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Introduction: This study aimed to investigate the correlation between fundus blood flow parameters and the severity of pathological biopsy in patients with diabetic kidney disease (DKD). Methods: Data of patients with type 2 diabetes mellitus who completed renal pathology biopsies and optical coherence tomography angiography (OCTA) examinations, including renal function, 24-h urine protein quantification, and macular flow imaging, were collected. DKD pathology biopsies were graded as stages 1–4, and differences and correlations of the parameters were compared between groups. The grading was transformed into early (stage 1) and late (stages 2–4), and regression analyses were conducted to develop a model, draw a nomogram, and test efficacy. Results: This study included 157 eyes from 157 individuals in total. Urinary microalbumin and to urinary creatinine ratio (mALB/NCR) increased with pathological grading, whereas while glomerular filtration rate was decreased (p < 0.01). Corresponding retinal blood flow in superficial, deep, and full paracentral rings was decreased, which correlated with pathological grading (p < 0.01), with the highest blood flow density in the whole layer (r2 = −0.707). Meaningfully, in the early DKD model (area under the curve = 0.929 [0.889–0.970], p < 0.01), whole-layer blood flow density, mALB/NCR, and diabetes duration were statistically significant. Conclusions: The decrease in macular retinal blood flow density detected by OCTA is closely associated with the increase in pathological grading of DKD and can be used as a noninvasive parameter for monitoring early changes in DKD. [ABSTRACT FROM AUTHOR]

Introduction: Three-dimensional fractional moving blood volume (3D-FMBV) may provide superior noninvasive measurement of feto-placental perfusion compared to current methods. This study investigated the feasibility and repeatability of producing 3D-FMBV measurements of the placenta, fetal liver, kidney, and brain in a single ultrasound consultation. Methods: The placenta, fetal liver, kidney, and brain were scanned in triplicate using 3D power Doppler ultrasound (3D-PDU) in 48 women ≥22 weeks of gestation with healthy fetuses. 3D-FMBV was calculated by two analyzers. Feasibility was assessed as the percentage of cases where 3D-FMBV could be evaluated; repeatability (intraobserver and interobserver) using two-way mixed measure intraclass correlation coefficients (ICCs). Results: 3D-FMBV was calculated for 100% of scanned organs. Intraobserver ICCs (95% CI) were good to excellent; 0.93 (0.88–0.96) and 0.87 (0.78–0.92) for placenta, 0.95 (0.92–0.97) and 0.98 (0.96–0.99) for fetal liver, 0.96 (0.94–0.98) and 0.91 (0.85–0.95) for fetal kidney, and 0.98 (0.97–0.99) and 0.97 (0.95–0.98) for fetal brain. Interobserver ICCs (95% CI) were 0.50 (0.08–0.73), 0.92 (0.85–0.96), 0.89 (0.78–0.94), and 0.71 (0.46–0.85) for placenta, fetal liver, kidney, and brain. Conclusion: Feto-placental perfusion assessment with 3D-FMBV is highly reliable in healthy pregnancies ≥22 weeks of gestation and can be feasibly calculated in four feto-placental vascular beds in a single ultrasound consultation. Plain Language Summary: Throughout pregnancy the placenta provides the fetus with nutrients and oxygen. If blood flow to the fetus is impaired (i.e., in placental disease), the fetus adapts by directing more blood to its brain and less to peripheral organs, called "brain-sparing." This has consequences including impaired growth, stillbirth, and chronic adulthood disease. Brain-sparing is currently detected by measuring how pulsatile blood flow is in the fetal brain and placental vessels. However, in many cases, brain-sparing is detected too late for interventions to be implemented, or not at all. Three-dimensional fractional moving blood volume (3D-FMBV) is a new noninvasive technique that may be able to earlier detect brain-sparing by measuring blood flow in whole fetal organs. If successful, this technique could be used to define normal blood flow ranges in different organs throughout pregnancy, allowing for early detection, intervention, and optimization of fetal outcomes. To do this, it must first be practical to take 3D-FMBV measurements in a single ultrasound consultation (and not be too time intensive) and produce reliable measurements between patients. Our study found that it is practical to measure blood flow in four organs; placenta, fetal liver, kidney, and brain, in a single ultrasound consult, taking a median 10 min and 12 s for scanning and 41 min and 59 s for offline analysis. We were able to calculate 3D-FMBV for all organs scanned. Following our proposed protocol for scanning and analysis, 3D-FMBV measurements can be reliably calculated to a good to excellent degree by the same observer and between observers. [ABSTRACT FROM AUTHOR]

\nIntroduction: The objective of this study was to explore the association between net vertebral artery flow volume (NVAFV), calculated through color duplex ultrasonography, and posterior circulation infarction (PCI) in patients with severe intracranial vertebral artery (VA) stenosis. Methods: 234 patients with severe intracranial VA stenosis (≥70%) were categorized into the PCI group (n = 139) and the non-PCI group (n = 95) based on cranial MRI diagnosis. The correlation between NVAFV and CT perfusion data was analyzed, and the occurrence of PCI under diverse PCI mechanisms was also investigated. Multifactorial logistic regression and stratified analysis was performed to analyze the association between NVAFV and PCI. Lastly, generalized additive models and smooth curve fitting was utilized to outline relationship between NVAFV and PCI. Results: NVAFV showed a significant correlation with cerebral blood flow, mean transmit time, and time to peak. In the large artery atherosclerosis mechanism, a reduction in NVAFV correlated with a gradual rise in PCI cases (p = 0.002), while this trend lacked significance in the branch artery occlusive disease mechanism (p = 0.993). In the fully adjusted model, each 10 mL/min increase in NVAFV reduced PCI incidence by 11% (OR 0.890, 95% CI 0.840–0.943, p < 0.001), Sensitivity analysis showed similar results; NVAFV presented different PCI risks among various glucose level subgroups, the OR (95% CI) for PCI was 0.788 (0.684, 0.906) in low-glucose group (T1), 0.968 (0.878, 1.066) in moderate-glucose group (T2), and 0.886 (0.801, 0.979) in high-glucose group (T3). Smooth curve fitting demonstrated a linear negative association between NVAFV and PCI. Conclusion: NVAFV demonstrated an association with PCI in patients with severe intracranial VA stenosis, it can serve as a reference for identifying high-risk populations of PCI; however, it must be considered in combination with glucose. This study investigates the relationship between vertebral artery (VA) blood flow and posterior circulation infarctions (PCI), which are strokes in the back of the brain. VAs play a crucial role in supplying blood to this area. Using color duplex ultrasonography, we measured blood flow in 234 patients with severe VA narrowing (≥70%). These patients were divided into two groups: those who had experienced PCI and those who had not. We analyzed the correlation between blood flow in the VAs and various brain imaging data to understand the occurrence of PCI under different conditions. The findings showed that lower blood flow through the VAs was significantly associated with a higher risk of PCI, particularly in cases involving large artery atherosclerosis (a type of artery disease). However, this association was not observed in cases of branch artery occlusive disease. A detailed analysis revealed that for every 10 mL/min increase in blood flow, the risk of PCI decreased by 11%. This relationship also varied according to the patients’ blood glucose levels: patients with lower blood glucose levels showed a stronger link between increased blood flow and reduced PCI risk compared to those with moderate or high blood glucose levels. In conclusion, measuring the blood flow in the VAs can help identify patients at high risk of strokes in the back part of the brain. However, it is important to consider this measurement in combination with blood glucose levels to improve the identification of high-risk patients. [ABSTRACT FROM AUTHOR]

Introduction: Acquisition of a deeper understanding of microvascular function across physiological and pathological conditions can be complicated by poor accessibility of the vascular networks and the necessary sophistication or intrusiveness of the equipment needed to acquire meaningful data. Laser Doppler fluximetry (LDF) provides a mechanism wherein investigators can readily acquire large amounts of data with minor inconvenience for the subject. However, beyond fairly basic analyses of erythrocyte perfusion (fluximetry) data within the cutaneous microcirculation (i.e., perfusion at rest and following imposed challenges), a deeper understanding of microvascular perfusion requires a more sophisticated approach that can be challenging for many investigators. Methods: This manuscript provides investigators with clear guidance for data acquisition from human subjects for full analysis of fluximetry data, including levels of perfusion, single- and multiscale Lempel-Ziv complexity (LZC) and sample entropy (SampEn), and wavelet-based analyses for the major physiological components of the signal. Representative data and responses are presented from a recruited cohort of healthy volunteers, and computer codes for full data analysis (MATLAB) are provided to facilitate efforts by interested investigators. Conclusion: It is anticipated that these materials can reduce the challenge to investigators integrating these approaches into their research programs and facilitate translational research in cardiovascular science. [ABSTRACT FROM AUTHOR]

