Novel oral anticoagulants in the treatment of acute coronary syndromes: is there any room for new anticoagulants?

Thrombosis plays a key role in the pathophysiology of acute coronary syndromes (ACS). The management of patients with ACS includes interventional procedures and use of antithrombotic agents acutely, and dual antiplatelet therapy (aspirin and a P2Y12 receptor antagonist) for secondary prevention. However, patients with recent ACS remain at a substantial residual risk for recurrent ischemic events or death. The idea of follow-up treatment with an oral anticoagulant on top of standard therapy seems promising. Warfarin was the first oral anticoagulant thoroughly investigated in this direction, but the widespread long-term use of warfarin in ACS has been limited by challenges associated with pharmacodynamic/pharmacokinetic deficiencies of the drug and the risk of bleeding. Novel oral anticoagulants, such as direct thrombin inhibitors (DTIs) and FXa inhibitors overcome the downsides of VKAs. Ximelagatran was the first DTI, investigated and proven to be effective in prevention of recurrent ischemic events in ACS patients, but the drug association with hepatotoxicity prompted its withdrawal. Dabigatran etexilate, apixaban, darexaban (YM150) and TAK-442 were studied in phase II dose-escalation trials in order to determine the balance between clinical effectiveness and bleeding risk in daily use with dual antiplatelet therapy, with both positive and negative results. Rivaroxaban is the only agent that completed a phase III trial, showing reduction in recurrent ischemic events rate and death from cardiovascular causes as well as all-cause death. This review summarizes the data from completed and ongoing clinical trials of the new oral anticoagulants in patients with ACS.     

Nitric oxide modulates apomorphine-induced recognition memory deficits in rats

Nitric oxide (NO) is an important intracellular messenger in the brain. The implication of NO in schizophrenia is well documented although it is not yet clear whether net over or underproduction of NO is typical of this disease. In line with this, either NO donors or NO synthase (NOS) inhibitors were found to abolish psychotomimetic effects, including cognition deficits, produced by N-methyl-d-aspartate (NMDA) receptor hypofunction. In addition, there is poor experimental evidence concerning the efficacy of NO to modulate memory deficits produced by dopamine (DA) dysfunction. The present study was designed to investigate the ability of NO modulators (NO donors and NOS inhibitors to reverse recognition memory impairments produced by the DA D₁/D₂ mixed receptor agonist apomorphine in rats. For these studies, the novel object recognition test (NORT) was used as the memory test. Apomorphine (0.05, 0.1, 0.5 and 1.0 mg/kg), dose-dependently, disrupted performance in this recognition memory procedure in rats. The NO donors molsidomine (2.0 and 4.0 mg/kg) and SNP (0.3 and 1.0 mg/kg), reversed the impairing effects of apomorphine (1.0 mg/kg) in the NORT. Administration of the NOS inhibitors L-NAME (1.0 and 3.0 mg/kg) or 7-NI (1.0 and 3.0 mg/kg) produced similar results. The present findings indicate a) that apomorphine dose-dependently impaired recognition memory and b) that a cognitive deficit produced by DA dysfunction is sensitive to NO.     

Fungemia due to Moesziomyces aphidis (Pseudozyma aphidis) in a premature neonate. Challenges in species identification and antifungal susceptibility testing of rare yeasts

Premature neonates are at particularly increased risk to develop invasive infections with excessive case fatality due to their low birth weight, enteral malabsorbtion, insufficient microbial defenses and underdeveloped anatomic barriers. We present a case of Moesziomyces aphidis (syn. Pseudozyma aphidis) fungemia in a newborn with severe morbidity and prolonged hospital stay. Phenotypic tests failed to identify the isolate whereas commercial antifungal susceptibility tests failed to detect resistance to fluconazole. To the best of our knowledge, this is the first case of M. aphidis fungemia in a premature neonate in whom complete clinical resolution occurred after liposomal amphotericin B administration. Our case is the third Pseudozyma spp. infection described in Europe. Twenty-one cases have been described globally. Common risk factors were central venus catheter (80%), previous antibiotic treatment (80%), hematologic malignancies (27%) and solid tumors (20%) with 3 cases reported in neonates. The most commonly used antifungal therapy was amphotericin B followed by oral voriconazole or itraconazole. Our report highlights the clinical importance of rare yeasts species in neonates, emphasizes the roles of prematurity and lower birth weight as major risk factors for invasive infections with high morbidity. Reliable identification and susceptibility testing of these rare yeasts is a key issue for an adequate therapy and better outcome.     

