Neutralizing antibodies are necessary and sufficient for protection against infection with vesicular stomatitis virus (VSV). The in vitro neutralization capacities and in vivo protective capacities of a panel of immunoglobulin G monoclonal antibodies to the glycoprotein of VSV were evaluated. In vitro, neutralizing activity correlated with avidity and with neutralization rate constant, a measure of on-rate. However, in vivo, protection was independent of immunoglobulin subclass, avidity, neutralization rate constant, and in vitro neutralizing activity; above a minimal avidity threshold, protection depended simply on a minimum serum concentration. These two biologically defined thresholds of antibody specificity offer hope for the development of adoptive therapy with neutralizing antibodies.
Heart-specific CD4+ T cells have been implicated in development and progression of myocarditis in mice and in humans. Here, using mouse models of experimental autoimmune myocarditis (EAM) we investigated the role of heart non-specific CD4+ T cells in the progression of the disease. Heart non-specific CD4+ T cells were obtained from DO11.10 mice expressing transgenic T cell receptor recognizing chicken ovalbumin. We found that heart infiltrating CD4+ T cells expressed exclusively effector (Teff) phenotype in the EAM model and in hearts of patients with lymphocytic myocarditis. Adoptive transfer experiments showed that while heart-specific Teff infiltrated the heart shortly after injection, heart non-specific Teff effectively accumulated during myocarditis and became the major heart-infiltrating CD4+ T cell subset at later stage. Restimulation of co-cultured heart-specific and heart non-specific CD4+ T cells with alpha-myosin heavy chain antigen showed mainly Th1/Th17 response for heart-specific Teff and up-regulation of a distinct set of extracellular signalling molecules in heart non-specific Teff. Adoptive transfer of heart non-specific Teff in mice with myocarditis did not affect inflammation severity at the peak of disease, but protected the heart from adverse post-inflammatory fibrotic remodelling and cardiac dysfunction at later stages of disease. Furthermore, mouse and human Teff stimulated in vitro with common gamma cytokines suppressed expression of profibrotic genes, reduced amount of α-smooth muscle actin filaments and decreased contraction of cardiac fibroblasts. In this study, we provided a proof-of-concept that heart non-specific Teff cells could effectively contribute to myocarditis and protect the heart from the dilated cardiomyopathy outcome.Electronic supplementary materialThe online version of this article (10.1007/s00395-019-0766-6) contains supplementary material, which is available to authorized users.
Background: Since diagnosis-related groups (SwissDRG) were established in Switzerland in 2012, small and medium-size hospitals have encountered increasing financial troubles. Even though hernia repair operations are frequent, most hospitals fail to cover their costs with these procedures. Previous studies have focused mainly on analyzing costs and the contributing factors but less on variables that can be positively influenced. Therefore, this study aims to identify the relevant and influenceable factors for revenue growth in hernia repair surgery. Methods: Data from all patients who underwent the SwissDRG G09 surgery for a hernia in 2019 were analyzed. The contribution margin (CM4), as well as any over- or under-coverage, was correlated to case-specific costs. Results: A total of 168 patients received hernia repair surgery with the SwissDRG code G09. The average revenue/loss generated by one procedure was CHF −623.84. Procedures covered by the General Health Insurance (OKP) generated a loss of CHF −830.70 on average, whereas procedures covered by private insurance companies (VVG) generated revenue of CHF +1100 on average. Significant factors impacting the profitability of hernia repair operations were teaching during surgery (p < 0.005), the surgical operating time (p < 0.001), the total anesthesia time (p < 0.001), the number of surgeons present (p = 0.022), the insurance state of patients (p < 0.001), and the type of surgery (p < 0.01 for Lichtenstein’s procedure). Conclusions: This study reveals that hernia repair surgery performed under cost coverage by OKP is generally unprofitable. Our results further imply that the most important and influenceable factors for revenue enhancement are the quality and process optimization of the surgical department. To compensate for this deficit, hospitals should aim to increase the percentage of patients with private health insurance coverage in their procedures. Since outpatient surgery does not provide a valid alternative due to the low reimbursement by insurance companies, the cost efficiency of inpatient hernia repair needs to be increased by process optimization of the surgical department; for instance, by providing specialized hernia teams performing with shorter operation times and high quality.
