Intravenous Glu-plasminogen attenuates cholesterol crystal embolism-induced thrombotic angiopathy, acute kidney injury and kidney infarction.

BACKGROUND: Cholesterol crystal (CC) embolism causes acute kidney injury (AKI) and ischaemic cortical necrosis associated with high mortality. We speculated that sustaining the fibrinolytic system with Glu-plasminogen (Glu-Plg) could be a safe way to attenuate AKI and prevent ischaemic infarction upon CC embolism. METHODS: We induced CC embolism by injecting CC into the left kidney artery of C57BL/6J mice. The primary endpoint was glomerular filtration rate (GFR). RESULTS: Starting as early as 2 h after CC embolism, thrombotic angiopathy progressed gradually in the interlobular, arcuate and interlobar arteries. This was associated with a decrease of GFR reaching a peak at 18 h, i.e. AKI, and progressive ischaemic kidney necrosis developing between 12-48 h after CC injection. Human plasma Glu-Plg extracts injected intravenously 4 h after CC embolism attenuated thrombotic angiopathy, GFR loss as well as ischaemic necrosis in a dose-dependent manner. No bleeding complications occurred after Glu-Plg injection. Injection of an intermediate dose (0.6 mg/kg) had only a transient protective effect on microvascular occlusions lasting for a few hours without a sustained protective effect on AKI at 18-48 h or cortical necrosis, while 1.5 mg/kg were fully protective. Importantly, no bleeding complications occurred. CONCLUSIONS: These results provide the first experimental evidence that Glu-Plg could be an innovative therapeutic strategy to attenuate thrombotic angiopathy, AKI, kidney necrosis and potentially other clinical manifestations of CC embolism syndrome.

Directing a dispersion cannula tip toward the aortic root during thoracic aortic arch surgery does not adversely affect cardiac function.

INTRODUCTION: Neurologic complications of open thoracic aortic surgery are devastating problems in patients with severely diseased aortas. This study aimed to clarify whether directing the aortic cannula tip toward the aortic root affects the postoperative cardiac function in patients undergoing open thoracic aortic surgery. METHODS: A total of 16 patients who underwent total or partial arch replacement between January 2014 and April 2019 were enrolled and divided into two groups. Ascending aorta perfusion was performed by placing the cannula tip toward the aortic root (reversed direction group, seven patients) or toward the aortic arch (standard direction group, nine patients). Intraoperative and perioperative data, including mortality, morbidity, and postoperative cardiac function, were compared between the groups. RESULTS: There were no hospital deaths or stroke events in either group. The aortic cross-clamping time was 102.4 ± 20.3 minutes in the reversed direction group and 87.1 ± 9.9 minutes in the standard direction group (p = 0.049). Furthermore, the intubation time was 28.4 ± 12.9 hours in the reversed direction group and 12.4 ± 6.8 hours in the standard direction group (p = 0.022). Both times were significantly longer in the reverse direction group. Postoperative serum creatine kinase-MB levels were significantly lower in the reversed direction group (6.2 ± 3.3 U/L vs 13.3 ± 4.8 U/L, respectively, p = 0.006). The cardiac output and cardiac index did not significantly differ. CONCLUSIONS: Directing the aortic cannula tip toward the aortic root does not adversely affect the postoperative cardiac function after aortic arch surgery.

Neurological complications are avoidable during CABG.

OBJECTIVE: To review the incidence of stroke in patients undergoing CABG and the impact of a preventive strategy adopted at tertiary care unit of cardiac surgery. METHODS: The data of all patients who underwent isolated CABG (N= 722) from July 2016 to August 2017 at Faisalabad Institute of Cardiology was retrieved for this retrospective study. All operations were done on cardiopulmonary bypass and cold blood cardioplegia. Numeric data was summarized as Mean ± Standard Deviation while categoric variables were summarized into frequency and percentage. RESULTS: Mean age of patients was 53.83±8.8 years. Mean Parsonnet and Logistic EuroScore were 4.3±3.2 and 3.3±0.9 respectively. Forty nine patients (6.78%) had significant carotid artery disease. Mean number of grafts was 2.8±0.82. Diabetes was present in 27.8% patients. Neurological complications were noticed in 14 patients (1.94%) who included 12 permanent paralyses. Further subgroup analysis revealed that 67 patients who were operated by single clamp technique remained free of neurological complications. This is clinically remarkable finding but due to small population size it is statistically non- significant. CONCLUSION: The incidence of neurological complications can be reduced significantly by adopting the appropriate preventing measures. Use of Single Clamp technique may be the reasons of such a low incidence of stroke in this study.