Introduction: Birth-related obstruction of umbilical blood flow may induce hypoxic insults that affect postnatal organ adaptation. Using newborn cesarean-delivered pigs, we hypothesized that cord obstruction during delivery negatively affects physiological transition and gut maturation. Further, we investigated if delayed cord clamping (DCC) improves gut outcomes, including sensitivity to formula-induced necrotizing enterocolitis (NEC)-like lesions. Methods: In experiment 1, preterm (n = 24) and near-term (n = 29) piglets were subjected to umbilical cord obstruction (UCO, 5–7 min in utero), with corresponding pigs delivered without obstruction (CON, n = 17–22). Experiment 2 assessed preterm pigs subjected to delayed cord clamping (n = 30, 60 s) or immediate cord transection with umbilical cord milking (UCM, n = 34). Postnatal vital parameters were recorded, together with a series of gut parameters after 3 days of formula feeding. Results: UCO induced respiratory-metabolic acidosis in near-term pigs at birth (pH 7.16 vs. 7.32, pCO2 12.5 vs. 9.2 kPa, lactate 5.2 vs. 2.5 mmol/L, p < 0.05). In preterm pigs, UCO increased failure of resuscitation and mortality shortly after birth (88 vs. 47%, p < 0.05). UCO did not affect gut permeability, transit time, macromolecule absorption, six digestive enzymes, or sensitivity to NEC-like lesions. In experiment 2, DCC improved neonatal hemodynamics (pH 7.28 vs. 7.20, pCO2 8.9 vs. 9.9 at 2 h, p < 0.05), with no effects on gut parameters. Conclusion: UCO and DCC affect neonatal transition and hemodynamics, but not neonatal gut adaptation or sensitivity to NEC-like lesions. Our findings suggest that the immature newborn gut is highly resilient to transient birth-related changes in cord blood flow. [ABSTRACT FROM AUTHOR]

Introduction: Accumulation of β2-microglobulin (B2M) in dialysis patients contributes to several comorbidities of end-stage kidney disease (ESKD). The LIXELLE® device adsorbs B2M from blood using sorbent bead technology. Studies in Japan showed that LIXELLE treatment during hemodialysis (HD) at blood flow rates up to 250 mL/min removes B2M above HD alone and is well tolerated. We investigated tolerance for LIXELLE treatment during HD at higher HD blood flow rates standard in the USA. Methods: A prospective, open-label, non-randomized, single-arm, early-feasibility study (EFS) assessed tolerance and safety of LIXELLE treatment during HD at blood flow rates up to 450 mL/min. ESKD patients (40–75 years old) on thrice weekly outpatient HD were eligible. After a 1-week HD run-in, patients received LIXELLE plus HD at a blood flow rate of 250 mL/min (1 week), followed by LIXELLE plus HD at a blood flow rate up to 450 mL/min (1 week). These blood flow rates were tested with three LIXELLE column sizes in sequence (treatment = 6 weeks). B2M removal was assessed for each combination. Results: Ten patients with a historic intradialytic hypotension (IDH) rate of 0.42 events/HD session/patient were enrolled. Nine patients completed all combinations without IDH events (treatment IDH rate: 0.56 events/HD session/patient). No treatment-emergent serious adverse events or significant changes in red blood cell, platelet, or complement indices except haptoglobin were reported. B2M reduction ratios and removal of select proteins (<40 kDa) increased with escalating column size and blood flow rate. Conclusion: LIXELLE plus HD across all column sizes was safe and well tolerated at blood flow rates up to 450 mL/min. Extent of B2M removal corresponded to column size-blood flow rate combinations. This EFS provides a risk profile to guide further studies of LIXELLE in ESKD patients at US-standard blood flow rates. [ABSTRACT FROM AUTHOR]

Introduction: Continuous renal replacement therapies (CRRTs) require constant monitoring and periodic treatment readjustments, being applied to highly complex patients, with rapidly changing clinical needs. To promote precision medicine in the field of renal replacement therapy and encourage dynamic prescription, the Acute Dialysis Quality Initiative (ADQI) recommends periodically measuring the solutes extracorporeal clearance with the aim of assessing the current treatment delivery and the gap from the therapeutic prescription (often intended as effluent dose). To perform this procedure, it is therefore necessary to obtain blood and effluent samples from the extracorporeal circuit to measure the concentrations of a target solute (usually represented by urea) in prefilter, postfilter, and effluent lines. However, samples must be collected simultaneously from the extracorporeal circuit ports, with the same suction flow at an unknown rate. Methods: The proposed study takes the first step toward identifying the technical factors that should be considered in determining the optimal suction rate to collect samples from the extracorporeal circuit to measure the extracorporeal clearance for a specific solute. Results: The results obtained identify the low suction rate (i.e., 1 mL/min) as an ideal parameter for an adequate sampling method. Low velocities do not perturb the external circulation system and ensure stability prevailing pressures in the circuit. Higher velocities can be performed only with blood flows above 120 mL/min preferably in conditions of appropriate filtration fraction. Discussion/Conclusions: The specific value of aspiration flow rate must be proportioned to the prescription of CRRT treatments set by the clinician. [ABSTRACT FROM AUTHOR]

Introduction: Microvascular perfusion is essential for post-exercise skeletal muscle recovery to ensure adequate delivery of nutrients and growth factors. This study assessed the relationship between various indices of muscle fiber capillarization and microvascular perfusion assessed by contrast-enhanced ultrasound (CEUS) at rest and during recovery from a bout of resistance exercise in older adults. Methods: Sixteen older adults (72 ± 6 y, 5/11 male/female) participated in an experimental test day during which a muscle biopsy was collected from the vastus lateralis and microvascular perfusion was determined by CEUS at rest and at 10 and 40 min following a bout of resistance exercise. Immunohistochemistry was performed on muscle tissue samples to determine various indices of both mixed and fiber-type-specific muscle fiber capillarization. Results: Microvascular blood volume at t = 10 min was higher compared with rest and t = 40 min (27.2 ± 4.7 vs. 3.9 ± 4.0 and 7.0 ± 4.9 AU, respectively, both p < 0.001). Microvascular blood volume at t = 40 min was higher compared with rest (p < 0.001). No associations were observed between different indices of mixed muscle fiber capillarization and microvascular blood volume at rest and following exercise. A moderate (r = 0.59, p < 0.05) and strong (r = 0.81, p < 0.001) correlation was observed between type II muscle fiber capillary-to-fiber ratio and the microvascular blood volume increase from rest to t = 10 and t = 40 min, respectively. In addition, type II muscle fiber capillary contacts and capillary-to-fiber perimeter exchange index were strongly correlated with the microvascular blood volume increase from rest to t = 40 min (r = 0.66, p < 0.01 and r = 0.64, p < 0.01, respectively). Conclusion: Resistance exercise strongly increases microvascular blood volume for at least 40 min after exercise cessation in older adults. This resistance exercise-induced increase in microvascular blood volume is strongly associated with type II muscle fiber capillarization in older adults. [ABSTRACT FROM AUTHOR]

Background/Aims: Recent studies have indicated that local inflammatory mediators are importantly involved in the regulation of renal function. However, it remains unknown how such local inflammation is triggered intracellularly in the kidney. The present study was designed to characterize the inflammasome centered by Nlrp3 in the kidney and also test the effect of its activation in the renal medulla. Methods and Results: By immunohistochemistry analysis, we found that inflammasome components, Nlrp3, Asc and caspase-1, were ubiquitously distributed in different kidney areas. The caspase-1 activity and IL-1β production were particularly high in the renal outer medulla compared to other kidney regions. Further confocal microscopy and RT-PCR analysis showed that Nlrp3, Asc and caspase-1 were particularly enriched in the thick ascending limb of Henle's loop. In anesthetized mice, medullary infusion of Nlrp3 inflammasome activator, monosodium urate (MSU), induced significant decreases in sodium excretion and medullary blood flow without changes in mean arterial blood pressure and renal cortical blood flow. Caspase-1 inhibitor, Ac-YVAD-CMK and deletion of Nlrp3 or Asc gene abolished MSU-induced decreases in renal sodium excretion and MBF. Conclusion: Our results indicate that renal medullary Nlrp3 inflammasomes represent a new regulatory mechanism of renal MBF and sodium excretion which may not depend on classical inflammatory response. [ABSTRACT FROM AUTHOR]

