Search Results (1,010)

Mesenchymal stromal cells (MSC) have been shown to mitigate IRI through their anti-inflammatory and immune-modulating capacities. This study aims to demonstrate the feasibility, safety, and effectiveness of hepatic administration of bone marrow-derived (BM)-MSCs in a large pig model relevant to human anatomy. After complete vascular exclusion for 45 min, 3 × 10⁶ human BM-MSCs/kg body weight were infused via the portal vein or hepatic artery. BM-MSC infusion did not cause obstruction of hepatic or pulmonary blood flow within 6 h after infusion. Cells were effectively retained in the liver, being undetectable in peripheral blood, lung, and spleen samples. Human B2M expression, as a marker for BM-MSC presence, was significantly higher for the left liver lobe in arterial infusion compared to portal infusion. In liver samples with high BM-MSC levels, we identified the prevention of up- or downregulation of some genes related to inflammation and energy metabolism that was present in non-treated control samples, indicating biological effects within 6 h of infusion. We conclude that hepatic BM-MSC infusion is feasible and safe, with the hepatic artery serving as the optimal administration route for homogenous distribution. These findings pave the way for clinical studies on MSC infusion in IRI, either in situ in liver conditions or ex situ during machine perfusion. Full article

Background and Objectives: Partial nephrectomy is the standard treatment for small renal tumors, balancing cancer control with renal function preservation. Robot-assisted partial nephrectomy (RAPN) has improved surgical precision and reduced morbidity. Near-infrared fluorescence (NIRF) imaging with indocyanine green (ICG) improves intraoperative visualization of renal vasculature and tissue perfusion, potentially enabling selective arterial clamping to reduce ischemic injury. This study updates contemporary evidence on NIRF/ICG-guided RAPN, focusing on intraoperative, perioperative, and renal function outcomes. Materials and Methods: We systematically queried PubMed, Scopus, and Web of Science databases up to June 2025 for controlled prospective and retrospective studies comparing NIRF/ICG-guided RAPN (selective clamping or zero-ischemia) versus conventional RAPN with main artery clamping in adults with renal masses. Data were synthesized narratively, and random-effects meta-analyses were performed on warm ischemia time (WIT), operative time, estimated blood loss, transfusion rate, length of hospital stay, complication rate, positive surgical margins, and variation in renal function. Results: Eleven studies (10 full-text and one abstract), including two randomized controlled trials, encompassing a patient population of 893 patients (403 NIRF/ICG-guided RAPN and 490 conventional RAPN), were included. Ischemia strategies varied between no clamping, selective or super-selective clamping for NIRF/ICG, and main artery clamping for controls. ICG doses ranging from 3 to 7.5 mg or 0.5–7 mL. Most evidence was classified as level 2b or 3b, indicating a moderate to serious risk of bias. Meta-analysis showed that compared to conventional RAPN, NIRF/ICG-guided RAPN was associated with a shorter WIT (MD: −1.30 min, 95% CI: −2.51 to −0.09; p = 0.039), with no differences in other outcomes. Renal function favored NIRF/ICG at discharge and short-term follow-up, although the difference was not statistically significant. Conclusions: NIRF/ICG reduces WIT during RAPN without increasing perioperative risks. The technique shows promise for better preserving functional outcomes. However, further well-designed, large-scale trials with longer follow-up are needed to confirm these benefits and define clinical indications. Full article