The effect of predisposing atheroembolic risk factors on renal functional recovery between laparoscopy and open technique in patients with T1-stage renal cell carcinoma who underwent partial nephrectomy: a retrospective comparison study.

Objective: The present study aimed to determine the effect of an increasing number of predisposing atheroembolic risk factors on the development of chronic kidney disease (CKD) after partial nephrectomy (PN) in patients with T1-stage renal cell carcinoma (RCC). Methods: The study included 147 patients with T1-stage RCC with a normal contralateral kidney and without preoperative CKD, who underwent open (OPN, N = 83, 56.5%) or laparoscopic PN (LPN, N = 64, 43.5%) between 2003 and 2014. Postoperative CKD was defined as an estimated glomerular filtration rate <60 ml/min/1.73 m2. The predictive factors for CKD between OPN and LPN were statistically assessed among various known clinicopathological factors associated with renal function in PN with a significance of two-sided P value <0.05. Results: During a median follow-up of 42 months, the recurrence rate was 0.7% (n = 1), and the rate of postoperative CKD was 11.6% (n = 17). Significant differences in CKD-free survival were observed among patients with atheroembolic risks 5-7, 3-4 and 1-2 (P = 0.027). Regarding the predictive factors for the postoperative development of CKD between OPN and LPN, a predisposing atheroembolic risk ≥3 was significant among other clinicopathological factors in multivariate analysis (hazard ratio, 3.007, P = 0.031). Conclusion: Patients with T1-staged RCC with ≥3 predisposing atheroembolic risk factors have a significantly higher risk of developing CKD after PN. Patients who underwent LPN had a lesser incidence of CKD development than patients who underwent OPN with ≥3 predisposing atheroembolic risk factors.

Numerical simulation of blood flow in femoral perfusion: comparison between side-armed femoral artery perfusion and direct femoral artery perfusion.

Computational numerical analysis was performed to elucidate the flow dynamics of femoral artery perfusion. Numerical simulation of blood flow was performed from the right femoral artery in an aortic model. An incompressible Navier-Stokes equation and continuity equation were solved using computed flow dynamics software. Three different perfusion models were analyzed: a 4.0-mm cannula (outer diameter 15 French size), a 5.2-mm cannula (18 French size) and an 8-mm prosthetic graft. The cannula was inserted parallel to the femoral artery, while the graft was anastomosed perpendicular to the femoral artery. Shear stress was highest with the 4-mm cannula (172 Pa) followed by the graft (127 Pa) and the 5.2-mm cannula (99 Pa). The cannula exit velocity was high, even when the 5.2-mm cannula was used. Although side-armed perfusion with an 8-mm graft generated a high shear stress area near the point of anastomosis, flow velocity at the external iliac artery was decreased. The jet speed decreased due to the Coanda effect caused by the recirculation behind sudden expansion of diameter, and the flow velocity maintains a constant speed after the reattachment length of the flow. This study showed that iliac artery shear stress was lower with the 5.2-mm cannula than with the 4-mm cannula when used for femoral perfusion. Side-armed graft perfusion generates a high shear stress area around the anastomotic site, but flow velocity in the iliac artery is slower in the graft model than in the 5.2-mm cannula model.

Recurrent Aortic Thromboembolism Associated With TET2 Mutation in Chronic Myelomonocytic Leukemia.

