Our study has determined the response of C-reactive protein (CRP) after total knee replacement (TKR). The peak level occurs on the second postoperative day and is significantly greater than that after total hip replacement (THR). The level returns to normal at similar times after both procedures. The physiological response to TKR as measured by the area under the CRP/ time curve is significantly greater than that after THR. Rising CRP levels after the third postoperative day may indicate a complication of surgery such as infection

Monomeric C reactive protein (mCRP) presents important proinflammatory effects in endothelial cells, leukocytes, or chondrocytes. However, CRP in its pentameric form exhibits weak anti-inflammatory activity. It is used as a biomarker to follow severity and progression in infectious or inflammatory diseases, such as intervertebral disc degeneration (IVDD). This work assesses for the first time the mCRP effects in human intervertebral disc cells, trying to verify the pathophysiological relevance and mechanism of action of mCRP in the etiology and progression of IVD degeneration.

We demonstrated that mCRP induces the expression of multiple proinflammatory and catabolic factors, like nitric oxide synthase 2 (NOS2), cyclooxygenase 2 (COX2), matrix metalloproteinase 13 (MMP13), vascular cell adhesion molecule 1 (VCAM1), interleukin (IL)-6, IL-8, and lipocalin 2 (LCN2), in human annulus fibrosus (AF) and nucleus pulposus (NP) cells. We also showed that nuclear factor-κβ (NF-κβ), extracellular signal-regulated kinase 1/2 (ERK1/2), and phosphoinositide 3-kinase (PI3K) are at play in the intracellular signaling of mCRP.

Our results indicate that the effect of mCRP is persistent and sustained, regardless of the proinflammatory environment, as it was similar in healthy and degenerative human primary AF cells. This is the first article that demonstrates the localization of mCRP in intravertebral disc cells of the AF and NP and that provides evidence for the functional activity of mCRP in healthy and degenerative human AF and NP disc cells.

To determine risk factors of infection in total knee arthroplasty. This descriptive study was conducted in the Department of Orthopedics for a duration of three years from January 2016 to January 2019. All patients undergoing primary total knee replacement were included in the study. Exclusion criteria were all patients operated in another hospital and revision total knee replacement. All patients were followed up at 2, 4, 8, 12 and 24 weeks post-operatively. Signs of inflammation and inflammatory markers such as total leukocyte count (TLC), C-reactive protein (CRP) and ESR were measured. Risk factors like age, body mass index (BMI), ASA, co-morbid conditions were also noted. A total of 78 patients underwent primary unilateral Total Knee Replacement (TKR) during the study period. Of these, 30 (34.09%) were male and 48 (61.54%) female patients. Mean age of patients was 68.32 ± 8.54 years. Average BMI 25.89 Kg/m2 .Osteoarthritis was the pre-dominant cause of total knee replacement (94.87%). Among co-morbid factors 33.33% were diabetic, 28.20% having ischemic heart disease and 12.82% with chronic lung disease. Upon anaesthesia fitness pre-operatively, 91.02% patients had an American society of anaesthesiologist score (ASA) between 0–2 while 07 (8.97%) between 3- 5. Average duration of surgery was 85.62± 4.11 minutes. 6.41% cases got infected. In majority of the infected cases (60%), Staphylococcus aureus was the infective organism. Diabetes Mellitus (p=0.01) and Obesity (p=0.02) had a significant relation to post-operative infection. Pre-operative risk evaluation and prevention strategies along with early recognition of infection and control can greatly reduce the risk of joint infection post-TKR which will not only improve the mobility of patient but also its morbidity and mortality as well. Key Words:. C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR), Staphylococcus aureus, Total Knee Arthroplasty (TKA)