Introduction: To study the prognostic factors of patients with chest pain and without obstructive coronary artery disease is of great significance for the management of such patients. We assessed whether a high-sensitivity troponin I (hs-TnI) is associated with prognosis in patients with chest pain and without obstructive coronary artery disease. Methods: From 2011 to 2017, 489 consecutively hospitalized patients with chest pain and without significant coronary artery stenosis (<50%) were tested for hs-TnI and underwent stress myocardial contrast echocardiography (MCE). Myocardial blood flow reserve (MBFR) was measured by stress MCE. Patients were followed (median, 41 months) for composite endpoints, including cardiovascular death and non-fatal myocardial infarction. Cox proportional hazards models were performed to determine associations between hs-TnI and the composite endpoints. Results: Among 489 patients with chest pain and without significant coronary artery stenosis, 257 patients (52.6%) had elevated hs-TnI. Compared to patients with normal hs-TnI, patients with elevated hs-TnI were older (p = 0.013) and had a higher prevalence of atrial fibrillation (p = 0.003), higher left ventricular mass index (p = 0.002) and E/e' septal (p < 0.001), and a lower MBFR (p < 0.001). After adjustment, there was still a significant association between hs-TnI and MBFR (odds ratio = 1.145; 95% confidence interval [CI], 1.079–1.214; p < 0.001). Compared with patients with normal hs-TnI, patients with elevated hs-TnI had a greater cumulative event rate (log-rank p = 0.002). Males (hazard ratio [HR], 4.770; 95% CI, 1.175–19.363; p = 0.029) and reduced MBFR (HR, 2.496; 95% CI, 1.446–4.311; p = 0.001) were risk factors associated with composite endpoints in patients with elevated hs-TnI. Conclusions: In patients with chest pain and without obstructive coronary artery disease, elevated hs-TnI is associated with decreased myocardial perfusion by contrast echocardiography as well as a higher incidence of cardiovascular events. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to examine the efficacy of pneumatic compression of the maternal lower extremities in increasing the amniotic fluid index (AFI) in pregnancies complicated by isolated oligohydramnios. Methods: Women with isolated oligohydramnios (AFI <5 cm) at 32–41 weeks of pregnancy were connected to a sequential compression device for 60 min. Prior and after the application, AFI and the pulsatility index (PI) of a number of arteries were measured. Results: The median (interquartile range) maternal age of the 21 women included was 29 years (26.50–32.00), the median parity was 1 (1–2), and the median gestational age at intervention was 37.60 weeks (37.00–39.40). The median AFI increased after the application from 4.00 (3.62–4.50) to 6.08 cm (4.90–7.03) (p < 0.001). The median PI of the fetal renal artery decreased from 2.30 (2.01–2.88) to 2.26 (1.68–2.71) (p = 0.01). The hourly fetal urine production did not increase. Changes were not significant in the PI of the umbilical artery, the middle cerebral artery, and the bilateral uterine arteries. Conclusion: Short-term activation of pneumatic compression on maternal lower extremities could increase the AFI in women with isolated oligohydramnios. [ABSTRACT FROM AUTHOR]

Introduction: The presence of a double aortic arch (DAA) is manifested by compressive symptoms, requiring surgery. DAA cases are classified as either complete or incomplete type. DAA and a right aortic arch with mirror image branching (mRAA) have a similar configuration to the first branch artery. The first branch of the mRAA is the left brachiocephalic artery, which appears to be the same as that of an incomplete DAA due to blood flow interruption. The present retrospective study aimed to evaluate the differences between DAA and mRAA by fetal echocardiography. Methods: This single retrospective cohort study included all patients diagnosed with complete DAA, incomplete DAA, or mRAA at our facility between 2010 and 2022. The patients were diagnosed with complete DAA, incomplete DAA, or mRAA after birth and remaining fetal echocardiograms. The patients were divided into the DAA (complete DAA: n = 4, incomplete DAA: n = 3) and mRAA (n = 4) groups. The following three outcomes were compared: (1) angle between the right aortic arch and first branch (RF angle), (2) ratio of height to width of the region bounded by the aortic arch, first branch of the aortic arch, and descending aorta, and (3) maximum tracheal diameter on a three-vessel trachea view. Results: The incomplete DAA cases were difficult to diagnose via fetal echocardiography. On fetal echocardiography, the RF angle was significantly steeper in the DAA group than in the mRAA group (median 57° [36°–69°] vs. 75° [62°–94°]; p < 0.05). The DAA and RAA groups showed no significant differences in the ratio of height to width of the region bounded by the aortic arch, first branch of the aortic arch, and descending aorta (median 0.57 [0.17–0.68] vs. 0.73 [0.56–1.0]) and maximum tracheal diameter (median 2.5 [1.4–3.3] vs. 3.2 [2.8–3.5] mm). The cut-off value for the presence of DAA was an RF angle <71°. Conclusion: The DAA group (complete and incomplete DAA) had a significantly steeper RF angle than the mRAA group. Therefore, RF angle measurement could improve the fetal diagnosis and postnatal prognosis of DAA. [ABSTRACT FROM AUTHOR]

Background: Cardiovascular diseases remain the leading cause of morbidity and mortality worldwide. Arteriolar tone regulation plays a critical role in maintaining appropriate organ blood flow and perfusion distribution, which is vital for both vascular and overall health. Summary: This scoping review aimed to explore the interplay between five major regulators of arteriolar tone: metabolism (adenosine), adrenergic control (norepinephrine), myogenic activation (intravascular pressure), perivascular oxygen tension, and intraluminal flow rates. Specifically, the aim was to address how arteriolar reactivity changes in the presence of other vasoactive stimuli and by what mechanisms. The review focused on animal studies that investigated the impact of combining two or more of these stimuli on arteriolar diameter. Overall, 848 articles were identified through MEDLINE and EMBASE database searches, and 38 studies were included in the final review. Key Messages: The results indicate that arteriolar reactivity is influenced by multiple factors, including competitive processes, structural limitations, and indirect interactions among stimuli. Additionally, the review identified a lack of research involving female animal models and limited insight into the interaction of molecular signaling pathways, which represent gaps in the literature. [ABSTRACT FROM AUTHOR]

Introduction: There is an ongoing debate whether to perform orchiectomy or orchidopexy following testicular torsion (TT) in cases where the testis seems non-viable. The main problem is lack of objective criteria defining testicular viability. The aim of this study was to investigate the grade of injury in orchiectomy specimens obtained from cases of TT and its association with clinical findings. Methods: This multicenter retrospective study involved double-blinded reassessment of the patient files and the pathological specimens using Mikuz classification to analyze the relation between clinical and pathological findings. Results: A total of 289 patient charts from 14 centers were reviewed and 228 were included in this study. Twenty (8.8%) patients had grade 1 injury which refers to reversible injury. The clinical findings of these 20 patients were compared to 208 patients with higher grades of injury. As expected, there was statistically significant difference regarding duration of symptoms (p < 0.001); however, range was wide in both groups (as long as 96 h for grade 1 and as short as 7 h for higher grades). There was no statistically significant difference in any other variable including age (median 14 for both, p = 0.531), symptoms (pain: 19/20 vs. 189/202, p = 0.801; swelling: 13/19 vs. 168/197, p = 0.094), absence of blood flow in Doppler US (15/19 vs. 164/197, p = 0.635), or degree of torsion (median 720° for both, p = 0.172). Conclusion: Our study revealed necessity for better criteria to define viability of testis following TT. Histopathological injury appeared to be reversible even in some patients with more severe perioperative findings, late admission, or high degree of twisting. Our findings support the tendency for testicular fixation instead of orchiectomy as none of the clinical or perioperative findings could be attributed to high-grade injury. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the correlation between skin blood flow and systemic blood flow and whether skin blood flow can determine the circulatory effects of dopamine and dobutamine on blood flow in very low birth weight (VLBW) infants. Methods: This study was a subanalysis of the PICC-MBF randomized controlled trial. The correlation between skin blood flow and echocardiographic findings was examined. Changes in skin blood flow and blood pressure before and after initiation or dose increase of dopamine and dobutamine were also evaluated. Results: Two hundred and thirty-four participants underwent echocardiography. Skin blood flow was significantly correlated with supra vena cava (SVC) flow (r = 0.31, p < 0.001). Receiver operator characteristic analysis revealed that skin blood flow <17 mL/min effectively detected SVC flow <41 mL/min (area under the curve = 0.83, p < 0.001). Dobutamine significantly increased skin blood flow after initiation or dose increase (p = 0.033) without increasing blood pressure. However, dopamine significantly increased both skin blood flow (p = 0.010) and blood pressure (p < 0.001). Conclusions: Our findings indicated that skin blood flow could be used as a surrogate marker of systemic blood flow in VLBW infants and revealed differences in the effects of dopamine and dobutamine on circulation. [ABSTRACT FROM AUTHOR]

Introduction: Hemoadsorption has emerged as an adjunctive therapy for sepsis, but its impact on antibiotic levels remains poorly defined. We conducted an in vivo experimental study to investigate the removal of vancomycin and gentamicin during hemoadsorption using the HA380 cartridge, a novel styrene-divinylbenzene copolymer cartridge. Methods: Six surgically prepared sheep were administered 2 g of vancomycin and 400 mg of gentamicin over 30 min, followed by a continuous infusion of vancomycin (20 mg/h). Hemoadsorption was implemented with a styrene-divinylbenzene copolymer HA380 cartridge at a blood flow of 120 mL/min. The removal ratio, sorbent-based clearance, and the mass removal rate were calculated for each time point. Results: The mean 10-min vancomycin removal ratio exceeded 90% and declined to 68.0% at 30 min; 52.8% at 60 min, and 28.0% by 4 h. Due to constant plasma flow, clearance varied proportionally with the removal ratio. Over 4 hours, the total mass removal was 556 mg (SD 106.3). For gentamicin, the mean 10-min removal ratio was 96.9% and the final ratio at 4 h remained 53.0%, with clearances changing proportionately. The total mass removal of gentamicin was 138 mg (SD 26.6) over 4 h. The sorbent-based clearance of vancomycin was significantly lower than that of gentamicin (Pgroup < 0.0001). Conclusion: The novel HA380 sorbent cartridge appears safe and achieves significant vancomycin and gentamicin removal over a four-hour period. This information can be used by clinicians to guide their prescription and consider the additional dosing of at least an extra 25–35% amount in patients receiving HA380 hemoadsorption therapy during sepsis. [ABSTRACT FROM AUTHOR]

