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Studying the placenta can provide information about the mechanistic pathways of pregnancy disease. However, analyzing placental tissues and manipulating placental function in real-time during pregnancy is not feasible. The ex vivo placental perfusion model allows observing important aspects of the physiology and pathology of the placenta, while maintaining its viability and functional integrity, and without causing harm to mother or fetus. In this review, we describe and compare setups for this technically complex model and summarize outcomes from various published studies. We hope that our review will encourage wider use of ex vivo placental perfusion, which in turn would generate more knowledge to improve pregnancy outcomes.

Ex vivo normothermic perfusion (EVNP) is increasingly recognised as a viability tool to increase organ utilisation in deceased donor transplantation. We report the use of EVNP to assess graft perfusion quality following indication nephrectomy and back-bench arterial reconstruction in a case of renal artery stenosis, unamenable to endovascular treatment. Once explanted, it was not possible to effectively cold perfuse the graft through the main renal artery or collaterals. An arterial reconstruction was performed with patch angioplasty using the largest collateral creating a single common stem. EVNP was used to assess organ perfusion and, therefore, viability. Excellent global perfusion was evident alongside urine production, demonstrating that the arterial reconstruction was satisfactory. A patient with end-stage renal disease was consented with particular attention to the uncertainty of the underlying donor disease process and long-term outcome of the reconstruction. Primary function was achieved and recipient estimated glomerular filtration rate (eGFR) remains stable at 58 mL/min/1.73 m² at 6 months.

Autoimmune pancreatitis (AIP) is a pancreatic phenotype of IgG4-related systemic disease. Since its first description in the literature, characteristic imaging features have gradually become known to many clinicians encompassing various specialties in the past quarter century. CT and MRI have been the workhorses for imaging diagnosis of AIP. Typical features include sausage-like swelling of the focal or entire pancreas, duct-penetrating sign, a capsule-like rim of the affected lesions, and homogeneous delayed enhancement or enhanced duct sign after contrast administration, as well as characteristic combined findings reflecting coexisting pathologies in the other organs as a systemic disease. In this review, recent and future developments in CT and MRI that may help diagnose AIP are discussed, including restricted diffusion and perfusion and increased elasticity measured using MR.

Acute oesophageal necrosis is a rare cause of haematemesis associated with high mortality and morbidity in elderly patients with multiple comorbidities. Acute oesophageal necrosis is thought to be caused by a combination of hypoperfusion, vascular disease and duodenal disease causing transient gastric outlet obstruction and therefore reflux of gastric contents. The subsequent necrosis is associated with significant morbidity and mortality. We present a case of an 83-year-old man presenting with sepsis secondary to gallstone cholangitis, who developed haematemesis 2 days post admission. Oesopho-gastro-duodenoscopy demonstrated necrosis to the oesophagus and duodenal ulceration. This was the first case of acute oesophageal necrosis observed within our hospital. We review the literature on the management of acute oesophageal necrosis and discuss the impact of acute oesophageal necrosis and its complications on the patient’s long-term outcome.

This is the unformatted version of the accepted review paper manuscript "Extended criteria grafts and emerging therapeutics strategy in liver transplantation. The unstable balance between damage and repair" published on Transplant Rev (Orlando)2021 Dec;35(4):100639. doi: 10.1016/j.trre.2021.100639., by Ghinolfi D, Melandro F, Torri F, Martinelli C, Cappello V, Babboni S, Silvestrini B, De Simone P, Basta G,Del Turco S. Due to increasing demand for donor organs, "extended criteria" donors are increasingly considered for liver transplantation, including elderly donors and donors after cardiac death. The grafts of this subgroup of donors share a major risk to develop significant features of ischemia reperfusion injury, that may eventually lead to graft failure. Ex-situ machine perfusion technology has gained much interest in liver transplantation, because represents both a useful tool for improving graft quality before transplantation and a platform for the delivery of therapeutics directly to the organ. In this review, we survey ongoing clinical evidences supporting the use of elderly and DCD donors in liver transplantation, and the underlying mechanistic aspects of liver aging and ischemia reperfusion injury that influence graft quality and transplant outcome. Finally, we highlight evidences in the field of new therapeutics to test in MP in the context of recent findings of basic and translational research.

Background The relationship between low oxygen delivery (DO2) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined. Methods We reviewed patients undergoing Society of Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO2 24 hours, stroke, sternal wound infection, and reoperation). Results Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO2 24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury Conclusions Low DO2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies.

We describe a complex case of liver transplant in a 70-year-old male patient with no known history of coronary artery disease, normal preoperative left ventricular function, and negative preoperative cardiac workup who developed progressive intra-operative left ventricular myocardial dysfunction secondary to class I acute myocardial infarction, ultimately requiring intraoperative intra-aortic balloon pump insertion to optimize myocardial perfusion. Management of myocardial ischemia was complicated by bleeding in the setting of coagulopathy necessitating correction. Once hemostasis was achieved, the patient immediately underwent coronary angiography and bare metal stent placement in the mid-left anterior descending coronary artery for an acute plaque rupture.

Introduction Although capsaicin has long been used as food additive and medication worldwide, its actions on gastrointestinal tract as its most delivery pathway have not been well addressed. Objectives In the present study, we aimed to study GI actions of capsaicin on mesenteric arterioles in normal and colitis mice and to elucidate the underlying mechanisms. Methods Vasorelaxation of human submucosal arterioles and the mesenteric arterioles from wide-type (WT) mice, TRPV1−/− and TRPV4−/− (KO) mice were measured. The expression and function of TRPV channels in endothelial cells were examined by q-PCR, immunostaining, Ca2+ imaging and membrane potential measurements. Results Capsaicin dose-dependently induced vasorelaxation of human submucosal arterioles and mouse mesenteric arterioles in vitro and in vivo through endothelium-dependent hyperpolarization (EDH), nitric oxide (NO), and prostacyclin (PGI2). Using TRPV1 and TRPV4 KO mice, we found that capsaicin-induced vasorelaxation was predominately through TRPV4/EDH, but marginally through TRPV1/NO/PGI2. Capsaicin induced hyperpolarization through activation of endothelial TRPV4 channels and intermediate-conductance of Ca2+-activated K+ channels to finally stimulate vasorelaxation. Importantly, capsaicin exerted anti-colitis action by rescuing the impaired ACh-induced vasorelaxation in WT colitis mice but not in TRPV4 KO colitis mice. Conclusions Capsaicin increases intestinal mucosal blood perfusion to potentially prevent/treat colitis through a novel TRPV4/EDH-dependent vasorelaxation of submucosal arterioles in health and colitis. This study further supports our previous notion that TRPV4/EDH in mesenteric circulation plays a critical role in the pathogenesis of colitis.

We report a simplified Zone 2 arch repair using a trifurcated graft for acute type A aortic dissection. The right axillary artery is cannulated. After completion of proximal aortic repair using a one-branched graft, a trifurcated graft is anastomosed to the ascending graft just above the proximal suture line or coronary buttons in case of Bentall procedure. Distal aortic anastomosis is performed at the Zone 2 level under unilateral antegrade cerebral perfusion. Full cardiopulmonary bypass flow is resumed via the right axillary and ascending graft using both Y-shaped arterial limbs. The left common carotid and innominate artery are sequentially anastomosed.

Background Vascular thrombosis secondary to frostbite can lead to ischemic tissue damage in severe cases. Threatened extremities may be salvaged with thrombolytics to restore perfusion; however, current data are limited to single institution case series. The authors performed a systematic review to determine the efficacy of thrombolytic therapy in treating upper extremity frostbite. Methods PubMed, EBSCO, and Google Scholar were queried using the keywords “thrombolytics,” “frostbite,” “fibrinolytics,” and “tPA.” Exclusion criteria were failure to delineate anatomic parts injured, failure to report number of limbs salvaged, animal studies, and non-English language publications. Thrombolytic therapy was defined as intraarterial (IA) or intravenous (IV) administration of tissue plasminogen activator (tPA), alteplase, urokinase, streptokinase, or any tPA derivative. Results A total of 42 studies were identified, with 13 satisfying inclusion criteria. Eight studies reported catheter-directed IA thrombolysis, four reported systemic IV administration, and 1 reported both methods. A total of 157 patients received thrombolytics. In all, 73 upper extremity digits were treated by IA route and 136 digits were treated by IV route. Overall upper extremity digit salvage rate was 59%. There was a significantly higher salvage rate in digits treated by the IA route compared to the IV route. Conclusions Thrombolytics, particularly when administered by the intra-arterial route, are emerging as a promising treatment of severe frostbite of the upper extremity, increasing digit salvage rates.