Aim. This study aims to define the normal postoperative presepsin kinetics in patients undergoing primary cementless total hip replacement (THR). Methods. Patients undergoing primary cementless THR at our Institute were recruited. At enrollment anthropometric data, smocking status, osteoarthritis stage according to Kellgren and. Lawrence, Harris Hip Score (HHS), drugs assumption and comorbidities were recorded. All the patients underwent serial blood tests, including complete blood count, presepsin (PS) and C-Reactive Protein (CRP) 24 hours before arthroplasty and at 24-, 48-, 72- and 96-hours postoperatively and at 3-, 6- and 12-months follow-up. Statistical analysis was performed with SPSS v25.0 (SPSS Inc, Chicago, IL, USA). The Wilcoxon and Kruskal-Wallis tests followed by the Dunn multiple comparison post hoc tests were carried out. Correlations between PS, CRP and TOT were assessed using the Spearman rank correlation coefficient. P values below 0.05 were considered significant. Results and conclusion. A total of 96 patients were recruited (51 female; 45 male; mean age= 65.74±5.58) were recruited. The mean PS values were: 137.54 pg/ml at baseline, 192.08 pg/ml at 24-hours post-op; 254.85 pg/ml at 48-hours post-op; 259 pg/ml at 72-hours post-op; 248.6 pg/ml at 96-hour post-op; 140.52 pg/ml at 3-months follow-up; 135.55 pg/ml at 6-months follow-up and 130.11 pg/ml at 12-months follow-up. In two patients (2.08%) a soft-tissue infection was observed; in these patients higher levels (>350pg/mL) were recorded at 3-months follow-up. The lack of a presepsin decrease at 96 hours post-operatively should be a predictive factor of infection

Osteoarthritis is a slowly progressive disease which includes the intervention of several cytokines and macrophage metalleinoproteinases reaction, leading to the degradation of the local cartilage but also having an impact on the serum acute phase proteins (APPs). Subsequently, biomarkers seem to be essential to estimate its progression and the need for any surgical intervention such as total arthroplasty, but also can be used as therapeutic agents. Recently, among APPs, fetuin-A drew attention regarding its possible anti-inflammatory role in animal models but also as a therapeutic agent in the inflammatory joint disease in clinical trials. The purpose of this study is to investigate the possible attenuating role of the intra-articular administration of Fetuin-A in post-traumatic induced secondary osteoarthritis in rats, and also its effect on the systematic levels of IL-2,4,7, BMPs 2,4,7, CRP and Fetuin-A. 30 male Sprague Dawley rats were separated in two groups where post-traumatic osteoarthritis was induced surgically by Anterior Cruciate Ligament Transection and the transection of the Medial Collateral Ligament of the right knee. In the Control Group, only surgical intervention took place. In Fetuin Group, along with the induction of osteoarthritis, a single dose of bovine fetuin was administrated intra-articularly intra-operatively in 5 and 8 weeks of the experimental protocol. Both groups were examined for 8 weeks. The levels of interleukins, bone morphogenetic proteins, Fetuin-A and C-Reactive Protein were evaluated by ELISA of peripheral blood in three time periods: preoperatively, 5 and 8 weeks post-operatively. Knee osteoarthritic lesions were classified according to Osteoarthritis Research Society International Grading System and Modified Mankin Score, by histologic examination. IL-2 levels were significantly decreased in the Fetuin Group. No statistical difference was signed on the levels of IL-7, BMP-2,4,7 and Fetuin-A between the two groups. CRP levels were significantly increased in the Fetuin Group in 5 weeks of the experiment. Fetuin Group signed better scores according to the OARSI classification system and Modified Mankin Score, without any statistical significance. Intra-articular administration of Fetuin-A restrictively affected the progression of post-traumatic arthritis in rats, as only the levels of IL-2 were decreased as well as limited osteoarthritic lesions were observed on the Fetuin Group