Background: The cerebral compliance (or compensatory reserve) index, RAP, is a critical yet underutilized physiological marker in the management of moderate-to-severe traumatic brain injury (TBI). While RAP offers promise as a continuous bedside metric, its broader cerebral physiological context remains partly understood. This study aims to characterize the burden of impaired RAP in relation to other key components of cerebral physiology. Methods: Archived data from 379 moderate-to-severe TBI patients were analyzed using descriptive and threshold-based methods across three RAP states (impaired, intact/transitional, and exhausted). Agglomerative hierarchical clustering, principal component analysis, and kernel-based clustering were applied to explore multivariate covariance structures. Then, high-frequency temporal analyses, including vector autoregressive integrated moving average impulse response functions (VARIMA IRF), cross-correlation, and Granger causality, were performed to assess dynamic coupling between RAP and other physiological signals. Results: Impaired and exhausted RAP states were associated with elevated intracranial pressure (p = 0.021). Regarding AMP, impaired RAP was associated with elevated levels, while exhausted RAP was associated with reduced pulse amplitude (p = 3.94 × 10⁻⁹). These two RAP states were also associated with compromised autoregulation and diminished perfusion. Clustering analyses consistently grouped RAP with its constituent signals (ICP and AMP), followed by brain oxygenation parameters (brain tissue oxygenation (PbtO₂) and regional cerebral oxygen saturation (rSO₂)). Cerebral autoregulation (CA) indices clustered more closely with RAP under impaired autoregulatory states. Temporal analyses revealed that RAP exhibited comparatively stronger responses to ICP and arterial blood pressure (ABP) at 1-min resolution. Moreover, when comparing ICP-derived and near-infrared spectroscopy (NIRS)-derived CA indices, they clustered more closely to RAP, and RAP demonstrated greater sensitivity to changes in these ICP-derived CA indices in high-frequency temporal analyses. These trends remained consistent at lower temporal resolutions as well. Conclusion: RAP relationships with other parameters remain consistent and differ meaningfully across compliance states. Integrating RAP into patient trajectory modelling and developing predictive frameworks based on these findings across different RAP states can map the evolution of cerebral physiology over time. This approach may improve prognostication and guide individualized interventions in TBI management. Therefore, these findings support RAP’s potential as a valuable metric for bedside monitoring and its prospective role in guiding patient trajectory modeling and interventional studies in TBI. Full article

Vascular dementia (VaD) represents the second-most common dementia type after Alzheimer’s disease since it results from complications of cerebrovascular disease. Mixed pathologies combining vascular and neurodegenerative processes are the rule rather than exception in elderly dementia patients. The condition known as VaD includes various types of vascular damage that affect both large and small blood vessels in the brain which results in cerebral hypoperfusion, blood–brain barrier disruption, glymphatic dysfunction, and molecular cascades causing neuronal damage. The mechanisms of VaD include endothelial dysfunction, oxidative stress, chronic neuroinflammation, impaired glymphatic clearance, white matter demyelination, and synaptic failure. The disease susceptibility of individuals depends on genetic factors which include NOTCH3 mutations and vascular risk polymorphisms. The diagnostic field uses neuroimaging tools and fluid biomarkers such as neurofilament light chain, inflammatory markers, and Aβ/tau ratios for mixed pathology. The current practice of vascular risk management combines with new therapeutic approaches that use phosphodiesterase inhibitors for cerebral perfusion and NLRP3 inflammasome inhibitors for neuroinflammation, senolytics for cellular senescence, and remyelination agents for white matter repair. However, the majority of new treatment methods remain investigational with limited Phase III data. Future medical treatment development will depend on precision medicine approaches which use biomarker-guided treatment selection and combination strategies targeting multiple pathological mechanisms. Full article

Peripheral artery disease is a common manifestation of atherosclerosis, characterized by insufficient tissue perfusion and chronic ischemia. Arteriogenesis and angiogenesis are essential endogenous mechanisms to restore blood flow and limit ischemic injury. The metalloprotease ADAMTS13, known for cleaving ultra-large von Willebrand factor, has been implicated in thrombotic and inflammatory regulation. However, its role in ischemic vascular remodeling remains unclear. Using a murine hind limb ischemia model, we investigated the effect of ADAMTS13 deficiency on arteriogenesis and angiogenesis by comparing male ADAMTS13^−/− and wild-type control mice. Perfusion recovery, vascular cell proliferation, immune cell infiltration, and thrombotic activity were evaluated using laser Doppler measurements, immunohistochemical analysis of adductor and gastrocnemius muscle tissues, and in vivo microscopy. ADAMTS13 deficiency did not impair perfusion recovery, collateral artery growth, or capillarization. While platelet adhesion was slightly increased in ADAMTS13^−/− mice, no thrombotic occlusions were observed. Inflammatory responses, including macrophage and neutrophil infiltration as well as macrophage polarization, were largely unaffected. Despite previous in vitro evidence indicating an angiogenic role for ADAMTS13, its absence did not compromise angiogenesis in vivo. Our findings suggest that ADAMTS13 does not play a critical role in ischemia-related angiogenesis and arteriogenesis under sterile conditions and may be relevant only in contexts involving acute and sufficiently strong thromboinflammatory stimuli. Full article

