Spinal anesthesia for cesarean section in a woman with an intrathecal baclofen pump.

BACKGROUND: Intrathecal baclofen pumps are commonly used for the management of lower extremity spasticity in the setting of spinal cord injury. There have been no reports of the performance of spinal anesthesia in patients with a pre-existing intrathecal baclofen pump. CASE PRESENTATION: A 29-year-old parturient presented for cesarean section. She had a history of spinal cord injury due to fractures of the thoracic vertebrae with lower extremity spasticity, which had been treated with an intrathecal baclofen pump inserted through lumbar (L) 3-L4 intervertebral space. Preoperative lumbosacral ultrasound was performed to identify the L4-5 interspace, and spinal anesthesia was performed through that space with a 25-gauge 3.5-inch-long Whitacre spinal needle. Thoracic (T) 4 dermatomal level anesthesia was achieved, and the patient underwent the cesarean section without requiring additional intravenous analgesic adjuncts. CONCLUSIONS: Spinal anesthesia can be successfully performed in patients with intrathecal baclofen pumps. Existing intrathecal catheters can be located with preoperative imaging, and ultrasound can be used to determine the vertebral levels below the intrathecal catheter through which spinal anesthesia can be performed safely.

In-Hospital Opioid Consumption After the Previous Cesarean Delivery Weakly Predicts Opioid Consumption After Index Delivery: A Retrospective Cohort Study.

BACKGROUND: To predict opioid consumption and pain intensity after the index cesarean delivery, we tested a hypothesis that opioid consumption after the previous cesarean delivery of the same patient can predict the opioid consumption after the index cesarean delivery. We further tested a secondary hypothesis that the pain scores after the previous cesarean delivery can predict the pain scores after the index cesarean delivery. METHODS: This is a retrospective cohort study of 470 women who underwent both previous and index cesarean deliveries at a single institution from January 2011 to June 2019. To predict the opioid consumption (primary outcome) and average pain scores (on 11-point numeric rating scale) after their index cesarean delivery, we used a linear regression model incorporating only the opioid consumption and average pain scores after the previous cesarean delivery, respectively (unadjusted models). Demographic and obstetric variables were then added as predictors (adjusted models). The bootstrap was used to compare these models with respect to proportion of variance of the outcome accounted for (R2). RESULTS: Unadjusted models were weakly predictive of opioid consumption (R2 = 0.268; 95% confidence interval [CI], 0.146-0.368) and average pain scores (R2 = 0.176; 95% CI, 0.057-0.250). An adjusted model for opioid consumption was weakly predictive (R2 = 0.363; 95% CI, 0.208-0.478), but an adjusted model for average pain scores was not predictive of the outcomes (R2 = 0.070; 95% CI, -0.143 to 0.219). Adjusted models failed to explain variances of opioid consumption and average pain scores significantly better than unadjusted models (P = .099 and P = .141, respectively). CONCLUSIONS: Opioid consumption and pain scores after women's previous cesarean delivery only explain 27% of variance of opioid consumption and 18% of variance of their pain after their index cesarean delivery. Therefore, previous cesarean delivery analgesic metrics are not robust enough to be used as clinically applicable predictors for index delivery.

Acute Pain Burden and Opioid Dose Requirements after Cesarean Delivery in Parturients with Preexisting Chronic Back Pain and Migraine.

INTRODUCTION: Preexisting chronic pain has been reported to be a consistent risk factor for severe acute postoperative pain. However, each specific chronic pain condition has unique pathophysiology, and it is possible that the effect of each condition on postoperative pain is different. METHODS: This is a retrospective cohort study of pregnant women with preexisting chronic pain conditions (i.e., migraine, chronic back pain, and the combination of migraine + chronic back pain), who underwent cesarean delivery. The effects of the three chronic pain conditions on time-weighted average (TWA) pain score (primary outcome) and opioid dose requirements in morphine milligram equivalents (MME) during postoperative 48 hours were compared. RESULTS: The TWA pain score was similar in preexisting migraine and chronic back pain. Chronic back pain was associated with significantly greater opioid dose requirements than migraine (12.92 MME, 95% CI: 0.41 to 25.43, P=0.041). Preoperative opioid use (P < 0.001) was associated with a greater TWA pain score. Preoperative opioid use (P < 0.001), smoking (P=0.004), and lower postoperative ibuprofen dose (P=0.002) were associated with greater opioid dose requirements. CONCLUSIONS: Findings suggest women with chronic back pain and migraine do not report different postpartum pain intensities; however, women with preexisting chronic back pain required 13 MME greater opioid dose than those with migraine during 48 hours after cesarean delivery.

Remifentanil infusion prolongs spinal anesthesia.

