Epidural bleeding after ACL reconstruction under regional anaesthesia: a case report

Introduction: Epidural bleeding as a complication of catheterization or epidural catheter removal is often associated with perioperative thromboprophylaxis especially in adult reconstructive surgery. Case presentation: We report on a case of a 19 years old male athlete that underwent anterior cruciate ligament reconstruction, receiving low molecular weight heparin for thromboprophylaxis and developed an epidural hematoma and subsequent cauda equina syndrome two days after removal of the epidural catheter. An urgent magnetic resonance imaging scan revealed an epidural hematoma from the level of L3 to L4. Emergent decompression and hematoma evacuation resulted in patient's significant neurological improvement immediately postoperatively. Conclusion: A high index of clinical suspicion and surgical intervention are necessary to prevent such potentially disabling complications especially after procedures on a day-case basis and early patient's discharge. © 2009 Roidis et al; licensee Cases Network Ltd

Anti-CTLA4 monoclonal antibodies: the past and the future in clinical application

Recently, two studies using ipilimumab, an anti-CTLA-4 monoclonal antibody (mab) demonstrated improvements in overall survival in the treatment of advanced melanoma. These studies utilized two different schedules of treatment in different patient categories (first and second line of treatment). However, the results were quite similar despite of different dosage used and the combination with dacarbazine in the first line treatment. We reviewed the result of randomized phase II-III clinical studies testing anti-CTLA-4 antibodies (ipilimumab and tremelimumab) for the treatment of melanoma to focus on practical or scientific questions related to the broad utilization of these products in the clinics. These analyses raised some considerations about the future of these compounds, their potential application, dosage, the importance of the schedule (induction/manteinance compared to induction alone) and their role as adjuvants. Anti-CTLA-4 antibody therapy represents the start of a new era in the treatment of advanced melanoma but we are on the steep slope of the learning curve toward the optimization of their utilization either a single agents or in combination

ICOS regulates the generation and function of human CD4+ Treg in a CTLA-4 dependent manner

Inducible co-stimulator (ICOS) is a member of CD28/Cytotoxic T-lymphocyte Antigen-4 (CTLA-4) family and broadly expressed in activated CD4+ T cells and induced regulatory CD4+ T cells (CD4+ iTreg). ICOS-related signal pathway could be activated by the interaction between ICOS and its ligand (ICOSL). In our previous work, we established a cost-effective system to generate a novel human allo-antigen specific CD4hi Treg by co-culturing their naïve precursors with allogeneic CD40-activated B cells in vitro. Here we investigate the role of ICOS in the generation and function of CD4hi Treg by interrupting ICOS-ICOSL interaction with ICOS-Ig. It is found that blockade of ICOS-ICOSL interaction impairs the induction and expansion of CD4hi Treg induced by allogeneic CD40-activated B cells. More importantly, CD4hi Treg induced with the addition of ICOS-Ig exhibits decreased suppressive capacity on alloantigen-specific responses. Dysfunction of CD4hi Treg induced with ICOS-Ig is accompanied with its decreased exocytosis and surface CTLA-4 expression. Through inhibiting endocytosis with E64 and pepstatin A, surface CTLA-4 expression and suppressive functions of induced CD4hi Treg could be partly reversed. Conclusively, our results demonstrate the beneficial role of ICOS-ICOSL signal pathway in the generation and function of CD4hi Treg and uncover a novel relationship between ICOS and CTLA-4. © 2013 zheng et al.published_or_final_versio

Defining the critical hurdles in cancer immunotherapy

Scientific discoveries that provide strong evidence of antitumor effects in preclinical models often encounter significant delays before being tested in patients with cancer. While some of these delays have a scientific basis, others do not. We need to do better. Innovative strategies need to move into early stage clinical trials as quickly as it is safe, and if successful, these therapies should efficiently obtain regulatory approval and widespread clinical application. In late 2009 and 2010 the Society for Immunotherapy of Cancer (SITC), convened an "Immunotherapy Summit" with representatives from immunotherapy organizations representing Europe, Japan, China and North America to discuss collaborations to improve development and delivery of cancer immunotherapy. One of the concepts raised by SITC and defined as critical by all parties was the need to identify hurdles that impede effective translation of cancer immunotherapy. With consensus on these hurdles, international working groups could be developed to make recommendations vetted by the participating organizations. These recommendations could then be considered by regulatory bodies, governmental and private funding agencies, pharmaceutical companies and academic institutions to facilitate changes necessary to accelerate clinical translation of novel immune-based cancer therapies. The critical hurdles identified by representatives of the collaborating organizations, now organized as the World Immunotherapy Council, are presented and discussed in this report. Some of the identified hurdles impede all investigators; others hinder investigators only in certain regions or institutions or are more relevant to specific types of immunotherapy or first-in-humans studies. Each of these hurdles can significantly delay clinical translation of promising advances in immunotherapy yet if overcome, have the potential to improve outcomes of patients with cancer

