Healthy Adult Volunteers Research Articles

Bioavailability of Liposomal Vitamin C in Powder Form: A Randomized, Double-Blind, Cross-Over Trial

The purpose of this study was to evaluate the properties and pharmacokinetics of liposomal vitamin C in powder form obtained by a method devoid of organic solvents. The powder and liposome morphology were analyzed using scanning electron microscopy (SEM) and cryogenic transmission electron microscopy (cryo-TEM), respectively. Additionally, the carrier particle size, size distribution (STEP-Technology®; L.U.M. GmbH, Berlin, Germany), and zeta potential value were determined. The pharmacokinetic parameters of liposomal and non-liposomal vitamin C (AUC, Cmax, C10h, and C24h) were compared in a randomized, single-dose, double-blind, cross-over trial (ClinicalTrials.gov ID: NCT05843617) involving healthy adult volunteers (n = 10, 1000 mg dose). The process of spray drying used to transform liquid suspensions of the liposomes into powder form did not adversely affect the quality of the carrier particles obtained. Compared to non-encapsulated vitamin C, oral administration of the liposomal formulation resulted in significantly better absorption of ascorbic acid into the bloodstream, which equated to a higher bioavailability of the liposomal product (30% increase in AUC, p < 0.05). The duration of elevated vitamin C blood levels was also longer (C24h increase of 30%, p < 0.05). Although the results obtained are promising and suggest higher bioavailability for the liposomal form of vitamin C, the limited sample size necessitates further research with a larger cohort to confirm these findings.

Evaluation of blood evacuation efficiency using 99m Tc-RBC imaging: a comparative study of exsanguination tourniquet rings and Esmarch bandages.

The objective of this study is to compare the effectiveness of the Esmarch bandage and exsanguination tourniquet rings (ETRs) in blood evacuation procedures using a controlled intra-subject design involving healthy volunteers. A total of 20 healthy adult volunteers (12 males, 8 females) were recruited from the community. Participants underwent blood evacuation procedures on both legs, using the Esmarch bandage on one leg and the ETR on the other. The order of the procedures was randomized. Blood evacuation time, overall blood evacuation rate, and calf blood evacuation rate were measured using 99m Tc-labeled red blood cell imaging. Paired t -tests were conducted to compare the effectiveness of the two methods. The ETRs demonstrated a significantly faster blood evacuation time compared to the Esmarch bandage (mean difference = -41.72 s, P < 0.0001). The overall blood evacuation rate was slightly higher for the ETRs (mean difference = 1.717%), though not statistically significant ( P = 0.3680). The calf blood evacuation rate was significantly higher for the ETRs (mean difference = 6.86%, P = 0.0225). No significant discomfort or adverse reactions were reported by any participants. ETRs are more efficient in terms of blood evacuation time and calf blood evacuation rate compared to the Esmarch bandage, without causing significant discomfort or adverse reactions. These findings suggest that ETRs could be a preferable option in clinical settings for blood evacuation procedures.

Kidney Dimensions and its Correlation with Anthropometric Parameters in Healthy North Indian Adults

Background: Knowledge of kidney size is important in the assessment of kidney function. Changes in kidney size can occur in various kidney diseases due to different causes, hence knowledge of normal kidney dimensions in a population is crucial for diagnosis, follow-up and prognostication. While data from other parts of the world does not apply to the Indian population due to differences in ethnicity, diet and body sizes, and there is also a lack of standardized data on normal kidney sizes in healthy Indian adults. Materials and Methods: Kidney dimensions from 600 healthy adult volunteers ranging between 20 and 70 years of age were measured with sonography by a single radiologist. Differences in dimensions between men and women, and right and left kidney were analyzed. Finally, kidney sizes were correlated with anthropometric variables such as weight, age, body surface area (BSA), height and body mass index. Estimated glomerular filtration rate (eGFR) was correlated with kidney length and renal parenchymal volume (RPV). Results: The mean kidney length of the whole cohort, irrespective of gender was found to be 9.6 ± 0.7 cm on the right and 9.9 ± 0.7 cm on the left. Mean kidney length in males was significantly more as compared to females on both sides. Both the kidney length and RPV were significantly associated with BSA, weight and height (in that order) in females, whereas in males, kidney length and RPV best correlated with height, BSA and weight (in that order). In both sexes, there was a significant negative correlation between age and kidney length, RPV. eGFR had a significant positive correlation with kidney length and RPV in the cohort. Conclusion: Normal sonographic mean kidney length was 9.6±0.7 cm and 9.9±0.7 cm on the right and left sides respectively in healthy North Indian population, with the left kidney being larger than the right in all dimensions (length, width, thickness and RPV). Kidney sizes in males were found to be larger than females. Correlation with anthropometric parameters in our study, emphasizes the need to give due consideration to normal variations in kidney sizes with age, gender, height, weight and BSA to differentiate between a normal and a pathologically small or large kidney.

