A Novel Nomogram to Identify Candidates for Extended Pelvic Lymph Node Dissection Among Patients with Clinically Localized Prostate Cancer Diagnosed with Magnetic Resonance Imaging-targeted and Systematic Biopsies

Background

Available models for predicting lymph node invasion (LNI) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP) might not be applicable to men diagnosed via magnetic resonance imaging (MRI)-targeted biopsies.

Hypointense transcerebral veins at T2*-weighted MRI: a marker of hemorrhagic transformation risk in patients treated with intravenous tissue plasminogen activator.

Prediction of hemorrhagic transformation (HT) in patients treated by intravenous recombinant tissue-type plasminogen activator (rt-PA) is a challenging issue in acute stroke management. HT may be correlated with severe hypoperfusion. Signal changes may be observed at susceptibility-weighted magnetic resonance imaging (MRI) within large perfusion defects. A signal drop within cerebral veins at T2*-weighted gradient-echo MRI may be expected in severe ischemia, and may indicate subsequent risk of HT. The authors prospectively searched for an abnormal visibility of transcerebral veins (AVV) within the ischemic area in patients with hemispheric ischemic stroke, before they were treated with intravenous rt-PA therapy. Any correlation between AVV and baseline clinical or MRI findings, or further HT, was noted. An AVV was present in 23 of 49 patients (obvious, n = 8; moderate, n = 15), and was supported by severe hemodynamic changes at baseline MRI. The AVV was correlated with the occurrence of parenchymal hematoma type 2 at computed tomography during the first week (r = 0.44, P = 0.002). Five of six type 2 parenchymal hematomas occurred in association with obvious AVV. At multiple regression analysis, two baseline MRI factors had an independent predictive value for HT risk during the first week: the AVV and the cerebral blood volume ratio (Nagelkerke R2 = 0.48).     

The Tempofilter®: A Multicenter Study of a New Temporary Caval Filter Implantable for up to Six Weeks

multicenter study was conducted to evaluate a new temporary caval filter (TempofilterT) designed to be implanted for up to 6 weeks. A total of 66 patients with a mean age of 51.8 years were enrolled in the study. All had documented high risk of pulmonary embolism: severe deep venous thrombosis in 89.5% of cases and previous symptomatic pulmonary embolism in 65% of cases. Filter placement was performed in association with a surgical or obstetrical procedure in 68.5% of cases. The indication for filter placement was contraindication to or failure of anticoagulant therapy in 85% of the cases. The mean duration of implantation was 29.9 days. Pulmonary embolism was not observed during the implantation period. Partial thrombosis of the filter was observed in 15% of cases due to trapping of clots by the filter. Thrombosis did not hinder filter removal when attempted. Filter-related complications were minor. Filter migration occurred in only 7.5% of cases. Migration never led to complications and did not hinder filter removal. In all cases migration was due to specific, preventable causes. The results of this study show that the TempofilterT is not only safe and easy to use but also effective in preventing pulmonary embolism. A significantly longer maximum implantation time is a major advantage of the TempofilterT over conventional temporary filters. We believe that this filter can be used for temporary protection against the risk of pulmonary embolism particularly in young patients and in a surgical setting. (Ann Vasc Surg 1997;11:520–528.)     

Causal pathways of the effects of age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on AIDS development

OBJECTIVE: To investigate the causal pathways by which age and the CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles influence progression to AIDS. DESIGN: Analysis of follow-up data from 2 cohort studies among homosexual men (n=400), having >10 years of follow-up. METHODS: The effects of the 4 cofactors on the CD4 and HIV-1 RNA trajectories after seroconversion were modeled in a random-effects model. A proportional hazards model was used to investigate their effect on the risk of AIDS after correction for CD4 cell count and RNA level. This approach allows investigation as to whether they influence AIDS progression by affecting CD4 count and RNA level or by other pathways. RESULTS: Persons of younger age or having the CCR2-64I or SDF-1 3'A mutation have significantly higher CD4 levels. Persons with the CCR5-Delta32 deletion or CCR2-64I mutation have significantly lower RNA levels. After correction for both CD4 count and RNA level, only the SDF-1 3'A mutation significantly increases the AIDS risk. CONCLUSIONS: Age and the CCR5-Delta32 deletion and CCR2-64I mutation influence AIDS progression by affecting CD4 and HIV-1 RNA. The SDF-1 3'A allele increases the AIDS risk, but this effect is countered by its effect on CD4 and HIV-1 RNA level.     

Genetic heterogeneity of the NS3 protease gene in hepatitis C virus genotype 1 from untreated infected patients

NS3 protease is essential for hepatitis C Virus (HCV) replication, and is one of the most promising targets for specific anti-HCV therapy. Its natural polymorphism has not been studied at the quasispecies level. In the present work, the genetic heterogeneity of the NS3 protease gene was analyzed in 17 HCV genotype 1 (5 subtypes 1a and 12 subtypes 1b) samples collected from infected patients before anti-viral therapy. A total of 294 clones were sequenced. Although the protease NS3 is considered to be one of the less variable genes in the HCV genome, variability of both nucleotide and amino acid sequences was found. In variants belonging to 1a and 1b subtypes, 224 and 267 of 543 positions showed one or more nucleotide substitutions, respectively. Forty and 74 of the 181 NS3 amino acid positions showed at least one mutation in HCV-1a and HCV-1b isolates, respectively. Most substitutions were conservative. This substantial polymorphism of the NS3 protease produced by HCV-1a and HCV-1b suggests that, despite the numerous functional and structural constraints, the enzyme is sufficiently flexible to tolerate substitutions.     

