Until recently, oral glucocorticoid (GC) therapies were the mainstay of treatment for uncontrolled inflammatory disease across many body systems. The last 30 years, however, have witnessed a transformation in the management of many diseases due to the development of targeted biological agents leading to a reduction, albeit not a removal, of the dependence on oral GCs. The need for new glucocorticoid-sparing therapies was urgent given the ever increasing and robust literature on the multisystem adverse effects related to chronic or repeated oral GC exposures –6. The iThe purpose of the GTI is to quantify toxicity change over time following the introduction of a steroid-sparing agent. A systematic assessment of the full range of toxicities is undertaken on starting a steroid-sparing agent, and is repeated following a designated treatment interval, e.g., six or twelve months. The severity of each domain of toxicity is scored according to pre-determined, weighted scores for every toxicity item ,8. The GThe Global Initiative of Asthma (GINA) reports the incidence of asthma is between 1–18% of the population in different countries , affectiApproval of mepolizumab for the treatment of severe, eosinophilic asthma by the U.S. Food & Drug Administration (FDA) in 2015 marked a global turning point in the treatment of severe asthma. Biological agents are designed to interrupt biological pathways known to cause disease. In this case, mepolizumab binds to IL5, inhibiting maturation, activation and longevity of eosinophils, thereby reducing airway inflammation and diminishing reliance upon oral GCs. There are now two agents which bind IL5  has suggested clinical review up to one year following the initiation of a biological agent. This guideline permits continuation of the biologic if there has been a “clinically significant reduction in GC-requiring exacerbations” or a “clinically-significant reduction in continuous oral GC” (50% reduction in the case of mepolizumab). However, no consensus exists with regard to the definition of “clinically significant reduction” — either in the number of exacerbations or in cumulative oral GC dose — and there is no mention of reducing GC toxicity.The multisystem adverse effects associated with GC use in severe asthma are well documented, and constitute not only a significant economic burden to healthcare systems, but also an enormous personal burden to patients ,5,24–26.8. All patients met criteria for eligibility for mepolizumab therapy at a severe asthma specialist clinic in the UK. Our aims were:to quantify the burden of GC toxicity in individual patients;to assess the spread of GC toxicity across the population;to elicit the factors that influence GC toxicity most strongly;to report toxicities not previously identified;to determine the minimal clinically important difference of toxicity change in GTI scores; and,to describe the development of the web-based GTI app (GTI 2.0).To explore GC toxicity at the level of individual patients with severe asthma, we used the validated Glucocorticoid Toxicity Index (GTI)  to assesThe cohort had substantial symptom and quality-of-life burdens from their asthma. The mean Asthma Control Questionnaire-5 (ACQ-5) score was 2.6 (1.3); the mean mini-Asthma quality-of-life questionnaire (mini-AQLQ) score was 3.6 (1.4); and the mean Saint George’s respiratory questionnaire score (SGRQ) was 55.8 (20.9). All of these measures confirm the severity of patients’ baseline asthma. Not surprisingly, the cohort had significant GC exposure in the 12 months preceding the initial GTI assessment: 82.2% had received maintenance oral prednisolone (median 10mg/day ) and theGiven the scale of GC exposure, a high prevalence of GC toxicity in these patients at baseline was expected. The most common manifestations of GC-toxicity were reflected in neuropsychiatric disturbances 81.2%), skin toxicities (79.2%), and elevated body mass indices (69.3%). Metabolic disturbances were also frequent: impaired glucose metabolism (HbA1C ≥ 5.7%) was present in 65.3% (≥ 6.0% in 43.5%) and 67.3% were hypertensive. All patients had some degree of GC toxicity with GTI scores ranging from 33–377 (mean 177.5 (73.7) [1.2%, skiPatient access guidelines define the need for steroid-sparing agents on the basis of recent GC exposure. However, in this cohort of biologic-naïve patients who met stringent national prescribing criteria in the UK, we show that GC-toxicity described by the GTI score correlated only modestly with recent prednisolone exposure . When performing multiple linear regression using variables thought to be clinically relevant to GTI toxicity , only age and mini-AQLQ were significant contributors to GTI toxicity. Each increasing year of age was associated with an increase in GTI score, likely to in part reflect the importance of the duration of GC exposure and possibly an increase in background incidence of many GC-toxicities with age.https://www.crestlabsgti.com/. A worked example of the GTI app can be viewed at https://www.youtube.com/watch?v=Pz4CSwZe7eI.Understanding the minimal clinically important difference (MCID) is important to the application of any clinical instrument. The MCID for the GTI was calculated using data from patients studied in the original GTI development , employiIn summary, assessment of GC-toxicity requires assessment both in the clinical setting as well as in trials designed to assess GC reduction with steroid-sparing therapies. Measuring GC-toxicity in a systematic manner in individuals aids optimisation of clinical care and management of unrecognised toxicities. Further knowledge of what constitutes a significant toxicity change will help to inform the definition of a clinical response to a steroid-sparing agent in individual patients. Given that the purpose of these expensive biological agents is to minimise GC use, toxicity reduction should be part of the discussion around the definition of response. Moreover, toxicity change may be a more relevant determinant of clinical response than recent GC exposure. Finally, when baseline toxicity within a patient cohort is known, toxicity change may have a role in measuring efficacy of steroid-sparing agents at a population level, thus enabling head-to-head comparison between different agents.The GTI is now in use across a number of diseases encompassing multiple sub-specialties. Important clinical trials using this instrument are now being completed –36. Furt


Background and Purpose: The purpose of the study was to evaluate the usefulness of thromboelastography with platelet mapping (TEG-PM) for predicting hematoma expansion (HE) and poor functional outcome in patients with intracerebral hemorrhage (ICH).Methods: Patients with primary ICH who underwent baseline computed tomography (CT) and TEG-PM within 6 h after symptom onset were enrolled in the observational cohort study. We performed univariate and multivariate logistic regression models to assess the association of admission platelet function with HE and functional outcome. In addition, a receiver operating characteristic (ROC) curve analysis investigated the accuracy of platelet function in predicting HE. A mediation analysis was undertaken to determine causal associations among platelet function, HE, and outcome.Results: Of 142 patients, 37 (26.1%) suffered HE. Multivariate logistic regression identified arachidonic acid (AA) and adenosine diphosphate (ADP) inhibition as significant independent predictors of HE. The area under the ROC curves was 0.727 for AA inhibition and 0.721 for ADP inhibition. Optimal threshold for AA inhibition was 41.75%  and ADP inhibition was 65.8% . AA and ADP inhibition were also associated with worse 3-month outcomes after adjusting for age, admission Glasgow Coma Scale score, intraventricular hemorrhage, baseline hematoma volume, and hemoglobin. The mediation analysis showed that the effect of higher platelet inhibition with poor outcomes was mediated through HE.Conclusions: These findings suggest that the reduced platelet response to ADP and AA independently predict HE and poor outcome in patients with ICH. Platelet function may represent a modifiable target of ICH treatment. Spontaneous intracerebral hemorrhage (ICH) accounts for 20% of all strokes and carries the highest stroke-related morbidity and mortality , 2. HemaThromboelastography (TEG), a whole-blood viscoelastic test, offers a rapid bedside assessment of coagulability and fibrinolysis . FurtherThe purpose of this prospective cohort study was to test the hypothesis that platelet dysfunction correlates with subsequent occurrence of HE and unfavorable outcome and then explore whether HE is the pathophysiological mechanism underlying this association. TEG-PM may be used as a clinically useful method to predict patients who will suffer HE and poor outcome and provide a possible direction concerning appropriate therapeutic interventions.This prospective study included spontaneous ICH patients aged 18 years or older who were admitted to our center between November 2019 and February 2021. Inclusion criteria were as follows: (1) baseline computed tomography (CT) scan was obtained within 6 h of symptom onset and (2) follow-up CT scan was acquired within 24 h of the baseline CT scan.3/μl; and (7) lost to follow-up. The Institutional Review Board of our hospital approved this study, and written informed consent was obtained from each patient or close relatives.Exclusion criteria were as follows: (1) the presence of vascular malformation, aneurysm, traumatic, brain tumor, ischemic stroke with hemorrhagic transformation, or any other cause of secondary ICH; (2) primary intraventricular hemorrhage; (3) preceding use of antiplatelet or anticoagulant drugs; (4) receiving any hemostatic agents before TEG-PM draw; (5) surgery or other neurosurgical intervention before follow-up CT scan; (6) evidence of coagulopathy on traditional laboratory testing , such asWe prospectively collected baseline demographic and clinical data including age, sex, cerebrovascular risk factors , onset to first CT scan time, admission systolic blood pressure (SBP), diastolic blood pressure (DBP), and baseline Glasgow Coma Scale (GCS) score at arrival. Laboratory information included hemoglobin (Hb), PLT, APTT, and INR.All participants received standard care according to the ICH treatment protocol of our hospital. Systolic blood pressure target was less than 140 mmHg after admission, according to the American Heart Association/American Stroke Association guidelines . FunctioTEG-PM testing was performed with whole blood drawn from a single clean puncture of the median cubital vein after the diagnostic CT scan. These samples were collected in heparinized or citrated tubes and processed within 2 h at room temperature. The tests were done using a computerized TEG-PM analyzer  by a trained clinical scientist. Daily quality assurance checks were carried out to ensure the validity of calibration.R, minutes), kinetics of the rate of clot formation , velocity of clot strength generation , maximal clot strength contributed by fibrinogen activity and platelet function , percent of amplitude reduction at 30 min after MA (LY30), and percent of clot dissolution 30 min after MA (EPL) (The standard TEG parameters were recorded as follows: time from the start of the test to clot formation (MA (EPL)  8)..R, minutThrombin reflects the maximal clot strength with contribution of platelet and fibrinogen together measured by a kaolin-activated sample. MAAA and MAADP reflect clot strength induced by stimulation of AA or ADP, respectively. MAFibrin represents individual contribution of fibrin to the clot strength measured by a reptilase and activator F-activated sample. The platelet inhibitions in response to AA and ADP were calculated with computerized software according to the equation:The platelet inhibition shows the degree of non-response of the platelet activated by exogenous arachidonic acid (AA) and adenosine diphosphate (ADP). MA 19)..19).According to trial protocol, a follow-up CT scan was performed within 24 h after the admission CT. The interval from symptom onset to admission CT was recorded. All CT scans were