Invasive mycoses in children receiving hemopoietic SCT

Invasive mycoses represent a rare but severe complication following hemopoietic SCT (HSCT) in children. Their incidence is related to the type of donor, being higher after allogeneic transplant, especially from alternative donors. Moreover, the incidence of invasive mycoses varies in the different post transplant phases. Neutropenia, lymphopenia, GvHD, high-dose steroids or other immunosuppressive drugs represent well-known risk factors. The clinical features of invasive mycoses after HSCT in children are similar to those observed in adults, and the diagnostic tools, including Aspergillus galactomannan antigen detection, are feasible also in pediatrics. Mortality due to invasive mycoses after HSCT in children is high.     

Usefulness of Reynolds Risk Score in men with stable angina

Introduction

Recently several risk scores have been proposed that, beyond traditional risk factors, also include additional inflammatory biomarkers underlying atherothrombosis. The Reynolds Risk Score (RRS) is a point scale assessing the risk of cardiovascular events over 10 years, which takes into account for the first time high-sensitivity C-reactive protein. The aim of this study was to establish clinical usefulness of RRS in men with stable coronary artery disease and preserved left ventricular systolic function.

Material and Methods

In total, 119 symptomatic non-diabetic man (mean age 63.9±9.23) who were directed for an elective coronary arteriography were enrolled in the study. Clinical data were collected including the elevated heart rate ≥70 bpm/min, basic laboratory results, placental growth factor and results of coronary angiography. Patients were analyzed related to RRS: low risk <10% (n=50), moderate risk 10-19% (n=46) and high risk >20% (n=23).

Results

Opposite to high RRS patients, in the low risk group more often occurred marginal or none atherosclerotic coronary arteries (13% vs. 44%, P=0.0214). The findings have revealed the relationship between the higher risk score and the lower frequency of marginal or no atherosclerotic coronary arteries (OR=0.19, 95%CI 0.05–0.67).

Conclusions

The Reynolds Risk Score appears to be useful in men with stable coronary artery disease and preserved left ventricular systolic function in stratifying the severity of coronary atherosclerosis.     

Six-month results following treatment of aggressive periodontitis with antimicrobial photodynamic therapy or amoxicillin and metronidazole

Objective

The use of antibacterial photodynamic therapy (aPDT) additionally to scaling and root planing (SRP) has been shown to positively influence the clinical outcomes. However, at present, it is unknown to what extent aPDT may represent a potential alternative to the use of systemic antibiotics in nonsurgical periodontal therapy in patients with aggressive periodontitis (AP). The aim of this study was to evaluate the outcomes following nonsurgical periodontal therapy and additional use of either aPDT or amoxicillin and metronidazole (AB) in patients with AP.

Material and methods

Thirty-six patients with AP displaying at least three sites with pocket depth (PD) ≥6 mm were treated with SRP and either systemic administration of AB for 7 days or with two episodes of aPDT. The following clinical parameters were evaluated at baseline and at 6 months: plaque index (PI), bleeding on probing (BOP), PD, gingival recession (GR) and clinical attachment level (CAL).

Results

Thirty-five patients have completed the 6-month evaluation. At 6 months, mean PD was statistically significantly reduced in both groups (from 5.0?±?0.8 to 3.0?±?0.6 mm with AB and from 5.1?±?0.5 to 3.9?±?0.8 mm with aPDT (p?p?p?p?=?0.03). Both therapies resulted in statistically significant reductions in all parameters compared to baseline.

Conclusion

While both treatments resulted in statistically significant clinical improvements, AB showed statistically significantly higher PD reduction and lower number of pockets ≥7 mm compared to aPDT.

Clinical relevance

In patients with AP, the two times application of aPDT in conjunction with nonsurgical periodontal therapy cannot be considered an alternative to the systemic use of amoxicillin and metronidazole.     

Clinical heterogeneity and diagnostic delay of autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy syndrome

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare autosomal recessive organ-specific autoimmune disorder that is characterized by a variable combination of (i) chronic mucocutaneous candidiasis, (ii) polyendocrinopathy and/or hepatitis and (iii) dystrophy of the dental enamel and nails. We analyzed the AIRE (autoimmune regulator) gene in subjects who presented any symptom that has been associated with APECED, including candidiasis and autoimmune endocrinopathy. We observed that 83.3% of patients presented at least two of the three typical manifestations of APECED, while the remaining 16.7% of patients showed other signs of the disease. Analysis of the genetic diagnosis of these subjects revealed that a considerable delay occurs in the majority of patients between the appearance of symptoms and the diagnosis. Overall, the mean diagnostic delay in our patients was 10.2 years. These results suggest that molecular analysis of AIRE should be performed in patients with relapsing mucocutaneous candidiasis for early identification of APECED.     

Identification of a third evolutionarily conserved gene within the RAG locus and its RAG1-dependent and -independent regulation

Recombination-activating gene (RAG)1 and RAG2 encode T and B lymphocyte-specific endonucleases indispensable for rearrangements of antigen-receptor gene segments but also capable of causing deleterious chromosome rearrangements. The mechanisms regulating RAG expression and repression are not clear. Here we identify NWC, a third evolutionarily conserved gene within the RAG locus, and show that it is ubiquitously expressed, with the notable exception of RAG-nonexpressing immature and mature T and B lymphocytes because in lymphocytes it is regulated by the RAG1 promoter and transcribed as RAG1-NWC hybrid mRNA molecules. We also show that in all other cells NWC is controlled by the RAG2 intragenic promoter, which in immature and mature T and B lymphocytes is silent. The possible implications of these findings for understanding the activation and inactivation of RAG genes in lymphocytes and their repression in other cells are discussed.     

