blood pressure, we observed a reduction after the mHealth intervention compared to usual care by an average of 1.39 mm Hg; however, it was not statistically significant. After conducting a leave-one-out analysis, a study by Kingue et al  had an iFor diastolic blood pressure, our study observed no lowering effect of the mHealth intervention, which reduced by an average of 0.36 mm Hg, which is inconsistent with studies performed by Lu et al  who repo1c outcomes compared with usual care [1c, saw a substantial reduction in fasting plasma glucose of −1.6 mmol/L. Although evidence is scarce about the effect of mHealth interventions on the management of patients with diabetes, the difference could be attributed to the better care the system generates from the health providers. Another reason is that long-term interventions likely result in more significant changes in glycemic control than short-term mHealth interventions.For glycemic control, the meta-analysis results showed no improvement after the mHealth interventions. Our study contradicts previous studies by Mao et al , Moattarual care ,35,37,38ual care  study inTo the best of our knowledge, this review was the first that assessed the effectiveness of mHealth interventions in diabetes and hypertension management in Africa. Quality appraisal suggests that the quality of the included studies was good. Additionally, the included studies show no publication bias. However, there are limitations to acknowledge. Despite a thorough search, the number of included studies was relatively small, signifying that using mHealth interventions in Africa on patients with hypertension and diabetes remains an emerging area. This review may not be able to capture some significant effects due to the small samples in the included studies. Given the above limitations, future studies with larger samples are needed to validate our findings.Our study showed no conclusive evidence on the effect of mHealth interventions on systolic blood pressure, diastolic blood pressure, or glycemic control. However, the sample sizes of the included studies were small; therefore, there is a need for larger RCT studies to confirm these findings.


However, with their relative newness in clinical use, these agents are frequently held because of concerns of worsening kidney function and AKI. These concerns largely stem from the occurrence of AKI during safety profile analysis of large randomized clinical trials with SGLT2is and from postmarketing reports that prompted the US Food and Drug Administration (FDA) to issue a warning that SGLT2is might cause AKI. The hemodynamic mechanism of action of SGTL2is corroborated with the concerns for AKI. By inhibiting sodium/glucose cotransporter 2 (SGLT2) in the S1 segment of the proximal convoluted tubule, where 90% of the filtered glucose reabsorption occurs, the consequent glucosuria and natriuresis increase macula densa sodium chloride delivery, stimulating tubuloglomerular feedback, resulting in afferent arteriolar vasoconstriction and reduced intraglomerular pressure. This hemodynamic effect can lower BP, induce a mild acute decline in eGFR, and raise creatinine at times enough to fulfill the creatinine-based criteria for AKI.24 SGTL2is may provide metabolic effects against AKI similar to the posited cardioprotective benefits. SGLT2i is believed to increase myocardial energy consumption of ketone bodies, which leads to a more energy-efficient cardiac workload. Similar findings have been reported in the kidneys where SGLT2i reduces the use of glucose and shifts metabolism to fatty acids and/or amino acids for oxidative phosphorylation. In addition, new findings have shown that increases in urine volume during SGLT2 inhibition are transient despite persistent glucosuria, suggesting osmotic diuresis to be limited with long-term SGLT2 inhibition, despite the continued excretion of glucose solutes.5 These hemodynamic and metabolic changes triggered by SGLT2is underlie the kidney protection.6However, despite this mechanism of action and contrary to the initial concerns, several large, prospective, and randomized studies and a meta-analysis have failed to show an increased AKI risk with SGLT2i and instead showed that they may even reduce AKI risk.et al. performed a retrospective analysis from the five hospitals in the Yale Health System aiming to gain clinical insights into the safety of continuing or starting SLGT2is in the setting of hospitalization with acute HF (AHF) in patients who develop AKI. The authors assessed the effect of SGLT2is on 30-day mortality and rate of renal recovery among AHF patients with AKI exposed and unexposed to SGLT2is within the first 10 days of AKI diagnosis. To adjust for potential biases introduced by the differences from nonrandom allocation of treatments and the potential effect of immortal bias because of different timing of SGLT2i initiation, the authors applied a sophisticated statistical analysis plan. First, they calculated a propensity score representing the probability of receiving SGLT2is using a logistic regression model that incorporated 36 covariates. Different than a traditional propensity score, they applied the inverse of the propensity score or the inverse probability of exposure for adjusting the risk in the exposed group and the inverse of the complementary probability (1—propensity score) for the non-exposed group. This strategy improves the balance of the covariates across treatment groups, making the groups more likely comparable and reducing the effect of confounding by covariates. In addition, to account for differences in duration of exposure to SGLT2i, the authors modeled SGLT2i as a time-varying covariate in the Cox regression