Relation between LRG1 and CD4+ T cells, cognitive impairment and neurological function in patients with acute ischemic stroke.

Objective: To assess the relationship between LRG1 and CD4+ T cells, cognitive impairment and neurological function in acute ischemic stroke (AIS). Methods: Plasma LRG1 was detected by ELISA in 175 patients with AIS at baseline, day (D) 1, D7, month (M) 1 and M3. Results: LRG1 was negatively related to Th2 and Treg cells and positively linked to Th17 (all p < 0.05). LRG1 increased from baseline to D1, then decreased until M3 (p < 0.001). LRG1 at each assessment point was increased in patients with cognitive impairment or poor neurological function at M3 versus those without (all p < 0.05). Conclusion: LRG1 is linked to decreased Th2 and Tregs, increased Th17, cognitive impairment and nonideal neurological function recovery in patients with AIS.

Nitinol overdose-rescue of acute limb ischemia caused by stenting of the common iliac, external iliac, common femoral, superficial femoral, and popliteal arteries in an actively smoking patient with claudication.

Intermittent claudication (IC) from peripheral arterial disease is typically managed with pharmacologic interventions and lifestyle changes. However, despite societal guidelines, initial endovascular interventions are being used more frequently with an increased incidence of complications, resulting in rapid disease progression to critical and acute limb-threatening ischemia (ALI). The present report describes the case of a patient who developed ALI after treatment of IC at another facility, with malpositioned bilateral common iliac stents, continuous stent extension into the popliteal artery, and acute occlusion of the entirety of the right lower extremity vasculature. This case illustrates how extensive endovascular intervention for IC can result in ALI requiring urgent revascularization.

Neuritin has a neuroprotective role in the rat model of acute ischemia stroke by inhibiting neuronal apoptosis and NLRP3 inflammasome.

OBJECTIVES: This study explored the anti-inflammatory, anti-neuronal apoptosis, and neuroprotective effects of Neuritin in rat models of acute ischemia stroke (AIS). METHODS: AIS was induced in male Sprague Dawley rats by middle cerebral artery occlusion (MCAO). Rats were divided into sham, MCAO, MCAO+neuritin, MCAO + neuritin + PBS, MCAO + neuritin+MCC950, and MCAO + neuritin + MSU groups. Neurological score assessment, brain water content measurement, HE staining, TTC staining, TUNEL staining, ELISA, and Western blot were performed. RESULTS: Neuritin significantly improved the neurobehavioral score, infarct size, brain water content, apoptosis, and neuroinflammatory response compared with the MCAO and MCAO + PBS groups within 24 h after AIS. Moreover, Neuritin inhibited the protein expression of NLRP3 inflammasome, and reduced the expression of IL-18 and IL-1B, thereby reducing the inflammatory response. Meanwhile, the neuroprotection, anti-inflammation, and anti-apoptosis effects of Neuritin were enhanced by MCC950 but partly counteracted by MSU. CONCLUSION: Neuritin may reduce brain injury after AIS by inhibiting the expression of NLRP3 inflammasome and then inhibiting the inflammatory response.

Clinical impact of the infrapatellar location in symptomatic peripheral arterial disease patients / Impacto clínico de la localización infrapatelar en pacientes con enfermedad arterial periférica sintomática

Abstract Background: Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes. Methods: We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints. Results: From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI] = [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients. Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death, MI, stroke, and MACE events were not different among groups (all p > 0.05). Conclusion: Infrapatellar disease was an independent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellar disease in symptomatic revascularized PAD patients.

