Appropriate end-points for right results in the age of antiangiogenic agents: Future options for phase II trials in patients with recurrent glioblastoma.

The progression-free survival rate at 6months (PFS-6) has long been considered the best end-point for assessing the efficacy of new agents in phase II trials in patients with recurrent glioblastoma. However, due to the introduction of antiangiogenic agents in this setting, and their intrinsic propensity to alter neuroradiological disease assessment by producing pseudoregression, any end-point based on neuroradiological modifications should be reconsidered. Further, statistically significant effects on progression-free survival (PFS) only should not automatically be considered reliable evidence of meaningful clinical benefit. In this context, because of its direct and unquestionable clinical relevance, overall survival (OS) represents the gold standard end-point for measuring clinical efficacy, despite the disadvantage that it is influenced by subsequent therapies and usually takes longer time to be evaluated. Therefore, while awaiting novel imaging criteria for response evaluation and/or new imaging tools to distinguish between 'true' and 'pseudo'-responses to antiangiogenic agents, the measurement of OS or OS rates should be considered primary end-points, also in phase II trials with these agents.

Lung infections: the radiologist's perspective.

Imaging plays a key role in lung infections. A CT scan must be carried out when there is a strong clinical suspicion of pneumonia that is accompanied by normal, ambiguous, or nonspecific radiography, a scenario that occurs most commonly in immunocompromised patients. CT allows clinicians to detect associated abnormalities or an underlying condition and it can guide bronchoalveolar lavage or a percutaneous or transbronchial lung biopsy. An organism can vary in how it is expressed depending on the extent to which the patient is immunocompromised. This is seen in tuberculosis in patients with AIDS. The infective agents vary with the type of immune deficiency and some infections can quickly become life-threatening. Clinicians should be aware of the complex radiological spectrum of pulmonary aspergillosis, given that this diagnosis must be considered in specific settings.

Chlamydia: signes d'appel, diagnostic et traitement [Chlamydia: diagnostic and treatment].

Chlamydia are obligate intracellular bacteria. Three species are considered human pathogens. Chlamydophila pneumoniae is one of the most common agents of atypical community-acquired pneumonia. Chlamydophila psittaci causes psittacosis, a severe zoonotic pneumonia transmitted by birds. Finally, Chlamydia trachomatis is the etiologic agent of trachoma and urogenital infections. The latter are commonly asymptomatic or paucisymptomatic. Thus, they may remain undiagnosed for years, leading to serious late complications such as salpingitis, ectopic pregnancy and infertility. Currently, the diagnosis of chlamydial infections is essentially based on molecular methods. Treatment should use an antibiotic with good intracellular bioavailability such as tetracycline, macrolides and new generation fluoroquinolones.

Comparison of three commercially available radio frequency coils for human brain imaging at 3 Tesla.

OBJECTIVE: To evaluate a transverse electromagnetic (TEM), a circularly polarized (CP) (birdcage), and a 12-channel phased array head coil at the clinical field strength of B0 = 3T in terms of signal-to-noise ratio (SNR), signal homogeneity, and maps of the effective flip angle alpha. MATERIALS AND METHODS: SNR measurements were performed on low flip angle gradient echo images. In addition, flip angle maps were generated for alpha(nominal) = 30 degrees using the double angle method. These evaluation steps were performed on phantom and human brain data acquired with each coil. Moreover, the signal intensity variation was computed for phantom data using five different regions of interest. RESULTS: In terms of SNR, the TEM coil performs slightly better than the CP coil, but is second to the smaller 12-channel coil for human data. As expected, both the TEM and the CP coils show superior image intensity homogeneity than the 12-channel coil, and achieve larger mean effective flip angles than the combination of body and 12-channel coil with reduced radio frequency power deposition. CONCLUSION: At 3T the benefits of TEM coil design over conventional lumped element(s) coil design start to emerge, though the phased array coil retains an advantage with respect to SNR performance.

Nevirapine vs efavirenz in virologically supressed patients: Differences in lipoprotein subclasses and inflammatory biomarkers.

Background: The interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation. Methods: 122 clinically stable HIV-infected patients with HIV-1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co-morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL-6, IL-8, t-PA, MCP-1, p-selectin and VCAM-1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy. Results: 82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs 62.3 [52.2] months, p=0.01) and were older (47.7 vs 40.7 years, p=0.001) than those on EFV. NVP-treated patients presented increased HDL-c (55.8 [16] vs 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV-treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found. Conclusions: Patients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTItreated patients are complex and do not show a linear relationship in this study.

Prevalence of and risk factors for biliary carriage of bacteria showing worrisome and unexpected resistance traits.

