Revealing the nature of cardiovascular disease using DERGA, a novel data ensemble refinement greedy algorithm.

BACKGROUND: The study aimed to determine the most crucial parameters associated with CVD and employ a novel data ensemble refinement procedure to uncover the optimal pattern of these parameters that can result in a high prediction accuracy. METHODS AND RESULTS: Data were collected from 369 patients in total, 281 patients with CVD or at risk of developing it, compared to 88 otherwise healthy individuals. Within the group of 281 CVD or at-risk patients, 53 were diagnosed with coronary artery disease (CAD), 16 with end-stage renal disease, 47 newly diagnosed with diabetes mellitus 2 and 92 with chronic inflammatory disorders (21 rheumatoid arthritis, 41 psoriasis, 30 angiitis). The data were analyzed using an artificial intelligence-based algorithm with the primary objective of identifying the optimal pattern of parameters that define CVD. The study highlights the effectiveness of a six-parameter combination in discerning the likelihood of cardiovascular disease using DERGA and Extra Trees algorithms. These parameters, ranked in order of importance, include Platelet-derived Microvesicles (PMV), hypertension, age, smoking, dyslipidemia, and Body Mass Index (BMI). Endothelial and erythrocyte MVs, along with diabetes were the least important predictors. In addition, the highest prediction accuracy achieved is 98.64%. Notably, using PMVs alone yields a 91.32% accuracy, while the optimal model employing all ten parameters, yields a prediction accuracy of 0.9783 (97.83%). CONCLUSIONS: Our research showcases the efficacy of DERGA, an innovative data ensemble refinement greedy algorithm. DERGA accelerates the assessment of an individual's risk of developing CVD, allowing for early diagnosis, significantly reduces the number of required lab tests and optimizes resource utilization. Additionally, it assists in identifying the optimal parameters critical for assessing CVD susceptibility, thereby enhancing our understanding of the underlying mechanisms.

Cardiotoxicity in Acute Myeloid Leukemia in Adults: A Scoping Study.

Introduction: According to the National Cancer Institute of the NIH, acute myeloid leukemia (AML) is a rapidly growing cancer with a large quantity of myeloblasts. AML is most often observed in adults over the age of 35, accounting for 1% of all cancer types. In 2023, the number of new cases being reported was estimated to reach around 20,380 in total and the rate of mortality in the same year was 1.9%, or 11,310 cases, in the US. Purpose: This scoping study aims to extensively assess and explore the degree of cardiotoxicity in patients with AML that can be caused due to pharmaceutical treatments prescribed by hematologists. This is achieved by performing extensive searches of different scientific databases including PubMed, Scopus, and ScienceDirect. Results: A variety of options are available that are summarized in tables included herein, with each having their advantages and risks of adverse effects, among these being cardiotoxicity. Important medications found to play a significant role include gemtuzumab ozogamicin, venetoclax, and vyxeos. Conclusions: It is understandable that being familiar with all the treatment options available and every potential adverse effect is impossible. However, hematologists and, in general, physicians must try to be updated with the most recent information released to improve the quality of life of their patients and minimize the risk of additional complications.

Cardiac safety of neoadjuvant chemotherapy with epirubicin and cyclophosphamide followed by docetaxel/pertuzumab/trastuzumab for HER2-positive breast cancer patients.

PURPOSE: Early-stage, HER2-positive breast cancer is increasingly treated with neoadjuvant chemotherapy (NAC). After the positive results of the Neosphere trial, the standard of care has been the combination of chemotherapy with two anti-HER2 agents, trastuzumab and pertuzumab. Many oncologists use the sequence of four cycles of anthracycline-containing regimen followed by four cycles of taxane with the two monoclonals. We report here the cardiac safety of four cycles of epirubicin with cyclophosphamide followed by four cycles of docetaxel with trastuzumab and pertuzumab, given at the neoadjuvant setting in early, HER2-positive breast cancer. METHODS: We retrospectively collected data from the medical records of patients treated at our clinic between 2014 and 2020. RESULTS: It total, 55 patients treated with the same regimen were identified. There were 20 estrogen receptor (ER)-negative and 35 ER-positive patients. Complete pathologic response was observed in 64.8% of the patients. After a median cardiac follow-up of 2.61 years, and a total of 283 echocardiograms, there was only one recorded asymptomatic Left Ventricular Ejection Fraction (LVEF) fall > 25% and no symptomatic left ventricular systolic dysfunction. LVEF consistently dropped during treatment, but the drop was not significant enough to necessitate treatment interruption, and improved during follow-up. CONCLUSION: Our data confirm the effectiveness and cardiac safety of the aforementioned neoadjuvant regimen.

