Impaired Blood Flow Research Articles

Impact of Surgical Revascularization on Regression of Enlarged Perivascular Spaces in Adult Moyamoya Disease.

Previous studies have suggested that enlarged perivascular spaces (EPVSs) are potential radiological markers of cerebral ischemia in moyamoya disease (MMD). However, serial changes in EPVSs after surgical revascularization have not yet been clarified. We aimed to elucidate the postoperative changes in EPVSs in adult patients with MMD, clinical and radiological factors affecting the number of EPVSs, and the degree of postoperative changes. We counted the EPVSs in the centrum semiovale in each hemisphere on a T2-weighted MRI performed before surgery. EPVSs were quantified 3months and 2years after combined bypass surgery in surgically treated patients and compared with the number of EPVSs before surgery. We performed multivariate logistic regression analysis to identify the clinical and radiological factors associated with the number of EPVSs. This study included 120 hemispheres of 65 adults with MMD. Older age (P < 0.01), posterior cerebral artery (PCA) involvement (P < 0.01), and cerebral blood flow (CBF) impairment (P = 0.02) were significantly associated with a large number of EPVSs. The number of EPVSs markedly decreased at 3months and 2years after surgery compared with that before surgery (P < 0.01). PCA involvement (P = 0.04) and CBF impairment (P = 0.02) were independent predictors of the regression of EPVSs after surgery. The number of EPVSs in the centrum semiovale was closely associated with age, PCA involvement, and CBF impairment in adult patients with MMD, which remarkably regressed after surgical revascularization, especially in the hemispheres with PCA involvement and CBF impairment. EPVSs are reversible radiological markers reflecting impaired cerebral hemodynamics in adult patients with MMD.

Blood Flow of the Infraspinatus Muscle in Individuals With and Without Shoulder Pain and Myofascial Trigger Points: A Color Doppler Ultrasound and Reliability Study.

Myofascial trigger points (MTrPs) are potential contributors to shoulder pain and can lead to local ischemia and hypoxia, thus causing pain. Color Doppler ultrasound (US) has been used to examine the vascular environment around MTrPs, but has not been used to examine blood flow impairments in patients with shoulder pain and MTrPs. The reliability of color Doppler US for measuring infraspinatus muscle blood flow also has not been established. This study aimed to investigate differences in blood flow between individuals with and without shoulder pain and the reliability of Doppler US for measuring infraspinatus muscle blood flow. Forty participants were enrolled, 20 with shoulder pain and MTrPs and 20 without. Color Doppler US examination was performed twice on each participant to measure peak systolic velocity (PSV), end-diastolic velocity (EDV), resistive index (RI), and pulsatile index (PI) of the infraspinatus muscle. The symptomatic participants had significantly higher PSV (ie, impaired blood flow) than the asymptomatic participants. There were no significant between-group differences in EDV, RI, and PI. The results also demonstrated good-to-excellent intra-rater reliability for color Doppler US measurements of PSV, EDV, RI, and PI for both groups. This study demonstrated differences in blood flow near MTrPs in the infraspinatus muscle between individuals with and without shoulder pain. It also established good-to-excellent reliability of color Doppler US in measuring infraspinatus muscle blood flow. These findings suggest color Doppler US is a useful tool to identify vascular impairments for shoulder pain associated with MTrPs.

Does cognitive function affect functional capacity and perceived fatigue severity after exercise in patients with coronary artery disease?

