Clinical and Radiographic Outcomes Following Volar-Locked Plating Versus Dorsal Bridge Plating for Distal Radius Factures.

Purpose: Distal radius fractures (DRFs) indicated for operative intervention are most commonly treated with volar-locked plating (VLP); however, dorsal bridge plating (DBP) has been used as an alternative fixation method. The purpose of this study was to use a propensity score to match and compare the radiographic and clinical outcomes of patients undergoing isolated VLP or DBP for DRFs. Methods: We performed a retrospective, propensity score-matched analysis of patients undergoing isolated VLP or DBP treatment for isolated DRFs from 2015 to 2022 at a single level-1 trauma center. Patients were propensity score-matched by a total of eight demographic and comorbidity factors, AO Foundation/Orthopedic Trauma Association classification, and preoperative Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Our primary outcomes included postoperative complications, wrist and forearm range of motion (ROM), grip strength, and radiographic measurements, including radial height, radial inclination, volar tilt, and articular step-off. Results: Overall, 415 DBP and 2075 VLP were successfully propensity score-matched and included in this study. Grip strength and ROM measurements at the 6-month follow-up, including wrist flexion, wrist extension, forearm pronation, forearm supination, radial deviation, and ulnar deviation, were increased in the VLP compared with DBP (P < .05). Complication rates among both the groups were relatively low; however, the rates of malunion and nonunion were significantly higher among the DBP group (P < .05). Radial height, radial inclination, and articular step-off were improved in the VLP group compared with the DBP group (P < .05); however, volar tilt was similar between groups. PROMIS upper extremity and physical function were significantly higher among the VLP group (P < .05). No significant difference was noted in PROMIS pain interference between the groups. Conclusions: When compared with DBP, patients undergoing VLP are more likely to have improved clinical and radiographic outcomes. Although improvement in wrist and forearm ROM and radiographic parameters is statistically significant, it may not be clinically relevant. Type of study/level of evidence: Therapeutic III.

Efficacy of intrathecal mesenchymal stem cell-neural progenitor therapy in progressive MS: results from a phase II, randomized, placebo-controlled clinical trial.

BACKGROUND: Mesenchymal stem cell-neural progenitors (MSC-NPs) are a bone marrow mesenchymal stem cell (MSC)-derived ex vivo manipulated cell product with therapeutic potential in multiple sclerosis (MS). The objective of this study was to determine efficacy of intrathecal (IT) MSC-NP treatment in patients with progressive MS. METHODS: The study is a phase II randomized, double-blind, placebo-controlled clinical trial with a compassionate crossover design conducted at a single site. Subjects were stratified according to baseline Expanded Disability Status Scale (EDSS) (3.0-6.5) and disease subtype (secondary or primary progressive MS) and randomized into either treatment or placebo group to receive six IT injections of autologous MSC-NPs or saline every two months. The primary outcome was EDSS Plus, defined by improvement in EDSS, timed 25-foot walk (T25FW) or nine-hole peg test. Secondary outcomes included the individual components of EDSS Plus, the six-minute walk test (6MWT), urodynamics testing, and brain atrophy measurement. RESULTS: Subjects were randomized into MSC-NP (n = 27) or saline (n = 27) groups. There was no difference in EDSS Plus improvement between the MSC-NP (33%) and saline (37%) groups. Exploratory subgroup analysis demonstrated that in subjects who require assistance for ambulation (EDSS 6.0-6.5) there was a significantly higher percentage of improvement in T25FW and 6MWT in the MSC-NP group (3.7% ± 23.1% and - 9.2% ± 18.2%) compared to the saline group (-54.4% ± 70.5% and - 32.1% ± 30.0%), (p = 0.030 and p = 0.036, respectively). IT-MSC-NP treatment was also associated with improved bladder function and reduced rate of grey matter atrophy on brain MRI. Biomarker analysis demonstrated increased MMP9 and decreased CCL2 levels in the cerebrospinal fluid following treatment. CONCLUSION: Results from exploratory outcomes suggest that IT-MSC-NP treatment may be associated with a therapeutic response in a subgroup of MS patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT03355365, registered November 14, 2017, https://clinicaltrials.gov/study/NCT03355365?term=NCT03355365&rank=1 .

Humoral and cellular responses to repeated COVID-19 exposure in multiple sclerosis patients receiving B-cell depleting therapies: a single-center, one-year, prospective study.