analyzed to determine the presence of intraventricular hemorrhage, ICH location , and hematoma volume. Hematoma volume measurement was performed using the 3D Slicer. Regions of interest of hematoma were identified using a semiautomatic method in each slice with a threshold range from 44 to 100 Hounsfield units. Then, we calculated hematoma volume by the accumulating volume of each slice –22. HE wt test (or Mann–Whitney U test for skewed distribution) for continuous variables and χ2 test (or Fisher's exact test) for categorical variables. To determine the independent predictors of HE and poor outcome, variables associated with a P < 0.10 in univariate analyses were entered into the multivariable logistic regression models. In addition, we performed a multivariable analysis in two models because GCS and baseline hematoma volume were collinear. A mediation analysis was performed to estimate whether HE (as the mediator) was the driving factor for any relationship between platelet inhibition (independent variable) and poor outcome (dependent variable) by regressing all three variables together (Quantitative variables were summarized as mean ± SD or as median with interquartile range (IQR) otherwise. Categorical variables were summarized as numbers with percentages. We compared baseline demographic, clinical, laboratory information, imaging characteristics, and TEG-PM parameters between patients with and without HE and then compared those between patients with good and poor outcome using together .P value < 0.05. Statistical analyses were performed using SPSS 19.0 software.To obtain diagnostic threshold values of inhibition, we used receiver operator characteristic (ROC) curves considering an area under the curve (AUC) of 0.70 or higher as indicating an acceptable prediction. From the ROC curve, we determined the optimal cut-off value (with sensitivity and specificity) for discriminating the risk of HE by maximizing the Youden index . StatistThere were 142 ICH subjects meeting the inclusion criteria for analysis. The study population consists of 96 (67.6%) men and 46 (32.4%) women, with a mean age of 61.5 years. The median time from onset to first CT scan was 2.5 h . The median baseline hematoma volume was 15 ml , and 48 patients (33.8%) had intraventricular hemorrhage on the first CT scan. HE occurred in 37 (26.1%) cases.P < 0.05). There were no statistically significant differences in TEG values of R, K, angle, MA, EPL, and LY30 (P > 0.05). In multivariate logistic analyses adjusted for relevant confounders, independent predictors of HE were time to baseline CT scan, AA, and ADP inhibition in both models 1 and 2 (Intergroup differences between ICH patients with and without HE are shown in  1 and 2 . The abiEighty-eight patients (62.0%) with ICH had unfavorable outcome. The results of bivariate analysis concerning predictors of 3-month outcomes are detailed in When regressing platelet inhibition, HE, and outcome together, the mediation analysis revealed that HE partially mediated the relationship between a high degree of AA inhibition and poor outcome. Additionally, HE also played a partially mediating role between ADP inhibition and poor outcome .Our data indicate that a higher degree of AA and ADP inhibition on admission was independently associated with increased odds of HE. Furthermore, AUC suggested the acceptable performance of platelet function to predict HE. In addition, our study demonstrated that admission platelet dysfunction was associated with poor outcome at 3 months, after adjustment for age and measures of disease severity. This relationship seemed to be mediated partly by HE.K and a trend toward longer R compared with patients without HE .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Arterial stiffness is associated with myocardial ischemia and incident coronary artery disease (CAD), and indexes of arterial stiffness are usually increased in patients with CAD. However, these indexes are often increased in elderly without CAD. Arterial stiffness in patients with CAD may become more evident after isometric handgrip exercise which increases systolic pressure and ventricular afterload. We investigated the association of the change of stiffness indexes after isometric handgrip exercise with the lesion extent of CAD and the necessity for coronary revascularization.Patients who were scheduled a routine coronary angiography via a femoral artery were enrolled. Arterial waveforms were traced at aortic root and external iliac artery using coronary catheters at baseline and 3 min after handgrip exercise. Augmentation index (AIx) was measured on the recorded aortic pressure waveform, and pulse wave velocity (PWV) was calculated using the ECG-gated time difference of the upstroke of arterial waveforms and distance between aortic root and external iliac artery.r = 0.344, P = 0.037). Patients were divided into higher and lower ΔPWV or ΔAIx groups based on the median values of 0.4 m/sec and 3.3%, respectively. Patients with higher PWV had more 2- or 3-vessel CAD , and underwent percutaneous coronary intervention (PCI) more frequently , but higher ΔAIx was not associated with either the lesion extent or PCI. Area under curve (AUC) of ΔPWV in association with PCI by C-statistics was 0.70 . In multiple logistic regression analysis, ΔPWV was significantly associated with PCI .Total 37 patients were evaluated. Both PWV and AIx increased after handgrip exercise. ΔPWV was significantly correlated with ΔAIx (Higher ΔPWV after isometric handgrip exercise was associated with the lesion extent of CAD and the necessity for coronary revascularization, but higher ΔAIx was not. Normal or accelerated vascular aging and hypertension are two main factors determining arterial stiffness because they are basically related to the change of the arterial media . HoweverOne of the popular methods evaluating arterial stiffness is measuring pulse wave velocity (PWV), a speed of an arterial pulsation through the arterial tree, usually between carotid and femoral arteries . A numbeIncreased PWV or AIx in patients with CAD may become more evident with a maneuver that influences the velocities of incident and reflected pressure waves. Isometric handgrip exercise, which increases systolic blood pressure (BP) and ventricular afterload –23, is aPatients who were scheduled a routine coronary angiography (CAG) via a femoral artery for the evaluation of the coronary atherosclerosis, and agreed to participate in the study were enrolled. Patients with acute coronary syndrome, or valvular heart disease were excluded. CAD was defined as ≥70% stenosis of the luminal diameter by the visual estimation of the operator in at least one major epicardial coronary artery or a past medical history of coronary revascularization. The extent of coronary atherosclerosis was classified as 1-, 2- or 3-vessel disease by the number of the major epicardial coronary arteries with a significant stenosis. Patients with a significant stenosis in the left main coronary artery were counted as having 2-vessel disease.The study protocol was approved by the institutional review board of Jeju National University Hospital. Written informed consents were obtained from participating patients or legal representative.The maximal voluntary forearm contraction power was measured with a JAMAR dynamometer , and a submaximal target at 30 ~ 40% of maximal handgrip power was used for 3-min isometric handgrip exercise.After routine CAG, arterial pressure waveforms were traced using a right coronary catheter and a fluid-filled pressure transducer system. Central arterial waveforms were recorded at the aortic root and traced before and at 1, 2 and 3 min after handgrip exercise. Forward pressure was measured at a merging point of the forward and the reflected waves on the recorded aortic pressure waveform. Augmentation pressure was defined as maximal central systolic pressure minus forward pressure. AIx was defined as augmentation pressure divided by central pulse pressure and expressed as a percentage  for categorical variables. Changes of hemodynamic parameters after handgrip exercise were analyzed using paired t-test, or where appropriate, Wilcoxon signed rank test. The association between changes of PWV (ΔPWV) and AIx (ΔAIx) after handgrip exercise was evaluated using correlation analysis. Patients were divided into higher and lower ΔPWV or ΔAIx groups based on the each median value. Data between groups were compared using unpaired t-test for continuous variables, and chi-square test for categorical variables. The association between higher ΔPWV or ΔAIx and coronary revascularization was evaluated using C-statistics and multiple logistic regression analysis after adjusting for age, gender, height, body mass index (BMI), hypertension, diabetes mellitus (DM) and chronic kidney disease (CKD). CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73mP < 0.05.All statistical analyses were performed with the statistical package SPSS version 23 . Clinical significance was defined as Total 42 patients were enrolled. After excluding 4 patients without a definite inflection point of augmentation pressure on the central arterial waveform and 1 patient without a peripheral arterial waveform, final 37 patients were evaluated. The mean age of study patients was 63.3 ± 9.4 years (range 41–82 years), 24 patients (65%) were older than 60 years, 26 patients (70%) had hypertension, and 27 patients (73%) had CAD. Percutaneous coronary intervention (PCI) was conducted in 25 patients (68%): 1 year ago in 20 patients and on the day of the study in 5 patients. One patient underwent both PCI and coronary artery bypass graft.r = 0.344, P = 0.037) . PCI was more frequently performed in patients with higher PWV  (Table Patients were divided into higher and lower ΔPWV (≥0.4 vs. < 0.4 m/sec) groups. Age, gender, BMI, smoker, co-morbid condition such as hypertension, DM, CKD or prior myocardial infarction, and medications were not significantly different between higher and lower ΔPWV groups except hyperlipidemia. Patients with higher PWV had more 2- or 3-vessel CAD , and PCI was similarly performed in both groups . Baseline central systolic BP and pulse pressure, augmentation pressure, AIx, peripheral systolic BP, and PWV were lower in higher ΔAIx group. However, after 3-min handgrip exercise, these hemodynamic parameters became not significantly different between both groups  groups. Age, BMI, smoker, co-morbid condition such as hypertension, DM, hyperlipidemia, CKD, prior myocardial infarction, or CAD, and medications except gender were not significantly different between higher and low ΔAIx groups Table . Patientps Table .Table 4P = 0.056). In contrast, it was 0.54  in case of ΔAIx , but ΔAIx was not .C-statistics showed the area under curve (AUC) of ΔPWV in association with PCI was 0.70 . Second, over half of patients were taking medications with a vasodilation property, which may influence the change of BP, PWV, and AIx after handgrip exercise. However such medications were equally taken in both higher and lower ΔPWV or ΔAIx groups, and baseline central and peripheral BP were not different between groups. Third, PCI performed not only on the day of the study but also 1 year ago was counted as having coronary revascularization. Including only prospectively conducted coronary revascularization would have increased the feasibility of the study. Fourth, the number of patients might not be enough to accurately evaluate the changes of PWV and AIx after handgrip exercise. Nevertheless, the association between higher ΔPWV and the lesion extent of CAD or the necessity for PCI was demonstrated.This was an invasive study that measured hemodynamic parameters during CAG. To be widely use, the applicability of a non-invasive method measuring ΔPWV or ΔAIx after handgrip exercise using an applanation tonometry needs to be validated in a future study.Both PWV and AIx increased after isometric handgrip exercise, and ΔPWV was significantly correlated with ΔAIx. However, higher ΔPWV was associated with the lesion extent of coronary atherosclerosis and the necessity for coronary revascularization, but higher ΔAIx was not.