Successful execution of exercise-based cardiac rehabilitation programs, an important branch of physiotherapy in individuals with coronary artery disease (CAD), depends on adequate cognitive abilities. It has been identified that coronary microvascular dysfunction, marked by reduced coronary flow reserve, is associated with impaired cerebral blood flow, affecting haemodynamic and cognitive performance. This study aimed to investigate how cognitive function influences functional capacity and differences in fatigue perception in CAD patients. Fifty CAD patients, with an average age of 59.40±6.58years, were evaluated for comorbidities (Charlson comorbidity index), number of CAD risk factors (hypertension, diabetes mellitus, dyslipidaemia, smoking, and physical inactivity), cognitive performance (Montreal cognitive assessment scale [MoCA]), functional capacity (incremental shuttle walk test [ISWT]), exercise-induced fatigue (Modified Bourg Scale), and physical activity (PA) levels (international physical activity questionnaire-short form). Analyses focused on the links between MoCA scores and CRF, ISWT outcomes, and differences in fatigue perception. Findings revealed a strong positive link between MoCA scores and ISWT performance (r=0.83, p<0.001), and a strong inverse relationship between CRF and MoCA scores (r=-0.95, p<0.001). In addition, MoCA score was positively correlated with differences in fatigue perception (r=0.88, p<0.001). These results highlight the critical role of cognitive function in determining functional capacity and managing fatigue in CAD patients. They also suggest that cognitive interventions may be a potential adjunctive approach in physiotherapy programmes.

Hypoxia Pathways in Parkinson’s Disease: From Pathogenesis to Therapeutic Targets

The human brain is highly dependent on oxygen, utilizing approximately 20% of the body’s oxygen at rest. Oxygen deprivation to the brain can lead to loss of consciousness within seconds and death within minutes. Recent studies have identified regions of the brain with spontaneous episodic hypoxia, referred to as “hypoxic pockets”. Hypoxia can also result from impaired blood flow due to conditions such as heart disease, blood clots, stroke, or hemorrhage, as well as from reduced oxygen intake or excessive oxygen consumption caused by factors like low ambient oxygen, pulmonary diseases, infections, inflammation, and cancer. Severe hypoxia in the brain can manifest symptoms similar to Parkinson’s disease (PD), including cerebral edema, mood disturbances, and cognitive impairments. Additionally, the development of PD appears to be closely associated with hypoxia and hypoxic pathways. This review seeks to investigate the molecular interactions between hypoxia and PD, emphasizing the pathological role of hypoxic pathways in PD and exploring their potential as therapeutic targets.

Identification and validation of endoplasmic reticulum stress-related genes in patients with steroid-induced osteonecrosis of the femoral head

Steroid-induced osteonecrosis of the femoral head (SONFH) is a debilitating condition caused by long-term corticosteroid use, leading to impaired blood flow and bone cell death. The disruption of cellular processes and promotion of apoptosis by endoplasmic reticulum stress (ERS) is implicated in the pathogenesis of SONFH. We identified ERS-associated genes in SONFH and investigated their potential as therapeutic targets. We analysed the GSE123568 GEO dataset to identify differentially expressed genes (DEGs) related to ERS in SONFH. We conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, identified hub genes by protein-protein interaction (PPI) analyses, and evaluated their functions by gene set enrichment analysis (GSEA). We constructed mRNA–miRNA networks, identified potential therapeutics, and assessed immune cell infiltration. We performed cross-validation using the GEO dataset GSE74089, qRT-PCR on clinical samples from patients with SONFH and controls, and a receiver operating characteristic (ROC) curve analysis to assess the diagnostic performance of the hub genes. We identified 195 ERS-related genes in SONFH, which were primarily involved in oxidative stress, immune responses, and metabolic pathways. The PPI network suggested CXCL8, STAT3, IL1B, TLR4, PTGS2, TLR2, CASP1, CYBB, CAT, and HOMX1 to be key hub genes, which were shown by GSEA to be involved in biological pathways related to metabolism, immune modulation, and cellular integrity. We also identified 261 microRNAs (miRNAs) as well as drugs such as dibenziodolium and N-acetyl-L-cysteine that modulated inflammatory responses in SONFH. Twenty-two immune cell subtypes showed significant correlations, such as a positive correlation between activated mast cells and Tregs, and patients with SONFH had fewer dendritic cells than controls. The hub genes CYBB and TLR4 showed significant correlations with M1 macrophages and CD8 T cells, respectively. Cross-validation and qRT-PCR confirmed the upregulation of STAT3, IL1B, TLR2, and CASP1 in patients with SONFH, validating the bioinformatics findings. An ROC curve analysis confirmed the diagnostic potential of the hub genes. The top 10 hub genes show promise as ERS-related diagnostic biomarkers for SONFH. We discovered that 261 miRNAs, including hsa-miR-23, influence these genes and identified potential therapeutics such as dibenziodolium and simvastatin. Immune profiling indicated altered immune functions in SONFH, with significant correlations among immune cell types. Validation confirmed the upregulation of STAT3, IL1B, TLR2 and CASP1, which had diagnostic potential. The findings suggest potential diagnostic markers and therapeutic targets for SONFH.