Optimizing scapulothoracic injections: the role of hand positioning in enhancing procedural ease.

Pathologies of the scapulothoracic articulation may lead to painful symptoms such as crepitus and bursitis. While conservative treatments are preferred, persistent symptoms may require image-guided injections. This study aims to determine the optimal hand positioning during ultrasound to maximize the distance between the scapula and thoracic wall, and improve itsaccessibility duringinjections. This cross-sectional observational study included ten healthy adult volunteers without scapulothoracic issues or history of trauma/surgery. Two musculoskeletal radiologists independently measured the scapulothoracic distance on Ultrasound in three hand positions: 1. Hands under the head; 2. Hands by the side of the trunk; and 3. Hands hanging by the side of the couch. Data was analyzed using SPSS 24.0. Continuous variables were described using mean and standard deviation (SD), with significance set at p < 0.05. Measurements on 20 scapulothoracic articulations (10 volunteers) showed the following findings: Position 1: Baseline value of 1. Position 2: Distance increased by 1.515mm ± 3.617 (95% CI [- 0.0178, 3.208]. Position 3: Distance increased by 2.175mm ± 0.66 (95% CI [0.793, 3.557]. Statistical analysis indicated no significant difference (p = 0.39) between positions. However, both radiologistssubjectively noted that positions 2 and 3 provided better access for interventions. This study highlights the importance of hand positioning in optimizing the scapulothoracic distance for therapeutic interventions. While no significant statistical differences were found, the results suggest potential benefits for clinical practice. Further research with larger samples is needed to establish evidence-based guidelines for scapulothoracic injections.

Two-Year Study on the Intra-Individual Dynamics of Gut Microbiota and Short-Chain Fatty Acids Profiles in Healthy Adults.

While the gut microbiome has been intensively investigated for more than twenty years already, its role in various disorders remains to be unraveled. At the same time, questions about what changes in the gut microbiota can be considered as normal or pathological and whether communities are able to recover after exposure to negative factors (diseases, medications, environmental factors) are still unclear. Here, we describe changes in the gut microbiota composition and the content of short-chain fatty acids in adult healthy volunteers (n = 15) over a 24 month-period. Intraindividual variability in gut microbial composition was 40%, whereas the short chain fatty acids profile remained relatively stable (2-year variability 20%, inter-individual 26%). The changes tend to accumulate over time. Nevertheless, both short-term and long-term changes in the gut microbiome composition were significantly smaller within individuals than interindividual differences (two-year interindividual variability was 75%). Seasonal changes in gut microbiota were found more often in autumn and spring involving the content of minor representatives (less than 1.5% of the community in average) in the phyla Actinobacteriota, Firmicutes and Proteobacteria.

Discovery of KT-474─a Potent, Selective, and Orally Bioavailable IRAK4 Degrader for the Treatment of Autoimmune Diseases.

Interleukin-1 receptor associated kinase 4 (IRAK4) is an essential mediator of the IL-1R and TLR signaling pathways, both of which have been implicated in multiple autoimmune conditions. Hence, blocking the activity of IRAK4 represents an attractive approach for the treatment of autoimmune diseases. The activity of this serine/threonine kinase is dependent on its kinase and scaffolding activities; thus, degradation represents a potentially superior approach to inhibition. Herein, we detail the exploration of structure-activity relationships that ultimately led to the identification of KT-474, a potent, selective, and orally bioavailable heterobifunctional IRAK4 degrader. This represents the first heterobifunctional degrader evaluated in a nononcology indication and dosed to healthy human volunteers. This molecule successfully completed phase I studies in healthy adult volunteers and patients with atopic dermatitis or hidradenitis suppurativa. Phase II clinical trials in both of these indications have been initiated.

