Antigen presentation by monocytes and monocyte-derived cells

Monocytes are circulating mononuclear phagocytes with a fundamental capacity to differentiate into macrophages. This differentiation can, in the presence of the right environmental cues, be re-directed instead to dendritic cells (DCs). Recent advances have been made in understanding the role of monocytes and their derivatives in presenting antigen to drive immune responses, and we review this topic herein. We briefly discuss the heterogeneity of monocytes in the blood and subsequently raise the possibility that one of the major monocyte phenotypes in the blood corresponds with a population of 'blood DCs' previously proposed to drive T-independent antibody reactions in the spleen. Then we evaluate the role of monocytes in T-dependent immunity, considering their role in acquiring antigens for presentation before exiting the bloodstream and their ability to differentiate into macrophages versus antigen-presenting DCs. Finally, we review recent literature on the role of monocyte-derived cells in cross-presentation and discuss the possibility that monocyte-derived cells participate critically in processing antigen for cross-priming, even if they do not present that antigen to T cells themselves.     

Clinical outcome of anterior cruciate ligament reconstruction with quadrupled hamstring tendon graft and bioabsorbable interference screw fixation

BACKGROUND: To date, there has been no publication of clinical follow-up data on patients who have undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable screw fixation. PURPOSE: To report the results of quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation. STUDY DESIGN: Retrospective review. METHODS: Sixty-five patients (66 knees) were retrospectively identified by chart review as having undergone quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation with a minimum 2-year follow-up. RESULTS: Data were collected on 48 knees in 47 patients (73%) at an average 30.2 months (range, 24 to 43) after surgery. Thirty-six patients (37 knees) returned for clinical evaluation (56% return) and subjective follow-up only was obtained in 11 patients (17%). The mean Lysolm knee score was 91 (range, 45 to 98), with a mean of 97 for the uninvolved knee. The mean Tegner activity score was 5.7 (range, 3 to 7). The KT-1000 arthrometer mean side-to-side difference for manual maximum displacement was 2.03 mm (range, -1 to 8). The mean International Knee Documentation Committee knee score was 83 (range, 47 to 100). Patients who underwent associated partial meniscectomy or meniscal repair had significantly lower International Knee Documentation Committee scores than patients without associated procedures (P < 0.01). CONCLUSIONS: Quadrupled hamstring tendon autograft anterior cruciate ligament reconstruction with bioabsorbable interference screw fixation is comparable with other methods of anterior cruciate ligament reconstruction in terms of patient satisfaction, knee stability, and function.     

Longitudinal Model of Periprosthetic Joint Infection in the Rat

The majority of periprosthetic joint infections occur shortly after primary joint replacement (<3 months) and require the removal of all implant components for the treatment period (~4 months). A clinically relevant animal model of periprosthetic infection should, therefore, establish an infection with implant components in place. Here, we describe a joint replacement model in the rat with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components inoculated at the time of surgery by methicillin-sensitive Staphylococcus aureus (S. aureus), which is one of the main causative microorganisms of periprosthetic joint infections. We monitored the animals for 4 weeks by measuring gait, weight-bearing symmetry, von Frey testing, and micro-CT as our primary endpoint analyses. We also assessed the infection ex vivo using colony counts on the implant surfaces and histology of the surrounding tissues. The results confirmed the presence of a local infection for 4 weeks with osteolysis, loosening of the implants, and clinical infection indicators such as redness, swelling, and increased temperature. The utility of specific gait analysis parameters, especially temporal symmetry, hindlimb duty factor imbalance, and phase dispersion was identified in this model for assessing the longitudinal progression of the infection, and these metrics correlated with weight-bearing asymmetry. We propose to use this model to study the efficacy of using different local delivery regimens of antimicrobials on addressing periprosthetic joint infections. Statement of clinical significance: We have established a preclinical joint surgery model, in which postoperative recovery can be monitored over a multi-week course by assessing gait, weight-bearing, and allodynia. This model can be used to study the efficacy of different combinations of implant materials and medication regimens. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1101-1112, 2020     

