Human(ized) monoclonal antibodies in atopic patients - state of the art.

Asthma is an important chronic disease affecting a lot of people worldwide. Treatment options for asthma like biological agents are being developed more frequently nowadays. Despite a lot of treatment options, some patients still remain symptomatic. As more and more practitioners choose treatment with biologic agents as a convenient way of therapy, biologic agents and other valuable methods must be discovered in order to cope with a growing number of treatment agents. This manuscript emphasizes on new generation monoclonal human(ized) antibodies in asthmatics and off-label use . The first developed biologic agent is the anti-immunoglobulin E monoclonal antibody called omalizumab. Currently it is an approved treatment option for asthma.

Confocal microscopy as an early relapse marker for acanthamoeba keratitis.

Acanthameoba keratitis is a serious ophthalmological condition with a potentially vision-threatening prognosis. Early diagnosis and recognition of relapse, and the detection of persistent Acanthamoeba cysts, are essential for informing the prognosis and managing the condition. We suggest the use of in vivo confocal microscopy not only to identify the early signs of relapse after keratoplasty in patients with Acanthamoeba keratitis, but also as an additional follow-up tool after antimicrobial crosslinking. This study shows that in vivo confocal microscopy is, in experienced hands, a quick and reliable diagnostic tool. Clin. Anat. 31:60-63, 2018. © 2017 Wiley Periodicals, Inc.

Effectivity of a T-cell-adapted induction therapy with anti-thymocyte globulin (Sangstat).

BACKGROUND: Cytolytic induction therapy with anti-thymocyte globulin (ATG) should induce effective immunosuppression, with a low rate of rejection in the initial phase after heart transplantation. Induction therapy with ATG allows post-operative renal recovery without the negative effects of highly nephrotoxic cyclosporine levels. An increased rate of infection is a common problem, however, and has been associated with "over-immunosuppression" early after transplantation. Therefore, we investigated whether reduced T-cell-adapted ATG induction therapy could be performed without increasing the risk of graft loss by rejection and whether reductions in infection rates and costs are possible. METHODS: Between March 1999 and December 2002, T-cell-adapted ATG induction therapy with ATG (Sangstat) (1.5 mg/kg) was given to 62 heart transplant recipients (study group) starting on post-operative Days 1 to 6. T-lymphocyte sub-populations were screened daily using flow cytometry. If total lymphocytes were <100/microl (reference 1,300 to 2,300/microl), T-helper lymphocytes (CD4+) <50/microl (reference >500/microl) and T-suppressor cells (CD8+) <50/microl (reference >300/microl), then no ATG was given. Further immunosuppression was continued with triple therapy consisting of methylprednisolone, azathioprine and cyclosporine. An historic group of heart transplant recipients given a full-dose ATG regimen for 8 days served as controls. These recipients were treated with ATG (Merieux 1.5 mg/kg) until reaching monoclonal cyclosporine levels of >300 mg/dl. Additional immunosuppressive treatment did not differ. Patients in both groups received systemic antibiotics (Imipenem) peri-operatively. Results of routine endomyocardial biopsies and rates of infections were examined. RESULTS: Study group patients were older (52 +/- 10 vs 49 +/- 14 years). In the study group, mean cumulative ATG dose was reduced significantly to 596 +/- 220 mg (p < 0.05) for 3.9 +/- 1.6 days compared with 1,159 +/- 376 mg for 6.9 +/- 1.1 days in the control group. The rate of cytomegalovirus (CMV) seroconversion was 23% in the study group compared with 13% in the control group. Rate of deep sternal infections was lower in the study group (1.6% vs 3.2%). The mean rejection rate in the first 3 months was 0.4 +/- 0.7 for the study patients (185 biopsies) vs 1.1 +/- 1.7 for controls (237 biopsies). All biopsies with ISHLT Grade >2 were treated successfully with 1,000 mg of methylprednisolone intravenously for 3 days. Both groups showed a similar 1-year survival rate (study 88%, control 89%). CONCLUSIONS: T-cell-adapted ATG induction therapy can be a helpful tool for individualized immunosuppression. It is not associated with an increased rate of rejection. Lower doses of immunosuppression help to minimize the rates of infection. In addition, cytolytic induction therapy combined with reduced ATG results in significant cost reduction.

Primary intrathoracic malignant mesenchymal tumours: computed tomography features of a rare group of chest neoplasms.

OBJECTIVES: To describe the computed tomography (CT) features in a case series of primary intrathoracic extracardiac malignant mesenchymal tumours (sarcomas). METHODS: A 5-year retrospective research was conducted, and 18 patients were selected. CT exams were reviewed by two chest radiologists, blinded to tumour pathological type, origin and grade. Lesions were described in relation to location, size, shape, margins, enhancement, presence of cavitation, calcifications, ground glass component, intratumoural enhanced vessels, pleural effusion, pleural tags, lymphangitis, chest wall/rib involvement and pathological lymph nodes. RESULTS: The readers described five pulmonary, six mediastinal and seven pleural/wall based lesions. Mean largest diameter was 103 mm. The most frequent shape was irregular (n = 12), most predominant margin was smooth (n = 12) and enhancement was mostly heterogeneous (n = 8). Intratumoural vessels and pleural effusion were seen in 11 patients. Pathological lymph nodes were present in four cases and calcifications in two cases. CONCLUSIONS: Some frequent radiological features were described independently of tumour location and subtype. A sarcoma should be included as a major differential diagnosis when the radiologist faces an intrathoracic mass of large size (>70 mm) but with well defined smooth or lobulated margins, especially if presenting intratumoural vessels, associated pleural effusion but no significant lymphadenopathy. MAIN MESSAGES: • Malignant mesenchymal tumours (sarcomas) are rare and can arise from any structure in the chest. • Intrathoracic sarcomas show some frequent radiological features, independent of location and type. • Some CT features may help the radiologist suspect for a sarcoma instead of other more common tumours.

