To assess different microperimetry (MP) macular sensitivity outcome measures capturing functional deterioration in eyes with geographic atrophy (GA) secondary to age-related macular degeneration (AMD).Patients were included from 2 identically designed, phase III, double-masked, randomized controlled clinical trials, Chroma (NCT02247479) and Spectri (NCT02247531).Patients enrolled were aged ≥ 50 years with bilateral GA and no evidence of previous or active neovascular AMD.Patients were randomized 2:1:2:1 to receive through 96 weeks intravitreal lampalizumab 10 mg every 4 weeks (LQ4W), every 6 weeks (LQ6W), or corresponding sham procedures. For this study, mesopic macular sensitivity of the central 20° was assessed using MP-1 microperimeter at selected sites.Two exploratory endpoints were developed, namely perilesional sensitivity (average of points adjacent to absolute scotomatous points) and responding sensitivity  by using customized masks for each patient. These were compared with conventional MP endpoints (mean macular sensitivity and number of absolute scotomatous points).2/year across treatment groups was accompanied by deterioration in all MP parameters. There was no difference in worsening of macular sensitivity or absolute scotomatous points among treatment groups. Perilesional and responding sensitivities showed greater decline over time than mean macular sensitivity. Change in GA lesion area at week 48 showed better correlation with perilesional sensitivity (r = −0.17) and responding sensitivity (r = −0.20) than mean macular sensitivity (r = −0.03), while the correlation was highest with the number of absolute scotomatous points (r = 0.37).Of 1881 Chroma and Spectri participants, 277 agreed to participate in the present study. Of these, 197  had reliable MP results. Enlargement of GA lesion area by approximately 2 mmPerilesional or responding macular sensitivity measured by MP should be considered more sensitive endpoints than mean macular sensitivity for monitoring functional decline over time in GA. Although perilesional, responding, and mean macular sensitivity had weak correlation with GA lesion area, the number of absolute scotomatous points may provide additional information on the anatomic/functional correlation.Proprietary or commercial disclosure may be found after the references. The most widely used primary endpoint is change in GA lesion area, which relies on evaluation of imaging features anchored on fundus autofluorescence (FAF) as the primary imaging modality.Functional studies that correlate with anatomic changes over time are necessary because visual function is of key importance to patients and physicians. Best-corrected visual acuity (BCVA), which is the traditional functional endpoint in ophthalmology clinical trials, does not have a strong correlation with GA progression.Mesopic microperimetry (MP) is a noninvasive psychophysical test that differs from traditional visual function tests, measuring mesopic macular sensitivity with focal light stimulation and using eye tracking technology.Currently in clinical research, the 2 most commonly evaluated MP endpoints are mean macular sensitivity and number of absolute scotomatous points . However, a limitation of using mean macular sensitivity as an outcome measure in GA clinical trials is that it is averaged across all tested points ; thus, the magnitude of change is blunted by scotomatous points and there is loss of spatial information.NCT02247479) and Spectri (NCT02247531) were 2 phase III trials evaluating the efficacy and safety of lampalizumab in patients with GA secondary to AMD. The primary efficacy outcome of these trials was mean change in GA lesion area from baseline to week 48, which was not met. Microperimetry was an exploratory endpoint to assess functional decline over time.Chroma  were included in this study. A detailed description of the trial designs has been published previously.Patients from the Chroma and Spectri trials (2) using a 68-loci circular grid centered at the preferred retinal locus, covering the central 20° of the macula (10-2 program). The stimulus was Goldmann size III (0.43° diameter) displayed for duration of 200 ms with 1.5-second intervals. A 4-2 staircase strategy was used, with testing intensities ranging from 127 to 1.27 cd/m2, which correspond to macular sensitivities of 0 to 20 dB. Patients were allowed 3 attempts to meet the MP screening test criteria. This involved the ability of the study eye to complete the 10-2 68-point exam in ≤ 30 minutes with a reliability ratio ≥ 80% .Mesopic macular sensitivity was assessed by MP at baseline and weeks 24, 48, 72, and 96 using the MP-1 microperimeter . Mean macular sensitivity was measured in the presence of a background luminance of 4 apostlibs , and the 68 loci grid was recreated as a matrix. Masks that identify each locus as belonging to a macular region according to these definitions were then generated on the baseline data . The aveColor fundus photographs, FAF, and spectral-domain OCT images were collected every 6 months for up to 24 months. Mean change in GA lesion area from baseline was measured by FAF and data were evaluated at the Doheny Image Reading Center .Mixed-effect model for repeated measure analyses showed no differences for any endpoint between treatment groups when adjusted for baseline GA lesion, subfoveal area, multifocal configuration, biomarkers, BCVA, and sexOf the 1881 participants from the Chroma and Spectri trials, 277 (14.7%) across 50 sites in 7 countries agreed to participate in the present study . After tBaseline characteristics were well distributed across the randomized treatment arms . The maj2 .At week 48, mean change in GA lesion area in this study population was 2.0 mm2 A; the CVMean BCVA in this study population steadily declined over time B, with awww.ophthalmologyscience.org). Eye-level changes in MP endpoints over time demonstrated high levels of variability (Macular sensitivity endpoints over time are shown in iability  to 4F.FiThe correlation between MP endpoints and change in GA lesion area as determined by FAF at week 48 is shown in 2/year, and all MP parameters deteriorated over time.In this exploratory study of the MP data from the Chroma and Spectri trials, we evaluated conventional as well as novel MP endpoints and determined their ability to detect visual function decline caused by GA secondary to AMD. We found that the mean GA lesion area enlarged by approximately 2 mmThe novel MP endpoints of perilesional and responding sensitivities were more sensitive than the conventional MP endpoint of mean macular sensitivity for the measurement of functional decline over time. The lower magnitude observed in mean macular sensitivity is likely due to using all tested points, including absolute scotomatous points, which dilutes the mean. Perilesional and responding sensitivity exclude absolute scotomatous points identified at baseline and are therefore more sensitive than mean macular sensitivity, demonstrating higher change in dB with lower variability. The results of this study can be taken into consideration when planning the utilization of various MP testing patterns and when interpreting their outputs, including a standard grid for all patients, such as the one utilized in this clinical development program, as well as linear/cross or custom tailored patterns.,The assessment of the anatomic/functional correlation in GA has been challenging with many visual function tests. The correlation between GA lesion area over time and change in MP endpoints was the strongest for absolute scotomatous points. In alignment with previous studies,The correlation between GA lesion area and mean macular sensitivity was not as robust.Perilesional sensitivity captures the area adjacent to absolute scotoma.,Poor or eccentric fixation can impose additional challenges to the execution and interpretation of MP exams. Most MP examination strategies use real-time retinal tracking of a spatial map that may overcome some of the fixation issues common in patients with low vision.Of note, to calculate the perilesional and responding sensitivities in this study, a mask of the MP map encompassing all absolute scotomatous points in the topography of the GA lesion area was created at baseline for each enrolled eye; this required the development of custom software . If simiThe present study analyzes one of the largest MP datasets ever collected in macular diseases with prospectively enrolled patients evaluated at stringent intervals; notably, a standardized clinical trial–determined protocol of MP examination was followed, including rigorous data collection and analysis. In both of the clinical trials included in this study, > 98% of the population was White . So, it


Critical illness may disrupt nutritional, protective, immune, and endocrine functions of the gastrointestinal tract, leading to a state of gastrointestinal dysmotility. We aimed to identify factors associated with the occurrence of gastrointestinal dysmotility in critically ill patients. A cross-sectional retrospective study was conducted, using patient files as a source of data. The study included 185 critically ill patients treated in the intensive care unit of the University Clinical Center, Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. Significant risk factors associated with some form of gastrointestinal dysmotility were acute kidney injury , recent abdominal surgery , mechanical ventilation , age (with ileus and constipation), and use of certain medication such as opioids , antidepressants , and antidiabetics (with ileus). On the other hand, Charlson comorbidity index had divergent effects, depending on the form of gastrointestinal dysmotility: it increased the risk of gastro-esophageal reflux but protected against ileus, nausea, and vomiting. In clonclusion, recognition of factors associated with gastrointestinal dysmotility should initiate preventative measures and, thus, accelerate the recovery of critically ill. As a rule, critically ill patients are treated in intensive care unit (ICU), where the attention of physicians is mainly focused on respiratory and cardiovascular functions . HoweverGastroparesis, or slowed gastric emptying occurs with a prevalence of 4–5% in the general population, while among critically ill patients in the ICU, it is encountered more frequently , head inConsidering the significant controversies concerning risk factors and their interaction, our study aimed to test known predictors and investigate some new potential predictors of GID in critically ill patients, as well as to quantify the strength of their effects.2A cross-sectional retrospective study design was used for the study. The study population consisted of critically ill patients treated in the ICU of the University Clinical Center Kragujevac in Kragujevac, Serbia, from January 1, 2016, to January 1, 2022. The criteria for the inclusion of patients were: the existence of an acutely occurring critical illness  and a stay in the ICU for longer than 48 h. Patients were excluded from the study if they were younger than 18 years, on a chronic hemodialysis program, with decompensated liver cirrhosis, with chronic gastrointestinal diseases , if the data from the medical history were not