Cutaneous melanoma with nodal metastases in elderly people

Background The impact of age on melanoma patient outcomes is uncertain. Objective The aim of the study was to analyze the characteristics and treatment outcomes in cutaneous melanoma patients ≥ 65 years of age with lymph node metastases. Methods We analyzed data from 849 consecutive patients with stage III cutaneous melanoma who were treated between 1994 and 2007 at one institution. Of these, 225 (26.5%) were ≥ 65 years of age. The characteristics and disease‐specific survival (DSS) from lymph node dissection (LND) date of patients ≥ 65 years of age were compared with those of younger patients. Median follow‐up time was 49 months (range: 6–140 months). Results In the ≥ 65 years group (51.6% men), the median Breslow thickness was 5.0 mm and 70% was ulcerated. The 5‐year DSS rate was significantly lower in older patients (34%). Multivariate analysis identified older age as an independent prognostic factor for DSS in the overall group. Independent negative prognostic factors of DSS in the group of older stage III patients were identified as features of nodal metastases (extracapsular invasion, HR = 1.74, P = 0.009; and ≥ 4 involved lymph nodes, HR = 1.5; P = 0.008) and male sex (HR = 1.5; P = 0.039). Conclusions This analysis showed that melanoma patients ≥ 65 years of age are characterized by a higher primary tumor stage and worse prognosis in the presence of regional node metastases than younger patients. Additionally, the results indicate that the same radical surgical therapy is necessary for patients ≥ 65 years old as in younger patients.     

Association Between IL-6 Concentration and Diabetes-Related Variables in DM1 Patients with and without Microvascular Complications

Interleukin 6 (IL-6) plays an important role in the initiation and acceleration of chronic inflammation and could contribute to development of microvascular complications in patients with type 1 diabetes (DM1). Therefore, this study was aimed to investigate the association between concentration of IL-6 in relation to glucose control, lipid profile, and body mass index (BMI) in 69 DM1 patients subdivided according to the absence or presence of microvascular complications. BMI, level of fasting plasma glucose (FPG), and concentrations of total cholesterol (TCH), LDL cholesterol (LDL-C), and IL-6 were higher in DM1 patients compared to the control group. In DM1 patients, IL-6 concentration was positively correlated with level of FPG, LDL-C, TCH concentrations, and BMI. These correlations were stronger in the subgroup of patients with microvascular complications. In addition, BMI independently influences IL-6 concentration in DM1 patients. In conclusion, elevated IL-6 concentration is associated with diabetes-related variables which could accelerate progression of microvascular complications in DM1 patients.     

Exercise increases mRNA levels for adhesion molecules N-CAM and L1 correlating with BDNF response

In situ hybridization was used to evaluate whether long-term moderate locomotor exercise, which up-regulates BDNF and TrkB levels in the spinal gray matter of the adult rat, similarly influences the expression of the cell adhesion molecules N-CAM and L1. Exercise doubled the level of N-CAM mRNA hybridization signal in the lumbar spinal gray. The increase in L1 mRNA was less consistent. N-CAM mRNA levels slightly increased in the white matter. BDNF mRNA levels also increased in cells of the ventral horn and the white matter due to the exercise. These results suggest that exercise-induced rearrangements of the spinal network involve N-CAM, L1 and BDNF, crucial in different aspects of synaptic plasticity and synapse formation.     

Glucocorticoid regulation of glial responses during hippocampal neurodegeneration and regeneration

Glucocorticoids can prevent or accelerate neurodegeneration in the adult rat hippocampus. To investigate these actions of glucocorticoids, we previously cloned genes from the hippocampus. Adrenalectomy specifically increased glial fibrillary acidic protein and transforming growth factor (TGF)-β1 mRNAs in the dentate gyrus and these effects were dependent on induced apoptosis. Corticosterone treatment prevented apoptosis, and decreased glial activation and the influx of activated microglia. Since these effects are opposite to injury and neurodegeneration, we propose that they represent adaptive actions of glucocorticoids, preventing cellular defense mechanisms from overshooting. We used adrenalectomy as a model to investigate how adult granule neurons die in vivo and the effects of neurotrophic factors in protecting against apoptosis. Neurotrophin-4/5 and TGF-β1 protected granule neurons against adrenalectomy-induced apoptosis. Since neurogenesis is also greatly increased in the dentate gyrus following adrenalectomy, we compared the time course of birth and death with glial responses. TGF-β1 mRNA increased before the detection of dying cells in the dentate gyrus, which was coincident with increased proliferation in the neurogenic zone. Glucocorticoids also increased Ndrg2 mRNA in glia in the neurogenic zone; Ndrg2 is a member of a novel gene family involved in neural differentiation and synapse formation. Therefore, studying the effects of glucocorticoid manipulation on the dentate gyrus is increasing our understanding of how mature neurons die by apoptosis and the role of glia in induced apoptosis and neurogenesis. Discovering how endocrine and inflammatory responses regulate neuron birth and survival is important for developing successful neuron replacement strategies to treat neurodegenerative diseases.