Chest Pain: Wellens Syndrome Due to Spontaneous Dissection of the Left Anterior Descending Coronary Artery - A Case Report and Literature Review.

Wellens syndrome is an abnormal electrocardiographic pattern characterized by biphasic (type A) or deeply inverted (type B) T waves in leads V2-V3. It is typically caused by temporary obstruction of the left anterior descending (LAD) coronary artery due to the rupture of an atherosclerotic plaque leading to occlusion. Spontaneous coronary artery dissection (SCAD) is a rare cause of acute coronary syndrome and even a rarer cause of Wellens Syndrome. It occurs when an intramural hematoma forms, leading to the separation of the tunica intima from the outer layers and creating a false lumen that protrudes into the real lumen, ultimately reducing blood flow and thus resulting in myocardial infarction. Here we report a case of SCAD presenting as an acute coronary syndrome with self-resolving chest pain, slightly elevated myocardial necrosis markers and electrocardiographic changes consistent with Wellens pattern type A first, and type B afterwards, that were not present upon arrival to the emergency department.

Molecular Pathways of Vulnerable Carotid Plaques at Risk of Ischemic Stroke: A Narrative Review.

The concept of vulnerable carotid plaques is pivotal in understanding the pathophysiology of ischemic stroke secondary to large-artery atherosclerosis. In macroscopic evaluation, vulnerable plaques are characterized by one or more of the following features: microcalcification; neovascularization; lipid-rich necrotic cores (LRNCs); intraplaque hemorrhage (IPH); thin fibrous caps; plaque surface ulceration; huge dimensions, suggesting stenosis; and plaque rupture. Recognizing these macroscopic characteristics is crucial for estimating the risk of cerebrovascular events, also in the case of non-significant (less than 50%) stenosis. Inflammatory biomarkers, such as cytokines and adhesion molecules, lipid-related markers like oxidized low-density lipoprotein (LDL), and proteolytic enzymes capable of degrading extracellular matrix components are among the key molecules that are scrutinized for their associative roles in plaque instability. Through their quantification and evaluation, these biomarkers reveal intricate molecular cross-talk governing plaque inflammation, rupture potential, and thrombogenicity. The current evidence demonstrates that plaque vulnerability phenotypes are multiple and heterogeneous and are associated with many highly complex molecular pathways that determine the activation of an immune-mediated cascade that culminates in thromboinflammation. This narrative review provides a comprehensive analysis of the current knowledge on molecular biomarkers expressed by symptomatic carotid plaques. It explores the association of these biomarkers with the structural and compositional attributes that characterize vulnerable plaques.

The Role of the Coagulation System in Peripheral Arterial Disease: Interactions with the Arterial Wall and Its Vascular Microenvironment and Implications for Rational Therapies.

Peripheral artery disease (PAD) is a clinical manifestation of atherosclerotic disease with a large-scale impact on the economy and global health. Despite the role played by platelets in the process of atherogenesis being well recognized, evidence has been increasing on the contribution of the coagulation system to the atherosclerosis formation and PAD development, with important repercussions for the therapeutic approach. Histopathological analysis and some clinical studies conducted on atherosclerotic plaques testify to the existence of different types of plaques. Likely, the role of coagulation in each specific type of plaque can be an important determinant in the histopathological composition of atherosclerosis and in its future stability. In this review, we analyze the molecular contribution of inflammation and the coagulation system on PAD pathogenesis, focusing on molecular similarities and differences between atherogenesis in PAD and coronary artery disease (CAD) and discussing the possible implications for current therapeutic strategies and future perspectives accounting for molecular inflammatory and coagulation targets. Understanding the role of cross-talking between coagulation and inflammation in atherosclerosis genesis and progression could help in choosing the right patients for future dual pathway inhibition strategies, where an antiplatelet agent is combined with an anticoagulant, whose role, despite pathophysiological premises and trials' results, is still under debate.

Role of Regular Physical Activity in Neuroprotection against Acute Ischemia.