An allogenic cell-based implant for meniscal lesions

BACKGROUND: Meniscal tears in the avascular zones do not heal. Although tissue-engineering approaches using cells seeded onto scaffolds could expand the indication for meniscal repair, harvesting autologous cells could cause additional trauma to the patient. Allogenic cells, however, could provide an unlimited amount of cells. HYPOTHESIS: Allogenic cells from 2 anatomical sources can repair lesions in the avascular region of the meniscus. STUDY DESIGN: Controlled laboratory study. METHODS: Both autologous and allogenic chondrocytes were seeded onto a Vicryl mesh scaffold and sutured into a bucket-handle lesion created in the medial menisci of 17 swine. Controls consisted of 3 swine knees treated with unseeded implants and controls from a previous experiment in which 4 swine were treated with suture only and 4 with no treatment. Menisci were harvested after 12 weeks and evaluated histologically for new tissue and percentage of interface healing surface; they were also evaluated statistically. RESULTS: The lesions were closed in 15 of 17 menisci. None of the control samples demonstrated healing. Histologic analysis of sequential cuts through the lesion showed formation of new scar-like tissue in all experimental samples. One of 8 menisci was completely healed in the allogenic group and 2 of 9 in the autologous group; the remaining samples were partially healed in both groups. No statistically significant differences in the percentage of healing were observed between the autologous and allogenic cell-based implants. CONCLUSION: Use of autologous and allogenic chondrocytes delivered via a biodegradable mesh enhanced healing of avascular meniscal lesions. CLINICAL RELEVANCE: This study demonstrates the potential of a tissue-engineered cellular repair of the meniscus using autologous and allogenic chondrocytes.     

Case for staged thyroidectomy

Recent modifications in the management of well‐differentiated thyroid cancer have resulted in significant alterations in clinical approach. Utilizing a series of preoperative and postoperative risk factors involving both the patient and the disease pathology, we offer the term “staged thyroidectomy” to help organize these risk factors for patients and the endocrine team to optimize management. This approach is intended to incorporate our latest nuanced understanding of certain endocrine pathology and may serve to optimize patient outcomes.     

Evaluation of decline in serum venom-specific IgE as a criterion for stopping venom immunotherapy

During a 7-year period, venom immunotherapy has been stopped in 57 patients because of a fall in IgE antibody titers to insignificant levels (RAST less than 10% STD). All patients had a history of venom anaphylaxis and elevated venom-specific IgE before therapy. Maintenance doses of 50 micrograms were administered every 4 to 6 weeks; 30 patients received yellow jacket venom, and 16 patients received honeybee venom only. Therapy was stopped after treatment from 1 to 8 years (mean 2.8 years). Repeat skin tests demonstrated an average two-log decrease in sensitivity; 35 of 55 tests remained positive at venom concentrations of less than or equal to 0.1 micrograms/ml. There were 55 re-stings in 24 patients, occurring from 3 months to 5 years after cessation of therapy, resulting in three systemic reactions. One patient, previously treated with bee venom, reacted to a yellow jacket sting. These re-sting reactors also had tolerated several other stings after therapy was stopped. Thus, the two actual reactions represent a "failure" rate of 8% per patient and 4% per sting, compared to reaction rates of 27% and 17% in patients who stopped therapy without physician advice. These data suggest that this criterion may be reliable for stopping therapy. However, subsequent tolerated re-stings may require continued patient evaluation.     

Operative treatment of chance injuries in the paediatric population

Purpose

Chance fractures are an uncommon spine injury in the paediatric population. As such there is a relative paucity of evidence in the literature to guide management decisions. We present our single centre experience in the operative management of these injuries.

Methods

All patients presenting to a tertiary paediatric trauma centre between 2000 and 2008 were included. Retrospective analysis of clinical (SRS-22 and Oswestry) and radiological outcomes was undertaken.

Results

Twelve patients underwent operative stabilization of a Chance type injury. Radiological and clinical outcome measures demonstrated excellent outcomes in the majority of patients with no significant complications.

Conclusions

Operative management of paediatric chance injuries with instrumentation results in excellent clinical and radiological outcomes.