Pharmacokinetics and bioequivalence of the generic and original dabigatran etexilate after a single dose in healthy volunteers

Aim. To study the comparative pharmacokinetics and confirmation of bioequivalence of the generic (T) and original (R) dabigatran etexilate in healthy volunteers after a single oral dose under fasted conditions.Material and methods. To confirm bioequivalence, an open-label, randomized, replication, crossover, four-step study was conducted to compare the pharmacokinetics and bioequivalence of generic and original dabigatran with a single oral dose 150 mg dabigatran etexilate under fasted conditions in adult healthy male and female volunteers. Sixty-eight subjects participated in the study. During the study, blood plasma samples were taken from volunteers, in which the concentration of total and free dabigatran was determined. Based on the data obtained, pharmacokinetic and statistical analysis was carried out and 90% confidence intervals were calculated for the ratio of mean pharmacokinetic parameters (Сmax, Tmax, AUC0-t, AUC0-∞, AUCt-∞, T1/2, AUCt-∞/AUC0-∞) for total and free dabigatran.Results. The established 90% confidence intervals for the ratio of AUC0-t, AUC0-∞ and Cmax values for total dabigatran were 82,56-96,36% (mean ratio, 89,19%), 82,39-95,90% (mean ratio, 88,89%) and 85,98-99,17% (mean ratio, 92,34%), respectively. The established 90% confidence intervals for the ratio of AUC0-t, AUC0-∞ and Сmax values for free dabigatran were 83,37-98,29% (mean ratio, 90,53%), 82,98-97,33% (mean ratio, 89,87%) and 85,04-99,28% (mean ratio, 91,88%), respectively. For the estimated pharmacokinetic parameters of dabigatran etexilate, 90% confidence intervals ranged from 80-125% for AUC0-t, AUC0-∞ and Cmax. Additional safety analysis was carried out. Generic and original dabigatran were well tolerated by the volunteers. There were no significant differences in vital signs, paraclinical characteristics throughout the study compared with the initial data, as well as significant differences between the drugs in all studied parameters of adverse events.Conclusion. The study showed that generic and original dabigatran are bio­equivalent. In addition, the data obtained indicate that the agents have similar safety profiles.

Mind the gap—What is the appropriate time interval between sequential dentine stimuli to elicit a dentine hypersensitivity pain response in clinical studies?

ObjectivesTo determine the time interval required for a tooth diagnosed with DH to recover from a stimulus (cold air-blast/tactile) and respond with a similar elicited pain response to a repeat stimulus. MethodsA single-centre, non-randomised, clinical study in healthy adult volunteers. Eligible participants with ≥1 tooth with either a qualifying Schiff score ≥2 following cold air-blast or tactile Yeaple score of ≤20 g were allocated to tactile or air-blast group. Following primary stimulation, the designated tooth was restimulated 10, 5, 2 min and immediately after initial pain cessation. Pain was recorded with participant VAS and investigator Schiff for air-blast. Results40 participants completed the study per group. There was a significant difference in VAS scores for tactile 4 delay intervals (p < 0.001) but not air-blast stimulus, and a significant difference in mean change in VAS score from immediate to two-minute delay between stimuli (8.0 tactile vs 0.8 air-blast, p = 0.011). VAS scores in response to either stimulus showed very wide variation between participants, but changes over delay intervals within participants were relatively slight. There was a significant progressive decrease in mean Schiff score with shortening delay intervals from 10 min (2.38) to stimulation immediately after pain cessation (2.15), p = 0.018. ConclusionsThe findings suggest healthy teeth recover after DH stimulation more quickly following an air-blast than tactile stimulus, with around 2 min allowing recovery from both. Many factors including habituation and pain measurement subjectivity need to be considered. It would be prudent for future studies to use of ≥3 min delays. Clinical significanceNo clinical study has attempted to determine the appropriate interval between successive stimuli in DH patients. The results will impact directly on the conduct of DH trials. These findings suggest the interval could be reduced to around 2-min, but the current standard of 5-min is sufficiently long to give valid results.