One of the major obstacles that prevents an effective therapeutic intervention against ischemic stroke is the lack of neuroprotective agents able to reduce neuronal damage; this results in frequent evolution towards a long-term disability with limited alternatives available to aid in recovery. Nevertheless, various treatment options have shown clinical efficacy. Neurotrophins such as brain-derived neurotrophic factor (BDNF), widely produced throughout the brain, but also in distant tissues such as the muscle, have demonstrated regenerative properties with the potential to restore damaged neural tissue. Neurotrophins play a significant role in both protection and recovery of function following neurological diseases such as ischemic stroke or traumatic brain injury. Unfortunately, the efficacy of exogenous administration of these neurotrophins is limited by rapid degradation with subsequent poor half-life and a lack of blood-brain-barrier permeability. Regular exercise seems to be a therapeutic approach able to induce the activation of several pathways related to the neurotrophins release. Exercise, furthermore, reduces the infarct volume in the ischemic brain and ameliorates motor function in animal models increasing astrocyte proliferation, inducing angiogenesis and reducing neuronal apoptosis and oxidative stress. One of the most critical issues is to identify the relationship between neurotrophins and myokines, newly discovered skeletal muscle-derived factors released during and after exercise able to exert several biological functions. Various myokines (e.g., Insulin-Like Growth Factor 1, Irisin) have recently shown their ability to protects against neuronal injury in cerebral ischemia models, suggesting that these substances may influence the degree of neuronal damage in part via inhibiting inflammatory signaling pathways. The aim of this narrative review is to examine the main experimental data available to date on the neuroprotective and anti-ischemic role of regular exercise, analyzing also the possible role played by neurotrophins and myokines.

The use of opioids in children receiving intrathecal baclofen therapy.

PURPOSE: We hypothesized that children on chronic intrathecal baclofen therapy (ITB) may require less analgesics for postoperative pain control and are at higher risk of developing opioid-induced respiratory depression postoperatively. The aims of this study are to review children on chronic intrathecal baclofen therapy receiving opioids after major surgery and to determine the incidence complications in this population. METHOD: We conducted a retrospective cohort study comparing 13 children on ITB, who underwent posterior spinal fusion surgery, to 17 children with spina bifida that received the same surgery. RESULTS: On postoperative day 0 (POD 0), four children (40%) had respiratory depression in the baclofen group compared to none in the control group. Desaturation was significantly more frequent in children in the ITB group compared to those of the control group on POD 0; oversedation was recorded in 8 (80%) children in the baclofen group vs. 3 (17.6%) in the control group. Desaturation, respiratory depression, and oversedation were significantly more frequent on POD 0 in children in the baclofen group compared with children in the control group. CONCLUSIONS: The findings of the current study suggest that children on chronic intrathecal baclofen therapy require lesser amounts of opioids for postoperative pain control and are at a greater risk of developing postoperative respiratory depression and excessive sedation compared to patients without baclofen therapy.

Occupational exposure to nitrous oxide during procedural pain control in children: a comparison of different inhalation techniques and scavenging systems.

BACKGROUND: Nitrous oxide (N2 O 50% in oxygen) is commonly used for painful procedures in children. Potential negative health effects associated with chronic workplace exposure limit its use. Safe occupational N2 O exposure concentrations are below 25 ppm environmental concentration as a time-weighted average (TWA) and below 200 ppm as a short-time exposure level (STEL) of 15 min. AIM: The aim was to assess occupational exposure of staff during nitrous oxide administration to children using different inhalation delivery devices and scavenging systems. METHODS: Staff nitrous oxide exposure during use of a double face mask (DFM) with or without a demand valve (DV) was compared with a conventional single face mask (FM). We also compared exposure using the hospital central scavenging system with a portable evacuation system. N2 O concentrations, representing exposure values, were monitored within proximity to staff. Urine N2 O concentration was measured in staff administering the N2 O at the end of the procedural session. RESULTS: The mean and median values of TWA and STEL within the working area were lower than recommended values in the DFM (10.8, 11.6 ppm for TWA; 13.9, 11.0 ppm for STEL) and DFM-DV groups (2.3, 2.8 ppm for TWA; 4.4, 3.5 ppm for STEL) using the portable evacuation system. The N2 O urine exposure in DFM-DV group was lower than DFM group: a mean difference of 9.56 ppm (95% CI 2.65-16.46). Staff N2 O urinary concentrations were within safe biological limits in both the DFM and DFM-DV groups. High exposure concentrations to N2 O were recorded in all FM and FM-DV environmental and biological samples. CONCLUSIONS: The DFM system, with or without a DV, connected to a portable evacuation system during N2 O administration to children for painful procedures kept N2 O levels within the local environment below recommended limits.

