2D perfusion angiography as quantitative method to evaluate iloprost effect on foot circulation

Summary: Background: Two-dimensional (2D) perfusion angiography is useful for the evaluation of foot perfusion in patients with critical limb-threatening ischemia (CLTI). Iloprost is a synthetic prostacyclin analogue presenting vasodilating properties. Aim of this study was to demonstrate the utility of 2D perfusion angiography as quantitative method to evaluate iloprost effect on foot circulation. Patients and methods: Between January 2020 and June 2020 25 patients with CLTI underwent below-the-knee (BTK) endovascular revascularization, intra-arterial administration of iloprost, and assessment of foot perfusion by 2D perfusion angiography. Iloprost was administered as an intra-arterial bolus of 3 μg over 1–3 minutes immediately after BTK revascularization. The 2D perfusion angiography was performed in a standardized manner with a 5-F catheter placed into the popliteal artery. A wide region of interest (ROI) was identified to assess the foot perfusion. Time–density curves were calculated by the perfusion software. Changes of the overall time-density curves before and after the administration of iloprost were evaluated. Results: Endovascular revascularization was successful in all cases. The mean reduction of systolic pressure value after iloprost administration was 23.1 mmHg. Eight patients (32%) experienced a minor complication (6 cutaneous rush, 2 symptomatic hypotension >40 mmHg). In 20 patients the time-density curves under ROI increased after the intra-arterial administration of iloprost (+31.6%, range from +4.9% to +78.7%). Five patients had no modification or a slight decrease of foot perfusion after iloprost administration (non-responders patients). Conclusions: Patients undergoing intra-arterial administration of iloprost accounted for a not negligible rate of minor complications. 2D perfusion angiography was valuable as quantitative method to evaluate the iloprost effect on foot circulation. This technique could be useful to classify the patients in responders or non-responders to iloprost therapy.

Coronary Microvascular Dysfunction

Coronary microvascular dysfunction (DMK) is a condition of patients who are accompanied by complaints of chest pain where the results of coronary angiography examination are normal and this is almost 49% with 60% of patients diagnosed with DMK. Another study said that about 40% of patients with DMK showed coronary flow reserve (CFR <2) of about 40% and the WISE study (Women's Ischaemia Syndrome Evaluation) showed that about 47% of patients with chest pain had normal coronary arteries. DMK can be divided into 4 groups; DMK with no coronary arterial disease (CAD) obstruction and myocardial disease, DMK with myocardial disease where this occurs due to remodeling of intramural coronary arteries, DMK with CAD (coronary arterial disease) or acute myocardial infarction with or without ST segment, iatrogenic typhoid DMK occurs after coronary recanalization caused by vasoconstriction and distal embolization. The mechanism of action of DMK can be caused by several factors, namely endothelial dysfunction, smooth muscle dysfunction, decreased diastolic perfusion time, damage to blood vessels and damage to the vascular and microvascular remodeling. And to enforce this DMK, there are several tests carried out in diagnosing the disease, some of which are invasive and non-invasive so that by enforcing the diagnosis of this disease, treatment for DMK can be done immediately and optimally.

MR imaging characteristics of uveal melanoma with histopathological validation

Purpose To evaluate the magnetic resonance imaging (MRI) characteristics of uveal melanoma (UM), to compare them with fundoscopy and ultrasound (US), and to validate them with histopathology. Methods MR images from 42 UM were compared with US and fundoscopy, and on 14 enucleated cases with histopathology. Results A significant relationship between the signal intensity on T1 and pigmentation on histopathology was found (p=0.024). T1 hyperintense UM were always moderately or strongly pigmented on histopathology, while T1-hypointense UM were either pigmented or non-pigmented. Mean apparent diffusion coefficient (ADC) of the UM was 1.16 ± 0.26 × 10−3 mm2/s. Two-thirds of the UM had a wash-out and the remaining a plateau perfusion time-intensity curve (TIC). MRI was limited in evaluating the basal diameter of flat tumors. US tends to show larger tumor prominence (0.5mm larger, p=0.008) and largest basal diameter (1.4mm larger, p<0.001). MRI was good in diagnosing ciliary body involvement, extrascleral extension, and optic nerve invasion, but limited on identifying scleral invasion. An increase of tumor prominence was associated with lower ADC values (p=0.030) and favored a wash-out TIC (p=0.028). An increase of tumor ADC correlated with a plateau TIC (p=0.011). Conclusions The anatomical and functional MRI characteristics of UM were comprehensively assessed. Knowing the MRI characteristics of UM is important in order to confirm the diagnosis and to differentiate UM from other intra-ocular lesions and because it has implications for treatment planning. MRI is a good technique to evaluate UM, being only limited in case of flat tumors or on identifying scleral invasion.