“Heart failure in COVID-19 patients: Critical care experience”: A letter to the editor

Coronavirus disease 2019 (COVID-19) is associated with poor cardiovascular outcomes in patients with heart failure (HF) of all categories of ejection fraction (EF), but mainly in patients with HF with reduced EF. Moreover, cardiac transplant patients exhibit worse cardiovascular prognosis, high mortality, and more admissions to the intensive care unit. In general, COVID-19 seems to de-teriorate the clinical status of HF and favors the development of acute respiratory distress syndrome and multiorgan failure, especially in the presence of cardiovascular comorbidities such as diabetes mellitus, kidney dysfunction, and older age. COVID-19 may induce new-onset HF with complex mechanisms that involve myocardial injury. Indeed, myocardial injury comprises a large category of detrimental effects for the myocardium, such as myocardial infarction type 1 or type 2, Takotsubo cardiomyopathy, microvascular dysfunction and myocarditis, which are not easily distinguished by HF. The pathophysiologic mechanisms mainly involve direct myocardial damage by severe acute respiratory syndrome coronavirus 2, cytokine storm, hypercoagulation, inflammation, and endothelial dysfunction. The proper management of patients with COVID-19 involves careful patient evaluation and ongoing monitoring for complications such as HF.     

Prevention, diagnosis, and treatment of hypertensive heart disease

Hypertensive heart disease (HHD), a result of long-standing hypertension, is characterized by changes in the myocardial structure and function in the absence of other primary cardiovascular abnormalities. Although increased blood pressure is the initiating stimulus, neurohormonal factors, particularly the renin-angiotensin system, play a key role in remodeling of cardiac chamber geometry and walls. Optimal antihypertensive therapy in the setting of therapeutic lifestyle changes is crucial in the prevention and control of HHD. Regression of left ventricular hypertrophy (LVH) is achievable and associated with improved prognosis. However, prevention of myocardial remodeling before LVH establishes would further increase the benefits to cardiac function and prognosis. Antihypertensive agents exhibit variable effectiveness in inducing LVH regression. Currently, renin-angiotensin system blocking agents seem to be the most effective approach for LVH regression and reverse remodeling in these patients.     

Body weight decreases induced by estradiol in female rhesus monkeys are dependent upon social status

Gonadal steroids regulate appetite and thus body weight. In addition, continuous exposure to stressors negatively influences appetite through circuits likely distinct from those of gonadal steroids. The occurrence of adverse metabolic consequences due to chronic exposure to psychosocial stressors is twice as frequent in women as men, implicating a role for ovarian hormones, estradiol (E2) and progesterone (P4), in modulating stress-induced changes in appetite. Using social subordination in female macaques as a model of social stress, the current study tested the hypothesis that subordinate females would lose more weight during E2 treatment and gain less weight during P4 administration than dominant females. Because polymorphisms in the gene encoding the serotonin transporter (5HTT; SCL6A4) are known to alter responsivity to stress, we hypothesized that weight loss during E2 administration would be greatest in females with the short variant (s-variant) allele of 5HTT. Dominant females were significantly heavier than subordinate animals throughout the study, a result consistent with previous accounts of food intake when animals are fed a low-fat, high-fiber diet. Females with the s-variant 5HTT genotype weighed significantly less than l/l animals. Dominant animals lost significantly more weight than subordinate animals during E2 treatment. Administration of P4 blocked the weight-reducing effects of E2 in all females, regardless of social status. These data provide evidence that social subordination modulates the influence of ovarian steroid hormones on body weight in female rhesus monkeys independent of 5HTT genotype. Given the prosocial effects of these steroids, future studies are necessary to determine whether status differences in E2-induced weight loss are due to diminished food intake and or increases in energy expenditure and how the change in energy availability during E2 treatments relates to a female's motivation to interact with conspecifics.     

A case of liver sarcoidosis mimicking cirrhosis

Although autopsy series report liver granulomas in up to 70% of patients, computed tomography detection of hepatic and splenic lesions is described in 5% and 15% of sarcoidosis cases, respectively. A rather rare case of liver sarcoidosis mimicking macronodular cirrhosis is presented by this current article. Imaging findings in our patient were in compliance with the diagnosis of liver cirrhosis, although liver biopsy findings eventually revealed sarcoid granulomas located in the portal and lobular areas without fibrotic lesions. Histological and imaging modalities in liver sarcoidosis are discussed.     

Misleading interpretation of distended post-op bowel images in Helical CT scan

Differential diagnosis of distended post-op colon can be misleading when based solely to imaging findings. A case report of an artefact giving the impression of faecal leak or foreign body (gossypiboma) in Spiral Computerized Tomography after colonic surgery is presented. The patient was managed conservatively due to the lack of clinical evidence of abdominal emergency, A second CT scan twenty days later revealed no findings besides minor colonic diverticulas.