Serratia marcescens prosthesis infection successfully treated with meropenem after imipenem failure

A 78-year-old woman developed an early knee-prosthesis infection due to multiresistant Serratia marcescens that was successfully treated with high-dose meropenem, after failure of a long-term therapy combining imipenem and multiple surgical interventions. Because of its lower neurotoxicity, meropenem might be preferred to imipenem/cilastatin for the treatment of osteo-articular infections due to multiresistant Gram-negative bacilli in the elderly.     

Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children

BACKGROUND: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected. PATIENTS: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV. METHODS: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation. RESULTS: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions. CONCLUSIONS: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.     

A three-gene signature based on MYC,BCL-2 and NFKBIA improves risk stratification in diffuse large B-cell lymphoma

Recent randomized trials focused on gene expression-based determination of the cell of origin in diffuse large B-cell lymphoma could not show significant improvements by adding novel agents to standard chemoimmunotherapy. The aim of this study was the identification of a gene signature able to refine current prognostication algorithms and applicable to clinical practice. Here we used a targeted gene expression profiling panel combining the Lymph2Cx signature for cell of origin classification with additional targets including MYC, BCL-2 and NFKBIA, in 186 patients from two randomized trials (discovery cohort) (clinicaltrials gov. Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00355199","term_id":"NCT00355199"}}NCT00355199 and {"type":"clinical-trial","attrs":{"text":"NCT00499018","term_id":"NCT00499018"}}NCT00499018). Data were validated in three independent series (two large public datasets and a real-life cohort). By integrating the cell of origin, MYC/BCL-2 double expressor status and NFKBIA expression, we defined a three-gene signature combining MYC, BCL-2 and NFKBIA (MBN-signature), which outperformed the MYC/BCL-2 double expressor status in multivariate analysis, and allowed further risk stratification within the germinal center B-cell/unclassified subset. The high-risk (MBN Sig-high) subgroup identified the vast majority of double hit cases and a significant fraction of activated B-cell-derived diffuse large B-cell lymphomas. These results were validated in three independent series including a cohort from the REMoDL-B trial, where, in an exploratory ad hoc analysis, the addition of bortezomib in the MBN Sig-high subgroup provided a progression free survival advantage compared with standard chemoimmunotherapy. These data indicate that a simple three-gene signature based on MYC, BCL-2 and NFKBIA could refine the prognostic stratification in diffuse large B-cell lymphoma, and might be the basis for future precision-therapy approaches.     

Platelet cyclic GMP levels in unstable angina and myocardial infarction

Background: Several studies showed that there is a state of platelet hyperactivaction in patients with coronary syndrome: the aim of this study is to investigate if the platelet nitric oxide-cyclicGMP (NO-cGMP) pathway, that regulates platelet aggregation is altered in patients with unstable angina (UA) and acute myocardial infarction (AMI). Methods and results: Population included 11 patients with UA, 12 patients with AMI and 23 controls. Platelet cGMP was measured by a radioimmunoassay kit, under basal conditions and after stimulation with sodium nitroprusside (SNP), which maximally stimulates soluble guanylate cyclase (sGC), used as an indirect measurement of active sGC. Basal platelet cGMP values were significantly ( P <0.001) higher in patients with UA and AMI than in controls (UA, 1089 - 412 pmol/10 10 platelets; AMI, 1071 - 507 pmol/10 10 platelets; controls, 492 - 201 pmol/10 10 platelets). The final cGMP level reached after SNP stimulation was significantly more elevated in UA, compared with both AMI ( P <0.05) and controls ( P <0.02) (UA, 4428 - 2723 pmol/10 10 platelets; AMI, 2728 - 655 pmol/10 10 platelets; controls, 2772 - 1031 pmol/10 10 platelets); on the contrary no significant difference between AMI and controls was observed. Conclusions: Basal platelet cGMP is significantly higher in both UA and AMI groups. This observation suggests that: (1) platelet-derived NO synthesis may be enhanced inUA and AMI, due to increase of intraplatelet calcium level and of platelet cNOS activation; (2) platelets from UA and AMI patients are continuously stimulated by the high-level NO production due to increased iNOS expression. As far as SNP-dependent cGMP production is concerned, UA and AMI behave as two separate conditions. SNP-stimulated activity in UA is higher than in controls, while a loss of functional sGC is observed in AMI.     

Cerebral activation by fasting induces lactate accumulation in the hypothalamus

Carbon‐13 (¹³C) high‐resolution magic angle spinning (HR‐MAS) spectroscopy was used to investigate the neuroglial coupling mechanisms underlying appetite regulation in the brain of C57BL/6J mice metabolizing [1‐¹³C]glucose. Control fed or overnight fasted mice received [1‐¹³C]glucose (20 μmol/g intraperitoneally [i.p.]), 15 min prior to brain fixation by focused microwaves. The hypothalamic region was dissected from the rest of the brain and ¹³C HR‐MAS spectra were obtained from both biopsies. Fasting resulted in a significant increase in hypothalamic [3‐¹³C]lactate and [2‐¹³C]γ‐aminobutyric acid (GABA) relative to the remaining brain. Administration of the orexigenic peptide ghrelin (0.3 nmol/g i.p.) did not increase hypothalamic [3‐¹³C]lactate or [2‐¹³C]GABA, suggesting that ghrelin signaling is not sufficient to elicit all the metabolic consequences of hypothalamic activation by fasting. Our results indicate that the hypothalamic regulation of appetite involves, in addition to the well‐known neuropeptide signaling, increased neuroglial lactate shuttling and augmented GABA concentrations. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.