complete, and if a patient was a pregnant woman. The sample used for the study was of convenient type, although consecutive, i.e., all patients who satisfied inclusion and without exclusion criteria within the study period were included.The main study outcomes were GID in general, and its specific types: paralytic ileus, gastroesophageal reflux, nausea, vomiting, and constipation. The specific types of GID were accounted for each of the study patients only if their diagnoses were recorded in the patient files by the responsible physician during the patients’ stay in the ICU, using the ICD-10 codes: K56.0 for paralytic ileus, K21.0 for gastroesophageal reflux, R11.0 for nausea, R11.1, R11.2, R11.10, R11.11, R11.12, and K91.0 for vomiting, and K59.01 for constipation. The patient was considered to have GID in general if at least one of the abovementioned specific types of GID was recorded in his/her file. Apart from several independent variables known from previous research that may influence gastrointestinal motility , a plethora of confounders was also extracted from the patient files: routine blood biochemistry and hematology, Charlson comorbidity index, prescribed medication, and diagnoses of acute events occurring during hospitalization in the ICU. The data were extracted by two independent investigators from electronic patients’ histories embedded in the hospital information system “ZIS”  and then harmonized among themselves by consensus.A minimal sample size was sufficient for the purpose of finding factors significantly associated with GID as the main outcome was calculated by the Schlesselman’s method . The folThe data collected from the ZIS information system were first numerically coded, tabulated, and checked for errors by both investigators independently. The data were then described by measures of central tendency and variability (if continuous), or by frequencies and relative numbers and percentages . Mean and standard deviation were used as descriptors of normally distributed continuous data, while median and interquartile range described the data distributed in other way. Effects of putative predictors and confounders on the study outcomes were analyzed by multivariate binary logistic regression. Before applying these multivariate techniques, their assumptions were checked whether being satisfied . The quality of the regression models was checked by the Hosmer and Lemeshow test, Cox & Snell R square, and Nagelkerke R square. The results were considered statistically significant if the probability of null hypothesis was 0.05 or below. All calculations were made by the Statistical Package for the Social Sciences (SPSS), version 18.0.Ethical approval: The research has been complied with all the relevant national regulations, institutional policies, and in accordance the tenets of the Helsinki Declaration and has been approved by the institutional review board, the Ethics Committee of University Clinical Center Kragujevac .Informed consent: This is a retrospective study, and for this type of study, formal consent is not required.3The study included a total of 185 patients treated in the ICU. The number of cases that had ileus is 95 (51.4%), and the total number of controls is 90 (48.6%). Patients were matched by gender and age. No controls were found for 5 subjects. A total of 121 patients (65.4%) had gastro-esophageal reflux. Nausea was experienced by 92 patients (49.7%). Vomiting was experienced by 60 patients (32.4%). Constipation was experienced by 104 patients (56.2%). A total of 160 patients (86.5%) had some form of GID. Detailed data of the study sample of patients are shown in The characteristics of the subjects according to the groups formed based on the outcome  are shown in Multivariate analysis was performed using binary logistic regression. The results are shown in p = 0.063), Cox & Snell R square 0.423, and Nagelkerke R square 0.564.Association of independent and confounding variables with ileus was tested by multivariate binary logistic regression. The model was built by backward conditional stepwise method starting with a full set of potential predictors: serum creatinine, acute kidney injury, Charlson comorbidity index, prescribed antidiabetics, opioids, antidepressants, antipsychotics, heparin, sepsis, recent abdominal surgery, and mechanical ventilation. The assumptions of binary outcome (ileus or not), independency of observations, no multicollinearity , no extreme outliers, and sufficiently large sample were all met. The linear relationship between explanatory variables and the logit of the outcome was confirmed for all variables by the Box-Tidwell test. The final model of binary logistic regression included variables shown in p = 0.842), Cox & Snell R square 0.118, and Nagelkerke R square 0.163.The association of independent and confounding variables with gastro-esophageal reflux was tested by multivariate binary logistic regression. The model was built by backward conditional stepwise method starting with a full set of potential predictors: serum creatinine, acute kidney injury, Charlson comorbidity index, prescribed antidiabetics, opioids, antidepressants, antipsychotics, heparin, sepsis, recent abdominal surgery, and mechanical ventilation. The assumptions of binary outcome , independency of observations, no multicollinearity , no extreme outliers, and sufficiently large sample were all met. The linear relationship between explanatory variables and the logit of the outcome was confirmed for all variables by the Box-Tidwell test. The final model of binary logistic regression included variables shown in p = 0.152), Cox & Snell R square 0.362, and Nagelkerke R square 0.482.The association of independent and confounding variables with nausea was tested by multivariate binary logistic regression. The model was built by backward conditional stepwise method starting with a full set of potential predictors: serum creatinine, acute kidney injury, Charlson comorbidity index, prescribed antidiabetics, opioids, antidepressants, antipsychotics, heparin, sepsis, recent abdominal surgery, and mechanical ventilation. The assumptions of binary outcome (nausea or not), independency of observations, no multicollinearity , no extreme outliers, and sufficiently large sample were all met. The linear relationship between explanatory variables and the logit of the outcome was confirmed for all variables by the Box-Tidwell test. The final model of binary logistic regression included variables shown in p = 0.390), Cox & Snell R square 0.228, and Nagelkerke R square 0.319.The association of independent and confounding variables with vomiting was tested by multivariate binary logistic regression. The model was built by backward conditional stepwise method starting with a full set of potential predictors: serum creatinine, acute kidney injury, Charlson comorbidity index, prescribed antidiabetics, opioids, antidepressants, antipsychotics, heparin, sepsis, recent abdominal surgery, and mechanical ventilation. The assumptions of binary outcome (vomiting or not), independency of observations, no multicollinearity , no extreme outliers, and sufficiently large sample were all met. The linear relationship between explanatory variables and the logit of the outcome was confirmed for all variables by the Box-Tidwell test. The final model of binary logistic regression included variables shown in p = 0.613), Cox & Snell R square 0.277, and Nagelkerke R square 0.371.The association of independent and confounding variables with constipation was tested by multivariate binary logistic regression. The model was built by backward conditional stepwise method starting with a full set of potential predictors: serum creatinine, acute kidney injury, Charlson comorbidity index, prescribed antidiabetics, opioids, antidepressants, antipsychotics, heparin, sepsis, recent abdominal surgery, and mechanical ventilation. The assumptions of binary outcome (constipation or not), independency of observations, no multicollinearity , no extreme outliers, and sufficiently large sample were all met. The linear relationship between explanatory variables and the logit of the outcome was confirmed for all variables by the Box-Tidwell test. The final model of binary logistic regression included variables shown in 4Significant risk factors associated with some form of GID in our study were acute kidney injury , recent abdominal surgery , mechanical ventilation (associated with ileus and nausea), advanced age (associated with ileus and constipation), as well as the use of certain drugs such as opioids , antidepressants , and antidiabetics (associated with ileus only). However, Charlson comorbidity index had a divergent effect depending on the form of GID: it increased the risk of gastroesophageal reflux, but it was protective against ileus, nausea, and vomiting.Previous studies have found that comorbidities are very common in patients with gastro-esophageal reflux , what coA recent surgery in the abdomen is another factor associated with the appearance of ileus; however, the mechanism of its inhibitory effect is unknown. Due to the activation of pain receptors, abdominal surgery leads to the hyperactivity of the sympathetic nervous system and hypertonia of intestinal sphincters; besides, electrolyte disorders that accompany blood loss, and an intensive administration of crystalloid solutions during and after operations can inhibit depolarization of neurons in the myenteric plexus and prevent initiation of peristalsis . MechaniOver 50% of our patients had nausea, so a large number of factors were associated with its occurrence. First, patients with acute kidney injury had nausea due to the acidosis and accumulation of degradational metabolic products ,22. The 2O), which increases pressure in semicircular channels of internal ear, and also in the abdomen due to its passage through esophagus and stomachs into the small bowel during general anesthesia [Postoperative vomiting was frequent in our patients; those submitted to longer operations experienced more often vomiting after the surgery: prolongation of surgery for 30 min increased the risk of vomiting by about 60% . At leasesthesia ,28.Constipation occurred in our study more often in patients with acute kidney injury. Possible reasons for the development of constipation in these patients are accumulation of inflammatory mediators and degradational products of metabolism in the GIT  and modiThis study has several limitations. As a unicentric study, it is subject to effect of local factors on outcomes . A relatively small number of patients and the small statistical power of this study have created conditions for falsely negative results, e.g., effect of antipsychotics did not reach significance because they were prescribed to a small percentage of patients. Due to the unavailability of some laboratory analyses during the study , we could not calculate Apache II score for many patients.5In conclusion, the factors we identified as associated with the GID should be kept in mind by physicians who work with critically ill patients in an ICU. Early detection of these factors enables the implementation of measures that can either prevent, or at least mitigate the GID, and thus accelerate the recovery of critically ill.