Effective management of chronic intestinal pseudo-obstruction in MELAS using acotiamide: A case report

Background: Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is reported to be a secondary cause of chronic intestinal pseudo-obstruction (CIPO). Although few case reports have described CIPO in MELAS, effective treatment for CIPO has not been established. Here, we present a case report of amelioration of CIPO symptoms using acotiamide in a patient with MELAS. Case Presentation: A 51-year-old Japanese female with a mitochondrial disorder with m.3243A&amp;gt;G mutation and a history of anorexia for two years presented to our hospital with a left temporal headache and acute paraphasia. A stroke-like episode of MELAS was suspected, and combined therapy with arginine, edaravone, and levetiracetam was initiated. Although her symptoms improved, she presented with nausea and vomiting and abdominal distension six days following admission. Abdominal contrast-enhanced computed tomography revealed dilatation from the stomach to the intestine, particularly marked the stomach, with neither obstruction nor impaired blood flow in the intestine. CIPO exacerbation with MELAS was suspected, and the patient’s symptoms gradually improved with acotiamide. Conclusion: Patients with MELAS could possibly experience stroke-like episodes during CIPO. Since acetylcholine possibly plays an important role in the pathophysiology of CIPO and acotiamide possesses prokinetic activity by inhibiting acetylcholinesterase, acotiamide could possibly improve CIPO symptoms.

Cardiomyopathies – genetic and molecular issues

Abstract Cardiomyopathy is a condition that may have a genetic basis. It is a serious ailment because it affects almost half of the individuals who die suddenly in childhood, adolescence, or related to heart transplant procedures. The inheritance patterns of this disease can vary. For example, as described in the work on HCM and ARVC, they are inherited in an autosomal dominant manner. De novo mutations may involve genes related to myofilaments, Z-discs, components related to cellular calcium handling, or desmosomes, among others. However, detailed molecular aspects should be correlated with clinical features because changes within a single gene may be associated with diverse abnormalities. Depending on the manifestation of the action of certain allele changes, they may range from microscopic deviations to causing heart failure and impaired blood flow through other organs, thereby disrupting the functionality of the entire body, hindering daily life and lowering its quality. Currently, the analysis of the degree of interaction of genetic determinants in cardiomyopathy is becoming increasingly accessible due to modernization and improvement of tools in the field of diagnosing anomalies in gene sequences and expression. A more precise understanding of causative mutations and associated conditions may contribute to determining strategic points for the future regarding the most beneficial course of action in specific circumstances and evaluating the effectiveness of the steps taken in the long run. In addition to mutations typically causing cardiomyopathy, there are also mutations contributing to their development within the spectrum of other diseases. This includes the PRKAG2-related cardiac syndrome, associated with abnormal metabolism, Danon disease, mitochondrial disorders, ion channelopathies, or conduction disorders.

Short- and long-term outcomes of antegrade versus retrograde approaches in patients undergoing percutaneous coronary intervention for chronic total occlusion: A meta-analysis