Bioequivalence and Safety of Generic Glecaprevir/Pibrentasvir Compared to a Branded Product: A Randomized, Crossover Study in Healthy Volunteers.

This was an open-label, randomized, single-dose, 2-period, crossover clinical trial with an adaptive design to evaluate the bioequivalence and comparative pharmacokinetics of generic glecaprevir/pibrentasvir versus the brand name product in healthy White male and female volunteers under fed conditions. Safety profiles were also assessed. A total of 56 healthy adult volunteers were enrolled and randomly assigned in a 1:1 ratio to receive a single dose of either the generic or reference formulation. After a 7-day washout period, subjects received the alternate product. Blood samples were collected at pre-specified time points up to 48hours post-dosing. Plasma concentrations of glecaprevir and pibrentasvir were determined using a validated high-performance liquid chromatography-tandem mass spectrometry method. The geometric mean ratios of the test to the reference formulation for maximum plasma concentration (Cmax) and area under the concentration-time curve from drug administration to the last measurable concentration (AUC0-t) fell within the predefined bioequivalence range of 80%-125%. Both formulations demonstrated comparable pharmacokinetic profiles for glecaprevir and pibrentasvir, and can be considered bioequivalent. No adverse events were reported, and both formulations were well tolerated by all participants.

A phase II study of oral chlorophyllin in haemorrhagic cystitis secondary to radiation therapy for pelvic malignancies (CLARITY).

48 Background: Chronic hemorrhagic cystitis (cHC) is seen in 5-15% of patients undergoing pelvic radiotherapy (pRT), often after a long cancer free survival. Hyperbaric oxygen therapy, the only modality with benefit proven in a randomized trial has limited utilization due of lack of availability, need of multiple sessions &amp; cost. In this phase II study, we aimed to evaluate the efficacy &amp; safety of Sodium-copper-chlorophyllin (CHL), a semi-synthetic mixture of sodium &amp; copper salts of chlorophyll, in pRT-induced cHC. This study was based on our preclinical findings where CHL offered radioprotection &amp; significantly reduced mortality &amp; morbidity in mice exposed to lethal doses of whole-body radiation.A subsequent phase 1 trial in adult healthy volunteers established the recommended phase 2 dose. Methods: This was a prospective, single centre, single arm, interventional phase II clinical trial (NCT05348239). Adult patients with grades II-IV hematuria (CTCAE v5.0) following pRT received at least 3 months prior were eligible. All patients received oral CHL 750 mg OD for a maximum of 3 months. A Simon two-stage minimax design with a type 1 error of 2.5% &amp; 80% power led to a sample size of 24 patients. The primary objective was the objective response rate (ORR), defined as the proportion of patients with complete response (CR) [resolution of gross hematuria] or partial response (PR) [decrease by at least one CTCAE grade of hematuria, but not complete resolution] from day 30-90 of starting the drug. At least seven objective responses were required to consider the drug for further development. Results: Thirty two patients were screened of whom 24 were enrolled, with median age of 63 (43-86) years. Indications for pRT included cervical (15), rectal (5) &amp; prostate cancer (4). The median time from RT to cHC was 45 (4-216) months. At enrolment, 6 (25%), 17 (70.8%) &amp; 1 (4.1%) patients had CTCAE grades 2, 3 &amp; 4 hematuria respectively, majority being refractory. An objective response occurred in 20 patients (83.3%; 95% CI, 62-95%), (Stable=1, PR=10, &amp; CR=10 as the best response).11 unrelated SAEs were observed in 8 patients. No treatment-related grade 4/5 adverse events were reported.No patient required angioembolisation, vesical artery ligation, or cystectomy.Proteomics studies indicated modulation of coagulation pathways and improved stem cell mediated regeneration and wound healing following chlorophyllin treatment. Conclusions: In this phase II study,oral CHL has shown objective &amp; sustained response in cHC related grade II-IV hematuria following pRT. A randomized, placebo-controlled, phase III trial assessing the efficacy of oral CHL is now planned. Clinical trial information: NCT05348239 .

Safety, Tolerability, and Pharmacokinetics of Nebulized GB05-Human IFNα1b Inhalation Solution: A Randomized, Placebo-Controlled, Dose-Escalation PhaseI Study in Healthy Chinese Adult Volunteers.

Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infection, especially in children and older people. However, no effective treatment is currently available. TypeI interferons (IFNs) are a group of cytokines that help regulate the activity of the immune system. GB05, human IFNα1b inhalation solution, was developed under US Food and Drug Administration (FDA) standard guidelines to combat RSV infection. This randomized, double-blind, placebo-controlled, dose-escalation phaseI trial evaluated the safety, tolerability, and pharmacokinetics of nebulized GB05. A total of 35 eligible healthy Chinese adult volunteers were enrolled in this study. In the single ascending dose (SAD) study, volunteers were randomized into 0.2, 0.6, 1.2, and 1.8million IU of GB05 or placebo. In the multiple ascending dose (MAD) study, volunteers received 1.2 or 1.8million IU of GB05 or placebo for four consecutive days. Safety, tolerability, immunogenicity, and plasma pharmacokinetics were assessed for all groups. All adverse events were mild or moderate and resolved spontaneously. The most common adverse event was decreased white blood cell count (8.6% in SAD and 10% in MAD). No serious adverse events, deaths, or adverse events that reached the termination criteria occurred during the study. In SAD, the maximum concentration and area under the curve increased across the dose range of 1.2-1.8million IU in a non-linear relationship. The maximum plasma concentration after GB05 nebulization (1.06IU/ml in the 1.8million IU group) reflected a low concentration in the blood, suggesting a better lung uptake of GB05 and reduced incidence or risks of adverse events. In MAD, a steady state was reached after continuous administrations of twice daily for 3days. Overall, nebulized GB05 exhibited satisfactory safety, tolerability, and favorable pharmacokinetic (PK) profiles in healthy adult volunteers, supporting further clinical investigation in patients infected with respiratory syncytial virus. ClinicalTrials.gov Identifier NCT06277167.

Influence of TPMT and NUDT15 Genetic Polymorphisms on Mercaptopurine Pharmacokinetics in Healthy Volunteers.

Aims: This study aimed to investigate the impact of genetic polymorphisms of thiopurine methyltransferase (TPMT) and NUDT15 on pharmacokinetics profile of mercaptopurine in healthy adults in China. Methods: Blood samples were obtained from 45 healthy adult volunteers who were administered azathioprine. Genomic DNA was extracted and sequenced for TPMT and NUDT15. The plasma concentrations of 6-mercaptopurine (6-MP) were determined by ultra-performance liquid chromatography-tandem mass spectrometry. Finally, pharmacokinetic parameters were calculated based on the time-concentration curve. Results: Among the 45 healthy adult volunteers enrolled in the study, two TPMT allelic variants and three NUDT15 allelic variants were detected. In total, six genotypes were identified, including TPMT*1/*1&NUDT15*1/*1, TPMT*1/*1&NUDT15*1/*2, TPMT*1/*1&NUDT15*1/*9, TPMT*1/*1&NUDT15*2/*5, TPMT*1/*6&NUDT15*1/*2, and TPMT*1/*3&NUDT15*1/*2. The results indicated that Area Under Curve (AUC) of 6-MP in volunteers with TPMT*1/*3&NUDT15*1/*2 and TPMT*1/*6&NUDT15*1/*2 were 1.57-1.62-fold higher than in individuals carrying the wild type (TPMT*1/*1&NUDT15*1/*1). Compared with wild type, the half-life (T1/2) of TPMT*1/*6&NUDT15*1/*2 was extended by 1.98 times, whereas T1/2 of TPMT*1/*3&NUDT15*1/*2 decreased by 67%. The maximum concentration (Cmax) of TPMT*1/*3&NUDT15*1/*2 increased significantly by 2.15-fold, whereas the corresponding clearance (CL/F) decreased significantly by 58.75%. Conclusion: The findings of this study corroborate the notion that various genotypes of TPMT and NUDT15 can impact the pharmacokinetics of mercaptopurine, potentially offering foundational insights for personalized mercaptopurine therapy.

