The safety and potential efficacy of exosomes overexpressing CD24 (EXO-CD24) in mild-moderate COVID-19 related ARDS.

INTRODUCTION: EXO-CD24 are exosomes genetically manipulated to over-express Cluster of Differentiation (CD) 24. It consists of two breakthrough technologies: CD24, the drug, as a novel immunomodulator that is smarter than steroids without any side effects, and exosomes as the ideal natural drug carrier. METHODS: A randomized, single blind, dose-finding phase IIb trial in hospitalized patients with mild to moderate Coronavirus disease 2019 (COVID-19) related Acute Respiratory Distress Syndrome (ARDS) was carried out in two medical centers in Athens. Patients received either 109 or 1010 exosome particles of EXO-CD24, daily, for five consecutive days and monitored for 28 days. Efficacy was assessed at day 7 among 91 patients who underwent randomization. The outcome was also compared in a post-hoc analysis with an income control group (n = 202) that fit the inclusion and exclusion criteria. RESULTS: The mean age was 49.4 (± 13.2) years and 74.4% were male. By day 7, 83.7% showed improved respiratory signs and 64% had better oxygen saturation (SpO2) (p < 0.05). There were significant reductions in all inflammatory markers, most notably in C-reactive protein (CRP), lactate dehydrogenase (LDH), ferritin, fibrinogen and an array of cytokines. Conversely, levels of the anti-inflammatory cytokine Interleukin-10 (IL-10) were increased (p < 0.05). Of all the documented adverse events, none were considered treatment related. No drug-drug interactions were noted. Two patients succumbed to COVID-19. Post-hoc analysis revealed that EXO-CD24 patients exhibited greater improvements in clinical and laboratory outcomes compared to an observational income control group. CONCLUSIONS: EXO-CD24 presents a promising therapeutic approach for hyper-inflammatory state and in particular ARDS. Its unique combination of exosomes, as a drug carrier, and CD24, as an immunomodulator, coupled with inhalation administration, warrants further investigation in a larger, international, randomized, quadri-blind trial against a placebo.

Validation of the automated oscillometric upper-arm cuff home blood pressure monitor AVITA BPM82 in a general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard.

OBJECTIVE: This study evaluated the accuracy of the automated oscillometric upper-arm cuff device AVITA BPM82 intended for home use in a general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01. METHODS: Participants were recruited to fulfill the age, sex, blood pressure (BP), and limb distribution criteria of the AAMI/ESH/ISO Universal Standard and its Amendment 1.2020-01 in a general population using the same arm sequential BP measurement method. Two cuffs of the test device were used for arm circumference 22-33 (medium) and 33-42 cm (large). RESULTS: One-hundred-one individuals were recruited and 85 were analyzed [mean age 57.3 ±â€…15.1 (SD) years, 46 men, arm circumference 32 ±â€…5.1 cm, range 22.3-42 cm]. For validation Criterion 1, the mean difference ±SD between the test device and reference BP readings (N = 255) was 1.3 ±â€…6.5/3.6 ±â€…5.9 mmHg (systolic/diastolic; threshold ≤5 ±â€…8 mmHg). For Criterion 2, the SD of the averaged BP differences between the test device and reference BP per individual (N = 85) was 5.70/5.25 mmHg (systolic/diastolic; threshold ≤6.82/5.89 mmHg). CONCLUSIONS: The automated oscillometric home BP monitor AVITA BPM82 comfortably fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01 in a general population and can be recommended for clinical use.

Validation of the oscillometric home blood pressure monitor Braun BUA4000 with wide-range cuff in a general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard.

OBJECTIVE: To evaluate the blood pressure (BP) measurement accuracy of the Braun BUA4000 automated oscillometric upper-arm cuff device for self-home use in a general population according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01. METHODS: Participants were recruited to fulfill the age, sex, BP and limb circumference distribution criteria of the AAMI/ESH/ISO Universal Standard in a general population using the same arm sequential BP measurement method. A single wide-range cuff of the test device was used for arm circumference range 22-42 cm. RESULTS: A total of 98 individuals were recruited and 85 were analyzed [mean age 60.3 ±â€…16.1 (SD) years, 44 men, arm circumference 31.5 ±â€…5.1 cm, range 22-41.5 cm]. For validation criterion 1, the mean difference ± SD between the test device and reference BP readings ( N  = 255) was 0.9 ±â€…6.4/-0.3 ±â€…6.4 mmHg (systolic/diastolic; threshold ≤5 ±â€…8 mmHg). For criterion 2, the SD of the averaged BP differences between the test device and reference BP per individual ( N  = 85) was 5.15/5.81 mmHg (systolic/diastolic; threshold ≤6.88/6.95 mmHg). CONCLUSION: The Braun BUA4000 automated oscillometric BP monitor fulfilled all the requirements of the AAMI/ESH/ISO Universal Standard in a general population and can be recommended for self-monitoring of BP by patients at home.

