Compromised Cerebral Arterial Perfusion, Altered Brain Tissue Integrity, and Cognitive Impairment in Adolescents with Complex Congenital Heart Disease.

(1) Introduction: Adolescents with complex congenital heart disease (CCHD) show brain tissue injuries in regions associated with cognitive deficits. Alteration in cerebral arterial perfusion (CAP), as measured by arterial transit time (ATT), may lead to perfusion deficits and potential injury. Our study aims to compare ATT values between CCHD patients and controls and assess the associations between ATT values, MD values, and cognitive scores in adolescents with CCHD. (2) Methods: 37 CCHD subjects, 14-18 years of age, who had undergone surgical palliation and 30 healthy controls completed cognitive testing and brain MRI assessments using a 3.0-Tesla scanner. ATT values and regional brain mean diffusivity [MD] were assessed for the whole brain using diffusion tensor imaging. (3) Results: The mean MoCA values [23.1 ± 4.1 vs. 28.1 ± 2.3; p < 0.001] and General Memory Index, with a subscore of WRAML2 [86.8 ± 15.4 vs. 110.3 ± 14.5; p < 0.001], showed significant cognitive deficits in CCHD patients compared to controls. The mean global ATT was significantly higher in CCHD patients versus controls (mean ± SD, s, 1.26 ± 0.11 vs. 1.19 ± 0.11, p = 0.03), respectively. The partial correlations between ATT values, MD values, and cognitive scores (p < 0.005) showed significant associations in areas including the hippocampus, prefrontal cortices, cerebellum, caudate, anterior and mid cingulate, insula, thalamus, and lingual gyrus. (4) Conclusions: Adolescents with CCHD had prolonged ATTs and showed correlation with clinical measurements of cognitive impairment and MRI measurements of brain tissue integrity. This suggests that altered CAP may play a role in brain tissue injury and cognitive impairment after surgical palliation.

The influence of tramadol on bowel function: A randomised, placebo-controlled trial.

Tramadol is a weak opioid used to treat moderate pain. Stronger opioids inhibit gastrointestinal function, but little is known about the gastrointestinal effects of tramadol. Our aim was to investigate if tramadol causes opioid-induced bowel dysfunction (OIBD). Twenty healthy male participants (mean age 24 [range 20-31] years) were included. Tramadol (extended-release formulation, 200 mg/day) or placebo was administered for 10 days in two study periods separated by 3 weeks. Gastrointestinal transit times and segmental volume, motility and water content were investigated with the 3D-transit system and magnetic resonance imaging. Bowel movements and gastrointestinal symptoms were recorded daily. Tramadol prolonged colonic transit time (34 h vs. 25 h, p < 0.001) and increased small bowel motility (p < 0.01) and water content (p = 0.002) compared to placebo. Across all days of treatment, tramadol reduced the number of mean daily bowel movements (p = 0.001) and increased mean stool consistency (p = 0.006). Gastrointestinal symptom scores increased with tramadol (indigestion: +358%, p = 0.01; constipation: +475%, p = 0.01). Additionally, more participants fulfilled the diagnostic criteria for constipation after tramadol treatment compared to placebo (40% vs. 0%, p < 0.001). This study showed that tramadol treatment is associated with OIBD, and management of constipation and other bowel symptoms should, therefore, be prioritised when treating pain patients with tramadol.

Cerebral perfusion metrics calculated directly from a hypoxia-induced step change in deoxyhemoglobin.