Ten-eleven translocation 2 (TET2) plays a pivotal role in epigenetic regulation, cell differentiation, and the inflammatory response. It also mediates the transcriptional regulation for inflammatory cytokines, particularly interleukin-6. While loss-of-function mutation in TET2 has been associated with hematological malignancies, it has been increasingly recognized to cause atherosclerotic disease. The increased atherogenicity is thought to be the result of increased production of pro-inflammatory interleukin-1ß cytokines following activation of NLRP3 inflammasomes. We present a unique case of recurrent atherothrombosis in an elderly man who was diagnosed with chronic myelomonocytic leukemia in the setting of TET2 mutation.

Impact of venous thromboembolism on incidence of arterial thromboembolism - An analysis of German outpatient claims data.

BACKGROUND: Venous thromboembolism (VTE) and arterial thromboembolism (ATE) are considered as two separate disease-entities. In recent years, studies have reported clear associations between VTE and atherosclerosis. We aimed to evaluate the long-term risk of ATE in VTE patients in comparison to controls without VTE. METHODS: Nationwide outpatient claims data of all inhabitants with statutory health insurance in Germany were used for secondary data analysis between the years 2011 and 2020. Patients treated in 2013 were stratified by VTE event, and groups were 1:2-matched by age and sex. The hazard for an ATE event in a 5-year follow-up period between patients with and without VTE was calculated with multivariable Cox regression adjusted for age, sex, cardiovascular risk factors, and comorbidities. RESULTS: Of 69,699,277 individuals treated in the year 2013 by German physicians in outpatient care, in total 686,382 individuals (age 59.8 ± 17.5 years, 65.4 % females) were included comprising 228,794 patients with VTE and 457,588 controls without VTE. VTE patients more often had cardiovascular risk factors (81.6 % vs. 62.2 %) and traditional VTE risk factors. The occurrence of ATE events during follow-up was 1.8 %-points higher in VTE patients in comparison to the controls (9.7 % vs. 7.9 %). VTE events were independently associated with increased occurrence of ATE events within follow-up (HRadjusted 1.19 [99%CI 1.16-1.23], p < 0.0001). CONCLUSIONS: Patients with a VTE event have an increased long-term risk for subsequent arterial cardiovascular events. Large prospective cohorts are needed to identify patient subgroups with a very high ATE risk after VTE.

Acute Kidney Injury Management Strategies Peri-Cardiovascular Interventions.

In many countries, the aging population and the higher incidence of comorbid conditions have resulted in an ever-growing need for cardiac interventions. Acute kidney injury (AKI) is a common complication of these interventions, associated with higher mortalities, chronic or end-stage kidney disease, readmission rates, and hospital and post-discharge costs. The AKI pathophysiology includes contrast-associated AKI, hemodynamic changes, cardiorenal syndrome, and atheroembolism. Preventive measures include limiting contrast media dose, optimizing hemodynamic conditions, and limiting exposure to other nephrotoxins. This review article outlines the current state-of-art knowledge regarding AKI pathophysiology, risk factors, preventive measures, and management strategies in the peri-interventional period.

Who shot first? Three possible causes of a kidney infarction. / ¿Quién disparó primero? Infarto renal de tres posibles causas.

Renal infarction is a rare disease whose incidence is less than 1%. The symptoms can be abdominal or flank pain, nausea, vomiting, fever or hypertension. The diagnosis is complex, and it is based on symptoms, blood analysis with an elevated level of lactate dehydrogenase and computed tomography angiography. The two major causes of renal infarction are thromboembolism and in situ thrombosis. The treatment depends on an adequate etiological diagnosis.

An Unusual Presentation of Cholesterol Embolization Syndrome.