Genetic justification of severe COVID-19 using a rigorous algorithm.

Recent studies suggest excessive complement activation in severe coronavirus disease-19 (COVID-19). The latter shares common characteristics with complement-mediated thrombotic microangiopathy (TMA). We hypothesized that genetic susceptibility would be evident in patients with severe COVID-19 (similar to TMA) and associated with disease severity. We analyzed genetic and clinical data from 97 patients hospitalized for COVID-19. Through targeted next-generation-sequencing we found an ADAMTS13 variant in 49 patients, along with two risk factor variants (C3, 21 patients; CFH,34 patients). 31 (32%) patients had a combination of these, which was independently associated with ICU hospitalization (p = 0.022). Analysis of almost infinite variant combinations showed that patients with rs1042580 in thrombomodulin and without rs800292 in complement factor H did not require ICU hospitalization. We also observed gender differences in ADAMTS13 and complement-related variants. In light of encouraging results by complement inhibitors, our study highlights a patient population that might benefit from early initiation of specific treatment.

The Mean Platelet Volume in the Prognosis of Coronary Artery Disease Severity and Risk Stratification of Acute Coronary Syndromes.

INTRODUCTION: Platelets play a crucial role in thrombotic episodes. Mean Platelet Volume (MPV) is the primary indicator of platelet's activation; its measurement is easy and time-effective. AIM: We tested the hypothesis that MPV is correlated with SYNTAX score in patients that suffered from an Acute Coronary Syndrome (ACS). MATERIAL AND METHODS: One hundred and four (104) patients (79 male-25 female, mean age 64.2±11.1 years), who were hospitalized for an ACS and underwent coronary angiography, were included in the study. Syntax score, as an indicator of the severity of coronary artery disease (CAD), was calculated. We tried to investigate the correlation between the first measured MPV, CRP, Creatinine and high sensitivity Troponin with the Syntax score of the patient and the association of MPV and a possible Major Advanced Cardiac Event (MACE) during hospitalization. RESULTS: The patients were divided into four groups according to the SYNTAX score: Group A (SYNTAX score: 0, n=12), group B: Mild CAD (SYNTAX score: 1-22, n=68), group C: Moderate CAD (SYNTAX score: 23-32, n=12), and group D: Severe CAD (SYNTAX score: ≥ 33, n=12). Four patients (3.8%) developed a MACE during their hospitalization. MPV was significantly correlated to Syntax score (r=0.658, p<0.001) and was found to be an independent predictor factor of MACE with HR=6.8 (95% Confidence Interval 1.46-33.36). The cut-off value of MPV was 7.5 with a sensitivity of 98% and a specificity of 30.8%. CONCLUSION: We determined a positive correlation between MPV and Syntax score, transforming this simple test in a possible factor of risk stratification in ACS.

Exertional dyspnea after myocardial infarction: thinking beyond the diagnosis of heart failure.

INTRODUCTION: We herein present an unusual case of a pseudoaneurysm of the left ventricular myocardium, which is a rare and fatal complication of myocardial infarction. CASE REPORT: A 64-year-old man with a history of bipolar disorder and arterial hypertension was hospitalized for delayed presentation ST-elevation myocardial infarction. He was admitted to our hospital 24 hours after symptom onset. Diagnostic coronary angiography revealed 95% stenosis at the distal third of the right coronary artery, and he underwent a primary percutaneous coronary intervention to the culprit lesion. Despite administration of a diuretic and optimization of other pharmaceutical treatment, his heart failure deteriorated. Electrocardiography showed a sinus rhythm with Q-wave formation in the inferior wall leads (II, III, aVF), T-wave inversion in the same leads, and borderline QT prolongation (QTc of 490 ms). No ST elevation suggestive of left ventricular aneurysm formation was noticed. Forty days later, cardiac ultrasound revealed a dyskinetic cavity (pseudoaneurysm) in continuity with the posterior-inferior wall of the myocardium, resulting in severe mitral valve regurgitation. Unfortunately, the patient died while awaiting surgical treatment. CONCLUSION: Although most patients with left ventricular pseudoaneurysm have a relatively benign outcome, those with symptoms of heart failure must be urgently diagnosed and treated.

Endovascular management of postoperative pseudoaneurysms of the external carotid artery.