Paraneoplastic Cerebellar Degeneration Associated with Breast Cancer: A Case Report and a Narrative Review.

Paraneoplastic neurological syndromes (PNSs) are an uncommon complication of cancer, affecting nearby 1/10,000 subjects with a tumour. PNSs can involve all the central and peripheral nervous systems, the muscular system, and the neuromuscular junction, causing extremely variable symptomatology. The diagnosis of the paraneoplastic disease usually precedes the clinical manifestations of cancer, making an immediate recognition of the pathology crucial to obtain a better prognosis. PNSs are autoimmune diseases caused by the expression of common antigens by the tumour and the nervous system. Specific antibodies can help clinicians diagnose them, but unfortunately, they are not always detectable. Immunosuppressive therapy and the treatment of cancer are the cornerstones of therapy for PNSs. This paper reports a case of PNSs associated with breast tumours and focuses on the most common paraneoplastic neurological syndromes. We report a case of a young female with a clinical syndrome of the occurrence of rigidity in the right lower limb with postural instability with walking supported and diplopia, with a final diagnosis of paraneoplastic cerebellar degeneration and seronegative rigid human syndrome associated with infiltrating ductal carcinoma of the breast.

Chemical Recycling of Fully Recyclable Bio-Epoxy Matrices and Reuse Strategies: A Cradle-to-Cradle Approach.

Currently, the epoxy resin market is expressing concerns about epoxy resins' non-recyclability, which can hinder their widespread use. Moreover, epoxy monomers are synthesized via petroleum-based raw materials, which also limits their use. So, it is crucial to find more environmentally friendly alternative solution for their formulation. Within this context, the aim of this paper is to exploit a Cradle-to-Cradle approach, which consists of remodeling and reshaping the productive cycle of consumer products to make sure that they can be infinitely reused rather than just being recycled with a downgrading of their properties or uses, according to the principle of the complete circular economy. Indeed, after starting with a fully-recyclable bio-based epoxy formulation and assessing its recyclability as having a process yield of 99%, we obtained a recycled polymer that could be reused, mixing with the same bio-based epoxy formulation with percentages varying from 15 wt% to 27 wt%. The formulation obtained was thoroughly characterized by a dynamic-mechanical analysis, differential scanning calorimetry, and flexural tests. This approach had two advantages: (1) it represented a sustainable disposal route for the epoxy resin, with nearly all the epoxy resin recovered, and (2) the obtained recycled polymer could be used as a green component of the primary bio-based epoxy matrix. In the end, by using replicated general factorial designs (as statistical tools) combined with a proper optimization process, after carrying out a complete thermo-mechanical characterization of the developed epoxy formulations, the right percentage of recycled polymer content was selected with the aim of identifying the most performing epoxy matrix formulation in terms of its thermo-mechanical properties.

Artificial Intelligence in Acute Ischemic Stroke Subtypes According to Toast Classification: A Comprehensive Narrative Review.

The correct recognition of the etiology of ischemic stroke (IS) allows tempestive interventions in therapy with the aim of treating the cause and preventing a new cerebral ischemic event. Nevertheless, the identification of the cause is often challenging and is based on clinical features and data obtained by imaging techniques and other diagnostic exams. TOAST classification system describes the different etiologies of ischemic stroke and includes five subtypes: LAAS (large-artery atherosclerosis), CEI (cardio embolism), SVD (small vessel disease), ODE (stroke of other determined etiology), and UDE (stroke of undetermined etiology). AI models, providing computational methodologies for quantitative and objective evaluations, seem to increase the sensitivity of main IS causes, such as tomographic diagnosis of carotid stenosis, electrocardiographic recognition of atrial fibrillation, and identification of small vessel disease in magnetic resonance images. The aim of this review is to provide overall knowledge about the most effective AI models used in the differential diagnosis of ischemic stroke etiology according to the TOAST classification. According to our results, AI has proven to be a useful tool for identifying predictive factors capable of subtyping acute stroke patients in large heterogeneous populations and, in particular, clarifying the etiology of UDE IS especially detecting cardioembolic sources.