Introduction: Free jejunal flap (FJF) reconstruction is a standard procedure for pharyngeal and cervical esophageal defects resulting from head and neck cancer resection. However, improvements in patients' quality of life after surgery require a further statistical approach. Methods: An observational, retrospective, multivariate analysis was designed to report the incidence of postoperative complications and their association with clinical factors in 101 patients who underwent total pharyngo-laryngo-esophagectomy and FJF reconstruction for head and neck cancer at a university hospital between January 2007 and December 2020. Results: Postoperative complications were observed in 69% of patients. In the reconstructive site, anastomotic leak, observed in 8% of patients was associated with vascular anastomosis in the external jugular vein system (age-adjusted odds ratio [OR]: 9.05, p = 0.044) and anastomotic stricture, observed in 11% of patients was associated with postoperative radiotherapy (age-adjusted OR: 12.60, p = 0.02). Cervical skin flap necrosis was the most common complication (34%) and was associated with vascular anastomosis on the right cervical side (age- and sex-adjusted OR: 4.00, p = 0.005). Conclusion: Although FJF reconstruction is a useful procedure, 69% of patients suffer a postoperative complication. We suppose that anastomotic leak is related to the low blood flow resistance of the FJF and inadequate drainage of the external jugular venous system, and anastomotic stricture is related to the vulnerability of the intestinal tissue to radiation. Furthermore, we hypothesized that the location of the vascular anastomosis may affect the mesenteric location of the FJF and the dead space in the neck, leading to the development of cervical skin flap necrosis. These data contribute to increasing our knowledge about postoperative complications related to FJF reconstruction. [ABSTRACT FROM AUTHOR]

Introduction: A cerebral vasospasm (CVSP) is a potent vasoconstriction of the cerebral vasculature and the primary cause of morbidity and mortality following a subarachnoid hemorrhage. The middle cerebral artery (MCA) is commonly affected by CVSPs. Concomitant administration of dantrolene and nimodipine synergistically reduces vasospasms in aortic rings from Sprague Dawley rats. To determine if the effects observed in the systemic vasculature extend to the cerebral circulation, we investigated the effect of intravenous administration of dantrolene (2.5 mg/kg) and nimodipine (1 mg/kg and 2 mg/kg) on MCA blood flow velocity (BFV) 7 days after the induction of CVSPs. Methods: Vasospasms were induced by bathing the left common carotid artery with autologous whole blood. Age-matched sham rats were used as controls. BFV, mean arterial pressure (MAP), and heart rate (HR) were measured with a PeriFlux 5000 Laser Doppler System, and a CODA non-invasive blood pressure system, before and after administering the drugs. Morphometric evaluations were also performed to assess vascular alterations. Results: BFV was reduced by 37% with dantrolene alone (n = 6, p ≤ 0.05) and by 27% with 2 mg/kg nimodipine (n = 6, p < 0.05), while it was not affected by 1 mg/kg nimodipine. The combination of 1 mg/kg nimodipine with dantrolene, however, decreased BFV by 35% (from 435.70 ± 21.53 to 284.30 ± 23.13 perfusion units, n = 7, p ≤ 0.05). A similar reduction (31%) was obtained with dantrolene and 2 mg/kg nimodipine (from 536.00 ± 32.61 to 367.80 ± 40.93 perfusion units, n = 6, p ≤ 0.05). Neither MAP nor HR was affected by dantrolene or nimodipine alone. The combination of dantrolene with 2 mg/kg nimodipine, however, decreased MAP and increased HR. Furthermore, 7 days after the induction of vasospasms, lumen area of the left common carotid artery decreased, whereas media thickness and the wall-to-lumen ratio increased when compared to contralateral controls. The latter finding suggests that vascular remodeling was present at this stage. Conclusion: Altogether, our results indicate that 2.5 mg/kg dantrolene significantly reduces BFV in the MCA without altering systemic hemodynamic parameters to a similar extent than the highest dose of nimodipine or the combination of dantrolene and the lowest dose of nimodipine. Therefore, dantrolene may provide a promising alternative to lower the risk, or partially revert, CVSP. [ABSTRACT FROM AUTHOR]

Background: In the elderly, the association of delirium and dementia can cause diagnostic problems because they share the same symptom of confusion. Delirium is often misdiagnosed as dementia and treated inappropriately, ignoring that it could be successfully addressed, which can lead to increased health risks up to death. Summary: Confusion indicates that functional reserve fails to compensate for the action of stressors. The decline in reserve is linked to aging-related changes in blood flow, mitochondria, cerebrospinal fluid, and immune function, as well as the appearance of structural precursors of disease. It is greater in dementia that adds a large burden of pathology, especially degenerative and vascular. Key Messages: Based on their common background linking normal and pathological brain aging, it can be argued that delirium and dementia are always associated to some extent and can aggravate each other. The clinical approach to their association, which currently relies on the preliminary diagnosis of delirium according to ad hoc protocols, could be simplified by taking delirium for granted so that its causative stressors, usually the most common diseases of old age and/or drug abuse, could be addressed immediately. This approach would benefit all demented patients: not only those who are in such a serious condition that they need to be hospitalized due to the risk of death, but also those with clouded delirium. [ABSTRACT FROM AUTHOR]

Introduction: Electrolyte derangements, acidosis, and volume overload remain life-threatening emergencies in people with acute kidney injury in austere environments. A single-lumen alternating micro-batch (SLAMB) dialysis technique was designed to perform renal replacement therapy using a single-lumen access, low-cost disposable bags and tubing, widely available premade fluids, and a dialysis filter. A manual variation (mSLAMB) works without electricity, battery, or a pump. We modeled mSLAMB dialysis and predicted it could achieve adequate small solute clearance, blood flow rates, and ultrafiltration accuracy. Methods: A 25- to 30-kg pediatric patient's blood volume was simulated by a 2-L bag of expired blood and spiked with 5 g of urea initially, then with 1–2 g between experiments. Experiments had 8 cycles totaling prescription volumes of 800–2,400 mL and were conducted with different ratios of hemofiltration fluid to blood volume. Concentrations of urea and potassium, final effluent volumes, and cycle duration were measured at the end of each cycle to determine clearance, ultrafiltration accuracy, and blood flow rates. Results: Each cycle lasted 70–145 s. Experiments achieved a mean urea reduction ratio of 27.4 ± 7.1% and a mean potassium reduction of 23.4 ± 9.3%. The largest urea and potassium reduction percentage occurred with the first cycle. Increased hemofiltration fluid to blood volume ratio did not increase clearance. Mean (+/− standard deviation) blood flow ranged from 79.7 +/− 4.4 mL/min to 90.8 +/− 6.5 mL/min and increased with larger batch volume and height difference between reservoirs. Ultrafiltration accuracy ranged from 0 to 2.4% per cycle. Discussion: mSLAMB dialysis is a simple, manual, cost-effective mode of dialysis capable of providing clearance and accurate ultrafiltration. With further refinement of technique, we believe this can be a potentially lifesaving treatment in austere conditions and low-resource settings. [ABSTRACT FROM AUTHOR]

Introduction: Both tissue Doppler imaging (TDI) and pulsed wave Doppler (PWD) Myocardial Performance Indices (MPIs) have been proposed as tools for functional fetal cardiology. We wished to determine if there was any correlation between TDI-MPI and PWD-MPI. Methods: A cohort of uncomplicated women with morphologically normal singleton fetuses between 22 and 39 weeks of gestation was recruited. A single sonologist acquired Doppler waveforms for evaluation of both left and right TDI-MPI and PWD-MPI. The PWD-MPI values were calculated using a previously published algorithm and the TDI-MPI time intervals were measured manually by a single operator. Results: Achievability and repeatability were high for both modalities. TDI produced significantly lower right MPI values yet significantly higher left MPI values, potentially reflecting their evaluation of physiologically different events, blood flow versus myocardial contraction. Conclusion: This study demonstrates that MPIs measured from PWD and TDI have a weak correlation and cannot be used interchangeably, even with the exclusion of suboptimal TDI-MPI scans from the analysis. Given the lack of correlation between the two methods, the high variation in TDI waveform, and the lack of unified approach to TDI analysis, we feel further research is needed before adoption of this technique. [ABSTRACT FROM AUTHOR]