Resting cerebral perfusion metrics can be calculated from the MRI ΔR2* signal during the first passage of an intravascular bolus of a Gadolinium-based contrast agent (GBCA), or more recently, a transient hypoxia-induced change in the concentration of deoxyhemoglobin ([dOHb]). Conventional analysis follows a proxy process that includes deconvolution of an arterial input function (AIF) in a tracer kinetic model. We hypothesized that the step reduction in magnetic susceptibility accompanying a step decrease in [dOHb] that occurs when a single breath of oxygen terminates a brief episode of lung hypoxia permits direct calculation of relative perfusion metrics. The time course of the ΔR2* signal response enables both the discrimination of blood arrival times and the time course of voxel filling. We calculated the perfusion metrics implied by this step signal change in seven healthy volunteers and compared them to those from conventional analyses of GBCA and dOHb using their AIF and indicator dilution theory. Voxel-wise maps of relative cerebral blood flow and relative cerebral blood volume had a high spatial and magnitude congruence for all three analyses (r > 0.9) and were similar in appearance to published maps. The mean (SD) transit times (s) in grey and white matter respectively for the step response (7.4 (1.1), 8.05 (1.71)) were greater than those for GBCA (2.6 (0.45), 3.54 (0.83)) attributable to the nature of their respective calculation models. In conclusion we believe these calculations of perfusion metrics derived directly from ΔR2* have superior merit to calculations via AIF by virtue of being calculated from a direct signal rather than through a proxy model which encompasses errors inherent in designating an AIF and performing deconvolution calculations.

Evaluation of cerebral microcirculation in a mouse model of systemic inflammation.

Significance: Perturbations in the microcirculatory system have been observed in neurological conditions, such as Alzheimer's disease or systemic inflammation. However, changes occurring at the level of the capillary are difficult to translate to biomarkers that could be measured macroscopically. Aim: We aim to evaluate whether transit time changes reflect capillary stalling and to what degree. Approach: We employ a combined spectral optical coherence tomography (OCT) and fluorescence optical imaging (FOI) system to investigate the relation between capillary stalling and transit time in a mouse model of systemic inflammation induced by intraperitoneal injection of lipopolysaccharide. Angiograms are obtained using OCT, and fluorescence signal images are acquired by the FOI system upon intravenous injection of fluorescein isothiocyanate via a catheter inserted into the tail vein. Results: Our findings reveal that lipopolysaccharide (LPS) administration significantly increases both the percentage and duration of capillary stalling compared to mice receiving a 0.9% saline injection. Moreover, LPS-induced mice exhibit significantly prolonged arteriovenous transit time compared to control mice. Conclusions: These observations suggest that capillary stalling, induced by inflammation, modulates cerebral mean transit time, a measure that has translational potential.

Immediate effects of simple palatal augmentation prosthesis in maximum tongue pressure and swallowing functions for acute stroke patients: An observational study.

PURPOSE: Acute stroke often leads to dysphagia. In the oral stage of dysphagia, there is a potential for immediate benefit from using a palatal augmentation prosthesis (PAP). We investigated whether our quickly fabricated, simple, and expedited version of PAP would result in an immediate improvement in swallowing function after an acute stroke. METHODS: We analyzed the records of stroke patients that were hospitalized between October 2019 and March 2022 and met the following criteria: they had a rehabilitation prescription and had paralysis of facial or hypoglossal nerves and either repeated salivary swallowing test ≤2 times or modified water swallow test ≤3, they were fasting, were within 3 weeks of onset, and had a simple PAP made for them. Outcomes included with/without PAP, maximum tongue pressure, repeated salivary swallowing test, and modified water swallow test on the day after starting to wear PAP was started. In addition, within one week, a videofluoroscopic examination was performed to measure the oral transit time, pharyngeal transit time, and penetration aspiration scale. Statistical analyses were performed using Wilcoxon signed-rank tests. Statistical significance was set at P < 0.05. RESULTS: Fifteen patients met the inclusion criteria and were included in this study. The mean age of the subjects was 76.9 ± 9.0 years. The use of PAP significantly increased maximum tongue pressure (P < 0.0001*) and shortened oral transit time (P < 0.0091*). There were no significant differences among the other items. CONCLUSIONS: Simple PAP immediately increased the maximum tongue pressure and improved swallowing function during the oral stage.

Changes of pulse wave transit time after haemodynamic manoeuvres in healthy adults: a prospective randomised observational trial (PWTT volunteer study).