The causal relationship between blood pressure variability (BPV) and arterial stiffness remains debated.This study aimed to explore the temporal and bidirectional associations between long-term BPV and arterial stiffness using a cohort design with multiple surveys.Participants from the Beijing Health Management Cohort who underwent health examinations from visit 1 (2010-2011) to visit 5 (2018-2019) were enrolled in this study. Long-term BPV was defined as intraindividual variation using the coefficient of variation (CV) and SD. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV). The bidirectional relationship between BPV and arterial stiffness was explored using cross-lagged analysis and linear regression models, with records before and after visit 3 categorized as phase 1 and phase 2, respectively.Of the 1506 participants, who were a mean of 56.11 (SD 8.57) years old, 1148 (76.2%) were male. The cross-lagged analysis indicated that the standardized coefficients of BPV at phase 1 directing to the baPWV level at phase 2 were statistically significant but not vice-versa. The adjusted regression coefficients of the CV were 4.708 (95% CI 0.946-8.470) for systolic blood pressure, 3.119 (95% 0.166-6.073) for diastolic pressure, and 2.205 (95% CI 0.300-4.110) for pulse pressure. The coefficients of the SD were 4.208 (95% CI 0.177-8.239) for diastolic pressure and 4.247 (95% CI 0.448-8.046) for pulse pressure. The associations were predominant in the subgroup with hypertension, but we did not observe any significant association of baPWV level with subsequent BPV indices.The findings supported a temporal relationship between long-term BPV and arterial stiffness level, especially among people with hypertension. Hypertension is one of the most significant risk factors for heart failure, atrial fibrillation, stroke, chronic kidney disease, and overall cardiovascular disease (CVD), with a largely increasing health burden ,2. AccorPrevious studies have shown that elevated blood pressure precedes arterial stiffness . In addiIn this study, we aimed to comprehensively investigate the temporal and bidirectional relationship between long-term BPV and arterial stiffness using a cross-lagged panel design and further explore the interaction effect of hypertension status in a large cohort.This study included participants from the Beijing Health Management Cohort, which is a large-scale longitudinal cohort study investigating the risk factors and biomarkers of cardiometabolic disorders. Our study is a secondary analysis of the Beijing Health Management Cohort under a longitudinal cohort design with multiple consecutive surveys. In total, 2381 individuals aged 18 years or above underwent multiple comprehensive biennial health examinations at visit 1 (2010-2011), visit 2 (2012-2013), visit 3 (2014-2015), visit 4 (2016-2017), and visit 5 (2018-2019), and arterial stiffness data were collected. We excluded 760 individuals with missing blood pressure data at any health visit. To minimize the possible effect of reverse causality, 115 participants with CVD  at visit 3 (as the baseline) were further excluded. Finally, this study was restricted to a subset of 1506 participants with complete data. The period from visit 1 to visit 3 was defined as phase 1, and the period from visit 3 to visit 5 was defined as phase 2, as illustrated in Figure S1 of This study was approved by the Ethics Committee of Capital Medical University (2020SY031). The study data were anonymous. All participants provided written informed consent before taking part in this study.The participants’ sociodemographic characteristics and lifestyle and health-related information were collected via a standard questionnaire by our trained staff, including age, sex, education, smoking status, drinking status, regular physical activity, diagnosis history of diseases, and medication information. Educational level was categorized as no or some primary school, middle school or high school, and bachelor’s degree or above. Smoking was defined as “current,” “former,” and “never.” Drinking status was defined as “currently drinking” and “not currently drinking.” Regular physical activity was defined as having moderate or intense activity at work or during leisure time more than 4 times and 80 minutes per week. Vigorous activities make breathing much harder than normal and include heavy lifting, digging, plowing, aerobics, fast bicycling, and cycling with a heavy load. Moderate activities make breathing somewhat harder than normal and include carrying light loads, bicycling at a regular pace, mopping the floor, doing Taiji, and walking briskly. Mild activity refers to waking at work, at home, walking to travel from place to place, and any other walking that one might do solely for recreation, sport, exercise, or leisure .The physical and biochemical examination data were acquired from the electronic medical record system. BMI was calculated as weight (in kg)/height (in meters squared). Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were presented as the average of 2 measurements on the right arm using a sphygmomanometer after resting for at least 10 minutes. The pulse pressure (PP) was calculated as SBP minus DBP. Hypertension status was defined as SBP ≥140 mmHg or DBP ≥90 mmHg or use of any antihypertensive medication or self-reported history of hypertension according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) criteria . Data onBPV was assessed at phase 1 (visit 1 to visit 3) and phase 2 (visit 3 to visit 5). Long-term BPV was defined as the intraindividual variation in SBP, DBP, and PP at 3 visits and measured by the coefficient of variation (CV) and SD. The mean value of 3 blood pressure indices at each phase was also calculated.The arterial stiffness level was measured by brachial-ankle pulse wave velocity (baPWV), which is a simple, noninvasive, automatic method widely used in population-based studies. The baPWV was measured with an Omron Colin BP-203RPE III device . The time interval between the wave front of the brachial waveform and the ankle waveform is expressed as the time interval between the brachium and ankle (∆Tba). La indicates the path length from the suprasternal notch to the ankle, and Lb refers to the path length from the suprasternal notch to the brachium based on the height of the subjects. The final baPWV was calculated as (La-Lb)/∆Tba, which has been previously described . The art25-P75), or number (percentage), as appropriate. We used the cross-lagged panel model to analyze the temporal relationship between BPV and baPWV levels. The lagged effect between the observed variables, the correlation between the variables at each phase, and the residual variance of the observed variables were estimated in the cross-lagged panel analysis, which elucidates the temporal relationship between correlated variables and indicates the precursor variable [Baseline characteristics were presented as the mean (SD), median  model 1 was adjusted for the individual-level mean blood pressure; (2) model 2 was adjusted for mean blood pressure, age, and sex; and (3) model 3 was further adjusted for BMI, education level, smoking, drinking, physical activity, hypertension, dyslipidemia, diabetes, triglyceride, TC, FBG, HbA1c, and hs-CRP. In total, there were 17 variables in the regression model. Thus, a group of 1506 participants in this study could satisfy the sample size requirement given the principle of 10 samples per variable in the regression model . FurtherP<.1, and a 90% CI was provided in the subgroup analysis [In addition, we analyzed the association of BPV with arterial stiffness levels in the subgroups with and without hypertension. The use of antihypertensive medication was additionally adjusted for in the subgroup with hypertension, considering that antihypertensive agents are an important determinant of BPV and are related to arterial stiffness levels. The difference was considered statistically significant at 2-sided analysis .lavaan for cross-lagged panel analysis and ggplot2 for visualization.All the analyses were conducted using R software , using the packages Among the 1506 participants, the mean age was 56.11 (SD 8.57) years, and 661 (43.9%) were diagnosed with hypertension at visit 3. The median value of the cumulative average level of baPWV was 1395.50 (IQR 1298.12-1544.34) cm/s at phase 1 and 1438.25 (IQR 1344.00-1588.67) cm/s at phase 2. Detailed characteristics of the study population and the variability indices of blood pressure are summarized in P<.01), while the standardized coefficients of baPWV level at phase 1 to the subsequent BPV indices were all weak and insignificant.Assessments of BPV indices and baPWV at phase 1 and phase 2 constituted a typical cross-lagged panel design. In the fully adjusted model (model 3), a 1-unit increase in the CV of SBP, DBP, and PP at phase 1 was associated with a 4.708 (95% CI 0.946-8.470), 3.119 (95% CI 0.166-6.073), and 2.205 (95% CI 0.300-4.110) increase, respectively, in the baPWV level at phase 2. Similarly, a 1-unit increase in the SD of DBP and PP at phase 1 was associated with a 4.208 (95% CI 0.177-8.239) and 4.247 (95% CI 0.448-8.046) increase in the baPWV level at phase 2 . The posThe results remained almost consistent when the blood pressure level at visit 3 was alternatively adjusted in the model, apart from PP (Table S2 of We found that the relationship between BPV indices at phase 1 and baPWV level at phase 2 was affected by hypertension status . The CV This study explored the temporal and bidirectional associations between long-term visit-to-visit BPV and arterial stiffness levels based on a Chinese general population. In the cross-lagged analyses, the BPV indices were shown to have a temporal relationship with subsequent arterial stiffness, indicating that BPV is an independent predictor of unfavorable arterial stiffness levels and precedes arteriosclerosis progression, especially in people with hypertension. The classification of the temporal relationship in this study provides a scientific basis for identifying individuals at a high risk of arterial stiffness, further offering opportunities to advance primary prevention and personalized interventions for arterial stiffness.Blood pressure usually stabilizes within a certain range under the complex interaction of environmental factors and normal cardiovascular regulation function. Due to baroreflex dysfunction associated with arteriole remodeling, BPV, and arterial stiffness levels increase with age, but the mutual associations between BPV and arterial stiffness remain unclear . PreviouThe pathological mechanism between BPV and arterial stiffness or CVD has not been completely determined ,28. AccoFurthermore, the hemodynamic environment changes caused by BPV may be an important reason for vascular endothelial dysfunction, which is closely related to the progression of arterial stiffness and atherosclerotic diseases ,46. The In addition, previous population-based studies have shown that high BPV is strongly associated with biomarkers of vascular inflammation, independent of the mean levels of blood pressure . In shorBased on the vicious cycle of hemodynamic stress and vascular disease, Kario et al  proposedIn addition, this study found that BPV preceded arterial stiffness, suggesting a high risk of CVD in people with higher BPV. Previous studies have shown that plant-based diets have protective effects against CVD. In particular, the Mediterranean diet significantly reduces arterial stiffness and blood pressure levels , and DieSeveral limitations of this study should be acknowledged. First, different antihypertensive drugs have distinct effects on BPV and arterial stiffness levels, but detailed information on medication use is lacking in our study. The interaction effect between different antihypertensive medications and BPV on arterial stiffness levels needs further investigation. Second, this study is based on a Chinese cohort, and the observed results warrant further validation in other populations with large sample sizes. Data on household socioeconomic status and food intake were not collected in the cohort. The estimated effect size could be biased given the potential effects of socioeconomic status and dietary patterns on the arterial stiffness level. Third, the specific effect of maintaining long-term stable blood pressure on suppressing arterial stiffening and promoting cardiovascular health warrants further research.Our findings suggested a temporal relationship between visit-to-visit BPV and arterial stiffness during 10-year surveys, especially in people with hypertension. Maintaining long-term stable blood pressure should be emphasized for suppressing arterial stiffness. This study further demonstrates that long-term BPV provides a new target for the early prevention of CVD in the public health setting, suggesting the potential benefit of incorporating long-term monitoring and assessment of BPV into community-level health examinations.