Background: Persistent müllerian duct syndrome (PMDS) is characterized by the persistence of müllerian duct derivatives in otherwise normally virilized 46,XY males. Biallelic mutations of the anti-müllerian hormone (AMH) and AMH receptor type 2 (AMHR2) genes lead to PMDS type 1 and 2, respectively. Aim: The aims of the study were to report the clinical, hormonal, and genetic findings in a patient with PMDS and discuss surgical strategies to achieve successful orchidopexy. Results: A 4-year-old boy was evaluated after the incidental finding of müllerian derivates during laparoscopy for nonpalpable gonads. Karyotype was 46,XY and laboratory tests revealed normal serum gonadotropin and androgen levels but undetectable serum AMH levels. PMDS was suspected. Molecular analysis revealed a novel variant c.902_929del in exon 5 and a previously reported mutation (c.367C>T) in exon 1 of the AMH gene. Successful orchidopexy was performed in two sequential surgeries in which the müllerian duct structure was preserved and divided to protect the vascular supply to the gonads. Histological evaluation of the testicular biopsy showed mild signs of dysgenesis. Doppler ultrasound showed blood flow in both testes positioned in the scrotum 1.5 years after surgery. Conclusion: PMDS is a rare entity that requires a high index of suspicion (from surgeons) when evaluating a patient with bilateral cryptorchidism. Surgical treatment is challenging and long-term follow-up is essential. Histological evaluation of the testis deserves further investigation. [ABSTRACT FROM AUTHOR]

The diagnosis of chronic mesenteric ischaemia is typically based on angiographic findings along with a classic symptomatology. Only a few methods are available for functional testing to establish the diagnosis, such as indirect measurement of the splanchnic blood flow and hepatic vein oxygenation. The present case is a 76-year-old woman with weight loss and intermittent abdominal pain who was clinically suspected of chronic mesenteric ischaemia based on severe stenosis of the celiac artery and superior mesenteric artery. Measurement of the total splanchnic blood flow and hepatic vein oxygenation, however, showed a normal perfusion after meal stimulation, as well as an increased hepatic vein oxygenation, indicating normal flow reserves. This was likely due to a richly developed Riolan's anastomosis arising from the inferior mesenteric artery. The present case advocates the need for functional testing when diagnosing chronic mesenteric ischaemia. [ABSTRACT FROM AUTHOR]

Background: Hemodialysis is one of the most resources consuming medical intervention. Due to its concept, the proper amount of dialysis fluid passed through dialyzer is crucial to obtain the expected outcomes. The most frequent source of dialysis fluid is production from liquid concentrate (delivered in containers or plastic bags) in dialysis machine. Alternatively, concentrates for dialysis may be produced in dialysis center by dilution in mixing devices dry or semidry premixed compounds connected with system of central dialysis fluid delivery system. Dialysate consumption depends on various factors like type of hemodialysis machine, session duration, prescribed flow, etc. Summary: Modern hemodialysis machines are equipped with the modules which automatically reduce flow rate of dialysis fluid to the patient blood flow and minimize dialysate consumption during preparation and after reinfusion. Smart using of available options offered by manufacturers allows to save additional portion of acid concentrate and water. The weight of concentrates to be delivered to the dialysis center is the major factor influencing the cost (financial and environmental) of transportation from the manufacturer to the final consumer. The crisis on the energy carriers market and extremely high fuel prices made the transportation cost one of the significant costs of the treatment, which must be bear by supplier and finally influence on the price of goods. Key Messages: The careful choice of the concentrate delivery system can improve cost-effectiveness of dialysis. Such solutions implemented in dialysis unit helps make significant savings and decrease the impact on natural environment by carbon footprint reduction. [ABSTRACT FROM AUTHOR]

Introduction: The objective of this study was to investigate the changes in the retina and choroid of children after 650 nm low-level red light therapy (LLRLT). Methods: In this prospective study, 25 subjects in the Shanghai Eye and ENT Hospital of Fudan University were included from August 2021 to September 2021. One eye was randomly selected to receive LLRLT for 3 min. Swept-source optical coherence tomography (OCT) and OCT angiography were used to measure retinal fovea perfusion density (RFPD), retinal fovea thickness (RFT), choroidal fovea blood flow (CFBF), and choroidal fovea thickness (CFT) before LLRLT, 5 min and 1 h after LLRLT. Baseline characteristics between LLRLT and non-LLRLT eyes were compared. Changes in the retinal and choroidal parameters were analyzed by ANCOVA models. SAS software was used for data analysis. The difference was considered statistically significant if p < 0.05. Results: There was no difference in baseline characteristics between LLRLT eyes and non-LLRLT eyes. The RFPD in LLRLT eyes significantly increased 5 min after LLRLT, and the increment was 1.70 ± 0.83% (p = 0.0389). The RFPD significantly decreased from 5 min to 1 h after LLRLT with a mean of −2.62 ± 0.86% decrement (p = 0.0031). The RFPD levels returned to baseline at 1 h after LLRLT (p = 0.8646). However, compared with insignificant RFPD changes in non-LLRLT eyes, there was no significant difference in RFPD changes at any sampling point. No significant changes in RFT, CFBF, and CFT were found in LLRLT eyes at each sampling point. Conclusion: Although 3 min of LLRLT has no effect on the choroid, it may cause a short-term transient increase in RFPD. It will provide theoretical support for the role of LLRLT in myopia control. [ABSTRACT FROM AUTHOR]

Research involving human subjects in ambulatory settings is a critical link in the chain comprising translational research, spanning preclinical research to human subject and patient cohort studies. There are presently a wide array of techniques and approaches available to investigators wishing to study blood flow, perfusion, and vascular structure and function in human subjects. In this multi-sectioned review, we discuss capillaroscopy, carotid intima-media thickness, flow-mediated dilation, laser Doppler flowmetry, near-infrared spectroscopy, peripheral arterial tonometry, pulse wave velocity, retinal fundus imaging, and vascular plethysmography. Each section contains a general overview and the physical basis of the technique followed by a discussion of the procedures involved and the necessary equipment, with attention paid to specific requirements or limitations. Subsequently, we detail which aspects of vascular function can be studied with a given technique, the analytical approach to the collected data, and the appropriate application and limitation(s) to the interpretation of the data collected. Finally, a modified scoping review provides a summary of how each assessment technique has been applied in previous studies. It is anticipated that this review will provide an efficient source of information and insight for preclinical investigators seeking to add translational aspects to their research programs. [ABSTRACT FROM AUTHOR]

Introduction: Omni® (B Braun, Melsungen, Germany) is able to run continuous renal replacement therapy (CRRT) in continuous veno-venous hemofiltration (CVVH), hemodialysis (CVVHD), and hemodiafiltration (CVVHDF) modes. However, to date, there is no validated protocol to guide the use of Omni® in CVVHDF mode with regional citrate anticoagulation (RCA). Methods: We designed a protocol for CVVHDF-RCA tailored for Omni®. This protocol was tested in patients included in an observational study conducted in our center between January and March 2021. For all study patients, we collected baseline characteristics, laboratory results, CRRT circuit lifespan as well as plasma and effluent samples at 12, 24, 48, and 72 h of CRRT circuit initiation. At each study time point, we computed urea, creatinine, and β2-microglobulin clearance as well as effluent/blood ratios. Data from circuits in CVVHDF-RCA mode are compared with those in standard therapy (CVVHD-RCA) with the same device. Results: We analyzed ten circuits (5 patients) in CVVHDF-RCA mode and 32 (13 patients) in CVVHD-RCA mode. No adverse events related to the therapy were observed. In CVVHDF-RCA mode, median circuit running time was 68 (IQR 8.1) hours versus 46 (IQR 9.0) in CVVHD mode, p = 0.053. Therapy adaptations (dialysate rate and/or blood flow) were required in one (10%) circuit (15.6% in CVVHD mode, p = 0.56). Compared to CVVHD, CVVHDF was able to achieve similar clearance and effluent/blood ratio for urea, creatinine, and β2-microglobulin across the entire duration of circuit lifetime. Conclusion: The proposed protocol for CVVHDF-RCA for Omni® was associated with similar circuit lifetime, number of required adaptations and clearances to standard CVVHD-RCA. It appears to be safe and feasible. [ABSTRACT FROM AUTHOR]

Introduction: Expanded hemodialysis (HD using a medium cut-off dialyzer [HD + MCO]) provides comparable or better removal of various uremic toxins, particularly large middle-molecule uremic toxins, than post-dilution online hemodiafiltration (olHDF). Uremic toxin-removing effectiveness between HD + MCO and mixed-dilution olHDF, one of the currently most efficient olHDF modalities, has not been assessed. Method: This randomized controlled trial was conducted in 14 prevalent thrice-a-week HD patients with blood flow rate above 400 mL/min. The patients were randomized into two sequences of 2-week treatment periods of HD + MCO and later mixed-dilution olHDF or vice versa. The reduction ratio (RR) values of small-molecule as well as middle-molecule uremic toxins and protein-bound uremic toxins were measured at baseline and at the end of the treatment. Results: When compared with mixed-dilution olHDF, HD + MCO provided slightly lower β2M RR, but the value was still higher than 75%; showed similar κFLC RR, IS RR, and URR; and yielded significantly higher RR values of α1M (p < 0.001) and λFLC (p < 0.001). Despite higher albumin loss in HD + MCO, the serum albumin levels at the end of the study were comparable between both groups. Conclusion: Expanded HD (HD + MCO) provided similar effectiveness in removing various uremic toxins and could exhibit greater removal of large middle-molecule uremic toxins, such as α1M and λFLC. Expanded HD can be used as an effective alternative option for mixed-dilution olHDF. [ABSTRACT FROM AUTHOR]