Morphological computed tomography features of surgically resectable pulmonary squamous cell carcinomas: impact on prognosis and comparison with adenocarcinomas.

OBJECTIVE: To characterize the morphological computed tomography (CT) features of pulmonary squamous cell carcinomas (SQCC) submitted to therapeutic resection; to correlate these features with patients' outcomes; and to compare with pulmonary adenocarcinomas (ADC). MATERIALS AND METHODS: Two chest radiologists retrospectively evaluated CT exams of 123 patients with SQCC resected between 2002 and 2008. Tumors' size, location (central vs. peripheral), shape, margins, attenuation, enhancement, presence of calcification, cavitation, internal air bronchograms and pleural tags were assigned by consensus. Prevalence of features was compared with patients' survival data and a previously studied population of ADC surgically resected at the same time period. RESULTS: Cavitation correlated negatively with overall (hazard ratio=3.04), disease-specific (HR=3.67) and disease-free survival (HR=2.69), independent from age, gender, tumor pathological stage, size, and location. In relation to ADC, SQCC presented different shape, margins, attenuation, enhancement, with more cavitation, rare internal air bronchograms, and less pleural tags. Differences were also significant when comparing only the peripheral type of tumors. CONCLUSIONS: Cavitation at CT was an independent and negative predictive factor for SQCC. Different CT morphological features were described for SQCC and ADC. Image evaluation of lung lesions should go beyond measuring and addressing adjacent structures invasion. Adequate imaging characterization not only helps to differentiate benign versus malignant disease and to determine malignancy staging, it may also imply the histologic subtype and improve the prognostic assessment of lung cancer patients.

Expression and mutation analysis of EGFR, c-KIT, and ß-catenin in pulmonary blastoma.

INTRODUCTION: Pulmonary blastoma (PB) is a rare malignant lung tumour with an immature mesenchymal and epithelial component resembling fetal lung. In order to define potential therapeutic targets in PB, the authors analysed the status and possible role of EGFR, HER2 and c-KIT in the pathogenesis of this tumour type, and the diagnostic value of ß-catenin mutation analysis in PB. METHODS: 5 PBs were analysed for EGFR, HER2, c-KIT, and ß-catenin expression, as well as for mutations in EGFR, c-KIT, k-ras and the ß-catenin gene (CTNNB1). RESULTS: EGFR expression was observed in all PBs. An EGFR mutation was found in one of the tumours. No overexpression of c-KIT or HER2 was seen. No mutations were found in k-ras or c-KIT. 3 of 5 PBs displayed CTNNB1 mutations. Nuclear translocation of ß-catenin was seen in 2 of these tumours. CONCLUSIONS: Detection of EGFR expression and mutation in PB suggest EGFR inhibition as a potential therapeutic option in the treatment of advanced PB. Moreover, the data confirm a crucial role of CTNNB1 mutations in the pathogenesis of PB, and indicate that CTNNB1 gene sequencing may be a useful in distinguishing PB from other types of lung cancer.

Coordinated expression of stathmin family members by far upstream sequence element-binding protein-1 increases motility in non-small cell lung cancer.

Dynamic instability of the microtubule network modulates processes such as cell division and motility, as well as cellular morphology. Overexpression of the microtubule-destabilizing phosphoprotein stathmin is frequent in human malignancies and represents a promising therapeutic target. Although stathmin inhibition gives rise to antineoplastic effects, additional and functionally redundant microtubule-interacting proteins may attenuate the efficiency of this therapeutic approach. We have systematically analyzed the expression and potential protumorigenic effects of stathmin family members in human non-small cell lung cancer (NSCLC). Both stathmin and stathmin-like 3 (SCLIP) were overexpressed in adenocarcinoma as well as squamous cell carcinoma (SCC) tissues and induced tumor cell proliferation, migration, and matrix invasion in respective cell lines. Accordingly, reduced stathmin and SCLIP levels affected cell morphology and were associated with a less malignant phenotype. Combined inhibition of both factors caused additive effects on tumor cell motility, indicating partial functional redundancy. Because stathmin and SCLIP expression significantly correlated in NSCLC tissues, we searched for common upstream regulators and identified the far upstream sequence element-binding protein-1 (FBP-1) as a pivotal inducer of several stathmin family members. Our results indicate that the coordinated overexpression of microtubule-destabilizing factors by FBP-1 is a critical step to facilitate microtubule dynamics and subsequently increases proliferation and motility of tumor cells.

Pulmonary epithelioid hemangioendothelioma: report of three cases.

Pulmonary epithelioid hemangioendothelioma (PEH) is a rare vascular tumor of low-grade malignancy, the prognosis of which remains unpredictable. Surgical and/or chemotherapeutic options have to be evaluated depending on intrathoracic tumor spread and systemic metastases. Three cases of PEH with both clinical and pathological findings are herein summarized and the relevant current literature discussed.