Purpose: The venous-to-arterial carbon dioxide partial pressure difference [P(v-a)CO₂] reflects the adequacy of tissue perfusion, with elevated values suggesting impaired clearance of CO₂. While its prognostic role has been investigated in septic shock and high-risk surgery, evidence in postoperative critically ill patients remains limited. This study aimed to evaluate the prognostic value of ΔP(v-a)CO₂ after major abdominal surgery and its relationship with microcirculatory markers. Methods: We retrospectively analyzed 86 patients admitted to the intensive care unit (ICU) after major abdominal surgery between September 2020 and October 2023. Arterial and central venous blood gas analyses were performed immediately postoperatively and at 24 h. Patients were stratified into groups according to ΔP(v-a)CO₂ (≤ 0 vs. >0). Postoperative outcomes and correlations with central venous oxygen saturation (ScvO₂) were assessed. Results: In the subgroup analysis of patients with an initial P(v-a)CO₂ > 6 mmHg, those in the ΔP(v-a)CO₂ > 0 group required mechanical ventilation (54.5% vs. 22.2%, p = 0.033) and continuous renal replacement therapy (36.4% vs. 8.9%, p = 0.020) more frequently, with longer durations of both interventions (p = 0.011 and p = 0.016, respectively). ICU length of stay and the incidence of acute kidney injury were significantly lower in the ΔP(v-a)CO₂ ≤ 0 group. In addition, a modest negative correlation was observed between ScvO₂ measured at 24 h postoperatively and ΔP(v-a)CO₂. Conclusions: ΔP(v-a)CO₂ may serve as a useful marker for postoperative risk stratification in critically ill patients undergoing major abdominal surgery. However, given the retrospective design, small sample size, and single-center setting, these findings should be considered hypothesis-generating and require confirmation in larger, prospective multicenter studies. Full article

Traumatic brain injury (TBI) is a major global health concern and a leading cause of long-term disability and mortality. While the primary mechanical insult is often the focus of acute care, secondary injury mechanisms—particularly cerebrovascular dysfunction—play a critical role in ongoing neural damage and poor outcomes. Increasing research highlights the role of neurovascular changes in TBI pathophysiology. This narrative review compiles evidence from the past decade on mechanisms, diagnostic methods, and treatments related to cerebrovascular dysfunction after TBI. A structured search of PubMed and Embase identified relevant clinical and preclinical studies. Key mechanisms include blood–brain barrier disruption, impaired cerebral autoregulation, microthrombosis, and oxidative stress. Diagnostic tools discussed include perfusion imaging, cerebrovascular reactivity testing, and blood-based biomarkers of vascular injury. Therapeutic strategies targeting the neurovascular unit are categorized by mechanism: anti-inflammatory agents (e.g., celecoxib, minocycline), mitochondrial protectors (e.g., Tanshinone IIA), and vasomodulators (e.g., sildenafil). We propose an integrated therapeutic approach for a multimodal treatment plan that integrates these interventions. The findings emphasize the importance of patient-specific vascular therapies to reduce secondary ischemic injury and enhance neurological recovery. Although promising preclinical data exist, clinical application remains limited. More well-designed trials are needed to confirm the safety and effectiveness of emerging therapies. Full article