Introduction Traditional liver transplant strategies with cold preservation usually result in ischemia reperfusion injury (IRI) to the donor liver. Regular normothermic machine perfusion (NMP) donor livers suffer IRI twice. Here, we aimed to introduce a novel technique called continuous normothermic machine perfusion (NMP) without recooling to avoid a second IRI and its application in livers from extended criteria donors (ECDs). Materials and methods Seven donor livers transplanted following continuous NMP without recooling, 7 donor livers transplanted following standard NMP and 14 livers under static cold storage (SCS) were included in this study. Perioperative outcomes were recorded and analyzed between groups. Result During the NMP without a recooling procedure, all livers cleared lactate quickly to normal levels in a median time of 100 minutes (IQR 60~180) and remained stable until the end of perfusion. In the NMP without recooling and standard NMP groups, posttransplant peak aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were both significantly lower than those in the SCS group (P=0.0015 and 0.016, respectively). The occurrence rate of early allograft dysfunction (EAD) was significantly lower in the NMP without recooling group than in the SCS group (P=0.022), while there was no difference in the NMP group with or without recooling (P=0.462). Conclusion Our pilot study revealed a novel technique designed to avoid secondary IRI. This novel technique is shown to have at least a comparable effect to the standard NMP, though more data are needed to show its superiority in the future.

Objective : The objectives of the study were to estimate the perfusion of tumors by drugs used in intra-arterial chemotherapy of head and neck cancer with magnetic resonance imaging (MRI) and to establish the factors involved in determining the optimal dose. Study Design : Contrast agent was administered intra-arterially into either the lingual or maxillary artery in 43 patients. Triple-phase continuous fast spin echo MRI was performed. Changes in blood water longitudinal relaxation rate (⊿R1) were measured in relation to imaging phase, type of artery, measurement site, and tumor size. Results : ⊿R1 was significantly higher at the tumor margin than at the center for both arteries, except in the first phase for the lingual artery. ⊿R1 was greatest in the third phase for the lingual artery and in the second phase for the maxillary artery. For both arteries, as the tumor size increased, there was a significant decrease in ⊿R1 at the center of the tumor compared to the margin. Conclusion : The factors associated with ⊿R1 were imaging phase, type of artery, measurement site, and tumor size. When determining a drug's optimal dose, the type of artery and tumor size must be taken into consideration.

Summary Purpose The aim of this study was to prove the hypothesis that intraoperative fluorescence-angiography using indocyanine-green (ICGFA) can be used to predict the occurrence of perfusion-associated complications following microvascular reconstruction. Materials and Methods Consecutively perioperative data of patients who received microvascular reconstruction of the head and neck region and underwent ICGFA immediately after anastomosis was established were analyzed. The flow parameters analyzed in the investigation were (1) the baseline (IntMin) and (2) peak intensity (IntMax) of fluorescence, (3) the quotient of the two aforementioned parameters (Fmax/min) as an expression of the relative total increase, (4) the absolute difference in the two parameters (DiffInt) in terms of amplitude, (5) the duration of the intensity increase (TRise) until the peak, and (6) the percent intensity increase per second (Rise/secrel). Within the first 2 weeks postoperatively, every flap complication was documented. Subsequently, statistical analysis of the flap outcome was performed based on the flow parameters obtained intraoperatively. Results Data of 67 patients (male/female: 41/26) with an average age of 64 years (range 29-84 years) were analyzed. In 10 of these patients, postoperative perfusion-associated complications were observed (arterial/venous/microcirculatory: 4/4/3; p=0.12). The analysis of the intraoperatively obtained flow parameters showed a significant difference in the ratio of maximum and minimum intensity in arterial pedicle perfusion (Fmax/min) of patients with and without complications (with vs. without complications: 2.3±1.0 vs. 5.0±4.9; p Conclusion The ratio of maximum and minimum intensity (Fmax/min) is a predictor for postoperative venous stasis, arterial hypoperfusion and impaired microcirculation of a microvascular flap. Anastomoses with Fmax/min

Objectives To examine the feasibility of performing ASL-MRI in paediatric patients with solid abdominal tumours. Methods Multi-delay ASL data sets were acquired in ten paediatric patients diagnosed with either a neuroblastoma (n = 4) or nephroblastoma (n = 6) during a diagnostic MRI examination at a single visit (n = 4 at initial staging, n = 2 neuroblastoma and n = 2 nephroblastoma patients; n = 6 during follow-up, n = 2 neuroblastoma and n = 4 nephroblastoma patients). Visual evaluation and region-of-interest (ROI) analyses were performed on the processed perfusion-weighted images to assess ASL perfusion signal dynamics in the whole tumour, contralateral kidney, and tumour sub-regions with/without contrast enhancement. Results The majority of the included abdominal tumours presented with relatively low perfusion-weighted signal (PWS), especially compared with the highly perfused kidneys. Within the tumours, regions with high PWS were observed which, at short PLD, are possibly related to labelled blood inside vessels and at long PLD, reflect labelled blood accumulating inside tumour tissue over time. Conversely, comparison of ASL perfusion-weighted image findings with T1w enhancement after contrast administration showed that regions lacking contrast enhancement also were void of PWS. Discussion This pilot study demonstrates the feasibility of utilizing ASL-MRI in paediatric patients with solid abdominal tumours and provides a basis for further research on non-invasive perfusion measurements in this study population.

Hypoxic-ischemic encephalopathy (HIE) in infants can have long-term adverse neurodevelopmental effects and markedly reduce quality of life. Both the initial hypoperfusion and the subsequent rapid reperfusion can cause deleterious effects in brain tissue. Cerebral blood flow (CBF) assessment in newborns with HIE can help detect abnormalities in brain perfusion to guide therapy and prognosticate patient outcomes. The review will provide an overview of the pathophysiological implications of CBF derangements in neonatal HIE, current and emerging techniques for CBF quantification, and the potential to utilize CBF as a physiologic target in managing neonates with acute HIE. The alterations of CBF in infants during hypoxia-ischemia have been studied by using different neuroimaging techniques, including nitrous oxide and xenon clearance, transcranial Doppler ultrasonography, contrast-enhanced ultrasound, arterial spin labeling MRI, 18F-FDG positron emission tomography, near-infrared spectroscopy (NIRS), functional NIRS, and diffuse correlation spectroscopy. Consensus is lacking regarding the clinical significance of CBF estimations detected by these different modalities. Heterogeneity in the imaging modality used, regional versus global estimations of CBF, time for the scan, and variables impacting brain perfusion and cohort clinical characteristics should be considered when translating the findings described in the literature to routine practice and implementation of therapeutic interventions.· Hypoxic ischemic injury in infants can result in adverse long-term neurologic sequelae.. · Cerebral blood flow is a useful biomarker in neonatal hypoxic-ischemic injury.. · Imaging modality, variables affecting cerebral blood flow, and patient characteristics affect cerebral blood flow assessment..

Mosaic perfusion (mosaic attenuation, the “mosaic lung” sign) refers to areas of decreased attenuation of lung parenchyma (↑) in the regions of reduced blood perfusion. The term “mosaic” reflects patchy distribution of abnormalities. This sign is usually seen in patients with small airways diseases (cystic fibrosis, bronchiolitis obliterans, and chronic obstructive lung disease) and pulmonary vascular disease (mosaic oligemia in chronic pulmonary embolism). In cases with mosaic perfusion, regional pulmonary artery branches are always reduced in size. This pattern gives opportunity to distinguish mosaic perfusion from ground-glass opacities.

