Background
Independent of HIV infection, extrapulmonary TB (EPTB) risk is increased in women, persons of black race or foreign birth, and by genetic variants in vitamin D receptor (VDR), interleukin-1 beta (IL-1β), and toll-like receptor (TLR)-2; functional correlates are unclear. We evaluated macrophage expression of VDR, TLR2, cathelicidin, and TNF-α, and production of IL-1β in HIV-seronegative persons with previous EPTB, previous pulmonary TB, latent
M. tuberculosis
infection, and uninfected TB contacts. Persons with previous pleural TB were excluded due to enhanced immune responses at the site of disease.
Methods
Macrophages were stimulated with TLR-2 agonist
M. tuberculosis
lipoprotein (LpqH), live and gamma-irradiated
M. tuberculosis
.
Results
M. tuberculosis
– infected macrophages from persons with previous EPTB had increased VDR expression (29.17 relative value unit increase in median expression vs. uninfected contacts, after adjusting for foreign-born status;
P
= 0.02). Macrophages from persons with previous EPTB had a 38.88 μg/mL increase in median IL-1β production after stimulation with LpqH compared to uninfected contacts (
P
= 0.01); the effect was similar (44.99 μg/mL) but not statistically significant after controlling for foreign-born status. Median 25-hydroxyvitamin D levels were low but not significantly different between groups.
Conclusions
There was increased macrophage expression of VDR after stimulation with live
M. tuberculosis
in persons with previous extrapulmonary TB. If post-treatment VDR expression reflects expression prior to disease, it may identify persons at risk for extrapulmonary TB.
Electronic supplementary material
The online version of this article (10.1186/s12879-019-3958-7) contains supplementary material, which is available to authorized users.
Context: Injury to the anterior cruciate ligament (ACL) is among the most common orthopaedic injuries, and reconstruction of a ruptured ACL is a common orthopaedic procedure. In general, surgical intervention is necessary to restore stability to the injured knee, and to prevent meniscal damage. Along with surgery, intense postoperative physical therapy is needed to restore function to the injured extremity. ACL reconstruction (ACLR) has been the standard of care in recent decades, and advances in surgical technology have reintroduced the prospect of augmented primary repair of the native ACL via a variety of methods. Evidence Acquisition: A search of PubMed database of articles and reviews available in English was performed through 2020. The search terms ACLR, anterior cruciate ligament repair, bridge enhanced acl repair, suture anchor repair, dynamic intraligamentary stabilization, internal bracing, suture ligament augmentation, and internal brace ligament augmentation were used. Study Design: Clinical review. Level of Evidence: Level 5. Results: No exact consensus exists on effective rehabilitation protocols after ACL repair techniques, as the variation in published protocols seem even greater than the variation in those for ACLR. For some techniques such as internal bracing and dynamic interligamentary stabilization, it is likely permissible for the patients to progress to full weightbearing and discontinue bracing sooner. However, caution should be applied with regard to earlier return to sport than after ACLR as to minimize risk for retear. Conclusion: More research is needed to address how physical therapies must adapt to these innovative repair techniques. Until that is accomplished, we recommend that physical therapists understand the differences among the various ACL surgery techniques discussed here and work with the surgeons to develop a rehabilitation protocol for their mutual patients. Strength of Recommendation Taxonomy (SORT): C.
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