Chronic osteomyelitis is historically treated in a two stage fashion with antibiotic-loaded polymethylmethacrylate (PMMA) as local antibacterial therapy. However, two-stage surgeries are associated with high morbidity, long hospitalization and high treatment costs. In recent years new biomaterials were developed that allow to change this treatment algorithm. S53P4 bioactive glass is such a novel biodegradable antibacterial bone graft substitute that enables a one-stage surgery in local treatment of chronic osteomyelitis. This study aimed to explore the eradication of infection and bone healing capacities of S53P4 bioactive glass in clinical practice. In this prospective longitudinal outcome study, clinical applicability of S53P4 bioactive glass in treatment of patients with chronic osteomyelitis was assessed. All patients with clinically, haematologically and radiologically evident chronic osteomyelitis were included. All patients were treated with an extensive debridement surgery, S53P4 bioactive glass implantation and systemic antibiotic administration. Primary endpoint of this study is eradication of infection. During follow-up eradication was analysed based on clinical outcomes, blood samples (inflammatory parameters) and radiological outcomes. The secondary endpoint, bone healing, is assessed using conventional radiographic images of the treated region. Between 2011 and 2016, 25 patients were included in this study, with a mean follow-up of 23 months (range 4 – 57). Hospital stay was short with a mean of 18 days (range 4 – 40) and patients required an average of 1,4 surgeries (range 1 – 4). The inflammatory parameter C-reactive protein (CRP) showed a normalization after a mean duration of 46 days (range 0 – 211). At the end of follow-up haematological and clinical outcomes showed eradication of infection in 24 (96%) of all patients. Radiologically none of all patients showed persisting signs of infection and bone healing was observed in 22 (88%) patients based on changes on conventional radiographic images. One patient had a persistent infection without any bone healing, this patient had an infected non-union prior to surgery. There were two other patients with an initial infected non-union fracture which was not consolidated at last follow-up, although they had successful infection treatment. Another patient had a femoral fracture after surgery that needed additional surgery which did not interfere with eradication of infection. Four (16%) of all patients had initial wound healing problems related to compromised skin and/or soft tissue prior to surgery. Based on the results of our clinical experience, S53P4 bioactive glass can successfully be used in a one-stage procedure for treatment of chronic osteomyelitis. Eradication of infection was successful in almost all patients and so far no patients required a second surgery due to infection recurrence. Bone healing (incorporation of the bioactive glass) was seen in all patients except for the patients with an initial infected non-union fracture. As a consequence of these results, we changed our institutional protocol for treatment of chronic osteomyelitis to a one-stage approach instead of a two-step approach

The treatment of chronic osteomyelitis requires both appropriate surgical and antibiotic management. Prolonged intravenous antibiotic therapy followed by oral therapy is widely adopted. Despite this, the long-term recurrence rate is around 20% to 30%. The aim of this cohort study was to examine the effectiveness of surgical marginal resection in combination with local application of antibiotics (Collatamp G - gentamicin in a collagen fleece). Post-operatively this was followed by a short course of intravenous antibiotics, then oral antibiotics, to 6 weeks in total. A cohort of 50 patients from a 10-year period, 2000 to 2010, with chronic osteomyelitis was identified. Most were male (n= 35, 70%) and the average age is 40.9 years (SD 15.9). The mean follow-up duration was 3.2 years (SD 1.8). The average length of admission was 9.8 days (SD 11.4). 6 patients (12%) suffered recurrence of infection requiring further treatment. We used the Cierny and Mader classification to further stratify the patients. ‘A’ hosts had a shorter duration of admission (7.1 days) than ‘B’ hosts (12.3 days). There was no significant difference between recurrence rates of ‘A’ and ‘B’ hosts. Where available, we found pre-operative C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) levels had no correlation with disease recurrence. Disease-free probability for this cohort compared favourably with a cohort treated with prolonged systemic and oral antibiotics (Simpson and colleagues, JBJS Br 2001). We believe local administration of gentamicin in a collagen fleece is a useful component in the management of chronic osteomyelitis