There has been discussion over where to draw the line between partial and radical nephrectomy ever since performing the surgery was deemed possible. In 1869 Gustav Simon made history by performing the first ever planned nephrectomy to cure a urinary fistula and later in 1870, the first partial nephrectomy to treat hydronephrosis (Beyond oncological control, the risk of chronic kidney disease, cardiovascular events, hospitalization and death are problems that we as urologists must keep in mind when discussing long term repercussions of kidney cancer treatment, to find a way to push it as far as possible from our patients waiting for a partial or radical nephrectomy .Many studies have shown -6 that lStill, the literature is teeming with retrospective, non-randomized, biased filled works that try to give us some direction but are yet to give us any definitive answer. With that in mind, one other aspect to discuss would be the benefit of NSS and renal function preservation in this scenario. The follow up becomes central when dealing with this subject, once it has been reported that average time to recover original kidney function rate could take up to 25 months for 49% of patients to regain their previous eGFR , 9.Tumor size is also significantly different between most partial and radical nephrectomy studied groups, and that may also impact in the final renal function recovery . Many stIn addition to a trend to lower opportunity to preserve nephrons in bigger tumors, as NSS advances towards larger specimens, the procedure itself becomes much more complex and in turn may not result in better final eGFR in some cases, although pooling studies in a meta-analysis  shows siIn the last issue of IBJU, Alvim et al.  attempt The limits for partial nephrectomy depend on many complex aspects involving not only the tumor but also the patient characteristics. The EORTC 30904 randomized trial  showed t


Retzius-sparing robot-assisted radical prostatectomy (RS-RARP) exhibits better postoperative urinary continence than conventional RARP (C-RARP) via the anterior approach. However, the reasons behind this are unknown. Herein, early postoperative urinary incontinence and anatomical differences of 51 propensity score-matched C-RARP and RS-RARP cases were compared. Dynamic magnetic resonance imaging (MRI) was performed before and after surgery to examine the pelvic anatomical changes under abdominal pressure. The median urine loss ratios in the early postoperative period after C-RARP and RS-RARP were 11.0% and 1.0%, respectively. Postoperative MRI revealed that the anterior bladder wall was fixed in a higher position after RS-RARP compared with its position after C-RARP. Dynamic MRI after C-RARP showed that cephalocaudal compression of the bladder while applying abdominal pressure caused the membranous urethra to expand and the urine to flow out. After RS-RARP, the rectum moved forward during abdominal pressure, and the membranous urethra was compressed by closure from behind. This is the first study using dynamic MRI to reveal the importance of high attachment of the anterior bladder wall for the urethral closure mechanism during abdominal pressure. RS-RARP, which can completely preserve this mechanism, is less likely to cause stress urinary incontinence compared with C-RARP. Despite reports stating that RARP provides better postoperative urinary continence than conventional open or laparoscopic radical prostatectomy (RP)3, the actual outcomes are not completely satisfactory4. Galfano et al.5 first introduced the transperitoneal posterior RARP approach, which preserves the Retzius space, aptly called Retzius-sparing RARP (RS-RARP). RS-RARP has been reported to exhibit better postoperative urinary continence compared with conventional RARP (C-RARP) via the anterior approach7. Several explanations for the improved urinary continence have been proposed, including descent bladder suppression, maintenance of a long membranous urethral length (MUL)8, and less bladder neck descent after RS-RARP, which was observed on postoperative cystogram, compared with C-RARP9. However, no clear explanation was obtained.Robot-assisted radical prostatectomy (RARP) is the standard treatment for localized prostate cancer (PCa). However, one of the primary complaints affecting the quality of life (QOL) after RARP is urinary incontinence10, was evaluated using dynamic MRI; anatomical changes during abdominal pressure before and after surgery were examined.We compared postoperative urinary continence in propensity score-matched patients who underwent C-RARP or RS-RARP. We also compared anatomical changes in the pelvic region before and after each procedure via magnetic resonance imaging (MRI). The mechanism of stress urinary incontinence (SUI), which is considered to be the main cause for urinary incontinence after RPPatients with clinically localized PCa undergoing C-RARP (191 patients) and RS-RARP (51 patients) performed by a single surgeon at Kanazawa University Hospital (Japan) between February 2016 and May 2020 were enrolled in the study. The study protocols were approved by the Medical Ethics Committee of Kanazawa University ). All patients provided written informed consent, and all data were prospectively collected. All methods were performed in accordance with relevant guidelines and regulations.5. Nerve-sparing (NS) procedures were performed depending on cancer status. Urethral catheters were removed 6–8 days postoperatively after cystographic evaluation.C-RARP was performed using a transperitoneal approach, whereas RS-RARP was performed similarly to the technique described by Galfano et al.12, distance from the bladder attachment to the pubic symphysis (BA-PS), the MUL, prostate length (PL), distance from the pubic symphysis to the prostate apex length (PAL)13, and the length from the bladder neck to the pubic symphysis (BN-PS)8. Figure MRI was performed using the 1.5-T or 3.0-T MR system  with a multichannel anterior array coil combined with a multichannel posterior table coil. MRI was performed preoperatively and within 1 week of postoperative indwelling catheter removal. MRI was performed 30–60 min after urination. The estimated bladder capacity in each patient was 30–100 mL based on the MRI results. After multiplanar T2-weighted axial section imaging, an adequate sagittal section was created to capture the prostatic urethra. Sagittal dynamic MRI was performed at rest and during the abdominal pressure phase using a fast spin-echo sequence with the following parameters: repetition time/echo time, 1500–3716 ms/85–104 ms; flap angle, 90°; slice thickness, 6 mm; field of view, 300 mm; and imaging matrix, 224–352 × 156–224. Figure The micturition volume (MV) and weight of urine loss (UL) in the pads were separately assessed after daily catheter removal. The UL ratio (ULR) was calculated using the formula UL/(UL + MV). Urinary continence recovery within 6 months was defined as patient-reported use of 0 pads or one security liner per day.Propensity score matching was performed between the C-RARP and RS-RARP groups. The following 10 parameters were used for matching: age, body mass index, prostate-specific antigen levels before biopsy, neoadjuvant androgen deprivation therapy, biopsy Gleason Grade Group, preoperative International Prostate Symptom Score (IPSS), IPSS-QOL score, International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form total score, clinical T stage measured by prostate MRI, and removed prostate weight. Each group comprised 51 cases.P < 0.05 was considered statistically significant.Categorical variables for calculating incidences and percentages and continuous variables are presented as medians and interquartile ranges. When making comparisons, the chi-square test was used for categorical variables, whereas the Mann–Whitney U test was used for continuous variables. Urinary continence recovery rates were calculated using the Kaplan–Meier method and compared between the groups using the log-rank test. All data analyses were performed using SPSS for Windows . No significant differences in the 10 variables used for propensity score matching were observed between patients who underwent C-RARP versus RS-RARP. The numbers of NS procedures and lymph node dissections were higher in patients who underwent C-RARP than in those who underwent RS-RARP. No statistically significant differences were found in console times, excluding lymph node dissections. Although the amount of blood loss was higher for RS-RARP, no patients in either group required blood transfusion or were Grade 3 or higher in the Clavien–Dindo classification. The positive surgical margin (PSM) tended to be higher in RS-RARP, but the difference was not statistically significant  than in those who underwent C-RARP (11.0%) Fig. A. KaplanIn total, 47 C-RARP and 50 RS-RARP patients underwent static MRI preoperatively and within 1 week of postoperative indwelling catheter removal for the anatomical examination of their bladder and membranous urethra. The preoperative MRI revealed a significant difference between groups in BA-PS only Table . No diffIn addition to static MRI, dynamic MRI was performed postoperatively in 45 C-RARP patients and 44 RS-RARP patients. Postoperatively, the compression distances were significantly longer in patients who underwent RS-RARP than in those who underwent C-RARP (Fig. 7. This improvement was attributed to the preservation of periurethral structures5, higher bladder position, and longer MUL9. Although previous reports have discussed the anatomical differences, the mechanism by which these differences contribute to urinary continence was unclear. Although researchers suggested that the main cause of urinary continence after RP is SUI10, few reports examined the anatomical pelvic changes during abdominal pressure that occur after RP. A dynamic MRI study after RP reported no evidence of urethral hypermobility with or without urinary incontinence14. Another dynamic MRI study compared incontinent and continent patients after RP and found that incontinent patients had a significantly wider membranous urethra angle during voiding and the Valsalva maneuver15. These studies suggest that the impairment of the suspensory mechanism of the pelvic floor and the external urethral sphincter disturb urethral closure in patients with severe urinary incontinence. However, the target cases in these studies were patients with severe urinary incontinence, which is different from the present study. In this study, dynamic MRI was performed before and after RARP to compare anatomical changes of the pelvis during abdominal pressure. Preoperatively, the bladder was compressed caudally during abdominal pressure, and rectum movement compressed the membranous urethra ventrally (Fig. 16. The present dynamic MRI study suggests that pressure is applied to the bladder during abdominal pressure, and at the same time, pressure is applied dorsoventrally at the membranous area, which increases the urethral closing pressure and prevents urinary incontinence. As the anterior surface of the bladder is widely fixed to the abdominal wall during abdominal pressure, the anterior surface of the bladder serves as a fulcrum, causing the pelvic