Non-T2 asthma is characterized by the absence of elevated type 2 inflammatory biomarkers such as blood-eosinophils, total and allergen-specific Immunoglobulin E and Fractional exhaled Nitric Oxide (FeNO). According to guidelines, inhaled corticosteroids (ICS) are the cornerstone of asthma management. However, ICS treatment is associated with a risk of local side effects, including hoarseness and thrush, and long-term high-dose therapy may cause systemic adverse effects. Furthermore, whereas treatment with ICS is highly effective in T2 asthma, studies have shown a markedly reduced ICS efficacy in patients with a lower degree of T2 inflammation, thus posing a clinical challenge in this subgroup of patients. Hence, owing to the ICS dosage step-up approach in current clinical guidelines, patients with low T2 biomarkers are at risk of being exposed to high doses of ICS, and by that at risk of side effects. Thus, an ICS-treatment regime guided by biomarkers that reflects the inflammatory phenotype is warranted in order to reduce the corticosteroid burden in patients with non-T2 asthma. This study combines a panel of non-T2 inflammatory markers , to determine if this group of patients can maintain asthma control during ICS withdrawal.n = 55 in each group) where the initial ICS dose is reduced by 50% for 8 weeks followed by total ICS removal. The primary endpoint is change in asthma control questionnaire (ACQ) from baseline to post-tapered ICS. The secondary endpoints are time from baseline to drop-out caused by loss of asthma control, changes in serum-periostin, blood-eosinophils, FeNO, Forced Expiratory Volume in 1 s (FEV1) and in sputum-eosinophils.This is an ongoing prospective multicenter open-label randomized, controlled trial aiming to assess if ICS can be safely tapered in patients with non-T2 asthma. The patients are randomized 1:1 to either standard of care or an ICS tapering regimen (This study aims to provide data on ICS tapering in non-T2 asthma patients and to contribute to a more individualized and corticosteroid-sparing treatment regime in this group of patients.th, 2017.Clinicaltrials.gov Identifier: NCT03141424. Registration date: May 5 Asthma is a heterogeneous disease that can be classified into phenotypes based on inflammatory characteristics as T2 and non-T2 , 2. T2 iNon-T2 asthma is poorly defined but is characterized by asthma with absence of signs of heightened T2-driven inflammation. The definition is thus traditionally based on the absence of eosinophils in sputum, blood, and bronchial mucosa and/or low values of other biomarkers of eosinophilic inflammation, such as fractional exhaled nitric oxide (FeNO) or serum-Periostin. T2 asthma also includes allergic asthma, which is triggered by a process dependent on allergen-specific immunoglobulin E (IgE). In contrast, non-T2 asthma does not involve the IgE inflammatory pathway.The prevalence of non-T2 asthma is difficult to estimate, as many studies are cross-sectional and influenced by concomitant corticosteroid treatment and airway infections . HoweverAccording to treatment guidelines, all asthma patients should be treated with inhaled corticosteroids (ICS), regardless of inflammatory phenotype . ICS treBecause of the need for high doses of corticosteroids in patients with severe asthma, the adverse effect profile of corticosteroids is a specific issue in these patients. Therefore, to reduce the burden of corticosteroids, non-steroid agents targeting asthmatic inflammation in severe asthma have been developed over the past decades. A panel of biological therapies have thus been approved for severe eosinophilic or allergic asthma –14, wherAnother pharmacological treatment option for patients with more severe non-T2 asthma include low-dose azithromycin  which haEvidence suggests leukotriene receptor antagonists (LTRAs) to be effective in reducing symptoms in asthma associated with allergic rhinitis, exercise-induced asthma, and aspirin-exacerbated respiratory disease . No studHowever, all taken together, because of the limited availability of effective treatment options for non-T2 these patients may suffer a risk of being overexposed to corticosteroids. There is a need for a refinement of the treatment algorithm to include biomarkers of the inflammatory phenotype, in order to identify the patients who may not benefit from treatment with ICS. A few studies addressing this issue are available. In one study, patients were switched from ICS to long-acting β2 agonist (LABA) , and shoIn 2006 the SMART study showed that add-on salmeterol to usual treatment with ICS for asthma reduced exacerbations and hospitalizations due to asthma, but also increased the risk of serious adverse events . It is iIn the SIENA study, the patients were divided into two inflammatory phenotypes based on sputum eosinophil count. Patients received ICS, long-acting muscarinic antagonist (LAMA), or placebo. In the low-eosinophil group, the treatment response to ICS (57%) did not differ significantly from the treatment response to LAMA (60%). In the high-eosinophil group, the ICS treatment was significantly better . These rn = 14) and that the ICS dose was reduced in 28% of the patients (n = 10). The symptom control or exacerbation rate were not affected [A real-life study of the treatment effect of ICS in non-T2 asthma patients with a mixed disease severity showed that complete tapering-off ICS was possible in 39% of the patients  from baseline to post-tapered ICS. Clinically significant change in ACQ will be defined as 0.5 points, and an increase in ACQ of at least 1.0 point will resolve in withdrawal from the study.Time from baseline to drop-out due to worsening of asthma control.Change from baseline in serum-periostin, blood-eosinophils, FeNO, forced exhaled volume in 1. second (FEV1) and sputum-eosinophils.This trial is a randomized, controlled, multicenter, non-inferiority study to evaluate the difference between ICS tapering and usual care in patients expressing non-T2 asthma.When all criteria are met, participants will be randomized 1:1 into the following treatment arms:Ai.Patients continue their inhaler therapy in unchanged doses throughout the study period.ii.Patients on single maintenance and reliever therapy regime (ICS/formoterol) continue ICS/formoterol as reliver therapy.Usual care:Bi.Patients on ICS as monotherapy: 50% reduction of the initial dose of ICS treatment for 8 weeks, followed by ICS removal.ii.Patients on ICS as a combination therapy: Same procedure for ICS tapering. LABA, LAMA, LTRA, and/or theophylline will continue in unchanged dose(s). Thus, most patients will have to change to two (or three) inhalers, as ICS will have to be delivered from an ICS-only containing inhaler. ICS not available in a single-medication inhaler will be replaced with budesonide in an equipotent dose.iii.Patients on single maintenance and reliever therapy regime (ICS/formoterol): Short-acting β2-agonist (SABA) will replace ICS/formoterol as reliever therapy.ICS tapering regime:The allocation sequence is in blocks of varying and blinded size and generated in R 4.1.0 by an employee who is not a part of the study. The allocation list is uploaded to Research Electronic Data capture (REDcap) where randomization is performed. The trial is not blinded.Patients with asthma followed in the respiratory outpatient clinics meeting the inclusion criteria and none of the exclusion criteria, based on routine measurements, and available for assessment, will be invited to a screening for non-T2 asthma Fig. Fig. 1FloAfter obtaining written informed consent, the screening visit will be performed, including clinical interviews, review of eligibility criteria, blood samples and measuring of FeNO. The principal and sub-investigators enroll and randomize participants and perform all study visits.◦ Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark◦ Amager Hospital, Copenhagen, Denmark◦ Glostrup Hospital,  Glostrup, DenmarkPatients with asthma followed in the respiratory outpatient clinic at◦ FEV1 reversibility of at least 12% (and at least 200 ml) after administration of bronchodilator or inhaled/oral corticosteroid.◦ Positive bronchial provocation test, e.g., mannitol or methacholine.◦ Peakflow-variation of at least 20% over a two-week period with peak-flow measured twice daily and during asthmatic symptoms.◦ Variability in FEV1 over time of at least 12% (and at least 200 ml).Eligible individuals are required to have at least one, at present or previously, positive asthma test:18 to 65 years of age.Treated with ICS daily in medium dose or higher, equivalent to 800 µg budesonide.ICS adherence of at least 80% during the last year.FeNO < 25 ppb at all visits at the outpatient clinic prior to the screening visit.9 cells/L at screening.Blood-eosinophils < 0,15 × 10Women of fertile age: negative urine-hCG and a statement of secure anticonception during the entire trial period.Signed informed consent.History of allergic asthma.Diagnosed pneumonia by a physician within the last 6 weeks before screening.Daily smoking or former daily smoking within the last 6 months.Known other respiratory conditions, including COPD and bronchiectasis.Known other chronic conditions that could impact or limit study participation, including severe heart disease and disorders requiring treatment with immunosuppressive drugs such as prednisolone, methotrexate, or biological therapy, as assessed by the investigator.Pregnancy or planning to become pregnant.Abuse of alcohol or other substances.Each participant randomized will be given a unique study ID, recorded in the electronic Case Record Form (e-CRF) together with the allocated treatment arm. The e-CRF are stored securely in REDcap, an electronic database. All study visits will be registered in the electronic patient file and the e-CRF, which will be the data sources. All data are anonymized and double-checked for errors when entered in the e-CRF in REDcap. Registrations and changes in the database are automatically logged in an audit trail. The investigators will have access to the database. The study will be monitored repeatedly by an independent monitor according to Good Clinical Practice (GCP) by the GCP unit at Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark.ACQ: A validated questionnaire used for assessing the level of asthma control .FeNO: Exhalation test used for assessing eosinophil airway inflammation. The test will be performed according to ERS/ATS guidelines.Spirometry: A test for lung function. The test will be performed according to ERS/ATS guidelines.Serum-periostin: Blood sample.Blood-eosinophils: Blood sample .Induced sputum: Analysis