Validation of a novel professional automated auscultatory upper-arm cuff blood pressure monitor in a general population according to the AAMI/ESH/ISO Universal Standard: KOROT V2 Doctor (InBody BPBIO280KV).

OBJECTIVE: A novel automated auscultatory upper arm cuff blood pressure (BP) monitor KOROT V2 Doctor (InBody BPBIO280KV) was developed for professional use. An electronic stethoscope embedded in the device cuff records the Korotkoff sounds, which are graphically displayed during deflation allowing visual evaluation by the healthcare professional. The device provides automated measurements of BP and this study evaluated its accuracy. METHODS: The requirements of the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01 were applied. Participants were recruited to fulfill the age, sex, BP, arm circumference, and cuff distribution criteria of the Universal Standard and its Amendment in a general population using the same arm sequential measurement method. Three cuffs of the test device were tested for arm circumference 23-28, 28-35, and 33-42 cm. RESULTS: Data from 85 individuals were analyzed [mean age: 56.4 ±â€…16.0 (SD) years, 50 men, arm circumference 23-42 cm]. For validation Criterion 1, the mean difference ±SD between the test device and reference BP readings (N = 255) was -1.3 ± 6.0/1.5 ± 5.0 mmHg (systolic/diastolic; threshold ≤5 ±â€…8 mmHg). For Criterion 2, the SD of the averaged BP differences per individual (N = 85) was 4.61/3.48 mmHg (systolic/diastolic; threshold ≤6.82/6.78 mmHg). CONCLUSION: The KOROT V2 Doctor (InBody BPBIO280KV) device for professional use, which provides automated auscultatory measurements with visual display of the Korotkoff sounds, comfortably fulfills all the requirements of the AAMI/ESH/ISO Universal Standard (ISO 81060-2:2018) in a general population and can be recommended for clinical use.

Visual assessment of Korotkoff sounds improves the accuracy of a validated professional automated auscultatory blood pressure monitor KOROT P3 Accurate.

OBJECTIVE: A novel automated auscultatory upper-arm cuff blood pressure (BP) monitor for office use (KOROT P3 Accurate, previously InBody BPBIO480KV), which displays Korotkoff sound curves for each BP reading was recently developed. This study investigated whether the review of Korotkoff sound curves by healthcare professionals further improves the accuracy of the device by identifying unreliable BP readings. METHODS: Three observers assessed independently the morphology of Korotkoff sound curves of BP measurements obtained during an ISO 81060-2:2018 validation study, and classified them as of good, fair, or poor quality (low amplitude or sound intensity, aberrant morphology, background noise, signal artifact, auscultatory gap, irregular rhythm). The observers were blinded to the study BP measurements. RESULTS: Korotkoff sound curves of 255 BP readings obtained in 85 individuals were analyzed (mean age 57.3 ±â€Š15.0 years, 53 men). Of the SBP readings 80.4/12.2/7.4% were classified as good/fair/poor, and DBP 76.9/12.2/10.9%. Inter-observer agreement in detecting poor-quality curves was 84.7/83.1% (systolic/diastolic). Of poor-quality curves, 10.5/60.7% (systolic/diastolic) clustered in the same individuals. The validation criterion 1 [mean test-reference BP difference ≤5 ±â€Š8 (SD) mmHg] was satisfied for readings with good (0.1 ±â€Š4.9/0.3 ±â€Š3.8 mmHg, systolic/diastolic) and fair-quality curves (-0.4 ±â€Š6.4/0.2 ±â€Š5.0), but not for poor-quality ones (2.7 ±â€Š8.8/3.6 ±â€Š8.1). By excluding poor-quality readings (40 of 255), criterion 1 of the validation study was improved (0.2 ±â€Š4.9/0.2 ±â€Š3.9 versus 0.3 ±â€Š5.5/0.6 ±â€Š4.7 mmHg). CONCLUSION: The visual assessment of Korotkoff sounds generated during automated auscultatory BP measurement by the KOROT P3 Accurate professional monitor identifies unreliable readings and further improves the device accuracy.

Seasonal effects on blood pressure variability in treated hypertensive patients assessed by office, home, and ambulatory measurements.