Investigation of attenuation correction in SPECT using textural features, Monte Carlo simulations, and computational anthropomorphic models

PurposeTo present and evaluate a new methodology to investigate the effect of attenuation correction (AC) in single-photon emission computed tomography (SPECT) using textural features analysis, Monte Carlo techniques, and a computational anthropomorphic model.Materials and methodsThe GATE Monte Carlo toolkit was used to simulate SPECT experiments using the XCAT computational anthropomorphic model, filled with a realistic biodistribution of Tc-99m-N-DBODC. The simulated gamma camera was the Siemens ECAM Dual-Head, equipped with a parallel hole lead collimator, with an image resolution of 3.54x3.54mm(2). Thirty-six equispaced camera positions, spanning a full 360 degrees arc, were simulated. Projections were calculated after applying a 20% energy window or after eliminating all scattered photons. The activity of the radioisotope was reconstructed using the MLEM algorithm. Photon attenuation was accounted for by calculating the radiological pathlength in a perpendicular line from the center of each voxel to the gamma camera. Twenty-two textural features were calculated on each slice, with and without AC, using 16 and 64 gray levels. A mask was used to identify only those pixels that belonged to each organ.ResultsTwelve of the 22 features showed almost no dependence on AC, irrespective of the organ involved. In both the heart and the liver, the mean and SD were the features most affected by AC. In the liver, six features were affected by AC only on some slices. Depending on the slice, skewness decreased by 22-34% with AC, kurtosis by 35-50%, long-run emphasis mean by 71-91%, and long-run emphasis range by 62-95%. In contrast, gray-level non-uniformity mean increased by 78-218% compared with the value without AC and run percentage mean by 51-159%. These results were not affected by the number of gray levels (16 vs. 64) or the data used for reconstruction: with the energy window or without scattered photons.ConclusionThe mean and SD were the main features affected by AC. In the heart, no other feature was affected. In the liver, other features were affected, but the effect was slice dependent. The number of gray levels did not affect the results. Copyright (C) 2015 Wolters Kluwer Health, Inc. All rights reserved

A "biologic technique" for the treatment of a disruption of the extensor mechanism after revision total knee arthroplasty: a case report

A modified technique for the reconstruction of the extensor mechanism after revision total knee arthroplasty, is described. A medial gastrocnemius flap, in combination with in situ use of semitendinosus tendon autograft through intraosseous patellar tunnel, was used. The patient was followed for 2 years after the final reconstruction. After the procedure, the patient who previously had been dependent on a walker was able to walk without a cane. The above mentioned technique provided good functional outcome in our case

Novel technology of multimodal ultrasound tomography detects breast lesions

Objectives: To introduce a new three-dimensional (3D) diagnostic imaging technology, termed "multimodal ultrasonic tomography" (MUT), for the detection of breast cancer without ionising radiation or compression. Methods: MUT performs 3D tomography of the pendulant breast in a water-bath using transmission ultrasound in a fixed-coordinate system. Specialised electronic hardware and signal processing algorithms are used to construct multimodal images for each coronal slice, corresponding to measurements of refractivity and frequency-dependent attenuation and dispersion. In-plane pixel size is 0.25 mm × 0.25 mm and the inter-slice interval can vary from 1 to 4 mm, depending on clinical requirements. MUT imaging was performed on 25 patients ("off-label" use for research purposes only), presenting lesions with sizes >10 mm. Histopathology of biopsy samples, obtained from all patients, were used to evaluate the MUT outcomes. Results: All lesions (21 malignant and four benign) were clearly identified on the MUT images and correctly classified into benign and malignant based on their respective multimodal information. Malignant lesions generally exhibited higher values of refractivity and frequency-dependent attenuation and dispersion. Conclusion: Initial clinical results confirmed the ability of MUT to detect and differentiate all suspicious lesions with sizes >10 mm discernible in mammograms of 25 female patients. Key Points: • Technical advances in ultrasound offer new diagnostic opportunities in breast imaging • 3D ultrasound can detect breast cancer without ionising radiation or compression • Multimodal 3D ultrasound assesses acoustic refractivity, frequency-dependent attenuation and dispersion • MUT can differentiate between benign and malignant breast lesions © 2012 European Society of Radiology