Onset Time of Lumbar Erector Spinae Plane Block Compared with Its Thoracic Counterpart: Case Reports.

The erector spinae plane block (ESPB) at the level of the fifth thoracic vertebra (T5) is a novel technique, first published in 2016, which was found to be effective in both acute and chronic pain control. The mechanism of action and spread of local anesthetic of the ESPB at the lumbar region are thought to differ from those of the thoracic ESPB; however, the difference in onset time has never been evaluated. As for the onset of lumbar ESPBs, we presented three cases: two received lumbar ESPBs (one with chronic low back pain and one with acute postoperative hip pain), and the third one with chronic back pain received a thoracic ESPB. We administered 30 mL of 0.3% ropivacaine in all three patients, but the analgesic effect did not reach its maximum until 3 and 1.5 h, respectively, in the lumbar ESPB cases. On the contrary, the thoracic ESPB case experienced noticeable pain relief within 30 min. The onset time was considerably longer than that reported in earlier reports on ESPBs, and the lumbar ESPB achieved its peak effect much later than the thoracic ESPB using the same formula of local anesthetic. While the delayed-onset lumbar ESPB may have some drawbacks for treating acute postoperative pain, it still could produce significant analgesia, once it took effect, when given to patients suffering from hip surgery with large incisions and intractable low back pain. The current data suggested that the onset time of a lumbar ESPB may be delayed compared with its thoracic counterpart. Therefore, the local anesthetic formula and injection timing should be adjusted for a lumbar ESPB when applied in the perioperative period to make the onset of the analgesic effect coincide with the immediate postoperative pain. Without this concept in mind, clinicians may consider a lumbar ESPB to be ineffective before it takes effect, and consequently treat the patients inadequately with this technique. Future randomized controlled trials should be designed according to our observations to compare lumbar ESPB with its thoracic counterpart regarding onset time.

BiTE-Secreting CAR-γδT as a Dual Targeting Strategy for the Treatment of Solid Tumors.

HLA-G is considered as an immune checkpoint protein and a tumor-associated antigen. In the previous work, it is reported that CAR-NK targeting of HLA-G can be used to treat certain solid tumors. However, the frequent co-expression of PD-L1 and HLA-G) and up-regulation of PD-L1 after adoptive immunotherapy may decrease the effectiveness of HLA-G-CAR. Therefore, simultaneous targeting of HLA-G and PD-L1 by multi-specific CAR could represent an appropriate solution. Furthermore, gamma-delta T (γδT) cells exhibit MHC-independent cytotoxicity against tumor cells and possess allogeneic potential. The utilization of nanobodies offers flexibility for CAR engineering and the ability to recognize novel epitopes. In this study, Vδ2 γδT cells are used as effector cells and electroporated with an mRNA-driven, nanobody-based HLA-G-CAR with a secreted PD-L1/CD3ε Bispecific T-cell engager (BiTE) construct (Nb-CAR.BiTE). Both in vivo and in vitro experiments reveal that the Nb-CAR.BiTE-γδT cells could effectively eliminate PD-L1 and/or HLA-G-positive solid tumors. The secreted PD-L1/CD3ε Nb-BiTE can not only redirect Nb-CAR-γδT but also recruit un-transduced bystander T cells against tumor cells expressing PD-L1, thereby enhancing the activity of Nb-CAR-γδT therapy. Furthermore, evidence is provided that Nb-CAR.BiTE redirectes γδT into tumor-implanted tissues and that the secreted Nb-BiTE is restricted to the tumor site without apparent toxicity.