Purpose To provide an update on the hemodynamic model of age-related macular degeneration (AMD). Design Evidence-based perspective. Methods Review of literature and experience of authors. Results Choroidal hemodynamics are not the primary cause of AMD as proposed by Ephraim Friedman in 1997. However, evidence is accumulating to suggest that choroidal perfusion is an important environmental influence that contributes to our understanding disease progression in this complex genetic disease. While early and intermediate AMD appear to be influenced to a large extent by the underlying genetics, the asymmetry of disease progression to the later stages of AMD cannot be explained by genetics alone. The progression of disease and the asymmetry of this progression appear to correlate with abnormalities in choroidal perfusion that can be documented by optical coherence tomography. These perfusion abnormalities in the setting of a thickened Bruch's membrane are thought to exacerbate the impaired nutritional exchange between the retinal pigment epithelium and the choriocapillaris. We propose that the genetic susceptibility to develop AMD combined with age-related changes in macular choroidal hemodynamics, such as increasing choriocapillaris perfusion deficits and decreasing choroidal vascular densities, play an important role in disease progression and may help explain the asymmetry between eyes, particularly in the later stages of AMD. Conclusions This updated hemodynamic model of AMD focuses on disease progression and highlights the importance of age-related changes in the choroidal circulation as a major environmental influence on disease severity in eyes that are genetically susceptible to develop AMD.

Rationale and Objectives To investigate the microperfusion and water molecule diffusion alterations in sensorimotor-related areas in amyotrophic lateral sclerosis (ALS) using intravoxel incoherent motion (IVIM) magnetic resonance imaging. Materials and Methods IVIM data were obtained from 43 ALS patients and 31 controls. This study employed the revised ALS Functional Rating Scale (ALSFRS-R) in evaluating disease severity. IVIM-derived metrics were calculated, including diffusion coefficient (D), pseudo-diffusion coefficient, and perfusion fraction. Conventional apparent diffusion coefficient was also computed. Atlas-based analysis was conducted to detect between-group difference in these metrics in sensorimotor-related gray/white matter areas. Spearman correlation analysis was employed to establish correlation between various metrics and ALSFRS-R. Results ALS patients had perfusion fraction (× 10-3) reduction in the left presupplementary motor area (60.72 ± 16.15 vs. 71.15 ± 12.98, p = 0.016), right presupplementary motor area (61.35 ± 17.02 vs. 72.18 ± 14.22, p = 0.016), left supplementary motor area (55.73 ± 12.29 vs. 64.12 ± 9.17, p = 0.015), and right supplementary motor area (56.53 ± 11.93 vs. 63.67 ± 10.03, p = 0.020). Patients showed D (× 10-6 mm2/s) increase in a white matter tract projecting to the right ventral premotor cortex (714.20 ± 39.75 vs. 691.01 ± 24.53, p = 0.034). A negative correlation between D of right ventral premotor cortex tract and ALSFRS-R score was observed (r = -0.316, p = 0.039). Conclusion These findings suggest aberrant microperfusion and water molecule diffusion in the sensorimotor-related areas in ALS patients, which are associated with motor impairment in ALS.

Perfusion collateral index (PCI) has been recently defined as a promising measure of collateral status. We sought to compare collateral status assessed via CT-PCI in comparison to single-phase CTA and their relationship to outcome measures including final infarction volume, final recanalization status and functional outcome in ELVO patients.ELVO patients with anterior circulation large vessel occlusion who had baseline CTA and CT perfusion and underwent endovascular treatment were included. Collateral status was assessed on CTA. PCI from CT perfusion was calculated in each patient and an optimal threshold to separate good vs insufficient collaterals was identified using DSA as reference. The collateral status determined by CTA and PCI were assessed against 3 measured outcomes: 1) final infarction volume; 2) final recanalization status defined by TICI scores; 3) functional outcome measured by 90-day mRS.A total of 53 patients met inclusion criteria. Excellent recanalization defined by TICI ≥2C was achieved in 36 (68%) patients and 23 patients (43%) had good functional outcome (mRS ≤2). While having good collaterals on both CTA and CTP-PCI was associated with significantly (p0.05) smaller final infarction volume, only good collaterals status determined by CTP-PCI was associated with achieving excellent recanalization (p = 0.001) and good functional outcome (p = 0.003).CTP-based PCI outperforms CTA collateral scores in determination of excellent recanalization and good functional outcome and may be a promising imaging marker of collateral status in patients with delayed presentation of AIS.

PURPOSE: Recent initial findings suggest that radiation therapy improves blood perfusion and cellular chemotherapy uptake in mice with leukemia. However, the ability of radiation therapy to influence drug accumulation in the extracellular bone marrow tissue is unknown, due in part to a lack of methodology. This study developed longitudinal quantitative multiphoton microscopy (L-QMPM) to characterize the bone marrow vasculature (BMV) and drug accumulation in the extracellular bone marrow tissue before and after radiation therapy in mice bearing leukemia. METHODS AND MATERIALS: We developed a longitudinal window implant for L-QMPM imaging of the calvarium BMV before, 2 days after, and 5 days after total body irradiation (TBI). Live time-lapsed images of a fluorescent drug surrogate were used to obtain measurements, including tissue wash-in slope (WIS(tissue)) to measure extracellular drug accumulation. We performed L-QMPM imaging on healthy C57BL/6 (WT) mice, as well as mice bearing acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). RESULTS: Implants had no effects on calvarium dose, and parameters for wild-type untreated mice were stable during imaging. We observed decreased vessel diameter, vessel blood flow, and WIS(tissue) with the onset of AML and ALL. Two to 10 Gy TBI increased WIS(tissue) and vessel diameter 2 days after radiation therapy in all 3 groups of mice and increased single-vessel blood flow in mice bearing ALL and AML. Increased WIS(tissue) was observed 5 days after 10 Gy TBI or 4 Gy split-dose TBI (2 treatments of 2 Gy spaced 3 days apart). CONCLUSIONS: L-QMPM provides stable functional assessments of the BMV. Nonmyeloablative and myeloablative TBI increases extracellular drug accumulation in the leukemic bone marrow 2 to 5 days posttreatment, likely through improved blood perfusion and drug exchange from the BMV to the extravascular tissue. Our data show that neo-adjuvant TBI at doses from 2 Gy to 10 Gy conditions the BMV to improve drug transport to the bone marrow.

Background The relationship between retrograde arterial perfusion and stroke in patients with peripheral vascular disease has been widely documented. Antegrade arterial perfusion has been favoured as an alternative approach in less invasive mitral valve (MV) operations. We aimed to analyse our experience in patients with peripheral arterial disease undergoing MV surgery through a right mini-thoracotomy adopting antegrade arterial perfusion. Method A single-institution retrospective study on prospectively collected data was performed on patients undergoing right mini-thoracotomy MV surgery with antegrade arterial perfusion. Since 2009, indication for the latter was dictated by the severity of atherosclerotic burden. Preoperative screening included computed tomography, angiography, or both for the evaluation of the aorta and ileo-femoral arteries. Results Consecutive patients (n=117) underwent MV surgery through a right mini-thoracotomy with antegrade arterial perfusion, established either by transthoracic central aortic cannulation in 65 (55.6%) cases or by axillary arterial cannulation in 52 (44.4%). Mean logistic EuroSCORE was 11%±2.3%. Twenty-five (25) (21.4%) patients had undergone one or more previous cardiac operations. Operative mortality was 4.3% (n=5). Nonfatal iatrogenic aortic dissection occurred in one case (0.8%). The incidence of stroke was zero. Conclusions Axillary or central aortic cannulation is a promising alternative route to provide excellent arterial perfusion in right mini-thoracotomy MV surgery, with a very low incidence of stroke and other major perioperative complications in patients with severe aortic or peripheral arterial disease.

