β-Glucan antigenemia assay for the diagnosis of invasive fungal infections in patients with hematological malignancies: a systematic review and meta-analysis of cohort studies from the Third European Conference on Infections in Leukemia (ECIL-3).

BACKGROUND: Invasive fungal infections (IFIs) are life-threatening complications in patients with hemato-oncological malignancies, and early diagnosis is crucial for outcome. The compound 1,3-β-D-glucan (BG), a cell wall component of most fungal species, can be detected in blood during IFI. Four commercial BG antigenemia assays are available (Fungitell, Fungitec-G, Wako, and Maruha). This meta-analysis from the Third European Conference on Infections in Leukemia (ECIL-3) assessed the performance of BG assays for the diagnosis of IFI in hemato-oncological patients. METHODS: Studies reporting the performance of BG antigenemia assays for the diagnosis of IFI (European Organization for Research and Treatment of Cancer and Mycoses Study Group criteria) in hemato-oncological patients were identified. The analysis was focused on high-quality cohort studies with exclusion of case-control studies. Meta-analysis was performed by conventional meta-analytical pooling and bivariate analysis. RESULTS: Six cohort studies were included (1771 adult patients with 414 IFIs of which 215 were proven or probable). Similar performance was observed among the different BG assays. For the cutoff recommended by the manufacturer, the diagnostic performance of the BG assay in proven or probable IFI was better with 2 consecutive positive test results (diagnostic odds ratio for 2 consecutive vs one single positive results, 111.8 [95% confidence interval {CI}, 38.6-324.1] vs 16.3 [95% CI, 6.5-40.8], respectively; heterogeneity index for 2 consecutive vs one single positive results, 0% vs 72.6%, respectively). For 2 consecutive tests, sensitivity and specificity were 49.6% (95% CI, 34.0%-65.3%) and 98.9% (95% CI, 97.4%-99.5%), respectively. Estimated positive and negative predictive values for an IFI prevalence of 10% were 83.5% and 94.6%, respectively. CONCLUSIONS: Different BG assays have similar accuracy for the diagnosis of IFI in hemato-oncological patients. Two consecutive positive antigenemia assays have very high specificity, positive predictive value, and negative predictive value. Because sensitivity is low, the test needs to be combined with clinical, radiological, and microbiological findings.

Anatomie chirurgicale du foie: ce qu'il faut savoir [Surgical anatomy of the liver: what you need to know]

A precise knowledge of arterial, portal, hepatic and biliary anatomical variations is mandatory when a liver surgery is planned. However, only certain variations must be searched when a precise intervention is planned. The main liver resection and biliary interventions will be precised. Related anatomical variations will be precised.

Effect of training-sample size and classification difficulty on the accuracy of genomic predictors.

Introduction: As part of the MicroArray Quality Control (MAQC)-II project, this analysis examines how the choice of univariate feature-selection methods and classification algorithms may influence the performance of genomic predictors under varying degrees of prediction difficulty represented by three clinically relevant endpoints. Methods: We used gene-expression data from 230 breast cancers (grouped into training and independent validation sets), and we examined 40 predictors (five univariate feature-selection methods combined with eight different classifiers) for each of the three endpoints. Their classification performance was estimated on the training set by using two different resampling methods and compared with the accuracy observed in the independent validation set. Results: A ranking of the three classification problems was obtained, and the performance of 120 models was estimated and assessed on an independent validation set. The bootstrapping estimates were closer to the validation performance than were the cross-validation estimates. The required sample size for each endpoint was estimated, and both gene-level and pathway-level analyses were performed on the obtained models. Conclusions: We showed that genomic predictor accuracy is determined largely by an interplay between sample size and classification difficulty. Variations on univariate feature-selection methods and choice of classification algorithm have only a modest impact on predictor performance, and several statistically equally good predictors can be developed for any given classification problem.

Profile of a serial killer: cellular and molecular approaches to study individual cytotoxic T-cells following therapeutic vaccination.

T-cell vaccination may prevent or treat cancer and infectious diseases, but further progress is required to increase clinical efficacy. Step-by-step improvements of T-cell vaccination in phase I/II clinical studies combined with very detailed analysis of T-cell responses at the single cell level are the strategy of choice for the identification of the most promising vaccine candidates for testing in subsequent large-scale phase III clinical trials. Major aims are to fully identify the most efficient T-cells in anticancer therapy, to characterize their TCRs, and to pinpoint the mechanisms of T-cell recruitment and function in well-defined clinical situations. Here we discuss novel strategies for the assessment of human T-cell responses, revealing in part unprecedented insight into T-cell biology and novel structural principles that govern TCR-pMHC recognition. Together, the described approaches advance our knowledge of T-cell mediated-protection from human diseases.

