Rybergodgaard1157

Monoclonal antibody (mAb) products are presently the dominant class of therapeutic proteins. When stressed, they are known to be prone to molecular instabilities like aggregation, fragmentation, oxidation and reduction, of which aggregation is typically the most significant concern. These stresses may be experienced during manufacturing, storage, filling, formulation development and shipping. This paper investigates how mAb aggregates generated by a variety of mechanical, thermal and chemical stresses impact the biological activity of a biotherapeutic. Increased aggregation resulted in a decrease in biological activity, as confirmed by cell based assays such as antibody dependent cell mediated cytotoxicity (ADCC) and complement dependent cytotoxicity (CDC) and ligand binding assays such as surface plasmon resonance (SPR). It was observed that aggregates formed due to extreme pH (pH 3.5 and pH 11.0), stirring (1 d stir and 3 d stir), thermal stress, and oxidation via CuSO4 have the most impact on potency of the therapeutic. In contrast, aggregates formed due to stresses from pipetting, milder pH (4.3 and 8.5), oxidation via H2O2, freeze-thaw (Ft-slow and Ft-fast) have relatively less impact on the potency of the mAb biotherapeutic. The results affirm that understanding of the mechanism of aggregation is critical for achieving consistent product quality and the resulting efficacy.Purpose Vestibular schwannomas (VSs) are benign, thus understanding long-term tumor control and late adverse radiation effects of stereotactic radiosurgery (SRS) through current radiosurgical techniques is important to inform treatment decisions. Our aim was to clarify long-term tumor control rates and incidence of late adverse radiation effects in VS patients followed for 5 years or longer after SRS. Methods and materials Altogether, 615 VS patients (excluding neurofibromatosis type 2 and partially treated tumors) followed for 5 years or longer after SRS using recent radiosurgical techniques were evaluated. All patients were treated at a margin dose of less than 14 Gy. All tumors were classified into 4 categories; type A [intracanalicular tumor, 87 patients (14%)], type B [cerebellopontine angle (CPA) tumor, 325 patients (53%)], type C [CPA tumor compressing the brainstem, 138 patients (22%)], and type D [CPA tumor compressing the brainstem with a deviation of the fourth ventricle, 65 patients (11%)]. Median tumor volume was 2.0 cm3 and median marginal dose was 12 Gy. Results Median follow-up period was 158 months. Actuarial 5-, 10-, and 15-year or longer local control (LC) were 93%, 91%, and 89%, respectively. Tumor type (p less then 0.001, hazard ratio 2.389) and number of prior surgeries (p=0.007, hazard ratio 1.698) were significant for LC. Depending on the tumor type, the actuarial 10-year LC rates were 100%, 93%, 88%, and 70% in type A, B, C, and D tumors, respectively. No patient developed persistent facial palsy. Twenty patients (3.3%) developed delayed cysts. One patient developed malignant transformation (0.2%). Conclusions SRS is a safe and effective treatment for VSs in the long term, excluding VSs compressing the brainstem with a deviation of the fourth ventricle. Delayed cysts such as cyst formation, enlarged preexisting cyst or extratumoral cyst, and malignant transformation should be considered possible causes of long-term treatment failures.Breast cancer is the most common nonskin cancer in women and the second leading cause of cancer death for women in the United States. Mammography screening is proven to significantly decrease breast cancer mortality, with a 40% or more reduction expected with annual use starting at age 40 for women of average risk. However, less than half of all eligible women have a mammogram annually. The elimination of cost sharing for screening made possible by the Affordable Care Act (2010) encouraged screening but mainly for those already insured. The United States Preventive Services Task Force 2009 guidelines recommended against screening those 40 to 49 years old and have left women over 74 years of age vulnerable to coverage loss. Other populations for whom significant gaps in risk information or screening use exist, including women of lower socioeconomic status, black women, men at higher than average risk of breast cancer, and sexual and gender minorities. Further work is needed to achieve higher rates of screening acceptance for all appropriate individuals so that the full mortality and treatment benefits of mammography screening can be realized.Background It remains to be clarified whether combined hepatectomy and microwave ablation for multifocal hepatocellular carcinoma (HCC) is feasible. This aim of this study was to examine the perioperative and oncological outcomes after combined hepatectomy and microwave ablation for multifocal HCC. Methods This retrospective study included 81 patients who underwent combined hepatectomy and microwave ablation for multifocal HCC in our institute between June 1998 and December 2017. We analyzed overall survival (OS) and recurrence-free survival (RFS), and evaluated factors related to prognosis. Results Median follow-up time was 45.6 months for the entire cohort. OS rates were 1-year 96%, 3-year 72%, and 5-year 54%; RFS rates were 1-year 77%, 3-year 37%, and 5-year 22%. The major complication rate (Clavien-Dindo classification IIIa or above) after surgery was 10%, with one patient of in-hospital mortality. Multivariate analysis revealed that des-γ-carboxy prothrombin level >200 mAU/mL and >5 tumors were independent risk factors for OS, and des-γ-carboxy prothrombin level >200 mAU/mL, > 5 tumors, and maximum tumor size >5 cm were independent risk factors for RFS. XMU-MP-1 Conclusions Our results indicate that combined hepatectomy and microwave ablation is safe and feasible for selected patients with multifocal HCC.Introduction Fibromyalgia is a chronic disease characterised by the presence of musculoskeletal pain, usually associated with other symptoms, including depression, fatigue, and sleep disorders. There is no objective information on the beliefs and perceptions of the diagnosis and treatment of fibromyalgia among rehabilitation and physical medicine specialists. The aim of this study was to describe these beliefs and perceptions among a group of physical medicine and rehabilitation specialists in Colombia. Methods We performed a cross-sectional study. A focus group was held with the participation of 2 rheumatologists, one physical medicine and rehabilitation specialist and an expert in qualitative research. The group designed a survey to assess the beliefs and perceptions of physical medicine and rehabilitation specialists of the diagnosis and treatment of fibromyalgia. The self-administered, anonymous questionnaire was completed during meetings of the Colombian Association of Physical Medicine and Rehabilitation.