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.     

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.     

Containment of an outbreak of KPC-3-producing Klebsiella pneumoniae in Italy

From March 2009 to May 2009, 24 carbapenem-resistant Klebsiella pneumoniae isolates were recovered from 16 patients hospitalized in an Italian intensive care unit (ICU). All isolates contained KPC-3 carbapenemase and belonged to a single pulsed-field gel electrophoresis (PFGE) clone of multilocus sequence type 258 (designated as ST258). A multimodal infection control program was put into effect, and the spread of the KPC-3-producing K. pneumoniae clone was ultimately controlled without closing the ICU to new admissions. Reinforced infection control measures and strict monitoring of the staff adherence were necessary for the control of the outbreak.     

Clinical features and personality traits associated with psychological distress in systemic sclerosis patients

OBJECTIVE: The aim of the present study was to identify certain clinical parameters and personality characteristics associated with various forms of psychopathology in systemic sclerosis (SSc) patients. METHODS: Fifty-six SSc patients participated in the study, and 74 healthy participants served as controls. A wide range of clinical information was collected, and the following self-report instruments were used: General Health Questionnaire, Symptom Distress Checklist-90-R, Defense Style Questionnaire, Sense of Coherence (SOC) Scale, and Hostility and Direction of Hostility Questionnaire. RESULTS: The odds of being assessed with a psychiatric diagnosis upon interview were 4.5 times greater among SSc patients compared with controls. Disease duration and lower rates of SOC were found to be associated with elevated symptoms of general psychological distress. Elevated symptoms of depression were strongly associated with esophageal involvement, hostility, and defense style used. Elevated symptoms of anxiety were mainly associated with arthritis-related painful conditions and SOC, while psychotic-like symptoms were only associated with age and a specific personality structure. CONCLUSIONS: SSc patients experience elevated symptoms of psychological distress. Several clinical parameters are associated with distress, but the role of various personality traits could not be disregarded. Early psychiatric assessment and intervention could prevent psychological distress in SSc patients.     

The clinical significance of non-malignant neutropenia in hospitalized children

Neutropenia in non-cancer patients is often discovered in the course of an evaluation for acute infection, and it is usually secondary to the infection itself rather than a predisposing factor of the infection. Although it is not a common finding in hospitalized pediatric patients, it causes a great concern to the treating physicians. The aim of this study was to determine the incidence, the etiology, and the clinical significance of neutropenia in previously healthy children admitted in a general pediatric ward. One thousand five hundred and forty-eight patients admitted during a period of 18 months were included in the study. The clinical characteristics, the complete blood count, and the sedimentation rate were recorded. A total of 143 (9.2%) pediatric patients were identified as neutropenic, with mean absolute neutrophilic count of 0.960 × 10⁹/l (SD 0.341 × 10⁹/l) and ranged from 0.200 to 1.499 × 10⁹/l. The neutropenic patients had lower hemoglobin of 11.2 mg/dl and ranged from 6.2 to 17.2 mg/dl compared to hemoglobin of 11.5 mg/dl, which ranged from 5.2 to 18.0 mg/dl of the individuals with normal neutrophils, p < 0.0001 and lower mean platelet count of 294 × 10⁹/l, which ranged from 122 to 929 × 10⁹/l compared to platelet count of 381 × 10⁹/l, which ranged from 90–165 × 10⁹/l of the individuals without neutropenia, p < 0.001. Additionally, those patients were significantly younger than the non-neutropenic ones. Infection was the most common cause of neutropenia, although none of them developed septicemia. The neutrophil count normalized in most of the patients before discharge. However, 12 (8.3%) of neutropenic patients were discharged with persistent findings. Two of those were finally diagnosed with autoimmune neutropenia. In conclusion, the acquired neutropenia in hospitalized patients without malignancy is mild to moderate. It has no influence on the clinical outcome. Importantly, it has short duration, and it is usually resolved before patient’s discharge.     

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.     

Cystine accumulation in the CNS results in severe age-related memory deficits

Cystinosis is a lysosomal storage disorder characterised by progressive cystine accumulation. The causative gene, CTNS, encodes cystinosin, the lysosomal cystine transporter. Neurological deterioration is one of the last symptoms to appear and the least well characterised. Visuospatial memory deficits have been documented in patients. To determine whether the cystinosis mouse model presents similar anomalies, we studied the learning and memory abilities of young and middle-aged Ctns(-/-) mice. We did not detect deficits in young Ctns(-/-) mice. In contrast, spatial reference and working memory deficits were detected in middle-aged Ctns(-/-) mice. Elevated cystine levels were detected in the hippocampus, cerebellum, forebrain and brainstem of all Ctns(-/-) mice, which increased with age and were consistent with the appearance of impairments. Our results strongly suggest that the cystinosis-associated CNS anomalies are due to progressive cystine accumulation. Furthermore, the Ctns(-/-) mice serve as a model to investigate the evolution of these anomalies and test the efficiency of existing and novel treatments to cross the blood-brain barrier and reduce lysosomal cystine levels.     

Fatigue resistance during high-intensity intermittent exercise from childhood to adulthood in males and females

This study examined the maturation pattern of fatigue resistance (FR) from childhood to adulthood in females and males during high-intensity intermittent exercise and compared FR between females and males in childhood and adolescence. Thirty males (boys 11.3 ± 0.5 years, teen-males 14.7 ± 0.3 years, men 24.0 ± 2.1 years) and 30 females (girls 10.9 ± 0.6 years, teen-females 14.4 ± 0.7 years, women 25.2 ± 1.4) participated in this study. They performed high-intensity intermittent exercise (4 × 18 maximal knee flexions and extensions with 1-min rest) on an isokinetic dynamometer at 120°s⁻¹. Peak torque of flexors (PTFL) and extensors (PTEX), and total work (TW) were measured. FR was calculated as % of PTEX, PTFL, and TW in 4th versus 1st set. FR was greater (P < 0.05) in boys versus teen-males and men, and in teen-males versus men. In females, FR was greater (P < 0.05) in girls versus teen-females and women, but not different between teen-females and women. FR was not different in boys versus girls and in teen-males versus teen-females. FR for PTFL, PTEX, and TW correlated negatively (P < 0.001) with the respective peak values (r = −0.68 to −0.84), and FR for TW with peak lactate (r = −0.58 to −0.69). In addition, age correlated (P < 0.01) with FR for males (r = −0.75) and females (r = −0.55). In conclusion, FR during high-intensity intermittent exercise undergoes a gradual decline from childhood to adulthood in males, while in females the adult profile establishes at mid-puberty (14–15 years). The maturation profile of FR in males and females during development appears to reflect the maturation profiles of peak torque, short-term muscle power, and lactate concentration after exercise. T. Tsirini and A. Zafeiridis contributed equally to this work.