The safety of ABO minor incompatible platelets transfusions using a rapid infuser.

BACKGROUND: Administering platelets through a rapid infuser is proven to be safe. However, the clinical significance of infusing ABO-incompatible platelets with red blood cells (RBCs) in a rapid infuser remains unclear. There is a theoretical risk that isoagglutinin in the plasma of a platelet unit can interact with RBCs and induce hemolysis. MATERIALS AND METHODS: Seven in vitro studies were performed including five cases (type A RBCs and type O platelets) and two controls (type A RBCs and platelets). Anti-A titers were measured in platelet units. An RBC unit and a platelet unit were mixed in the rapid infuser reservoir and incubated for 30 min. The primary outcome was the presence of hemolysis based on the following parameters: free hemoglobin concentration, hemolysis check, direct antiglobulin test (DAT), and direct agglutination. RESULTS: The post-mix DAT was positive for IgG in all test samples (5/5), and weakly positive for complement in 3/5. The changes in free Hb in test cases between measured and calculated post-mix spanned -2.2 to +3.4 mg/dL. Post-mix hemolysis check was negative in 3/5 and slightly positive in 2/5 cases, with no significant differences compared to the control case. Anti-A titers ranged from 16 to 512 and were not associated with hemolysis. All samples were negative for direct agglutination. CONCLUSION: Our study suggested that mixing ABO-incompatible platelets with RBCs in a rapid infuser does not induce in vitro hemolysis. These findings support the use of rapid infusers regardless of platelet compatibility in support of hemostatic resuscitation.

Mortality Associated With Proportionality of Secondary Mitral Regurgitation After Transcatheter Mitral Valve Repair: North American Mitraclip for Functional Mitral Regurgitation Registry.

The association, if any, between the effective regurgitant orifice area (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients who undergo mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip system (Abbott Vascular, Santa Clara, CA). This study's objective was to determine the association between EROA/LVEDV and 1-year mortality in patients who undergo m-TEER with MitraClip. In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. We studied 525 patients with secondary MR who underwent m-TEER. Most patients were male (63%) and were New York Heart Association class III (61%) or IV (21%). Mitral regurgitation was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely, with median = 0.19 mm2/ml, interquartile range [0.12,0.28] mm2/ml, and 187 patients (36%) had values <0.15 mm2/ml. Postprocedural mitral regurgitation severity was substantially alleviated, being 1+ or less in 74%, 2+ in 20%, 3+ in 4%, and 4+ in 2%; 1-year mortality was 22%. After adjustment for confounders, the logarithmic transformation (Ln) of EROA/LVEDV was associated with 1-year mortality (odds ratio 0.600, 95% confidence interval 0.386 to 0.933, p = 0.023). A higher Society of Thoracic Surgeons risk score was also associated with increased mortality. In conclusion, lower values of Ln(EROA/LVEDV) were associated with increased 1-year mortality in this multicenter registry. The slope of the association is steep at low values but gradually flattens as Ln(EROA/LVEDV) increases.

Initial experience with the fourth generation MitraClip™: Outcomes, procedural aspects, and considerations for device selection.

OBJECTIVES: We present our initial experience with the fourth-generation MitraClip™ (G4) system and propose preliminary criteria for device selection. BACKGROUND: The MitraClip™ G4 system recently underwent a "controlled release" for transcatheter edge-to-edge mitral valve repair. The four new devices include technical improvements such as controlled gripper actuation (independent leaflet capture) and continuous left atrial pressure monitoring. To date, a patient-specific device selection algorithm, and the technology's impact on procedural times and success, have not been described. METHODS: We present an initial multi-center experience and short-term outcomes with the new system, suggest procedural and imaging considerations, and propose initial guidance for device selection. RESULTS: Sixty-one procedures performed by three operators at two centers between November 2019 and May 2020 were analyzed. At 30-day follow-up, there were three deaths (4.9%), four neurological events (6.6%), and seven re-hospitalizations (11.5%). Fifty-nine patients achieved device and procedural success (96.7%), and there was one device-related technical issue (1.6%). Compared to the same operators utilizing the third generation MitraClip™, the G4 system resulted in a significant reduction in the median number of clips used per patient (1 IQR 1-2 vs. 2 IQR 1-3, p = .023) and a trend toward shorter device times. CONCLUSION: Based on our initial experience, we found that the MitraClip™ G4 system is associated with high procedural success and fewer devices needed per procedure. The expanded device options may allow a more targeted approach to the myriad of pathologic presentations of mitral regurgitation. This early experience should provide a foundational opportunity for further refinement.