Resumen Objetivo: La enfermedad vascular periférica (EVP) afecta generalmente múltiples segmentos de los miembros. Existe información contradictoria con respecto al pronóstico de pacientes con enfermedad aortoilíaca, sin embargo, la diabetes y la enfermedad critica de miembros inferiores habitualmente afecta el territorio infrapatelar. Nuestro objetivo es determinar el impacto de la afectación infrapatelar en eventos cardiovasculares. Métodos: Estudio retrospectivo, observacional en un hospital universitario de Argentina. Se revisó la historia clínica electrónica de pacientes con EVP con requerimiento de revascularización. Se generó un modelo de regresión multivariado incluyendo variables clínicamente relevantes. El punto final primario fue un combinado de hospitalización por isquemia crítica y amputaciones mayores entre pacientes con afectación infrapatelar y suprapatelar. Amputaciones menores, muerte por todas las causas, infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV) y un combinado de eventos cardiovasculares (MACE) fueron los puntos secundarios. Resultados: Se reclutó un total de 309 pacientes desde enero de 2014 hasta julio de 2020. 151 pacientes presentaron enfermedad suprapatelar y 158 infrapatelar. El punto final primario ocurrió en 35 pacientes (22.2%) en el grupo infrapatelar y en 18 pacientes (11.9%) en suprapatelares (HR 2.16; intervalo de confianza 95% [1.22-3.82]; p = 0.008). Ambos componentes ocurrieron con mayor frecuencia en pacientes con afectación infrapatelar. Los eventos de amputación menor fueron mas prevalentes en pacientes con afectación infrapatelar (HR 5.09; IC95% [1.47-17.6]; p = 0.010) La mortalidad por todas las causas, IAM, ACV y MACE no fueron diferentes entre los grupos (p > 0.05). Conclusión: La enfermedad infrapatelar fue un factor independiente para mayor riesgo de hospitalización por isquemia critica, amputación mayor y menor comparado con pacientes con afectación suprapatelar en EVP sintomática revascularizada.

Left subclavian artery pseudoaneurysm after blunt chest trauma with left upper extremity ischemia.

We describe a 74-year-old male with delayed onset of acute left upper extremity ischemia after blunt chest trauma with left clavicular fracture, resulting in left subclavian artery injury, including pseudoaneurysm formation, intramural hematoma, thrombosis, and distal embolization to the brachial artery. The patient presented with left upper extremity pain, forearm and hand numbness, and digital cyanosis. The patient was treated with a hybrid approach, consisting of transfemoral percutaneous deployment of a covered stent in the left subclavian artery and concomitant surgical thrombectomy of the left brachial artery, resulting in excellent recovery and resolution of symptoms.

Longitudinal Change of Plasma Retinol-Binding Protein 4 and its Relation to Neurological-Function Recovery, Relapse, and Death in Acute Ischemic Stroke Patients.

Retinol-binding protein 4 (RBP4) promotes dyslipidemia, insulin resistance, inflammation, and atherosclerosis, etc. which may participate in the progression of acute ischemia stroke (AIS). This study aimed to evaluate the longitudinal change of RBP4 after disease onset and its correlation with prognosis in AIS patients. Plasma RBP4 was measured by enzyme-linked immunosorbent assays in 402 AIS patients at admission, one day (D1), 3 days (D3), 7 days (D7), and 30 days (D30) after admission; and in 100 healthy controls after enrollment. The neurological-function recovery was evaluated by the modified Rankin Scale (mRS) at 3 months (M3); disease relapse and death were also recorded during a median 20-month follow-up in AIS patients. Our study revealed that RBP4 was elevated in AIS patients compared with healthy controls. RBP4 was related to a history of diabetes mellitus, a history of cardiovascular disease, and elevated National Institutes of Health Stroke Scale score in AIS patients. Longitudinally, RBP4 was increased from admission to D1/D3, then reduced gradually to D30 in AIS patients. Notably, RBP4 at admission and D1 was elevated in AIS patients with mRS > 2 compared to those with mRS ≤ 2. Meanwhile, RBP4 at admission, D1, D3, D7, and D30 were all higher in AIS patients occurred relapse than those without; RBP4 at D3, D7, and D30 were also higher in AIS patients who died later than those who survived. In conclusion, plasma RBP4 originally elevates and continuously decreases during disease, which forecasts neurological-function recovery status, relapse, and death risk of AIS.

Clinical impact of the infrapatellar location in symptomatic peripheral arterial disease patients.