The adequacy of hemodialysis is now assessed by measuring the removal of the single-solute urea. The urea clearance provided by contemporary dialysis is a large fraction of the blood flow through the dialyzer and therefore cannot be increased much further. Other solutes however likely contribute more than urea to the residual uremic illness suffered by hemodialysis patients. We here review methods which could be employed to increase the clearance of nonurea solutes. We will separately consider the clearances of free low-molecular-mass solutes, free larger solutes, and protein-bound solutes. New clinical studies will be required to test the extent to which increasing the clearance on nonurea solutes with these various characteristics can improve patients' health. [ABSTRACT FROM AUTHOR]

Introduction: Newborns exposed to sildenafil citrate (SC) in utero have increased rates of persistent pulmonary hypertension. The mechanism behind this has not yet been fully elucidated. We aimed to utilize a combination of clinically relevant MRI techniques to comprehensively characterize the haemodynamics of the fetal sheep whilst under the influence of SC. We hypothesized that these MRI techniques would detect SC-induced increases in pulmonary blood flow and oxygen delivery prior to birth. Methods: At 116–117 days gestational age (term, 150 days), pregnant Merino ewes (n = 9) underwent fetal catheterization surgery. MRI scans were performed during a basal state and then repeated during a constant umbilical vein infusion of SC to measure blood flow and oxygenation within the major vessels of the fetal circulation using phase-contrast-MRI and T2 oximetry. Results: Right and left ventricular cardiac outputs were not different between states. Pulmonary blood flow increased during the SC state resulting in elevated pulmonary oxygen delivery. Right to left heart shunting through the foramen ovale was reduced without reducing cerebral oxygen delivery. Conclusion: SC induces alterations to pulmonary haemodynamics in utero; a characteristic that if maintained may underlie or act as a precursor towards the elevated rates of poor pulmonary outcomes after birth. These MRI techniques are the first to comprehensively characterize sildenafil's direct impact on the pulmonary vasculature and its indirect detriment to the flow of oxygen-rich blood through the foramen ovale. [ABSTRACT FROM AUTHOR]

Proliferative diabetic retinopathy (PDR) is a vision-threatening complication of diabetes. Panretinal photocoagulation (PRP) and anti-vascular endothelial growth factor (anti-VEGF) are approved treatment modalities aimed at regressing neovascularization. Data are lacking about abnormalities in retinal vascular and oxygen metrics before and after combination treatments. A 32-year-old Caucasian male diagnosed with PDR in the right eye was treated by a combination of PRP and multiple anti-VEGF treatments over a 12-month period. The subject underwent optical coherence tomography (OCT) angiography, Doppler OCT, and retinal oximetry before treatment and at 12 months, which was 6 months following the last treatment. Measurements of vascular metrics (vessel density [VD] and mean arterial and venous diameters [DA, DV]) and oxygen metrics (total retinal blood flow [TRBF], inner retinal oxygen delivery [DO2], metabolism [MO2], and extraction fraction [OEF]) were obtained. Both before and after treatments, VD, TRBF, MO2, and DO2 were below the normal lower confidence limits. Additionally, DV and OEF were decreased after treatments. Alterations in retinal vascular and oxygen metrics were reported for the first time in untreated and treated PDR. Future studies are warranted to evaluate the clinical value of these metrics in PDR. [ABSTRACT FROM AUTHOR]

Introduction: Activation of the locus coeruleus-noradrenergic (LC-NA) system during awakening is associated with an increase in plasma corticosterone and cardiovascular tone. These studies evaluate the role of the LC in this corticosterone and cardiovascular response. Methods: Male rats, on day 0, were treated intraperitoneally with either DSP4 (50 mg/kg body weight) (DSP), an LC-NA specific neurotoxin, or normal saline (SAL). On day 10, animals were surgically prepared with jugular vein (hypothalamic-pituitary-adrenal [HPA] axis) or carotid artery (hemodynamics) catheters and experiments performed on day 14. HPA axis activity, diurnally (circadian) and after stress (transient hemorrhage [14 mL/kg body weight] or air puff-startle), and basal and post-hemorrhage hemodynamics were evaluated. On day 16, brain regions from a subset of rats were dissected for norepinephrine and corticotropin-releasing factor (CRF) assay. Results: In DSP rats compared to SAL rats, (1) regional brain norepinephrine was decreased, but there was no change in median eminence or olfactory bulb CRF content; (2) during HPA axis acrophase, the plasma corticosterone response was blunted; (3) after hemorrhage and air puff-startle, the plasma adrenocorticotropic hormone response was attenuated, whereas the corticosterone response was dependent on stressor category; (4) under basal conditions, hemodynamic measures exhibited altered blood flow dynamics and systemic vasodilation; and (5) after hemorrhage, hemodynamics exhibited asynchronous responses. Conclusion: LC-NA modulation of diurnal and stress-induced HPA axis reactivity occurs via distinct neurocircuits. The integrity of the LC-NA system is important to maintain blood flow dynamics. The importance of increases in plasma corticosterone at acrophase to maintain short- and long-term cardiovascular homeostasis is discussed. [ABSTRACT FROM AUTHOR]

Introduction: Persistent hyperplastic primary vitreous (PHPV) involves a spectrum of congenital ocular abnormalities characterized by the presence of a vascular membrane behind the lens. Retinoblastoma is a life-threatening intraocular malignancy that can cause blindness, eye loss, or even death. PHPV and retinoblastoma are extremely rare prenatal diseases. Case Presentation: Here, we present a case of fetal PHPV with retinoblastoma diagnosed using prenatal ultrasound. The unilateral lenses were hyperechoic, and irregular echogenic bands between the lenses and posterior eye walls were observed. In cases where the blood flow signal continues in the band-shaped hyperechoic area, PHPV with retinoblastoma should be suspected. Conclusion: PHPV with retinoblastoma can be prenatally diagnosed. [ABSTRACT FROM AUTHOR]

Background: Critically ill patients with acute respiratory failure frequently present concomitant lung and kidney injury, within a multiorgan failure condition due to local and systemic mediators. To face this issue, extracorporeal carbon dioxide removal (ECCO2R) systems have been integrated into continuous renal replacement therapy (CRRT) platforms to provide a combined organ support, with efficient clearance of CO2 with very low extracorporeal blood flows (<400 mL/min). Objectives: To evaluate efficacy and safety of combined ECCO2R-CRRT support with PrismaLung®-Prismaflex® in patients affected by hypercapnic respiratory acidosis associated with AKI in a second level intensive care unit. Methods: We carried out a retrospective observational study enrolling patients submitted to PrismaLung®-Prismaflex® due to mild to moderate acute respiratory distress syndrome (ARDS) or acute exacerbation of chronic obstructive pulmonary disease (aeCOPD). The primary endpoints were the shift to protective ventilation and extubation of mechanically ventilated patients and the shift to invasive mechanical ventilation of patients receiving noninvasive ventilation (NIV). Clinical-laboratoristic data and operational characteristics of ECCO2R-CRRT were recorded. Results: Overall, 12/17 patients on mechanical ventilation shifted to protective ventilation, CO2 clearance was satisfactorily maintained during the whole observational period, and pH was rapidly corrected. Treatment prevented NIV failure in 4 out of 5 patients. No treatment-related complications were recorded. Conclusion: ECCO2R-CRRT was effective and safe in patients with aeCOPD and ARDS associated with AKI. [ABSTRACT FROM AUTHOR]

Introduction: Hypertension is known to impact the structure and function of the ocular vascular system and is an established risk factor for many eye diseases. This study aimed to detect the blood flow in the optic disc and macula in patients with essential hypertension and to analyze its correlation with serum cystatin C (Cys-C) levels. Methods: This single center, cross-sectional study included 100 patients with primary hypertension without hypertensive retinopathy, who were divided into an experimental group (50 cases, 50 eyes) with elevated serum Cys-C levels and a control group (50 cases, 50 eyes) with normal serum Cys-C. The optic disc and macular vessel density (VD) and vascular perfusion density (PD) were assessed using optical coherence tomography angiography. Data such as the area, perimeter, and circularity of the foveal avascular zone (FAZ) were analyzed. Results: There were statistically significant between-group differences in the VD and PD of the optic disc (p < 0.05). Spearman correlation analysis of related indicators revealed that serum Cys-C was positively correlated with creatinine, uric acid, and FAZ circularity (p < 0.05). Furthermore, serum Cys-C was negatively correlated with optic disc VD and PD in some regions (p < 0.05). Conclusion: In patients with essential hypertension, serum Cys-C is negatively correlated with VD and PD in the inner layer of the optic disc (zone 10). [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to assess the influence of different doses of tadalafil on coronary flow and oxidative stress in isolated rat hearts. Methods: The hearts of male Wistar albino rats (n = 48) were retrogradely perfused according to the Langendorff technique at gradually increased constant perfusion pressure (CPP) (40–120 mm Hg). Coronary flow and oxidative stress markers: nitrite oxide (NO) outflow and superoxide anion production in coronary effluent were measured. The experiments were performed during control conditions and in the presence of tadalafil (10, 20, 50, and 200 nM) alone or with Nω-nitro-L-arginine monomethyl ester (L-NAME) (30 μM). Results: Tadalafil administration significantly increased coronary flow at all CPP values at all administered doses. Tadalafil led to an increase in the NO levels, but a statistically significant NO release increase was found only at the highest dose and highest CPP. Tadalafil did not significantly affect the release of O2−. After inhibiting the nitrite oxide synthase system by L-NAME, tadalafil-induced changes in cardiac flow and NO levels were reversed. L-NAME administration had no pronounced effect on the O2− release. Conclusion: Tadalafil causes changes in the heart vasculature in a dose-dependent manner. It does not lead to a significant increase in the production of superoxide anion radicals. [ABSTRACT FROM AUTHOR]