organs to rotate as if sliding from the bottom to the front of the pelvic floor. As a result, the membranous urethra is thought to be compressed posteroventrally (Fig. In agreement with our study, many reports demonstrate that postoperative urinary continence is better after RS-RARP than after C-RARPlly Fig. B, F. A plly Fig. B, F. Simlly Fig. H. Howevelly Fig. D. It woully Fig. , which c17. Urethral hypermobility has been reported as a cause of SUI in women, and changes in pelvic anatomy during abdominal pressure have been reported in dynamic MRI studies18. In women with urethral hypermobility, dynamic MRI shows that all of the pelvic organs evacuate inferiorly and anteriorly, in a rotational motion, during abdominal pressure, and clinically, the urethra rotates anteriorly from a vertical position as seen in the Q-tip test19. In these women, the supporting structure of the vaginal wall lining the urethra is damaged, and the urethral closure pressure does not work properly, resulting in SUI17.In women, the urethra is lined posteriorly by the vaginal wall. It is thought that during abdominal pressure, the pressure applied to the bladder and urethra also results in pressure on the vaginal wall, which increases postoperative urinary continence and prevents urinary incontinence14. The mechanism of SUI after RP is slightly different from the mechanism of SUI associated with urethral hypermobility in women. However, similar to women, urinary incontinence is caused by insufficient urethral closing pressure when pressure is applied distally from the bladder neck during abdominal pressure17.In men, no structure lining the urethra from the posterior side exists. A dynamic MRI study after RP reported no evidence of urethral hypermobility with or without urinary incontinence20. When performing NS, the dissection line is closer to the prostate, resulting in the preservation of the structures around the urethral sphincter, which is likely to improve urinary continence. In the present study, few cases of NS were found in RS-RARP patients, but NS may further improve postoperative urinary continence in patients who are eligible5.Previous reports showed that NS techniques may improve postoperative urinary continence9. In RS-RARP, the anterior bladder wall is fixed at a high position and the bladder neck is thin and stretched, as observed on postoperative MRI. When measuring the bladder neck via cystography, the boundary between the stretched bladder neck and the membranous urethra is difficult to identify because it depends on the amount of stored urine in the bladder. We suspect that simple cystography might cause variations in bladder base measurements. Although we previously reported a slight shift of the membranous urethra to the cephalad side immediately after RP12, the postoperative DMU-PO did not differ between the two groups, and the position of the membranous urethra immediately after surgery was similar in both groups (Table In this study, we examined the pelvic anatomy before and after RARP using MRI. Preoperative MRI at rest revealed no significant differences in the measured parameters between patients who underwent C-RARP and those who underwent RS-RARP. Postoperative MRI revealed no significant differences in PBN and MUL between patients who underwent C-RARP and those who underwent RS-RARP Table . A previ21. Therefore, we consider RS-RARP the best technique for preserving urinary continence because it does not damage the pelvic floor muscles or change the position of the anterior bladder wall22. In addition, the combination of NS techniques may further improve postoperative urinary continence20.In transabdominal C-RARP, the peritoneum is incised, and the anterior bladder space is opened to approach the prostate. During reattachment after surgery, the anterior wall of the bladder is fixed more caudally than before surgery because it is moved by vesicourethral anastomosis. However, even if the peritoneum is sutured after transperitoneal RP or even if the retroperitoneal approach is used without peritoneal incision, the bladder is still strongly pulled caudally so that when the anterior bladder wall is reattached, the peritoneum is stretched and fixed more caudally than before the surgery. In radical perineal prostatectomy, the position of the anterior bladder wall after surgery is the same as that before surgery because the pelvic floor muscles are incised when approaching the prostate; the pelvic floor muscles supporting the membranous urethra from the periphery may be damaged, and urethral closing pressure may not be maintained. A previous report comparing postoperative urinary continence after C-RARP versus radical perineal prostatectomy showed that early improvement was superior after C-RARP23. C-RARP was considered to be a relatively technically stable procedure, whereas for RS-RARP, the surgeon of this study was only starting to execute this procedure and thus was in the middle of the learning curve for it. The PSM rate tended to be higher in the RS-RARP group than in the C-RARP group, although no significant differences were noted. The learning curve for RS-RARP has been reported previously24, and the PSM rate is expected to decrease in the future. The console time in case of C-RARP, excluding lymph node dissection time, was comparable to that of the early stage of RS-RARP, and RS-RARP was relatively safe to introduce without blood transfusion and complications in cases with Clavien–Dindo classification 3 or higher. However, in RS-RARP, the case selection may have been more favorable in the initial stage due to unfamiliarity within the narrow surgical field23.In this study, C-RARP and RS-RARP were performed by a single surgeon, and propensity score matching was used after the single surgeon performed more than 200 C-RARP surgeries. We introduced RS-RARP surgeries at our institute in July 2017; however, up to 30 cases since July 2017, the selection criteria for surgery did not include patients with difficult cases. These criteria were as follows: estimated prostate weight of ≤ 40 g, no prostate protrusion into the bladder, and no need for lymph node dissection25. The present study suggests that RS-RARP is effective only for urinary continence and that NS may be necessary to preserve sexual function. In the present dynamic MRI evaluation, changes during abdominal pressure were evaluated, but urethral closing pressure at rest was not evaluated. Urethral closing pressure is important for preventing urinary incontinence at rest, and leaving the urethra long and sparing the nerves are important for preserving the periurethral structures. The bladder is loosely fixed by the vascular pedicles; and after RP, there is resistance to dropping the bladder neck to the pelvic floor during urethrovesical anastomosis, which might pull the anastomosis cephalad12. In C-RARP, the urethrovesical anastomosis is thought to be pulled cephalodorsally because the bladder vasculature is fixed from both dorsolateral sides. Conversely, in RS-RARP, the anterior bladder wall is widely fixed, and the urethrovesical anastomosis is thought to be pulled cephaloventrally. After RS-RARP, the urethra is pushed toward the pubic bone, and the urethral closing pressure at rest may be higher than that after C-RARP (Fig. It is also important to discuss the limitations of this study. First, the present study was focused on short-term postoperative urinary continence and did not evaluate sexual function. Favorable sexual function results after RS-RARP have not been shown previouslyARP Fig. . In the To the best of our knowledge, this is the first dynamic MRI study to reveal the importance of the high attachment of the anterior bladder wall for the urethral closure mechanism during abdominal pressure. Among the RP techniques reported thus far, RS-RARP can completely preserve this mechanism and is considered to be the least likely cause of SUI.Supplementary Information 1.Supplementary Video 1.


Knowledge on normal progress and treatment of Henoch-Schönlein purpura nephritis (HSPN) is limited. This study reviews outcome, clinical, pathological, and therapeutic factors affecting the prognosis of HSPN patients.Forty-nine children with biopsy-confirmed HSPN diagnosed between September 2008 and 2018 were included. Demographics, clinical and laboratory data, treatment, and outcome were recorded at the time of biopsy, 3, 6, 12, and 24 months and at last visit. Clinical outcome was graded according to Meadow’s criteria.2. Biopsy specimens were classified according to International Study of Kidney Diseases in Children (ISKDC) and Oxford Classification MEST-C scoring systems. Forty-one patients received angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, 37 patients steroids, and 35 patients other immunosuppressive medications. At last visit, 24 patients had stage 1 chronic kidney disease (CKD), three stage 2 CKD, and two had stage 5 CKD. Neither clinical parameters nor ISKDC biopsy grade or treatment modalities effected the final outcome. The Oxford classification showed significantly increased segmental glomerulosclerosis in patients with unfavorable outcome. Favorable outcome was associated with shorter time from kidney involvement to biopsy and start of treatment.The median age at time of biopsy was 10.1 years (IQR:5.7) and female/male ratio 24/25. At presentation, 40.8% of patients had nonnephrotic proteinuria, 18.4% nephrotic syndrome (NS), 4.1% nephritic syndrome (NephrS), and 36.7% NephrS+NS. There were 11 patients with an estimated glomerular filtration rate below 90 ml/min/1.73 mA large proportion of patients continued to show signs of CKD at last follow-up while only a small proportion developed stage 5 CKD. Henoch-Schönlein Purpura (HSP) or IgA vasculitis is the most common vasculitis seen in children, with an estimated annual incidence of 3 to 26.7 per 100.000 children [Kidney involvement is the most serious complication and its occurrence varies from 20 to 50% –7. A majTreatment of HSPN is not well defined as randomized controlled trials are scarce. Pediatric nephrologists face a dilemma of delaying treatment in a small group of children with active inflammatory disease which could increase their chance of developing CKD. This needs to be balanced against a high chance of overtreatment of children with spontaneous regression of their nephritis. The lack of proven effective treatment together with substantial potential side-effects from the treatments used makes the decision even more difficult.The aim of this study is to review the outcome of biopsy-proven HSPN children seen at Great Ormond Street Hospital for Children to describe the chances of developing CKD in the short- to medium-term perspective and to see if we could find any signal that the treatments used had made any difference.Children with a biopsy-proven diagnosis of HSPN between September 2008 and September 2018 were included in the study. The study was registered with the hospital’s Clinical Audit Committee (audit ref. no: 2502). Patients with an age of < 18 years at time of disease onset were included. A follow-up time of more than 6 months was required for inclusion. Demographic characteristics, clinical and laboratory data, treatment, and