BackgroundChronic Total Occlusion (CTO) involves severe coronary artery blockage that impairs blood flow and affects 15–20 % of patients undergoing coronary angiography and over 40 % with diabetes or heart failure. Percutaneous Coronary Intervention (PCI) is used to restore blood flow in such cases. The retrograde approach, developed due to lower success with the antegrade method in complex cases, improves outcomes but increases complications. This meta-analysis compares the efficacy and safety of both approaches to guide clinical practice. MethodsA comprehensive literature search was conducted on PubMed, Embase, Google Scholar, and Scopus until June 5, 2024, to find studies comparing antegrade and retrograde approaches in CTO-PCI patients. Pooled risk ratios (RR) with 95 % confidence intervals (CI) were calculated using R software (version 4.4.1), with significance set at p < 0.05. Random-effects models were used for all analyses. ResultsOur analysis included 22 observational studies with 49,152 CTO-PCI patients: 35,844 in the antegrade arm and 13,308 in the retrograde arm. The antegrade approach showed significantly lower risks of in-hospital outcomes, including mortality [RR: 0.45; p < 0.001], myocardial infarction [RR: 0.37; p < 0.001], major adverse cardiovascular events [RR: 0.34; p < 0.001], and cerebrovascular events [RR: 0.50; p = 0.011]. Long-term outcomes, such as all-cause mortality [RR: 0.71; p = 0.157] and myocardial infarction [RR: 0.76; p = 0.438], were comparable between both approaches. ConclusionThe antegrade technique shows better outcomes and procedural advantages over retrograde revascularization, though long-term outcomes are similar. Further studies, especially randomized controlled trials are needed to confirm these findings.

Zibotentan in Microvascular Angina: A Randomized, Placebo-Controlled, Crossover Trial.

Background: Microvascular angina is associated with dysregulation of the endothelin system and impairments in myocardial blood flow, exercise capacity, and health-related quality of life. The G allele of the noncoding single nucleotide polymorphism RS9349379 enhances expression of the endothelin-1 gene (EDN1) in human vascular cells, potentially increasing circulating concentrations of Endothelin-1 (ET-1). Whether zibotentan, an oral ET-A receptor selective antagonist, is efficacious and safe for the treatment of microvascular angina is unknown. Methods: Patients with microvascular angina were enrolled in this double-blind, placebo-controlled, sequential crossover trial of zibotentan (10 mg daily for 12 weeks). The trial population was enriched to ensure a G allele frequency of 50% for the RS9349379 single nucleotide polymorphism. Participants and investigators were blinded to genotype. The primary outcome was treadmill exercise duration (seconds) using the Bruce protocol. The primary analysis estimated the mean within-participant difference in exercise duration after treatment with zibotentan versus placebo. Results: A total of 118 participants (mean ±SD; years of age 63.5 [9.2 ]; 71 [60.2% ] females; 25 [21.2% ] with diabetes) were randomized. Among 103 participants with complete data, the mean exercise duration with zibotentan treatment compared with placebo was not different (between-treatment difference, -4.26 seconds [95 ] CI, -19.60 to 11.06] P=0.5871). Secondary outcomes showed no improvement with zibotentan. Zibotentan reduced blood pressure and increased plasma concentrations of ET-1. Adverse events were more common with zibotentan (60.2%) compared with placebo (14.4%; P<0.001). Conclusions: Among patients with microvascular angina, short-term treatment with a relatively high dose (10 mg daily) of zibotentan was not beneficial. Target-related adverse effects were common.

Real-time fMRI neurofeedback of the anterior insula using arterial spin labelling.

Arterial spin labelling (ASL) is the only non-invasive technique that allows absolute quantification of perfusion and is increasingly used in brain activation studies. Contrary to the blood oxygen level-dependent (BOLD) effect ASL measures the cerebral blood flow (CBF) directly. However, the ASL signal has a lower signal-to-noise ratio (SNR), than the BOLD signal, which constrains its utilization in neurofeedback studies. If successful, ASL neurofeedback can be used to aid in the rehabilitation of health conditions with impaired blood flow, for example, stroke. We provide the first ASL-based neurofeedback study incorporating a double-blind, sham-controlled design. A pseudo-continuous ASL (pCASL) approach with background suppression and 3D GRASE readout was combined with a real-time post-processing pipeline. The real-time pipeline allows to monitor the ASL signal and provides real-time feedback on the neural activity to the subject. In total 41 healthy adults (19-56 years) divided into three groups underwent a neurofeedback-based emotion imagery training of the left anterior insula. Two groups differing only in the explicitness level of instruction received real training and a third group received sham feedback. Only those participants receiving real feedback with explicit instruction showed significantly higher absolute CBF values in the trained region during neurofeedback than participants receiving sham feedback. However, responder analyses of percent signal change values show no differences in activation between the three groups. Persisting limitations, such as the lower SNR, confounding effects of arterial transit time and partial volume effects still impact negatively the implementation of ASL neurofeedback.