Background: Peripheral artery disease (PAD) frequently affects multiple segments of the limbs. Contradictory data have reported worse prognosis in aortoiliac lesions, nevertheless, diabetes and chronic limb ischemia frequently affects the infrapatellar territory. Our aim was to assess the impact of infrapatellar disease in cardiovascular outcomes. Methods: We performed a retrospective, observational cohort study at a university hospital in Argentina. Electronic health records were retrospectively reviewed including symptomatic PAD patients requiring revascularization. A multivariable regression model was performed to account for confounders. The primary endpoint was a composite of hospitalizations due to chronic limb threatening ischemia (CLTI) and major amputation events between infrapatellar and suprapatellar patients. Minor amputation events, all-cause death, myocardial infarction (MI), stroke, and major cardiovascular events (MACE) were secondary endpoints. Results: From January 2014 through July 2020, a total of 309 patients were included in the analysis. 151 patients had suprapatellar disease, and 158 had infrapatellar disease. The primary composite endpoint occurred in 35 patients (22.2%) in the infrapatellar patients and 18 patients (11.9%) in the suprapatellar patients (HR = 2.16; 95% confidence interval [CI]= [1.22-3.82]; p = 0.008). Both components of the primary outcomes occurred more frequently in infrapatellar patients.Minor amputation events were more prevalent in infrapatellar patients (HR = 5.09; 95% CI = [1.47-17.6]; p = 0.010). Death,MI, stroke, and MACE events were not different among groups (all p > 0.05). Conclusion: Infrapatellar disease was anindependent factor for increased hospitalization of CLTI, major and minor amputations events, compared to suprapatellardisease in symptomatic revascularized PAD patients.

Objetivo: La enfermedad vascular periférica (EVP) afecta generalmente múltiples segmentos de los miembros. Existe información contradictoria con respecto al pronóstico de pacientes con enfermedad aortoilíaca, sin embargo, la diabetes y la enfermedad critica de miembros inferiores habitualmente afecta el territorio infrapatelar. Nuestro objetivo es determinar el impacto de la afectación infrapatelar en eventos cardiovasculares. Métodos: Estudio retrospectivo, observacional en un hospital universitario de Argentina. Se revisó la historia clínica electrónica de pacientes con EVP con requerimiento de revascularización. Se generó un modelo de regresión multivariado incluyendo variables clínicamente relevantes. El punto final primario fue un combinado de hospitalización por isquemia crítica y amputaciones mayores entre pacientes con afectación infrapatelar y suprapatelar. Amputaciones menores, muerte por todas las causas, infarto agudo de miocardio (IAM), accidente cerebrovascular (ACV) y un combinado de eventos cardiovasculares (MACE) fueron los puntos secundarios. Resultados: Se reclutó un total de 309 pacientes desde enero de 2014 hasta julio de 2020. 151 pacientes presentaron enfermedad suprapatelar y 158 infrapatelar. El punto final primario ocurrió en 35 pacientes (22.2%) en el grupo infrapatelar y en 18 pacientes (11.9%) en suprapatelares (HR 2.16; intervalo de confianza 95% [1.22-3.82]; p = 0.008). Ambos componentes ocurrieron con mayor frecuencia en pacientes con afectación infrapatelar. Los eventos de amputación menor fueron mas prevalentes en pacientes con afectación infrapatelar (HR 5.09; IC95% [1.47-17.6]; p = 0.010) La mortalidad por todas las causas, IAM, ACV y MACE no fueron diferentes entre los grupos (p > 0.05). Conclusión: La enfermedad infrapatelar fue un factor independiente para mayor riesgo de hospitalización por isquemia critica, amputación mayor y menor comparado con pacientes con afectación suprapatelar en EVP sintomática revascularizada.

Bilateral Acute Hippocampal Ischemia in Two Patients Abusing Cocaine: What is the Outcome?