outcome were recorded from the hospital records at the time of biopsy, at 3, 6, 12, and 24 months follow-up and at last visit.2), stage 2—mildly decreased GFR (60–89 ml/min/1.73 m2), stage 3a—mildly moderately decreased GFR (45–59 ml/min/1.73 m2), stage 3b—moderately severely decreased GFR (30–44 ml/min/1.73 m2), stage 4—severely decreased GFR (15–29 ml/min/1.73m2), and stage 5—kidney failure (< 15 ml/min/1.73 m2) [The validated EULAR/PRINTO/PRES criteria for HSP diagnosis were used . Kidney 1.73 m2) . Kidney Kidney biopsy indications were NephrS, NS, persistent severe proteinuria (urine protein/creatinine > 200 mg/mmol for 4 weeks), persistent moderate proteinuria (urine protein/creatinine 100–200 mg/mmol for 3 months), and acute kidney injury by KDIGO . Patholo2), D: abnormal kidney function (eGFR < 60 ml/min/1.73 m2) [Clinical outcome was graded according to Meadow’s criteria; A: normal , B: minor urinary abnormalities , C: active kidney disease  . CompletU test and categorical variables by chi-square or Fisher’s exact test as appropriate. A P value of < 0.05 was considered statistically significant.Data analyses were performed by using SPSS Version 21.0 . Samples were tested with Shapiro–Wilk test to determine normality of distributions. According to the results, nonparametric tests were preferred. Continuous variables were compared by Mann–Whitney 2 and 63% low serum albumin levels (< 35 g/L). All C-reactive protein (CRP) values were normal, and 83% of erythrocyte sedimentation rate (ESR) values were less than 10 mm/h. The white cell counts were above 10,000/ mm3 in 44.6% of the children.Forty-nine children with biopsy-proven HSPN were followed for at least 6 months, median follow-up period was 22 (IQR:27) months. Table 2. There were four children with grade 5 pathology, all of whom presented with NS-NephrS, three with eGFR less than 90 ml/min/1.73 m2. The Oxford classification defined M1 in 45 (91.8%), E1 in 28 (57.1%), S1 in 17 (34.6%), C0 in 8 (16.3%), C1 in 24 (49%), and C2 in 17 (34.%) of the biopsies. None of the patients showed any signs of tubular atrophy, T0 was thus seen in all of the pathology specimens.Table Eight children received treatment with more than four different drugs and, 16 had three, 18 two, and 4 children only one medicine. Three patients were followed conservatively, all had grade 3 HSPN pathology, two had an outcome of Meadow’s grade A and one of B. Mycophenolate mofetil (MMF) was the most commonly used immunosuppressive agent other than steroids with a median duration of 9  months. Cyclophosphamide was used in six children, three times as one dose, twice as four, and once in five doses. Three patients were treated with azathioprine and four with a calcineurin inhibitor. Rituximab was trialed in two children. Drug side effects were observed in three patients receiving angiotensin converting enzyme inhibitor , and in one patient on MMF (mild neutropenia).2, received steroids, cyclophosphamide, plasmapheresis without benefit and at 16th month kidney transplantation was performed. Initial kidney biopsies of both children showed grade 3 pathology. Among four patients whose biopsies showed grade 5 pathology, three had Meadow’s grade A outcome and one grade B. Using the Oxford classification, a statistically significant worse outcome was observed in children with segmental glomerulosclerosis (S score) (Table 2 and six (30%) patients with NS presentation, whereas in the unfavorable group (Meadow’s B–D), there were four (13.7%) patients with low GFR and three (10.3%) with NS presentation.There were 20 patients whose outcome was classified as Meadow’s grade A, 24 as B, three as C, and two as D. During follow-up, no patient death was observed. The relationship between clinical and laboratory findings at onset and clinical outcome according to Meadow’s criteria is given in Table p = 0.004). Twenty-eight (57.1%) patients were free of albuminuria by 24 months and 34 patients at last visit (69.3%). Hematuria was cleared in 18 (36.7%) patients by 24 months and in 20 (40.8%) at last visit. The courses of hematuria and albuminuria during follow-up are depicted in Figs. Important clinical and laboratory characteristics of patients at last follow-up are given in Table eight 57.% patientIn this study, we found that children with severe pathologies on kidney biopsy more often presented with nephrotic range proteinuria and hypoalbuminemia. Time to kidney biopsy from onset of HSPN and onset of treatment with ACEi and steroids were the only factors associated with a favorable outcome. Neither clinical presentation, nor choice of immunosuppressive treatment nor underlying pathology was linked to the final outcome. The rate of kidney failure was less than 5%.2 at presentation.The median duration from onset of HSP to onset of HSPN was 1 month in our present study, which is in accordance with the literature; 85% HSP kidney involvement within 4 weeks, 91% in 6 weeks, 97% within 6 months , 26. HemIn the present study, 40% of patients were in complete remission at last follow-up, more than half had some degree of CKD with a low rate for kidney failure, less than 5%. At last visit, albuminuria had resolved in 70% of patients and hematuria in 40%. Different case series give varying results regarding progression to CKD , 29, 30.There are conflicting results on the relationship between the clinical severity and outcome. A systematic review reported that risk of long-term kidney impairment ranged between 0.5–3.8% for isolated hematuria and/or proteinuria, while this ratio increased to 11.1–31.7% for NephrS or NS . RonkainEarly kidney biopsy and treatment in pediatric HSPN has been suggested to be beneficial , 33. Les2) should be treated with ACE-I or ARB, and after a trial of ACE-I or ARB children with persistent proteinuria (> 1 g/day/1.73 m2) and GFR of > 50 ml/min/1.73 m2 may be given a 6 month-course of steroids. Pulse steroids, cyclophosphamide, and plasmapheresis may be considered in crescentic HSPN, NS, and/or impaired kidney function [Consensus on HSPN treatment is still lacking and there are currently no widely accepted recommendations for treatment of moderately severe and severe HSPN in children. The KDIGO guideline for HSPN suggests that children with persistent proteinuria (> 0.5–1 g/day/1.73 mfunction . Some otfunction , 39, 40.function , 42. Onefunction —all but Tudorache et al.  also, liThe main limitations of our study are a relatively small sample size and the retrospective nature of the analyses. Another limitation is the nonstandardized treatment used and relatively short follow-up period.In conclusion, even in a large center, there are very low numbers of children developing kidney failure due to HSPN in the short to medium term. There are however a number children with CKD of differing severity who later might go on to develop kidney failure. In this study, no clinical or laboratory parameters could be shown to predict the long-term prognosis, nor could any superior treatment modality be defined. Larger scale studies—preferably prospective—are needed to define which children need to be treated, and which treatments are effective.


This cross-sectional study investigates US population changes in chronic kidney disease (CKD) G stage and 4 CKD-related complications, comparing the 2021 equation for estimating glomerular filtration rate with the 2009 equation, which included a race coefficient. We investigated US population changes in CKD G stage and in 4 CKD-related complications, comparing the race-free serum creatinine–based 2021 CKD-EPI equation with the 2009 equation.Estimating glomerular filtration rate (eGFR) from serum creatinine is common in medicine. The 2009 Chronic Kidney Disease–Epidemiology Collaboration (CKD-EPI) equation uses age, sex, race (Black vs non-Black), and creatinine level. Concerns were raised that the use of race in estimating GFR could contribute to care inequities.5 This cross-sectional study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guideline.In this cross-sectional study, we used data from the US National Health and Nutrition Examination Survey (NHANES 2011-2018). NHANES was approved by the National Center for Health Statistics research ethics review board, and participants gave written informed consent. This analysis used publicly available deidentified data and was not considered human participant research per Baylor College of Medicine institutional review board policy. Appropriate survey methods were used.6 was calculated for eGFRs of less than 60 mL/min/1.73 m2. Anemia was defined as hemoglobin level of less than 12 g/dL in female participants and less than 13 g/dL in male participants , acidosis as serum bicarbonate levels of 22 mEq/L or lower , hyperphosphatemia as serum phosphate levels of 4.5 mg/dL or greater, and hypertension as systolic blood pressure of 140 mm Hg or greater or diastolic blood pressure of 90 mm Hg or greater. Multiple imputation was performed for missing laboratory values (creatinine was missing in 10.3% of participants). Analyses were performed with Stata version 14.2 (StataCorp). Additional details are in the eAppendix in the We included NHANES participants aged 20 years and older and classified them by self-reported race into Black vs non-Black groups . We calculated eGFR using serum creatinine–based CKD-EPI equations (2009 and 2021); G stage2 using either equation. The mean (SD) age was 71 (13) years, and an estimated 10.5  million were female. An estimated 5.5  million adults were reclassified in G stage with the 2021 equation: 1.0  million into a more severe stage and 4.5  million into a less severe stage. All persons reclassified into more severe stages self-reported as Black, and all persons reclassified into less severe stages self-reported as non-Black. Of all Black adults, 3.9%  were recategorized into a more severe stage  million adults had an eGFR of less than 60 ml/min/1.73 mre stage . Of all 2 and CKD stage G3a, ie, eGFR 45-59 mL/min/1.73 m2). The 2021 equation increased the prevalence of eGFR less than 60 mL/min/1.73 m2 among Black persons by 2.9 percentage points (7.1% to 9.9%), larger than the 2 percentage points reported using 1999 to 2002 NHANES data.2 The decrease in the prevalence of eGFR less than 60 mL/min/1.73 m2 among individuals identifying as non-Black of 1.6 percentage points (7.5% to 5.9%) was similar to that observed in 1999 to 2002 data.2 The prevalence estimates of CKD complications were qualitatively similar in reclassified and adjacent nonreclassified groups.Transitioning from the 2009 equation to the 2021 equation resulted in more than 5 million US adults changing CKD G stage classification, mostly in moderate CKD stages (between eGFR >60 mL/min/1.73 mLimitations include use of single laboratory measurements. Limited numbers in some subgroups prevented precise estimates, including of complications, and prevented separate analysis of smaller racial and ethnic groups. Cystatin C levels are not available for these years.In this study, estimation of eGFR using the 2021 CKD-EPI equation resulted in substantial reclassification in CKD G stage in US adults. However, CKD-related complication prevalence estimates were not substantially altered.