Monitoring of Cerebral Blood Flow Autoregulation after Cardiac Arrest.

Background: Cardiac arrest remains one of the leading causes of death. After successful resuscitation of patients in cardiac arrest, post-cardiac arrest syndrome develops, part of it being an impaired cerebral blood flow autoregulation. Monitoring cerebral blood flow autoregulation after cardiac arrest is important for optimizing patient care and prognosticating patients' survival, yet remains a challenge. There are still gaps in clinical implications and everyday use. In this article, we present a systematic review of studies with different methods of monitoring cerebral blood flow autoregulation after non-traumatic cardiac arrest. Methods: A comprehensive literature search was performed from 1 June 2024 to 27 June 2024 by using multiple databases: PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were studies with an included description of the measurement of cerebral blood flow autoregulation in adult patients after non-traumatic cardiac arrest. Results: A total of 16 studies met inclusion criteria. Our data show that the most used methods in the reviewed studies were near-infrared spectroscopy and transcranial Doppler. The most used mathematical methods for calculating cerebral autoregulation were cerebral oximetry index, tissue oxygenation reactivity index, and mean flow index. Conclusions: The use of various monitoring and mathematical methods for calculating cerebral blood flow autoregulation poses a challenge for standardization, validation, and daily use in clinical practice. In the future studies, focus should be considered on clinical validation and transitioning autoregulation monitoring techniques to everyday clinical practice, which could improve the survival outcomes of patients after cardiac arrest.

Decoding Pulmonary Embolism: Pathophysiology, Diagnosis, and Treatment.

Pulmonary Embolism (PE) is a life-threatening condition initiated by the presence of blood clots in the pulmonary arteries, leading to severe morbidity and mortality. Underlying mechanisms involve endothelial dysfunction, including impaired blood flow regulation, a pro-thrombotic state, inflammation, heightened oxidative stress, and altered vascular remodeling. These mechanisms contribute to vascular diseases stemming from PE, such as recurrent thromboembolism, chronic thromboembolic pulmonary hypertension, post-thrombotic syndrome, right heart failure, and cardiogenic shock. Detailing key risk factors and utilizing hemodynamic stability-based categorization, the review aims for precise risk stratification by applying established diagnostic tools and scoring systems. This article explores both conventional and emerging biomarkers as potential diagnostic tools. Additionally, by synthesizing existing knowledge, it provides a comprehensive outlook of the current enhanced PE management and preventive strategies. The conclusion underscores the need for future research to improve diagnostic accuracy and therapeutic effectiveness in PE.

Injectable, reversibly thermoresponsive captopril-laden hydrogel for the local treatment of sensory loss in diabetic neuropathy

A major and irreversible complication of diabetes is diabetic peripheral neuropathy (DPN), which can lead to significant disability and decreased quality of life. Prior work demonstrates the peptide hormone Angiotensin II (Ang II) is released locally in neuropathy and drives inflammation and impaired endoneurial blood flow. Therefore, we proposed that by utilizing a local thermoresponsive hydrogel injection, we could deliver inhibitors of angiotensin-converting enzyme (ACE) to suppress Ang II production and reduce nerve dysfunction in DPN through local drug release. The ACE inhibitor captopril was encapsulated into a micelle, which was then embedded into a reversibly thermoresponsive pluronics-based hydrogel matrix. Drug-free and captopril-loaded hydrogels demonstrated excellent product stability and sterility. Rheology testing confirmed sol properties with low viscosity at ambient temperature and increased viscosity and gelation at 37 °C. Captopril-loaded hydrogels significantly inhibited Ang II production in comparison to drug-free hydrogels. DPN mice treated with captopril-loaded hydrogels displayed normalized mechanical sensitivity and reduced inflammation, without side-effects associated with systemic exposure. Our data demonstrate the feasibility of repurposing ACE inhibitors as locally delivered anti-inflammatories for the treatment of sensory deficits in DPN. To the best of our knowledge, this is the first example of a locally delivered ACE inhibitor for the treatment of DPN.