Ultrasound-based Measurement of the Intra-scaphoid angle

IntroductionUltrasound is gaining popularity for diagnosing scaphoid fractures. However, it hasn't been used to assess fracture displacement, such as humpback deformity. We propose a sonographic method to measure the intra-scaphoid angle, potentially serving as an alternative to CT scans for detecting fragment malposition after a scaphoid fracture. MethodsWe recruited 11 healthy adult volunteers without wrist pathology and performed bilateral wrist ultrasounds, totaling 22 examinations. Each wrist was splinted at 50 ° extension and fully supinated. Two hand surgeons independently performed the ultrasounds. All images were then evaluated separately by two evaluators. The following measurements were taken: 1. Inter-poles distance (IPD): Distance between the summits of the two scaphoid poles on the palmar cortex. 2. Palmar cortical intra-scaphoid angle (PCISA): Angle between the two summits and the deepest point of the waist on the palmar cortex. Measurements were compared for inter-investigator and inter-evaluator reliability using the intraclass correlation coefficient (ICC). ResultsThe study included four males and seven females, with an average age of 35 years (range 21–56). The mean PCISA was 142 ° (SD 10 °) and the mean IPD was 16.3 mm (SD 2.1 mm). Differences in IPD measurements averaged 0.3 mm (range 0–5.2 mm) among investigators and 1.0 mm (range 0.1–3.8 mm) among evaluators. For PCISA, the differences averaged 4 ° (range 0–17 °) among investigators and 6 ° (range 0–15 °) among evaluators. The ICC for IPD was 0.804 (investigators) and 0.572 (evaluators); for PCISA, it was 0.704 (investigators) and 0.602 (evaluators). ConclusionThis study presents a cost-effective and accessible sonographic technique to measure the intra-scaphoid angle. Further research is required to assess its effectiveness in scaphoid fractures and compare it to CT-based measurements like the H/L ratio, LISA, and DCA.

Multi-Dimensional Morphometric and Volumetric Analysis of the Posterior Cranial Fossa to Study Type I Chiari Malformation

Chiari malformation type I (CM-1) is a complex disorder in which tonsillar herniation through the foramen magnum manifests with a spectrum of clinical symptoms. This work analyzes morphometric and volumetric characteristics of CM-1 patients. With Institutional Review Board (IRB) approval, we retrospectively reviewed a total of 72 adult CM-1 patients and 26 healthy adult volunteers who underwent volumetric magnetic resonance brain imaging. Clinical data was retrospectively extracted from the electronic medical record. We analyzed multi-dimensional morphometric and volumetric features within the posterior cranial fossa and correlated these features with syrinx formation and the decision to undergo surgical decompression. In our study, CM-1 patients had decreased cerebellar, brainstem and 4th ventricular volumes but larger tonsillar volume with increased total tonsillar length. CM-1 patients who underwent surgery had significantly more neural tissue within the cross-sectional area of cisterna magna. Logistic regression demonstrated that combining neural tissue at foramen magnum with cerebellar & 4th ventricular volumes led to great degree of correlation with syrinx formation (AUC 0.911). Our findings suggest that the amount of tissue at the foramen magnum correlates with CM-1 patients who underwent decompressive surgery, more so than tonsillar length. Additionally, the combination of neural tissue at foramen magnum, cerebellar & 4th ventricular volumes led to great degree of correlation with syrinx formation. Together, these findings suggest that a global compressive phenomenon within the posterior fossa leads to CM-1 symptomatology and syrinx formation.

Reliability of Digital Artery Palpation and Pulse Oximetry Waveform As Alternatives to Radial Pulse in the Assessment of Upper Limb Injuries.

Radial pulse palpation is widely accepted as a gold standard clinical method to assess distal vascular perfusion of the upper limb. In some instances, the radial pulse may not be accessible due to splints, casts, or swelling, or the injury may be at the level or distal to the radial artery. Here, the authors assess two alternative methods of assessing perfusion of the hand more distally: palpation of the digital pulse and pulse oximetry (PO) waveform. Twenty-four healthy adult volunteers (48 hands) were assessed by two assessors. Digital artery pulses were palpated, and ease of location was recorded. A brachial cuff pressure was inflated to 20 mmHg above systolic pressure to occlude distal perfusion. Radial pulse, digital artery pulse, and PO waveform were monitored as the brachial cuff pressure was deflated in 5 mmHg increments to ascertain when each returned and compare the reliability of these tests to the gold standard of the radial pulse. The digital artery pulse was easily located in 20/24 participants, most reliably over the proximal phalanx of the index finger. With occlusion of the brachial artery, no distal pulses could be felt, and PO showed no waveform. As the brachial artery cuff pressure was incrementally deflated, the digital pulse returned with the same cuff pressure or a lower cuff pressure than the radial pulse in all cases, suggesting a high positive predictive value of radial pulse presence. PO waveform returned at a higher cuff pressure or with the same cuff pressure as the return of the radial pulse, suggesting a higher sensitivity than radial pulse palpation in assessing hand perfusion. Digital pulse palpation can be used as a surrogate method of assessing hand perfusion. When present, it can be assumed a radial pulse is present due to a high positive predictive value and no false positives seen in any participant. When absent, further investigation is required. The PO waveform was found to be more sensitive than digital or radial pulse palpation as a measure of distal perfusion, with a return of waveform prior to palpable pulses. This likely represents a more accurate clinical test of distal perfusion and can be relied upon even when pulses are not palpable.

