Specific and rapid detection methods for spinal tuberculosis, with sufficient sensitivity in HIV-1 co-infected individuals, are needed, to ensure early initiation of appropriate treatment to prevent physical disability and neurological fallout. In addition, understanding the systemic and local pathophysiology of spinal tuberculosis, and its interaction with HIV-1 infection, is crucial to guide future therapeutic interventions. We prospectively enrolled adult patients presenting with signs and symptoms of suspected spinal tuberculosis, at Groote Schuur Hospital, between November 2020 and December 2021. TB diagnostic testing was performed on open and CT-guided spinal biopsies using Xpert MTB/RIF Ultra compared to gold standards TB culture and histology. A highly sensitive droplet digital PCR assay for detecting and quantifying Mycobacterium tuberculosis complex (MTBC) and HIV-1 DNA was tested. Plasma inflammatory proteins were measured to assess systemic inflammation. Xpert Ultra had a high sensitivity of 94.7% and specificity of 100% for STB against TB culture and histology in both open and CT-guided biopsy samples. The ddPCR assay confirmed TB detection in 94% of patients with positive Xpert Ultra results. Four patients with negative TB diagnostic results had MTBC DNA detected by ddPCR. HIV-1 DNA was detected in the spinal tissues from all HIV-1-infected patients. MTBC DNA levels were significantly higher in HIV-1-co-infected spinal tissue samples (p< 0.01). We identified four biomarkers significantly associated with higher bacterial burden at the disease site (p< 0.01). Xpert Ultra and MTBC ddPCR improve the detection of STB. DdPCR can be utilized as an additional, highly sensitive tool for detecting and quantifying Mtb, in pathological samples that may be paucibacillary. These findings provide novel diagnostic and pathophysiologic insight into STB, in the context of HIV-1 infection, and provide rationale to include these tests in hospital and research settings for patients from communities burdened by TB and HIV-1

Aim. Infection is one of the worst complications following total joint arthroplasty, which is often associated with significant morbidity. Currently, due to the global burden of multidrug-resistant Gram-negative bacteria (MDR-GNB) infections, few multicentre studies have described a microbiological shift from Gram-positive cocci (GPC) towards MDR-GNB PJI (prosthetic joint infection). Additionally, the emergence of MDR-GNB impacts the therapeutic options and may increase the rate of PJI treatment failure. The purpose of the present study was to describe the predisposing factors associated to failure of treatment in an orthopaedic reference hospital in Brazil from 2014 through 2019. Method. Retrospective case-control analysis of patients treated for MDR-GNB PJI over a five-year period. Data were collected from medical, surgical and laboratory records. PJI were defined according the current MSIS criteria. MDR was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Patients with PJI with at least two positive tissue cultures for MDR-GNB were selected. The control group was patient with PJI caused by multisensitive organism (GNB or GPC). Absence of signs and symptoms of infection during the follow-up period was defined as cure. Definition of failure: death, need for another course of antibiotic, or the need for another surgical procedure to control the infectious site (relapse). Results. A total of 104 patients were selected, 59 patients in the MDR-GNB PJI group and 44 in the control group. Two outcomes were compared: cure or failure. The overall 1-year survival rate was 65.3% with the median survival time being 207.08 days. In the MDR-BGN infection group the 1-year survival rate was 59.3% and the average time of survival was 141.14 days. In contrast, in the Control group the 1-year survival rate was 73.8% with an average survival time of 230.29 days (p = 0.023). HR: 2.447, IC 1.099–5.448. The independent variables in the multivariate analysis associated to treatment failure were MDR-BGN infection (p = 0.023) HR 2,447 IC 1,099 –5,448, revision surgery (p = 0.042) HR 2,027 IC: 2,027–4,061, presence of comorbidities (p = 0.048) HR 2,508 IC: 0,972- 6,469 and previous antimicrobial use in the last 3 months (p = 0.022). HR 2,132 IC: 1,096- 4,149. Conclusions. GNB-MDR PJI increases approximately 2.5 times the chance of unfavourable outcome such as death and infectious relapse compared to infections with other multisensitive microorganism