Aortic arch surgery remains associated with significant mortality and morbidity especially in the setting of acute type A aortic dissection. Adequate cerebral protection is essential, and several methods have been proposed to avoid neurological injury during aortic arch surgery. The most common techniques include selective antegrade perfusion of brachiocephalic arteries or an interval of deep hypothermic circulatory arrest. A range of cannulation strategies have been employed safely to provide adequate cerebral protection. Optimal cannulation selection is based on the consideration of air or particulate embolism risk; limitation in operative field visibility; end organ perfusion; and interactions with surgical maneuvers. Overall, no technique has been shown to fully mitigate the risk of neurological injury, rather each has utility in different scenarios. Innominate artery cannulation offers high flows on CPB and avoids additional incisions. Right axillary artery is rarely involved in aortic dissections, versatile for use in redo surgery, and altered blood flow patterns reduce embolic stroke rates. Left axillary artery can be utilized when both right axillary and femoral arteries are involved in a dissection process. Novel bi-axillary approach has additionally shown good results. Future multicenter, randomized trials should focus on establishing the relative benefits and risks of each cannulation approach with the aim of delineating the optimal cannulation strategy for different clinical situations to guide aortic surgeons, particularly in the emergency setting of aortic dissection. Full article

Cerebral autoregulation refers to the ability of cerebral vasculature to maintain stable blood flow by adjusting vascular resistance in response to changes in perfusion pressure. With advancing age, this regulatory capacity gradually declines, and its early, real-time, and dynamic monitoring holds potential as a promising approach for the prevention and treatment of cerebrovascular diseases. Given the absence of an established “gold standard” for assessing cerebral autoregulation, this study aimed to develop a non-invasive, continuous method for assessing cerebral autoregulation based on bioelectrical impedance technology. Using a wearable headband in combination with a Finapres device, blood pressure and cerebral blood flow were continuously monitored. A novel impedance recovery curve method was developed and, together with systemic blood pressure data, used to construct a hierarchical cerebral autoregulation assessment model via system identification. Moreover, the utility of this method in differentiating autoregulatory capacity across age groups (young adult and middle-aged) was assessed. The results demonstrated that the time constant (τ_REG), which characterizes the speed of cerebral blood flow recovery, differed significantly between the young adult and middle-aged groups (p < 0.001). These findings suggest the potential of τ_REG as a quantitative indicator for distinguishing cerebral autoregulatory function between healthy age cohorts. Full article

Background/Objectives: To validate an artificial intelligence-based arterial input function (AI-AIF) deep learning model for myocardial blood flow (MBF) quantification during stress perfusion and assess its extension to rest perfusion, enabling myocardial perfusion reserve (MPR) calculation. Methods: Sixty patients with or at risk for vascular cognitive impairment, prospectively enrolled in the CRUCIAL consortium, underwent quantitative stress and rest myocardial perfusion imaging using a 3 T MRI system. Perfusion imaging was performed using a dual-sequence (DS) protocol after intravenous administration of 0.05 mmol/kg gadobutrol. Retrospectively, the AI-AIF was estimated from standard perfusion images using a 1-D U-Net model trained to predict an unsaturated AIF from a saturated input. MBF was quantified using Fermi function-constrained deconvolution with motion compensation. MPR was calculated as the stress-to-rest MBF ratio. MBF and MPR estimates from both AIF methods were compared using Bland–Altman analyses. Results: Complete stress and rest perfusion datasets were available for 31 patients. A bias of −0.07 mL/g/min was observed between AI-AIF and DS-AIF for stress MBF (median 2.19 vs. 2.30 mL/g/min), with concordant coronary artery disease classification based on the optimal MBF threshold in over 92% of myocardial segments and coronary arteries. Larger biases of 0.12 mL/g/min and −0.30 were observed for rest MBF (1.12 vs. 1.02 mL/g/min) and MPR (2.31 vs. 1.84), respectively, with lower concordance using the optimal MPR threshold (85% of segments, 72% of arteries). Conclusions: The AI-AIF model showed comparable performance to DS-AIF for stress MBF quantification but requires further training for accurate rest MBF and MPR assessment. Full article