Assessing Aortic Motion with Automated 3D Cine Balanced SSFP MRI Segmentation

PurposeTo apply free-running three-dimensional (3D) cine balanced steady state free precession (bSSFP) CMR framework in combination with AI segmentations to quantify time-resolved aortic displacement, diameter and diameter change. MethodsIn this prospective study, we implemented a free-running 3D cine bSSFP sequence with scan time of about 4minutes facilitated by pseudo-spiral Cartesian undersampling and compressed-sensing reconstruction. Automated segmentation of all cardiac timeframes was applied through the use of nnU-Net. Dynamic 3D motion maps were created for three repeated scans per volunteer, leading to the detailed quantification of motion, as well as the measurement and change in diameter of the ascending aorta. ResultsA total of 14 adult healthy volunteers (median age, 28 years (IQR: 26.0-31.3), 6 female) were included. Automated segmentation compared to manual segmentation of the aorta test set showed a Dice score of 0.93 ± 0.02. The median (interquartile range) over all volunteers for the largest maximum and mean ascending aorta (AAo) displacement in the first scan was 13.0 (4.4) mm and 5.6 (2.4) mm, respectively. Peak mean diameter in the AAo was 25.9 (2.2) mm and peak mean diameter change was 1.4 (0.5) mm. The maximum individual variability over the three repeated scans of maximum and mean AAo displacement was 3.9 (1.6) mm and 2.2 (0.8) mm, respectively. The maximum individual variability of mean diameter and diameter change were 1.2 (0.5) mm and 0.9 (0.4) mm. ConclusionA free-running 3D cine bSSFP CMR scan with a scan time of four minutes combined with an automated nnU-net segmentation consistently captured the aorta’s cardiac motion-related 4D displacement, diameter, and diameter change.

Hand Acceleration Time is a Valuable Ultrasonographic Tool in Hand Perfusion as Adjuvant Evaluation for Diagnosing Chronic Upper Limb Ischemia

Diagnosis of chronic upper limb ischemia is mainly clinical. Although hand perfusion can be evaluated by different noninvasive methods (e.g., digital-brachial index, digital pressures, oxygen saturation measurements, and plethysmography), these have not been standardized for the diagnosis of chronic upper limb ischemia. Initial reports suggested that the hand acceleration time (HAT) measured by duplex ultrasound could be a useful diagnostic tool. However, the HAT has neither been properly characterized nor validated. This study aimed to provide evidence that HAT is a sensitive diagnostic tool for chronic upper limb ischemia. We conducted a prospective, single-center, cross-sectional study with adult patients diagnosed with chronic upper limb ischemia and healthy adult volunteers without cardiovascular risk factors. Hand vascular duplex ultrasound and HAT measurement were performed in 4 artery locations: princeps pollicis artery, radialis indicis artery, first common digital palmar artery, and third common digital palmar artery. It was also measured in the ulnar and radial arteries. Descriptive and exploratory analyses were performed between patients and healthy volunteers. Thirty participants were included, being 15 patients (median [standard deviation] age: 51 [18] years; 47% women) and 15 healthy volunteers (median [standard deviation] age: 35 [10] years; 60% women). In total, 15 ischemic and 30 nonischemic hands were analyzed. Humeral artery stenosis/occlusion (n=6, 40.0%) and distal artery stenosis (n=5, 33.3%) were the main causes of ischemia. Median (interquartile range) HAT measurements were significantly different between patients and healthy volunteers in the 4 hand arterial locations, the radial artery, and ulnar artery: princeps pollicis artery: 164 (124-252) vs. 60 (40-88), P<0.001; radialis indicis artery: 176 (140-348) vs. 60 (36-80), P<0.001; first common digital palmar artery: 180 (92-320) vs. 64 (36-88), P<0.001; third common digital palmar artery: 180 (104-240) vs. 56 (44-92), P<0.001; radial artery: 156 (120-248) vs. 68 (55-76), P<0.001; and ulnar artery: 152 (76-220) vs. 61 (48-76), P<0.001. Vascular duplex ultrasound with HAT measurement seems to be an easy-access, sensitive diagnostic tool for chronic upper limb ischemia. HAT provides valuable information on hand perfusion and may be complementary to current noninvasive methods.

