Navraj S Nagra

Integrin – Dependent Mechanotransduction in Mechanically Stimulated Human Annulus Fibrosus Cells: Evidence for an Alternative Mechanotransduction Pathway Operating with Degeneration

Intervertebral disc (IVD) cells derived from degenerate tissue respond aberrantly to mechanical stimuli, potentially due to altered mechanotransduction pathways. Elucidation of the altered, or alternative, mechanotransduction pathways operating with degeneration could yield novel targets for the treatment of IVD disease. Our aim here was to investigate the involvement of RGD-recognising integrins and associated signalling molecules in the response to cyclic tensile strain (CTS) of human annulus fibrosus (AF) cells derived from non-degenerate and degenerate IVDs. AF cells from non-degenerate and degenerate human IVDs were cyclically strained with and without function blocking RGD – peptides with 10% strain, 1.0 Hz for 20 minutes using a Flexercell® strain device. QRT-PCR and Western blotting were performed to analyse gene expression of type I collagen and ADAMTS -4, and phosphorylation of focal adhesion kinase (FAK), respectively. The response to 1.0 Hz CTS differed between the two groups of AF cells, with decreased ADAMTS -4 gene expression and decreased type I collagen gene expression post load in AF cells derived from non-degenerate and degenerate IVDs, respectively. Pre-treatment of non-degenerate AF cells with RGD peptides prevented the CTS-induced decrease in ADAMTS -4 gene expression, but caused an increase in expression at 24 hours, a response not observed in degenerate AF cells where RGD pre-treatment failed to inhibit the mechano-response. In addition, FAK phosphorylation increased in CTS stimulated AF cells derived from non-degenerate, but not degenerate IVDs, with RGD pre-treatment inhibiting the CTS – dependent increase in phosphorylated FAK. Our findings suggest that RGD -integrins are involved in the 1.0 Hz CTS – induced mechano-response observed in AF cells derived from non-degenerate, but not degenerate IVDs. This data supports our previous work, suggesting an alternative mechanotransduction pathway may be operating in degenerate AF cells.

Mechanical properties of all-suture anchors for rotator cuff repair

Objectives All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Results Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (se) 17.6) compared with the all-suture anchors (mean 133.1 N se 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm se 2.5 versus 12.5 mm se 0.3; and 29.6 mm se 4.8 versus 17.0 mm se 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1

Single-stage bilateral medial Oxford Unicompartmental Knee Arthroplasty: a case-control study of perioperative blood loss, complications and functional results

BACKGROUND The benefits and risks of a single-stage medial UKA remains a subject of debate because of the theoretically higher risk of complications and specifically blood loss. The aim of this study was to evaluate the perioperative blood loss, risks and the functional results of single-stage bilateral medial Oxford Unicompartmental Knee Arthroplasty (OUKA) compared to a standard unilateral medial OUKA procedure (control group). HYPOTHESIS The blood loss observed during bilateral single-stage medial Oxford UKA is not different from that of the control group. METHODS In this case-control prospective study, fifty patients (100 knees) who underwent single-stage bilateral medial OUKA (study group) were compared to a hundred patients (100 knees) with unilateral medial OUKA (control group), performed by the same surgeon. The real blood loss (in mL of hematocrit at 100%), incidence of blood transfusions, and complication rates were compared. Clinical results were assessed at 6 month and at a two-year minimum follow-up (FU) using IKS, KOOS and OKS scores, in addition to a satisfaction questionnaire. RESULTS Groups were deemed comparable. Concerning blood loss, no significant difference was observed compared to the control group (465mL±225 vs. 396±190; p=0.07). No difference was found, either, between groups regarding the complication rates (p=0.36), nor the clinical results (p=0.61) and patient satisfaction (p=0.23) at last FU. CONCLUSION Single-stage bilateral procedure does not cause increased blood loss compared with controls. Moreover, clinical results were deemed good and excellent in spite of a slightly greater complication rate than those found in the literature but similar to controls. LEVEL OF EVIDENCE Case-control study, level III.