Background: Pulse wave transit time (PWTT) shows promise for monitoring intravascular fluid status intraoperatively. Presently, it is unknown how PWTT mirrors haemodynamic variables representing preload, inotropy, or afterload. Methods: PWTT was measured continuously in 24 adult volunteers. Stroke volume was assessed by transthoracic echocardiography. Volunteers underwent four randomly assigned manoeuvres: 'Stand-up' (decrease in preload), passive leg raise (increase in preload), a 'step-test' (adrenergic stimulation), and a 'Valsalva manoeuvre' (increase in intrathoracic pressure). Haemodynamic measurements were performed before and 1 and 5 min after completion of each manoeuvre. Correlations between PWTT and stroke volume were analysed using the Pearson correlation coefficient. Results: 'Stand-up' caused an immediate increase in PWTT (mean change +55.9 ms, P-value <0.0001, 95% confidence interval 46.0-65.7) along with an increase in mean arterial pressure and heart rate and a drop in stroke volume (P-values <0.0001). Passive leg raise caused an immediate drop in PWTT (mean change -15.4 ms, P-value=0.0024, 95% confidence interval -25.2 to -5.5) along with a decrease in mean arterial pressure (P-value=0.0052) and an increase in stroke volume (P-value=0.001). After 1 min, a 'step-test' caused no significant change in PWTT measurements (P-value=0.5716) but an increase in mean arterial pressure and heart rate (P-values <0.0001), without changes in stroke volume (P-value=0.1770). After 5 min, however, PWTT had increased significantly (P-value <0.0001). Measurements after the Valsalva manoeuvre caused heterogeneous results. Conclusion: Noninvasive assessment of PWTT shows promise to register immediate preload changes in healthy adults. The clinical usefulness of PWTT may be hampered by late changes because of reasons different from fluid shifts. Clinical trial registration: German clinical trial register (DRKS, ID: DRKS00031978, https://www.drks.de/DRKS00031978).

The effect of post-labeling delay on cerebral blood flow is influenced by age and sex: a study based on arterial spin-labeling magnetic resonance imaging.

Background: Whether the effect of post-labeling delay (PLD) on cerebral blood flow (CBF) is influenced by age and sex in adults is unknown. In this study, we mainly aimed to explore the potential influence of age and sex on the effect of PLD on CBF. Methods: This prospective study enrolled 90 healthy adult volunteers (49.47±15.63 years of age; age range, 20-77 years; 47 female; 43 male). All participants underwent 3-dimensional (3D) pseudo-continuous arterial spin labeling (ASL) imaging with 3 different PLDs (1,525, 2,025, and 2,525 ms). The CBF values for each PLD, the arterial transit time (ATT), and the spatial coefficient of variation (spatial CoV) were computed for 21 regions of interest (ROIs) in every participant. Multivariate regression analysis was conducted to assess the potential influence of age and sex on the effect of PLD on CBF and the relationships among CBF, ATT, PLD, age, sex, and spatial CoV. Results: The CBF increased for 7.32 to 9.87 mL/100 g/min as the PLD increased per 1 second in the global gray matter, bilateral frontal, temporal lobes, the vascular territories of bilateral anterior and middle carotid artery. When the age increased per 1 year, the speed of the changes for CBF decreased for 0.26 to 0.3 mL/100 g/min/s in these regions. However, the CBF decreased for 12 to 17 mL/100 g/min as the PLD increased per 1 second in the bilateral limbic lobes, insula, and deep gray matter. In these regions, the speed of the changes for CBF increased for 0.2 to 0.28 mL/100 g/min/s as the age increased per 1 year. Furthermore, compared to the female, the speed of the changes for CBF decreased for 3.58 to 4.6 mL/100 g/min/s for the male in global gray matter, bilateral frontal, limbic lobes, and the vascular territories of bilateral anterior carotid artery, and the speed increased 4.49 to 5.09 mL/100 g/min/s for the male in the limbic lobes. In addition, the CBF decreased with aging and the CBF tended to be higher in females compared to males. At the same time, we found that the ATT of all ROIs increased with age and manifested higher in males than females. Moreover, we found that CBF decreased with the increase of ATT, and the effect of ATT on CBF was less influenced by PLD. Finally, we found that the spatial CoV of ASL in certain regions increased with the increase of ATT and age, and was greater in males. Conclusions: The effect of PLD on CBF can be influenced by age and sex. The relationships among CBF, ATT, PLD, age, sex, and spatial CoV found in this study may have certain significance for the study of ASL imaging in the future.

MoPill a novel gastrointestinal positioning system (GPS): New technology to navigate the alimentary tract highway.

