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BackgroundWhile magnetic resonance imaging contrast-enhancing lesions represent an excellent screening tool for disease-modifying treatments in relapsing–remitting multiple sclerosis (RRMS), this biomarker is insensitive for testing therapies against compartmentalized inflammation in progressive multiple sclerosis (MS). Therefore, alternative sensitive outcomes are needed. Using machine learning, clinician-acquired disability scales can be combined with timed measures of neurological functions such as walking speed (e.g. 25-foot walk; 25FW) or fine finger movements (e.g. 9-hole peg test; 9HPT) into sensitive composite clinical scales, such as the recently developed combinatorial, weight-adjusted disability scale (CombiWISE). Ideally, these complementary simplified measurements of certain neurological functions could be performed regularly at patients’ homes using smartphones.ObjectivesWe asked whether tests amenable to adaptation to smartphone technology, such as finger and foot tapping have comparable sensitivity and specificity to current non-clinician-acquired disability measures.ResultsWe observed that finger and foot tapping can differentiate RRMS and progressive MS in a cross-sectional study and can also measure yearly and two-year disease progression in the latter, with better power (based on z-scores) in comparison to currently utilized 9HPT and 25FW.ConclusionsReplacing the 9HPT and 25FW with simplified tests broadly adaptable to smartphone technology may enhance the power of composite scales for progressive MS.

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In this study, we examine the contributions of periprosthetic impingement to a seldom recognized source of PE damage resulting in gouging, abrasion, and severe localized damage in cemented and cementless total knee replacement. One hundred sixty two tibial components of 34 different designs in a retrieval collection were examined. The presence and location of abrasive wear to the nonarticulating edges of the insert were measured, with representative specimens examined using SEM. Significant abrasive wear was observed in 35% of the retrievals with cemented femoral components and 25% from noncemented components. Within the group of worn inserts, abrasive scars were seen with a frequency of 75% on the extreme medial edge, 20% on the extreme lateral edge, 26% on the posteromedial edge, and 16% on the posterolateral edge. The role of extraarticular impingement in this damage mode was confirmed by examination of retrieved femoral components with overhanging cement or embedded osteophytes. In the majority of cases, this complication may be avoided by careful removal of excess cement and extracortical osteophytes.

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ObjectiveIt was previously demonstrated that daclizumab therapy normalizes cellular cerebrospinal fluid (CSF) abnormalities typical of multiple sclerosis (MS) in the majority of treated patients. However, CSF cells represent only the mobile portion of intrathecal immune responses. Therefore, we asked whether daclizumab also reverses compartmentalized inflammation and if not, whether residual inflammation correlates with clinical response to the drug.MethodsForty MS patients treated with an intravenous or subcutaneous injection of daclizumab were followed for up to 16 years in two open‐label clinical trials. MRI contrast‐enhancing lesions (CELs), clinical scales, and CSF biomarkers quantified residual disease.ResultsRapid decreases in CELs, sustained throughout the observation period, were observed with daclizumab treatment. Daclizumab therapy induced modest but statistically significant (P < 0.0001) decreases in CSF levels of T‐cell activation marker CD27 and IgG index. Interleukin 2 (IL‐2) CSF levels increased from baseline levels during treatment, consistent with reduced IL‐2 consumption by T cells, as a consequence of daclizumab's saturation of high‐affinity IL‐2 receptors. CSF levels of IL‐12p40, chitinase‐3‐like protein‐1 (CHI3L1), chemokine C‐X‐C motif ligand 13, and neurofilament light chain (NFL) were also significantly reduced by daclizumab. Among them, inhibition of CHI3L1 correlated with inhibition of NFL and with lack of disease progression.InterpretationThese observations confirm daclizumab's direct pharmacodynamics effects on immune cells within central nervous system tissues and identify inhibition of CSF biomarkers of myeloid lineage as a stronger determinant of reduction in clinical MS activity than inhibition of biomarkers of adaptive immunity.

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BackgroundWe evaluated effects of botulinum toxin A (Botox) and cast immobilization on tendon healing in a rat model. Injection of Botox into rat supraspinatus was hypothesized to reduce muscle active force and improved healing.MethodsEighty-four supraspinatus tendons were surgically transected and repaired in 42 Sprague-Dawley rats (transosseous technique). After repair, supraspinatus muscle was injected with saline or Botox (3 or 6 U/kg). Half the shoulders were cast-immobilized for the entire postoperative period; half were allowed free cage activity. Histology was examined at 2, 4, 8, and 12 weeks. A healing zone cross-sectional area was measured, and biomechanical testing of repair strength and tendon viscoelastic properties was conducted at 4 and 12 weeks.ResultsBotox alone and cast immobilization alone exhibited increased ultimate load compared with controls (saline injection, no immobilization) at 4 weeks. No difference in ultimate load occurred between Botox-only and cast-only groups. At 12 weeks, the Botox (6 U/kg) plus cast immobilization group was significantly weakest (p < 0.05). A trend was shown toward decreased healing zone cross-sectional areas in casted groups.ConclusionsSupraspinatus Botox injection after rotator cuff repair might help protect the repair. However, cast immobilization plus Botox administration is harmful to rotator cuff healing in a rat tendon model.