Valproic acid related idiosyncratic drug induced hepatotoxicity in a glioblastoma patient treated with temozolomide.

Glioblastoma patients undergoing treatment with surgery followed by radiation and temozolomide chemotherapy often develop a state of immunosuppression and are at risk for opportunistic infections and reactivation of hepatitis and herpes viruses. We report the case of a 48-year-old glioblastoma patient who developed acute cholestatic hepatitis with hepatic failure during adjuvant treatment with temozolomide and the integrin inhibitor cilengitide. A viral hepatitis was excluded and valproic acid treatment was stopped. Upon normalisation of the liver tests, temozolomide treatment was resumed without perturbation of the liver tests. Valproic acid related idiosyncratic drug induced hepatotoxicity should be considered as a differential diagnosis in glioblastoma patients undergoing adjuvant therapy.

Sémiologie de l'atteinte bronchique en scanner [Bronchial diseases: CT imaging features].

Multidetector row computed tomography (MDCT) is the imaging modality of reference for the diagnosis of bronchiectasis. MDCT may also detect a focal stenosis, a tumor or multiple morphologic abnormalities of the bronchial tree. It may orient the endoscopist towards the abnormal bronchi, and in all cases assess the extent of the bronchial lesions. The CT findings of bronchial abnormalities include anomalies of bronchial division and origin, bronchial stenosis, bronchial wall thickening, lumen dilatation, and mucoid impaction. The main CT features of bronchiectasis are increased bronchoarterial ratio, lack of bronchial tapering, and visibility of peripheral airways. Other bronchial abnormalities include excessive bronchial collapse at expiration, outpouchings and diverticula, dehiscence, fistulas, and calcifications.

Psychosocial care for the caregivers of primary malignant brain tumor patients.

Despite clinical experience that suggests a high burden of care among relatives of individuals with a primary malignant brain tumor (PMBT), little is known about their actual needs. In this study, the caregivers' personal experiences, quality of life, burden of care, and psychological well-being were examined. Fifty-nine percent did not receive any financial aid for home care, 33% had increased risk for psychosomatic problems, 45% had anxiety, and 33% increased depression levels. The caregiver's quality of life was most strongly affected by the burden of care (p < .001) and the patient's mental state (p < .03). To improve the situation, empathetic professionals and an early implementation of palliative care and social work are required.

The reasons for discrepancies in target volume delineation : a SASRO study on head-and-neck and prostate cancers.

PURPOSE: To understand the reasons for differences in the delineation of target volumes between physicians. MATERIAL AND METHODS: 18 Swiss radiooncology centers were invited to delineate volumes for one prostate and one head-and-neck case. In addition, a questionnaire was sent to evaluate the differences in the volume definition (GTV [gross tumor volume], CTV [clinical target volume], PTV [planning target volume]), the various estimated margins, and the nodes at risk. Coherence between drawn and stated margins by centers was calculated. The questionnaire also included a nonspecific series of questions regarding planning methods in each institution. RESULTS: Fairly large differences in the drawn volumes were seen between the centers in both cases and also in the definition of volumes. Correlation between drawn and stated margins was fair in the prostate case and poor in the head-and-neck case. The questionnaire revealed important differences in the planning methods between centers. CONCLUSION: These large differences could be explained by (1) a variable knowledge/interpretation of ICRU definitions, (2) variable interpretations of the potential microscopic extent, (3) difficulties in GTV identification, (4) differences in the concept, and (5) incoherence between theory (i.e., stated margins) and practice (i.e., drawn margins).

Plasmacytoid dendritic cells: one-trick ponies or workhorses of the immune system?

Plasmacytoid dendritic cells (pDCs) were first described as interferon-producing cells and, for many years, their overlapping characteristics with both lymphocytes and classical dendritic cells (cDCs) created confusion over their exact ontogeny. In this Viewpoint article, Nature Reviews Immunology asks five leaders in the field to discuss their thoughts on the development and functions of pDCs--do these cells serve mainly as a major source of type I interferons or do they also make other important contributions to immune responses?