including cell count of mucus collected after inhalation of hypertonic saline. The test will be performed according to standardized method , 33.Adherence: At screening adherence is measured as medical possession rate (MPR), defined as the number of doses the patient had access to divided by the total number of doses the patient was supposed to take based on their prescription obtained from the Common Medication Card, a Danish data registration of prescribed pharmaceuticals. At study visit 1 – 7 adherence is monitored on the dose counter of the inhaler.These will be collected as described in Table This study will include patients treated with ICS approved for asthma treatment in Denmark, including combination treatment with LABAs and/or LAMAs. The following drugs have been defined as IMPs  in the study (approved by the Danish Medicines Agency): Budesonide (ATC: R03BA02), fluticasone propionate (ATC: R03BA05), mometasone furoate (ATC: R03BA07), fluticasone furoate (ATC: R03AK10), beclometasone dipropionate (ATC: R03BA01), and ciclesonide (ATC: R03BA08).The study drugs will be additionally labelled  with the following information: Name of sponsor/investigator, trial reference code “PERIOSTIN”, trial site, and participant ID (randomization number).Increase in ACQ of at least 1.0 point  as compared to baseline.A FeNO measurement > 50 ppb that is attributed to increased asthma activity and not other factors such as infection.Asthma exacerbation, defined as the need for systemic corticosteroids for at least 3 days’ duration and/or hospitalization due to worsening of asthma symptoms.New fulfilling of an exclusion criteria during the trial period, including (pregnancy and daily smoking).Withdrawal of consent. In addition, participant data may be omitted after study completion upon request of the participant.In case of the occurrence of one or more of the following criteria during the trial period, the participant will be withdrawn from the study at the day of the event.If a patient is withdrawn from the study due to a significantly increase in ACQ, FeNO and/or an asthma exacerbation, the following data will be collected at the day of the event: ACQ, FeNO, spirometry, blood-eosinophils, serum-periostin, sputum-eosinophils and adherence.The decision of exclusion not requested by the participant will be made by the investigator. The participant will be informed.Hereafter, the patient will attend the outpatient ward in a standard asthma course, as assessed by the study physician.Adverse events (AE) and serious adverse events (SAE) will be registered in the e-CRF. SAEs that are suspected to be associated to the IMP are reported by the investigator to the sponsor within 24 h. An annual safety report regarding the SAEs will be conducted to the Ethics Committee of The Capital Region of Denmark and the Danish Medicines Agency.Based on the incidence of SAEs the sponsor may conduct an interim analysis, which will be analyzed by the study group. The sponsor and investigators can in collaboration decide to terminate the study.Based on a previous study we expect it is possible to include a maximum of 50 patients in each treatment arm . The priCategorical variables will be presented as number of observations and percentages. Whereas continuous variables will be presented as mean and standard deviation or median.To evaluate the effect of the intervention on the primary endpoint (change in ACQ), data will be analyzed with two-sample t-test and linear regression. Subgroup analyses on patients with different disease severity will be performed with interaction analysis in linear regression models. The variables adjusted for are BMI and previous smoking (pack years).Secondary outcomes will be analyzed with two-sample t-test.Time to drop-out due to worsening of symptoms or asthma exacerbation will be estimated as a hazard ratio in a Kaplan–Meier curve.If normality assumptions cannot be met, data will be analyzed with non-parametric tests such as Wilcoxon rank test or transformed to meet the normality assumptions. Study outcomes are analyzed in the intention-to-treat and per-protocol population.Statistical analyses are performed with R 4.1.0 .The findings from the present trial, positive, negative as well as inconclusive, will be sought published in English-language peer-reviewed journals. Results that cannot be published in peer-reviewed journals will be presented at scientific conferences as posters or oral presentations. The Vancouver declaration will be applied also regarding co-authors. CHM, NSG, CSU, and CGW can, in agreement, decide to include other co-authors.The results are planned to be submitted for publication within 12 months after last patient last visit.In this multicenter randomized controlled trial, we apply a panel of biomarkers to phenotype asthma patients, thus identifying patients who do not express T2 inflammation, in order to investigate whether ICS can be tapered in this subgroup of patients.The true prevalence of non-T2-asthma remains uncertain. Some studies suggest that non-T2 asthma may account for up to 50% of all asthma patients , while oMedium- to high-dose ICS are expected to reduce FeNO levels and potentially blood-eosinophils. Thus, this study is designed with frequent follow-up visits with measurements of T2 biomarkers, ensuring that suppressed T2-inflammation will be revealed during ICS tapering. A strength of the present study is that with a low threshold of non-T2 biomarkers we include patients with a good probability of success in tapering ICS. Finally, there may be limitations in the diagnostic tests used to identify non-T2 asthma, particularly in clinical settings where more advanced biomarker testing may not be available. This can lead to underdiagnosis or misclassification of patients with non-T2 asthma. The biomarkers applied in this study are characterized by being non-invasive, fast, available, relatively cheap, and easily applicable in a busy everyday clinical setting. The study has been designed to resemble a standard asthma management setting, to make the results of the trial easily transferrable to a clinical setting. To continue a pragmatic approach, it is conducted as an unblinded study.Adherence to ICS are crucial in the management of asthma, and it has a significant impact on treatment outcomes . Non-adhPatients in both arms go through the same follow up visits and undergo the same examinations Table . When ICIn summary, the rationale of this study is that a subgroup of asthma patients expressing T2 low asthma have limited effect of the treatment with ICS. These patients will not suffer from loss of asthma control within one year after withdrawal of treatment with ICS. The aim is to investigate whether asthma patients expressing low T2-activity, assessed by serum-periostin, blood-eosinophils, and FeNO can sustain their level of disease control during tapering of ICS. The overall aim of the study is thus to reduce the burden of corticosteroids in these patients. The study will contribute to a more targeted and individualized treatment than the current one-size fits all inhalation therapy.Patient recruitment commenced in June 2022 and is ongoing.


Central aortic stiffness is established as a reliable measure of cardiovascular disease. While pulse wave velocity (PWV) analysis measures arterial distensibility, risk profile of cardiovascular diseases can be expanded with following pulse wave analysis measurements: central aortic systolic blood pressure (CABPS), central aortic pulse pressure (CAPP), central aortic reflection magnitude (CARM), central aortic augmented pressure (CAAP) and central aortic augmentation index (CAAIx). The aim of this study is to evaluate the clinical usefulness and importance of pulse wave analysis measurements in specific cardiovascular conditions and diseases, both in term of diagnosis and therapeutic monitoring.One thousand sixty-six subjects were included. According to age bracket, four cohorts were investigated—healthy subjects (NL), hypertensive patients (HP), ischemic heart disease (IHD) and valvular heart disease (VHD) patients. Arterial stiffness was analyzed through Sphygmocor XCEL Central Blood Pressure Measurement System and Sphygmocor XCEL PWV Measurement System. Furthermore we observed the pulse wave analysis measurements of 14 patients with diagnose of ADHD who were referred by a child psychiatrist, in order to investigate the initiation of methylphenidate treatment.Statistically significant differences were found between NL and HP cohorts, across almost all age brackets, regarding pulse wave analysis measurements. In the risk stratification of arterial stiffness hypertension and especially central aortic blood pressure systolic (CABPS) seems a determining factor. Pulse wave analysis measurements for IHD and VHD cohort comparisons with NL counterparts, revealed non- statistically significant variations. Elevated CAAP, CAAIx and CARM within the youngest age group (0–10 years) in attention-deficit-hyperactivity-disorder (ADHD) patients warrant attention.Following such investigations, CABPS appears as a robust predominant factor in problems of arterial stiffness. Pulse wave analysis and PWV are important parameters in the evaluation and monitoring of arterial hypertension and cardiovascular diseases. There is a hypothesis that CAAP could be an important and even decisive parameter in the diagnosis of ADHD. Further investigation needed. Central aortic augmented pressure (CAAP) could represent an important and even decisive parameter in the diagnosis of ADHD.The quality of the arterial vascular wall system is of paramount importance for the health and well-being of cardiovascular patients and—by extension—for global human health. Central aortic stiffness is established as a reliable measure of cardiovascular disease.Increased arterial stiffness is considered as one of the earliest stages of the atherosclerotic process. Carotid-femoral pulse wave velocity (PWV) is commonly used and widely accepted as an accurate and non-invasive method for assessing arterial stiffness .While PWV is a direct measure of arterial distensibility, the risk profile of cardiovascular and cerebrovascular diseases can be expanded and supplemented with other pulse wave analytical measurements, such as central aortic systolic blood pressure (CABPS), central aortic pulse pressure (CAPP), central aortic reflection magnitude (CARM), central aortic augmented pressure (CAAP) and central aortic augmentation index (CAAIx), which represent more complex parameters—depending upon vascular elasticity, compliance and peripheral resistance .Arterial wall rigidity is considered to be an independent predictor of all-cause and cardiovascular morbidity/mortality within several clinical settings. These include hypertension, overweight status/morbid obesity , diabeteThe aim of this study was to determine and evaluate arterial wall stiffness through pulse wave analysis measurements, according to age brackets, and findings were compared across cardiovascular conditions.