Hemorrhage secondary to postoperative pseudoaneurysm is a rare event, but may complicate the clinical course of straightforward and common interventions such as sinonasal procedures, tonsillectomy, and maxillofacial and plastic surgeries. We report our experience with the endovascular management of iatrogenic pseudoaneurysm in eight patients who had undergone recent craniomaxillofacial surgery. Computed tomography (CT), including CT-angiography, detected only three of the eight lesions. In all patients, endovascular embolization achieved successful occlusion of the pseudoaneurysm without local or general procedure-related complications. Immediate proximal arterial occlusion with detachable coils was performed in every case, and pseudoaneurysm coiling was performed in three cases presenting with active hemorrhage. Endovascular therapy proved to be safe and effective in the management of postoperative pseudoaneurysms. Surgeons involved in the craniomaxillofacial procedures should be aware of this complication and its management.

Endovascular reperfusion therapy for acute ischemic stroke: a meta-analysis.

Intra-arterial thrombolysis has been advocated for treatment of acute ischemic stroke and several prognostic factors were identified in these patients. Other endovascular methods aiming to recanalize occluded vessels including balloon angioplasty, stenting and use of mechanical clot retrieving devices were devised. To date, this approach is replaced by a multi-modal reperfusion therapy (MMRT) approach that emphasizes combination of various methods to achieve reperfusion. MMRT includes intra-arterial infusion of thrombolytics and/or antiplatelet agents, mechanical clot disruption and retrieval and balloon angioplasty with stent placement. Recent results suggest that MMRT results in higher chances for both recanalization of the occluded artery and reperfusion of the ischemic tissue.

Recanalization of symptomatic carotid artery dissections causing occlusion with multiple stents: the use of delayed double-contrast road map.

BACKGROUND AND PURPOSE: Internal carotid artery dissections (ICADs) with occlusion present with a high morbidity and mortality. No specific medical treatment has proven to be effective in this setting. In selected cases of ICAD with occlusion, stent-assisted angioplasty has been shown to be effective in restoring the perfusion. Spontaneous ICAD causing occlusion successfully recanalized with multiple telescoped stents extending intracranially has only been reported exceptionally. METHODS: We report cases of symptomatic acute carotid occlusion after spontaneous dissection extending from the cervical to the petrocavernous ICA segments. Imaging studies revealed the presence of an extensive penumbra area in every case. Patients were treated by means of multiple stents deployed in a telescoped fashion with the aid of a delayed double-contrast road map. RESULTS: Post-procedural angiography demonstrated restitution of the carotid lumen with no signs of residual dissection or intracranial emboli. The patients improved rapidly, showing no residual neurological deficit after a week. At follow-up, patients are clinically asymptomatic and the vessel is patent with no radiological signs of myointimal hyperplasia. CONCLUSIONS: The successful angiographic and clinical results observed in our cases of extraintracranial stenting of a long carotid dissection causing occlusion contribute to the literature of carotid dissection treated with multiple stents.

Complete and persistent occlusion of arteriovenous malformations of the mandible after endovascular embolization.

OBJECTIVE: Arteriovenous malformation (AVM) of the mandible is a rare but potentially life-threatening entity. Traditional treatment involved complex surgical procedures that usually failed to completely cure the malformation without disfigurement and functional difficulties. We report our experience in transarterial and transvenous embolizations of mandibular AVMs using different embolization agents and discuss the potential use of Onyx and new detachable-tip microcatheters. CLINICAL PRESENTATION: Patients presented with progressive mandibular swelling, pain, soft-tissues discoloration and dental misalignment with tooth loosening. INTERVENTION: The AVMs were completely and persistently occluded by endovascular transarterial and transvenous approaches. CONCLUSION: Less invasive endovascular approaches proved to be highly effective in curing certain types of mandibular AVMs. Every malformation requires a tailored endovascular strategy in terms of approach and selection of an embolizing agent.

Microglial involvement in neuroprotection following experimental traumatic brain injury in heat-acclimated mice.