BACKGROUND: Conventional ultrasound and contrast-enhanced ultrasound play an important role in the application of carotid plaque. AIMS: To establish carotid artery vulnerable plaques model by conventional ultrasound combined with contrast-enhanced ultrasound, identify high-risk plaques that may lead to cerebrovascular events, and provide clinical risk warning of high-risk plaques of stroke. METHODS: 205 cases of patients selected in 5053 patients with symptoms from 2018 to 2019 who were verified carotid plaques by conventional ultrasound and contrast-enhanced ultrasound image characteristics, 147 cases as a training set, establishing the carotid artery plaque model, analyzing the characteristic of the plaques and the relationship between cerebrovascular event, with 58 cases as a test set, verify the model. Routine carotid ultrasound and contrast-enhanced carotid ultrasound were performed in all enrolled patients. RESULTS: The gray-level characteristics of conventional ultrasound in the training concentration showed statistical differences in plaque morphology, fibrous cap morphology, uniformity and calcification degree in cerebrovascular events. The contrast enhanced ultrasound characteristics of plaques showed statistical differences in neovascularization and perfusion mode in cerebrovascular events. In the test set, there were statistical differences in the above conventional gray scale features and CEUS features. CONCLUSION: The vulnerable plaque model established by conventional ultrasound combined with contrast-enhanced ultrasound has good diagnostic value for the characteristic plaque of carotid artery with cerebrovascular events.

The objective of this study was to evaluate the correlation between contrast-enhanced ultrasound (CEUS) parameters and histopathological features in patients with diabetic nephropathy (DN). Sixty-two patients with DN (44 men, mean age: 52.61 ± 10.63 y) were enrolled. They underwent renal biopsy for DN at the Department of Ultrasound, PLA Hospital, between May 2017 and February 2020. Renal tissue was obtained by ultrasound-guided percutaneous needle biopsy. CEUS was performed, and time-intensity curves (TICs) and renal perfusion parameters were analyzed. Differences in CEUS parameters were analyzed according to the glomerular classification and interstitial fibrosis-tubular atrophy (IFTA) score. Continuous variables were evaluated using the analysis of variance or Mann-Whitney U-test. Discontinuous variables were compared with the χ2-test. Spearman correlation analyses evaluated associations among quantitative ultrasound perfusion parameters and histopathological characteristics. Peak enhancement (PE), wash-in rate (WiR), wash-in perfusion index (WiPI) and wash-out rate (WoR) of the cortex, and their cortex/medulla ratios, decreased with increasing glomerular classification grade (p < 0.05). The fall time (FT) of the cortex, and their cortex/medulla ratios, increased with increasing glomerular classification grade (p < 0.05). There were no significant differences in the CEUS parameters for different IFTA scores. The perfusion volume-relevant parameters (such as PE, WiR and WiPI) had a negative correlation (p < 0.05), while the perfusion time-relevant parameters (such as RT and FT) had a positive correlation (p < 0.05), with the severity of glomerular lesions, glomerulosclerosis rate and number of Kimmelstiel-Wilson lesions. The CEUS parameters of the cortex could reflect pathological characteristics, especially changes in glomerular lesions.

Background Necroptosis plays an important role in cell death during pulmonary ischemia-reperfusion injury (IRI). We hypothesized that therapy with necrosulfonamide (NSA), a mixed-lineage kinase domain-like protein inhibitor, would attenuate lung IRI. Methods Rats were assigned at random into the sham operation group (n = 6), vehicle group (n = 8), or NSA group (n = 8). In the NSA and vehicle groups, the animals were heparinized and underwent left thoracotomy, and the left hilum was clamped for 90 minutes, followed by reperfusion for 120 minutes. NSA (0.5 mg/body) and a solvent were administered i.p. in the NSA group and the vehicle group, respectively. The sham group underwent 210 minutes of perfusion without ischemia. After reperfusion, arterial blood gas analysis, physiologic data, lung wet-to-dry weight ratio, histologic changes, and cytokine levels were assessed. Fluorescence double immunostaining was performed to evaluate necroptosis and apoptosis. Results Arterial partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) was better, dynamic compliance was higher, and mean airway pressure and lung edema were lower in the NSA group compared with the vehicle group. Moreover, in the NSA group, lung injury was significantly alleviated, and the mean number of necroptotic cells (55.3 ± 4.06 vs 78.2 ± 6.87; P = .024), but not of apoptotic cells (P = .084), was significantly reduced compared with the vehicle group. Interleukin (IL)-1β and IL-6 levels were significantly lower with NSA administration. Conclusions In a rat model, our results suggest that NSA may have a potential protective role in lung IRI through the inhibition of necroptosis.

Open and endovascular repairs of the descending thoracic and thoracoabdominal aorta are associated with a substantial risk of spinal cord injury, namely paraplegia. Endovascular repairs seem to have a lower incidence of spinal cord injury, but there have been no randomized trials comparing outcomes of open and endovascular repairs. Paraplegia occurs when collateral blood supply to the anterior spinal artery is impaired. The risk of spinal cord injury can be mitigated with perioperative protocols that include drainage of cerebrospinal fluid, avoidance of hypotension and anemia, intraoperative neurophysiologic monitoring, and advanced surgical techniques. Drainage of cerebrospinal fluid using a spinal drain decreases the risk of spinal cord ischemia by improving spinal cord perfusion pressure. However, cerebrospinal fluid drainage has risks including neuraxial and intracranial bleeding, and these risks need to be carefully weighed against its potential benefit. This review discusses current surgical management of descending thoracic and thoracoabdominal aortic disease, incidence of and risk factors for spinal cord injury, and elements of spinal cord protection protocols that pertain to anesthesiologists, with a focus on cerebrospinal fluid drainage.

Background We investigated the ability of magnetic resonance imaging (MRI) to distinguish primary central nervous system vasculitis (PCNSV) from glioblastoma to facilitate the development of an appropriate treatment for PCNSV. Methods We enrolled patients who were treated for PCNSV or glioblastoma at our center between January 2007 and August 2018. We compared the diagnoses of the two conditions by retrospectively reviewing patients’ data for contrast-enhanced MRI, perfusion MRI, flow-sensitive black-blood (FSBB) imaging, and 1H-magnetic resonance spectroscopy (MRS). Results We evaluated 108 patients (6, PCNSV; 102, glioblastoma). We found a statistically significant correlation between diagnosis and the contrast pattern on MRI. Perivascular enhancement was observed in all cases of PCNSV as follows: ring-like, homogeneous, and irregular patterns were observed in 53 (60%), 18 (20%), and 17 (19%) cases of glioblastoma, respectively. We identified a statistically significant correlation between diagnosis and cerebral blood volume (CBV) in three patients with PCNSV who underwent perfusion MRI; and all had low CBVs. Among the 55 patients with glioblastoma who underwent perfusion MRI, low and high CBVs were detected in 3 and 52 patients, respectively. There was no significant correlation between diagnosis and FSBB findings. Evaluation of 1H-MRS data showed statistically significant differences between PCNSV and glioblastoma as functions of neuronal amino acid levels on long echo time MRS, with a slightly different amino acid profile, including glutamine + glutamate on short echo time MRS. Conclusion Contrast-enhanced MRI, perfusion MRI, and quantitative analysis of 1H-MRS are valuable techniques for distinguishing PCNSV from glioblastoma before surgery.

Background This study reviews the outcomes of our reoperative total arch repair technique using a trifurcated graft and selective antegrade cerebral perfusion. Methods Fifty patients underwent reoperative total arch repair from January 2005 to September 2020, with either a one-stage repair (n = 9) or two-stage repair (n = 41). The two-stage technique includes minimal dissection of the mediastinal structures, an arch-first technique using a trifurcated graft, and construction of a classical elephant trunk through a partial transverse incision distally in the old graft or in the aorta just distal to the old graft. Results The median age was 63 years. Chronic dissection was the most frequent indication (88%), and 98% had undergone a previous proximal aortic repair at a median interval of 3 years. The median cardiopulmonary bypass, myocardial ischemic, selective antegrade cerebral perfusion, and lower body circulatory arrest times were 226, 103, 97, and 98 minutes, respectively. The minimum nasopharyngeal and bladder temperature were 16.5°C and 20.0°C, respectively. Operative mortality was 2%, the incidence of stroke was 2%, and the incidence of spinal cord injury was 0%. Stage II repair was performed in 37 patients (open, 33 patients; endovascular, 4 patients), with 2 mortalities and no spinal cord injury. The median duration between stage I and II was 63 days. Survival and aortic event free rates at 3 years were 88.4% ± 4.9%, and 89.8% ± 5%, respectively. Conclusions We report a reoperative total arch repair technique that minimizes dissection of the cardiac structures, simplifies the distal anastomosis, and protects vital organs, such as the brain, heart, and spinal cord.