Bone is a connective tissue that undergoes constant remodeling. Any disturbances during this process may result in undesired pathological conditions. A single nucleotide substitution (596T-A) in exon eight which leads to a M199K mutation in human RANKL was found to cause osteoclast-poor autosomal recessive osteopetrosis (ARO). Patients with ARO cannot be cured by hematopoietic stem cell transplantation and, without proper treatments, will die in their early age. To date, how this mutation alters RANKL function has not been characterized. We thus hypothesized that hRANKL M199 residue is a structural determinant for normal RANKL-RANK interaction and osteoclast differentiation. By sharing our findings, we aim to achieve an improved clinical outcome in treating bone-related diseases such as osteoporosis, ARO and osteoarthritis. Site-directed mutagenesis was employed to create three rat RANKL mutants, replacing the methionine 200 (human M199 equivalent residue) with either lysine (M200K), alanine (M200A) or glutamic acid (M200E). Recombinant proteins were subsequently purified through affinity chromatography and visualized by Coomassie blue staining and western blot. MTS was carried out before osteoclastogenesis assay in vitro to measure the cellular toxicity. Bone resorption pit assay, immuno-fluorescent staining, luciferase reporter assay, RT-PCR, western blot and calcium oscillation detection were also conducted to explore the biological effect of rRANKL mutants. Computational modeling, thermal Shift Assay, western blot and protein binding affinity experiments were later carried out for structural analyses. rRANKL mutants M200K/A/E showed a drastically reduced ability to induce osteoclast formation and did not demonstrate features of competitive inhibition against wild-type rRANKL. These mutants are all incapable of supporting osteoclastic polarization and bone resorption or activating RANKL-induced osteoclast marker gene transcription. Consistently, they were unable to induce calcium flux, and also showed a diminished induction of IκBa degradation and activation of NF-kB and NFATc1 transcriptional activity. Furthermore, the transcriptional activation of the antioxidant response element (ARE) crucial in modulating oxidative stress and providing cytoprotection was also unresponsive to stimulation with rM200s. Structural analyses showed that rM200 is located in a hydrophobic pocket critical for protein folding. Thermal shift and western blot assays suggested that rM200 mutants formed unstructured proteins, with disturbed trimerisation and the loss of affinity to its intrinsic receptors RANK and OPG. Taken together, we first demonstrates the underlying cause of M199-meidated ARO in a cellular and molecular level by establishing a phenotype in BMMs similar to observed in human samples. Further investigation hints the structural significance of a hydrophobic pocket within the TNF-like region. Combined with pharmaceutical studies on small-molecule drugs, this finding may represent a therapeutic target motif for future development of anti-resorptive treatments

Prosthetic joint infections (PJI) are caused by a variety of microorganisms but most frequently by staphylococci. The results of treatment of PJI due to organisms other than staphylococci are less known. The aim of this study is to evaluate the outcomes after streptococcal PJI. The data of 26 streptococcal (13 hip and 13 knee PJI from 24 patients) were retrieved from hospital based PJI register, and analyzed. There were 15 female and 11 male patients (mean age 66 y). Most (13) PJI were hematogenous. 15 PJI had been treated with debridement and retention (D&R) of the infected joint, 1 with permanent resection arthroplasty, 9 had two stage revision and 1 patient had one stage partial replacement. After the microbiological diagnosis was established most patients received 2–3 weeks of penicillin G or ceftriaxone followed by 2–6 months of oral amoxicillin. All patients had regular follow-ups after the procedure at least at 1 month, three months and one year. The results were classified as: PJI cure (in absence of clinical signs and symptoms of infection and with negative CRP), probable failure (in absence of clinical signs and symptoms of infection but with elevated CRP), definite failure (if a new treatment was necessary), and mechanical failure (aseptic loosening, periprosthetic fracture, quadriceps rupture). One foreign patient was lost to follow up. The mean follow up time for the rest was 60 months (from 16 to 167) months. There was probable prosthesis failure in 1 case, definite prosthesis failure in 7 cases and mechanical failure in 3 cases. The mean survival time of the failed prostheses was 28 (range from 2 to 83) months. 6 failures (40 %) occurred in group of cases that had undergone D&R, and 1 (6 %) in the two stage revision group. Among the 7 definite failures in 4 patients antibiotic treatment was empirically started after the symptoms reappeared resulting in long remission periods. Comparing to the published results of staphylococcal PJI it seems that D&R of the prosthesis for streptococcal PJI is considerably less successful. Rifampicin as a proven treatment of choice for staphylococcal infections is probably the main reason for the difference. An unexpected feature of streptococcal PJI is that definite failures are easily suppressed for long time with a short course of oral antibiotics