Hippocampal ischemia is a rare complication of cocaine abuse that has been thought to arise from vasospasm, anoxic injury, and/or catecholaminergic excitotoxicity. We present two cases of patients abusing cocaine, who presented with an acute onset anterograde amnesia due to bilateral hippocampal ischemia, and had different outcomes. Case 1 is a 49-year-old male with a history of IV heroin abuse who presented after being found down for an unknown period of time. He awoke with no memory of events leading up to hospitalization and was unable to retain new information. Urine toxicology was positive for cocaine and opiates. Traditional vascular risk factors included obesity, hypertension, and hyperlipidemia. His recovery was complicated by continued drug use and one episode of cardiac arrest. Despite cognitive rehabilitation, only minimal improvements in his anterograde memory were observed during his annual follow-up. Case 2 is a 23-year-old male with a history of attention deficit disorder treated with dexmethylphenidate and a history of consistent marijuana and cocaine abuse, who presented with nausea, vomiting, chest pain, shortness of breath, and acute-onset short-term memory loss. Urine toxicology was negative for cocaine and opiates and positive for marijuana. He had no known vascular risk factors. With cognitive rehabilitation and discontinuation of illicit drug use, he demonstrated a significant improvement in his memory function over the course of six months. Brain MRI in both patients showed symmetric bilateral hippocampal diffusion restriction without post-contrast enhancement with corresponding hyperintensities on fluid-attenuated inversion recovery sequences. In both patients, cerebrospinal fluid (CSF) studies were unremarkable for inflammation or infection, and electroencephalograms were normal in awake and drowsy states. Bilateral hippocampal ischemia should be considered as a potential cause of acute onset anterograde amnesia in patients with a history of cocaine abuse. Other substances such as heroin and dexmethylphenidate may potentially increase susceptibility for hippocampal ischemia in patients using cocaine. Discontinuation of illicit drug abuse can influence the degree of recovery from acute bilateral hippocampal ischemia.

Exposure-Response Analysis and Mechanism of Ginkgolide B's Neuroprotective Effect in Acute Cerebral Ischemia/Reperfusion Stage in Rat.

Ginkgolide B (GKB) is a well-established neuroprotectant for acute ischemia stroke. However, its cerebral exposure and real-time response remain elusive in acute ischemia/reperfusion stage, and it hinders its usage in therapeutic window of ischemia stroke. Therefore, we investigate the exposure-response relationship of GKB (10 mg/kg, intravenously (i.v.)) as well as its neuroprotective mechanism in acute ischemia/reperfusion rats. Cerebral and plasma exposure of GKB is comparatively explored in both of normal rats and acute ischemia/reperfusion rats. Correspondingly, neurological function and brain jury indexes were assessed at each time point, and superoxide dismutase (SOD), malondialdehyde (MDA), platelet activator factor (PAF) and thromboxane A2 (TXA2) are indexed as pharmacological response to GKB. Exposure-response relationships are analyzed by using linear regression. Additionally, cerebral expressions of proteins in PAF-regulated pathways are tested at each time point. Results show cerebral and plasma concentrations of GKB are much higher in acute ischemia/reperfusion rats than those in normal rats. Cerebral infarction, neurological function (NF) score, abnormal PAF and excessive MDA are significantly alleviated in 24 h after GKB injection, and PAF is reduced in exposure-response manner with significant concentration-response relationship (R2 = 0.9123). Regarding downstream proteins in intracellular PAF-regulated pathway, GKB progressively inhibits Bax, Caspase-3, p-p65 and p-IKK, while gradually restoring LC3B, p62 and p-mammalian target of rapamycin (mTOR) to the basic level within 24 h. Conclusively, GKB exhibits greater cerebral exposure in acute ischemia/reperfusion rats and neuroprotective effect through reducing PAF in exposure-response manner and mediating PAF-regulated intracellular signaling pathways. Our finding highlights clinical implications of GKB in therapeutic time window of ischemic stroke.

Are Small Popliteal Aneurysm so Innocent?

BACKGROUND: We recently recorded 5 lower limb ischemia related to a small (diameter≤20 mm) popliteal artery aneurysm (PAA) thrombosis hence we performed a retrospective data analysis on small symptomatic PAA management from our database. METHODS: We performed a retrospective cohort study on 48 acute leg ischemia from aneurysm's thrombosis. All of them underwent surgical distal thrombectomy and bypass creation. Patients were divided into 2 different cohorts: GROUP A (diameter ≥20 mm) and GROUP B (diameter ≤20 mm). Differences in terms of the limb salvage (end-point: the amputation rate) was analyzed and considered significative for P ≤ 0.05. Secondary objectives were: vessel runoff recovery and patency rate. Adverse events were collected at 12 and 24 months postoperative. RESULTS: Two-year overall amputation rate was: 22.9% (11/48); 21.8% (7/32) in GROUP A and 25% (4/16) in GROUP B (RR:0.87, CI:0.29-2.55, p.80). The mean age was 68 ± 13 years, No statistically significant differences were identified in term of primary and secondary patency (RR:0.95, CI:0.55-1.6, p.85 and (RR:0.95, CI:0.53-1.7, p.88 respectively) no differences were found in terms of comorbidities. Patients' follow-up ranged from 8 to 36 months. In 90% of those amputated patients, the length of ischemia exceeded 4 days. Amputation rate was correlated with one runoff vessel recovery, only. CONCLUSION: s According these results small PAA are not as innocent as it is often presumed and was associated with not negligible incidence of limb loss due to thrombosis or distal embolizations also if compared to larger aneurysm. The immediate surgery is mandatory also when the ischemia exceeds 2 days.