-Group I: Normal healthy subjects (NL)-Group II: Hypertensive patients without other underlying medical pathologies (HP).-Group III: Patients with ischemic heart disease, consisting of severe 2-/3-coronary artery disease, treated with either stent implantation or surgical myocardial revascularization and without major valvular heart disease or specific antihypertensive medication (IHD).-Group IV: Patients with hemodynamically important poly-valvular heart disease, without significant coronary atherosclerotic lesions and without specific antihypertensive medication (VHD). The demographic values per age bracket and diagnosis are presented in All patients were ambulatory/self-supporting, and consulted for a cardiac investigation, consisting of a clinical cardiac examination, electrocardiography with stress-test, together with three dimensional (3D) echocardiography with speckle-tracking echocardiography and advanced cardiac 3D quantification. These diagnostic procedures were employed to definitively exclude the presence of arrhythmias and heart failure.Between September 2021 and November 2022, a total of 1,066 subjects/patients were included in this study, divided into 10 age brackets. Each age bracket was further subdivided into 4 groups, as follows:In order to evaluate arterial wall elasticity/stiffness, the Sphygmocor™ XCEL Central Blood Pressure Measurement System and Sphygmocor™ XCEL Pulse Wave Velocity Measurement System were employed.Pulse wave analysis was performed identically for all study participants, placed in a seated position for a minimum of 10 min of absolute rest with the back and right arm supported throughout all measurements. All patients were examined at the same time and environmental conditions. The measurements were always taken at the end of expiration.-CABPS is the pressure that target organs such as the heart kidneys and the brains experience and with which they are confronted in their function. Central aortic blood pressure systolic (CABPS) is the maximum pressure during ejection.-CAPP is the central aortic systolic pressure minus the central aortic diastolic pressure. CAPP readings >50 mmHg were found to predict cardiovascular disease .-CAAP is the difference between the two pressure peaks during ventricular systole. In case of increased arterial stiffness, superposition of forward and reflected pressure waves cause an increase in CAAP .-CAAIx is the ratio of central aortic augmented pressure to central aortic pulse pressure, expressed as a percentage. A high CAAIx indicates increased arterial stiffness and exacerbated risk of organ damage.-CARM is the ratio of reflected pulse height (backward wave) to forward pulse height (forward wave), expressed as a percentage.-PWV measurement was performed through a femoral pressure cuff placed on the right upper thigh and a tonometer placed on the right carotid pulse in order to obtain a pulse wave reading. This study employed the subtraction method, namely, measurement of the distance from sternal notch to cuff, together with the distance from carotid to sternal notch and femoral-to-cuff distance , 11.All pulse wave analytical measurements were all based upon central aortic blood pressure readings.Regarding parameters for assessing arterial stiffness, this investigation relied on the measurements of cuff brachial blood pressure systolic (CBBPS), central aortic blood pressure systolic (CABPS), central aortic pulse pressure (CAPP), central aortic augmented pressure (CAAP), central aortic augmentation index (CAAIx), central aortic reflection magnitude (CARM) and pulse wave velocity (PWV). All such measurements are defined as follows:Stress and anxiety appear to have an impact on pulse wave analysis measurements. The finding that stress plays an important role in pulse wave analysis measurements is supported by the consistent observation of heart rates above 100 beats per minute, even following a sufficient rest and acclimatization period. The LF/HF ratio was assessed in these patients, and it was consistently observed that stress patients exhibited a value exceeding 3, indicating a dominance of the orthosympatical nerve system over the parasympatical nerve sytstem. This can be seen as a sign of supplementary stress disorders. Consequently, additional 2–3 control examinations were warranted within these patients during this study. In these circumstances, only measurements with lowest heart rates were included in the study.A series of multivariate analysis of variance (MANOVAs) were conducted to compare the means of group I against all other groups  across all differing age brackets for CBBPS, CBBPD, CABPS, CABPD, CAPP, CAAP, CAAIx, CARM and PWV readings.The interaction effects were examined further by splitting the dataset by age bracket and through performing MANOVAs for the differing age brackets separately.Post-hoc pairwise comparisons (with Bonferroni correction) on the estimated marginal means of both groups in each age bracket determined the nature of this interaction.The tables and interaction graphs highlight the comparison between the means (per parameter) between NL and HP, NL and IHD together with NL and VHD groups across the differing age brackets.F = 10.79, df = 27, p < .001) and for age bracket . The main effect of diagnosis indicated a difference in the overall means of the differing parameters between group I and group II, and the main effect of age bracket indicated a difference within overall means across the differing age brackets.The multivariate outcomes demonstrated significant major effects for diagnosis  = 4.636, p < 0.001.Consequently, the interaction between diagnosis and age bracket was significant; Pillai's Trace = 0.076, In the following sections we will discuss the post-hoc comparisons of next measurements: cuff brachial blood pressure and central aortic blood pressure, pulse wave velocity, central aortic pulse pressure, central aortic augmented pressure, central aortic augmentation index and finally central aortic reflection magnitude.Upon probing arterial wall stiffness and cardiovascular diseases, this study analyzed four patient groups, each subdivided into 10 age brackets. These consisted of: 513 NL subjects; 322 HP patients; 136 IHD patients; 95 VHD patients.t-test with Bonferroni correction indicated that the mean score for CBBPS and the mean score CBBPD were significantly lower in NL compared with HP cohort over all age brackets, except for the 91–100 year age bracket. The results for CBBPS are presented in Post hoc comparisons employing Concerning the cuff brachial diastolic blood pressure, this study reported a slight increase in both group I and group II, up to the age of 50 years, and a progressive decrease thereafter. Here too, this study maintained statistically significant differences between both groups, though less pronounced .Similar findings were recorded for central aortic blood pressure measurements, both systolic (CABPS) , and diaThe pairwise comparisons (with Bonferroni correction) for CABPS between group I and group II were significantly different for the age bracket 51–60 years till the age bracket 81–90 years, in which the means of group I were lower than the means of group II .When comparing the means for CABPD between group I and group II, significantly different results were obtained in all age brackets, except in age bracket 71–80 years and age bracket 91–100 years .Within group III, IHD patient cohort, CABPS and CABPD readings appeared slightly elevated compared to group I (NL), both without statistically significant differences , 6.Within group IV, VHD patient cohort, this study noted slightly increased CABPS readings compared to group I (NL), though without statistically significant differences .Slightly reduced—though statistically not significant—differences between CABPD readings were observed for group IV (VHD) compared to group I (NL) .Main clinical signs of systemic hypertension in elderly patients are the divergent changes in central aortic systolic blood pressure and central aortic diastolic pressure, resulting in an increased CAPP, termed as isolated systolic hypertension, which is inherently associated with increased aortic stiffness .post hoc tests (t-tests with Bonferroni correction) for PWV means between group I (NL) and group II (HP) are presented. Significant results were obtained for the 51–60 years, 61–70 years, 71–80 years and 81–90 years age brackets, in which the mean PWV was lower for group I in comparison with group II  for CAPP means between group I (NL) and group II (Hp) are presented. Results indicated that CAPP was lower in group I than in group II for the age bracket 31–40 years up until the age bracket of 91–100 years  and II (HP) from the age of 40 years, caused by divergent changes in central aortic systolic pressure and central aortic diastolic blood pressure, resulting in an increased central aortic pulse pressure .When comparing patients of group III (IHD) and of group IV (VHD) with subjects from group I (NL), a slight increase in CAPP was noted with similar progressive course, according to age brackets, however without statistically significant differences , 14.post hoc tests for CAAP means between group I and group II are presented, whereby such results were significantly different for the age brackets of 31–40 years up to 81–90 years.Within CAAP increased linearly with age. Statistically significant differences between group I healthy subjects (NL) and group II hypertensive patients (HP), were progressively more pronounced within the older age bracket .Compared to normal healthy subjects (NL), this study noted—in IHD and VHD cohorts—a slight increase in CAAP within the age brackets between 40 and 70 years, though not with statistically significant variations , 17.Furthermore, elevated CAAP readings within the age bracket 1–10 years were highly striking, which require our full attention .The 14 patients in the age bracket 1–10 years, all demonstrated a normal cardiovascular examination and exercise capacity. However 10 patients were referred for cardiac examination with the diagnosis of ADHD syndrome, before starting a methylphenidate medication. The mean CAAP of the entire group was +4.71 mmHg; the mean for such ten ADHD patients was +6.3 mmHg, while in four