Candidemia in Patients with Body Temperature Below 37°C and Admitted to Internal Medicine Wards: Assessment of Risk Factors

Background

An increasing number of candidemia episodes has been reported in patients cared for in internal medicine wards. These usually older and frail patients may not be suspected as having candidemia because they lack fever at the onset of the episode. To identify the risk factors associated with the lack of fever at the onset of candidemia (ie, the collection of the first positive blood culture for Candida spp.) in patients cared for in internal medicine wards, we compared 2 group of patients with or without fever.

Methods

We retrospectively review data charts from 3 tertiary care, university hospitals in Italy, comparing patients with or without fever at onset of candidemia. Consecutive candidemic episodes in afebrile patients and matched febrile controls were identified during the 3-year study period. Patient baseline characteristics and several infection-related variables were examined. Random forest analysis was used, given the number of predictors to be considered and the potential complexity of their relations with the onset of fever.

Results

We identified 147 candidemic episodes without fever at onset and 147 febrile candidemia episodes. Factors associated with the lack of fever at onset of candidemia were diabetes, Clostridium difficile infection, and a shorter delta time from internal medicine wards admission to the onset of candidemia. The only variable associated with fever was the use of intravascular devices. Quite unexpectedly, antifungal therapy was administered more frequently to patients without fever, and no differences on 30-day mortality rate were documented in the 2 study groups.

Conclusions

Clinicians should be aware that an increasing number of patients with invasive candidiasis cared for in internal medicine wards may lack fever at onset, especially those with diabetes and C. difficile infection. Candidemia should be suspected in patients with afebrile systemic inflammatory response syndrome or in worsening clinical condition: blood cultures should be taken, and a timely and appropriate antifungal therapy should be considered.     

Reduction of blood coagulation and monocyte-platelet interaction following the use of a minimal extracorporeal circulation system (Synergy) in coronary artery bypass grafting (CABG)

Cardiovascular surgery with cardiopulmonary bypass (CPB) induces activation of blood coagulation and systemic inflammation involved in post-operative complications. Our study evaluated the impact of the minimal extracorporeal circulation (mini-CPB) system (Synergy, Sorin Group) on these functional aspects. Twenty patients were randomly assigned to standard CPB (n = 10) or to Synergy (n = 10). Platelet expression of PAC-1, and monocyte/granulocyte-platelet conjugates were evaluated by flow cytometry. A leukocyte-platelet adhesion index was calculated after cell number normalization. ELISAs were performed to measure IL-6 and TNF-alpha, thrombin-antithrombin III complexes (TAT), prothrombin fragments (F1+2), beta-thromboglobulin (beta-TG) and sP-selectin (sCD62P). Blood samples were drawn at the time of anesthesia (T1), at the end of CPB (T2), and at 4 (T3) and 24 hours (T4) after weaning from CPB. All patients were similar for clinical characteristics. When compared to standard CPB, the Synergy showed lower levels of the monocyte-platelet adhesion index at T2 (0.023 +/- 0.005 vs 0.063 +/- 0.013, P = 0.0092) and T4 (0.031 +/- 0.003 vs 0.055 +/- 0.005, P = 0.0017), TAT complexes at T2 (27.175 +/- 5.967 vs 86.592 +/- 5.415, P = 0.0005) and T3 (26.977 +/- 2.468 vs 45.146 +/- 4.365, P = 0.0041), F1+2 fragments at T2 (2.222 +/- 0.226 vs 4.249 +/- 0.292, P = 0.0009), and sP-selectin at T3 (115.17 +/- 19.623 vs 169.554 +/- 19.709, P = 0.0703) and T4 (108.542 +/- 6.429 vs 140.799 +/- 14.771, P = 0.0833). In summary, the Synergy exhibited a lower post-operative activation of blood coagulation, together with a reduced interaction between circulating monocytes and platelets.     

The Role of Autophagy in the Maintenance of Stemness and Differentiation of Mesenchymal Stem Cells

Regulated self-consumption, also known as autophagy, is an evolutionary conserved process that degrades cellular components by directing them to the lysosomal compartment of eukaryotic cells. As a major intracellular degradation and recycling pathway, autophagy is crucial for maintaining and remodeling cellular homeostasis during normal cellular and tissue development. Recent studies have demonstrated that autophagy is necessary for the maintenance of cellular stemness and for a number of differentiation processes, including the lineage determination of mesenchymal stem cells. These are multipotent progenitor cells with self-renewal capacities that can give rise to a subset of tissues and thus hold a consistent potential in regenerative medicine. Here, we review the current literature on the complex liaison between autophagy induced by various extra- or intracellular stimuli and the molecular targets that affect mesenchymal stem cells proliferation and differentiation.     