Successful Thrombolysis of Acute Upper Limb Ischemia Using Ekosonic Endovascular System Ultrasound Catheter in a Patient With Atrial Fibrillation.

Acute upper limb ischemia is considered a vascular emergency. These events are mostly thromboembolic and are often detected in patients with atrial fibrillation (AF). Surgical thrombectomy and percutaneous mechanical thrombectomy are the usual methods to treat this medical emergency. In this case, we report the case of a 75-years old woman with a history of AF who initially presented to our center because of syncope resulting from Torsades de pointes due to a known long-QT syndrome. Those episodes were treated adequately from the implanted ICD. In addition to the symptoms of syncope, the patient also noted symptoms of right upper-limb ischemia. Using duplex sonography, we noticed a thrombotic occlusion at the level of the axillary artery. Using femoral access, we performed an antegrade angiography of the axillary artery, which confirmed a fresh thrombotic occlusion. The initially performed thrombus aspiration wasn't successful, and the decision was made to use an ekosonic endovascular system (Ekosonic ™ Endovascular System, Boston Scientific, EKOS) catheter to perform catheter-directed thrombolysis. Locally, 10 mg Actilyse were administrated. Then an EKOS Catheter was delivered to the occlusion area and was placed for 6 h. Symptoms of ischemia were resolved, and the angiographic control showed normal flow in the axillary artery. The patient was discharged without any local deficits of the right hand.

Hyperbaric oxygen therapy does not alleviate tourniquet-induced acute ischemia-reperfusion injury in mouse skeletal muscles.

During tourniquet application, blood flow is restricted to a limb to stop excessive limb hemorrhage in a trauma setting and to create a bloodless operating field in the surgical setting. During tourniquet-related ischemia, aerobic respiration stops, and ATP is depleted, and during subsequent reperfusion, there is an increase in reactive oxygen species (ROS) production and other endogenous substances, which leads to acute ischemia-reperfusion (IR) injuries, including tissue necrosis and skeletal muscle contractile dysfunction. Hyperbaric oxygen (HBO) therapy can increase the arterial oxygen tension in the tissues of patients with general hypoxia/anoxia, including carbon monoxide poisoning, circulatory arrest, and cerebral and myocardial ischemia. Here, we studied the protective effects of HBO pretreatment with 100% oxygen at 2.5 ATA against tourniquet/IR injury in mice. After one hour of HBO therapy with 100% oxygen at 2.5 ATA was administered to C57/BL6 mice, a rubber band was placed at the hip joint of the unilateral hindlimb to induce 3 h of ischemia and then released for 48 h of reperfusion. We analyzed gastrocnemius muscle morphology and contractile function and measured the levels of ATP and ROS accumulation in the muscles. HBO pretreatment did not improve tourniquet/IR-injured gastrocnemius muscle morphology and muscle contraction. Tourniquet/IR mice with HBO pretreatment showed no increase in ATP levels in IR tissues, but they did have a decreased amount of ROS accumulation in the muscles, compared to IR mice with no HBO pretreatment. These data suggest that one hour of HBO pretreatment with 100% oxygen at 2.5 ATA increases the antioxidant response to lower ROS accumulation but does not increase ATP levels in IR muscles and improve tourniquet/IR-injured muscle morphology and contractile function.

Improvement of tube formation model of cell: Application for acute hypoxia in in vitro study of angiogenesis.