This study addresses a crucial gap in the knowledge of normative spinal growth in children. The objective of this study is to provide detailed and accurate 3D reference values for global and segmental spinal dimensions in healthy children under the age of 11. Radiographic spine examinations of healthy children conducted to rule out scoliosis were reviewed in four scoliosis referral centers in North America. All consecutive children aged three to eleven years old with EOS biplanar good quality x-rays, but without diagnosed growth-affecting pathologies, were included. Postero-Anterior and Lateral calibrated x-rays were used for spine 3D reconstruction and computation of vertebral body height and spine length. Median and interquartile range were calculated from cross-sectional data. Smooth centiles growth curves for 3D True Spinal Length (3DTSL) between T1 and S1, as well as for mid-vertebral heights of T5, T12 and L3, where fit and calibrated from data using the Lambda-Mu-Sigma method (GAMLSS package for R). This method automatically selects the best performing distribution from a familly of choices. Tables of centiles were then predicted from the computed models for selected ages. A total of 638 full spine examinations from asymptomatic patients were reconstructed in 3D, 397 in girls and 241 in boys. Medians and interquartile ranges were calculated for 3DTSL (T1-S1): 285 (24) mm, 314 (26) mm and 349 (31) mm, and for selected vertebral heights T5: 10 (1) mm, 11 (1) mm and 12 (1) mm, T12: 13 (2) mm, 14 (1) mm and 16 (2) mm, and L3: 14 (1) mm, 16 (2) mm and 18 (2) mm, respectively for the 3–6, 6–8 and 8–11 age groups. Centile curves ready for clinical use of the 3DTSL (T1-S1) and of the vertebral heights of T5, T12 and L3 as a function of age were derived for the 5, 10, 25, 50, 75, 90 and 95th centiles. In general, boys presented linear relationships between spinal dimensions and age, and girls presented more diverging trends with increased variance for older ages. Accordingly curves for boys follow the Normal distribution whereas those for girls follow the original Box-Cox-Cole-Green distribution. Model diagnostic tests (normally distributed residuals, adequate wormplots and |Z statistics| < 2) confirmed adequacy of the models and the absence of significant misfit. Accurate reference values were derived for spinal dimensions in healthy children. Spinal dimension charts showed that the spinal lengths and vertebral heights changed relatively constantly across the age groups closely resembling WHO total body height charts. The reference values will help physicians better assess their patients' growth potential. It could also be used to predict expected spinal dimensions at maturity or changes in pathologic conditions as well as to assess the impact of growth friendly interventions in the correction of spinal deformities