analysis, so exposed individuals contributing time to their cohort only after SGLT2i receipt.Despite the accumulating evidence over the past 5 years on the beneficial actions of SLGT2is on acute and CKD, these agents are still often withheld in patients at risk of AKI or during early stages of kidney injury. Because most kidney protective studies have been conducted in the outpatient setting, Aklilo Using this approach and a definition for kidney recovery of a decline in serum creatinine (sCr) to a level below the threshold for the sCr Kidney Disease Improving Global Outcomes AKI criterion, they found the rate of kidney recovery over time was not proportional between the groups, but there was no difference in time to recovery or rate of recovery at 14 days in the SGLT2i-exposed and unexposed groups. Similar results were found after modeling with a term for interaction with time to address the bias resulting from the violation of the proportional hazards assumption. Time to recover was also similar between groups. In addition, the authors found that individuals prescribed SGLT2is had a remarkable 55% lower risk of death at 30 days. Overall, these findings make a compelling argument for the continuation of SGLT2is in AKI.7 and stage 1 AKI is a common occurrence. In this study, stage 1 AKI was the highest stage in 69% of the unexposed group and 75% in the exposed group, and the median time to recovery was <2 days in both groups. Thus, considering both the magnitude of serum creatinine elevation and the duration of AKI, the transient mild elevation of sCr was likely a result of hemodynamic fluctuations from diuresis or medications.9 However, the unexposed groups were significantly less often on a loop diuretic before an AKI event (64% versus 80%), suggesting that the unexposed group was less likely to have hemodynamic-associated AKI and thus less prone to be affected by the hemodynamic effects of SGLT2is. In this scenario, it is also not expected that SGLT2is would further interfere with kidney recovery. However, on the basis of the data from this study, it is still unclear whether in patients with more severe kidney injury, SGLT2is can be safely continued.However, there are some important factors to consider when interpreting and applying these findings. First, the cause of AKI may be distinctly different in the exposed versus unexposed group, and AKI in AHF is not the same as AKI in other conditions, such as sepsis. Kidney function changes dynamically in many patients hospitalized with AHF,10; thus, even if patients with HFpEF in the unexposed group were given a SGLT2i, it is unlikely they would derive mortality benefit. Mortality rates are similar in patients with HFpEF and HFrEF; however, patients with HFpEF more often die of non-HF and non-cardiac causes of death, which again is a risk SGLT2i is less likely to mitigate.Second, patients in the SGLT2i-exposed group more often had HF with a reduced ejection fraction (HFrEF) while most patients in the unexposed group had HF with a preserved ejection fraction (HFpEF). It is important to note that empaglfilozin was not FDA-approved for HFpEF until February 2022, 3 months before the end of this study period, and dapaglifozin, the main SGLT2i used in this study, was not FDA-approved until May 2023. While probably used off-label before FDA approval, as the authors noted cardiologists in the Yale system were allowed to use SGLT2i as adjuvant diuretics in AHF, SGLT2i was likely not applied as readily in patients with HFpEF than in patients with HFrEF before 2022. Furthermore, the primary benefit of SGLT2is in patients with HFpEF is a reduction in HF readmission and not mortalityβ-blockers and angiotensin antagonists were often withdrawn during episodes of AHF or AKI. Years went by though until it was recognized that this practice was unnecessary in most patients and potentially harmful. With these findings, hopefully we will not repeat the past mistakes, waiting for years to learn that holding SGLT2is leads to harm. A little permissive hypercreatinimenia in HF may go a long way.While these are important considerations when translating these findings into real-world practice, we agree that continuing SGLT2i in patients with mild AKI is warranted, especially given that when these drugs are discontinued during AKI and are frequently not resumed at discharge. However, it may be important to differentiate between initiation and continuation because the initial hemodynamic effect can worsen kidney perfusion acutely and may delay AKI recovery in more severe injuries. In addition, these findings reassert the importance of continuing guideline-directed medical therapy in patients with AHF regardless of kidney function. This is especially important so as not to commit the same errors from the past. Previously,


BackgroundUrinary tract infections (UTIs) are the most common infections following kidney transplantation. Risk factors for UTIs in kidney transplant recipients include female gender, age, pre-transplant urinary tract abnormalities, diabetes, and recurrent UTIs. Infections of the bladder or urethra are termed lower UTIs, while those involving the kidneys or ureters are called upper UTIs.MethodsWe retrospectively screened our hospital information system to identify all patients who underwent kidney transplantation in the surgery department at King Abdulaziz Medical Center in Riyadh. A total of 553 records were ultimately included in the final analysis.ResultsEscherichia coli (51.0%) and Klebsiella pneumoniae (21.8%). UTIs were significantly more prevalent among females, accounting for 73.6% of cases. Antibiotics were used in 86.5% of patients, with trimethoprim/sulfamethoxazole (65.8%) and ciprofloxacin (54.8%) being the most commonly prescribed.A total of 553 patients were ultimately included in the analysis. More than half of the patients were males (62.4%), and 31.1% were aged between 45 and 60 years. Of these, 230 patients had a UTI, representing 41.59% of the sample. The most commonly reported causes were hypertensive nephrosclerosis (43.4%) and diabetic nephropathy (28.8%). The most frequently isolated causative agents were ConclusionE. coli and K. pneumoniae were the most commonly isolated organisms. Trimethoprim/sulfamethoxazole and ciprofloxacin were the most frequently prescribed antibiotics. A significant association was found between acquiring a UTI and being female (p < 0.001), as well as having pre-existing bladder dysfunction (p = 0.024).About half of the patients in this study suffered from UTIs.  