BACKGROUND: Evaluation of gut motility in clinical practice is currently limited. A novel medical system (MoPill™) consisting of a capsule that wirelessly transmits radiofrequency signals to assess motility via 3D location, was used to conduct this study. The objectives were to: (1) confirm the safety of the MoPill™ system; (2) compare the 3D location transmitted by the capsule to its location captured by abdominal x-rays; 3 determine gastric emptying (GE), whole gut transit time (WGTT) and segmental transit times. METHODS: The MoPill™ system consists of an electronic capsule (2 × 1.2 cm), eight color-coded adhesive sensors (6 × 5.5 cm), a recorder (15 × 11 × 2 cm), and software on a laptop. Four sensors were applied to the abdomen and four to the back. Healthy subjects who had fasted overnight ingested a 250-calorie protein bar, 17 oz. of water, followed by an activated capsule. No further caloric contents were permitted for the next 5 h. At 1, 5, and 24 h (if the capsule had not been expelled), upright abdominal X-rays (AP and lateral) were obtained to assess the location of the capsule, which was compared to the gastrointestinal positioning system (GPS) location determined by the MoPill™ system. Identification of the capsule's anatomical location by the MoPill™ system was based on (1) the 3D (x, y, z) location; (2) time; (3) trajectory (e.g., going up the right side of the body signified ascending colon); (4) frequency of contractions (e.g., 3 cycles/min for the stomach); and (5) milestone relationship (e.g., pyloric passage must follow the end of gastric contractions). GE was determined first by the end of the 3 cycles/min rhythmic movement of the stomach and then again by pyloric expulsion on 3D location. Small intestine transit was taken as the duration from pyloric expulsion to arrival in the cecum. Colon transit time was determined by calculating the duration from 3D arrival in the cecum to passage of the capsule out of the body (i.e., loss of signal accompanying a bowel movement). KEY RESULTS: Ten healthy subjects (five women; mean age 34; mean BMI 24) were enrolled, and nine provided reliable data. The variation between the x-ray and the estimated (i.e., identified by the MoPill™ system) location of the capsule was within an average of 3.5 cm (range 0.9-9.4 cm). The mean GE was 3.1 h. The small intestine's mean transit time was 4.3 h. The mean colonic transit time was 17.6 h. There were no adverse events recorded during the study. CONCLUSIONS & INFERENCES: MoPill™ is a novel gastrointestinal positional system that accurately identifies the location of a capsule compared to an X-ray. MoPill™ system also recognizes GE, small bowel, colonic, and WGTT as well as segmental gut location and movement characteristics. MoPill™ offers the potential for new insights into GI motility disorders not attainable by current modalities.

Functional Assessment of Cerebral Capillaries using Single Capillary Reporters in Ultrasound Localization Microscopy.

The brain's microvascular cerebral capillary network plays a vital role in maintaining neuronal health, yet capillary dynamics are still not well understood due to limitations in existing imaging techniques. Here, we present Single Capillary Reporters (SCaRe) for transcranial Ultrasound Localization Microscopy (ULM), a novel approach enabling non-invasive, whole-brain mapping of single capillaries and estimates of their transit-time as a neurovascular biomarker. We accomplish this first through computational Monte Carlo and ultrasound simulations of microbubbles flowing through a fully-connected capillary network. We unveil distinct capillary flow behaviors which informs methodological changes to ULM acquisitions to better capture capillaries in vivo. Subsequently, applying SCaRe-ULM in vivo, we achieve unprecedented visualization of single capillary tracks across brain regions, analysis of layer-specific capillary heterogeneous transit times (CHT), and characterization of whole microbubble trajectories from arterioles to venules. Lastly, we evaluate capillary biomarkers using injected lipopolysaccharide to induce systemic neuroinflammation and track the increase in SCaRe-ULM CHT, demonstrating the capability to detect subtle capillary functional changes. SCaRe-ULM represents a significant advance in studying microvascular dynamics, offering novel avenues for investigating capillary patterns in neurological disorders and potential diagnostic applications.

Development of a Personalized Multiclass Classification Model to Detect Blood Pressure Variations Associated with Physical or Cognitive Workload.