SARS-CoV-2 has hampered healthcare systems worldwide, but some countries have found new opportunities and methods to combat it. In this study, we focused on the rapid growth of telemedicine during the pandemic around the world. We conducted a systematic literature review of all the articles published up to the present year, 2021, by following the requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) framework. The data extracted comprised eHealth and telemedicine in surgery globally, and independently in Europe, the United States, and Switzerland. This review explicitly included fifty-nine studies. Out of all the articles included, none of them found that telemedicine causes poor outcomes in patients. Telemedicine has created a new path in the world of healthcare, revolutionizing how healthcare is delivered to patients and developing alternative methods for clinicians.
The intrinsic properties of antibodies has resulted in them becoming widely exploited as tools in both basic research and the treatment of human disease. This, especially the latter, has been made possible through our increased understanding of antibody structure. The sequences of thousands of antibodies has been determined , and as an early example of the use of bioinfor-matics, the mechanism by which antibodies are able to recognise antigens was proposed. Elucidation of the three-dimensional structure of antibodies including complexes of the antibody with its antigen, has enabled the structure / function relationship of antibodies to be determined. This presentation will introduce the domain organisation of antibodies and how the understanding of an-tibody architecture, has been exploited in the design of therapeutic antibodies. The use of naked antibodies and antibody drug conjugates will be discussed. Additionally the use, progress and limitations of antibody fragments in the clinic. Recent data on an alterative technology to the use of hy-bridoma technology for the selection and cloning of antibodies will also be discussed. [09.20-09.40] The n-CoDeR TM antibody libraries: Concept and applications Eskil Soderlind BioInvent Therapeutic AB SE-223 The n-CoDeR TM antibody libraries are built by letting diverse in vivo formed complementarity determining regions (CDR:s) recombine into one single master framework. These CDR:s are sampled from in vivo processed and proofread gene sequences, resulting in an optimal level of correctly folded and reac-tive molecules. Highly specific and functional human antibody fragments have been selected using the n-CoDeR TM libraries and selected specificities can be converted to IgG-molecules with high affinities and productivity levels. The latest results will be presented.
This study investigated whether or not the localization of persisting Ag influenced the localization of memory B and/or of Ab-forming cells (AFC). As a model Ag, we used vesicular stomatitis virus, which does not measurably replicate extraneuronally in adult mice after peripheral infection. Our results show that memory B cells and AFC are induced at the site where Ag is present; induced memory B cells then recirculate throughout the lymphoid system independently of Ag localization. In contrast, AFC are induced only at the sites of Ag persistence. These triggered Ab producing cells do not recirculate through the lymphoid tissue but migrate to the bone marrow.
Background: Ventral hernia repairs (VHR) are frequent but loss- making. This study aims to identify epidemiological and procedure related factors in VHR and their influence on surgical training. Methods: Data from 86 consecutive patients who underwent VHR in 2019 was collected. Moreover, 66 primary ventral hernias and 20 incisional hernias were repaired in open procedures. Linear regression models were made. Results: Primary VHR procedures showed a mean deficit of −378.17 CHF per case. Incisional hernia repair procedures resulted in a deficit of −1442.50 CHF per case. The two hernia groups were heterogeneous. For the primary VHR procedures, the surgery time (β = 0.564, p < 0.001) had the greatest influence, followed by the costs of the mesh (β = −0.215, p < 0.001). The epidemiological factors gender (β = 0.143, p < 0.01) and body mass index (BMI) (β = −0.087, p = 0.074) were also influential. For incisional hernia procedures a surgeon’s experience had the most significant influence (β = 0.942, p < 0.001), and the second largest influence was the price of the mesh (β = -.500, p < 0.001). The epidemiological factor BMI (β = −0.590, p < 0.001), gender (β = −0.113, p = 0.055) and age (β = −0.026, p < 0.050) also had a significant influence. Conclusion: Our analysis shows a way of improving financial results in the field of ventral hernia repair. Costs can be visualized and reduced to optimize revenue enhancement in surgical departments. In our analysis primary ventral hernias are an appropriate training operation, in which the experience of the surgeon has no significant impact on costs. In primary VHR procedures, revenue enhancement is limited when using an expensive mesh. However, the treatment of incisional hernias is recommended by specialists. The financial burden is significantly higher with less experience. Therefore, these operations are not suitable for surgical training. The re-operation rate decreases with increasing experience of the surgeon. This directly affects the Patient Related Outcome (PROM) and quality of treatment. Therefore, high-quality training must be enforced. Since financial pressure on hospitals is increasing further, it is crucial to investigate cost influencing factors. The majority of Swiss public hospitals will no longer be able to operate ventral hernias profitably without new concepts. In addition to purchasing management, new construction projects, and mergers, improving the results of individual departments is a key factor in maintaining the profitability of hospitals in the future regarding hernia repair without losing the scope of teaching procedures.
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