Bioengineered particles expand myelin-specific regulatory T cells and reverse autoreactivity in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an autoimmune disease characterized by autoreactive immune cells damaging myelinated nerves, impairing brain function. Treatments aim for tolerance induction to reeducate the immune system to recognize myelin as "self" rather than "foreign." As peripheral immune tolerance is primarily mediated by regulatory T cells (Tregs), we developed a therapy to support Treg expansion and activity in vivo. To target, engage, and activate myelin-specific Tregs, we designed a biodegradable microparticle (MP) loaded with rapamycin and functionalized with a biased interleukin-2 (IL-2) fusion protein and a major histocompatibility complex (MHC) class II loaded with a myelin peptide. These tolerogenic MPs (Tol-MPs) were validated in vitro and then evaluated in a mouse model of MS, experimental autoimmune encephalomyelitis (EAE). Tol-MPs promoted sustained disease reversal in 100% of mice and full recovery in 38% of mice with symptomatic EAE. Tol-MPs are a promising platform for treatment of autoimmune diseases.

Organ Donors with Human Immunodeficiency Virus and Hepatitis C Virus: Expanding the Donor Pool.

Using organs from donors with treatable infections is a strategy to increase the quality and number of organs for transplantation. For HIV, pilot studies of kidney and liver transplantation from donors with HIV to recipients with HIV demonstrate excellent early outcomes. However, the number of donors and transplants per year remains lower than projected due to several barriers. For HCV, the use of organs from donors with HCV has expanded to recipients without HCV due to safe, effective direct-acting antivirals for HCV, which are well-tolerated in transplant recipients. Studies across organ types demonstrate good outcomes and shorter wait times.

A racial analysis of pain outcomes following microvascular decompression for trigeminal neuralgia.

OBJECTIVE: Pain outcomes by race in trigeminal neuralgia (TN) are not well investigated. The authors aimed to compare microvascular decompression (MVD) outcomes in TN patients on the basis of self-identified race. METHODS: The authors retrospectively reviewed all patients with TN who underwent MVD at their institution from 2007 to 2020. Each patient's self-reported race was recorded, and Barrow Neurological Institute (BNI) scores for pain and numbness were compared. Factors associated with pain recurrence were assessed using survival analyses and multivariate regressions. RESULTS: Of 1011 patients, 925 reported their racial demographic characteristics, and patients who identified as Native American or American Indian and Native Hawaiian or Pacific Islander were excluded due to small sample sizes. Of the resulting 921 patients, 697 (75.7%) patients identified as White, 108 (11.7%) as Black or African American, 39 (4.2%) as Asian, and 77 (8.4%) as other. Compared with White patients, Black TN patients were more likely to present with type 1 TN (p = 0.02). At final follow-up, the mean BNI pain score of Black patients was significantly higher (p < 0.001) compared with that of White patients, although pain scores did not differ preoperatively. The adjusted multivariate ordinal regression model showed that Black patients were associated with higher BNI pain scores at final follow-up (p = 0.01). Furthermore, compared with White patients, Black patients were at increased risk for postoperative pain recurrence (p = 0.04), which additionally occurred after a shorter median pain-free duration (p = 0.03). CONCLUSIONS: TN patients who identify as Black or African American exhibit worse postoperative pain outcomes after MVD compared with White patients. Future studies investigating the factors driving these racial differences are warranted.

Sex-Specific Pain Outcomes Following Microvascular Decompression for Trigeminal Neuralgia.

BACKGROUND: Trigeminal neuralgia (TN) is more prevalent among women. However, while microvascular decompression (MVD) is the most effective long-term surgical treatment for TN, it is unclear whether it is equally efficacious for men and women. We sought to characterize the relationship between sex and pain outcomes following MVD for TN. METHODS: From 2007 to 2020, 938 unilateral TN patients were treated with MVD at our institution. Patient demographics, clinical characteristics, operative features, and pain outcomes were recorded. Differences between men and women were analyzed via t-test and chi-squared analyses. A multivariate ordinal regression was used to establish significant predictors of pain outcome. Differences in time to pain recurrence were assessed via Cox proportional hazards and Kaplan-Meier nonparametric survival analysis. RESULTS: A majority (67%) of the 938 patients analyzed were female. Men and women presented with similar preoperative pain severity (P = 0.17). Female sex (P = 0.048) and younger age (P = 0.03) were independently associated with worsened Barrow Neurological Institute pain scores at 3-month follow-up on multivariate analysis. Women were also more likely to experience recurrence than men (P = 0.01), and time to recurrence was shorter among women (P = 0.02). Only female sex was independently associated with increased risk of postoperative pain recurrence on multivariate Cox proportional hazards regression (P = 0.01). CONCLUSIONS: Female TN patients undergoing MVD had worse pain outcomes, more frequent pain recurrence, and shorter time to recurrence. Our results indicate a sex-specific dimorphism in response to MVD among TN patients.