Background: This study assessed whether repeated monitoring of peripheral and organ perfusion predicts mortality in severe SARS-CoV-2 patients. Methods: Peripheral perfusion was measured with finger oxygen saturation (SpO2), capillary refill time (CRT), and finger infrared thermography (FIT). Organ perfusion was measured with the color Doppler renal cortex perfusion (RCP) and Renal Cortical Resistive Index (RCRI). Patients with severe COVID-19 pneumonia were examined after a mean of 7 days of intensive treatment. Results: A total of 46 patients (16 women, 30 men, age 55.2 ± 12.7 years) completed the study. SpO2 and CRT emerged as independent key bedside indicators of prognosis, with an OR for death of 0.665 (CI 0.472–0.938) and 2.223 (CI 1.144–4.322). An SpO2 of 95% (sensitivity 58.3%, specificity of 64.7%) and CRT of ≥4 s (sensitivity 66.7%, specificity of 83.9%) were found as the best threshold values for the elevated risk of mortality. From estimated blood tests, only C-reactive proteins (OR 1.252, CI 1.023–1.542) and ferritin (OR 1.001, CI 1.000–1.002) were independently associated with mortality. Moreover, the elevation in CRP was a substantial death indicator (OR 1.707, CI 1.046–2.784). Conclusions: The estimation of peripheral perfusion using SpO2 and CRT after initial intensive treatment is helpful in the prediction of outcomes in patients with severe COVID-19. Full article

Background/Objectives: APOL1 renal-risk variants (RRVs) are of increasing relevance to kidney disease and transplant outcomes. It is currently understood that the presence of RRVs in donors negatively impacts kidney allograft survival in an autosomal recessive pattern of inheritance. Less well known is the interplay between ischemia and alternative allograft preservation methods, such as normothermic machine perfusion (NMP), on APOL1 gene expression. To investigate this, we examined the effects of APOL1 RRVs on APOL1 gene expression in ischemic donor kidneys and compared the differences in cytokine and APOL1 expression patterns between the alternative preservation methods, static cold storage (CS) and NMP. Methods: Non-utilized deceased donor kidney pairs from donors of African ancestry were procured from Mid-America Transplant after being deemed unsuitable for kidney transplant. Samples were collected from each donor kidney pair and DNA was extracted for APOL1 genotyping. APOL1 RRVs G1 (rs73885319) (rs60910145) and G2 (rs71785313) were identified by Sanger sequencing. From each pair, one kidney underwent 6 h NMP (n = 3) and the contralateral kidney 6 h of CS (n = 3) following the initial CS. Renal perfusion and biochemical, and histologic parameters were recorded. NMP was directly compared with CS using paired donor kidneys using NMP with allogeneic red blood cells, followed by assessment of perfusion, biochemical, and histologic parameters, in addition to gene expression. Results: Donor genotyping identified kidney pairs as heterozygous for the G1 RRV (G1/G0), homozygous for the G0 allele (G0/G0), and homozygous for the G2 RRV (G2/G2), respectively. All kidneys were successfully reperfused, with mRNA transcript levels of APOL1-related genes subsequently measured. Significant differences in APOL1 gene expression were observed among all three groups of kidneys. In paired kidneys from baseline to hour 6 of NMP, mRNA expression varied significantly between G1/G0 and G2/G2 homozygous pairs (p = 0.002) as well as between the G0/G0 and G2/G2 pairs (p = 0.002). APOL1 expression shifted by a significantly higher-fold change of 2.4 under NMP conditions in the G2/G2 genotype (p < 0.001). The inflammatory cytokine marker IFN-γ was also significantly upregulated in the G2/G2 genotype kidney, in both CS and NMP groups (p = 0.001). Other related genes such as KIM-1 were upregulated by a change of 3.9-fold in the NMP group for the G2/G2 kidney. Conclusion: Donor kidney pairs with the high-risk APOL1 genotype, especially G2/G2, show increased APOL1 expression and inflammation, particularly under NMP conditions. NMP enables detection of genotype-specific molecular changes in an ischemic reperfusion injury model, supporting its potential to improve donor kidney assessment before transplantation. Full article