Urinary tract infections (UTIs) that occur early after surgery are the most common infections after kidney transplantation (KT) . AccordiKlebsiella, Proteus, and Pseudomonas aeruginosa, are also frequently isolated. Meanwhile, Gram-positive pathogens like Streptococcus species and Staphylococcus saprophyticus are less common [Risk factors for UTIs in kidney transplant recipients are similar to those in the general population and include female gender, age, pre-transplant urinary tract abnormalities, diabetes, and recurrent UTI . Furthers common .Escherichia coli and Klebsiella pneumoniae were the most common pathogens identified. The mean glomerular filtration rate at 12 months in patients with a urinary tract infection was significantly lower than in patients without an infection [Globally, one Turkish study investigated the risk factors for urinary tract infections in kidney transplant patients and their effects on graft function . A totalnfection .2). Therefore, symptomatic UTIs that recur in the first year after transplantation have a long-term adverse effect on graft function [A retrospective cohort study of 380 recipients who developed symptomatic UTI within one year of transplantation was conducted . During function .E. coli (47.5%) and Klebsiella (16.2%) were the most frequently isolated pathogens [Moreover, another study was conducted to investigate the impact of severe UTIs after renal transplantation on both graft function and healthcare resources . They peE. coli 4.5% and KLocally, a study was conducted at the Hamed Al-Essa Organ Transplant Center in Kuwait to evaluate risk factors for recurrent UTIs and their long-term outcomes in kidney transplant recipients. The study included 1,019 patients who underwent kidney transplants between 2000 and 2012. Factors such as age, gender, pre-transplant urinary tract abnormalities, retransplantation, mode of induction and maintenance of immunosuppression, and associated comorbidities were identified as risk factors. The study particularly focused on recipients who experienced recurrent UTIs, defined as four or more episodes a year or two or more every six months. Graft function levels and timing of graft outcomes were compared using serum creatinine levels after one year, and no significant difference was found (P > .05). It was observed that recurrent UTI was most common among women and increased the risk of vaginal colonization by uropathogens .Another retrospective chart review was conducted at King Abdulaziz Medical City and included 279 renal transplant recipients. Of these, 35% experienced a UTI within the first six months following the transplant, with the majority occurring in the second month. The recurrence of UTI was also most frequent in the second month and decreased over time. The study found no association between UTIs and acute rejection or between UTIs and post-transplant renal function. It concluded that UTIs may have little or no adverse impact on long-term graft survival outcomes. However, UTIs and their first recurrence were associated with increased hospitalization rates after transplantation, at 49% and 32% respectively. UTIs were most commonly seen in the first six months post-transplant, and the risk increased with factors such as older age, female gender, neurogenic bladder, and receiving the transplant abroad [Multiple studies have been conducted to assess the impact of urinary tract infections (UTIs) following kidney transplantation. However, limited data is available on this subject in Saudi Arabia. In this study, our aim was to assess the impact of post-transplant UTIs on a cohort of renal transplant recipients who were followed and treated at King Abdulaziz Medical City (KAMC) from 2016 to 2022. Additionally, we sought to investigate potential recipient-related risk factors for the development of UTIs, identify the most frequently occurring pathogens causing UTIs, and examine the rate of acute rejection incidents following kidney transplantation in relation to UTIs. Finally, we aimed to identify the most common causes of end-stage renal disease (ESRD) that led to kidney transplantation in this patient group.Study population and data selection Our hospital information system was retrospectively reviewed for all kidney transplant patients at the surgery department at King Abdulaziz Medical Center in Riyadh, Saudi Arabia. All adult patients (age ≥ 18 years) with early UTI who underwent KT at our center between 2016 and 2022 were included in the final analysis. Young patients (age ≤ 18 years) were excluded. A list of patients who had a kidney transplant during this period was obtained from the Patient Information Department. Medical records were reviewed for demographic data, including patient’s gender, age, time on dialysis, and cause of end-stage renal disease; such as diabetic nephropathy, glomerulonephritis, hypertensive