Spinal anesthesia was given to a patient undergoing transurethral resection ofprostate (TURP). A total of 3.2 ml of bupivacaine 0.5% mixed with fentanyl 20 mcg were used. The patient started experiencing sensation after 150 min. Remifentanil intravenous infusion prolonged the duration of anesthesia for an additional 105 minutes.

CD24 on thymic APCs regulates negative selection of myelin antigen-specific T lymphocytes.

Negative selection plays a key role in the clonal deletion of autoreactive T cells in the thymus. However, negative selection is incomplete; as high numbers of autoreactive T cells can be detected in normal individuals, mechanisms that regulate negative selection must exist. In this regard, we previously reported that CD24, a GPI-anchored glycoprotein, is required for thymic generation of autoreactive T lymphocytes. The CD24-deficient 2D2 TCR transgenic mice (2D2(+) CD24(-/-) ), whose TCR recognizes myelin oligodendrocyte glycoprotein (MOG), fail to generate functional 2D2 T cells. However, it was unclear if CD24 regulated negative selection, and if so, what cellular mechanisms were involved. Here, we show that elimination of MOG or Aire gene expression in 2D2(+) CD24(-/-) mice - through the creation of 2D2(+) CD24(-/-) MOG(-/-) or 2D2(+) CD24(/) ∼Aire(-/-) mice - completely restores thymic cellularity and function of 2D2 T cells. Restoration of CD24 expression on DCs, but not on thymocytes also partially restores 2D2 T-cell generation in 2D2(+) CD24(-/-) mice. Taken together, we propose that CD24 expression on thymic antigen-presenting cells (mTECs, DCs) down-regulates autoantigen-mediated clonal deletion of autoreactive thymocytes.

Tumor expression of CD200 inhibits IL-10 production by tumor-associated myeloid cells and prevents tumor immune evasion of CTL therapy.

CD200 is a cell-surface glycoprotein that functions through interaction with the CD200 receptor on myeloid lineage cells to regulate myeloid cell functions. Expression of CD200 has been implicated in multiple types of human cancer; however, the impact of tumor expression of CD200 on tumor immunity remains poorly understood. To evaluate this issue, we generated CD200-positive mouse plasmacytoma J558 and mastocytoma P815 cells. We found that established CD200-positive tumors were often completely rejected by adoptively transferred CTL without tumor recurrence; in contrast, CD200-negative tumors were initially rejected by adoptively transferred CTL but the majority of tumors recurred. Tumor expression of CD200 significantly inhibited suppressive activity and IL-10 production by tumor-associated myeloid cells (TAMC), and as a result, more CTL accumulated in the tumor and exhibited a greater capacity to produce IFN-gamma in CD200-positive tumors than in CD200-negative tumors. Neutralization of IL-10 significantly inhibited the suppressor activity of TAMC, and IL-10-deficiency allowed TAMC to kill cancer cells and their antigenic variants, which prevented tumor recurrence during CTL therapy. Thus, tumor expression of CD200 prevents tumor recurrence via inhibiting IL-10 production by TAMC.

Targeting activation-induced cytidine deaminase overcomes tumor evasion of immunotherapy by CTLs.

Activation-induced cytidine deaminase (AID) is an enzyme essential for the generation of Ab diversity in B cells and is considered to be a general gene mutator. In addition, AID expression was also implicated in the pathogenesis of human B cell malignancies and associated with poor prognosis. In this study, we report that small interfering RNA silencing of AID in plasmacytoma dramatically increased its susceptibility to immunotherapy by CTLs. AID silencing did not decrease the mutation frequencies of tumor Ag gene P1A. Gene-array analysis showed dramatically altered expression of a number of genes in AID-silenced plasmacytoma cells, and upregulation of CD200 was shown to be in favor of tumor eradication by CTLs. Taken together, we demonstrate a novel function of AID in tumor evasion of CTL therapy and that targeting AID should be beneficial in the immunotherapy of AID-positive tumors.

Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway.

Despite negative selection in the thymus, significant numbers of autoreactive T cells still escape to the periphery and cause autoimmune diseases when immune regulation goes awry. It is largely unknown how these T cells escape clonal deletion. In this study, we report that CD24 deficiency caused deletion of autoreactive T cells that normally escape negative selection. Restoration of CD24 expression on T cells alone did not prevent autoreactive T cells from deletion; bone marrow chimera experiments suggest that CD24 on radio-resistant stromal cells is necessary for preventing deletion of autoreactive T cells. CD24 deficiency abrogated the development of experimental autoimmune encephalomyelitis in transgenic mice with a TCR specific for a pathogenic autoantigen. The role of CD24 in negative selection provides a novel explanation for its control of genetic susceptibility to autoimmune diseases in mice and humans.