patients without ADHD this was 0.5 mmHg. It seems that CAAP is a very decisive measurement in the diagnosis of ADHD.The striking increased values of “central aortic augmented pressure” in otherwise apparently healthy children and in the young adults, in the absence of any underlying somatic pathology, require our further attention. This subject requires an attempt at interpretation and explanation, and potentially a more comprehensive control research, given the relatively small sample size of patients analyzed.Within the age bracket of 11–20 years, this study investigated CAAP in 69 normal healthy subjects (NL). Following 99% confidence interval testing, this study found an outlier with a CAAP value of +12 mmHg and a second outlier with a CAAP value of −19 mmHg .Boxplots of CAAP across all age brackets seem to indicate that cases of “possible supernormal vascular aging” appears to be limited to very young age brackets, while “early vascular aging” or “exaggerated vascular aging” was essentially only noticed within older age brackets .post hoc tests for CAAIx means between group I and group II. These results indicated that the mean CAAIx was significantly lower within group I (NL) in comparison to group II (HP) across all age brackets, except for the last two age brackets (81–90 years and 91–100 years).CAAIx progressively increased with age in both group I (NL) and group II (HP). Particularly within Group I, this study noted a steep rise of the curve up to the age of 50 years. Within younger individuals, CAAIx rose steeply with age up to 50 years, with further progressive—though more smooth and slower rise—up to 100 years of age.In group III IHD patients  and in gpost hoc comparisons indicated that the CARM mean score was significantly lower in group I (NL) than in group II (HP) in the following age brackets: 41–50 years, 51–60 years, 61–70 years and 71–80 years  and higher compared to group I (NL) with statistical significance within age brackets 41–50 years, 51–60 years, 61–70 years and 71–80 years .Within this study there was a strong positive correlation between CAAP and CARM .1. Overall, elevated blood pressure increases pulsatile aortic wall stress, consequently accelerating elastic degradation. Hypertension is viewed as an accelerated form of vascular aging that leads to aortic stiffening. Stiff arteries result in reduced diastolic pressure due to less elastic recoil to support diastolic pressure. This study consequently remained focused upon CABPS.2. Aortic PWV is a non-invasive measure of aortic stiffness and arterial aging. Increase in PWV results in reflected pressure waves that return to the heart earlier in the cardiac cycle, which can augment the net central systolic pressure and concomitantly attenuate net central diastolic pressure, thereby increasing cardiac workload and decreasing coronary perfusion.Within all four groups, this study noted a progressive increase in aortic PWV with age. Following the age of 50 years, the increase in PWV appeared more pronounced, especially in the hypertensive group (HP), resulting in distinct statistically significant variations between groups I (NL) and II (HP). These findings suggest—within elder age brackets—a less-compliant aorta with increased rapidity and earlier return of the reflected wave . Such da3. Concerning cases of decreased arterial elasticity and increased arterial stiffness, the reflected pressure wave in the arterial system becomes more important and increases central aortic systolic blood pressure. Conversely, within age brackets, this study observed a decrease in central aortic diastolic blood pressure, resulting in an increased CAPP reading. Increased CAPP is accompanied by increase in peripheral artery stiffness, which can lead to microvascular endothelial dysfunction, including coronary angiopathy and structural brain diseases . ElevateCentral aortic pulse pressure essentially appears to have considerable clinical value as an independent predictor of cardiovascular disease and mortality .4. CAAP represents the effect of wave reflection upon the aortic pressure wave-form, being the difference between the two pressure peaks during ventricular systole. Superposition of forward and reflected pressure waves results in specific amounts of augmented pressure, with a characteristic inflection point located to the left of pressure peak in elderly individuals. Within younger individuals, the inflection point is typically found to the right-hand-side of pressure peaks, which results in negative values of augmented pressure .The linear increase of CAAP with age suggests an increased wave refection, and—more specifically—an increase in the magnitude of wave refection.Concerning the results of the 14 ADHD-patients, emotional factors undoubtedly play a role, though even following repeated reassuring measurements, similar results were always noted. Consequently, this study postulated whether hormonal factors or neurotransmitters  could influence CAAP pulse wave analysis measurements.This study also probed if issues of “early vascular aging” (outlier +12 mmHg) and “super-normal vascular aging” (outlier −19 mmHg) could be taken into account .5. Age, central aortic pulse pressure and isolated systolic hypertension are powerful determinants of cardiovascular risk, morbidity and mortality, due to increased arterial stiffness. The importance of increased arterial stiffness was further demonstrated by the observations that PWV and CAAIx are independent predictors of cardiovascular morbidity and mortality. CAAIx is defined as the reflected wave amplitude divided by pulse pressure, and expressed as a percentage. Large CAAIx readings indicate increased magnitude of wave reflection from the lower body or earlier return of the reflected wave towards the heart, as a result of increased pulse wave velocity and a less-compliant aorta .Changes in CAAIx were more prominent in younger individuals (<50 years), where shifts in aortic PWV were more marked in older individuals (>50 years). Consequently, CAAIx might be a more sensitive marker of arterial aging and stiffness in younger patients, with aortic PWV being more sensitive within individuals over 50 years of age.6. CARM is the ratio of Reflected Pulse Height to Forward Pulse Height, expressed as a percentage. The initial wave moves towards the periphery (Forward wave), while the reflected wave behave as a single wave moving towards the heart (Backward wave). The reflected pressure wave causes an aortic pressure augmentation and enhances coronary blood supply. Conversely, an excess of aortic pressure augmentation increases the risk of cardiovascular disease . IncreasIssues such as obesity and diabetes also affect CARM, and increase both forward and backward reflections, resulting in increased arterial stiffness .Interestingly, within this study, there was a strong positive correlation between CAAP and CARM. A lower heart rate increases central aortic blood pressure through enhanced backward wave pressure. There was also an inverse relationship between heart rate and backward wave pressures, which could have been amplified by underlying central aortic stiffness . TherapyDespite intense researcher efforts, this study had some limitations. Patients had to meet strict criteria to be included in the study. Possible drug therapy was not a contra-indication for inclusion, although treatment with calcium antagonists, beta blockers, diuretics, ACE inhibitors, sartans and statins might influence pulse wave analysis and PWV measurements to some extent.Although the middle age groups exhibit a substantial and homogeneous population, the first three and the final age group are comparatively less in size. Within these age groups, the numbers of VHD and IHD are borderline normal. Within these groups we are careful in drawing definite conclusions. In groups aged 50 and over, these diagnoses are more common, and the numbers are therefore higher, which support more valid statistical analysis.We could also mention the rather limited number of examined subjects in the age group 0–10 years, notwithstanding, on the other hand, the clear conclusive findings.-Research probing arterial vascular wall stiffness through pulse wave analysis, PWV and CABPS reading appear to have clinical value. In the risk stratification of arterial stiffness, hypertension and especially central aortic blood pressure are primordial and determining factors.-Pulse wave analysis and PWV measurements do not yield definitive and fixed results, though do concern variable values, depending upon lifestyles, hormonal changes, drug treatments and other therapeutic interventions. Pulse wave analysis and PWV are important parameters in the evaluation, monitoring and treatment of arterial hypertension.-Cause for concern were the elevated values for CAAP, CAAIx and CARM in the youngest age bracket 0–10 years. Furthermore, clear differences were established between non-ADHD and ADHD patients, with even a suspicion of variations between ADHD patients, depending on whether it mainly concerned an issue of attention deficit or hyperactivity disorder. Central aortic augmented pressure could be an important parameter in the diagnosis of ADHD. In this context, the results and findings within ADHD patients warrant confirmation and further investigation.-The measured parameters for arterial stiffness can be affected by stress/anxiety and possibly also by neuro-hormonal regulation, neurotransmitters and a disturbed balance between the ortho-sympathetic and parasympathetic nervous system.-The “Early Vascular Aging” syndrome and “supernormal vascular aging” values at young age deserves further attention.-In patients with ischemic heart disease and valvular heart disease, the divergent PWV and pulse wave analysis measurements, compared to NH group, could be mainly attributed to the simultaneously slightly increased blood pressure values, unrelated to underlying heart disease.Pulse wave analysis and pulse wave velocity measurements are of great value, not only in the diagnosis of arterial stiffness, though also in the evaluation and follow-up of drug treatments or other therapeutic initiatives to reduce arterial stiffness.Striking measurements with elevated values for CAAP, CAAIx and CARM within the youngest age bracket (0–10 years) indicated clear differences between non-ADHD and ADHD patients, with even a suspicion of variations between such ADHD patients, depending on whether this mainly concerned an attention deficit or hyperactivity disorder issue. Within this context, more extensive research is necessary, partly due to the scarce number of subjects examined in this study.