Angiogenesis caused by acute vascular occlusion occurs in various ischemic diseases. The in vitro tube formation assay by endothelial cells is a rapid, quantitative method for drug discovery on angiogenesis. Tube formation assay on Matrigel has been widely used to identify the angiogenesis, however, there are some problems to limit its application. In this study, we found for the first time that sodium dithionite (SD) could induce endothelial cell tube formation without Matrigel under hypoxia condition. To further verify our findings, the angiogenesis related proteins and mRNA at different time points after tube formation were measured both in primary human large-vessel endothelial cell (HUVECs) and murine microvascular endothelial cell line (Bend.3). In conclusion, compared with traditional tube formation on Matrigel, the novel model exhibits the following advantages: (1) Combination oxygen glucose deprivation with sodium dithionite (OGD-SD) model is operated more easily than traditional tube formation. (2) OGD-SD can be used for not only cell imaging, but also immunofluorescence, protein extraction and gene analysis. (3) OGD-SD is more applicable to acute hypoxia model of endothelial cell in vitro. (4) OGD-SD may be more suitable to identify molecular mechanism of compound that intervenes processes of pro-tube formation, tube formation and tube disconnection.

Assessing cortical cerebral microinfarcts on iron-sensitive MRI in cerebral small vessel disease.

Recent studies suggest that a subset of cortical microinfarcts may be identifiable on T2* but invisible on T1 and T2 follow-up images. We aimed to investigate whether cortical microinfarcts are associated with iron accumulation after the acute stage. The RUN DMC - InTENse study is a serial MRI study including individuals with cerebral small vessel disease (SVD). 54 Participants underwent 10 monthly 3 T MRIs, including diffusion-weighted imaging, quantitative R1 (=1/T1), R2 (=1/T2), and R2* (=1/T2*) mapping, from which MRI parameters within areas corresponding to microinfarcts and control region of interests (ROIs) were retrieved within 16 participants. Finally, we compared pre- and post-lesional values with repeated measures ANOVA and post-hoc paired t-tests using the mean difference between lesion and control ROI values. We observed 21 acute cortical microinfarcts in 7 of the 54 participants (median age 69 years [IQR 66-74], 63% male). R2* maps demonstrated an increase in R2* values at the moment of the last available follow-up MRI (median [IQR], 5 [5-14] weeks after infarction) relative to prelesional values (p = .08), indicative of iron accumulation. Our data suggest that cortical microinfarcts are associated with increased R2* values, indicative of iron accumulation, possibly due to microhemorrhages, neuroinflammation or neurodegeneration, awaiting histopathological verification.

Effect of age and sex on the incidence of ventricular arrhythmia in a rat model of acute ischemia.

BACKGROUND: The impact of sex and age on the arrhythmic susceptibility within the setting of acute ischemia is masked by the fact that acute coronary events result from coronary artery disease appearing with age much earlier among men than among women. METHODS AND RESULTS: LAD ligation or sham operations were performed in rats of both sexes at the age 3 and 24 months. An ECG was recorded continuously for 6 h after the operation. The number of early and late premature ventricular beats (PVBs), episodes of ventricular tachycardia (VT) and fibrillation (VF), heart rate, QRS, QT and Tpeak-Tend duration were analysed. Epicardial action potentials were recorded in vivo, Ca2+ signaling was evaluated in isolated cardiomyocytes, fibrosis and connexin-43 expression and localization were measured in the septum. PVBs, VT and VF episodes are much more common in older males than in young males and females independently from their age. Fibrosis with varying intensity in different muscle layers, hypertrophy of cardiomyocytes, reduced number of gap junctions and their appearance on the lateral myocyte membrane, QT prolongation, increase transmural dispersion of repolarisation and a decreased function of SERCA2a may increase the propensity to arrhythmia within the setting of acute ischemia. CONCLUSION: We show that the male sex, especially in case of older individuals is a strong predictor of increased arrhythmic susceptibility within the acute ischemia setting regardless of its impact on the occurrence of cardiovascular diseases. A personalized sex-dependent prevention treatment is needed to reduce the mortality in acute phases of myocardial infarction.