Background: Microcirculatory alterations have been observed at the early phase of sepsis, although macrocirculation seems preserved. The aim of this study was to analyze the effect of crystalloid fluid therapy on mesenteric microcirculation, assessed by using the confocal laser endomicroscope Cellvizio®, in an endotoxic porcine model. Methods: It is a prospective endotoxic shock (lipopolysaccharide infusion) experimental trial. Piglets were divided into 3 groups: 6 in the sham group (no LPS injection, no fluid), 9 in the control group (LPS infusion, no fluid), and 6 in the crystalloids group (LPS infusion and fluid resuscitation with crystalloids). Fluid resuscitation consisted in a fluid bolus of 20 mL/kg 0.9% saline over 30 min followed by a 10 mL/kg/h fluid rate over 4 h. Mesenteric microcirculation was assessed using a confocal laser endomicroscope (Cellvizio®). Blood flow within capillaries was visually assessed according to the point of care microcirculation (POEM) score. Results: At baseline, the 3 groups were similar regarding hemodynamic, biological, and microcirculatory parameters. At T360, the POEM score significantly decreased in the control and crystalloids groups, whereas it remained unchanged in the sham group (respectively, 1.62 ± 1.06, 1.2 ± 0.45, and 5.0 ± 0, p = 0.011). There was no significant difference in cardiac output at T360 between the sham and crystalloids groups (3.1 ± 0.8 vs. 2.3 ± 0.6, p = 0.132) or between the control and crystalloids groups (2.0 ± 0.6 vs. 2.3 ± 0.6, p = 0.90). Conclusion: There was no significant improvement of microcirculatory alterations after crystalloids resuscitation despite improvement in macrocirculatory parameters in early experimental sepsis. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to study the influence of extracorporeal blood flow rate (BFR) on the accuracy of central venous pressure (CVP) measurement during continuous renal replacement therapy (CRRT). Methods: Eligible patients were randomly divided into 3 groups based on the location of catheters used for their CRRT and CVP measurement. CVP levels measured at increased extracorporeal BFR (from 0 to 300 mL/min) in the normal and reverse positions of inlet and outlet lines connected to the CV catheter (CVC) in the course of the CRRT session were collected. Results: CVP levels measured at different extracorporeal BFRs did not significantly differ between and among the 3 groups. Inversion of inlet and outlet lines connected to the catheters did not affect the accuracy of CVP measurement. BFR had a negative correlation with inflow/access pressure but a positive correlation with outflow/return pressure. Neither inflow pressure nor outflow pressure was correlated with CVP. Conclusions: Extracorporeal BFR has no influence on the accuracy of CVP measurement during CRRT with the net machine balance adjusted to zero regardless of the location of the catheter and the connection method between catheters and CRRT lines. Thus, CRRT does not need to be discontinued to obtain an accurate CVP measurement. [ABSTRACT FROM AUTHOR]

Title: Low blood flow continuous veno-venous haemodialysis (CVVHD) compared with higher blood flow continuous veno-venous haemodiafiltration (CVVHDF): effect on alarm rates, filter life, and azotaemic control. Introduction: Continuous renal replacement therapy (CRRT) can be delivered via convective, diffusive, or mixed approaches. Higher blood flows have been advocated for convective clearance efficiency and promotion of filter life. It is unclear whether a lower blood flow predominantly diffusive approach may benefit filter life and alarm rates. Materials and Methods: Sequential cohort study of 284 patients undergoing 874 CRRT circuits from January 2015 to August 2018 in a single university-associated tertiary referral hospital in Australia. Patients underwent a protocol of either CVVHDF at blood flow 200–250 mL/min or CVVHD at blood flow 100–130 mL/min. Machine and patient data were analysed. Outcomes of azotaemic control, filter life, and warning alarm rates were log transformed and analysed with mixed linear modelling with patient as a random effect. Results: Both groups had similar azotaemic control (effect estimate on log creatinine CVVHD vs. CVVHDF 1.04 [0.87–1.25], p = 0.68) and median filter life (CVVHDF 16.8 [8.4–90.5] h and CVVHD 16.4 [9.4–82.3] h, p = 0.97). However, circuit pressures were less extreme with a narrower distribution during CVVHD. Multivariate analysis showed CVVHD had a reduced risk of warning alarms (incidence risk ratio [IRR] 0.51 [0.38–0.70]) and femoral access placement also had a reduced risk of alarms (IRR 0.55 [0.41–0.73]). Conclusion: Low blood flow CVVHD and femoral vascular access reduce alarms while maintaining azotaemic control and circuit patency thus minimizing bedside clinician workload. [ABSTRACT FROM AUTHOR]

Fetal, perinatal, and neonatal asphyxia are vital health issues for the most vulnerable groups in human beings, including fetuses, newborns, and infants. Severe reduction in oxygen and blood supply to the fetal brain can cause hypoxic-ischemic encephalopathy (HIE), leading to long-term neurological disorders, including mental impairment and cerebral palsy. Such neurological disorders are major healthcare concerns. Therefore, there has been a continuous effort to develop clinically useful diagnostic tools for accurately and quantitatively measuring and monitoring blood and oxygen supply to the fetal and neonatal brain to avoid severe consequences of asphyxia HIE and neonatal encephalopathy. Major diagnostic technologies used for this purpose include fetal heart rate monitoring, fetus scalp blood sampling, ultrasound imaging, magnetic resonance imaging, X-ray computed tomography, and nuclear medicine. In addition, given the limitations and shortcomings of traditional diagnostic methods, emerging technologies such as near-infrared spectroscopy and photoacoustic imaging have also been introduced as stand-alone or complementary solutions to address this critical gap in fetal and neonatal care. This review provides a thorough overview of the traditional and emerging technologies for monitoring fetal and neonatal brain oxygenation status and describes their clinical utility, performance, advantages, and disadvantages. [ABSTRACT FROM AUTHOR]

Introduction: To investigate the relationship between retinal blood flow and the presence or absence of macular edema (ME) recurrence after intravitreal ranibizumab injection (IRI) in patients with central retinal vein occlusion (CRVO). Methods: We reviewed the medical records of 16 eyes with ME associated with CRVO. All eyes had received pro re nata IRI. Repeat IRI was performed if the central macular thickness was ≥300 µm. At 12 months, patients without additional IRI in the past 6 months were assigned to the resolved group, and those with additional IRI, to the recurrence group. We used laser speckle flowgraphy (LSFG) to measure the mean blur rate (MBR) of the optic disc before and after IRI. Results: Ten of the 16 eyes were assigned to the resolved group, and the other 6 eyes to the recurrence group. At several visits in the 12 months after IRI, MBR was significantly higher in the resolved group than in the recurrence group. Percent change of MBR (%Δ MBR) from baseline was significantly higher in the resolved group than in the recurrence group at 1 month (initial %Δ MBR) and 11 and 12 months. Multivariate stepwise analysis showed that the initial %Δ MBR was significantly and negatively correlated with the number of IRIs. Discussion/Conclusion: These findings suggest that determining %Δ MBR in LSFG may be a useful way to determine the likelihood of ME recurrence in CRVO patients. [ABSTRACT FROM AUTHOR]

Monotremes diverged from therian mammal ancestors approximately 184 million years ago and have a number of novel reproductive characteristics. One in particular is their penile morphology. There are differences between echidna and platypus phalluses, but both are somewhat similar in structure to the reptilian phallus. The echidna penis consists of 4 rosette glans, each of which contains a termination of the quadrifurcate urethra, but it appears that only 2 of the 4 glans become erect at any one time. Despite this, only a few historical references describe the structure of the echidna penis and none provides an explanation for the mechanisms of unilateral ejaculation. This study confirmed that the echidna penis contains many of the same overall structures and morphology as other mammalian penises and a number of features homologous with reptiles. The corpus cavernosum is well supplied with blood, extends up to the base of the glans penis and is primarily responsible for erection. However, the echidna possesses 2 distinct corpora spongiosa separated by a septum, each of which surround the urethra only distal to the initial urethral bifurcation in the glans penis. Together with the bifurcation of the main penile artery, this provides a mechanism by which blood flow could be directed to only one corpus spongiosum at a time to maintain an open urethra that supplies 2 of the 4 glans to facilitate unilateral ejaculation. [ABSTRACT FROM AUTHOR]