Background Vasodilator capacity of coronary circulation is an important diagnostic and prognostic tool in patients with coronary artery disease (CAD). We aimed to clarify the incidence of coronary microvascular dysfunction (CMD), defined as impaired modified coronary flow capacity (mCFC) proposed by Johnson and Gould and measured by 13N-ammonia myocardial perfusion positron emission tomography (PET), in patients without obstructive CAD and to evaluate the risk of future cardiovascular events. Methods This retrospective study recruited 407 consecutive CAD-suspected patients who underwent both pharmacological stress/rest 13N-ammonia PET and coronary angiography. Of the 407 patients, 137 patients (median age, 70 years; 63 women) were eligible and followed up (median, 19.8 months). Endpoints were defined as cardiovascular death or major adverse cardiovascular events (MACEs), such as cardiovascular death, nonfatal myocardial infarction, unplanned hospitalization for any cardiac reasons, and unplanned coronary revascularization. The impaired mCFC group included patients with mildly to severely reduced regional CFC in, at least, one vascular territory (n=34), while the remaining patients (n=103) were categorized as having preserved mCFC. Results Overall, cardiovascular death and MACEs occurred in five (4%) patients. The Kaplan–Meier curve showed a significant reduction in event-free survival for cardiovascular death (p=0.004) and MACEs (p Conclusions In CAD-suspected patients without obstructive coronary arteries, impaired mCFC was observed in approximately 25% and was associated with a higher risk of cardiovascular death and MACEs. The mCFC concept can help identify patients who would benefit from specific therapies or lifestyle modifications to prevent future MACEs and can clarify potential mechanisms of CMD.

Purpose Radiation therapy (RT) can increase the risk of cardiac events in patients with breast cancer (BC), but biomarkers predicting risk for developing RT-induced cardiac disease are currently lacking. We report results from a prospective clinical trial evaluating early magnetic resonance imaging (MRI) and serum biomarker changes as predictors of cardiac injury and risk of subsequent cardiac events after RT for left-sided disease. Methods Women with node-negative and node-positive (N-/+) left-sided BC were enrolled on 2 institutional review board (IRB)–approved protocols at 2 institutions. MRI was conducted pretreatment (within 1 week of starting radiation), at the end of treatment (last day of treatment ±1 week), and 3 months after the last day of treatment (±2 weeks) to quantify left and right ventricular volumes and function, myocardial fibrosis, and edema. Perfusion changes during regadenoson stress perfusion were also assessed on a subset of patients (n = 28). Serum was collected at the same time points. Whole heart and cardiac substructures were contoured using CT and MRI. Models were constructed using baseline cardiac and clinical risk factors. Associations between MRI-measured changes and dose were evaluated. Results Among 51 women enrolled, mean heart dose ranged from 0.80 to 4.7 Gy and mean left ventricular (LV) dose from 1.1 to 8.2 Gy, with mean heart dose 2.0 Gy. T1 time, a marker of fibrosis, and right ventricular (RV) ejection fraction (EF) significantly changed with treatment; these were not dose dependent. T2 (marker of edema) and LV EF did not significantly change. No risk factors were associated with baseline global perfusion. Prior receipt of doxorubicin was marginally associated with decreased myocardial perfusion after RT (P = .059), and mean MHD was not associated with perfusion changes. A significant correlation between baseline IL-6 and mean heart dose (MHD) at the end of RT (ρ 0.44, P = .007) and a strong trend between troponin I and MHD at 3 months post-treatment (ρ 0.33, P = .07) were observed. No other significant correlations were identified. Conclusions In this prospective study of women with left-sided breast cancer treated with contemporary treatment planning, cardiac radiation doses were very low relative to historical doses reported by Darby et al. Although we observed significant changes in T1 and RV EF shortly after RT, these changes were not correlated with whole heart or substructure doses. Serum biomarker analysis of cardiac injury demonstrates an interesting trend between markers and MHD that warrants further investigation.

Стаття присвячена одному з найбільш тяжких та прогностично несприятливих гострих захворювань органів черевної порожнини — гострому панкреатиту. Наведені дані дослідження клінічної ефективності та ролі перфузійних розчинів у комплексному хірургічному лікуванні хворих із гострим панкреатитом на ранньому етапі лікування. Отримані результати дозволили зробити висновок, що включення перфузійних розчинів гідроксіетилкрохмалю у схему корекції гіповолемічних порушень сприяє стабілізації стану пацієнтів, чинить мікроциркулярний ефект та забезпечує раннє відновлення перистальтики.

Selection of infusion therapy in acute cerebral ischemia is one of the most difficult problems in the complex of conservative treatment of patients. For a detailed understanding of the influence of isoosmolar 0.9% NaCl solution and hyperosmolar mannitol solution on the course of acute ischemic stroke, it was of interest to study the effect of therapy with these solutions on the state of cerebral hemodynamics in ischemic brain. The studied solutions were administered in a conventionally effective dose (determined experimentally) immediately upon confirmation of the diagnosis, then — daily every 12 hours, for 7 days. Evaluation of cerebral hemodynamics was performed using Doppler ultrasound of cerebral arteries. Results of Doppler examination of extracranial cerebral arteries demonstrated the absence of any advantages of using mannitol solution in patients with acute ischemic stroke compared with the group treated with only 0.9% NaCl. In the studied patients, during infusion therapy with 0.9% NaCl and mannitol, there was a decreasing tendency in cerebral blood flow, which may lead to hypoperfusion of the brain.

У статті проаналізовано вплив базисної фармакотерапії на стан екстра- та інтракраніальної церебральної гемодинаміки у хворих на бронхіальну астму (БА) дітей. Монотерапія антилейкотрієновими препаратами нормалізує найбільшу кількість показників церебральної гемодинаміки, на другому місці — комбіноване лікування глюкокортикостероїдами та антилейкотрієновими препаратами, найменш ефективна базисна інгаляційна глюкокортикостероїдна терапія. Жодна проаналізована схема не усуває явища гіпоперфузії у вертебробазилярній зоні у хворих на БА дітей. У період ремісії декілька показників церебральної гемодинаміки, щодо яких усі перелічені схеми базисної фармакотерапії БА були ефективними, погіршилися та статистично не відрізнялись від аналогічних показників хворих із неконтрольованим перебігом БА. Хворі на БА діти повинні перебувати під наглядом дитячого невролога та потребують планового допплерографічного дослідження магістральних судин голови та шиї незалежно від ступеня контролю основного захворювання.

C-Reactive protein and erythrocyte sedimentation rate are crucial parameters used to monitor giant cell arteritis (GCA). Given that tocilizumab is approved for the treatment of GCA, these parameters are less sensitive because of the effects of interleukin-6 receptor blockade. Thus, the optimal method for monitoring GCA patients undergoing tocilizumab therapy, especially patients exhibiting a persistent thickened vessel wall in large vessels, remains unclear. Contrast-enhanced ultrasonography (CEUS) can increase the visibility of tissue perfusion by slow blood flow, which cannot be detected by power color doppler. We used CEUS to investigate patients with active and inactive GCA of the large vessels (active large vessel arteritis [aLVV]/inactive large vessel arteritis [iLVV]) who were not administered tocilizumab in this proof-of-concept study. After injection of the ultrasound contrast agent, the contrasted area (CA) of large vessels in a transverse section was calculated twice: first when the lumen was contrasted completely and once again 4–8 s later. We investigated the value of increase in CA that exhibited the best sensitivity and specificity for aLVV. Twenty-four patients were included in this study: 15 with aLVV and 9 with iLVV. The CA increased from 32.2 ± 16.8 to 52.5 ± 21.3 mm2 (p