Acute Upper Limb Ischemia: Prompt Surgery and Long-Term Anticoagulation Prevent Limb Loss and Debilitation.

BACKGROUND: Acute upper limb ischemia is an uncommon clinical manifestation of thromboembolism seen predominantly in patients with atrial fibrillation. Treatment can be by conservative or surgical means but the consensus is that after conservative treatment, symptoms still persist. In this series, an attempt was made at limb preservation and return to functional capacity by early surgery in all patients diagnosed with acute limb ischemia. METHODS: Patients referred with upper limb ischemia (22) were stratified into non-acute (6) treated with anticoagulation alone and those with acute ischemia. Sixteen (16) patients, age range 30-92 years (median 62.4 years) comprising mainly females (13), had clinical evidence of severe ischemia and underwent immediate brachial embolectomy with postoperative anticoagulation. RESULTS: Sixteen patients underwent 20 embolectomies with immediate reperfusion of limbs and relief of symptoms. Two patients had two re-operations each due to recurrent symptoms but both recovered with good outcome, one going on to have an axillary-radial bypass. There was no limb disability nor limb loss, but one postoperative mortality. All other patients were seen at their 1-year review and at 5 years, eleven out of 15 patients were still alive with most resuming an active lifestyle and some returning to work. CONCLUSION: Good outcomes were obtained in this series in both the short and long term. Despite one mortality, there was no limb loss nor disability in a mainly elderly population. Prompt surgery and meticulous long-term anticoagulation reduced complications and improved limb salvage rates ensuring that patients had a good quality of life after surgery.

Silent strokes after thoracoscopic epicardial ablation and catheter ablation for atrial fibrillation: not all lesions are permanent on follow-up magnetic resonance imaging.

BACKGROUND: Invasive treatments for atrial fibrillation (AF) pose a risk of ischemic stroke due to periprocedural brain embolization, which may be manifest or silent. The primary aim of our study was to compare the rate of silent strokes after percutaneous catheter-based and thoracoscopic epicardial ablation for AF. The secondary aim was to evaluate the development of silent strokes over time. METHODS: We included 39 subjects (aged 64.1±8.9 years) treated for persistent symptomatic AF with thoracoscopic ablation and 30 subjects (aged 64.1±10.5 years) treated for paroxysmal or persistent symptomatic AF with catheter ablation. Subjects underwent brain MRI before and early after the ablation, moreover, the surgical group underwent late MRI 6 months after therapy. On early MRI, the presence of silent strokes and their number and size were evaluated. On late MRI, transformation of previously-detected acute ischemic lesions into chronic infarction or their reversibility were assessed. RESULTS: Initially, different chronic ischemic findings were found in 64% of patients from the surgical group and in 70% from catheter group. Early MRI results: acute ischemic lesions were detected in 2 (6.7%) subjects (overall 3 lesions sized <5 mm) in the catheter group and in 17 (43.6%) subjects in surgical group. Most subjects in the surgical group showed multiple lesions (88%); 195 lesions were detected, a median 6 (IQR 8) lesions per case. Eighty-two percent of lesions were <5 mm, 12% 5-10 mm, 5% 10-30 mm, and 2% were large territorial ischemia. Only 1 case was symptomatic, the rest were silent strokes. On late MRI, 53.5% of all acute lesions were reversible. Lesions <5 mm were reversible in 63.1% of cases, lesions 5-10 mm were reversible in 21.7% and all lesions larger than 10 mm persisted. In 29.4% of patients all acute ischemic lesions were fully reversible. CONCLUSIONS: Periprocedural silent strokes were significantly more common after thoracoscopic epicardial ablation compared to catheter ablation considering both the number of affected patients and number of lesions. The majority of acute ischemic brain lesions were small, up to 5 mm in diameter, roughly half of which were reversible. Reversibility of acute ischemic lesions decreased with size. However, in 29.4% of affected patients, all lesions were fully reversible.

Multiple paradoxical embolisms revealing a patent foramen ovale in a patient with deep venous thrombosis: A case report.