nephrosclerosis, polycystic kidney disease, chronic interstitial nephritis, lupus nephritis, and IgA nephropathy. Information on previous transplantations, type of transplantation, pre- and post-transplant diabetes mellitus, postoperative antimicrobial therapy, and immunosuppressive regimen was also reviewed. We identified patients who had ureteral double-J stents implanted during the transplant and recorded the stent duration for them. Serum creatinine and estimated glomerular filtration rate (eGFR) were recorded after one month of transplantation.Urinary tract infection UTI was classified into four different categories: asymptomatic bacteriuria, with no associated symptoms of UTI and no systemic clinical symptoms; uncomplicated acute simple cystitis, associated with local urinary symptoms; complicated UTI, associated with systemic manifestations; and recurrent UTI. A systematic review of each UTI episode was conducted, including time to onset after transplantation, type of infection, causative agent, microbiological diagnosis, treatment regimens, and duration of antibiotic treatment.Immunosuppressive treatment Depending on the patient’s immunological risk, one of three induction therapies was used: none, basiliximab, or antithymocyte globulin (ATG). Postoperatively, patients were treated with tacrolimus, mycophenolate sodium, and prednisolone. Additionally, based on their follow-up presentation, they could be given cyclosporine, mammalian target of rapamycin (mTOR) inhibitors (such as sirolimus and everolimus), and mycophenolate mofetil.Statistical analysisStatistical analysis was performed using RStudio (R version 4.3.0). We used frequencies and percentages to express categorical variables, whereas numerical variables were expressed as median and interquartile ranges (IQRs). Statistical differences between patients with and without UTI were assessed using Pearson's chi-squared test or Fisher's exact test for categorical variables where applicable. The differences in terms of the continuous variables were explored using a Wilcoxon rank sum test. Statistical significance was considered at p < 0.05.Demographic and clinical characteristics2 . The majority of patients (89.7%) were on dialysis with a cumulative time of 18.0 months (9.0 to 36.0) on dialysis , and 31.1% of them were aged 45 to <60 years. The median (IQR) BMI was 27.2 kg/mPost-transplantation characteristicsThe laboratory parameters of patients under study one month after kidney transplantation are demonstrated in Table Factors associated with UTIUTI was significantly more prevalent among females  and those with pre-existing bladder dysfunction (100.0%) compared to those with other pre-existing urinary tract abnormalities (p = 0.024). Additionally, patients with UTI had significantly longer cumulative periods on dialysis  compared to those without UTI  and Klebsiella pneumoniae (21.8%). Antibiotics were used among 86.5% of patients, of whom trimethoprim/sulfamethoxazole (65.8%) and ciprofloxacin (54.8%) were the most frequently prescribed antibiotics  of the patients experienced a UTI post-transplant. Of these, asymptomatic bacteriuria (AB) was reported in 37.8% and recurrent UTIs in 28.4%. Despite a recent decline in the incidence of post-transplant UTIs, the numbers remain high . This suEscherichia coli was the most common, accounting for 51% of cases, followed by Klebsiella pneumoniae at 21.8%. These findings corroborate a previous study where Escherichia coli and Klebsiella pneumoniae were identified in 82% of UTI cases among renal transplant patients [In terms of the primary causes of end-stage renal disease (ESRD) in our patient population, the most common were hypertensive nephrosclerosis (43.4%) and diabetic nephropathy (28.8%), findings that align with other studies ,13. Whenpatients .Concerning treatment modalities, antibiotics were prescribed for 86.5% of the UTI cases in our study. The most commonly used antibiotics were trimethoprim/sulfamethoxazole (65.8%) and ciprofloxacin (54.8%). Multiple studies have shown the efficacy of trimethoprim/sulfamethoxazole as a prophylactic measure to reduce UTI incidence when compared to a placebo ,16. For Our study corroborates previous findings by highlighting the significant association between UTIs and female gender (p < 0.001) as well as pre-existing bladder dysfunction (p = 0.024). Prior research has already identified female gender, older age, and the use of catheterization instruments as authentic risk factors for UTIs in both the general population and kidney transplant recipients ,19,20.In the context of kidney transplantation, specific factors like ureteral stent placement have been linked to a heightened risk of UTI ,22. AddiThe role of immunosuppressive therapy in influencing UTI incidence cannot be overstated. Induction therapy has been associated with UTIs in some previous studies when analyzed univariately . In anotSeveral factors might contribute to the elevated risk of UTIs in females. First, the anatomical proximity of the female urethra to the anus increases susceptibility to intestinal flora like E. coli, thus making retrograde infections more likely . Second,Regarding the impact of UTI on graft survival, a previous study conducted among 601 kidney transplant patients revealed that recurrent UTI episodes increased the risk of graft loss by more than 2.5-fold . In contSince the data for this study were collected from a single center within a specific setting, they may represent a highly selected group of cases. Therefore, it may be difficult to generalize these findings to the broader community of kidney recipients.Escherichia coli and Klebsiella pneumoniae as the most common causative organisms. Most