In reconstructive surgery, usage of different flaps is essential to cover tissue defects. Twisting, stretching or damaging the vascular pedicle may jeopardize the flaps’ viability. The aim of our experiment was to monitor tissue perfusion parameters of local versus rotated musculocutaneous flaps. In rats, musculus cutaneus maximus-based muscle–skin flaps were prepared bilaterally: one was sutured back to its original position, while the other flap was rotated to the ventral chest region (Flap group). In the Control group, flaps were not prepared. Tissue microcirculation was monitored intraoperatively, and on the 7th and 14th postoperative days. Blood samples were taken for testing hematological and hemorheological parameters. At the end of the observation period, biopsies were taken for biomechanical (tensile strengths) and histological investigations. We found that leukocyte and platelet counts significantly increased in the Flap group, while erythrocyte deformability decreased and aggregation increased. Although both local and rotated flaps survived and wound healing progressed well, in microcirculatory recordings, hypoperfusion and visible red blood cell aggregates were seen mostly in the rotated flaps. The rotated flaps were biomechanically weaker compared to local flaps or intact skin regions. This new model seems to be suitable for studying further flap pathophysiology focusing on tissue perfusion. Full article

Background: This study evaluated the effects of veno-arterial (V-A) and veno-venoarterial (V-VA) ECMO in a porcine model of septic endotoxemia-induced acute pulmonary arterial hypertension (PAH). Our hypotheses were as follows: (1) V-VA ECMO lowers pulmonary vascular resistance (PVR) by delivering oxygenated blood to the pulmonary circulation, and (2) both V-A and V-VA ECMO improve perfusion to vital organs while simultaneously unloading the right ventricle (RV). Methods: Acute PAH was induced with Salmonella abortus equi lipopolysaccharide (LPS) in 34 pigs. Animals were randomized to either a control group without ECMO or to two groups receiving V-A or V-VA ECMO. Results: All animals developed PAH after one hour of LPS infusion: mean pulmonary artery pressure (PAP) increased significantly from 26 (24–30) mmHg to 40 (34–46) mmHg (p < 0.0001), and PVR increased from 314 (221–390) to 787 (549–1073) (p < 0.0001). Neither V-A nor V-VA ECMO significantly reduced PVR compared to controls. RV end-diastolic area increased in the control group [6.1 (4.3–8.6) cm vs. 8.5 (7.8–9.7) cm, p = 0.2], but not in the V-A [4.7 (3.3–7.6) cm] and V-VA [4.3 (2.5–8.3) cm] ECMO groups. Blood flow in the cranial mesenteric artery and celiac trunk did not differ significantly with or without ECMO. Conclusions: Elevating pulmonary artery oxygen tension through V-A or V-VA ECMO did not reduce PVR or PAP. However, both ECMO configurations effectively unloaded the RV and maintained perfusion to abdominal organs. Full article

The current management of severe traumatic brain injury (TBI) focuses on maintaining cerebral perfusion pressure (CPP) to prevent or minimize secondary brain injury, limit cerebral edema, optimize oxygen delivery to the brain, and reduce primary neuronal damage by addressing contributing risk factors such as hypotension and hypoxia. Hypotension and cardiac dysfunction are common in patients with severe TBI, often requiring treatment with intravenous fluids and vasopressors. The primary categories of resuscitation fluids include crystalloids, colloids (such as albumin), and blood products. Fluid osmolarity is a critical consideration in TBI patients, as hypotonic fluids, such as balanced crystalloids, may increase the risk of cerebral edema development and worsening. Hyperosmolar therapy is a common therapeutic approach in patients with intracranial hypertension; however, its use as a resuscitation fluid is not associated with benefits in patients with TBI and is not recommended. Given the contradictory results of trials on blood transfusion strategies in patients with TBI, the transfusion approach should be tailored to individual systemic and cerebral physiological parameters. The evaluation of recent randomized clinical trials will provide insight into whether a liberal or restrictive transfusion strategy is preferred for this patient population. Hemodynamic and multimodal neurological monitoring to assess cerebral oxygenation, autoregulation, and metabolism are essential tools for detecting early hemodynamic alterations and cerebral injury, guiding resuscitation management, and contributing to improved outcomes. Full article