INTRODUCTION: Paradoxical embolism is a rare medical phenomenon. Depending on the site of embolisation, it can cause different symptoms. Although rare, mesenteric ischemia can reveal paradoxical embolism, and the embolisation of two different sites is rarely described in the literature. CASE PRESENTATION: We report the observation of a patient with a table associating an acute mesenteric ischemia and an acute ischemia of the upper limb; whose the etiological assessment revealed a deep venous thrombosis of the lower limbs complicated by pulmonary embolism. CLINICAL DISCUSSION: These paradoxical embolisms occurred through a patent foramen ovale. The diagnosis of the patent foramen ovale in this patient was revealed by transthoracic echocardiography, with bubble test. The patient benefited from an embolectomy of the superior mesenteric artery and an embolectomy using fogarty catheter by approching humeral artery at the elbow crease with good postoperative evolution. The patient was put on long-term anticoagulation with Acenocoumarol (because of low socio-economic level of our patient). We didn't recommended the closure of the PFO because of the small size of the shunt and especially because the patient refuses that procedure. CONCLUSION: Paradoxical embolism remains a pathology rarely mentioned by clinicians, although it can engage the functional and vital prognosis of the patient, hence the interest of a good cardiac evaluation in any patient with embolic ischemia.

Quantifying the spatiotemporal influence of acute myocardial ischemia on volumetric conduction velocity.

INTRODUCTION: Acute myocardial ischemia occurs when coronary perfusion to the heart is inadequate, which can perturb the highly organized electrical activation of the heart and can result in adverse cardiac events including sudden cardiac death. Ischemia is known to influence the ST and repolarization phases of the ECG, but it also has a marked effect on propagation (QRS); however, studies investigating propagation during ischemia have been limited. METHODS: We estimated conduction velocity (CV) and ischemic stress prior to and throughout 20 episodes of experimentally induced ischemia in order to quantify the progression and correlation of volumetric conduction changes during ischemia. To estimate volumetric CV, we 1) reconstructed the activation wavefront; 2) calculated the elementwise gradient to approximate propagation direction; and 3) estimated conduction speed (CS) with an inverse-gradient technique. RESULTS: We found that acute ischemia induces significant conduction slowing, reducing the global median speed by 20 cm/s. We observed a biphasic response in CS (acceleration then deceleration) early in some ischemic episodes. Furthermore, we noted a high temporal correlation between ST-segment changes and CS slowing; however, when comparing these changes over space, we found only moderate correlation (corr. = 0.60). DISCUSSION: This study is the first to report volumetric CS changes (acceleration and slowing) during episodes of acute ischemia in the whole heart. We showed that while CS changes progress in a similar time course to ischemic stress (measured by ST-segment shifts), the spatial overlap is complex and variable, showing extreme conduction slowing both in and around regions experiencing severe ischemia.

Presentation with perforation of the terminal ileum and acute limb ischemia in Crohn's disease: A case report.

INTRODUCTION AND IMPORTANCE: Crohn's disease is a chronic inflammatory bowel disease with complex pathophysiology and multiple complications, some of which can be fatal. We report herein the management of an unusual case of Crohn's disease revealed by two life-threatening complications. CASE PRESENTATION: A 59-year-old patient presented with an acute abdominal pain evolving for one day with a clinical presentation in favor of peritonitis by perforation of the last ileal loop and acute limb ischemia. At emergency laparotomy, we found a fecal peritonitis by perforation of the last ileal loop. The patient underwent an ileo-caecal resection with rifle barrel ileo-colostomy associated with embolectomy using a Fogarty catheter of the femoral artery. Pathological examination of the specimen showed an aspect consistent with an ileo-caecal Crohn's disease and blood clot embolus of the femoral artery. Postoperative course was uneventful and the patient was kept in remission with immunosuppressants. DISCUSSION: Several complications may arise during the evolution of the disease. However, Life-threatening complication scarcely inaugurate crohn's disease like in our patient. Free perforation of the small intestine in crohn's disease occurs rarely, which makes its statistical study difficult. Risk factors for perforation are still poorly identified. Patients diagnosed with crohn's disease have a higher risk of thromboembolic complications. Indeed, there is an association between the activity of the disease and thromboembolic events. In our case, the severity of the clinical presentation as well as its inaugural character are unique. CONCLUSION: The management of inaugural two uncommon acute conditions in Crohn's disease is challenging.