Aims

Adenosine, lidocaine, and Mg²⁺ (ALM) therapy exerts differential immuno-inflammatory responses in males and females early after anterior cruciate ligament (ACL) reconstruction (ACLR). Our aim was to investigate sex-specific effects of ALM therapy on joint tissue repair and recovery 28 days after surgery.

Aims. Synovial fluid white blood cell (WBC) count and percentage of polymorphonuclear cells (%PMN) are elevated at periprosthetic joint infection (PJI). Leucocytes produce different interleukins (IL), including IL-6, so we hypothesized that synovial fluid IL-6 could be a more accurate predictor of PJI than synovial fluid WBC count and %PMN. The main aim of our study was to compare the predictive performance of all three diagnostic tests in the detection of PJI. Methods. Patients undergoing total hip or knee revision surgery were included. In the perioperative assessment phase, synovial fluid WBC count, %PMN, and IL-6 concentration were measured. Patients were labeled as positive or negative according to the predefined cut-off values for IL-6 and WBC count with %PMN. Intraoperative samples for microbiological and histopathological analysis were obtained. PJI was defined as the presence of sinus tract, inflammation in histopathological samples, and growth of the same microorganism in a minimum of two or more samples out of at least four taken. Results. In total, 49 joints in 48 patients (mean age 68 years (SD 10; 26 females (54%), 25 knees (51%)) were included. Of these 11 joints (22%) were infected. The synovial fluid WBC count and %PMN predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 82%, 97%, 94%, 90%, and 95%, respectively. Synovial fluid IL-6 predicted PJI with sensitivity, specificity, accuracy, PPV, and NPV of 73%, 95%, 90%, 80%, and 92%, respectively. A comparison of predictive performance indicated a strong agreement between tests. Conclusions. Synovial fluid IL-6 is not superior to synovial fluid WBC count and %PMN in detecting PJI. Level of Evidence: Therapeutic Level II. Cite this article: Bone Jt Open 2020;1-12:737–742

There is good scientific rationale to support the use of growth factors to promote musculoskeletal tissue regeneration. However, the clinical effectiveness of platelet-rich plasma (PRP) and other blood-derived products has yet to be proven. Characterization and reporting of PRP preparation protocols utilized in clinical trials for the treatment of musculoskeletal disease is highly inconsistent, and the majority of studies do not provide sufficient information to allow the protocols to be reproduced. Furthermore, the reporting of blood-derived products in orthopaedics is limited by the multiple PRP classification systems available, which makes comparison of results between studies challenging. Several attempts have been made to characterize and classify PRP; however, no consensus has been reached, and there is lack of a comprehensive and validated classification. In this annotation, we outline existing systems used to classify preparations of PRP, highlighting their advantages and limitations. There remains a need for standardized universal nomenclature to describe biological therapies, as well as a comprehensive and reproducible classification system for autologous blood-derived products.

Cite this article: Bone Joint J 2019;101-B:891–896.

Compartment syndrome, a devastating consequence of limb trauma, is characterised by severe tissue injury and microvascular perfusion deficits. We hypothesised that leucopenia might provide significant protection against microvascular dysfunction and preserve tissue viability. Using our clinically relevant rat model of compartment syndrome, microvascular perfusion and tissue injury were directly visualised by intravital video microscopy in leucopenic animals. We found that while the tissue perfusion was similar in both groups (38.8% (standard error of the mean (sem) 7.1), 36.4% (sem 5.7), 32.0% (sem 1.7), and 30.5% (sem 5.35) continuously-perfused capillaries at 45, 90, 120 and 180 minutes compartment syndrome, respectively versus 39.2% (sem 8.6), 43.5% (sem 8.5), 36.6% (sem 1.4) and 50.8% (sem 4.8) at 45, 90, 120 and 180 minutes compartment syndrome, respectively in leucopenia), compartment syndrome-associated muscle injury was significantly decreased in leucopenic animals (7.0% (sem 2.0), 7.0%, (sem 1.0), 9.0% (sem 1.0) and 5.0% (sem 2.0) at 45, 90, 120 and 180 minutes of compartment syndrome, respectively in leucopenia group versus 18.0% (sem 4.0), 23.0% (sem 4.0), 32.0% (sem 7.0), and 20.0% (sem 5.0) at 45, 90, 120 and 180 minutes of compartment syndrome in control, p = 0.0005). This study demonstrates that the inflammatory process should be considered central to the understanding of the pathogenesis of cellular injury in compartment syndrome.

Cite this article: Bone Joint J 2015;97-B:539–43

We assessed the predictive value of the macroscopic and detailed microscopic appearance of the coracoacromial ligament, subacromial bursa and rotator-cuff tendon in 20 patients undergoing subacromial decompression for impingement in the absence of full-thickness tears of the rotator cuff. Histologically, all specimens had features of degenerative change and oedema in the extracellular matrix. Inflammatory cells were seen, but there was no evidence of chronic inflammation. However, the outcome was not related to cell counts.

At three months the mean Oxford shoulder score had improved from 29.2 (20 to 40) to 39.4 (28 to 48) (p < 0.0001) and at six months to 45.5 (36 to 48) (p < 0.0001). At six months, although all patients had improved, the seven patients with a hooked acromion had done so to a less extent than those with a flat or curved acromion judged by their mean Oxford shoulder scores of 43.5 and 46.5 respectively (p = 0.046). All five patients with partial-thickness tears were within this group and demonstrated less improvement than the patients with no tear (mean Oxford shoulder scores 43.2 and 46.4, respectively, p = 0.04). These findings imply that in the presence of a partial-thickness tear subacromial decompression may require additional specific treatment to the rotator cuff if the outcome is to be improved further.