Stratégies d’immunothérapie dans les cancers colorectaux

Recent studies have underlined the close link between immune response and prognosis of patients with colorectal cancer (CRC). Immune response understanding combined with biotechnology progress of the last years has allowed development of immunotherapy strategies in CRC. Immunotherapy strategies are divided in “active” or “passive” strategies (patients immune system stimulation or not) and considering the activation of antigen specific immune response or not. These immunotherapy strategies are well tolerated and induced cellular and humoral response correlated with clinical response. Many monoclonal antibodies targeting signalisation pathways or angiogenic growth factors have demonstrated their efficacy in CRC. Multiple vaccine strategies, using different tumour associated antigens, have demonstrated a biological efficacy but with poor clinical results. Results are more promising in adjuvant setting but need to be confirmed by randomized trials. Adoptive immunotherapy with transfer of tumour associated antigen specific T cell is probably the most promising strategy. Actually, except monoclonal antibodies, immunotherapy is not used in clinical practice in CRC due to the lack of results and absence of standardisation.     

The Impact of Job-Demand-Control-Support on Leptin and Ghrelin as Biomarkers of Stress in Emergency Healthcare Workers

Despite the available literature on the consequences of night shiftwork on stress and food intake, its impact on leptin and ghrelin has never been studied. We previously demonstrated that leptin and ghrelin were biomarkers related to stress, and acute stress-induced a decrease in leptin levels and an increase in ghrelin levels. We performed a prospective observational study to assess the influence of night work, nutrition, and stress on the levels of ghrelin and leptin among emergency healthcare workers (HCWs). We took salivary samples at the beginning of a day shift and/or at the end of a night shift. We also monitored stress using the job demand-control-support model of Karasek. We recorded 24-h food intake during the day shift and the consecutive night shift and during night work and the day before. We included 161 emergency HCWs. Emergency HCWs had a tendency for decreased levels of leptin following the night shift compared to before the dayshift (p = 0.067). Furthermore, the main factors explaining the decrease in leptin levels were an increase in job-demand (coefficient −54.1, 95 CI −99.0 to −0.92) and a decrease in job control (−24.9, −49.5 to −0.29). Despite no significant changes in ghrelin levels between shifts, social support was the main factor explaining the increase in ghrelin (6.12, 0.74 to 11.5). Food intake (kcal) also had a negative impact on leptin levels, in addition to age. Ghrelin levels also decreased with body mass index, while age had the opposite effect. In conclusion, we confirmed that ghrelin and leptin as biomarkers of stress were directly linked to the job demand-control-support model of Karasek, when the main cofounders were considered.     

Antipsychotics increase vesicular glutamate transporter 2 (VGLUT2) expression in thalamolimbic pathways

Recently the two vesicular-glutamate-transporters VGLUT1 and VGLUT2 have been cloned and characterized. VGLUT1 and VGLUT2 together label all glutamatergic neurons, but because of their distinct expression patterns in the brain they facilitate our ability to define between a VGLUT1-positive cortical and a VGLUT2-positive subcortical glutamatergic systems. We have previously demonstrated an increased cortical VGLUT1 expression as marker of antidepressant activity. Here, we assessed the effects of different psychotropic drugs on brain VGLUT2 mRNA and protein expression. The typical antipsychotic haloperidol, and the atypicals clozapine and risperidone increased VGLUT2 mRNA selectively in the central medial/medial parafascicular, paraventricular and intermediodorsal thalamic nuclei; VGLUT2 protein was accordingly amplified in paraventricular and ventral striatum and in prefrontal cortex. The antidepressants fluoxetine and desipramine and the sedative anxiolytic diazepam had no effect. These results highlight the implication of thalamo-limbic glutamatergic pathways in the action of antipsychotics. Increased VGLUT2 expression in these neurons might constitute a marker for antipsychotic activity and subcortical glutamate neurotransmission might be a possible novel target for future generation antipsychotics.     

Internal Jugular Vein Tumor Thrombus: A Tricky Question for the Thyroid Surgeon

Internal jugular vein tumor thrombus is an extremely rare condition in thyroid carcinoma, but it does exist. Correlated with greater aggressiveness with a higher incidence of distant metastases at diagnosis and a higher recurrence rate, this important prognostic element should be systematically investigated by ultrasound operators in all patients presenting with thyroid carcinoma. The patient’s follow-up must be careful. This can be a trap that surgeons must look for in their preoperative checklist. We report the case of a 58-year-old woman with an IJV thrombus associated with multiple bone metastases. She underwent successful surgical treatment, and postoperative pathology showed a poorly differentiated follicular carcinoma of the thyroid and a tumor thrombus in the internal jugular vein.