RESUMO
Clinically, peripheral nerve reconstructions in neonates are most frequently applied in brachial plexus birth injuries. Most surgical concepts, however, have investigated nerve reconstructions in adult animal models. The immature neuromuscular system reacts differently to the effects of nerve lesion and surgery and is poorly investigated due to the lack of reliable experimental models. Here, we describe an experimental forelimb model in the neonatal rat, to study these effects on both the peripheral and central nervous systems. Within 24 hours after birth, three groups were prepared: In the nerve transfer group, a lesion of the musculocutaneous nerve was reconstructed by selectively transferring the ulnar nerve. In the negative control group, the musculocutaneous nerve was divided and not reconstructed and in the positive control group, a sham surgery was performed. The animal´s ability to adapt to nerve lesions and progressive improvement over time were depict by the Bertelli test, which observes the development of grooming. Twelve weeks postoperatively, animals were fully matured and the nerve transfer successfully reinnervated their target muscles, which was indicated by muscle force, muscle weight, and cross sectional area evaluation. On the contrary, no spontaneous regeneration was found in the negative control group. In the positive control group, reference values were established. Retrograde labeling indicated that the motoneuron pool of the ulnar nerve was reduced following nerve transfer. Due to this post-axotomy motoneuron death, a diminished amount of motoneurons reinnervated the biceps muscle in the nerve transfer group, when compared to the native motoneuron pool of the musculocutaneous nerve. These findings indicate that the immature neuromuscular system behaves profoundly different than similar lesions in adult rats and explains reduced muscle force. Ultimately, pathophysiologic adaptations are inevitable. The maturing neuromuscular system, however, utilizes neonatal capacity of regeneration and seizes a variety of compensation mechanism to restore a functional extremity. The above described neonatal rat model demonstrates a constant anatomy, suitable for nerve transfers and allows all standard neuromuscular analyses. Hence, detailed investigations on the pathophysiological changes and subsequent effects of trauma on the various levels within the neuromuscular system as well as neural reorganization of the neonatal rat may be elucidated. This study was approved by the Ethics Committee of the Medical University of Vienna and the Austrian Ministry for Research and Science (BMWF-66.009/0187-WF/V/3b/2015) on March 20, 2015.
RESUMO
Background: Patients receiving a variety of chemotherapy regimens often develop chemotherapy-induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs. Methods: A retrospective study analyzed 10,269 University of Pennsylvania Health System patients with malignancies of various type, stage, and histopathology who developed CIA between 2008 and 2017. Using multivariate Cox regression, we determined adjusted hazard ratios (and corresponding 95% confidence intervals) of VTE development after adjusting for RBC and ESA intervention (all during the 90 days following CIA diagnosis). Results: Among the 10,269 patients with CIA, 2,642 (25.7%) developed a VTE within the 90-day period. VTE risk following RBC transfusion (HR = 1.37, 95% CI 1.24-1.50, P < .001) was more than twice as common as VTE risk following ESA administration (HR = 0.53, 95% CI 0.40-0.69, P < .001). Conclusion: While both RBC transfusion and ESA are independently associated with VTE, our data suggest a greater risk of VTE development with RBC transfusion as compared with ESA.