Data on biliary carriage of bacteria and, specifically, of bacteria with worrisome and unexpected resistance traits (URB) are lacking. A prospective study (April 2010 to December 2011) was performed that included all patients admitted for <48 h for elective laparoscopic cholecystectomy in a Spanish hospital. Bile samples were cultured and epidemiological/clinical data recorded. Logistic regression models (stepwise) were performed using bactobilia or bactobilia by URB as dependent variables. Models (P < 0.001) showing the highest R(2) values were considered. A total of 198 patients (40.4% males; age, 55.3 ± 17.3 years) were included. Bactobilia was found in 44 of them (22.2%). The presence of bactobilia was associated (R(2) Cox, 0.30) with previous biliary endoscopic retrograde cholangiopancreatography (ERCP) (odds ratio [OR], 8.95; 95% confidence interval [CI], 2.96 to 27.06; P < 0.001), previous admission (OR, 2.82; 95% CI, 1.10 to 7.24; P = 0.031), and age (OR, 1.09 per year; 95% CI, 1.05 to 1.12; P < 0.001). Ten out of the 44 (22.7%) patients with bactobilia carried URB: 1 Escherichia coli isolate (CTX-M), 1 Klebsiella pneumoniae isolate (OXA-48), 3 high-level gentamicin-resistant enterococci, 1 vancomycin-resistant Enterococcus isolate, 3 Enterobacter cloacae strains, and 1 imipenem-resistant Pseudomonas aeruginosa strain. Bactobilia by URB (versus those by non-URB) was only associated (R(2) Cox, 0.19) with previous ERCP (OR, 11.11; 95% CI, 1.98 to 62.47; P = 0.006). For analyses of patients with bactobilia by URB versus the remaining patients, previous ERCP (OR, 35.284; 95% CI, 5.320 to 234.016; P < 0.001), previous intake of antibiotics (OR, 7.200; 95% CI, 0.962 to 53.906; P = 0.050), and age (OR, 1.113 per year of age; 95% CI, 1.028 to 1.206; P = 0.009) were associated with bactobilia by URB (R(2) Cox, 0.19; P < 0.001). Previous antibiotic exposure (in addition to age and previous ERCP) was a risk driver for bactobilia by URB. This may have implications in prophylactic/therapeutic measures.

Drug-induced autoimmune liver disease: A diagnostic dilemma of an increasingly reported disease.

The aetiology of autoimmune hepatitis (AIH) is uncertain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs. AIH usually develops in individuals with a genetic background mainly consisting of some risk alleles of the major histocompatibility complex (HLA). Many drugs have been linked to AIH phenotypes, which sometimes persist after drug discontinuation, suggesting that they awaken latent autoimmunity. At least three clinical scenarios have been proposed that refers to drug- induced autoimmune liver disease (DIAILD): AIH with drug-induced liver injury (DILI); drug induced-AIH (DI-AIH); and immune mediated DILI (IM-DILI). In addition, there are instances showing mixed features of DI-AIH and IM-DILI, as well as DILI cases with positive autoantibodies. Histologically distinguishing DILI from AIH remains a challenge. Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however, a detailed standardised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diagnosis between both entities. Growing information on the relationship of drugs and AIH is being available, being drugs like statins and biologic agents more frequently involved in cases of DIAILD. In addition, there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepatotoxicity. Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of disease.

Imaging of human leukemic T-cell xenografts in nude mice by radiolabeled monoclonal antibodies and F(ab')2 fragments.

Monoclonal antibodies (MoAb) that react with the T-lymphocyte markers called cluster of differentiation CD5 and CD2 were labeled with iodine 131 (131I) and were injected intravenously in nude mice bearing solid subcutaneous xenografts derived from the human T-cell leukemia line Ichikawa. Both MoAb anti-CD5 and anti-CD2 yielded favorable mean tumor to whole-body ratios of 3.8 and 5.1, respectively. These ratios were further increased up to 10.0 for MoAb anti-CD5 and 15.5 for MoAb anti-CD2 by using their F(ab')2 fragments. The tumors could be imaged clearly by external scanning after injection of F(ab')2 fragments from both MoAb. F(ab')2 fragments from MoAb anti-CD2 and of a third MoAb recognizing the clonotypic determinant (Ti) of the antigen receptor expressed by the human T-cell line Jurkat were injected in mice bearing intrasplenic Jurkat xenografts. A selective localization of both fragments in tumor tissue was demonstrated with mean tumor to whole-body ratios of 7.5 and 4.1 for MoAb anti-CD2 and anti-Ti, respectively. These in vivo experimental results may provide useful information for the potential use of radiolabeled MoAb and fragments in the diagnosis and treatment of patients with T-cell lymphoma and different other forms of T-cell malignancies.

Scimitar Syndrome in an Asymptomatic Adult: Fortuitous Diagnosis by Imaging Technique

Congenital cardiopathies in adults are a rare clinical entity in the cardiology consultations. Advances in imaging techniques allow the fortuitous diagnosis of mild forms of these congenital abnormalities. We describe a case of an asymptomatic 41-year-old man, with a medical history of recurrent pneumonia during childhood and an established diagnosis of scimitar syndrome by computed tomography.

Temsirolimus in overtreated metastatic renal cancer with subsequent use of sunitinib: A case report.