Necrotizing Fasciitis (NF) is a life-threatening infectious condition which requires expedient diagnosis to proceed with urgent surgical debridement. However, it can be difficult to establish an early diagnosis and expedite operative management as signs and symptoms are often non-specific and may mimic other pathology. Scoring systems such as The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) have been proposed to incorporate laboratory findings to predict whether a soft tissue infection is likely to be NF. Recent studies have found the sensitivity and specificity of the LRINEC tool to be lower than originally cited by the LRINEC authors in a validation cohort. Furthermore, there seems to be a predilection for certain geographic locations of patients with NF transferred to our tertiary care center for management, however, to our knowledge, geographic risk factors for NF have not been reported. This study also aims to determine the morbidity and mortality rate of NF at our Canadian tertiary hospital in recent years. Comorbidities such as smoking, diabetes, and steroid use will be analyzed for any correlation with developing NF. Identification of patient factors in correlation with laboratory values may help identify patients at higher risk for having NF upon their presentation to the emergency department. A resultant earlier diagnosis of necrotizing soft tissue infections would allow for earlier surgical debridement and positively influence patient outcomes. A retrospective chart review of 125 cases of NF at Kingston Health Sciences Centre from 2005 to 2017 was carried out to assess the validity of the LRINEC in our population and to examine the effect of comorbid factors such as smoking, diabetes, and corticosteroid use on the development of NF. The study cohort included patients treated by all surgical disciplines at our institution over twelve years. A separate cohort of 125 cellulitis or abscess cases was analyzed to assess the validity of the LRINEC tool in differentiating necrotizing fasciitis from non-necrotizing infections such as cellulitis and soft tissue abscess. The 30-day mortality rate of NF treated at our institution during the study period was 21%. Advanced age was found to be a significant risk factor for death within 30 days of diagnosis (p=0.001). Smoking and steroid use were both found to increase risk for developing NF (p=0.01 and p=0.03, respectively). Diabetes did not appear to increase risk NF. There was no statistical difference in mortality rates between males and females with NF. The sensitivity of LRINEC in detecting NF was only 47% with a specificity of 74%. The mortality rate of NF at our center is similar to that of other countries in recent years. Males and females have nearly equal mortality rates from NF. Smoking and steroid use appear to increase risk for developing NF, while diabetes may not. The LRINEC assessment tool alone may underestimate risk for developing NF, however, use of other clinical factors such as comorbidity analysis will further aide in the diagnosis of NF allowing for earlier surgical debridement

Tendinopathy is one of the most common orthopaedic pathological conditions characterized by tendon degenerative changes. Excessive mechanical loading is considered as a major causative factor in the development of tendinopathy, but the mechanisms of pathogenesis remain unclear. High mobility group box-1 (HMGB1), a potent inflammatory mediator when released into the matrix, has been identified in the early stage tendinopathy patients. Since the release and contribution of HMGB1 in tendinopathy development due to mechanical overloading is unknown, we investigated the role of HMGB1 in tendinopathy using a mouse intensive treadmill running (ITR) model and injection of glycyrrhizin (GL), a specific inhibitor of HMGB1. A total of 48 mice were divided into four groups, Cage Control group: The animals were allowed to move freely in their cage, GL group: The animals were received daily IP injection of GL (50 mg/kg body weight) for 24 weeks, ITR group: The animals ran on treadmill at 15 meters/min for three h/ day, five days a week for 12 or 24 weeks, GL+ITR group: The animals ran the same protocol as that of ITR group plus daily IP injection of GL for 12 or 24 weeks. Six mice/group were sacrificed at 12 or 24 weeks and the Achilles and patellar tendon tissues were harvested and used for histochemical staining and immunostaining. Mechanical overloading induced HMGB1 released from the cell nuclei to the matrix (Fig. 1a, b) caused tendon inflammation (Fig. 1c, d) and led to tendon degenerative changes (Fig. 1e-j). After 12 weeks of ITR, the tendon tissue near the bone insertion site showed typical tendinopathic changes in cell shape, accumulation of glycosaminoglycans (GAG) (Fig. 1e, f), and increase in SOX-9 staining (Fig. 1g-j). After 24 weeks ITR, the distal site of Achilles tendon showed considerable changes in cell shape (Fig. 2A, g, arrows), which is round compared to more elongated in the control and GL groups (Fig. 2A, e, f). However, daily treatment with GL prior to ITR blocked the cell shape change (Fig. 2A, h) and, ITR induced extensive GAG accumulation in ITR group (Fig. 2B, bottom panel). Furthermore, GL inhibited ITR-induced expression of chondrogenic markers (SOX-9 and collagen II) in the tendons (Fig. 3). Our results showed that mechanical overloading-induced HMGB1 plays a critical role in the development of tendinopathy by initiating tendon inflammation and eventual degeneration characterized by the presence of chondrocyte-like cells, accumulation of proteoglycans, high levels of collagen type II production, and chondrogenic marker SOX-9 expression. These results provide the first evidence for the role of HMGB1 as a therapeutic target to prevent tendinopathy before its onset and block further development at its early inflammation stages. The inhibition of tendinopathy development by GL administration in this study also suggests the putative therapeutic potential of this natural triterpene that is already in clinical use to treat other inflammation-related diseases. For any figures or tables, please contact authors directly