In conclusion, this study identified long NE therapy and maximum daily increase in tacrolimus plasma levels as risk factors for AKI requiring RRT in HTX patients with preserved renal function.Acute kidney injury (AKI), requiring renal replacement therapy (RRT). is a serious complication after orthotopic heart transplantation (HTX). In patients with preexisting impaired renal function, postoperative AKI is unsurprising. However, even in patients with preserved renal function, AKI requiring RRT is frequent. Therefore, this study aimed to identify risk factors associated with postoperative AKI requiring RRT after HTX in this sub-cohort. This retrospective cohort study included patients ≥ 18 years of age with preserved renal function (defined as preoperative glomerular filtration rate ≥ 60 mL/min) who underwent HTX between 2010 and 2021. In total, 107 patients were included in the analysis . Based on univariate logistic regression, use of extracorporeal membrane oxygenation, postoperative infection, levosimendan therapy, duration of norepinephrine (NE) therapy and maximum daily increase in tacrolimus plasma levels were chosen to be included into multivariate analysis. Duration of NE therapy and maximum daily increase in tacrolimus plasma levels remained as independent significant risk factors (NE: OR 1.01, 95%CI: 1.00–1.02,  Acute kidney injury (AKI) is a common complication after orthotopic heart transplantation (HTX) ,2. A recThe present study was a retrospective, single-center cohort study and was conducted in compliance with the declaration of Helsinki and the International Society for Heart and Lung Transplantation (ISHLT) ethics statement. Ethical approval was obtained from the University of Duesseldorf’s ethic committee (Reference-number: 4567). All patients were registered in the local dedicated prospective heart transplantation database and gave written informed consent to be registered. This report follows the “Strengthening the Reporting of Observational Studies in Epidemiology” (STROBE) guidelines for cohort studies.All patients ≥ 18 years of age who underwent HTX at the University Hospital Duesseldorf, Germany, between 2010 and 2021 were screened for this study. The main inclusion criterium was preserved renal function before surgery. This was defined as a glomerular filtration rate (GFR) of ≥60 mL/min calculated from creatinine clearance on the day of HTX using the “Chronic Kidney Disease Epidemiology Collaboration” (CKD-EPI) formula, according to our local laboratory standards . PatientThe primary endpoint of this study was AKI requiring RRT within 72 h after HTX. AKI was defined according to the Kidney Disease Improving Global Outcome (KDIGO) criteria. RRT was performed as continuous veno-venous hemodialysis (CVVHD). For data collection, the local prospective HTX database was screened. Data from this database or the patient’s medical records were extracted by members of the study team. All data were double-checked by two persons trained in the study protocol.In our center, HTX patients are treated according to standard operating procedures. Additionally, to ensure a high quality of care, all HTX patients are treated by a small specialized team. In terms of AKI and RRT, volume management and infusion regimes may have a strong impact. Infusion regimes did not change during the study period. All patients received crystalloids as first line infusion therapy. Colloids such as hydroxyethyl starch or gelatin were not administered after heart transplantation. Albumin was only administered if the albumin plasma level was low, with a target area of 2.5–4.5 g/dL. Fresh frozen plasma, platelets and erythrocytes were given according to the cross-sectional guidelines of therapy with blood components and plasma derivatives by the German Medical Association.To identify candidate variables for analysis, all variables relating to the patient, diagnosis, or associated organ dysfunction available in our database were considered. As an additional variable explored beyond the standard database contents, a maximum daily increase in tacrolimus plasma levels was separately calculated from daily tacrolimus levels. Firstly, all of these variables were assessed in a univariate analysis. As we observed 49 events in this study, a maximum of 5 covariables could be included into multivariate analysis . Therefot-tests were used to compare categorical or continuous variables for descriptive statistics. Binary logistic regression was used for univariate analysis screening of continuous or dichotomous variables, respectively. For multivariate analysis, binary multivariate logistic regression was performed to assess independent associations between chosen variables and AKI requiring RRT. A p-value of <0.05 was considered as significant.All statistical analyses were performed using IBM SPSS version 25. Continuous variables are presented as means with standard deviation or median with interquartile range as appropriate. Categorical variables are presented as counts and percentages. Fisher’s exact test and A total of 206 patients were screened for this study. A sum of 13 patients had haemodialysis prior to HTX and 86 patients had baseline GFR < 60mL/min. Based on the inclusion and exclusion criteria, 107 patients were used in the statistical analysis. p = 0.0004), post-HTX new onset of any infection , post-HTX levosimendan therapy , post-HTX duration of norepinephrine (NE) therapy , post-HTX amount of blood products on ICU , post-HTX length of ICU stay , post-HTX length of mechanical ventilation , peak tacrolimus plasma level within first 72 h , and maximum daily increase in tacrolimus plasma levels within first 72 h post-HTX .From our local HTX database, we could assess 41 variables in univariate analysis see . The folp = 0.005; increase in tacrolimus plasma level: OR 1.18, 95%CI: 1.01–1.37, p = 0.036). In addition, there was a nonsignificant trend for VA-ECMO due to primary graft dysfunction after HTX .Based on the literature research, the following five of the nine significant variables were included into multivariate binary logistic regression see : ECMO 99,10,11, With our results we could show that prolonged NE therapy and maximum daily increase in tacrolimus plasma levels seem to be associated with early postoperative AKI requiring RRT after HTX in patients with preserved renal function.According to a recent meta-analysis, incidence of AKI is high, with up to 62.8% after HTX. Therefore, its prevention is a topic of interest for clinicians as AKI is associated with higher mortality rates . Hence, Tacrolimus is a crucial component of immunosuppressive therapy after HTX and is commonly started directly after surgery. However, nephrotoxicity by reduced renal blood flow is an adverse side effect, which can potentially aggravate the risk for early onset AKI ,27. PrevIn the present study, we found that duration of NE therapy was associated with AKI requiring RRT in patients with preserved renal function after HTX. Nephrotoxic properties of vasoactive agents by constriction of afferent renal blood vessels are critically discussed. In this context, Jocher et al. showed that elevated vasoactive inotropic score at 24 h after surgery was an independent risk factor for early onset AKI in 228 HTX patients . The vasThis study has several limitations that need to be addressed. Firstly, the incidence of early onset AKI requiring RRT in this study was high. This must be taken into account when interpreting our results. Secondly, as our sample size was rather small, we were not able to include all significant variables of the univariate model into multivariate analysis. However, some of these variables, such as prolonged ICU stay, might rather be associated with AKI than being a predictor for AKI. Thus, a larger sample size might enable the identification of more independent risk factors for AKI requiring RRT. Thirdly, this study had a retrospective design, therefore data assessment was limited to our database. Unfortunately, we could not assess vasoactive inotropic score. However, a huge amount of our data could be extracted from this prospectively conducted database, which should ensure a higher quality of data. Nevertheless, further studies should re-investigate our findings with a prospective design.This study identified prolonged vasopressor therapy and high maximum daily increase in tacrolimus plasma concentrations as independent risk factors for early onset AKI requiring RRT after HTX in patients with preserved renal function. These results are clinically relevant and new therapeutic approaches for HTX patients are urgently needed. In this context, the role of calcineurin inhibitor free induction therapy or extended-release tacrolimus should be investigated.