Objective:Neovascularization can maintain and even improve tissue perfusion in the setting of limb ischemia during peripheral artery disease. The molecular and cellular mechanisms mediating this process are incompletely understood. We investigate the potential role(s) for Id3 (inhibitor of differentiation 3) in regulating blood flow in a murine model of hindlimb ischemia (HLI).Approach and Results:HLI was modeled through femoral artery ligation and resection and blood flow recovery was quantified by laser Doppler perfusion imaging. Mice with global Id3 deletion had significantly impaired perfusion recovery at 14 and 21 days of HLI. Endothelial- or myeloid cell-specific deletion of Id3 revealed no effect on perfusion recovery while B-cell–specific knockout of Id3 (Id3BKO) revealed a significant attenuation of perfusion recovery. Flow cytometry revealed no differences in ischemia-induced T cells or myeloid cell numbers at 7 days of HLI, yet there was a significant increase in B-1b cells in Id3BKO. Consistent with these findings, ELISA (enzyme-linked immunoassay) demonstrated increases in skeletal muscle and plasma IgM. In vitro experiments demonstrated reduced proliferation and increased cell death when endothelial cells were treated with conditioned media from IgM-producing B-1b cells and tibialis anterior muscles in Id3BKOmice showed reduced density of total CD31+and αSMA+CD31+vessels.Conclusions:This study is the first to demonstrate a role for B-cell–specific Id3 in maintaining blood flow recovery during HLI. Results suggest a role for Id3 in promoting blood flow during HLI and limiting IgM-expressing B-1b cell expansion. These findings present new mechanisms to investigate in peripheral artery disease pathogenesis.

e23539 Background: Induction isolated limb perfusion (ILP) followed by limb-sparing resection or extended resection are frequently used limb salvation strategies (LSS) in locally advanced extremity soft tissue sarcoma (eSTS) to prevent amputation. However little is known about the long term health-related quality of life (HRQoL) in these patients. The aim of this study was to compare long-term patient reported outcomes (PROs) such as HRQoL after ILP compared to extended resection or amputation. Methods: Patients treated with an ILP, extended resection, or amputation were selected from the respondents of a multi-institutional cross-sectional cohort survivorship study (SURVSARC) conducted 2-10 years after diagnosis among sarcoma survivors registered in the Netherlands Cancer Registry (NCR). Extended resection was defined as resection for stage III eSTS, details regarding amputation levels other than upper or lower extremity are unknown. Used PROs were the EORTC QLQ-C30, Cancer worry scale (CWS), the Hospital Anxiety and Depression Scale (HADS), and the Toronto Extremity Salvage Score (TESS). Results: We identified 96 eSTS survivors and assigned them into four groups: ILP (N = 20), extended resection (N = 48), primary amputation (N = 20), and amputation after ILP (N = 8). While there were no differences in PROs between ILP and extended resections, results showed better functioning and functionality after these two LSS groups versus the amputation groups. The amputation groups scored significantly lower on the EORTC QLQ-C30 physical functioning scale (p < 0.001, 62.7 and 65.7 versus 78.0 and 84.1) and role functioning scale (p = 0.038, 67.5 and 52.8 versus 79.2 and 80.9), which both account for a difference with ‘medium’ clinical relevance. Also for the TESS, the scores were significantly lower for the amputation groups compared to the LSS groups (upper extremity p = 0.007 with 68.9 and 71.6 versus 93.3 and 91.1; lower extremity p < 0.001 with 72.2 and 50.9 versus 84.5 and 85.5). There were no significant differences on cancer worry, anxiety and depression were found between all groups. Conclusions: Based on this survivorship study, HRQoL in eSTS survivors treated with ILP followed by limb-sparing resection is not inferior to extended resections, however it is superior in maintenance of physical functioning and functionality compared to an amputation.[Table: see text]

AIM To construct a novel nomogram by integrating computed tomography perfusion (CTP) and clinical parameters for individualised prediction of haemorrhagic transformation (HT) in intravenous thrombolysis (IVT)-treated acute ischaemic stroke (AIS) patients. METHODS Anterior circulation AIS patients who underwent IVT at a single centre from January 2018 to June 2020 were reviewed retrospectively. The CTP parameters of two regions of interest (ROI), the entire perfusion lesion areas, and the infract core areas, were assessed. HT was documented by follow-up CT 24 ± 2 h after IVT. Multivariable logistic regression was conducted by including clinical variables and CTP parameters to identify the independent predictors of HT. A nomogram was developed based on the independent predictors. The discriminative value and calibration of the nomogram were tested by concordance indexes (C-indexes) and calibration plots. Internal validation was performed using fivefold cross-validation. RESULTS The nomogram was generated using the complete data from 341 patients. Seven variables were included in the final nomogram, including: the relative cerebral blood volume (rCBV), permeability surface (PS), and relative PS (rPS) in infract core areas, the relative time to maximum (rTmax) and rPS in entire perfusion lesion areas, the National Institutes of Health Stroke Scale (NIHSS), and atrial fibrillation (AF). The C-indexes were 0.815 and 0.817 for the nomogram and internal validation. The calibration plots showed excellent agreement. CONCLUSION This is the first study establishing a nomogram based on CTP and clinical parameters to predict HT after stroke thrombolysis.

Contains fulltext : 248292.pdf (Publisher’s version ) (Open Access) BACKGROUND: Skin microvasculature changes are crucial in psoriasis development and correlate with perfusion. The noninvasive Handheld Perfusion Imager (HAPI) examines microvascular skin perfusion in large body areas using laser speckle contrast imaging (LSCI). OBJECTIVES: To (i) assess whether increased perilesional perfusion and perfusion inhomogeneity are predictors for expansion of psoriasis lesions and (ii) assess feasibility of the HAPI system in a mounted modality. METHODS: In this interventional pilot study in adults with unstable plaque psoriasis, HAPI measurements and color photographs were performed for lesions present on one body region at week 0, 2, 4, 6 and 8. The presence of increased perilesional perfusion and perfusion inhomogeneity was determined. Clinical outcome was categorized as increased, stable or decreased lesion surface between visits. Patient feedback was collected on a 10-point scale. RESULTS: In total, 110 lesions with a median follow-up of 6 (IQR 6.0) weeks were assessed in 6 patients with unstable plaque psoriasis. Perfusion data was matched to 281 clinical outcomes after two weeks. A mixed multinomial logistic regression model revealed a predictive value of perilesional increased perfusion (OR 9.90; p

Early detection and prompt reversal of sepsis-induced tissue hypoperfusion are key elements while treating patients with septic shock. Fluid administration is widely accepted as the first-line therapy followed by vasopressor use in persistently hypotensive patients or in those with insufficient arterial pressure to ensure adequate tissue perfusion. Recent evidence suggests a beneficial effect of combining fluids with vasopressors in the early phase of sepsis. Compared with fluids alone, combining fluids and vasopressors increases mean systemic pressure and venous return and corrects hypotension better. This approach also limits fluid overload, which is an independent factor of poor outcomes in sepsis. It produces less hemodilution than fluids alone. As a consequence of these effects, combined treatment may improve outcomes in septic shock patients.

OBJECTIVE Digital subtraction angiography (DSA) is commonly performed after pial synangiosis surgery for pediatric moyamoya disease to assess the degree of neovascularization. However, angiography is invasive, and the risk of ionizing radiation is a concern in children. In this study, the authors aimed to identify whether arterial spin labeling (ASL) can predict postoperative angiogram grading. In addition, they sought to determine whether patients who underwent ASL imaging without DSA had similar postoperative outcomes when compared with patients who received ASL imaging and postoperative DSA. METHODS The medical records of pediatric patients who underwent pial synangiosis for moyamoya disease at a quaternary children’s hospital were reviewed during a 10-year period. ASL-only and ASL+DSA cohorts were analyzed. The frequency of preoperative and postoperative symptoms was analyzed within each cohort. Three neuroradiologists assigned a visual ASL grade for each patient indicating the change from the preoperative to postoperative ASL perfusion sequences. A postoperative neovascularization grade was also assigned for patients who underwent DSA. RESULTS Overall, 21 hemispheres of 14 patients with ASL only and 14 hemispheres of 8 patients with ASL+DSA were analyzed. The groups had similar rates of MRI evidence of acute or chronic stroke preoperatively (61.9% in the ASL-only group and 64.3% in the ASL+DSA group). In the entire cohort, transient ischemic attack (TIA) (p = 0.027), TIA composite (TIA or unexplained neurological symptoms; p = 0.0006), chronic headaches (p = 0.035), aphasia (p = 0.019), and weakness (p = 0.001) all had decreased frequency after intervention. The authors found a positive association between revascularization observed on DSA and the visual ASL grading (p = 0.048). The visual ASL grades in patients with an angiogram indicating robust neovascularization demonstrated improved perfusion when compared with the ASL grades of patients with a poor neovascularization. CONCLUSIONS Noninvasive ASL perfusion imaging had an association with postoperative DSA neoangiogenesis following pial synangiosis surgery in children. There were no significant postoperative stroke differences between the ASL-only and ASL+DSA cohorts. Both cohorts demonstrated significant improvement in preoperative symptoms after surgery. Further study in larger cohorts is necessary to determine whether the results of this study are validated in order to circumvent the invasive catheter angiogram.