Leucocytes are white blood cells that help the body fight against bacteria, viruses and tumour cells. However, the activity of leucocytes has been implicated in other clinically important inflammatory conditions such as ischaemic heart disease, stroke, and during cardio-aortic and orthopaedic surgery. The main objectives of this study was to optimise methods for the isolation of leucocyte subpopulations (neutrophils and monocytes), and to assess in vitro the effects of PMA and fMLP on markers of leucocyte adhesion (CD11b, CD62L) and activation (intracellular hydrogen peroxide) (n=10). Leucocyte subpopulations were labelled by incubation with fluorescein isothiocya-nate (FITC) conjugated anti-human CD11b and CD62L antibodies. The cell surface expression of these labelled adhesion molecules were measured by flow cytometry. Intracellular production of hydrogen peroxide by neutrophils and monocytes was measured by flow cytometry, using the fluorochrome dichloroflurorescin diacetate (DCFH-DA). These were visualised by Immunofluorescence microscopy. During this study, methods of isolating leucocyte subpopulations from whole blood were optimised. This ensured that these cells were isolated with consistently high yields, purity and with no changes in cellular function. Following incubation with PMA and fMLP, neutrophils and monocytes displayed an increase in CD11b cell surface expression; a decrease in CD62L cell surface expression; and increased leucocyte activation. Leucocyte activation was represented by the intracellular production of hydrogen peroxide. In conclusion this study confirms that both PMA and fMLP have an intrinsic effect on markers of leucocyte function. These findings are in agreement with previous studies performed

Leucocytes represent a very important host defence against a number of invading pathogens and neoplasia. However, the activity of phagocytic leucocytes has been heavily implicated in the development of ischaemia-reperfusion injury, and as an aetiological factor in the pathology of other clinically important inflammatory conditions. Ischaemia-reperfusion injury occurs in diseases such as stroke and ischaemic heart disease (IHD), and during surgical procedures such as orthopaedic surgery. Investigations presented here employed a model of tourniquet-induced forearm ischaemia-reperfusion injury to investigate the effect on leucocyte adhesion and trapping (n=20). Neutrophil and monocyte leucocyte subpopulations were isolated by density gradient centrifugation techniques. Neutrophil and monocyte cell surface expression of the adhesion molecule CD11b was measured by labelling with fluorescent anti-CD11b monoclonal antibody via flow cytometry. Plasma concentrations of the soluble intercellular adhesion molecule-1 (sICAM-1) and soluble L-selectin (sL-selectin) adhesion molecules were measured using commercially available ELISA kits. Leucocyte trapping was investigated by measuring the concentration of leukocytes in venous blood leaving the arm. During ischaemia-reperfusion there was an increase in CD11b expression on neutrophils (p=0.040) and monocytes (p=0.049), a decrease in sL-selectin (p=0.387) and sICAM-1 (p=0.089) concentrations, and a decrease in peripheral blood leucocyte concentration (p=0.019). Evidence of increased leucocyte adhesion and trapping during ischaemia-reperfusion injury was supported by an increase in CD11b cell surface expression of neutrophils and monocytes. CD11b is expressed on phagocytic leucocytes and binds to ICAM-1 expressed on the surface of vascular endothelium. This increased expression of CD11b on leucocytes may therefore play a central role as the mechanism by which leucocyte trapping in the microcirculation occurs. The measured decrease in plasma concentration of sICAM-1 and sL-selectin suggests that these adhesion molecules retain their functional activity, and may bind to their corresponding cell surface ligands. It is therefore reasonable to believe that ICAM-1 expressed on the endothelium and L-selectin expressed on leucocytes is also binding to their corresponding cell surface ligands. A decrease in the number of leucocytes in the peripheral circulation may be due to increased trapping of leucocytes in the microcirculation. When leucocytes become trapped their concentration in blood leaving the microcirculation decreases, resulting in the measured decrease in leucocyte concentration. In conclusion, this study confirms the important role of leucocytes during ischaemia-reperfusion injury, which could allow for the possibility of future research that may provide therapeutic intervention for inflammatory conditions

We have studied cellular and vascular changes in different stages of full thickness tears of the rotator cuff. We examined biopsies from the supraspinatus tendon in 40 patients with chronic rotator cuff tears who were undergoing surgery and compared them with biopsies from four uninjured subscapularis tendons. Morphological and immunocytochemical methods using monoclonal antibodies directed against leucocytes, macrophages, mast cells, proliferative and vascular markers were used.

Histological changes indicative of repair and inflammation were most evident in small sized rotator cuff tears with increased fibroblast cellularity and intimal hyperplasia, together with increased expression of leucocyte and vascular markers. These reparative and inflammatory changes diminished as the size of the rotator cuff tear increased. Marked oedema and degeneration was seen in large and massive tears, which more often showed chondroid metaplasia and amyloid deposition. There was no association between the age of the patient and the duration of symptoms. In contrast, large and massive tears showed no increase in the number of inflammatory cells and blood vessels.

Small sized rotator cuff tears retained the greatest potential to heal, showing increased fibroblast cellularity, blood vessel proliferation and the presence of a significant inflammatory component. Tissue from large and massive tears is of such a degenerative nature that it may be a significant cause of re-rupture after surgical repair and could make healing improbable in this group.