Postprandial hypotension as a predictor of respiratory failure in patients with foodborne botulinum intoxication - a case-control study in outbreak investigation.

OBJECTIVES: Botulism is a rare syndrome characterized by acute, flaccid paralysis with possible involvement of respiratory muscle-producing pump failure requiring mechanical ventilation. A predominance of autonomic involvement can occur. METHODS: We enrolled patients affected by foodborne botulism during an outbreak. All patients underwent the detection of the toxin in stool specimens, and 24-hour ambulatory blood pressure monitoring (ABPM). A blinded expert operator analyzed ABPM data for the diagnosis of hypertension and postprandial hypotension (PPH). RESULTS: Twenty male patients met the inclusion and exclusion criteria. Thirty-four healthy subjects matched for sex and age were enrolled as a control group. PPH was significantly more frequent in the botulin group than in healthy subjects (40% vs 2.9%, P <0.0001). At the logistic regression, the probability that patients affected by botulinum could require ventilation was increased by 733% (adjusted odds ratio: 8.33) when PPH is encountered. CONCLUSIONS: The likelihood of resorting to ventilation in subjects with botulinum intoxication was seven times greater in patients presenting PPH. These results could allow the prompt identification of patients at high risk for requiring ventilation.

Non-Coding RNA Networks as Potential Novel Biomarker and Therapeutic Target for Sepsis and Sepsis-Related Multi-Organ Failure.

According to "Sepsis-3" consensus, sepsis is a life-threatening clinical syndrome caused by a dysregulated inflammatory host response to infection. A rapid identification of sepsis is mandatory, as the extent of the organ damage triggered by both the pathogen itself and the host's immune response could abruptly evolve to multiple organ failure and ultimately lead to the death of the patient. The most commonly used therapeutic strategy is to provide hemodynamic and global support to the patient and to rapidly initiate broad-spectrum empiric antibiotic therapy. To date, there is no gold standard diagnostic test that can ascertain the diagnosis of sepsis. Therefore, once sepsis is suspected, the presence of organ dysfunction can be assessed using the Sepsis-related Organ Failure Assessment (SOFA) score, although the diagnosis continues to depend primarily on clinical judgment. Clinicians can now rely on several serum biomarkers for the diagnosis of sepsis (e.g., procalcitonin), and promising new biomarkers have been evaluated, e.g., presepsin and adrenomedullin, although their clinical relevance in the hospital setting is still under discussion. Non-codingRNA, including long non-codingRNAs (lncRNAs), circularRNAs (circRNAs) and microRNAs (miRNAs), take part in a complex chain of events playing a pivotal role in several important regulatory processes in humans. In this narrative review we summarize and then analyze the function of circRNAs-miRNA-mRNA networks as putative novel biomarkers and therapeutic targets for sepsis, focusing only on data collected in clinical settings in humans.

New Insights in Prevention and Treatment of Cardiovascular Disease.

Cardiovascular (CV) disease (CVD) is still a major cause of morbidity and mortality in many countries in Europe although considerable efforts have been made in recent decades to address this disease in an even more "comprehensive" approach [...].

Echocardiographic Evaluation of the Cardiac Chambers in Asthmatic Patients: The BADA (Blood Pressure Levels, Clinical Features and Markers of Subclinical Cardiovascular Damage of Asthma Patients) Study-ECO.