Selecting optimal wearables for measuring physiological arousal in robot-delivered mindfulness-based exercises

While social robots show promise for therapeutic interventions, accurate assessments of (vulnerable) participants' affective outcomes require attention. The careful selection of devices for recording autonomic processes in response to stress-inducing and relaxing exercises is essential to ensure data quality recordings and participants' comfort. This foundational study assessed two commonly utilized devices to record electrodermal activity (EDA), indexed through skin conductance, concerning their sensitivity to stress-relaxation manipulations and social validity during a robot intervention: a sock with a Shimmer device and a wrist-worn Empatica E4. We aimed to select the most sensitive and easy-to-wear one as a precursor to a larger intervention study featuring mindfulness-based relaxation exercises delivered by an NAO robot. The findings, based on 28 healthy Dutch-speaking adult volunteers wearing both devices, revealed sensitivity in detecting EDA variations in arousal following stressful (increase) and Robot-delivered mindfulness-based relaxation (decrease) exercises, further corroborated by self-reports. Bland-Altman results suggested little agreement between the two devices and lower sensitivity for the Empatica E4. No statistically significant differences concerning wearing comfort between the Empatica E4 and the Shimmer devices emerged. Although both devices independently showed sensitivity to stress/relaxation manipulation, the choice for one or the other should be informed by the activities in the intervention.

Pharmacokinetics, Safety, Tolerability, and Immunogenicity of BP02 (Trastuzumab Biosimilar) Compared to EU- and US-Approved Trastuzumab in Healthy Adult Male Volunteers: A Phase 1, Randomized, Double-Blind Study.

This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab). In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78days. Serum drug concentration-time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80-125% bioequivalence criteria. Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration-time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects-three in the US-trastuzumab group and one in the BP02 group-discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies. This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab. ANZCTR number: ACTRN12621000573853.

The Role of Chitinase-3-like Protein 1 (YKL-40) as a Marker of Disease Activity in Ankylosing Spondylitis Patients

Abstract Background Ankylosing spondylitis is a prototype of spondyloarthritides that primarily affects the axial skeleton. Sacroiliitis is the hallmark and accompanied by inflammation of the entheses and formation of syndesmophytes, leading to spinal ankylosis in later stages. Prevalence estimates vary between 0.1% and 2% in different populations.The most utilized peripheral blood biomarkers of ankylosing spondylitis activity in clinical practice and clinical trials are ESR and CRP. However, they have low sensitivity and specificity. Objective To detect the role of YKL-40 as an objective Marker of disease activity in ankylosing Spondylitis Patients. Patient and Methods This study was a case control study, included fifteen ankylosing spondylitis patients were recruited from the outpatient clinic and inpatient department of Physical Medicine, Rheumatoloy and Rehabilitation of Ain Shams university hospitals and fifteen adult healthy volunteers as a control group. Approval of the Ain shams university research and ethical committee was obtained. Results There was no statistically significant difference between patient and control group as regard age and sex. YKL-40 showed 100% sensitivity and 100% specificity. large scale studies with follow up of patients in response to drug treatment are needed to be done to assess its uses as a disease activity marker. large scale prospective studies are needed with the assessment of comorbidities and their time of development in correlation to YKL-40 as it has an excellent potential for prediction of these comorbidities. Conclusion YKL-40 marker is a good predictor for ankylosing spondylitis disease.