Comprehending the regulatory mechanisms influencing blood pressure control is pivotal for continuous monitoring of this parameter. Implementing a personalized machine learning model, utilizing data-driven features, presents an opportunity to facilitate tracking blood pressure fluctuations in various conditions. In this work, data-driven photoplethysmograph features extracted from the brachial and digital arteries of 28 healthy subjects were used to feed a random forest classifier in an attempt to develop a system capable of tracking blood pressure. We evaluated the behavior of this latter classifier according to the different sizes of the training set and degrees of personalization used. Aggregated accuracy, precision, recall, and F1-score were equal to 95.1%, 95.2%, 95%, and 95.4% when 30% of a target subject's pulse waveforms were combined with five randomly selected source subjects available in the dataset. Experimental findings illustrated that incorporating a pre-training stage with data from different subjects made it viable to discern morphological distinctions in beat-to-beat pulse waveforms under conditions of cognitive or physical workload.

Myocardial Transit Time Mapping by CMR: A Novel Indicator of Microcirculatory Dysfunction in Cardiac Amyloidosis.

Cardiac amyloidosis (CA) is characterized by the deposition of amyloid fibrils within the myocardium, resulting in a restrictive physiology. Although microvascular dysfunction is a common feature, it is difficult to assess. This study aimed to explore myocardial transit time (MyoTT) by cardiovascular magnetic resonance (CMR) as a potential novel parameter of microcirculatory dysfunction in CA. This prospective study enrolled 20 CA patients and 20 control subjects. CMR acquisition included cine imaging, pre- and post-contrast T1 mapping, and MyoTT assessment, which was calculated from the time delay in contrast agent arrival between the aortic root and coronary sinus (CS). Compared to the control group, patients with CA exhibited significantly reduced left ventricular (LV) ejection fraction and myocardial strain, an increase in LV global peak wall thickness (LVGPWT), extracellular volume fraction (ECV), and prolonged MyoTT (14.4 ± 3.8 s vs. 7.7 ± 1.5 s, p < 0.001). Moreover, patients at Mayo stage III had a significantly longer MyoTT compared to those at stage I/II. MyoTT showed a positive correlation with the ECV, LVGPWT, and LV global longitudinal strain (LV-GLS) (p < 0.05). The area under the curve (AUC) for MyoTT was 0.962, demonstrating diagnostic performance comparable to that of the ECV (AUC 0.995) and LV-GLS (AUC 0.950) in identifying CA. MyoTT is significantly prolonged in patients with CA, correlating with fibrosis markers, remodeling, and dysfunction. As a novel parameter of coronary microvascular dysfunction (CMD), MyoTT has the potential to be an integral biomarker in multiparametric CMR assessment of CA.

Is cortical transit time a parameter to prove relief of obstruction after pyeloplasty in antenatally diagnosed ureteropelvic junction obstruction.

PURPOSE: The study aims to determine the possible improvement in cortical transit time (CTT) after surgery in infants with antenatally diagnosed ureteropelvic junction obstruction (UPJO), and investigate the correlation of CTT with preoperative renal function and parenchymal thickness. PATIENTS AND METHODS: Medical charts of 32 antenatally diagnosed children with UPJO operated on between 2014 and 2021 were reviewed. Patients' demographics, preoperative and postoperative anteroposterior diameter (APD), parenchymal thickness (PT) ratio, differential renal function (DF), drainage patterns and CTT were compared to determine operative benefit. Preoperative CTT of each patient was also grouped as severely delayed (> 6 min) and moderately delayed (3-5 min) and compared. The correlation between the preoperative CTT and preoperative DF and PT ratio was investigated. RESULTS: The median age of the patients was 8.8 months (1-24 months). The CTT (mean: 6.8 ± 3.0 min) was prolonged before surgery and was significantly improved (mean 4.6 ± 1.0 min) after the operation (p < 0.001). A significant negative correlation was detected between the CTT and preoperative DF and between the CTT and preoperative PT ratio. Preoperative DF was found significantly impaired in patients within the severely prolonged CTT group compared to those within the moderately prolonged CTT group. Significant improvement in DF was detected in patients in the severely prolonged CTT group after surgery. CONCLUSION: CTT is a parameter to prove relief of obstruction in patients with antenatally diagnosed UPJO after surgery. CTT is negatively correlated with preoperative DF and PT ratio. Severely prolonged CTT may be considered to be an indication of early surgical intervention.