The "Blood pressure levels, clinical features and markers of subclinical cardiovascular Damage of Asthma patients" (BADA) study is aimed at defining the cardiovascular risk profile and the markers of subclinical and clinical vascular and cardiac damage in asthmatic patients. Very few studies have assessed asthmatic patients without concomitant heart disease through a transthoracic echocardiogram. The goal of the present study is to investigate the prevalence of morphology and/or function changes in the cardiac chambers of a sample of 86 patients with chronic asthma, referred to the dedicated outpatient unit of the Division of Respiratory Diseases of the AOUP "P. Giaccone" of the University of Palermo, and the results obtained were compared with those of a control group without respiratory or cardiovascular diseases. Patients with asthma showed a marked and widespread involvement of the four cardiac chambers compared with the controls: enlargement of the two atria, greater left ventricular remodeling with interventricular septal thickening, increased indexed left ventricular mass with a significantly greater percentage of patients with overt left ventricular hypertrophy, worse left ventricular diastolic function proven by the significant difference in the E/A ratio, and worse right ventricular systolic function with global right ventricular dysfunction estimated by the Myocardial Performance Index (Tei Index). Multivariate regression analysis, after adjustment for essential hypertension, hypertension severity, diabetes, Body Mass Index, and creatinine clearance, seems to indicate that the indexed left ventricular mass, right atrial volume, and right ventricular Tei index (but not left ventricular hypertrophy) correlate significantly with asthma, severe asthma, and FEV1 (and to a lesser extent with asthma duration). No correlation is apparent between inhaled therapy (ICS, SABA) and myocardial involvement. These results seem to confirm that a more in-depth cardiovascular evaluation in patients with chronic respiratory disease allows the identification of unrecognized cardiovascular involvement. A transthoracic echocardiogram performed in asthmatic patients without clinically overt signs or symptoms of cardiovascular impairment has identified some features indicative of an early subclinical cardiac impairment not found in the control group. These findings, considering also the higher frequency of hypertension in the asthma group, deserve further validation in the future.

Ketogenic Diet, Physical Activity, and Hypertension-A Narrative Review.

Several studies link cardiovascular diseases (CVD) with unhealthy lifestyles (unhealthy dietary habits, alcohol consumption, smoking, and low levels of physical activity). Therefore, the strong need for CVD prevention may be pursued through an improved control of CVD risk factors (impaired lipid and glycemic profiles, high blood pressure, and obesity), which is achievable through an overall intervention aimed to favor a healthy lifestyle. Focusing on diet, different recommendations emphasize the need to increase or avoid consumption of entire classes of food, with only partly known and only partly foreseeable consequences on the overall level of health. In recent years, the ketogenic diet (KD) has been proposed to be an effective lifestyle intervention for metabolic syndrome, and although the beneficial effects on weight loss and glucose metabolism seems to be well established, the effects of a prolonged KD on the ability to perform different types of exercise and the influence of KD on blood pressure (BP) levels, both in normotensives and in hypertensives, are not so well understood. The objective of this review is to analyze, on the basis of current evidence, the relationship between KD, regular physical activity, and BP.

Cardiac Remodeling According to the Nocturnal Fall of Blood Pressure in Hypertensive Subjects: The Whole Assessment of Cardiac Abnormalities in Non-Dipper Subjects with Arterial Hypertension (Wacanda) Study.

OBJECTIVE: Several epidemiological studies suggest that the preservation of the physiological circadian rhythm of blood pressure or its disruption affects the extent of the organ damage developed by the patient. If we classify the circadian rhythm of blood pressure into four nocturnal profiles, significant differences emerge in terms of organ damage burden and prognosis: reverse dippers have the worst prognosis while dippers and mild dippers fall into an intermediate risk range. The risk profile of extreme dippers is still debated, and the available data are very conflicting and inconclusive. Starting from this gap of knowledge, we aimed to evaluate, retrospectively, in a cohort of hypertensive subjects, the degree of cardiac involvement in relation to the different nocturnal blood pressure profiles. METHODS: We retrospectively evaluated 900 patients with essential hypertension, of whom 510 met our study criteria. We graded the 510 patients in relation to the percentage of reduction in mean systolic blood pressure (SBP) at night-time compared with day-time, considering this as a continuous variable, and then compared the extreme quintiles with each other and with the middle quintile (considered as reference). RESULTS: Patients with less (or no) reduction in nocturnal SBP (reverse dipper) showed a higher level of organ damage and comorbidities. With regard to echocardiographic indexes, patients with maximum nocturnal pressure reduction (extreme dipper) showed a lower level of remodeling and/or impairment of E/e' ratio, Right Atrium Area, Basal Right Ventricular Diameter, Inferior Vena Cava Average Diameter, and Tricuspidal Anular Plane Systolic Excursion compared also with hypertensive patients with a physiological nocturnal pressure reduction, even after correction for the main confounders. CONCLUSIONS: These data suggest that extreme dippers may constitute the subgroup of hypertensive patients with the lowest 24-h pressure load and, therefore, less cardiac remodeling.