Nutraceutical value and safety of tomato fruits produced by mycorrhizal plants

Tomato fruit has assumed the status of 'functional food' due to the association between its consumption and a reduced likelihood of certain types of cancers and CVD. The nutraceutical value of tomatoes can be affected by the cultivation conditions, e.g. the phytochemical content of the fruits may increase with the establishment of beneficial mycorrhizal symbioses in the plants. A multidisciplinary study was carried out to gain knowledge on the antioxidant, oestrogenic/anti-oestrogenic and genotoxic activity of tomato fruits produced by mycorrhizal plants. The present results showed that the symbiosis positively affected the growth and mineral nutrient content of tomato plants and enhanced the nutritional and nutraceutical value of tomato fruits through modifications of plant secondary metabolism, which led to increased levels of lycopene in fruits obtained from mycorrhizal plants, compared with controls. Moreover, such changes did not result in the production of mutagenic compounds, since tomato extracts induced no in vitro genotoxic effects. Fruit extracts, both hydrophilic and the lipophilic fractions, originating from mycorrhizal plants strongly inhibited 17-β-oestradiol-human oestrogen receptor binding, showing significantly higher anti-oestrogenic power compared with controls. The present study shows that beneficial plant symbionts, such as mycorrhizal fungi, can lead to the production of safe and high-quality food, which is an important societal issue strongly demanded by both consumers and producers.     

Platelet activation predicts recurrent ischemic events after percutaneous coronary angioplasty: a 6 months prospective study

Introduction

An increasing amount of evidence indicates that platelet reactivity, despite a standard anti-thrombotic therapy, is a potential risk factor for recurrent myocardial ischemia in patients with coronary artery disease. We now hypothesize that this condition, measured by collagen-epinephrine (CEPI) or collagen-ADP (CADP) closure times (CT) by Platelet Function Analyzer (PFA-100), may predict the recurrence of coronary events after percutaneous coronary intervention (PCI).

Materials and methods

CEPI and CADP-CT were measured 30 ± 8 h after PCI in 175 consecutive patients admitted with a diagnosis of stable angina (n = 94) or acute coronary syndromes (n = 81) and prospectively followed up for a mean period of 6 months. We stratified the patients in accordance to both the CEPI-CT (<or> 190 s), reflecting the intensity of cycloxygenase inhibition by aspirin and the distribution into quartiles for CADP-CT.

Results

CEPI-CT < 190 s as well as CADP-CT < 82 s were associated with a higher rate of clinical recurrence (hazard ratio 8.5, p < 0.001 and 22.9, p < 0.001, respectively). Multivariate analysis after adjustment for other risk factors confirmed that the lowest CADP-CT quartile significantly correlates with the risk of recurrent coronary events (hazard ratio 36.5, p < 0.01), as well as CEPI-CT < 190 s (hazard ratio 6.7, p = 0.01).

Conclusions

An enhanced platelet function after PCI when measured under high shear rates by PFA-100 is an independent predictor of a worst clinical outcome, even during a short term follow-up and may help in patients risk stratification.     

New N-n-propyl-substituted 3-aryl- and 3-cyclohexylpiperidines as partial agonists at the D4 dopamine receptor

We have previously reported that compounds dimethyl-substituted on the phenyl ring of N-n-propyl-3-phenylpiperidines (PPEs) have a high (nM) affinity and selectivity toward the D(4) dopamine receptor (D(4) DAR) with m,p-dimethyl PPE (1) having the highest affinity and selectivity. In the present paper we have investigated the role of the methyl substitution by the synthesis of monomethylated (2a-c) and nonmethylated (2d) PPEs followed by the characterization of their biological properties using receptor binding assays. Our findings reveal that the methyl substitution of the phenyl ring is not necessary for a high and selective binding affinity to the D(4) DAR. Moreover, we have also synthesized cyclohexylpiperidines (CHPEs, 3a-d), which all showed higher binding affinities for the D(4) DAR than their aromatic counterparts. These results indicate that a pi-pi type interaction of the phenyl ring of PPEs with the D(4) DAR might not be essential, whereas a simple hydrophobic attraction between the cyclohexyl substituent of CHPEs and a hypothesized lipophilic pocket of the receptor might be crucial. Furthermore, functional assays indicate that 3d, as well as 1, are partial agonist at the D(4) DAR and therefore might represent new pharmacological tools to investigate the role of D(4) DAR activation in the control of cognitive functions and emotional states in health and disease.     