Pulmonary transit time is a predictor of outcomes in heart failure: a cardiovascular magnetic resonance first-pass perfusion study.

BACKGROUND: Pulmonary transit time (PTT) can be measured automatically from arterial input function (AIF) images of dual sequence first-pass perfusion imaging. PTT has been validated against invasive cardiac catheterisation correlating with both cardiac output and left ventricular filling pressure (both important prognostic markers in heart failure). We hypothesized that prolonged PTT is associated with clinical outcomes in patients with heart failure. METHODS: We recruited outpatients with a recent diagnosis of non-ischaemic heart failure with left ventricular ejection fraction (LVEF) < 50% on referral echocardiogram. Patients were followed up by a review of medical records for major adverse cardiovascular events (MACE) defined as all-cause mortality, heart failure hospitalization, ventricular arrhythmia, stroke or myocardial infarction. PTT was measured automatically from low-resolution AIF dynamic series of both the LV and RV during rest perfusion imaging, and the PTT was measured as the time (in seconds) between the centroid of the left (LV) and right ventricle (RV) indicator dilution curves. RESULTS: Patients (N = 294) were followed-up for median 2.0 years during which 37 patients (12.6%) had at least one MACE event. On univariate Cox regression analysis there was a significant association between PTT and MACE (Hazard ratio (HR) 1.16, 95% confidence interval (CI) 1.08-1.25, P = 0.0001). There was also significant association between PTT and heart failure hospitalisation (HR 1.15, 95% CI 1.02-1.29, P = 0.02) and moderate correlation between PTT and N-terminal pro B-type natriuretic peptide (NT-proBNP, r = 0.51, P < 0.001). PTT remained predictive of MACE after adjustment for clinical and imaging factors but was no longer significant once adjusted for NT-proBNP. CONCLUSIONS: PTT measured automatically during CMR perfusion imaging in patients with recent onset non-ischaemic heart failure is predictive of MACE and in particular heart failure hospitalisation. PTT derived in this way may be a non-invasive marker of haemodynamic congestion in heart failure and future studies are required to establish if prolonged PTT identifies those who may warrant closer follow-up or medicine optimisation to reduce the risk of future adverse events.

Preoperative Quantitative Flow Ratio, Intraoperative Transit Time Flow Measurement Parameters, and Their Predictive Value for Short-Term Graft Failure After Coronary Artery Bypass Grafting.

BACKGROUND: Studies on the relationship between the preoperative quantitative flow ratio (QFR) and parameters of intraoperative transit time flow measurement (TTFM) are extremely rare. In addition, the predictive value of QFR and TTFM parameters for early internal mammary artery (IMA) failure after coronary artery bypass grafting still needs to be validated.Methods and Results: We retrospectively collected data from 510 patients who underwent in situ IMA grafting to the left anterior descending (LAD) artery at Fuwai Hospital. Spearman correlation coefficients between preoperative QFR of the LAD artery and intraoperative TTFM parameters of the IMA were -0.13 (P=0.004) for mean graft flow (Qm) and 0.14 (P=0.002) for the pulsatility index (PI). QFR and TTFM exhibited similar and good predictive value for early IMA failure (5.7% at 1 year), and they were better than percentage diameter stenosis (area under the curve 0.749 for QFR, 0.733 for Qm, 0.688 for PI, and 0.524 for percentage diameter stenosis). The optimal cut-off value of QFR was 0.765. Both univariate and multivariable regression analyses revealed that QFR >0.765, Qm ≤15 mL/min, and PI >3.0 independently contributed to early IMA failure. CONCLUSIONS: There were statistically significant correlations between preoperative QFR of the LAD artery and intraoperative TTFM parameters (Qm, PI) of the IMA. Preoperative QFR and intraoperative Qm and PI exhibited excellent predictive value for early IMA failure.

Improving Intraoperative Parathyroid Hormone Specimen Handling and Processing.