Differentiating optic neuropathies using laser speckle flowgraphy: Evaluating blood flow patterns in the optic nerve head and peripapillary choroid.

To compare blood flow (BF) impairment patterns in different optic neuropathies using laser speckle flowgraphy (LSFG). This retrospective study enrolled 24 eyes of 24 patients with non-arteritic anterior ischemic optic neuropathy (NAAION), 59 eyes of 59 patients with optic neuritis (ON), 677 eyes of 677 patients with open-angle glaucoma (OAG), and 110 eyes of 110 controls. The patient backgrounds of all groups were compared. Ophthalmologic findings were evaluated, adjusting for age, sex, blood pressure, pulse rate, and underlying systemic diseases with 1:1 optimal propensity score matching. We used LSFG to obtain optic nerve head (ONH) vessel-area mean blur rate (MBR; ONH-MV), ONH tissue-area MBR (ONH-MT), and choroidal MBR. The NAAION and ON groups were compared with the control and OAG groups. Best-corrected visual acuity was worse in the NAAION, ON, and OAG groups than in controls (p < 0.001). Circumpapillary retinal nerve fibre layer thickness was higher in the NAAION and ON groups and lower in the OAG group than in controls (p < 0.001). Compared to controls, the NAAION and OAG groups had significantly lower ONH-MV, ONH-MT, and choroidal MBR (p < 0.05). Additionally, the NAAION group had lower ONH-MV and choroidal MBR than the OAG group (p = 0.003 and p < 0.001, respectively) but no difference in ONH-MT (p = 0.857). The ON group had significantly lower ONH-MV and choroidal MBR compared to the controls (p < 0.001 and p = 0.022, respectively) but no difference in ONH-MT (p = 0.773). Optic neuropathies showed different patterns of ocular BF impairment. Therefore, LSFG can be a useful tool for differentiating optic neuropathies.

Resistance exercise breaks during prolonged sitting augment the blood flow response to a subsequent oral glucose load in sedentary adults.

Sitting-induced impairments in postprandial blood flow are an important link between sedentary behaviour and cardiometabolic disease risk. The objective of this work was to examine the effects of resistance exercise breaks (REB) performed every 30min during an otherwise sedentary 3-h period on the vasodilatory response to a subsequent oral glucose load in sedentary adults. Twenty-four sedentary adults (27±7 years, 16 females) completed two conditions.Fasting blood glucose, insulin, popliteal artery blood flow (PABF) and gastrocnemius perfusion were measured immediately before standardized breakfast consumption. After breakfast, the 3-h REB or uninterrupted (SIT) intervention period commenced. Participants sat at a workstation, and popliteal artery shear rate (PASR) was measured 60 and 120min into this period. In the REB condition, participants performed a 3-min REB (3 × [20s squats, 20s high knees, 20s calf raises]) every 30min. Following the intervention period, baseline measurements were repeated. Participants then consumed a 75g glucose beverage, and PABF and perfusion were measured every 30-60min for the following 120min. Relative to SIT, REB increased PASR at 60min (+31.4±9.2/s, P=0.037) and 120min (+37.4±10.2/s, P=0.019) into the intervention period. Insulin and glucose increased (P<0.001) in response to glucose consumption, with no differences between conditions (P≥0.299). In response to the glucose load, perfusion (1.57vs. 1.11mL/100mL/min, P=0.023) and PABF (+45.3±11.8mL/min, P=0.001) were greater after REB versus SIT. Performing 3-min REB every 30min during an otherwise sedentary 3-h period augmented leg blood flow responses to an oral glucose load. HIGHLIGHTS: What is the central question of this study? Can 3-min resistance exercise breaks (REB) performed during an otherwise sedentary 3-h period augment the vasodilatory response to a subsequent oral glucose load in sedentary adults? What is the main finding and its importance? Performing 3-min REB, which included squats, high knees, and calf raises, every 30min augmented lower limb blood flow responses to a subsequent oral glucose load compared to 3h of uninterrupted sitting in sedentary adults. Sitting-induced impairment in postprandial vasodilatory function has been identified as a link between sedentary behaviour and cardiometabolic disease. Thus, the current study presents a potentially effective strategy to offset this risk.