Brain-derived neurotrophic factor (BDNF) conveys neuroprotection in various settings of experimental central nervous system injury. Using a model of endogenous neuroprotection, induced in mice by chronic exposure to moderate ambient heat (heat acclimation, HA), we have previously shown that neuroprotection following traumatic brain injury involves reduced post-injury tumor necrosis factor alpha (TNFalpha) expression. As glial cells play a pivotal role in post-injury inflammation on one hand, and are also capable of inducing neuroprotection by harboring trophic factors and BDNF in particular, the effects of injury and HA on overall BDNF content at the trauma area, gliosis and glial BDNF expression were investigated. Western blotting indicated higher overall BDNF levels in HA sham-operated mice. Following injury, a decrease was observed in the HA group only, reaching levels similar to normothermic mice. Immunohistochemical studies demonstrated BDNF-positive resting microglia in non-injured HA but not normothermic animals. Post-injury astrocytosis and microglial immunoreactivity were enhanced in the HA group. Particularly, an increase in the amount of ramified microglia was observed within the penumbra, accompanied by a concomitant decrease in globular microglia, a major source of pro-inflammatory mediators. BDNF labeling on and around microglia and their processes was intensified in HA mice. Furthermore, BDNF immunoreactivity in HA mice was evident in the degenerated edges of axons. These findings, taken together with the growing body of evidence indicating the neuroprotective potential of both BDNF and microglia, suggest a possible role of these cells in HA-induced neuroprotection.

Urgent endovascular stent-graft placement for traumatic penetrating subclavian artery injuries.

Penetrating injuries may infrequently cause pseudoaneurysms, lacerations and arteriovenous fistulas involving the subclavian artery. These injuries present with life-threatening bleedings, associated regional injuries and critical limb ischemia and although surgery has been considered the treatment of choice, subclavian injuries pose a real surgical challenge. We prospectively examined data of six patients presenting with penetrating subclavian artery injuries that were treated by urgent endovascular stent-graft placements. All stent-grafts were deployed successfully achieving complete exclusion of the pseudoaneurysm, control of bleeding and reconstruction of the injured artery. No procedural complications, stent thrombosis or stent infections occurred during hospitalization. One patient developed stenosis at 7 months, which required angioplasty. The series mean clinical and ultrasound-CTA follow-up is 38+/-19.7 months (range 11-60 months) and 28+/-19.1 months (range 6-58 months), respectively. This series shows the feasibility of endovascular repair by means of stent-grafts for selected patients with acute penetrating injuries of the subclavian arteries. This approach proved to be safe and effective in restoring the arterial lumen and patency, excluding the pseudoaneurysms and controlling the bleeding caused by subclavian lacerations. Mid-term follow-up on stent-graft patency rates are encouraging.

Endovascular treatment of congenital carotid-cavernous fistulas in infancy.

Congenital dural arteriovenous fistulas have been infrequently described in pediatric population and they generally affect the transverse, sigmoid, straight or sagittal sinuses. Congenital carotid-cavernous fistulas in infancy are considered very rare and to our knowledge, only four cases have been reported in literature. Currently, the preferred treatment is endovascular embolization through trans-arterial route. We review the literature on congenital carotid cavernous fistulas in infancy focusing on the endovascular treatment of this rare entity and present our experience.

Prenatal thrombosis of torcular Herophili with spontaneous resolution and normal outcome.

BACKGROUND: Prenatal thrombosis of torcular Herophili is a rare condition. It may be suspected during the routine ultrasonographic follow-up of the fetus, but MRI is necessary to establish the diagnosis. There are 7 reported cases with various results. METHODS: We report a case of prenatal torcular Herophili thrombosis. We present 2 series of fetal MRIs. The first one was performed at 21 and the second at 37 weeks' gestation. RESULTS: The second MRI revealed a total resolution of the thrombus. The product was a neurologically intact infant with normal development. CONCLUSIONS: This is the fourth reported case of fetal torcular Herophili thrombosis with normal outcome. There are no sufficient data regarding the best management of this rare condition; however, following up with fetal MRIs seems to be the most rational choice.

Incensole acetate: a novel neuroprotective agent isolated from Boswellia carterii.

Boswellia resin has been used as a major anti-inflammatory agent and for the healing of wounds for centuries. Incensole acetate (IA), isolated from this resin, was shown to inhibit the activation of nuclear factor-kappaB, a key transcription factor in the inflammatory response. We now show that IA inhibits the production of inflammatory mediators in an in vitro model system of C6 glioma and human peripheral monocytes. Given the involvement of postinjury inflammation in the pathophysiology and outcome of traumatic brain injury, we examined the effect of IA on the inflammatory process and on the recovery of neurobehavioral and cognitive functions in a mouse model of closed head injury (CHI). In the brains of post-CHI mice, IA reduced glial activation, inhibited the expression of interleukin-1beta, and tumor necrosis factor-alpha mRNAs, and induced cell death in macrophages at the area of trauma. A mild hypothermic effect was also noted. Subsequently, IA inhibited hippocampal neurodegeneration and exerted a beneficial effect on functional outcome after CHI, indicated by reduced neurological severity scores and improved cognitive ability in an object recognition test. This study attributes the anti-inflammatory activity of Boswellia resin to IA and related cembranoid diterpenes and suggests that they may serve as novel neuroprotective agents.