Background. Establishing the diagnosis in a child presenting with an atraumatic limp can be challenging. There is particular difficulty distinguishing septic arthritis (SA) from transient synovitis (TS) and consequently clinical prediction algorithms have been devised to differentiate the conditions using the presence of fever, raised erythrocyte sedimentation rate (ESR), raised white cell count (WCC) and inability to weight bear. Within Europe measurement of the ESR has largely been replaced with assessment of C-reactive protein (CRP) as an acute phase protein. We have evaluated the utility of including CRP in a clinical prediction algorithm to distinguish TS from SA. Method. All children with a presentation of ‘atraumatic limp’ and a proven effusion on hip ultrasound between 2004 and 2009 were included. Patient demographics, details of the clinical presentation and laboratory investigations were documented to identify a response to each of four variables (Weight bearing status, WCC >12,000 cells/m3, CRP >20mg/L and Temperature >38.5 degrees C. The definition of SA was based upon microscopy and culture of the joint fluid collected at arthrotomy. Results. 311 hips were included within the study. Of these 282 were considered to have transient synovitis. 29 patients met criteria to be classified as SA based upon laboratory assessment of the synovial fluid. The introduction of CRP eliminated the need for a four variable model as the use of two variables (CRP and weight bearing status) had similar efficacy. An algorithm that indicated a diagnosis of SA in individuals who could not weight-bear and who had a CRP >20mg/L correctly classified SA in 94.8% individuals, with a sensitivity of 75.9%, specificity of 96.8%, positive predictive value of 71.0%, and negative predictive value of 97.5%. CRP was a significant independent predictor of septic arthritis. Conclusions. CRP was a strong independent risk factor of septic arthritis, and its inclusion within a regression model simplifies the diagnostic algorithm, such that a two-variable model correctly classified 95% individuals with SA. Nevertheless, this and similar algorithms are generally more reliable in excluding SA, than confirming SA, and therefore a clinician's acumen remains important in identifying SA in those individuals with a single abnormal variable

Summary. Pyogenic spondylodiscitis is an uncommon but severe spinal infection. In majority of cases treatment is based on intravenous antibiotics and rigid brace immobilization. Posterior percutaneous spinal instrumentation is a safe alternative procedure in relieving pain, preventing deformity and neurological compromise. Introduction. Pyogenic spondylodiscitis (PS) is an uncommon but severe spinal infection. Patients affected by a non-complicated PS and treatment is based on intravenous antibiotics and rigid brace immobilization with a thoracolumbosacral orthosis (TLSO) suffices in most cases in relieving pain, preventing deformity and neurological compromise. Since January 2010 we started offering patients percutaneous posterior screw-rod instrumentation as alternative approach to TLSO immobilization. The aim of this study was to evaluate safety and effectiveness of posterior percutaneous spinal instrumentation for single level lower thoracic (T9-T12) or lumbar pyogenic spondylodiscitis. Materials and Methods. Retrospective cohort analysis on 27 patients diagnosed with PS who were offered to choose between 24/7 TLSO rigid bracing for 3 to 4 months and posterior percutaneous screw-rod instrumentation bridging the infection level followed by soft bracing for 4 weeks after surgery. All patients underwent antibiotic therapy. Fifteen patients chose conservative treatment, 12 patients chose surgical treatment. Patients were seen at 1, 3, 6, 9 months after diagnosis. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and complete blood count were measured at each follow-up visit. Segmental kyphosis was measured at diagnosis and at 9 months. VAS, SF-12, and EQ-5D questionnaires were recorded at each follow-up visit. Baseline groups’ demographic characteristics were assessed using independent sample t-tests for continuous variables and χ2 tests for frequency variables. Results. Complete healing was achieved in all patients, no difference was observed in healing time between the two groups (77.3±7.2 days vs 80.2±4.4). Instrumentation failure and screw loosening was not observed in any patient. In both group CRP and ESR decreased accordingly with response to antibiotic therapy. Surgically treated patients had significantly lower VAS scores at 1 month (3.05±0.57 in surgery group vs 5.20±1.21 in TLSO group) and 3 months (2.31±0.54 in surgery group vs 2.85±0.55 in TLSO group) post-diagnosis. Both groups had similar trends toward fast recovery in both mental (MCS) and physical components (PCS) of SF-12 questionnaire, surgically treated patients showed steeper and statistically significative improvement at 1 month (37.83±4.57 MCS in surgery group vs 24.52±3.03 MCS in TLSO group and 35.46±4.43 PCS in surgery group vs 27.07±4.45 PCS in TLSO group, p<0.001), 3 months (52.94±3.82 MCS in surgery group vs 39.45±4.92 MCS in TLSO group and 44.93±3.73 PCS in surgery group vs 35.33±6.44 PCS in TLSO group, p<0.001), and 6 months (54.93±3.56 MCS in surgery group vs 49.99±5.82 MCS in TLSO group) post-diagnosis, no statistically significant differences were detected at the other time points (9 months post-diagnosis). EQ-5D index was significantly higher in surgery patients at 1 month (0.764±0.043 in surgery group vs 0.458±0.197 in TLSO group) and 3 months (0.890±0.116 in surgery group vs 0.688±0.142 in TLSO group); no statistically significant changes were observed in segmental kyphosis between the two groups. Conclusion. Posterior percutaneous spinal instrumentation is a safe, feasible, and effective procedure in relieving pain, preventing deformity and neurological compromise. Surgical stabilization was associated with faster recovery, lower pain scores, and improved quality of life compared with TLSO conservative treatment at 1 and 3 months after diagnosis