Multiple sclerosis patients treated with anti-CD20 therapy (aCD20-MS) are considered especially vulnerable to complications from SARS-CoV-2 infection due to severe B-cell depletion with limited viral antigen-specific immunoglobulin production. Therefore, multiple vaccine doses as part of the primary vaccination series and booster updates have been recommended for this group of immunocompromised individuals. Even though much less studied than antibody-mediated humoral responses, T-cell responses play an important role against CoV-2 infection and are induced efficiently in vaccinated aCD20-MS patients. For individuals with such decoupled adaptive immunity, an understanding of the contribution of T-cell mediated immunity is essential to better assess protection against CoV-2 infection. Here, we present results from a prospective, single-center study for the assessment of humoral and cellular immune responses induced in aCD20-MS patients (203 donors/350 samples) compared to a healthy control group (43/146) after initial exposure to CoV-2 spike antigen and subsequent re-challenges. Low rates of seroconversion and RBD-hACE2 blocking activity were observed in aCD20-MS patients, even after multiple exposures (responders after 1st exposure = 17.5%; 2nd exposure = 29.3%). Regarding cellular immunity, an increase in the number of spike-specific monofunctional IFNγ+-, IL-2+-, and polyfunctional IFNγ+/IL-2+-secreting T-cells after 2nd exposure was found most noticeably in healthy controls. Nevertheless, a persistently higher T-cell response was detected in aCD20-MS patients compared to control individuals before and after re-exposure (mean fold increase in spike-specific IFNγ+-, IL-2+-, and IFNγ+/IL-2+-T cells before re-exposure = 3.9X, 3.6X, 3.5X/P< 0.001; after = 3.2X, 1.4X, 2.2X/P = 0.002, P = 0.05, P = 0.004). Moreover, cellular responses against sublineage BA.2 of the currently circulating omicron variant were maintained, to a similar degree, in both groups (15-30% T-cell response drop compared to ancestral). Overall, these results highlight the potential for a severely impaired humoral response in aCD20-MS patients even after multiple exposures, while still generating a strong T-cell response. Evaluating both humoral and cellular responses in vaccinated or infected MS patients on B-cell depletion therapy is essential to better assess individual correlations of immune protection and has implications for the design of future vaccines and healthcare strategies.

Strong T-cell activation in response to COVID-19 vaccination in multiple sclerosis patients receiving B-cell depleting therapies.

Immunocompromised individuals, including multiple sclerosis (MS) patients on certain immunotherapy treatments, are considered susceptible to complications from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and specific vaccination regimens have been recommended for suitable protection. MS patients receiving anti-CD20 therapy (aCD20-MS) are considered especially vulnerable due to acquired B-cell depletion and impaired antibody production in response to virus infection and COVID-19 vaccination. Here, the humoral and cellular responses are analyzed in a group of aCD20-MS patients (n=43) compared to a healthy control cohort (n=34) during the first 6 months after a 2-dose cycle mRNA-based COVID-19 vaccination. Both IgG antibodies recognizing receptor binding domain (RBD) from CoV-2 spike protein and their blocking activity against RBD-hACE2 binding were significantly reduced in aCD20-MS patients, with a seroconversion rate of only 23.8%. Interestingly, even under conditions of severe B-cell depletion and failed seroconversion, a significantly higher polyfunctional IFNγ+ and IL-2+ T-cell response and strong T-cell proliferation capacity were detected compared to controls. Moreover, no difference in T-cell response was observed between forms of disease (relapsing remitting- vs progressive-MS), anti-CD20 therapy (Rituximab vs Ocrelizumab) and type of mRNA-based vaccine received (mRNA-1273 vs BNT162b2). These results suggest the generation of a partial adaptive immune response to COVID-19 vaccination in B-cell depleted MS individuals driven by a functionally competent T-cell arm. Investigation into the role of the cellular immune response is important to identifying the level of protection against SARS-CoV-2 in aCD20-MS patients and could have potential implications for future vaccine design and application.

Transarterial Embolization for the Treatment of Chronic Musculoskeletal Pain: A Systematic Review of Indications, Safety, and Efficacy.

OBJECTIVE: The study objective was to evaluate the safety and efficacy of transcatheter arterial "embolization" (TAE) in the treatment of chronic "musculoskeletal pain" refractory to standard therapy. METHODS: PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched for original research articles evaluating TAE in patients with musculoskeletal conditions from database inception to January 21, 2020. Search terms employed were as follows: "embolization", "pain", "knee osteoarthritis", joint replacement, epicondylitis, tenderness, inflammation, WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index), microspheres, Embozene, geniculate artery, neovascularity, transcatheter, embolic, imipenem/cilastatin sodium, angiogenesis, and "musculoskeletal". Studies involving particle "embolization" for painful musculoskeletal conditions were included. Studies of TAE for hemarthrosis or malignancy-related "musculoskeletal pain" were excluded. RESULTS: The primary search yielded 1,099 sources; 7 articles and 4 abstracts were included for data extraction. All were cohorts or case series, with low risk of bias and moderate to poor level of evidence. Heterogeneity between studies was high, precluding meta-analysis. The reviewed studies reported the safety and efficacy of TAE for the treatment of "knee osteoarthritis"; adhesive capsulitis of the shoulder; tendinopathy/enthesopathy of the knee, shoulder, elbow, and ankle; and cervical myalgia. All TAEs were reported as technically successful without major complications or subsequent serious adverse events, including no reported osteonecrosis, cutaneous ulceration, limb ischemia, cartilage degeneration, or myotendinous injury. TAE significantly reduced pain and improved function for all of the treated conditions, with durable response up to 24 months post procedure. CONCLUSION: TAE appears to be a safe and effective treatment for some types of chronic refractory "musculoskeletal pain". Randomized placebo-controlled studies are necessary to confirm these findings.