Cholesterol embolization syndrome (CES) is a rare presentation of systemic atherosclerosis, which commonly presents in patients with risk factors of coronary artery disease and usually occurs after cardiac or vascular procedures. Laboratory tests are nonspecific, and imaging studies may visualize the plaque. Management includes supportive care directed to relieve the end-organ damage. The prognosis of CES is poor, with high mortality of up to 29% if the CES resulted in atheroembolic renal disease (AERD). In our report, we present a 90-year-old Caucasian female who was diagnosed with CES and complicated with AERD. The patient did not undergo any cardiac or vascular procedures. This case highlights the importance of considering CES and AERD as a potential cause of renal failure, especially in high-risk patients, even if the patients did not have any history of cardiac or vascular intervention.

Cholesterol crystal embolism-related cerebral infarction: Magnetic resonance imaging and clinical characteristics.

BACKGROUND AND AIMS: Cholesterol crystal embolism-related cerebral infarction (CCE-CI) is frequently misdiagnosed due to the lack of specific symptoms. To aid in differential diagnosis, this study comprehensively characterized the magnetic resonance imaging (MRI) and clinical manifestations of CCE-CI and compared these features to those of atherothrombotic cerebral infarction (ACI). METHODS: This single-center, retrospective, observational study was conducted at Kitasato University Hospital, Kanagawa, Japan. We identified 37 clinically or histopathologically confirmed CCE-CI cases and 110 ACI cases treated from January 2006 to May 2020. Groups were compared for mean age, sex ratio, clinical presentations, imaging manifestations, precipitating factors, comorbid conditions, medications, and smoking history. RESULTS: Of 37 eligible patients with CCE-CI, 10 (27.0%) received brain MRI, of which 8 (21.6%) exhibited high-intensity signals indicative of brain lesions on diffusion-weighted imaging (DWI). However, two patients with DWI lesions exhibited no detectable neurological abnormalities. Patients with CCE-CI frequently demonstrated bilateral DWI lesions involving the bilateral anterior and posterior circulation, a pattern absent in ACI (50% vs. 0%, p < 0.001). Compared to patients with ACI, CCE-CI patients also demonstrated significantly lower estimated glomerular filtration rate (p < 0.001) as well as more frequent eosinophilia (p = 0.006), atherosclerotic plaques ≥4-mm thick in the ascending aorta or proximal arch (p = 0.001), and aortic aneurysm (p < 0.001). CONCLUSIONS: Patients with CCE-CI develop multiple DWI lesions across several vascular territories, even in the absence of neurological symptoms. Comorbid aortic aneurysm may increase CCE-CI risk. These findings could help in the differential diagnosis of CCE-CI.

[Update on cholesterol crystal embolism]. / État des lieux de la maladie des emboles de cholestérol.

Cholesterol crystal embolism is a systemic pathology associated with diffuse atherosclerosis. Pathophysiology corresponds to tissue necro-inflammation secondary to arteriolar occlusion associated with microembolism from atherosclerotic plaques of large diameter arteries. The clinical presentation is heterogeneous and polymorphic. Multiple organs may be the targets, but preferential damage is skin, kidneys and digestive system. It is a serious pathology, underdiagnosed, with a poor prognosis. The risk factors for developing the disease remain the same risk factors as atheroma. The factors favouring migration of microembolism remain mainly vascular interventional procedures; easy to diagnose, they oppose spontaneous embolic migrations or secondary to the introduction of antithrombotic treatment, whose diagnosis is more difficult and the prognosis more severe. The diagnosis of the disease remains mostly a diagnosis of elimination and often refers to a bundle of clinical, biological, morphological and histologic arguments. The treatment is poorly codified and the subject of few publications. It will favour both symptomatic treatment (and mainly that of pain) and complications (high blood pressure, renal insufficiency). The aetiological support remains less consensual. The treatment of atherosclerotic plaques consists, of course, in the correction of classical cardiovascular risk factors, the introduction of a statin. It will be discussed in the implementation of surgery or angioplasty to exclude potentially responsible atherosclerotic lesions. Eviction of antithrombotic therapy should be considered in terms of the benefit-risk balance, but often in favour of maintaining it. Finally, other treatments may be proposed in a case-by-case basis, such as oral or intravenous corticosteroid therapy, colchicine or LDL aphaeresis.