This study investigated the seasonal effect on blood pressure (BP) variability. Patients on stable antihypertensive drug treatment were assessed with office (OBP), home (HBP), and ambulatory BP (ABP) measurements in winter, next summer, and in next winter. Fifty-eight participants with full data for winter and summer were analyzed (mean age 65.2 ± 7.9 [SD], 64% males). OBP, HBP and ABP (24-h; daytime) were lower in summer than in winter (P < 0.01), whereas nighttime ABP was unchanged (p = NS). Standard deviation (SD), coefficient of variation (CV) and average real variability (ARV) for systolic OBP were higher in winter than summer (p < 0.01/ < 0.05/ < 0.01, respectively). These indices for HBP and ABP measurements did not differ in winter and summer (p = NS). Forty participants had complete data for winter-summer-next winter and HBP/ABP variability indices did not differ for both winters versus summer. These preliminary data suggest that BP variability is unaffected by seasonal changes in contrast to average BP levels.

A novel professional automated auscultatory blood pressure monitor with visual display of Korotkoff sounds: InBody BPBIO480KV validation according to the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization Universal Standard.

OBJECTIVE: A novel automated auscultatory upper arm-cuff blood pressure (BP) monitor (InBody BPBIO480KV) for office use was developed. An electronic stethoscope embedded in the device cuff records the Korotkoff sounds, which are audible to the user and graphically displayed during cuff deflation. Automated BP measurements are provided, while allowing the user to assess the Korotkoff sounds. The device accuracy was tested using the Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Universal Standard (ISO 81060-2:2018) and its Amendment 1.2020-01. METHODS: Participants were recruited to fulfil the age, sex, BP, arm circumference and cuff distribution criteria of the Universal Standard in general population using the same arm sequential measurement method. Three cuffs of the test device were used for arm circumference 23-28, 28-35 and 33-42 cm. RESULTS: Data from 85 individuals were analysed [mean age 57.3 ±â€Š15.0 (SD) years, 53 men, arm circumference 23-42 cm]. For validation criterion 1, the mean ±â€ŠSD of the differences between the test device and reference BP readings ( N  = 255) was 0.3 ±â€Š5.5/0.6 ±â€Š4.7 mmHg (systolic/diastolic; threshold ≤5 ±â€Š8 mmHg). For criterion 2, the SD of the averaged BP differences per individual ( N  = 85) was 3.76/3.61 mmHg (systolic/diastolic; threshold ≤6.95/6.91 mmHg). CONCLUSION: The InBody BPBIO480KV device for office use, which provides automated auscultatory measurements while reproducing and displaying the Korotkoff sounds, comfortably fulfilled the AAMI/ESH/ISO Universal Standard requirements in general population and can be recommended for clinical use. The assessment of Korotkoff sounds by healthcare professionals for evaluating the quality of automated measurements requires further evaluation.

Endothelial dysfunction in acute and long standing COVID-19: A prospective cohort study.

BACKGROUND: Coronavirus disease-19 (COVID-19) is implicated by active endotheliitis, and cardiovascular morbidity. The long-COVID-19 syndrome implications in atherosclerosis have not been elucidated yet. We assessed the immediate, intermediate, and long-term effects of COVID-19 on endothelial function. METHODS: In this prospective cohort study, patients hospitalized for COVID-19 at the medical ward or Intensive Care Unit (ICU) were enrolled and followed up to 6 months post-hospital discharge. Medical history and laboratory examinations were performed while the endothelial function was assessed by brachial artery flow-mediated dilation (FMD). Comparison with propensity score-matched cohort (control group) was performed at the acute (upon hospital admission) and follow-up (1 and 6 months) stages. RESULTS: Seventy-three patients diagnosed with COVID-19 (37% admitted in ICU) were recruited. FMD was significantly (p < 0.001) impaired in the COVID-19 group (1.65 ± 2.31%) compared to the control (6.51 ± 2.91%). ICU-treated subjects presented significantly impaired (p = 0.001) FMD (0.48 ± 1.01%) compared to those treated in the medical ward (2.33 ± 2.57%). During hospitalization, FMD was inversely associated with Interleukin-6 and Troponin I (p < 0.05 for all). Although, a significant improvement in FMD was noted during the follow-up (acute: 1.75 ± 2.19% vs. 1 month: 4.23 ± 2.02%, vs. 6 months: 5.24 ± 1.62%; p = 0.001), FMD remained impaired compared to control (6.48 ± 3.08%) at 1 month (p < 0.001) and 6 months (p = 0.01) post-hospital discharge. CONCLUSION: COVID-19 patients develop a notable endothelial dysfunction, which is progressively improved over a 6-month follow-up but remains impaired compared to healthy controls subjects. Whether chronic dysregulation of endothelial function following COVID-19 could be accompanied by a residual risk for cardiovascular and thrombotic events merits further research.