Surgeons request intraoperative parathyroid hormone (PTH) monitoring during parathyroidectomy procedures to confirm identification of abnormal gland tissue. Generally, a 50% decrease in the baseline PTH level indicates the abnormal tissue has been removed. A delay in collecting and processing PTH blood samples can complicate intraoperative decision making and prolong the procedure. The purpose of this quality improvement project was to develop tools to facilitate the specimen management process (eg, requesting, transporting, analyzing) for PTH blood samples and decrease the average total time required for transit and assay. We implemented a two-pronged initiative that involved improving the laboratory requisition form and creating a parathyroid tote box to contain all the needed information and supplies. The average total time for transit and assay decreased from 31.36 minutes before implementation to 22.06 minutes after implementation. Perioperative nurses expressed satisfaction with the changes and continue to use the revised process.

A Novel Herbal Composition Alleviates Functional Constipation, Reduces Gastrointestinal Transit Time, and Improves Bowel Function in Adults: A Double-Blind, Randomized Clinical Study.

BACKGROUND AND OBJECTIVE: A recent proof-of-concept pilot clinical study has demonstrated that consumption of CL18100F4, a proprietary herbal blend of Withania somnifera root and Abelmoschus esculentus fruit extracts, significantly relieved the participants from functional constipation and improved their quality of life. The objective of the present randomized, double-blind, placebo-controlled study was to reevaluate the efficacy and tolerability of CL18100F4 in a larger number of subjects. METHODS: Male and female subjects (n = 135; age: 25-60 years), selected through Rome-IV criteria for functional constipation, were randomized into placebo and 300 or 500 mg of CL18100F4 groups and supplemented daily over 60 consecutive days. The primary efficacy outcome measure was Patient Assessment of Constipation-Symptoms (PAC-SYM), evaluated at baseline and on days 7, 30, and 60 of supplementation. The secondary efficacy parameters included Patient Assessment of Constipation-Quality of Life (PAC-QOL), Gastrointestinal Symptom Rating Scale (GSRS) scores, Gastrointestinal Transit Time (GIT), and Complete Spontaneous Bowel Movement (CSBM). Serum levels of Interleukin (IL)-6, IL-10, cortisol, gastrin, serotonin, Diamine oxidase (DAO), and Zonulin were measured. RESULTS: CL18100F4 supplementation significantly (p < 0.001) reduced the PAC-SYM, PAC-QOL, GSRS scores, and GIT and improved CSBM scores. CL18100F4 significantly improved (p < 0.001) sleep quality and decreased depression and anxiety symptoms in the participants. Notably, relief in constipation symptoms and improved gastrointestinal (GI) function were reported starting from day 7. Furthermore, CL18100F4 supplementation significantly (p < 0.001) increased the serum levels of IL-10, DAO, serotonin, gastrin, reduced IL-6, cortisol, and Zonulin. No major adverse events were observed. Participants' vital signs, hematology, clinical biochemistry, and urinalysis parameters were within the normal ranges. CONCLUSION: The present investigation demonstrates that CL18100F4 is tolerable and efficacious in relieving functional constipation, alleviating GI dysfunction, and improving associated non-GI factors in male and female adults.

Optimum Parameters in Ultrasound Coherent Plane Wave Compounding for High LPWV Estimation: Validation on Phantom and Feasibility in 10 Subjects.

OBJECTIVES: The aim of this study is to determine the optimum and fine values of the number and transmission angles of tilted plane waves for coherent plane-wave compounding (CPWC)-based high local pulse wave velocity (LPWV) estimation. METHODS: A Verasonics system incorporating a linear array probe L14-5/38 with 128 elements and a pulsatile pump, CompuFlow1000, were used to acquire radio frequency data of 3, 5, 7, and 9 tilted plane wave sequences with angle intervals from 0° to 12° with a coarse interval increment step of 1°, and the angle intervals from 0° to 2° with a fine interval increment step of 0.25° from a carotid vessel phantom with the LPWV of 13.42 ± 0.90 m/s. The mean value, standard deviation, and coefficients of variation (CV) of the estimated LPWVs were calculated to quantitatively assess the performance of different configurations for CPWC-based LPWV estimation. Ten healthy human subjects of two age groups were recruited to assess the in vivo feasibility of the optimum parameter values. RESULTS: The CPWC technique with three plane waves (PRF of 12 kHz corresponding to a frame rate of 4000 Hz) with an interval of 0.75° had LPWVs of 13.52 ± 0.08 m/s with the lowest CV of 1.84% on the phantom, and 5.49 ± 1.46 m/s with the lowest CV of 12.35% on 10 subjects. CONCLUSIONS: The optimum parameters determined in this study show the best repeatability of the LPWV measurements with a vessel phantom and 10 healthy subjects, which support further studies on larger datasets for potential applications.