Atheroembolic Renal Disease: A Case Series.

Atheroembolic renal disease (AERD), a part of systemic cholesterol embolization syndrome, is caused by the occlusion of small arteries in the kidneys by cholesterol crystal emboli from ulcerated atherosclerotic plaques. Kidney is commonly involved because of its proximity to the abdominal aorta and its enormous blood supply. AERD is an under diagnosed condition. We report eight cases of AERD, highlighting the variability in its clinical presentation and the importance of a renal biopsy to arrive at a definitive diagnosis.

Risks of Stroke After Coronary Artery Bypass Graft - Recent Insights and Perspectives.

Stroke is one of the most devastating complications after coronary artery bypass graft (CABG) surgery, entailing permanent disability, a 3-6 fold increased risk of mortality, an incremental hospital resource consumption and a longer length of hospital stay. Notwithstanding advances in surgical, anaesthetic and medical management across the last 10 years, the risk of stroke after CABG has not significantly declined, likely because an older and sicker population is now deemed suitable to undergo CABG. The pathogenesis of stroke is multifactorial, but two variables are believed to play a major role - cerebral embolisation of atheromatous debris arising from the ascending aorta during surgical manipulation and hypoperfusion during surgery. Identification of vulnerable patients at increased risk of stroke before CABG is of paramount importance for the surgical decision-making approach and informed consent. Several models including demographic, clinical and procedural variables have been developed to risk-stratify the hazard of stroke in patients undergoing CABG, but identification of severe atherosclerosis of the ascending aorta and pre-existing cerebrovascular disease are key determinants for appropriate risk stratification and decision-making. Atherosclerotic disease of the ascending aorta can be identified before surgery using transoesophageal echocardiography, computed tomography and magnetic resonance imaging. However, intra-operative ultrasound scanning of the ascending aorta is the diagnostic tool with the best sensitivity and specificity for the detection of atheromatous debris in the ascending aorta. Although many investigators have advocated the use of off-pump CABG to minimise the risk of peri-operative stroke, results from randomised trials and meta-analyses have been inconsistent. Anaortic approaches, including total arterial revascularisation with in situ grafting of both mammary arteries, or the use of the HEARTSTRING® seal device avoid any manipulation of the aorta, thus potentially minimising the risk of stroke in high-risk patients. Assessment and treatment of severe carotid artery disease, and aggressive and prompt treatment of post-operative atrial fibrillation are other important strategies that should be routinely implemented to reduce the risk of stroke in patients undergoing CABG.

Arterial embolism.

Surgical and intensive care patients are at a heightened risk for arterial embolization due to pre-existing conditions such as age, hypercoagulability, cardiac abnormalities and atherosclerotic disease. Most arterial emboli are clots that originate in the heart and travel to distant vascular beds where they cause arterial occlusion, ischemia, and potentially infarction. Other emboli form on the surface of eroded arterial plaque or within its lipid core. Thromboemboli are large clots that dislodge from the surface of athesclerotic lesions and occlude distal arteries causing immediate ischemia. Atheroemboli, which originate from fracturing the lipid core tend to cause a process of organ dysfunction and systemic inflammation, termed cholesterol embolization syndrome. The presentation of arterial emboli depends on the arterial bed that is affected. The most common manifestations are strokes and acute lower limb ischemia. Less frequently, emboli target the upper extremities, mesenteric or renal arteries. Treatment involves rapid diagnosis, which may be aided by precise imaging studies and restoration of blood flow. The type of emboli, duration of presentation, and organ system affected determines the treatment course. Long-term therapy includes supportive medical care, identification of the source of embolism and prevention of additional emboli. Patients who experienced arterial embolism as a result of clots formed in the heart should be anticoagulated. Arterial emboli from atherosclerotic disease of the aorta or other large arteries should prompt treatment to reduce the risk for atherosclerotic progression, such as anti-platelet therapy and the use of statin drugs. The use of anticoagulation and surgical intervention to reduce the risk of arterial embolization from atherosclerotic lesions is still being studied.