A large chronic pericardial effusion in an ultramarathon runner with anti-CCP positive rheumatoid arthritis

Pericardial effusions arise as an extra-articular manifestation of rheumatoid arthritis (RA). Pericardial effusions are often asymptomatic, particularly in the early phase, but patients are at risk of cardiac tamponade as the effusion progresses. We discuss the case of a 40-year-old male ultramarathon runner with RA who presented with mild pleuritic chest pain and exertional dyspnoea after a recent long-haul flight. Despite a relative tachycardia, his observations were otherwise unremarkable. His blood tests revealed a C-reactive protein (CRP) of 86 mg/L and an anti-cyclic citrullinated peptide (anti-CCP) titre of 360 units/mL. He was initially diagnosed with a pulmonary embolism; however, a large pericardial effusion was found incidentally on CT pulmonary angiogram with over 1500 mL subsequently drained. The patient’s symptoms resolved and CRP normalised 2 weeks later. This unique case illustrates that physically fit patients may physiologically compensate for large pericardial effusions and that arthritic symptoms do not correlate with the severity of extra-articular features in RA.

Athletic Population with Spondylolysis: Review of Outcomes following Surgical Repair or Conservative Management.

Study Design Narrative review. Objective The study aims to critically review the outcomes associated with the surgical repair or conservative management of spondylolysis in athletes. Methods The English literature listed in MEDLINE/PubMed was reviewed to identify related articles using the term “spondylolysis AND athlete.” The criteria for studies to be included were management of spondylolysis in athletes, English text, and no year, follow-up, or study design restrictions. The references of the retrieved articles were also evaluated. The primary outcome was time to return to sport. This search yielded 180 citations, and 25 publications were included in the review. Results Treatment methods were dichotomized as operative and nonoperative. In the nonoperative group, 390 athletes were included. A combination of bracing with physical therapy and restriction of activities was used. Conservative measures allowed athletes to return to sport in 3.7 months (weighted mean). One hundred seventy-four patients were treated surgically. The most common technique was Bucks, using a compression screw (91/174). All authors reported satisfactory outcomes. Time to return to play was 7.9 months (weighted mean). There were insufficient studies with suitably homogenous subgroups to conduct a meta-analysis. Conclusion There is no gold standard approach for the management of spondylolysis in the athletic population. The existing literature suggests initial therapy should be a course of conservative management with thoracolumbosacral orthosis brace, physiotherapy, and activity modification. If conservative management fails, surgical intervention should be considered. Two-sided clinical studies are needed to determine an optimal pathway for the management of athletes with spondylolysis.

A perianal presentation of myeloid sarcoma

Myeloid sarcoma is a rare tumour associated with acute myeloid leucaemia (AML). Infrequently, it can occur in myelodysplastic/myeloproliferative overlap syndrome conditions such as chronic monomyelocytic leucaemia (CMML), where it often heralds the transformation towards an AML. We discuss a rare presentation of myeloid sarcoma in the perianal region of a 51-year-old man, who was seen by various clinicians and treated for haemorrhoids and perianal abscess. There were no gross abnormalities in initial haematological investigations and the patient was systemically well. A histological biopsy demonstrated myeloid sarcoma and bone marrow aspirate, and trephine confirmed CMML transforming to AML. Treatment of myeloid sarcoma is dependent on whether there is associated AML in the bone marrow. Dual chemotherapy with cytarabine and daunorubicin remains the gold standard treatment in these patients. Sending histology samples of atypical lesions when performing incision and drainage procedures is extremely important, as it contributes to early detection of rare and malignant tissue diagnoses.

An Analysis of Post-Operative Haemoglobin in Patients with Fractured Neck of Femur

OBJECTIVE The aim of this study was to analyze the changes of hemoglobin levels in patients undergoing fixation for femoral neck fracture. METHODS Peroperative hemoglobin levels of patients who underwent either dynamic hip screw (DHS) fixation (n=74; mean age: 80 years) or hip hemiarthroplasty (n=104; mean age: 84 years) for femoral neck fracture was monitored. RESULTS There was a statistically and clinically significant mean drop of 31.1 g/L between the preoperative (D0) and postoperative Day 5 Hb levels (p<0.001), with significant reductions from D0 to Day 1 and Day 1 to Day 2 (p<0.001). At each postoperative measurement, DHS patients had lower hemoglobin values over hemiarthroplasty patients (p=0.046). CONCLUSION The decrease in hemoglobin in the first 24-hour postoperative period (D0 to Day 1) is an underestimation of the ultimate lowest value in hemoglobin found at Day 2. Relying on the Day 1 hemoglobin level could be detrimental to patient care. We propose a method of predicting patients likely to be transfused and recommend a protocol for patients undergoing femoral neck fracture surgery to standardize postoperative hemoglobin monitoring.