Psychotic features in borderline patients: is there a connection to mood dysregulation?

OBJECTIVE: To investigate the relationship between lifetime mood and psychotic spectrum features in patients with borderline personality disorder (BPD). Method: The study sample consisted of BPD patients with (n=39, BPD-M) or without (n=21, BPD-no M) lifetime mood disorders. The diagnostic assessment was conducted with the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I). The diagnosis of BPD was made clinically and then confirmed by Gunderson's diagnostic interview for borderlines. Subjects were also administered the Structured Clinical Interview for Psychotic Spectrum (SCI-PSY) and the Mood Spectrum self-report questionnaire (MOODS-SR). RESULTS: BPD-M had significantly higher scores than BPD-no M on the 'lifetime' mood spectrum subdomains 'depressive mood' and 'depressive cognition'. The two groups did not differ on the scores of psychotic spectrum except for higher 'hypertrophic self-esteem' scores in BPD-no M. In BPD-no M both the depressive and the manic-hypomanic component of mood spectrum were significantly correlated with the 'delusion' subdomain of the psychotic spectrum. The depressive component was correlated with 'depersonalization/derealization' and the manic-hypomanic component was correlated with 'hypertrophic self-esteem'. In BPD-M, the manic-hypomanic component of mood spectrum was correlated with different subdomains of the psychotic spectrum: 'hypertrophic self-esteem', 'self-reference', 'interpretive attitude', 'anger/overreactivity, 'unusual and odd thoughts', 'illusions', 'delusions', 'hallucinations' and 'catatonia'. The depressive component of mood spectrum was 'uncorrelated' with the subdomains of the psychotic spectrum. CONCLUSIONS: Our data support the hypothesis that 'lifetime' manic-hypomanic mood dysregulations are correlated with psychotic spectrum features in borderline patients. The assessment of these spectrum features in borderline patients may be useful to inform treatment choices.     

Oxidative and genotoxic damage after radio-iodine therapy of Graves' hyperthyroidism

PURPOSE: To evaluate genetic damage and oxidative stress following a single therapeutic dose of 131I in Graves' disease patients monitored up to 180 days after treatment. MATERIALS AND METHODS: Genetic damage induction was estimated as the increase in micronuclei in peripheral lymphocytes of patients. As indicators of radiogenic oxidative stress, vitamin E and lipoperoxide levels were assessed in the plasma of patients, as well as the release of plasmic clastogenic factors measured by the induction of micronuclei in vitro in peripheral lymphocytes of a healthy donor. RESULTS: Vitamin E depletion lasted at least 3 days and the basal level was restored within 7 days. No statistically significant variations were observed in lipoperoxide plasma levels. A sharp increase of micronuclei in the peripheral lymphocytes of patients was correlated (p < 0.001) with the release of clastogenic factor in the plasma. The highest micronucleus value was negatively correlated (p < 0.03) with the lowest vitamin E level observed in each patient. CONCLUSIONS: Micronuclei induction was the direct consequence not only of the energy deposition of 131I on the genetic material, but also of oxidative stress, likely via the release of clastogenic factor.     

The spectrum of substance use in mood and anxiety disorders

This study evaluates the prevalence of threshold and subthreshold use of substances among patients with psychiatric disorders and 2 comparison groups. Participants were outpatients and inpatients with mood and anxiety disorders, subjects with opiate dependence, and a comparison group of individuals not undergoing treatment for psychiatric disorders. Assessments included the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition , Axis I Disorders, an interview exploring the spectrum of substance use (Structured Clinical Interview for the Spectrum of Substance Use), and a self-report instrument exploring the spectrum of 5 psychiatric disorders (General 5-Spectrum Measure). The overall frequency of substance use disorder (SUD) and that of subthreshold use were 46% and 8% in patients with bipolar disorder, 4% and 26% in those with panic disorder, 8% and 26% in those with obsessive-compulsive disorder, and 6% and 10% in the control group, respectively ( Idouble dagger 2 = 51.6, P < .001). Inspection of standardized residuals indicated that alcohol use disorder and SUD were significantly ( P < .05) more frequent in subjects with bipolar disorder than among those with obsessive-compulsive disorder or panic disorder. The latter showed a significantly higher subthreshold use of substances than control subjects. The pattern of motivations for use varied according to the psychiatric disorder. Our results suggest that the well-established relationship between SUDs and psychiatric disorders might be the end point of a process that starts from increased proneness to substance use, which first leads to self-medication and then may eventually develop into substance abuse or dependence, among subjects with psychiatric symptoms.