Objectives

To determine the pattern of mutations of the WISP3 gene in clinically identified progressive pseudorheumatoid dysplasia (PPD) in an Indian population.

The treatment of chronic osteomyelitis often includes surgical debridement and filling the resultant void with antibiotic-loaded polymethylmethacrylate cement, bone grafts or bone substitutes. Recently, the use of bioactive glass to treat bone defects in infections has been reported in a limited series of patients. However, no direct comparison between this biomaterial and antibiotic-loaded bone substitute has been performed.

In this retrospective study, we compared the safety and efficacy of surgical debridement and local application of the bioactive glass S53P4 in a series of 27 patients affected by chronic osteomyelitis of the long bones (Group A) with two other series, treated respectively with an antibiotic-loaded hydroxyapatite and calcium sulphate compound (Group B; n = 27) or a mixture of tricalcium phosphate and an antibiotic-loaded demineralised bone matrix (Group C; n = 22). Systemic antibiotics were also used in all groups.

After comparable periods of follow-up, the control of infection was similar in the three groups. In particular, 25 out of 27 (92.6%) patients of Group A, 24 out of 27 (88.9%) in Group B and 19 out of 22 (86.3%) in Group C showed no infection recurrence at means of 21.8 (12 to 36), 22.1 (12 to 36) and 21.5 (12 to 36) months follow-up, respectively, while Group A showed a reduced wound complication rate.

Our results show that patients treated with a bioactive glass without local antibiotics achieved similar eradication of infection and less drainage than those treated with two different antibiotic-loaded calcium-based bone substitutes.

Cite this article: Bone Joint J 2014; 96-B:845–50.

Ciprofloxacin hydrochloride-loaded microspheres were prepared by a spray-drying method using pectin and chitosan. The effects of different polymers and drug ratios were investigated.

The most appropriate carriers were selected by in vitro testing. A rat methicillin-resistant Staphylococcus aureus osteomyelitis model was used to evaluate the effects of the loaded microspheres.

The drug was released rapidly from the pectin carrier but this was more sustained in the chitosan formulation.

Chitosan microspheres loaded with ciprofloxacin hydrochloride were more effective for the treatment of osteomyelitis than equivalent intramuscular antibiotics.