Compact Linear Flow Phantom Model for Retinal Blood-Flow Evaluation.

Impaired retinal blood flow is associated with ocular diseases such as glaucoma, macular degeneration, and diabetic retinopathy. Among several ocular imaging techniques developed to measure retinal blood flow both invasively and non-invasively, adaptive optics (AO)-enabled scanning laser ophthalmoscopy (AO-SLO) resolves individual red blood cells and provides a high resolution with which to measure flow across retinal microvasculature. However, cross-validation of flow measures remains a challenge owing to instrument and patient-specific variability in each imaging technique. Hence, there is a critical need for a well-controlled clinical flow phantom for standardization and to establish blood-flow measures as clinical biomarkers for early diagnosis. Here, we present the design and validation of a simple, compact, portable, linear flow phantom based on a direct current motor and a conveyor-belt system that provides linear velocity tuning within the retinal microvasculature range (0.5-7 mm/s). The model was evaluated using a sensitive AO-SLO line-scan technique, which showed a <6% standard deviation from the true velocity. Further, a clinical SLO instrument showed a linear correlation with the phantom's true velocity (r2 > 0.997). This model has great potential to calibrate, evaluate, and improve the accuracy of existing clinical imaging systems for retinal blood flow and aid in the diagnosis of ocular diseases with abnormal blood flow.

Rate of Free Flap Failure and Return to the Operating Room in Lower Limb Reconstruction: A Systematic Review.

Background: Soft tissue defects of the lower limbs pose significant challenges in reconstructive surgery, accounting for approximately 10% of all reconstructive free flaps performed. These reconstructions often encounter higher complication rates due to various factors such as inflammation, infection, impaired blood flow, and nerve injuries. Methods: A systematic review was conducted following PRISMA guidelines, reviewing literature from 2017 to 2024. Eligible studies included those on free flap reconstruction of lower limb defects in living human subjects, with more than three cases and reported rates of flap failure and return to the operating room. Systematic reviews and metanalysis were excluded. Results: A total of 17 studies comprising 5061 patients and 5133 free flap reconstructions were included. The most common defects were in the lower leg (52.19%) due to trauma (79.40%). The total flap necrosis rate was 7.78%, the partial necrosis rate was 9.15%, and the rate of return to the operating room for suspected vascular compromise was 13.79%. Discussion: Lower limb reconstruction presents challenges due to diverse etiologies and variable tissue requirements. Factors such as recipient vessel availability, flap selection, and multidisciplinary approaches influence outcomes. Muscle and fasciocutaneous flaps remain common choices, each with advantages and limitations. This systematic review underscores the importance of individualized treatment planning. Conclusions: Microsurgical reconstruction of lower limb defects demonstrates safety and reliability, with overall favorable outcomes. Flap selection should be tailored to specific patient needs and defect characteristics, emphasizing meticulous surgical techniques and multidisciplinary collaboration. This systematic review provides valuable insights into current standards and encourages adherence to best practices in lower limb reconstruction.

Application of transcranial transmission ultrasound in the detection of vasospasm in patients with aneurysmal subarachnoid hemorrhage: illustrative cases.