Left uterine displacement (LUD) has been questioned as an effective strategy to prevent aortocaval compression after spinal anesthesia (SA) for cesarean delivery (CD). We tested if LUD has a significant impact on cardiac output (CO) in patients undergoing CD under SA during continuous non-invasive hemodynamic monitoring with Clearsight.dyn) at the different timepoints. Data on fetal Apgar scores and umbilical arterial and venous pH were collected.Forty-six patients were included in the final analysis. We considered 4 timepoints of 5 min each: T1 = baseline with LUD; T2 = baseline without LUD; T3 = after SA with LUD; T4 = after SA without LUD. LUD was then repositioned for CD. The primary outcome was to assess if CO decreased from T3 to T4 of at least 1.0 L/min. We also compared CO between T1 and T2 and other hemodynamic variables: mean, systolic and diastolic blood pressure , heart rate (HR), stroke volume (SV), stroke volume variation (SVV), pulse pressure variation (PPV), contractility (dP/dt), dynamic arterial elastance (EaP = 1). No significant variation was registered for any variable at any timepoint.CO did not vary from T3 to T4   Since 1953, the gravid uterus in pregnancies at term has been recognized as a cause of aortic and caval compression in the supine position . Later, The introduction of a 15° left uterine displacement (LUD) was proposed for the first time by Crawford and colleagues in 1972, as a result of their experiments on 150 women undergoing CD under general anesthesia . HoweverThe introduction of an optimized vasopressor and fluid therapy posed questions on its effective utility –11.A Cochrane review found no differences in hypotensive events between supine and LUD patients .Lee and colleagues measured CO, stroke volume (SV) and systemic vascular resistances by suprasternal Doppler ultrasound in not anesthetized parturients with four levels of left lateral tilt  , showingOn the other hand, Tsai and colleagues showed that NICOM hemodynamic monitoring could not detect any difference in cardiac index between patients with LUD and supine patients ; while Cmax) and dynamic arterial elastance (EaN =dy PPV/SVV) with and without LUD before and after SA to asses for significative differences.The aim of this prospectic observational study was to evaluate if CO decreased of at least 1.0 L/min after removing LUD after SA for CD during continuous non-invasive monitoring. We also compared values of mean arterial pressure (MAP), systolic arterial pressure (SAP), diastolic arterial pressure (DAP), SV, stroke volume variation (SVV), heart rate (HR), pulse pressure variation (PPV), contractility .Written informed consent was obtained from each participant.We included adult (≥ 18 years old) pregnant patients at term (36th to 40th week of gestation) scheduled for elective CD under SA, who, in addition to standard monitoring , underwent perioperative non-invasive monitoring by ClearSight system on the Edwards Lifesciences HemoSphere platform .2, fetal complications, coagulation disorders or contraindication to neuraxial block, emergency surgery, preoperative infection, patient’s refusal.Exclusion criteria were: American Society of Anesthesiologists status > 3, cardiac arrhythmias or aortic regurgitation, pregnancy-induced hypertension, pre-eclampsia, body mass index (BMI) > 35 kg/mThe ClearSight system consists of a finger cuff positioned at the middle phalanx of the third finger of the non-dominant hand of the patient, able to detect continuous noninvasive blood pressure and advanced hemodynamic parameters .max and PPV/SVV recorded at 20 s-intervals.The parameters we evaluated from the ClearSight system for the analysis were CO, MAP, SAP, DAP, SV, SVV, HR, PPV, dP/dtAll patients had a peripheral vein cannulated in the pre-anesthesia room and received metoclopramide 10 mg, pantoprazole 40 mg and cefazoline 2 gr delivered with a total of 100 ml of normal saline. Fluids were then stopped until spinal anesthesia. Anesthesia was delivered in sitting position using a 25-G Whitacre spinal needle, at the L3-4 vertebral interspace, with hyperbaric 0.5% bupivacaine, sufentanil 5 mcg and morphine 100 mcg. The bupivacaine dose administered was standardized according to patient’s height, as usual practice in our Institution: 8 mg for women < 160 cm tall, 9 mg for women between 160 and 170 cm, and 10 mg for those > 170 cm. Once the anesthetic procedure was completed, all patients received a rapid crystalloid co-load of 7 ml/kg over 10 min. During surgery and after delivery, fluid management was left to the attending anesthesiologist.We considered 4 timepoints. We indicated as T1 the baseline values recorded for 5 min, after initial stabilization of parameters, with the patient laying down on the operating table with LUD. At T2, LUD was removed and we considered for the analysis hemodynamic data of the subsequent 5 min. We indicated as T3 the 5 min following SA with a satisfactory sensory block and as T4 the subsequent 5 min following LUD removal. Figure LUD was accomplished by positioning a wooden wedge and wrapped with cotton, to make it comfortable, and medical sheets with a measured angle of 15° under the right flank of the laying down patient. The correct lateral tilt inclination was measured with a bubble level. In all patients, after T4, the 15° wooden wedge was repositioned in all patients and surgery was performed with LUD.The attending anesthesiologist was blinded to the advanced hemodynamic parameters from the ClearSight system except for the continuous BP values. We defined hypotension as an absolute value of MAP < 65 mmHg. This value was considered as trigger for the attending anesthesiologist for the administration of norepinephrine 5 mcg. Norepinephrine boluses were repeated to reach a MAP > 65 mmHg. Bradycardia was defined as a heart rate of < 60 bpm. Atropine 0.5 mg was administered for the treatment of bradycardia combined with hypotension, or for an absolute value of heart rate < 45 bpm for more than 20 s. After delivery, Oxytocin was administered to facilitate the uterine contraction.We also evaluated the impact of maternal blood pressure and CO on fetal outcome collecting neonatal Apgar scores at 1 and 5 min after birth, and umbilical cord arterial and venous pH.We estimated the sample size based on the CO reported in a recently published randomized controlled trial comparing patients with and without LUD during CD under SA . The rephttps://clincalc.com/stats/samplesize.aspx), we estimated a minimum sample size of 35 patients to detect the same variation of CO after LUD removal. We included all patients whose data were recorded and complete, who did not meet any exclusion criteria, for a total of 46 patients, to account for dropouts.Considering a significance level of 0.05 and a power of the test of 0.90 (p > 0.05). Bonferroni’s adjustments for multiple comparisons was applied for pairwise comparisons among group means.Continuous variables were reported as mean  if normally distributed, and as median and interquartile range (IQR) or as median (minimum–maximum) if not normally distributed. Categorical variables were reported as number and percentage. Shapiro–Wilk test was used to assess normality of data distribution and the equality of variances was verified with the variance ratio test. Repeated measure analysis of variance (ANOVA) or its non-parametric alternative Friedman test for non-normally distributed variables were used to compare patients’ longitudinal hemodynamic data from baseline until ten minutes after SA was performed. Sphericity assumption was not violated and it was assessed with the Mauchly’s test . Four patients were excluded due to incomplete data records. We used for the final analysis data from 46 women, including 6 twin pregnancies with mean gestational age of 38 ± 2 weeks. The consort diagram is represented in Fig. We screened 90 pregnant women at term scheduled for elective CD. Forty cases were excluded because they did not meet the inclusion criteria  and arterial (UA) blood gas analysis are summarized in Table P = 1.0)  L/min  at baseline and -0.028 (SE 0.32) L/min  after SA (P = 1.0) , nor after LUD removal at baseline (CO mean difference 0.34 (SE 0.32) L/min ) and -0.028 (SE 0.32) L/min  after SA  did not need vasopressors during the first 10 min after SA. No patient experienced nausea or vomiting. Only one patient had bradycardia which required atropine. There were no episodes of cardiac arrest.At T3, during the first 5 min after SA, 22 patients received norepinephrine to treat hypotension and at T4, during the subsequent 5 min after removal of LUD, vasopressor was administered to 20 patients [mean dose 13 (± 5.87 SD) mcg at T3 vs. 9 (± 5.91 SD) mcg at T4; Mean Apgar scores at 1 and 5 min were, respectively, 8.6  and 9.4 , with one case of Apgar score of 2 at 1 and 5 min in a baby with trisomy 18 disease born at 36 weeks of gestation, which was undiagnosed until birth in a patient with poor assistance during pregnancy. Mean UV pH was 7.32 (± 0.05), and mean UA pH was 7.29 (± 0.09).max and Eadyn did not vary significantly with and without LUD either at baseline or after SA.In this prospective observational study, we found that under continuous hemodynamic monitoring, CO did not show any significant variation after LUD removal under SA for CD. LUD showed no impact on CO neither at baseline, before SA. Blood pressure, HR, SV, SVV, PPV, dP/dtOf 46 patients, 22 (48%) needed vasopressor support right after SA with LUD, and 20 (43%) needed vasopressor support after LUD removal under SA. The total amount of norepinephrine was significantly higher after LUD removal under SA, but SAP, MAP and DAP were not significantly influenced. This may suggest that, even if LUD may have a role in maintaining MAP, prompt vasopressor administration is able to correct hypotensive events even without LUD. The continuous blood pressure monitoring and the prompt medical intervention triggered by a conservative threshold (MAP < 65 mmHg) allowed an efficient hemodynamic control, as demonstrated by the lack of emetic symptoms, such as nausea and vomiting. We should consider that in everyday practice blood pressure during CD is not measured continuously, but international recommendations suggest non-invasive blood pressure measurements every minute and prophylactic vasopressor infusion . In 2017Previous studies showed mixed results on the hemodynamic impact of LUD –20. A CoMost studies on maternal hemodynamics focused on systolic blood pressure. This parameter is reliable and easily reproducible, hence its wide use. CO is not routinely measured in elective cesarean deliveries, and non-invasive monitoring devices are expensive and not widely available. On the other hand, CO is a better indicator of fetal perfusion than blood pressure, due to the changes in peripheral resistances that occur in pregnancy, which do not necessarily reflect fetal perfusion .Recently, Chungsamarnyart and colleagues published their randomized-controlled trial comparing non-invasive monitoring of CO in patients with LUD and without LUD, showing that LUD provided modest hemodynamic advantages  pre-delivery. The results support maternal hemodynamic benefits of LUD until delivery in women with term pregnancies undergoing CD with SA .Preventing hypotension and hemodynamic derangement after SA for CD is a challenge for the obstetric anesthesiologist in order to avoid maternal and fetal complications.In this study we open new questions on the hemodynamic benefit of LUD, suggesting that preventive vasopressor therapy and optimized fluid management may allow an optimal uterine perfusion  independently from aortocaval compression.This study has some limitations. Firstly, its design does not include a control group, but patients act as their own control after LUD removal before and after SA. On the other hand, the continuous hemodynamic monitoring allowed to better evaluate the impact of LUD on CO with standard anesthetic management, correcting for inter-individual variables.Also, we defined hypotensive events as MAP < 65 mmHg, even if in obstetric anesthesia the most common definition of hypotension refers to SAP (< 80% baseline or < 100 mmHg) , 23. NevCO did not decrease significantly after LUD removal in patients under SA for CD during continuous hemodynamic monitoring. Optimization of fluid and vasopressor therapy may be sufficient to prevent aorto-caval compression by the gravid uterus and the consequent reduction of venous return after SA for CD.