Perfusate metabolomics content and tubular transporters expression during kidney graft preservation by hypothermic machine perfusion

BackgroundIschemia-related injury during the pre-implantation period impacts kidney graft outcome. Evaluating these lesions by a non-invasive approach before transplantation could help to understand the mechanisms of graft injury and identify potential biomarkers predictive of graft outcomes. This study aims to determine metabolomic content of graft perfusion fluids and its dependence on preservation time and to explore whether tubular transporters are possibly involved in the metabolomics variations observed.MethodsKidneys were stored on hypothermic perfusion machines. We evaluated the metabolomic profiles of perfusion fluids (n=35) using Liquid Chromatography coupled with tandem Mass Spectrometry and studied the transcriptional expression of tubular transporters on pre-implantation biopsies (n=26). We used univariate and multivariate analyses to assess the impact of perfusion time on these parameters and their relationship with graft outcome.ResultsSeventy-two metabolites were found in preservation fluids at the end of perfusion, of which 40% were already present in the native conservation solution. We observed an increase of 23 metabolites with longer perfusion time and a decrease for 8. The predictive model for time-dependent variation of metabolomics content showed good performance (R2= 76%, Q2= 54%, accuracy= 41%, permutations test significant). Perfusion time had no effect on the mRNA expression of transporters. We found no correlation between metabolomics and transporters expression. Neither the metabolomics profile nor the transporters expression were predictive of graft outcome.ConclusionOur results open the way for further studies, focusing on both intra- and extra-tissue metabolome, to investigate whether transporter alterations can explain the variations observed in pre-implantation period.

Hemoperfusion with CytoSorb® in Critically Ill COVID-19 Patients

<b><i>Introduction:</i></b> Systematic inflammatory response occurred in some critically ill patients with COVID-19. Cytokine reduction by hemadsorption is a mechanism of treatment. However, whether CytoSorb hemoperfusion works for critically ill COVID-19 patients remains unknown. <b><i>Materials and Methods:</i></b> We observed case series of critically ill COVID-19 patients receiving CytoSorb hemoperfusion as rescue therapy from 3 hospitals in Hubei, China from February 28, 2020, to April 7, 2020. Their demographic, laboratory, and clinical data were collected. The parameters for organ function and IL-6 levels were compared before and after treatments. <b><i>Results:</i></b> A total of 10 cases were included. The median age of the patients was 67.7 years (range = 50–85) with APACHE II (23.5) and SOFA (11.4). Patients received a median of 3 attempts of hemoperfusion (range = 1–6). The median CytoSorb perfusion time was 47 h (12–92 h). The level of IL-6 significantly decreased after treatments (712.6 [145–5,000] vs. 136.7 [46.3–1,054] pg/mL, <i>p</i> = 0.005). Significant improvement was found in PaO₂/FiO₂ (118 [81–220] vs. 163 [41–340] mm Hg, <i>p</i> = 0.04) and lactate levels (2.5 [1–18] vs. 1.7 [1.1–10] mmol/L, <i>p</i> = 0.009). The hemodynamics measured by norepinephrine/MAP slightly improved after treatment (17 [0–68] vs. 8 [0–39], <i>p</i> = 0.09). Albumin mildly decreased after CytoSorb. No significant changes were found in red blood cell counts, white cell counts, and platelets. <b><i>Conclusion:</i></b> Treatment with CytoSorb in critically ill COVID-19 patients was associated with decreased IL-6 improvement in oxygenation. However, these effects cannot be confirmed as the direct effects of CytoSorb owing to lack of controls. Establishing causality requires large-scale randomized clinical trials.

Normative distribution of posterior circulation tissue time-to-maximum: Effects of anatomic variation, tracer kinetics, and implications for patient selection in posterior circulation ischemic stroke

The generalization of perfusion-based, anterior circulation large vessel occlusion selection criteria to posterior circulation stroke is not straightforward due to physiologic delay, which we posit produces physiologic prolongation of the posterior circulation perfusion time-to-maximum (Tmax). To assess normative Tmax distributions, patients undergoing CTA/CTP for suspected ischemic stroke between 1/2018-3/2019 were retrospectively identified. Subjects with any cerebrovascular stenoses, or with follow-up MRI or final clinical diagnosis of stroke were excluded. Posterior circulation anatomic variations were identified. CTP were processed in RAPID and segmented in a custom pipeline permitting manually-enforced arterial input function (AIF) and perfusion estimations constrained to pre-specified vascular territories. Seventy-one subjects (mean 64 ± 19 years) met inclusion. Median Tmax was significantly greater in the cerebellar hemispheres (right: 3.0 s, left: 2.9 s) and PCA territories (right: 2.9 s; left: 3.3 s) than in the anterior circulation (right: 2.4 s; left: 2.3 s, p < 0.001). Fetal PCA disposition eliminated ipsilateral PCA Tmax delays (p = 0.012). Median territorial Tmax was significantly lower with basilar versus any anterior circulation AIF for all vascular territories (p < 0.001). Significant baseline delays in posterior circulation Tmax are observed even without steno-occlusive disease and vary with anatomic variation and AIF selection. The potential for overestimation of at-risk volumes in the posterior circulation merits caution in future trials.