Internal Mammary Artery-saphenous Vein Y Anastomosis in Coronary Artery Bypass Grafting - Is there a Possibility of Coronary Steal?

Recent advances in coronary revascularization include total arterial grafting, however, in a few cases, harvesting the right internal thoracic artery (RITA) is not possible due to various reasons. In such cases, where the aorta is also calcified, few surgeons perform Y anastomosis configuration with the left internal thoracic artery(LITA) and saphenous vein which can have disastrous complications. Our patient is a 65-year-old man who was diagnosed with multivessel coronary disease and presented with a coronary steal during coronary artery bypass grafting surgery. The RITA was not harvested due to osteoporosis sternum. LITA-saphenous vein Y anastomosis configuration was done as the aorta was calcified. The anastomosis was done between the LITA to the left anterior descending (LAD) artery and the Y arm saphenous vein was anastomosed to an obtuse marginal (OM)branch. He developed coronary steal following anastomosis of the Y graft to the OM branch. The patient had ischemic changes inside the operation theatre in LAD territory, hence grafts were revised following which the patient became stable. There is a high possibility of a coronary steal when the caliber of the Y arm does not match with the LITA. LITA-saphenous vein Y anastomosis can cause more complications as the saphenous vein is much bigger in caliber compared to the LITA.

Determinants of hand pulse wave velocity and hand pulse transit time in healthy adults.

Arterial pulse wave velocity (PWV) is recognized as a convenient method to assess peripheral vascular stiffness. This study explored the clinical characteristics of hand PWV (hPWV) and hand pulse transit time (hPTT) in healthy adults (sixty males = 42.4 ± 13.9 yrs; sixty-four females = 42.8 ± 13.9 yrs) voluntarily participated in this study. The arterial pulse waveform and the anatomical distance from the radial styloid process to the tip of the middle finger of both hands were recorded in the sitting position. The hPWV was calculated as the traversed distance divided by hPTT between those two points. Male subjects showed significantly greater hPWV, systolic blood pressure, and pulse pressure than age-matched female subjects, while the hPTT was not significantly different between genders. Multiple linear regression analysis showed that gender is a common determinant of hPWV and hPTT, and that age and heart rate (HR) were negatively correlated with hPWV and hPTT, respectively. We conclude that male subjects have greater hPWV than female subjects. Ageing is associated with decreased hPWV, while increased HR is associated with a smaller hPTT. The hPWV and hPTT might be used as non-invasive indices to characterise the ageing and arterial stiffness of peripheral blood vessels.

The use of pulse transit time in diagnostics of sleep-disordered breathing in children.

INTRODUCTION: Sleep is the physiological state of the body where proper morphology and duration are indispensable for human functions throughout both, physical and mental spheres. Disordered breathing during sleep impairs its morphology and results in major disorders in any age group. Adverse effects of Obstructive Sleep Apnea Syndrome in children and poor availability of centers offering children's polysomnography call for a reliable and easily accessible screening method. AIM: The aim of the study were to evaluate the usefulness of pulse transit time in the diagnostics of disordered sleep breathing in children and to attempt to employ the parameter in screening tests. Pulse transit time is a physiological parameter determining the time needed for the pulse wave to travel between two measurement points. MATERIAL AND METHODS: Enrolled in the retrospective study were 153 patients (100 boys and 53 girls) suspected of obstructive sleep apnea syndrome who underwent polysomnography at I. Moscicki ENT Hospital in Chorzów. RESULTS: Statistically significant relations between apnea/hypopnea index and pulse transit time were observed in both, individual age groups and all of the patients. Pulse transit time results proved a negative correlation with apnea/hypopnea index values commonly accepted as a parameter concluding the polysomnography procedures. CONCLUSIONS: The results of the study indicate that pulse transit time measurements may find application in screening tests of sleep-disordered breathing in children.