Effective management of patients with aneurysmal subarachnoid hemorrhage (aSAH) demands vigilant monitoring and treatment, given the risks of complications such as cerebral vasospasm and delayed ischemic neurological deficits (DINDs). Transcranial transmission ultrasound (TTUS) is a well-established technique for assessing brain pulsatility. This pilot study aims to explore the utility of TTUS in detecting impaired intracerebral blood flow associated with DINDs. The authors examined 2 male patients, ages 45 and 52 years, with aSAH Hunt and Hess grades 4 and 2, respectively, who developed DINDs during their clinical course. Simultaneous recordings of arterial blood pressure, heart rate, and TTUS measurements were obtained in the intensive care unit. TTUS analysis revealed abnormal arrhythmic wave patterns during DIND episodes, whereas baseline measurements on DIND-free days showed no abnormalities. Following endovascular spasmolysis, TTUS demonstrated a normalization of abnormal waves, returning to baseline levels, alongside the resolution of neurological symptoms. TTUS, a noninvasive method for assessing brain pulsatility, shows promise as a novel tool for monitoring aSAH patients, potentially aiding in prompt diagnostics and additional therapeutic interventions. Its capacity to provide further insights for individuals at risk of delayed cerebral ischemia warrants further investigation in clinical studies. https://thejns.org/doi/10.3171/CASE24146.

A critical review of therapeutic interventions in sickle cell disease: Progress and challenges.

Sickle cell disease (SCD) is an autosomal recessive genetic disorder that occurs due to the point mutation in the β-globin gene, which results in the formation of sickle hemoglobin (HbS) in the red blood cells (RBCs). When HbS is exposed to an oxygen-depleted environment, it polymerizes, resulting in hemolysis, vaso-occlusion pain, and impaired blood flow. Still, there is no affordable cure for this inherited disease. Approved medications held promise but were met with challenges due to limited patient tolerance and undesired side effects, thereby inhibiting their ability to enhance the quality of life across various individuals with SCD. Progress has been made in understanding the pathophysiology of SCD during the past few decades, leading to the discovery of novel targets and therapies. However, there is a compelling need for research to discover medications with improved efficacy and reduced side effects. Also, more clinical investigations on various drug combinations with different mechanisms of action are needed. This review comprehensively presents therapeutic approaches for SCD, including those currently available or under investigation. It covers fundamental aspects of the disease, such as epidemiology and pathophysiology, and provides detailed discussions on various disease-modifying agents. Additionally, expert insights are offered on the future development of pharmacotherapy for SCD.

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice.

Microvascular endothelial dysfunction, characterized by impaired neurovascular coupling, reduced glucose uptake, blood-brain barrier disruption, and microvascular rarefaction, plays a critical role in the pathogenesis of age-related vascular cognitive impairment (VCI). Emerging evidence points to non-cell autonomous mechanisms mediated by adverse circulating milieu (an increased ratio of pro-geronic to anti-geronic circulating factors) in the pathogenesis of endothelial dysfunction leading to impaired cerebral blood flow and cognitive decline in the aging population. In particular, age-related adipose dysfunction contributes, at least in part, to an unfavorable systemic milieu characterized by chronic hyperglycemia, hyperinsulinemia, dyslipidemia, and altered adipokine profile, which together contribute to microvascular endothelial dysfunction. Hence, in the present study, we aimed to test whether thermogenic stimulation, an intervention known to improve adipose and systemic metabolism by increasing cellular energy expenditure, could mitigate brain endothelial dysfunction and improve cognition in the aging population. Eighteen-month-old old C57BL/6J mice were treated with saline or CL (β3-adrenergic agonist) for 6 weeks followed by functional analysis to assess endothelial function and cognition. CL treatment improved neurovascular coupling responses and rescued brain glucose uptake in aged animals. In addition, CL treatment also attenuated blood-brain barrier leakage and associated neuroinflammation in the cortex of aged animals. More importantly, these beneficial changes in microvascular function translated to improved cognitive performance in radial arm water maze and Y-maze tests. Our results suggest that β3-adrenergic agonist treatment improves multiple aspects of brain microvascular endothelial function and can be potentially repurposed for treating age-associated cognitive decline.