Radiation therapy for the solitary plasmacytoma

Plasma-cell neoplasms are classically categorized into four groups as: multiple myeloma (MM), plasma-cell leukemias, solitary plasmacytomas (SP) of the bone (SPB), and extramedullary plasmacytomas (EMP). These tumors may be described as localized or diffuse in presentation. Localized plasma-cell neoplasms are rare, and include SP of the skeletal system, accounting for 2-5% of all plasma-cell neoplasms, and EMP of soft tissue, accounting for approximately 3% of all such neoplasms. SP is defined as a solitary mass of neoplastic plasma cells either in the bone marrow or in various soft tissue sites. There appears to be a continuum in which SP often progresses to MM. The main treatment modality for SP is radiation therapy (RT). However, there are no conclusive data in the literature on the optimal AT dose for SP. This review describes the interrelationship of plasma-cell neoplasms, and attempts to determine the minimal RT dose required to obtain local control.

Predictors of early hospital readmission after acute pulmonary embolism.

BACKGROUND: Risk factors for early mortality after pulmonary embolism (PE) are widely known. However, it is uncertain which factors are associated with early readmission after PE. We sought to identify predictors of readmission after an admission for PE. METHODS: We studied 14 426 patient discharges with a primary diagnosis of PE from 186 acute care hospitals in Pennsylvania from January 1, 2000, to November 30, 2002. The outcome was readmission within 30 days of presentation for PE. We used a discrete proportional odds model to study the association between time to readmission and patient factors (age, sex, race, insurance, discharge status, and severity of illness), thrombolysis, and hospital characteristics (region, teaching status, and number of beds). RESULTS: Overall, 2064 patient discharges (14.3%) resulted in a readmission within 30 days of presentation for PE. The most common reasons for readmission were venous thromboembolism (21.9%), cancer (10.8%), pneumonia (5.2%), and bleeding (5.0%). In multivariable analysis, African American race (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.02-1.38), Medicaid insurance (OR, 1.54; 95% CI, 1.31-1.81), discharge home with supplemental care (OR, 1.40; 95% CI, 1.27-1.54), leaving the hospital against medical advice (OR, 2.84; 95% CI, 1.80-4.48), and severity of illness were independently associated with readmission; readmission also varied by hospital region. CONCLUSIONS: Early readmission after PE is common. African American race, Medicaid insurance, severity of illness, discharge status, and hospital region are significantly associated with readmission. The high readmission rates for venous thromboembolism and bleeding suggest that readmission may be linked to suboptimal quality of care in the management of PE.

Targeting mTORC2 inhibits colon cancer cell proliferation in vitro and tumor formation in vivo.

The mammalian target of rapamycin (mTOR), which exists in two functionally distinct complexes, mTORC1 and mTORC2 plays an important role in tumor growth. Whereas the role of mTORC1 has been well characterized in this process, little is known about the functions of mTORC2 in cancer progression. In this study, we explored the specific role of mTORC2 in colon cancer using a short hairpin RNA expression system to silence the mTORC2-associated protein rictor. We found that downregulation of rictor in HT29 and LS174T colon cancer cells significantly reduced cell proliferation. Knockdown of rictor also resulted in a G1 arrest as observed by cell cycle analysis. We further observed that LS174T cells deficient for rictor failed to form tumors in a nude mice xenograft model. Taken together, these results show that the inhibition of mTORC2 reduces colon cancer cell proliferation in vitro and tumor xenograft formation in vivo. They also suggest that specifically targeting mTORC2 may provide a novel treatment strategy for colorectal cancer.

Expression of a functional single chain antibody on the surface of extracellular enveloped vaccinia virus as a step towards selective tumour cell targeting.

Recombinant vaccinia virus with tumour cell specificity may provide a versatile tool either for direct lysis of cancer cells or for the targeted transfer of genes encoding immunomodulatory molecules. We report the expression of a single chain antibody on the surface of extracellular enveloped vaccinia virus. The wild-type haemagglutinin, an envelope glycoprotein which is not required for viral infection and replication, was replaced by haemagglutinin fusion molecules carrying a single chain antibody directed against the tumour-associated antigen ErbB2. ErbB2 is an epidermal growth factor receptor-related tyrosine kinase overexpressed in a high percentage of human adenocarcinomas. Two fusion proteins carrying the single chain antibody at different NH2-terminal positions were expressed and exposed at the envelope of the corresponding recombinant viruses. The construct containing the antibody at the site of the immunoglobulin-like loop of the haemagglutinin was able to bind solubilized ErbB2. This is the first report of replacement of a vaccinia virus envelope protein by a specific recognition structure and represents a first step towards modifying the host cell tropism of the virus.