Myocardial oxygen consumption during histidine-tryptophan-ketoglutarate cardioplegia in young human hearts

OBJECTIVES Energy demand and supply need to be balanced to preserve myocardial function during paediatric cardiac surgery. After a latent aerobic period, cardiac cells try to maintain energy production by anaerobic metabolism and by extracting oxygen from the given cardioplegic solution. Myocardial oxygen consumption (MVO2) changes gradually during the administration of cardioplegia. METHODS MVO2 was measured during cardioplegic perfusion in patients younger than 6 months of age (group N: neonates; group I: infants), with a body weight less than 10 kg. Histidine-tryptophan-ketoglutarate crystalloid solution was used for myocardial protection and was administered during a 5-min interval. To measure pO2 values during cardioplegic arrest, a sample of the cardioplegic fluid was taken from the inflow line before infusion. Three fluid samples were taken from the coronary venous effluent 1, 3 and 5 min after the onset of cardioplegia administration. MVO2 was calculated using the Fick principle. RESULTS The mean age of group N was 0.2 ± 0.09 versus 4.5 ± 1.1 months in group I. The mean weight was 3.1 ± 0.2 versus 5.7 ± 1.6 kg, respectively. MVO2 decreased similarly in both groups (min 1: 0.16 ± 0.07 vs 0.36 ± 0.1 ml/min; min 3: 0.08 ± 0.04 vs 0.17 ± 0.09 ml/min; min 5: 0.05 ± 0.04 vs 0.07 ± 0.05 ml/min). CONCLUSIONS We studied MVO2 alterations after aortic cross-clamping and during delivery of cardioplegia in neonates and infants undergoing cardiac surgery. Extended cardioplegic perfusion significantly reduces energy turnover in hearts because the balance procedures are both volume- and above all time-dependent. A reduction in MVO2 indicates the necessity of a prolonged cardioplegic perfusion time to achieve optimized myocardial protection.

Pharmacokinetics and toxicity of carboplatin used for hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of epithelial ovarian cancer

ObjectivesCarboplatin is frequently used in various doses for hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of epithelial ovarian cancer (EOC) although its pharmacokinetics, including focus on the perfusion time, has not been evaluated when used in modern era cytoreductive surgery (CRS). The aim was to evaluate the pharmacokinetics and hematological toxicity of carboplatin used for HIPEC with a perfusion time of 90 min.MethodsFifteen patients with stage III–IV primary EOC received CRS and 90 min of HIPEC with carboplatin at dose 800 mg/m2. For the pharmacokinetic analysis, perfusate and blood samples were obtained during HIPEC and up to 48 h after HIPEC (blood only). Hematological toxicity within 30 days was graded according to Common Terminology Criteria for Adverse Events. Severe toxicity (grades 3–5) is reported.ResultsMean maximum concentration of carboplatin was 12 times higher in perfusate than plasma (mean CmaxPF=348 µg/mL (range: 279–595 µg/mL) versus mean CmaxPL=29 µg/mL (range: 21–39 µg/mL)). Mean terminal half-life of carboplatin in perfusate was 104 min (range: 63–190 min) and mean intraperitoneal-to-plasma area under the concentration-time curve (AUC) ratio was 12.3 (range: 7.4–17.2). Two patients (13%) had grade 3 neutropenia within 30 days. No grade 4–5 hematological toxicities were identified.ConclusionsCarboplatin has a favorable pharmacokinetic profile for 90 min HIPEC administration, and the hematological toxicity was acceptable at dose 800 mg/m2. Large interindividual differences were found in the pharmacokinetic parameters, making risk of systemic exposure difficult to predict.

Femoral artery cannulation combined with axillary artery cannulation is safe for Stanford type A aortic dissection

Background The optimal cannulation strategy in surgery for Stanford type A aortic dissection is critical to the patients’ survival, but remains controversial. Different cannulation strategies have their own advantages and drawbacks during cardiopulmonary bypass. Our center used femoral and axillary artery cannulation for Stanford type A aortic dissection. The purpose of this study was to review and clarify the clinic outcome of femoral artery cannulation combined with axillary artery cannulation for the treatment of type A aortic dissection. Methods We performed a retrospective study that included 327 patients who were surgically treated for type A aortic dissection in our institution from January 2017 to June 2019.Using femoral and axillary artery cannulation to establish cardiopulmonary bypass in patients with type A aortic dissection. The demographics data and surgical data, clinical results of the patients were calculated. Results Femoral artery combined with axillary artery cannulation was technically successful in 327 patients. The cardiopulmonary bypass time was 141.60 ± 34.89 minutes, and the selective antegrade cerebral perfusion time was 14.94 ± 2.76 minutes. The early mortality was 3.06%. The incidence of permanent neurologic dysfunction was 0.92%. Sixteen patients had post-operative renal insufficiency and five patients with liver failure. Two patients ended up with paraplegia. Conclusion Femoral artery combined with axillary artery cannulation for type A aortic dissection can significantly reduce the occurrence of malperfusion syndrome and nervous system complications, especially for cerebral protection.