Focal stimulation of the temporoparietal junction improves rationality in prosocial decision-making.

We tested the hypothesis that modulation of neurocomputational inputs to value-based decision-making affects the rationality of economic choices. The brain's right temporoparietal junction (rTPJ) has been functionally associated with both social behavior and with domain-general information processing and attention. To identify the causal function of rTPJ in prosocial decisions, we administered focal high definition transcranial direct current stimulation (HD-tDCS) while participants allocated money between themselves and a charity in a modified dictator game. Anodal stimulation led to improved rationality as well as increased charitable giving and egalitarianism, resulting in more consistent and efficient choices and increased sensitivity to the price of giving. These results are consistent with the theory that anodal stimulation of the rTPJ increases the precision of value computations in social decision-making. Our results demonstrate that theories of rTPJ function should account for the multifaceted role of the rTPJ in the representation of social inputs into value-based decisions.

Dual Epidural Catheter Therapy for Abdominal Surgery Pain: 2 Case Reports.

Dual epidural catheter (DEC) therapy improves postoperative pain control in scoliosis correction surgery, esophagectomies, and labor. Reports about the use of a second epidural catheter to improve pain control after abdominal surgeries are sparse. We describe the successful use of unplanned DEC therapy in 2 complex pain patients who underwent large exploratory laparotomies. In both patients, the addition of the second catheter led to improved pain control and mobility and reduced side effects from adjuvant intravenous analgesics. DEC therapy merits consideration as an additional tool for managing postoperative pain after large abdominal surgeries despite existing incomplete epidural analgesia.

Regulation of protein kinase C Apl II by serotonin receptors in Aplysia.

Serotonin (5-hydroxytryptamine, 5HT) is the neurotransmitter that mediates dishabituation in Aplysia. Serotonin mediates this behavioral change through the reversal of synaptic depression in sensory neurons (SNs). However, the 5HT receptors present in SNs and in particular, the receptor important for activation of protein kinase C (PKC) have not been fully identified. Using a recent genome assembly of Aplysia, we identified new receptors from the 5HT(2) , 5HT(4) , and 5HT(7) families. Using RT-PCR from isolated SNs, we found that three 5HT receptors, 5HT(1Apl(a)) , 5HT(2Apl) , and 5HT(7Apl) were expressed in SNs. These receptors were cloned and expressed in a heterologous system. In this system, 5HT(2Apl) could significantly translocate PKC Apl II in response to 5HT and this was blocked by pirenperone, a 5HT(2) receptor antagonist. Surprisingly, pirenperone did not block 5HT-mediated translocation of PKC Apl II in SNs, nor 5HT-mediated reversal of depression. Expression of 5HT(1Apl(a)) in SNs or genistein, an inhibitor of tyrosine kinases inhibited both PKC translocation and reversal of depression. These results suggest a non-canonical mechanism for the translocation of PKC Apl II in SNs.

Structural basis of substrate recognition and specificity in the N-end rule pathway.

The N-end rule links the half-life of a protein to the identity of its N-terminal residue. Destabilizing N-terminal residues are recognized by E3 ubiquitin ligases, termed N-recognins. A conserved structural domain called the UBR box is responsible for their specificity. Here we report the crystal structures of the UBR boxes of the human N-recognins UBR1 and UBR2, alone and in complex with an N-end rule peptide, Arg-Ile-Phe-Ser. These structures show that the UBR box adopts a previously undescribed fold stabilized through the binding of three zinc ions to form a binding pocket for type 1 N-degrons. NMR experiments reveal a preference for N-terminal arginine. Peptide binding is abrogated by N-terminal acetylation of the peptide or loss of the positive charge of the N-terminal residue. These results rationalize and refine the empirical rules for the classification of type 1 N-degrons. We also confirm that a missense mutation in UBR1 that is responsible for Johanson-Blizzard syndrome leads to UBR box unfolding and loss of function.