Background Conventional topical antimicrobial therapy cannot maintain a constant local concentration, resulting in uncontrolled infection and complications. We propose continuous local antibiotic perfusion (CLAP), which can maintain a constant appropriate local antibiotic concentration for a long time with less invasiveness and complications. CLAP is clearly different from traditional treatment because it uses negative pressure to direct the continuously infused antibiotic solution to the center of infection and excrete it outside the body. This study aimed to demonstrate the effectiveness of CLAP by presenting cases in which even refractory bone and soft-tissue infections caused by the hypervirulent Klebsiella pneumoniae (hvKp) could be cured without significant tissue loss and dysfunction. Methods This study is a case series in which four patients with limb infection due to hvKp were treated by CLAP. hvKp was defined by a positive string test. The therapy included intra-soft-tissue antibiotic perfusion and intramedullary antibiotic perfusion. Gentamicin (60 mg/50 cc) was infused continuously through dual-lumen tubes and bone marrow needles at low-flow rates (2 mL/h). Negative pressure was used to collect the antimicrobial solution and eliminate the dead space. Results The infection was controlled in all four patients after a mean period of 44.3 days. The mean maximum blood concentration of gentamicin was 1.6 μg/dL, and no cases of renal dysfunction or ototoxicity occurred. After CLAP, wound closure was required in two patients and iliac bone grafting was required in one patient. As sequelae, there were one case of osteoarthritis and one case of higher brain dysfunction due to hypoxia. Conclusions Our results suggest that intractable hvKp infections can be controlled by CLAP. CLAP may give us the option to directly control local infections with less systemic complications. Therefore, it is considered a valuable treatment for further basic and clinical research, and this research report may be a first step.

The physical connection of mother and offspring during pregnancy allows the bi-directional exchange of a small number of cells through the placenta. These cells, which can persist long-term in the recipient individual are genetically foreign to it and therefore fulfill the principle of microchimerism. Over the last years, pioneer research on microchimeric cells revealed their role in immune adaptation during pregnancy and priming of tolerogenic responses in the progeny. However, the mechanisms involved in cell transfer across the placenta barrier remain poorly investigated. In this review, we summarize the evidence of fetomaternal microchimerism, propose a mechanism for cell trafficking through the placenta and discuss the different models and techniques available for its analysis. Likewise, we aim to generate interest in the use of ex vivo placenta perfusion to investigate microchimerism in physiological and pathological settings.

Stress myocardial perfusion imaging (MPI) is the preferred test in patients with intermediate-to-high clinical likelihood of coronary artery disease (CAD) and can be used as a gatekeeper to avoid unnecessary revascularization. Cardiac magnetic resonance (CMR) has a number of favorable characteristics, including: (1) high spatial resolution that can delineate subendocardial ischemia; (2) comprehensive assessment of morphology, global and regional cardiac functions, tissue characterization, and coronary artery stenosis; and (3) no radiation exposure to patients. According to meta-analysis studies, the diagnostic accuracy of perfusion CMR is comparable to positron emission tomography (PET) and perfusion CT, and is better than single-photon emission CT (SPECT) when fractional flow reserve (FFR) is used as a reference standard. In addition, stress CMR has an excellent prognostic value. One meta-analysis study demonstrated the annual event rate of cardiovascular death or non-fatal myocardial infarction was 4.9% and 0.8%, respectively, in patients with positive and negative stress CMR. Quantitative assessment of perfusion CMR not only allows the objective evaluation of regional ischemia but also provides insights into the pathophysiology of microvascular disease and diffuse subclinical atherosclerosis. For accurate quantification of myocardial perfusion, saturation correction of arterial input function is important. There are two major approaches for saturation correction, one is a dual-bolus method and the other is a dual-sequence method. Absolute quantitative mapping with myocardial perfusion CMR has good accuracy in detecting coronary microvascular dysfunction. Flow measurement in the coronary sinus (CS) with phase contrast cine CMR is an alternative approach to quantify global coronary flow reserve (CFR). The measurement of global CFR by quantitative analysis of perfusion CMR or flow measurement in the CS permits assessment of microvascular disease and diffuse subclinical atherosclerosis, which may provide improved prediction of future event risk in patients with suspected or known CAD. Multi-institutional studies to validate the diagnostic and prognostic values of quantitative perfusion CMR approaches are required.

Purpose: This study aimed to apply doxorubicin-loaded nanoparticle microbubble (Dox-NP-MB) therapy in an orthotopic rat model of hepatocellular carcinoma (HCC) and investigate the utility of contrast-enhanced ultrasound (CEUS) and intravoxel incoherent motion diffusion-weighted magnetic resonance imaging (IVIM-DWI) for response evaluation.Methods: Twenty-eight N1S1 HCC model rats were treated with either Dox-NP-MB (group [G] 1, n=8), doxorubicin (Dox) alone (G2, n=7), nanoparticle microbubbles alone (G3, n=7), or saline (G4, control, n=6) on days 0 and 7, and were sacrificed on day 11. IVIM-DWI and CEUS were performed before each treatment and before euthanasia. Efficacy was estimated by the percentage of tumor volume growth inhibition compared with control. Toxicity was assessed by body weight changes and blood tests. Post-treatment changes in IVIM-DWI and CEUS parameters were analyzed.Results: Tumor volume growth was inhibited by 48.4% and 90.2% in G1 and G2 compared to G4, respectively. Compared to G2, G1 had a significantly lower degree of body weight change (median, 91.0% [interquartile range, 88.5%-97.0%] vs. 88.0% [82.5%-88.8%], P

Sepsis is the leading cause of acute respiratory distress syndrome (ARDS) in adults and carries a high mortality. Utilizing a previously validated porcine model of sepsis-induced ARDS, we sought to refine our novel therapeutic technique of in vivo lung perfusion (IVLP). We hypothesized that 2 hours of IVLP would provide non-inferior lung rehabilitation compared to 4 hours of treatment. Adult swine (n = 8) received lipopolysaccharide to develop ARDS and were placed on central venoarterial extracorporeal membrane oxygenation. Animals were randomized to 2 vs 4 hours of IVLP. The left pulmonary vessels were cannulated to IVLP using antegrade Steen solution. After IVLP treatment, the left lung was decannulated and reperfused for 4 hours. Total lung compliance and pulmonary venous gases from the right lung (control) and left lung (treatment) were sampled hourly. Biochemical analysis of tissue and bronchioalveolar lavage was performed along with tissue histologic assessment. Throughout IVLP and reperfusion, treated left lung PaO2/FiO2 ratio was significantly higher than the right lung control in the 2-hour group (332.2 ± 58.9 vs 264.4 ± 46.5, P = 0.01). In the 4-hour group, there was no difference between treatment and control lung PaO2/FiO2 ratio (258.5 ± 72.4 vs 253.2 ± 90.3, P = 0.58). Wet-to-dry weight ratios demonstrated reduced edema in the treated left lungs of the 2-hour group (6.23 ± 0.73 vs 7.28 ± 0.61, P = 0.03). Total lung compliance was also significantly improved in the 2-hour group. Two hours of IVLP demonstrated superior lung function in this preclinical model of sepsis-induced ARDS. Clinical translation of IVLP may shorten duration of mechanical support and improve outcomes.