To explore the characteristics of renal artery variation in patients with renal cell carcinoma and to evaluate the predicting value of accessory renal artery in the pathological grading of renal cell carcinoma.The clinicopathological data of patients with clear cell renal cell carcinoma diagnosed in the Department of Urology of the First Hospital of Shanxi Medical University from September 2019 to March 2023 were retrospectively analyzed. All patients underwent visual three-dimensional model reconstruction from computed tomography images. All kidneys were divided into two groups: the affected kidney and the healthy kidney, and the incidence of renal artery variation in the two groups was analyzed. Then, according to the existence of accessory renal artery in the affected kidney, the patients were divided into two groups, and the relationship between accessory renal artery and clinicopathological features of patients with clear cell renal cell carcinoma was analyzed. Finally, univariate and multivariate logistic regression analyses were performed to determine the predictors of Fuhrman grading of clear cell renal cell carcinoma, and the predictive ability of the model was evaluated by the receiver operating characteristic curve.The incidence of renal artery variation and accessory renal artery in the affected kidney was significantly higher than them in the healthy kidney. The patients with accessory renal artery in the affected kidney had larger tumor maximum diameter, higher Fuhrman grade and more exophytic growth. The presence of accessory renal artery on the affected kidney and the maximum diameter of tumor are independent predictors of high-grade renal cell carcinoma. The receiver operating characteristic curve suggests that the model has a good predictive ability.The existence of accessory renal artery on the affected kidney may be related to the occurrence and development of clear cell renal cell carcinoma, and can better predict Fuhrman grade of clear cell renal cell carcinoma. The finding provides a reference for the future diagnostic evaluation of RCC, and provides a new direction for the study of the pathogenesis of RCC. Renal cell carcinoma (RCC) is one of the common malignant tumors of the urinary system, and it ranks third for incidence, after prostate and bladder cancer, accounting for 2%-3% of adult malignant tumors . Among tThe evaluation of tumors has been one of the core tasks in clinical diagnosis and treatment of diseases, especially for ccRCC, a malignant tumor with poor prognosis. Tumor grade describes the degree of differentiation of tumor cells relative to normal cells, and it is a reliable indicator of tumor growth and metastasis. Studies have pointed out that the pathological grade of RCC is one of the major predictors of prognosis. Usually, the higher the grade, the worse the prognosis . FuhrmanStudies have found that the incidence of renal artery variation (RAV) in patients with RCC ranges between 17.5% and 25.1%, which is higher than 14.01% in the general population , 11. AndWe retrospectively collected the clinical data of patients with ccRCC in the Department of Urology of First Hospital of Shanxi Medical University from September 2019 to March 2023. The clinicopathological features of patients included sex, age, body mass index (BMI), tumor location, maximum tumor diameter, tumor growth pattern, Fuhrman grade, and hypertension. Inclusion criteria were as follows: (1) patients had unilateral single tumor; (2) patients underwent plain and enhanced urinary CT scans or abdominal and pelvic CT scans, as well as visual 3D model reconstruction from CT images; and (3) ccRCC was confirmed by renal puncture or postoperative pathology report. Patients with incomplete data were excluded. This study complied with the Declaration of Helsinki. The study was approved by the ethics committee of the First Hospital of Shanxi Medical University . The written informed consent was waived by the First Hospital of Shanxi Medical University of the Institutional Review Board.All patients underwent CT scanning, and CT images were used for 3D model reconstruction. The typical reconstructed 3D models are shown in Fig. There are different classification methods of RAV. ARA and branches of renal artery before renal hilum are the most clinically significant, which have attracted much attention from scholars. According to the study of Satyapal et al. , we defiThe pathological grading was conducted by the pathologists of our hospital using the Fuhrman grading system. Patients with ccRCC were grouped into a low-grade group (Fuhrman grades I and II) and a high-grade group (Fuhrman grades III and IV).P < 0.05.Continuous variables were expressed as means ± standard deviation and analyzed by the Student’s t-test, while categorical variables were presented as counts (percentages) and analyzed by the Chi-squared test. All kidneys were divided into two groups: the affected kidney and the healthy kidney. The incidence of RAV in the two groups was analyzed. Then, according to the presence or absence of ARA on the affected kidney, the patients were divided into two groups, and the relationship between ARA and clinicopathological features of patients with ccRCC was analyzed. Finally, the presence or absence of ARA on the affected kidney, sex, age, body mass index (BMI), tumor location, maximum tumor diameter, tumor growth pattern, and hypertension were included in univariate and multivariate logistic regression analysis to determine the independent predictors of tumor pathological grade. The receiver operating characteristic (ROC) curve and AUC were used to evaluate its predictive ability. All statistical analyses were performed using SPSS version 26 (IBM Corporation). Differences were considered statistically significant at A total of 99 patients with ccRCC were enrolled in the study. The baseline characteristics of the patients are summarised in Table P = 0.003). Furthermore, we divided RAV into ARA and the branches of renal artery before renal hilum. The incidence of ARA in the affected kidney was significantly higher than that in the healthy kidney  and maximum tumor diameter  were found to be significantly associated with high-grade ccRCC. Logistic regression was then performed for these two variables for the multivariate model (Table P = 0.013) and maximum tumor diameter  remained significant predictors of high-grade ccRCC. As shown in Fig. P = 0.000), indicating that this model had high predictive ability.To explore the association between ARA and Fuhrman grade of ccRCC, Logistic regression analysis was performed on each variable for the univariate model Table . In the In general, each kidney of a normal adult is supplied by a single artery. However, in the embryonic stage, the developing mesonephros, metanephros, suprarenal glands, and gonads are supplied by nine pairs of lateral mesonephric arteries arising from the dorsal aorta. These nine pairs of arteries are divided into three groups: cranial (1st and 2nd pair), middle (3rd–5th pair), and caudal (6th–9th) . The renIn order to explore the correlation between RAV and ccRCC, we divided all kidneys into two groups: the affected kidney and the healthy kidney, and found that the incidence of RAV in the affected kidney was significantly higher than that in the healthy kidney. Furthermore, we found that the incidence of ARA in the affected kidney was significantly higher than that in the healthy side of kidney, but we did not find significant difference in the incidence of branches of renal artery before renal hilum between the two groups. This result indicated that the significant difference in the incidence of RAV between the two groups is caused by the difference of in the incidence of ARA.Furthermore, we found that the group with ARA in the affected kidney had a larger tumor maximum diameter and higher Fuhrman grades, and ccRCC showed more exophytic growth. The reason may be that the blood supply of the tumor with ARA in the affected kidney is so abundant that the tumor grows faster, which leads to high tumor invasiveness and a high degree of malignancy. Previous studies have shown that tumor growth patterns can predict ccRCC pathological grade –20 and hP = 0.047) was one of the independent risk factors for high-grade RCC. Hu et al. [P = 0.045) and multivariate  models. Our study obtained the same results through univariate and multivariate logistic regression analysis. In addition, previous studies have confirmed that obesity is closely related to the occurrence and development of RCC [Previous studies have shown that tumor diameter, BMI and tumor growth pattern can well predict the pathological grade of RCC. Zhu et al.  analyzedu et al.  found tht of RCC , 24. A mt of RCC  suggest An important new finding of this study is that the presence of ARA in the affected kidney is an independent risk factor for high-grade ccRCC, which has not been reported in previous studies. Moreover, AUC showed that the multivariate prediction model of ARA combined with tumor maximum diameter could better predict high-grade ccRCC. At present, the mechanism of RAV and its effect on the pathological grade of RCC are still unclear. A study  performeThe limitations of this study are as follows: (1) this study was a retrospective study, which might lead to selection bias although strict screening had been carried out; (2) this study was a single-center study with a small sample size, and the number of patients with high-grade ccRCC was small; and (3) only patients with ccRCC were included in this study, without comparison with normal population.In patients with ccRCC, the incidence of RAV in the affected kidney was significantly higher than that in the healthy kidney due to the influence of ARA. Importantly, this study found for the first time that ARA could be used as an independent predictor for Fuhrman grades of ccRCC. The finding provides a reference for the future diagnostic evaluation of RCC, and provides a new direction for the study of the pathogenesis of RCC. More prospective clinical studies with a large sample size, as well as relevant basic research, are needed in the future to explore the underlying biological mechanisms by which ARA affects the Fuhrman grade of ccRCC.


Background: Patients often conflate the problem of lightheadedness from hypertension (HTN) and vertigo from a vestibular impairment, describing both problems as dizziness. The goal of the study was to learn if there is a relationship between measures of vestibular function and blood pressure.Methods: This retrospective study consisted of women who participated in a longitudinal study of the human immunodeficiency virus (HIV) and a control cohort of age-matched women without HIV. We used data from the point in time when participants were tested for vestibular functions with bi-thermal caloric tests and cervical vestibular evoked myogenic potentials; the data also included the blood pressure of the participants.Results: High odds ratios (1.48 to 2.05) suggest a relationship between HTN and vestibular impairment, although the sample size was too small to reach statistical significance.Conclusion: The data suggest that high blood pressure may be related to vestibular impairments. Clinicians whose patients complain of vertigo and balance disorders consistent with vestibular impairments should consider blood pressure as a related problem during the initial visit. Vertigo and dizziness have a lifetime prevalence of >20% and are among the most common reasons for patients to visit physicians . HyperteSubjectsThis retrospective study was conducted between February 2018 to March 2019 and included participants from the Georgetown University WIHS site who had previously participated in a study on vestibular functions . The stuTest measuresThe VNG included bi-thermal caloric tests with air  and cervical vestibular evoked myogenic potentials (VEMP). For calorics, eye movements were recorded with infrared video-oculography. The collection of these measures was described previously . The tesBlood pressure was measured by a physician assistant using a digital sphygmomanometer. Using published ranges for normal blood pressure  HTN was All testing was performed on outpatients at an academic medical center in a large city. Subjects in the study were seen for blood pressure testing at the Department of Medicine of the WIHS clinic. They were also tested on VNGs by audiologists at the Department of Otolaryngology.Statistical analysesThis study was a retrospective review of existing data. We generated descriptive statistics and used Fisher’s exact test to test the differences in distribution by HTN and HIV status. We used logistic regression to model the odds of abnormal vestibular outcomes and HTN status, which was adjusted for age and HIV status. All analyses were performed in SAS version 9.4 .The analyses included 77 female participants (81.8% PLWH/18.2% PLWOH) with a median age of 54.0 years (interquartile range: 49-61). HTN was reported in 59.7% (N=46) of the participants , 1.3% (n=1), and 18.2% (n=14) of the participants, respectively. The odds ratios (OR) for caloric and caloric + VEMP were as follows: (OR: 1.48 [95% CI: 0.48-5.48]) and (OR: 2.015 [95% CI: 0.56-7.25]), respectively. When the cut-point of blood pressure was set at > 140/90 (stage 2 HTN), having HTN-2 was associated with increased odds of abnormal caloric (OR:1.63 [95% CI: 0.46-5.77]) and caloric + VEMP measurements (OR: 1.56 [95% CI: 0.47-5.2])  . Also, tWe achieved the goal of the study in finding a relationship between vestibular impairment and HTN. The data from this study are the first evidence supporting the idea that some vestibular impairments may be related to HTN in HIV. This finding may explain why some complaints of patients are often difficult to understand. Because patients often cannot describe their sensory experiences clearly, patients and clinicians can easily conflate the sensations of vertigo and lightheadedness. This may be partly responsible for a large number of different clinician visits and tests that patients have to go through before being correctly diagnosed with vestibular impairments, resulting in high costs to the individual and the healthcare system. Clinicians should consider this issue when working up patients who complain of dizziness.