Prevalence of Arterial Hypertension and Characteristics of Nocturnal Blood Pressure Profile of Asthma Patients According to Therapy and Severity of the Disease: The BADA Study.

BACKGROUND: several studies report an increased risk for asthmatic subjects to develop arterial hypertension and the relationship between these two diseases, frequently co-existing, still has some unclear aspects. METHODS: The BADA (blood pressure levels, clinical features and markers of subclinical cardiovascular damage of asthma patients) study is aimed to evaluate the prevalence of the cardiovascular comorbidities of asthma and their impact on the clinical outcome. The main exclusion criteria were the presence of other respiratory diseases, current smoking, any contraindication to ambulatory blood pressure monitoring (ABPM). RESULTS: The overall percentage of asthmatics having also hypertension was 75% (30 patients) vs. 45% (18 patients) of the control group (p: 0.012). Reduced level of FEV1 (but not inhaled steroid therapy) was associated to newly-diagnosed hypertension (p: 0.0002), higher day SBP levels (p: 0.003), higher day DBP levels (p: 0.03), higher 24 h-SBP levels (p: 0.005) and higher 24h-DBP levels (p: 0.03). The regression analysis performed taking into account sex, age, diabetes, fasting glucose, and body mass index confirms the independent role played by asthma: odds ratio (OR): 3.66 (CI: 1.29-11.1). CONCLUSIONS: hypertension is highly prevalent in asthma; the use of ABPM has allowed the detection of a considerable number of unrecognized hypertensives.

Neurotoxicity during ifosfamide treatment in children.

BACKGROUND: Neurotoxicity has been reported in about 5% of children treated with ifosfamide for tumors not involving the central nervous system. The entity of ifosfamide neurotoxicity can be of different degree, from very light and transient to fatal. CASE REPORTS: All cases of ifosfamide neurotoxicity recorded at the Pediatric Hematology and Oncology Unit in the 15-year period between 1989 and 2003 are reported. Five cases of neurotoxicity occurring during or immediately after ifosfamide infusion were recorded in children with both solid tumors or leukemia. The drug was administered in different chemotherapeutic associations and dosages. Concomitant clinical conditions possibly playing a role as risk factors were the administration of other neurotoxic drugs, the presence of cerebral metastasis, a subclinical lysis syndrome, and altered respiratory function. Symptoms were transient in all cases and consisted in all but one of partial or generalized seizures. In four cases the treatment was continued, substituting ifosfamide with cyclophosphamide. CONCLUSIONS: Particularly in patients presenting risk factors, we advise paying attention to the risk of ifosfamide neurotoxicity and rapidly suspending the drug administration to avoid irreparable damage to the central nervous system. Thereafter the treatment can be reassessed. If ifosfamide is considered the best option for the given case, it could be safely readministered in association with methylene blue or thiamine. If encephalopathy reappears, substitution of ifosfamide with cyclophosphamide could offer the same opportunities of cure to the patient.

Extensive lower limb injuries in a child complicated by complex pain management and profound anemia.

We describe a case of severe pain associated with extensive lower limb injures in a 5-year old, complicated by profound anemia in a Jehovah's Witness family. The study was carried out in a pediatric intensive care unit of a tertiary level university hospital. The patient was 5-year-old girl, with multiple open fractures and extensive soft tissue loss on her left foot and ankle due to a lawnmower injury leading to severe pain and profound anemia with management of the latter complicated by family beliefs. The interventions given were multi-modal pain management and treatment of severe anemia with avoidance of transfusion. A drop in hemoglobin from 11.6 g.dl(-1) at admission to a nadir of 4.3 g.dl(-1) on day 7 was observed. Effective pain control was achieved with nurse- and then patient-controlled analgesia plus adjuncts. Effective pain management and control of anxiety can be achieved by a multi-modal approach in young children. Profound anemia was treated without transfusion and without compromise of tissue healing.