Intra-arterial thrombolysis and stent placement for traumatic carotid dissection with subsequent stroke: a combined, simultaneous endovascular approach.

Traumatic carotid dissection is a well-known cause of ischemic stroke and although the treatment of the dissection itself has received some attention in recent years, the treatment of the concomitant stroke has been less investigated. We present a 43-year-old patient with blunt traumatic internal carotid artery dissection associated with subocclusive stenosis and major cerebral thromboembolic complication. Combined, simultaneous intra-arterial fibrinolysis and carotid stenting through a bilateral approach was successfully performed allowing the complete clinical recovery of the patient. Contralateral carotid artery approach allowed the beginning of intra-arterial thrombolysis without delay, while stent-assisted angioplasty of the injured carotid was simultaneously performed. This approach was proved to be safe and effective and may deserve further evaluation.

Dural arteriovenous fistula of the greater sphenoid wing region in neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) has been infrequently associated with different cerebrovascular conditions that may lead to either ischemic or hemorrhagic stroke. Intracranial dural arteriovenous fistulas have not been described in NF1 patients. In this paper we present a unique case of an 8-year-old child with florid NF1 that presented a greater sphenoid wing dural arteriovenous fistula draining directly through the superior ophthalmic vein and causing exophthalmos. The fistula was cured by direct trans-superior ophthalmic vein approach, by means of detachable coils. Only a few cases of dural fistulas in the lesser sphenoidal wing region have been described in the literature but a fistula of the greater sphenoid wing has not been previously described.

Single-staged sequential endovascular stenting in patients with in tandem carotid stenoses.

BACKGROUND AND PURPOSE: Simultaneous stenoses at the origin of the internal carotid artery and the carotid siphon, also known as 'in tandem stenoses', are not uncommon. However, the clinical importance of this condition is still a subject of controversy. Surgical and endovascular approaches have been proposed to manage symptomatic patients who fail antithrombotic therapy. METHODS: We present a series of eight patients with symptomatic in tandem carotid artery stenoses treated by sequential endovascular stent-assisted angioplasty. In all the cases, the intracranial stenosis was equal to, or greater, than the extracranial stenosis. RESULTS: Procedural success, defined as residual stenosis of less than 30% in extracranial and intracranial lesions, was obtained in all the cases. No patient sustained myocardial infarction, stroke or transient ischemic attack (TIA) during the procedure or hospital stay. During a mean clinical follow-up of 12 +/- 3.4 months (range: 7-20 months), there were no neurological events and on angiographic follow-up after 6 months, no patient presented in-stent de novo stenosis. CONCLUSION: Endovascular stent-assisted angioplasty appears to be a valid alternative for selected patients with symptomatic in tandem carotid stenoses that are refractory to medical treatment. In most of the cases, the characteristics of intracranial stenoses determine the feasibility of the procedure.

Petrous carotid artery pseudoaneurysm in bilateral carotid fibromuscular dysplasia: treatment by means of self-expanding covered stent.

BACKGROUND: Pseudoaneurysms of the petrous carotid artery may occur in the setting of trauma, dissection, invasive tumors, or as a complication of surgery. These aneurysms may grow and constitute a potential source of thromboembolic complications or rupture. CASE DESCRIPTION: We present a patient with bilateral carotid FMD presenting with a large petrous pseudoaneurysm. Because carotid occlusion was not appropriate, a self-expandable covered stent was implanted. This treatment allowed complete exclusion of the pseudoaneurysm and preservation of the parent artery. CONCLUSION: The accepted treatment of psuedoaneurysms located at petrous ICA is either sacrifice of the carotid artery or exclusion of the aneurysm from the preserved carotid artery. These procedures have specific limitations, and they are technically demanding and associated with a substantial morbidity rate. The endovascular treatment of these lesions is the preferred alternative. Among the various endovascular techniques that have been tested so far, we propose self-expandable covered stents as ideal for treating arterial aneurysms and pseudoaneurysms of the petrous and cavernous carotid segments.