patients were prescribed antibiotics as part of their treatment plan, with trimethoprim/sulfamethoxazole and ciprofloxacin being the most frequently prescribed options. A heightened risk for contracting a UTI was observed particularly among females and those with pre-existing urinary tract abnormalities. Importantly, our study found that UTIs had no negative impact on short-term graft survival. We recommend future studies to explore other potential variables affecting graft function in kidney transplant recipients. Additionally, we suggest monitoring the risk of UTI in patients who undergo ureteral stent placement after kidney transplantation, as existing literature indicates a possible correlation.In conclusion, our study comprised 553 adult kidney transplant recipients. Our results indicated that nearly half of these recipients experienced a UTI, with


Atopic dermatitis (AD) is considered a systemic type 2 immune driven disease, and it is associated to many atopic comorbidities including asthma. The aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to severe AD (sAD).We enrolled eligible patients with sAD for dupilumab treatment from September 2018 to December 2020. We then selected the subgroup of patients sensitized to perennial allergens. Dupilumab's efficacy and safety on AD and comorbid asthma were assessed at baseline, one month, four months, and then every 4 months up to one year.A total of 437 patients with sAD were enrolled for dupilumab treatment due to sAD, and 273 reached 48 weeks of therapy. Respiratory outcomes were evaluated in the 85 asthmatic patients with positivity only to perennial allergens. Our patients showed statistically and clinically significant improvement in asthma control (Asthma Control Test and Asthma Control Questionnaire) and airway obstruction parameters (FEV1), in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months, regardless of asthma severity.Our results showed the overall improvement of the clinical picture that dupilumab offers for patients with severe AD and persistent allergic asthma of any severity, highlighting the importance of a global multidisciplinary approach of type 2 driven disease. Atopic dermatitis (AD) is associated with impaired skin barrier function and systemic immune dysregulation. It is considered a systemic type 2 immune driven disease with a substantial burden on quality of life, and it is associated to many comorbidities. These are mainly due to the shared pathophysiology and the complex interplay of inflammatory cytokines that have different effects on the skin and other susceptible tissue .AD is often the beginning of the so called “atopic march”, that refers to the propensity for AD to begin early in life, and be followed by the serial occurrence of food allergy, asthma, allergic rhinitis, chronic rhinosinusitis (CRS) with or without nasal polyposis (NP), and eosinophilic esophagitis , 3. The α-subunit of the IL-4 receptor, thereby inhibiting the IL-4 and IL-13 signalling. It has proven to be effective and safe for atopic dermatitis (AD)  , asthma tis (AD) , and othtis (AD) . In Italtis (AD) . In JanuThe aim of our study was to prospectively evaluate the respiratory outcomes in patients with persistent allergic asthma treated with dupilumab due to sAD.Between September 2018 and December 2020 patients aged 18 years and older, with sAD eligible for dupilumab according to the Italian Drug Agency (AIFA) criteria, were enrolled. Inclusion criteria were: sAD with an Eczema Area Severity Index (EASI) score of 24 or greater, and contraindication, inadequate response, or intolerance to cyclosporin A . All patAll procedures were in accordance with the ethical standards of the responsible committee on human experimentation , and with the Helsinki Declaration of 1975, as revised in 2013. Informed written consent was obtained from the patients.AD was evaluated with the following parameters: EASI score (range: 0–72), Investigator's Global Assessment (IGA) (range: 0–4), Patient-Oriented Eczema Measure (POEM) (range: 0–30), peak score on the Numerical Rating Scale (NRSp) for pruritus (range: 0–10), peak score on the Numerical Rating Scale (NRSs) for sleep (range: 0–10), Dermatology Life Quality Index (DLQI) (range: 0–28) and Hospital Anxiety and Depression Scales (HADS).The diagnosis and the assessment of severity of allergic asthma were based on a history of variable respiratory symptoms, confirmed by the evidence of variable expiratory airflow limitation and by skin prick test and/or specific IgE positivity to perennial allergens. Asthma was evaluated with pulmonary function testing , Asthma Control Test (ACT) (range: 0–25), seven-item Asthma Control Questionnaire (ACQ-7) (range: 0–6), and exhaled nitric oxide (FeNO) . Asthma exacerbation was defined as requiring either the use of oral corticosteroids for at least 3 days, hospitalization, or emergency room visit . Minimalt-tests, Wilcoxon tests  for quantitative variables, and Fisher's exact tests for qualitative variables. All statistical analyses were performed with IBM® SPSS® Statistics version 20. The threshold for statistical significance was set at P < .05.Patients' characteristics and outcomes were compared using Student's A total of 437 patients with sAD were enrolled for dupilumab treatment and 273 reached 48 weeks of therapy. Out of 273, 153 (56.0%) were male, and the median ± interquartile range (IQR) for age was 38.0 ± 12.0 years. AD was categorized as early-onset in 201 patients (73.6%) and as late-onset in 72 patients (26.4%). Median age at diagnosis was 2.0 ± 11.0 years. At baseline (T0) EASI score was 39.5 ± 12.0, IGA was 4.0 ± 0.0, POEM was 22.0 ± 5.0. Type 2 immune comorbidities were common: allergic oculorhinitis (86.1%), asthma (67.8%), food allergy (26.4%), nasal polyposis (9.5%), eosinophilic esophagitis (0.7%) . Almost P < .001). All the other parameters also showed a significant reduction: the median ± IQR percentage from baseline in the POEM score was −69.5 ± 8.0 (P < .001), in peak score on NRS for pruritus −69.9 ± 12.0 (P < .001), in the peak score on NRS for sleep −85.6 ± 12.8 (P < .001) and in the DLQI score −81.8 ± 16.2 (P < .001). After 12 months of dupilumab therapy, 243 patients (89.0%) achieved ≥75% improvement from baseline as measured by EASI score (EASI-75) (P < .001) and 177 (64.8%) achieved ≥90% improvement (EASI-90).in vivo and vitro tests for inhalant allergens and 94 patients (42.1%) with seasonal allergies were excluded. The effect of dupilumab was evaluated in the remaining group of asthmatic patients (84 patients) with positivity only to perennial allergens.Considering the group of 185 asthmatic patients, 7 patients (3.8%) with negative P < .001), and this trend was maintained over time at T8 and T12. Median ± IQR of FEV1  was 96.3 ± 17.8 at baseline, 97.0 ± 17.8 at T1, 101.8 ± 18.1 at T4 (P < .001) and 103.0 ± 20.4 at T12 (P < .001). The same trend was observed for ratio FEV1/FVC: at baseline 78.0 ± 14.6, after 1 month 79.9 ± 14.1, after 4 months 82.0 ± 9.7 (P < .001), after 12 months 81.8 ± 11.5 (P < .001). By studying the flows at the lower lung volumes, we noted a significant improvement already after 1 month of FEF 50% (P < .05), and after 4 months for FEF 75% and 25% (P < .001).P < . 001), and of ACQ-7 showed a reduction from 1.4 ± 1.1 to 0.6 ± 0.6 at T4 (P < .001). The improvement of both scores were confirmed at T8 and T12 (P < .001).Asthma questionnaires also showed a significant improvement after 4 months, and this was maintained over time: the median ± IQR score of ACT significantly improved from 20.0 ± 4.0 at baseline to 23.0 ± 2.0 at T4 (P < .001), 24 ± 10 after 8 months and 22 ± 11 after 12 months.Likewise, the median ± IQR measure of the exhaled nitric oxide (FeNO) significantly decreased from 35 ± 21 ppb at baseline to 25 ± 12 ppb after 4 months  progressively increased: from 72.2% at T0 to 79.8% at T1, 89.3% at T4. Almost all patients (96.4%) showed a controlled asthma at T12. At the same time, the ACQ score gradually decreased, reaching values of less than 0.5 in the majority of patients. Considering the minimal clinically significant difference, the number of patients exceeding this threshold was progressively higher over time: at T12 almost half (48.8%) of patients achieved an improvement of at least 3 points in ACT score, while 65.5% achieved a reduction in ACQ-7 score of at least 0.5.P < .001).Furthermore, at baseline a total of 13 patients (15.5%) had developed at least one severe asthma exacerbation during the 12 months prior to dupilumab treatment, instead only 1 patient (1.2%) developed at least one during the treatment period . The most common adverse effects reported were Dupilumab Facial Redness (DFR) (15.0%), local injection site reactions (13.9%), conjunctivitis (12.1%), and blefaritis (2.9%). Three patients (1.0%) developed 3 after one month of treatment.Only 4% (12/273) discontinued treatment for different reasons, mainly intolerance to side effects. In one patient dupilumab was stopped as a precaution due to the elevation of the blood eosinophil count up to 18,000/mmAllergic diseases are dominated by systemic type 2 inflammation with overexpression of cytokines such as IL-4 and IL-13, which, in the skin, regulate the epidermal barrier and the effector phase of the immune response , 8. BlocMost of adult patients affected by moderate to severe AD reported one or more comorbid type 2 inflammatory diseases, among which asthma, allergic rhinitis, and food allergy were most common . Therefopost hoc analysis of more than 2000 patients including LIBERTY AD SOLO 1 (NCT02277743), SOLO 2 (NCT02755649), CHRONOS (NCT02260986), and CAFÉ (NCT02755649), reported that nearly 40% of adult patients with moderate to severe AD also had comorbid asthma; and in this population about 20% were uncontrolled or only partially controlled (ACQ-5 ≥ 0.5) and 15% were uncontrolled (ACQ-5 ≥ 1.0) despite receiving concomitant asthma medications  and respiratory parameters, in addition to the expected AD-related skin outcomes. Specifically, a significant improvement was achieved at the fourth month of dupilumab therapy, and this trend was maintained up to twelve months. Of note, only one patient developed one severe exacerbation during the treatment period. The results of our study are consistent with the ACQ improvements observed in AD patients treated with dupilumab at week 16 of the CAFE, SOLO1 and SOLO2, and CHRONOS trials . LikewisWe also evaluated the improvement in FeNO, which significantly decreased by the fourth month. A study of patients with uncontrolled asthma in dupilumab trials showed a significant correlation between decrease of FeNO and improvement in FEV1 . The redAs reported from previous studies, dupilumab-treated patients had an initial increase in eosinophil count reaching its peak in the first month of therapy, with subsequent slow decrease towards baseline level . In our Our study further confirms the safety profile of dupilumab in patients with AD and comorbid asthma, since only a minority of patients experienced mild, non-life-threatening adverse effects: facial redness dermatitis, injection site reactions, and conjunctivitis .Dupilumab treatment confers clinical benefits across multiple type 2 comorbid diseases. In our study improvements were observed in all cutaneous objective and subjective AD scores, and, of relevance, in all respiratory objective and subjective scores in the asthmatic subgroup of patients. This is in accordance with previous results , 20, thuThe limitations of our study are: the lack of control group, the lack of measurements on other biomarkers, and the lack of evaluation of other atopic comorbidities.The inhibition of the IL-4/IL-13 axis by dupilumab should be recognized as a multisystemic effect , 31. Our