Background: Orthostatic hypotension (OH) in Parkinson’s disease (PD) can lead to falls, impair quality of life, and increase mortality. A trajectory analysis of OH could be useful to predict and prevent the hypotension incidence early.Methods: The longitudinal data of 660 patients with PD with disease duration up to 12 years were extracted from an integrated PD database. We used latent class mixed modeling (LCMM) to identify patient subgroups, demonstrating trajectories of changes in orthostatic blood pressure (BP) over time. The optimal number of subgroups was selected by several criteria including the Bayesian Information Criterion. Baseline information comparison between groups and backward stepwise logistic regression were conducted to define the distinguishing characteristics of these subgroups and to investigate the predictors for BP trajectory.Results: We identified three trajectories for each orthostatic change of systolic blood pressure (ΔSBP), namely, Class 1  consisted of 18 participants with low ΔSBP that increased continuously during the follow-up; Class 2  consisted of 610 participants with low ΔSBP that remained low throughout the follow-up; and Class 3  consisted of 32 participants with high ΔSBP at baseline that was relatively stable throughout the follow-up. Several parameters differed among subgroups, but only male sex , lower supine diastolic blood pressure (DBP) , and lower level of total protein at baseline  were significant predictors of an increasing ΔSBP trajectory.Conclusion: This study provides new information on the longitudinal development of ΔSBP in patients with PD with distinct trajectories of rapidly increasing, low-stable, and high-stable class. The parameters such as male sex, lower supine DBP, and lower total proteins help to identify the rapidly increasing class. Orthostatic hypotension (OH), a sustained fall in blood pressure (BP) upon standing, is among the most debilitating manifestations of autonomic dysfunction in Parkinson’s disease (PD). Classical OH is defined as a sustained reduction of at least 20 mmHg of systolic blood pressure (SBP) or 10 mmHg of diastolic blood pressure (DBP) within 3 min of standing or the head-up tilt-table testing . CurrentSeveral confounding variables may influence the extent to which orthostatic BP falls, such as gender, age, hydration, blood glucose, deconditioning, and anemia . OH is aHowever, there have been few studies investigating the longitudinal orthostatic BP changes of patients with PD. BP trajectory could facilitate the prediction of hypotension and hence may be useful in OH prevention. This study was based on the data from the Parkinson’s Progression Markers Initiative (PPMI). The aim of this study was to identify latent subgroups of orthostatic BP trajectories and to investigate the associated factors that influence the different trajectory types. The analysis of orthostatic BP change was based on SBP because the systolic criteria seem to be sufficient to identify 95% of subjects with OH . In addi1. The data were accessed on August 1, 2020. The patients with PD with available BP measurements at two or more visits during a 12-year duration of disease were included. A duration of 12 years was chosen as the upper limit because the majority of participants were patients with de novo PD at baseline. Data volumes decrease significantly at longer durations, reducing the reliability of results. From the relationship between disease duration and the number of patients whose BP was measured   every yeBlood pressure  was measured at every visit. The supine BP was determined after 1–3 min of quiet rest, and the standing pressure was determined after 1–3 min in the standing position. The orthostatic SBP change was calculated as ΔSBP . The same was ΔDBP (supine DBP minus standing DBP). Weight and height were collected at the baseline visit and annually or bi-annually according to the visit schedule.Routine clinical laboratory tests consisting of complete blood count and metabolic panel were performed at screening and annually. A central laboratory was implemented to guarantee identical analysis methods, consistent normal ranges, and, thus, common interpretation of laboratory changes. In this research, laboratory parameters possibly related to OH were extracted from all test results, including red blood cell count, hematocrit, hemoglobin, serum glucose, serum sodium, serum potassium, serum chloride, total protein, albumin, creatinine, urea nitrogen, and serum uric acid.Continuous variables were expressed as the median and interquartile range (IQR), due to the non-normal data distributions evident upon graphical inspection and application of the Shapiro-Wilk test. Categorical variables were expressed as frequencies and percentages.We used latent class mixed modeling (LCMM) to model longitudinal ΔSBP. LCMM is a statistical approach that identifies the heterogeneity between patients by classifying them into unobserved subgroups . The time from disease onset (years) was used as the time indicator. The best model was chosen according to (1) Bayesian information criterion (BIC), (2) high mean posterior probability greater than 0.7, (3) sufficient group sizes, and (4) the clinical significance of the models . To mainComparisons of baseline information among subgroups were performed using the Kruskal-Wallis test for quantitative variables and the chi-square test for categorical variables. In the case of significant results, pairwise comparisons were performed, and a Bonferroni correction was applied. Variables with significant differences were further analyzed in the backward stepwise logistic regression of the latent classes.2 with the package “LCMM” for the latent class analysis. A p-value of less than 0.05 was considered statistically significant.All data analyses were performed using the SPSS software version 26  and R software version 4.0.3n = 439, 66.5%), PIGD , or indeterminate . The median of LEDD at baseline was 0 mg . Among all participants, 88 patients (13.4%) presented OH.A total of 660 participants with available BP at two or more visits during the 12-year duration of disease were included. Characteristics of the study population at the time of entry are presented in Considering that long-term PD medication and hypertension may influence ΔSBP, we also calculated the average LEDD and prevalence of hypertension during the follow-up. The median of average LEDD was 473.75 mg (IQR: 300.00–713.24), and a total of 232 patients (35.2%) developed hypertension at baseline or during follow-up.On the basis of longitudinal ΔSBP, patients were classified into groups using disease duration as the preferred time indicator. The baseline characteristics of participants in different trajectory subgroups are shown in Since Class 2 and Class 3 both showed relatively stable trajectories, it was of clinical significance to identify Class 1 with consistently increasing ΔSBP from the two types. In the regression analysis, Class 2 and Class 3 were collapsed into one agreement group, given their similar flat slopes. Due to the interdependent nature of standing BP, supine BP and orthostatic change of BP, only supine BP and BP changes were included in the regression. Regression results revealed that male , lower supine DBP , and lower level of total protein  were significant predictors of an increasing ΔSBP trajectory, as presented in We identified subgroups of ΔSBP trajectory in patients with PD based on a longitudinal analysis of PPMI data. The best fit was identified for a three-class model, reflecting three subgroups of the ΔSBP change. Class 1 was characterized by rapidly increasing ΔSBP. Class 2 displayed a lower level of ΔSBP throughout the follow-up, while Class 3 was characterized by a greater ΔSBP at baseline, which kept relatively stable over time. The main predictors of rapidly increasing ΔSBP in PD were male sex, lower supine DBP, and lower level of total protein at baseline.Orthostatic hypotension is associated with target organ damage and typically manifests with recurrent syncope and orthostatic intolerance. Previous research has demonstrated that OH increases the risk of falls in patients with PD and is associated with cognitive impairment and greater deterioration in daily living activities, regardless of whether or not OH is symptomatic . Our resp-value of 0.718 in further logistic regression. In a longitudinal study conducted by In previous studies, there are contradictory results about the association between disease duration and OH. Clinical variables have been shown to play different roles in cross-sectional studies of PD-OH, as well as in the longitudinal trajectory of PD-OH. In the previous studies, PD-OH has been significantly related to older age, lower body mass index (BMI), more severe motor symptoms, higher LEDD, and higher blood glucose . SimilarIn PD, gender is significantly related to multiple motor and non-motor symptoms. In some previous studies, no correlations were identified between OH and gender in patients with PD . OH was Another key predictor of increasing OH incidence is supine DBP. Although a decline in diastolic BP during orthostasis may be less relevant in the clinical diagnosis of OH, its potential impact on long-term prognosis requires attention. The diastolic component of BP reflects the real pressure of coronary perfusion as the coronary flow is substantially reduced during systole . DecreasMalnutrition is also an important risk factor for OH . It has de novo PD with short follow-up durations, so, the data for late-stage PD was insufficient. Fourth, the conditions for BP measurement were not rigorously defined. For example, room temperature during BP measurement was not uniform across different centers. Fifth, supine BP was measured after 1–3 min of quiet rest, which was shorter than the standard procedure requirement of 5 min . For up-to-date information on the study, visit ppmi-info.org.Data used in the preparation of this article were obtained from the Parkinson’s Progression Markers Initiative (PPMI) database (Each participating PPMI site received ethical approval before study initiation and written informed consent was obtained from all participants.KC and YaZ designed the study. KC and KD collected the data. KD and YiZ performed the statistical analysis. KC and YG analyzed the results and drafted the manuscript. All authors contributed to the manuscript revision and read and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Only an estimated 43.7% of patients with hypertension achieve target blood pressure (BP).Bioimpedance or impedance cardiography (IC) is a novel tool in the management of hypertension with most of these studies using thoracic IC technology.P < 0.001. For the study group, hemodynamic data obtained using NICaS were used in the selection and titration of antihypertensive medications according to a predetermined algorithm .The hemodynamic profiles of the groups at baseline and final time points are illustrated in P = 0.025) along with a significantly greater mean (SD) decrease in diastolic BP of 12.8 (10.1) mm Hg versus 7.3 (9.7) mm Hg, P = 0.031 and mean arterial pressure of 16.4 (10.8) mm Hg versus 9.5 (12.7) mm Hg, P = 0.018. Significantly more patients in the study group met the hard target criteria: 57.53% versus 25.00%, P = 0.010, and for the soft target of 130/80 mm Hg at 50.88% versus 15.38% P = 0.029 (P = 0.026). Within-group vital signs and hemodynamic data at baseline and final time points are found in  = 0.029 . CompareThe percentage of study group patients who had resistant hypertension, defined by uncontrolled BP despite 3 antihypertensives including a diuretic, was 13.7% versus 15.0% in the control group. There were no differences between the groups at study end regarding medication classes or number of antihypertensive medications . NeverthPrevious studies suggested that management strategies incorporating hemodynamic data may be superior to standard care.et al.We did not observe an increase in the use of thiazide or loop diuretics at the final period in contrast with the findings of Taler There are several limitations in this study. First, because it was a continuous quality improvement project, intervals between visits were not standardized but instead reflect normal practice patterns. Next, the control group is small and our inferences were potentially underpowered though we observed statistically significant differences between groups in many key variables. This pragmatic project includes the possibility of bias based on physician practice styles and treatment effect. Another limitation is that the assessment of volume status using IC has not been validated in hypertensive cohorts. Therefore, it is possible that our definition of hypervolemia underestimated the percentage who may have responded to diuretic therapy. Finally, we did not exclude patients with congestive heart failure whose management is complicated by episodes of decompensation with more loop diuretics and/or holding renin angiotensin system inhibitors with increasing creatinine and/or potassium. Consequently, our findings may not be generalizable to this subpopulation of patients with hypertension.In summary, this pragmatic continuous quality improvement program reveals the feasibility and effectiveness of a hemodynamically directed management algorithm to individualize hypertension management in a busy nephrology practice. This approach was associated with improved brachial and central BP control and normalization of cardiovascular hemodynamics in a cohort of patients with and without CKD. Although this study is hypothesis generating, the results suggest that hemodynamically guided hypertension management may result in more patients achieving target BP and improved physiology.BG and MJG report receiving funding, through their medical practice, from NiMed. All the other authors declared no competing interests.