Four-factor prothrombin complex concentrate improves thrombin generation and prothrombin time in patients with bleeding complications related to rivaroxaban: a single-center pilot trial.

BACKGROUND: Direct oral anticoagulants (DOACs) pose a great challenge for physicians in life-threatening bleeding events. The aim of this study was to test the efficacy of reversing the DOAC rivaroxaban using four-factor PCC (prothrombin complex concentrate), a non-specific reversing agent. METHODS: Patients with life-threatening bleeding events during rivaroxaban treatment were included and administered 25 U kg-1 of PCC. Blood samples were collected immediately prior to as well as after PCC treatment at predefined time intervals. The primary endpoint was defined as the difference in thrombin generation (TG) parameters ETP (endogenous thrombin potential) and Cmax (peak thrombin generation) prior to and ten minutes subsequent to PCC treatment. RESULTS: Thirteen patients, of whom the majority suffered from intra-cranial haemorrhage (ICH) or subdural haemorrhage (SDH), were included and administered PCC. The results show that the ETP (TG) significantly (p = 0.001) improved by 68% and Cmax (TG) by 54% (p = 0.001) during PCC treatment. In addition, the Quick value (prothrombin time: QuickPT) significantly improved by 28% and the activated partial thromboplastin time (aPTT) was decreased by 7% ten minutes after PCC administration. Cmax was reduced at baseline, but not ETP, aPTT or QuickPT. Lag time until initiation (TG, tlag), thromboelastometry clotting time (CTEXTEM) and time to peak (TG, tmax) correlated best with measured rivaroxaban levels and were out of normal ranges at baseline, but did not improve after PCC administration. In 77% of the patients bleeding (ICH/SDH-progression) ceased following PCC administration. During the study three participants passed away due to other complications not related to PCC treatment. The possibility of thrombosis formation was also evaluated seven days after administering PCC and no thromboses were found. CONCLUSIONS: This study shows that use of PCC improved ETP, Cmax, QuickPT and aPTT. However, of these parameters, only Cmax was reduced at the defined baseline. It can be concluded that CTEXTEM, tlag and tmax correlated best with the measured rivaroxaban levels. The study drug was found to be safe. Nonetheless, additional studies specifically targeting assessment of clinical endpoints should be performed to further confirm these findings. CLINICAL TRIAL REGISTRATION: EudraCT trial No. 2013-004484-31.

Biomechanical Study of a Novel, Expandable, Non-Metallic and Radiolucent CF/PEEK Vertebral Body Replacement (VBR).

Vertebral body replacement is well-established to stabilize vertebral injuries due to trauma or cancer. Spinal implants are mainly manufactured by metallic alloys; which leads to artifacts in radiological diagnostics; as well as in radiotherapy. The purpose of this study was to evaluate the biomechanical data of a novel carbon fiber reinforced polyetheretherketone (CF/PEEK) vertebral body replacement (VBR). Six thoracolumbar specimens were tested in a six degrees of freedom spine tester. In all tested specimens CF/PEEK pedicle screws were used. Two different rods (CF/PEEK versus titanium) with/without cross connectors and two different VBRs (CF/PEEK prototype versus titanium) were tested. In lateral bending and flexion/extension; range of motion (ROM) was significantly reduced in all instrumented states. In axial rotation; the CF/PEEK combination (rods and VBR) resulted in the highest ROM; whereas titanium rods with titanium VBR resulted in the lowest ROM. Two cross connectors reduced ROM in axial rotation for all instrumentations independently of VBR or rod material. All instrumented states in all planes of motion showed a significantly reduced ROM. No significant differences were detected between the VBR materials in all planes of motion. Less rigid CF/PEEK rods in combination with the CF/PEEK VBR without cross connectors showed the smallest reduction in ROM. Independently of VBR and rod material; two cross connectors significantly reduced ROM in axial rotation. Compared to titanium rods; the use of CF/PEEK rods results in higher ROM. The stiffness of rod material has more influence on the ROM than the stiffness of VBR material.

How does a novel knitted titanium nucleus prosthesis change the kinematics of a cervical spine segment? A biomechanical cadaveric study.

BACKGROUND: Total disc replacement is a possible treatment alternative for patients with degenerative disc disease, especially in the cervical spine. The aim is to restore the physiological flexibility and biomechanical behavior. A new approach based on these requirements is the novel nucleus prosthesis made of knitted titanium wires. METHODS: The biomechanical functionalities of eight human cervical (C4-C7) spine segments were investigated. The range of motion was quantified using an ultra-sound based motion analysis system. Moreover, X-rays in full flexion and extension of the segment were taken to define the center of rotation before and after implantation of the nucleus prosthesis as well as during and after complex cyclic loading. FINDINGS: The mean range of motion of the index segment (C5/6) in flexion/extension showed a significant reduction of range of motion from 9.7° (SD 4.33) to 6.0° (SD 3.97) after implantation (P = 0.037). Lateral bending and axial rotation were not significantly reduced after implanting and during cyclic loading in our testing. During cyclic loading the mean range of motion for flexion/extension increased to 7.2° (SD 3.67). The center of rotation remained physiological in the ap-plane and moved cranially in the cc-plane (-27% to -5% in cc height) during the testing. INTERPRETATION: The biomechanical behavior of the nucleus implant might lower the risk for adjacent joint disorders and restore native function of the index segment. Further in vivo research is needed for other factors, like long-term effects and patient's satisfaction.

A Sandwich Technique for Prevention of Cerebrospinal Fluid Rhinorrhea and Reconstruction of the Sellar Floor after Microsurgical Transsphenoidal Pituitary Surgery.

BACKGROUND: Cerebrospinal fluid (CSF) leaks are a well-known complication of transsphenoidal surgery. Several autologous and artificial grafts have been used to close the sellar floor in an attempt to prevent postoperative CSF rhinorrhea. OBJECTIVE: To evaluate and describe a sandwich technique to close the sellar floor using autologous bone, absorbable gelatin sponge, and coated collagen fleece. METHODS: We reviewed 50 consecutive patients between April 2010 and August 2011 who underwent transsphenoidal surgery ending with reconstruction of the sellar floor with a particular sandwich technique. Patients with an intraoperative CSF leak received an additional lumbar drain. RESULTS: There were no cases of CSF rhinorrhea at postoperative follow-up after 6 weeks and no revision surgery. CONCLUSION: The proposed sandwich technique for closure of the sellar floor to the sphenoid sinus is a suitable alternative to autologous grafts and seems to be effective in preventing CSF rhinorrhea.