BACKGROUND: Negative pressure wound therapy (NPWT) has been established over years for treatment of chronic and complex wounds. OBJECTIVE: Aim of this study was to investigate the effect NPWT on the microperfusion. METHODS: Prospective single centre analysis of patients treated with NPWT due to acute (ACUTE) wounds after fasciotomy or patients with chronic wounds (CHRONIC) due to a chronic limb threatening ischemia was performed. NPWT was conducted through a three days sequence with a negative pressure of –120 mmHg. Before after and during the entire period of therapy the microperfusion was assessed (O2C™, LEA Medizintechnik). RESULTS: Comparison of the perfusion values of 28 patients (CHRONIC/ACUTE 5/23, women/men 8/20) before and after the NPWT sequence showed a non-significant improvement in the CHRONIC group (supine position: p = 0.144, elevated position p = 0.068) and a significant decrease in the ACUTE group (supine position p = 0.012, elevated position p = 0.034). This effect could also been demonstrated during the NPWT over time (CHRONIC: supine position: p = 0.320, elevated position: p = 0.053, ACUTE: supine position: p = 0.021, elevated position: p = 0.012). CONCLUSION: Microperfusion measurements showed alterations and differences in wound bed perfusion of acute and chronic wounds; acute wounds tended to a decrease of blood flow, whereas this effect was not seen in chronic wounds in peripheral artery disease.

Toward the goal of using more livers for transplantation, transplant centers are looking to increase the use of organs from "marginal" donors. Livers from these donors, however, have been shown to be more susceptible to preservation and reperfusion injury.Using a porcine model of donation after circulatory death, we studied the use of antibody-mediated CD47 blockade to further improve liver graft function undergoing normothermic machine perfusion. Livers from 20 pigs (5 per group) were brought under either 30 or 60 min of warm ischemia time followed by the administration of CD47 monoclonal antibody (CD47mAb) treatment or immunoglobulin G control antibodies and 6 h of normothermic extracorporeal liver perfusion.After 6 h of normothermic extracorporeal liver perfusion, CD47mAb-treated livers with 30 or 60 min warm ischemia time had significantly lower alanine transaminase levels and higher bile production compared with their respective control groups. Blockade of the CD47 signaling pathway resulted in significantly lower thrombospondin-1 protein levels, lower expression of caspase-3, and higher expression of phosphorylated extracellular signal-regulated kinase.These findings suggested that CD47mAb treatment decreases ischemia/reperfusion injury through CD47/thrombospondin-1 signaling downregulation and the presence of necrosis/apoptosis after reperfusion and could increase liver regeneration during normothermic perfusion of the liver.

Background Strain analysis has become commonly used in clinical practice in various heart diseases. Purpose To explore whether late gadolinium enhancement (LGE)-negative areas with coronary artery chronic total occlusion (CTO) appear normal when analyzed for longitudinal strain using cardiac magnetic resonance (CMR) imaging. Material and Methods A total of 16 patients and 31 healthy controls who underwent 1.5-T MR at our hospital between January 2015 and July 2017 were included in the study. The LGE-CMR of patients with CTO was negative. Left ventricular functional parameters, segmental longitudinal strain/strain rate, and perfusion parameters were measured using CVI42 software. Results For myocardial segments supplied by CTO vessels, systolic longitudinal strain rate (SLSR)was significantly lower than that of healthy controls, and diastolic longitudinal strain rate (DLSR) was significantly higher (1.19 1/s vs. 1.02 1/s; P = 0.018). Moreover, longitudinal strain (LS), SLSR, and DLSR did not differ between good and poor collateral circulation. Perfusion index of CTO territory segments was lower than non-CTO territory segments (0.20 vs. 0.22; P = 0.027). No correlation was found between longitudinal strain parameters and perfusion parameters. Conclusion Although LGE-CMR was negative in patients with CTO, the myocardial SLSR of CTO territory segments was significantly lower than that of healthy controls.

BACKGROUND Dynamic contrast-enhanced magnetic resonance imaging (MRI) of the liver in pediatric Fontan patients often shows peripheral reticular areas of hypoenhancement, which has not been studied in detail. OBJECTIVE To semiquantitatively score the hepatic MR perfusion abnormality seen in pediatric Fontan patients, and to correlate the perfusion abnormality with functional clinical and hemodynamic parameters. MATERIALS AND METHODS All children (

Background In ischemic stroke, cerebral autoregulation and neurovascular coupling may become impaired. The cerebral blood flow (CBF) response to spreading depolarization (SD) is governed by neurovascular coupling. SDs recur in the ischemic penumbra and reduce neuronal viability by the insufficiency of the CBF response. Autoregulatory failure and SD may coexist in acute brain injury. Here, we set out to explore the interplay between the impairment of cerebrovascular autoregulation, SD occurrence, and the evolution of the SD-coupled CBF response. Methods Incomplete global forebrain ischemia was created by bilateral common carotid artery occlusion in isoflurane-anesthetized rats, which induced ischemic SD (iSD). A subsequent SD was initiated 20–40 min later by transient anoxia SD (aSD), achieved by the withdrawal of oxygen from the anesthetic gas mixture for 4–5 min. SD occurrence was confirmed by the recording of direct current potential together with extracellular K+ concentration by intracortical microelectrodes. Changes in local CBF were acquired with laser Doppler flowmetry. Mean arterial blood pressure (MABP) was continuously measured via a catheter inserted into the left femoral artery. CBF and MABP were used to calculate an index of cerebrovascular autoregulation (rCBFx). In a representative imaging experiment, variation in transmembrane potential was visualized with a voltage-sensitive dye in the exposed parietal cortex, and CBF maps were generated with laser speckle contrast analysis. Results Ischemia induction and anoxia onset gave rise to iSD and aSD, respectively, albeit aSD occurred at a longer latency, and was superimposed on a gradual elevation of K+ concentration. iSD and aSD were accompanied by a transient drop of CBF (down to 11.9 ± 2.9 and 7.4 ± 3.6%, iSD and aSD), but distinctive features set the hypoperfusion transients apart. During iSD, rCBFx indicated intact autoregulation (rCBFx 0.3) because CBF followed the decreasing MABP. CBF dropped 15–20 s after iSD, but the onset of hypoperfusion preceded aSD by almost 3 min. Taken together, the CBF response to iSD displayed typical features of spreading ischemia, whereas the transient CBF reduction with aSD appeared to be a passive decrease of CBF following the anoxia-related hypotension, leading to aSD. Conclusions We propose that the dysfunction of cerebrovascular autoregulation that occurs simultaneously with hypotension transients poses a substantial risk of SD occurrence and is not a consequence of SD. Under such circumstances, the evolving SD is not accompanied by any recognizable CBF response, which indicates a severely damaged neurovascular coupling.

BackgroundIn patients with stroke, current guidelines recommend non-invasive vascular imaging to identify intracranial vessel occlusions (VO) that may benefit from endovascular treatment (EVT). However, VO can be missed in CT angiography (CTA) readings. We aim to evaluate the impact of consistently including CT perfusion (CTP) in admission stroke imaging protocols.MethodsFrom April to October 2020 all patients admitted with a suspected acute ischemic stroke underwent urgent non-contrast CT, CTA and CTP and were treated accordingly. Hypoperfusion areas defined by time-to-maximum of the tissue residue function (Tmax) >6 s, congruent with the clinical symptoms and a vascular territory, were considered VO (CTP-VO). In addition, two experienced neuroradiologists blinded to CTP but not to clinical symptoms retrospectively evaluated non-contrast CT and CTA to identify intracranial VO (CTA-VO).ResultsOf the 338 patients included in the analysis, 157 (46.5%) presented with CTP-VO (median Tmax >6s: 73 (29–127) mL). CTA-VO was identified in 83 (24.5%) of the cases. Overall CTA-VO sensitivity for the detection of CTP-VO was 50.3% and specificity was 97.8%. Higher hypoperfusion volume was associated with increased CTA-VO detection (OR 1.03; 95% CI 1.02 to 1.04). EVT was performed in 103 patients (30.5%; Tmax >6s: 102 (63–160) mL), representing 65.6% of all CTP-VO. Overall CTA-VO sensitivity for the detection of EVT-VO was 69.9% and specificity was 95.3%. Among patients who received EVT, the rate of false negative CTA-VO was 30.1% (Tmax >6s: 69 (46–99.5) mL).ConclusionSystematically including CTP in acute stroke admission imaging protocols may increase the diagnosis of VO and rate of EVT.