During the last decade, we have been developing new therapeutic strategies for the treatment of renal cancer, based on knowledge derived from molecular biology. We report a case of long-term renal metastatic cancer progression despite therapy with sunitinib and interleukin, which are the most active drugs in renal cancer. Disease stabilization for 58 weeks was achieved upon sequential use of temsirolimus, following the occurrence of disease progression during angiogenic therapy. The patient demonstrated excellent tolerance without marked symptoms for 10 months. Hypothyroidism and mumps-related adverse events were present. The survival time from diagnosis to lung metastasis was 8 years. Thus, this case demonstrates promising therapeutic effects of the sequential use of tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors during different stages of the disease.

Edge vascular response after polymer-free vs. polymer-based paclitaxel-eluting stent implantation.

BACKGROUND It is unknown if lack of polymer can provoke a different edge response in drug-eluting stents. The aim of this study was to compare edge vascular response between polymer-free paclitaxel-eluting stent (PF-PES) and polymer-based paclitaxel-eluting stents (PB-PES). METHODS AND RESULTS: A total of 165 eligible patients undergoing percutaneous coronary intervention were prospectively randomized 1:1 to receive either PF-PES or PB-PES. Those patients with paired intravascular ultrasound (IVUS) after procedure and at 9-month follow-up were included in this analysis.Seventy-six patients with 84 lesions, divided into PB-PES (38 patients, 41 lesions) and PF-PES groups (38 patients, 43 lesions) had paired post-procedure and 9-month follow-up IVUS and were therefore included in this substudy. There was a significant lumen decrease at the proximal edge of PF-PES (from 9.02±3.06 mm(2)to 8.47±3.05 mm(2); P=0.040), and a significant plaque increase at the distal edges of PF-PES (from 4.39±2.73 mm(2)to 4.78±2.63 mm(2); P=0.004). At the distal edge there was a significant plaque increase in the PF-PES compared to PB-PES (+8.0% vs. -0.6%, respectively; P=0.015) with subsequent lumen reduction (-5.2% vs. +6.0%, respectively; P=0.024). CONCLUSIONS PF-PES had significant plaque increase and lumen reduction at the distal edge as compared to PB-PES, probably due to difference in polymer-based drug-release kinetics between the 2 platforms.

Results of a combination of bleomycin and triamcinolone acetonide in the treatment of keloids and hypertrophic scars.

While treatment of keloids and hypertrophic scars normally shows modest results, we found that treatment with bleomycin was more promising. The present study was divided into two parts. In the first part the aim was to show the results using a combination of bleomycin and triamcinolone acetonide per cm2 (BTA). In the second part the objective was to determine the response to both drugs in large keloids that were divided into 1 cm2 squares, treating each square with the dose previously used. In the first part of the study, the clinical response of 37 keloids ranging from 0.3 to 1.8 cm2 treated with BTA were followed up over a period of 1- 2 years. 0.375 IU bleomycin and 4 mg triamcinolone acetonide were injected every 3 months. In the second part of the study we reviewed the clinical response in six patients with large keloids. The monthly dose administered never exceeded 3 IU of bleomycin. The first study showed 36 keloids (97.29%) softening after the first dose. In the second study, 5 showed different responses (the response was complete in the four smaller keloids). The largest keloid needed 9 doses to achieve an improvement of 70%. In conclusion, combined treatment with 0.375 IU of bleomycin and 4mg of triamcinolone acetonide to 1 cm2 was considered to be an acceptable procedure for the treatment of keloids. The best results were obtained in keloids over 1 cm2 or when divided into 1 cm2 square areas. Larger series need to be performed in order to confirm these results..

An in vitro iron superoxide dismutase inhibitor decreases the parasitemia levels of Trypanosoma cruzi in BALB/c mouse model during acute phase.

In order to identify new compounds to treat Chagas disease during the acute phase with higher activity and lower toxicity than the reference drug benznidazole (Bz), two hydroxyphthalazine derivative compounds were prepared and their trypanocidal effects against Trypanosoma cruzi were evaluated by light microscopy through the determination of IC50 values. Cytotoxicity was determined by flow cytometry assays against Vero cells. In vivo assays were performed in BALB/c mice, in which the parasitemia levels were quantified by fresh blood examination; the assignment of a cure was determined by reactivation of blood parasitemia levels after immunosuppression. The mechanism of action was elucidated at metabolic and ultra-structural levels, by (1)H NMR and TEM studies. Finally, as these compounds are potentially capable of causing oxidative damage in the parasites, the study was completed, by assessing their activity as potential iron superoxide dismutase (Fe-SOD) inhibitors. High-selectivity indices observed in vitro were the basis of promoting one of the tested compounds to in vivo assays. The tests on the murine model for the acute phase of Chagas disease showed better parasitemia inhibition values than those found for Bz. Compound 2 induced a remarkable decrease in the reactivation of parasitemia after immunosuppression. Compound 2 turned out to be a great inhibitor of Fe-SOD. The high antiparasitic activity and low toxicity together with the modest costs for the starting materials render this compound an appropriate molecule for the development of an affordable anti-Chagas agent.