Post-intubation hypotension (PIH) after prehospital emergency anaesthesia (PHEA) is prevalent and associated with increased mortality in trauma patients. The objective of this study was to compare the differential determinants of PIH in adult trauma patients undergoing PHEA.This multi-centre retrospective observational study was performed across three Helicopter Emergency Medical Services (HEMS) in the UK. Consecutive sampling of trauma patients who underwent PHEA using a fentanyl, ketamine, rocuronium drug regime were included, 2015–2020. Hypotension was defined as a new systolic blood pressure (SBP) < 90 mmHg within 10 min of induction, or > 10% reduction if SBP was < 90 mmHg before induction. A purposeful selection logistic regression model was used to determine pre-PHEA variables associated with PIH.During the study period 21,848 patients were attended, and 1,583 trauma patients underwent PHEA. The final analysis included 998 patients. 218 (21.8%) patients had one or more episode(s) of hypotension ≤ 10 min of induction. Patients > 55 years old; pre-PHEA tachycardia; multi-system injuries; and intravenous crystalloid administration before arrival of the HEMS team were the variables significantly associated with PIH. Induction drug regimes in which fentanyl was omitted (0:1:1 and 0:0:1 (rocuronium-only)) were the determinants with the largest effect sizes associated with hypotension.The variables significantly associated with PIH only account for a small proportion of the observed outcome. Clinician gestalt and provider intuition is likely to be the strongest predictor of PIH, suggested by the choice of a reduced dose induction and/or the omission of fentanyl during the anaesthetic for patients perceived to be at highest risk. In the United Kingdom (UK), a significant proportion of the most seriously injured trauma patients have airway compromise requiring intervention that exceeds the capabilities of the statutory ambulance service . UK HeliDrug-assisted rapid sequence induction (RSI) is used to facilitate prehospital emergency intubation , 5. SimpThe factors associated with PIH in critically injured patients are not well understood but are likely to be a combination of haemorrhage, cardiac depression from contusions and/or hypoxia, negative inotropy and vasoplegia from anaesthetic agents, acidaemia secondary to hypercapnia during peri-intubation apnoea, and reduced venous return from positive-pressure ventilation. Previous publications on this topic include small sample sizes with an inherent inability to reliably characterise the determinants of PIH , 18. The2  for continuous variables as appropriate.Data manipulation and statistical analyses were performed using the R statistical programming language . Statistical significance was pre-defined as p-value < 0.25 and variables of known clinical importance were included in the multivariable analysis. Variables were then sequentially eliminated until only statistically significant variables remained and the model achieved the best fit based on likelihood ratio tests. The assumptions of logistic regression were tested, checking for linear relationships in the logit of the outcomes, unduly influential values and multicollinearity. Plausible interactions were tested, with likelihood ratio tests and McFadden’s pseudo R-squared used to determine the final best model.A purposeful selection logistic regression model was used . Each vaAdministration of vasoactive medication pre-PHEA was not defined a-priori as a determinant of hypotension. Therefore, vasopressor administration was not included in the purposeful model build. In recognition that post-PHEA vasopressor administration could confound the results or attenuate the outcome, the sensitivity of the final model to including vasopressor administration was evaluated.For categorical variables, the group containing the largest number of cases was used as the reference group in the regression model. Patients were divided into four age groups. Pre-PHEA SBP was grouped as: Low (< 90 mmHg), Mid (90–140 mmHg), High (> 140 mmHg), heart rate was grouped as: Low (< 60 beats/min), Mid (60–100 beats/min), High (> 100 beats/min), and respiratory rate was grouped as: Low (< 10 breaths/min), Mid (10–25 breaths/min), High (> 25 breaths/min) . For druEthical approval for the study was granted by Anglia Ruskin University Research Ethics Panel (AH-SREP-20-047). The study was registered and approved by each participating organisation. The STROBE  reporting guideline was followed .n = 426 (42.7%), EAAA n = 416 (41.7%), Magpas n = 156 (15.6%), Fig. During the study period 21,848 patients were attended by HEMS, and 1,583 trauma patients underwent PHEA. 998 cases were included in the final analysis: EHAAT n = 112 (11.2%) patients had a pre-PHEA SBP < 90 mmHg. The most prevalent drug regime was 3:2:1. The most common PHEA indication was ‘reduced consciousness’, and just over a quarter of patients were administered intravenous crystalloid before HEMS arrival, Table The median average time to PHEA from the initial emergency call was 58 48–71] minutes. Most injuries resulted from blunt trauma, and ‘transport’ was the most prevalent mechanism of injury. Suspected isolated head injury was the most frequently observed injury pattern. The median pre-PHEA SI was 0.71 [0.55–0.95], and  minutes.218 (21.8%) patients had one or more new episode(s) of hypotension ≤ 10 min post-PHEA. Figure Table After the elimination of all non-significant variables and establishing the best-fit model, the final multivariate regression model was summarised, Table Five variables were associated with PIH: patient age > 55 years old was associated with an increased hypotension risk, compared to those aged 16–34 years old; pre-PHEA heart rate of > 100 beats/minute was associated with hypotension, in contrast to a pre-PHEA SBP of > 140 mmHg, which was protective against the outcome; multi-system injuries , and intravenous crystalloid administration by the ambulance service before arrival of the HEMS team were also significantly associated with PIH. Drug regimes that omitted fentanyl (0:1:1 and 0:0:1 (rocuronium-only)) were the determinants with the largest effect sizes.n = 27), compared with the combined group of no vasopressor use, given outside of this time, or given but time not known. 17 (63.0%) were hypotensive after PHEA, and a further two patients (7.4%) were hypotensive at induction but their SBP did not drop by an additional 10%. In the adjusted multivariate regression model, the odds ratio for hypotension in the vasopressor group (compared with the baseline) was 5.25 (95%CI 2.26–12.84). Including vasopressor use in the model made no difference to the significance level of other variables and had negligible impact on effect sizes.The multivariable regression model was re-run including administration of vasopressors within 10 min pre-or post-induction , affirming that major trauma is no longer a disease of the young [Older people represent the fastest-growing proportion of society and the largest proportion of major trauma patients in England . Consisthe young . The reshe young .‘the aim of fluid therapy to maintain a palpable peripheral pulse or SBP > 90 mmHg’ [Major trauma patients are physiologically fragile, owing to a combination of insults such as haemorrhagic volume depletion, hypoperfusion, acidaemia, and hypoxaemia leading to reduced cardiac function and a reflex tachycardia. In this study, a baseline heart rate > 100 beats/minute was associated with PIH, in contrast to a baseline SBP > 140 mmHg that was protective. In addition, concomitant head, chest and/or abdominal injuries and intravenous crystalloid administration from the ambulance service before arrival of HEMS, were associated with PIH. In the UK, the ambulance service adheres to Joint Royal Colleges Ambulance Liaison Committee (JRCALC) guidance that advises cautious crystalloid administration in blunt polytrauma with 90 mmHg’ . Whilst Tachycardia and later hypotension are the normal physiological responses to haemorrhage . This isThe addition of an opioid to the traditional RSI was introduced to attenuate the hypertensive response to laryngoscopy , 34. Debhas been able to demonstrate is that clinician gestalt outperforms any other captured physiological variable or combination of variables for predicting prehospital PIH. Traditional data capture focuses on objective and binary physiological variables, rather than clinical intuition or learned experience, for example, the “Hateful Eight” clinical signs of haemorrhage that are recognised at scene but not translated into prehospital datasets [The aspiration at the outset of this study was to identify determinants of PIH and build a clinical decision model to reduce the risk of this outcome. Despite a large heterogenous dataset with excellent data completeness, it is clear from current data collection that this aspiration is not possible. What this study datasets . If effeMost patients in this study sustained blunt traumatic head injuries without airway obstruction or ventilatory failure necessitating immediate airway intervention on the arrival of the HEMS team. Therefore, there is a potential window of opportunity to optimise patients before anaesthesia to avoid a deleterious haemodynamic insult. Proposed solutions that require further exploration and feasibility testing include the provision of invasive arterial monitoring to identify physiological trends earlier , volume This study included the largest heterogeneous group of patients and clinicians exploring the haemodynamic effects of PHEA in the UK. Whilst this is a strength, it is possible that differences in practice may have influenced the results. Furthermore, these results report association and not causation, and therefore conclusions should be considered as hypothesis-generating.The quality and completeness of data is often recognised as a challenge in prehospital academia, especially in retrospective analyses. However, missing data in physiological data capture work is less likely to be due to omissions in recording or documentation, and indeed more likely to reflect extreme physiological frailty, for example profound hypotension. In this study, 157 patients were excluded for missing data (mostly post-PHEA SBP), posing a risk of selection bias. These data are unlikely to be missing at random, and probably represent a cohort of patients with an unrecordable (low) blood pressure meeting the outcome definition. Therefore, this study may underestimate the true effect size.Patients > 55 years old; pre-PHEA tachycardia; multi-system injuries; and intravenous crystalloid administration before arrival of the HEMS team were the variables significantly associated with PIH. Induction drug regimes in which fentanyl was omitted (0:1:1 and 0:0:1 (rocuronium-only)) were the determinants with the largest effect sizes associated with hypotension. These variables only account for a small proportion of the observed outcome and clinician gestalt may play an important part.