Introduction: In Doppler flow diagnosis of a large placental chorioangioma with vascularization, there may be fetal consequences as cardiac output failure and polyhydramnios. Prenatal percutaneous fetoscopic laser photocoagulation of chorioangioma is a therapeutic option. First, we present 2 cases of chorioangioma treated by fetoscopic laser photocoagulation. Second, we conducted a narrative review to identify all reported cases of chorioangioma treated by fetoscopic laser photocoagulation. Case Presentation: Case 1 presented a chorioangioma measuring 48 × 36 × 42 mm, and the Doppler flow study showed vascularization with a high flow rate. The fetus showed dilatation of the right cardiac chambers, moderate tricuspid insufficiency, normal Doppler indices, and polyhydramnios. Case 2 presented a chorioangioma measuring 58 × 36 × 31 mm associated with polyhydramnios and elevated peak systolic velocity of the middle cerebral artery at 49 cm/s, that is, 1.65 MoM. The procedure was performed at 22+2 and 23+5 WG for both cases. Photocoagulation of the chorioangioma vessels was performed first on the small superficial vessels (capillaries) and then on the feeding vessels (artery first and then vein), until complete cessation of blood flow on ultrasound. Successful devascularization was achieved when flow within the chorioangioma's feeding vessels was no longer visualized on intraoperative ultrasound examination using Doppler flow. The ultrasound follow-up showed complete cessation of blood flow in the chorioangioma, normalization of fetal signs, and normal fetal growth in both cases. In case 1, a 2,350-g boy was delivered vaginally after spontaneous labor at 33+6 WG. In case 2, a 2,700-g boy was delivered vaginally after spontaneous labor at 39+2 WG. Neonatal findings were normal, and the outcome at 1 year was normal for both children. Conclusion: Prenatal percutaneous fetoscopic laser photocoagulation improves survival in large chorioangioma, despite a risk of fetal death in utero. [ABSTRACT FROM AUTHOR]

We report a case of binocular retinitis pigmentosa (RP) with completely different visual acuity between 2 eyes, which may be contributed by the presence of cilioretinal arteries (CRAs) in 1 eye. A 66-year-old female patient complained of blurred vision after binocular cataract surgeries. Examinations revealed her right eye had 20/25 central visual acuity, but the fellow eye only had light perception. Subsequent fundus photography of both eyes firmed the diagnosis of binocular RP. However, there were some significant differences in retinal vessels, which were attenuated in her left eye in contrast to several spared retinal arterioles in the right eye. Optical coherence tomography angiography showed that the spared vessels might be CRAs. Our case provides an evidence that macular blood flow may contribute to the survival of cone cells in RP. [ABSTRACT FROM AUTHOR]

Background: Chronic mental stress is recognized as a modifiable risk factor for cardiovascular disease. The aim of this study was to demonstrate that noise annoyance-induced stress is associated with changes in renal hemodynamics. Methods: Renal hemodynamic parameters were measured using steady-state input clearance with infusion of para-aminohippuric acid and inulin in individuals with normal, high normal, and elevated blood pressure. All individuals ranked subjective annoyance due to noise in everyday life on a 7-grade Likert scale. The median of all rankings was used as a cutoff point to divide the group into noise-annoyed and non-noise-annoyed individuals. Different renal hemodynamic parameters were calculated based on the Gomez equation. Results: Noise-annoyed individuals (n = 58) showed lower renal plasma flow (599 ± 106 vs. 663 ± 124 mL/min, p = 0.009), lower renal blood flow (1,068 ± 203 vs. 1,172 ± 225 mL/min, p = 0.047), higher filtration fraction (22.7 ± 3.3 vs. 21.3 ± 3.0, p = 0.012), higher renal vascular resistance (88.9 ± 25.6 vs. 75.8 ± 22.9 mm Hg/[mL/min], p = 0.002), and higher resistance of afferent arteriole (2,439.5 ± 1,253.4 vs. 1,849.9 ± 1,242.0 dyn s−1 cm−5, p = 0.001) compared to non-noise-annoyed individuals (n = 55). There was no difference in measured glomerular filtration rate (133 ± 11.8 vs. 138 ± 15 mL/min, p = 0.181), resistance of efferent arteriole (2,419.4 ± 472.2 vs. 2,245.8 ± 370.3 dyn s−1 cm−5, p = 0.060), and intraglomerular pressure (64.0 ± 3.1 vs. 64.6 ± 3.5 mm Hg, p = 0.298) between the groups. After adjusting for age, renal plasma flow, renal blood flow, and renal vascular resistance remained significantly different between the groups, with a trend in increased afferent arteriolar resistance and filtration fraction. Conclusion: In this study, noise annoyance was associated with reduced renal perfusion attributed to increased renal vascular resistance predominantly at the afferent site. Long-term consequences of this renal hemodynamic pattern due to noise annoyance need to be investigated. [ABSTRACT FROM AUTHOR]

Objective: To study the hemodynamic response to lower leg heating intervention (LLHI) inside the abdominal and iliac arterial segments (AIAS) of young sedentary individuals. Methods: A Doppler measurement of blood flow was conducted for 5 young sedentary adults with LLHI. Heating durations of 0, 20, and 40 min were considered. A lumped parameter model (LPM) was used to ascertain the hemodynamic mechanism. The hemodynamics were determined via numerical approaches. Results: Ultrasonography revealed that the blood flow waveform shifted upwards under LLHI; in particular, the mean flow increased significantly (p < 0.05) with increasing heating duration. The LPM showed that its mechanism depends on the reduction in afterload resistance, not on the inertia of blood flow and arterial compliance. The time-averaged wall shear stress, time-averaged production rate of nitric oxide, and helicity in the external iliac arteries increased more significantly than in other segments as the heating duration increased, while the oscillation shear index (OSI) and relative residence time (RRT) in the AIAS declined with increasing heating duration. There was a more obvious helicity response in the bilateral external iliac arteries than the OSI and RRT responses. Conclusion: LLHI can effectively induce a positive hemodynamic environment in the AIAS of young sedentary individuals. [ABSTRACT FROM AUTHOR]

Left atrial appendage (LAA) closure has recently been approved as an alternative management for stroke prevention in patients with chronic atrial fibrillation who have difficulties with long-term oral anticoagulation. The various shapes and sizes of LAA and orientation of the atrial ostium may contribute to the incomplete LAA closure from circular design devices and orientation of the non-steerable delivery catheter. Incomplete closure of LAA leads to a high-velocity blood flow through the peri-device gap, resulting in peri-device leak (PDL). Residual leaks are frequently diagnosed after LAA closure procedures, regardless of closure methods. There is a controversy in the clinical significance of the leaks, particularly about its association with thromboembolic events. PDL <5 mm was not associated with any increase of risk for thromboembolism. Current literatures with small study population have not been sufficient to clarify the role of the leaks after LAA closure. Nevertheless, management of severe leaks has been a challenging concern for cardiologists. Leaks after epicardial LAA closures are at the neck of the incompletely closed LAA and have shown to increase the risk of thromboembolism. Percutaneous closure of the leaks after LAA closure has been attempted with good safety and success, but long-term safety and efficacy remains unclear. Further large long-term studies which aim to assess the role of leaks or PDLs in predicting thromboembolic events and management strategies are warranted. [ABSTRACT FROM AUTHOR]

This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH. [ABSTRACT FROM AUTHOR]

Introduction: Our previous study indicated that coronary collateral microcirculation reserve (CCMR), native collaterals, transports blood flow to an ischemic area to reduce ischemic tissue injury. This study aimed to observe the changes of CCMR in the hearts of different month-old rats. Methods: We selected 2-, 8-, 16-, and 24-month-old rats as the research objects to monitor the changes of CCMR in rats with aging. After acute myocardial infarction, lectin-FITC was injected into the femoral vein vessels of rats to mark CCMR vessels in the ischemic area. Results: Results of the lectin-FITC perfusion experiment indicated that the number and collagen IV coverage of CCMR vessels declined with aging. Moreover, data suggested a correlation between endothelial nitric oxide synthase and a decline in the number of CCMR vessels. Conclusion: Aging causes CCMR decline in rats. [ABSTRACT FROM AUTHOR]

In anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, progressive cerebellar atrophy potentially leads to severe sequelae. We encountered a patient with anti-NMDAR antibody encephalitis who showed a decrease of blood flow in the cerebellum. A 15-year-old girl presented with consciousness disturbance. Influenza encephalopathy was suspected, and she was treated with glucocorticoid pulse therapy, high-dose intravenous immunoglobulins, and plasma exchange sequentially. She subsequently underwent left oophorectomy due to the presence of anti-NMDAR antibodies and a left ovarian teratoma. In spite of the surgery, her neuropsychiatric symptoms persisted, and she recovered slowly after the introduction of oral methotrexate (MTX). Sequential cerebral blood flow monitoring with single-photon emission computed tomography showed marked cerebellar hypoperfusion. Although mild impairments including working memory and verbal fluency persisted, she eventually returned to high school 3 years after onset. Profound cerebellar hypoperfusion including lobules VI and VII may be the reason for her working memory impairment and speaking problems. Oral MTX may be a promising alternative treatment for some refractory cases of anti-NMDAR encephalitis. [ABSTRACT FROM AUTHOR]