Removal of EpCAM-positive tumor cells from blood collected during major oncological surgery using the Catuvab device- a pilot study

Background Intraoperative blood salvage (IBS) is regarded as an alternative to allogeneic blood transfusion excluding the risks associated with allogeneic blood. Currently, IBS is generally avoided in tumor surgeries due to concern for potential metastasis caused by residual tumor cells in the erythrocyte concentrate. Methods The feasibility, efficacy and safety aspects of the new developed Catuvab procedure using the bispecific trifunctional antibody Catumaxomab was investigated in an ex-vivo pilot study in order to remove residual EpCAM positive tumor cells from the autologous erythrocyte concentrates (EC) from various cancer patients, generated by a IBS device. Results Tumor cells in intraoperative blood were detected in 10 of 16 patient samples in the range of 69–2.6 × 105 but no residual malignant cells in the final erythrocyte concentrates after Catuvab procedure. IL-6 and IL-8 as pro-inflammatory cytokines released during surgery, were lowered in mean 28-fold and 52-fold during the Catuvab procedure, respectively, whereas Catumaxomab antibody was detected in 8 of 16 of the final EC products at a considerable decreased and uncritical residual amount (37 ng in mean). Conclusion The preliminary study results indicate efficacy and feasibility of the new medical device Catuvab allowing potentially the reinfusion of autologous erythrocyte concentrates (EC) produced by IBS device during oncological high blood loss surgery. An open-label, multicenter clinical study on the removal of EpCAM-positive tumor cells from blood collected during tumor surgery using the Catuvab device is initiated to validate these encouraging results.

Development of a Lyophilization Process for Long-Term Storage of Albumin-Based Perfluorodecalin-Filled Artificial Oxygen Carriers

Every day, thousands of patients receive erythrocyte concentrates (ECs). They are indispensable for modern medicine, despite their limited resource. Artificial oxygen carriers (AOCs) represent a promising approach to reduce the need for ECs. One form of AOCs is perfluorodecalin-filled albumin-based nanocapsules. However, these AOCs are not storable and need to be applied directly after production. In this condition, they are not suitable as a medicinal product for practical use yet. Lyophilization (freeze drying) could provide the possibility of durable and applicable nanocapsules. In the present study, a suitable lyophilization process for perfluorodecalin-filled nanocapsules was developed. The nanocapsules were physicochemically characterized regarding capsule size, polydispersity, and oxygen capacity. Even though the perfluorodecalin-filled albumin-based nanocapsules showed a loss in oxygen capacity directly after lyophilization, they still provided a remarkable residual capacity. This capacity did not decline further for over two months of storage. Furthermore, the nanocapsule size remained unaltered for over one year. Therefore, the AOCs were still applicable and functional after long-term storage due to the successful lyophilization.

Removal of EpCAM-positive tumor cells from blood collected during major oncological surgery using the Catuvab device- a pilot study

Background:Intraoperative blood salvage (IBS) is regarded as an alternative to allogeneic blood transfusion excluding the risks associated with allogeneic blood. Currently, IBS is generally avoided in tumor surgeries due to concern for potential metastasis caused by residual tumor cells in the erythrocyte concentrate. Methods:The feasibility, efficacy and safety aspects of the new developed Catuvab procedure using the bispecific trifunctional antibody Catumaxomab was investigated in an ex-vivo pilot study in order to remove residual EpCAM positive tumor cells from the autologous erythrocyte concentrates (EC) from various cancer patients, generated by a IBS device. Results:Tumor cells in intraoperative blood were detected in 10 of 16 patient samples in the range of 69 - 2.6x105 but no residual malignant cells in the final erythrocyte concentrates after Catuvab procedure. IL-6 and IL-8 as pro-inflammatory cytokines released during surgery, were lowered in mean 28-fold and 52-fold during the Catuvab procedure, respectively, whereas Catumaxomab antibody was detected in 8 of 16 of the final EC products at a considerable decreased and uncritical residual amount (37 ng in mean). Conclusion:The preliminary study results indicate efficacy and feasibility of the new medical device Catuvab allowing potentially the reinfusion of autologous erythrocyte concentrates (EC) produced by IBS device during oncological high blood loss surgery. An open-label, multicenter clinical study on the removal of EpCAM‑positive tumor cells from blood collected during tumor surgery using the Catuvab device is initiated to validate these encouraging results.

Gender-Specific Differences in Presentation and Management of Spinal Infection: A Single-Center Retrospective Study of 159 Cases

Study Design: A retrospective single-center analysis of 159 cases. Objective: To investigate differences between male and female patients, as spinal infection (SI) represents a life-threatening condition and numerous factors may facilitate the course and outcome of SI, including patients’ age and comorbidities, as well as gender. To date, no comparative data investigating sex differences in SI is available. Thus, the purpose of the present retrospective trial was to investigate differences between male and female patients. Methods: A total of 159 patients who were treated for a spinal infection between 2010 and 2016 at our department were included in the analysis. The patients were categorized into 2 groups based on gender. Evaluation included magnetic resonance imaging, laboratory values, clinical outcome, and conservative/operative management. Results: Male patients suffered from SI significantly more often than female patients (n = 101, 63.5% vs n = 58, 36.5%, P = .001). However, female patients were initially affected more severely, as infection parameters were significantly higher ( P = .032) and vertebral destruction was more serious ( P = .018). Furthermore, women suffered from intraoperative complications more often ( P = .024) and received erythrocyte concentrates more frequently ( P = .01). Nevertheless, mortality rates and outcome were comparable. Pain scales were significantly higher in female patients at 12-month follow-up ( P = .042). Conclusion: Although male patients show a higher incidence for SI, the course of disease and the management is more challenging in female patients. Nevertheless, outcome after 12 months is comparably good. Underlying mechanisms may include a better immune response and dissimilar effects of antibiotic treatment in women. Pain management in female patients is still unsatisfactory after 12 months.

RBC Transfusion Triggers: Is There Anything New?

For many years, in daily clinical practice, the traditional 10/30 rule (hemoglobin 10 g/dL – hematocrit 30%) has been the most commonly used trigger for blood transfusions. Over the years, this approach is believed to have contributed to a countless number of unnecessary transfusions and an unknown number of overtransfusion-related deaths. Recent studies have shown that lower hemoglobin levels can safely be accepted, even in critically ill patients. However, even these new transfusion thresholds are far beyond the theoretical limits of individual anemia tolerance. For this reason, almost all publications addressing the limits of acute anemia recommend physiological transfusion triggers to indicate the transfusion of erythrocyte concentrates as an alternative. Although this concept appears intuitive at first glance, no solid scientific evidence supports the safety and benefit of physiological transfusion triggers to indicate the optimal time point for transfusion of allogeneic blood. It is therefore imperative to continue searching for the most sensitive and specific parameters that can guide the clinician when to transfuse in order to avoid anemia-induced organ dysfunction while avoiding overtransfusion-related adverse effects. This narrative review discusses the concept of anemia tolerance and critically compares hemoglobin-based triggers with physiological transfusion for various clinical indications.