Aim. Infection is one of the worst complications following total joint arthroplasty, which is often associated with significant morbidity and increased medical costs. Although Gram–positive bacteria remains the most prevalent causative agents, an increase in prosthetic joint infections (PJI) due to gram-negative bacteria (GNB) has been reported. Additionally, the emergence of multidrug resistant resistance (MDR) in GNB impacts the therapeutic options and may increase the rate of treatment failure and drug toxicity adverse effects due the prescription of harmful and toxics antimicrobial schemes. The purpose of the present study was to describe the predisposing factors associated to PJI caused by MDR-GNB in a specialized orthopedic reference hospital in Brazil from 2014 through 2018. Method. Retrospective case-control analysis of patients treated for MDR-GNB PJI over a four-year period (2014–2018). Data were collected from medical, surgical and laboratory records. PJI were defined according the criteria of MSIS. MDR was defined as non-susceptibility to at least one agent in three or more antimicrobial categories. Patients with prosthetic infection with at least two positive tissue cultures for MDR-GNB were selected. Univariate and multivariate logistic regression models were used to determine the independent risk factors associated with MDR-GNB PJI. Controls: patients with PJI with at least two positive tissue culture for non MDR- GNB. Results. A total of 104 patients were selected, 59 patients in the MDR-GNB PJI group and 44 in the control. Patients with MDR-GNB PJI were elderly (mean age of 68.36), distribution among sex was similar (49.2% female and 50.8% male) and 72.3% had one or more comorbidities. Most frequently identified comorbidities were diabetes (10.2%), malnutrition (5.5%), hypertension (4.7 %) and obesity (3.9%). Hip replacement accounted for 91.5% of the cases and 59.3% were revision arthroplasty. The mean time between the placement of the prothesis and the onset of PJI signs and symptoms was 438 days. In the univariate regression, the significant risk factors for MDR-GNB PJI were revision arthroplasty, alcoholism, nonelective arthroplasty, prior antimicrobial use, presence of concomitant infection and blood transfusion. However, in the multivariate analysis, prior use of antimicrobials (OR 9.31, CI95% 3.02–28.64) and the nonelective arthroplasty (OR 6.29, CI95% 1.75–22.6) remained as independent risk factors for MDR-GNB PJI. Conclusions. Previous use of antimicrobial and nonelective arthroplasty are important risk factors for PJI by GNB MDR

Total knee arthroplasty (TKA) is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leucocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11- 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimization of patient co-morbidities to help avoid preventable complications, use of pre-operative and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery

Aims

The standard of wide tumour-like resection for chronic osteomyelitis (COM) has been challenged recently by adequate debridement. This paper reviews the evolution of surgical debridement for long bone COM, and presents the outcome of adequate debridement in a tertiary bone infection unit.

Metal-on-metal bearing surfaces were reintroduced to take advantage of the reduction in volumetric wear afforded by these bearings and reduce the complications of osteolysis and aseptic loosening. In addition, metal-on-metal hip resurfacing and many metal-on-metal total hip replacement systems employed large diameter femoral heads, thereby reducing the risk of dislocations. Unfortunately, many metal-on-metal systems demonstrated poor survivorship and were associated with adverse local tissue reactions (ALTRs) related to metal debris generated from the bearings and/or modular connections. Careful clinical surveillance of patients with metal-on-metal bearings is warranted to identify patients with ALTR at an early stage in order to intervene prior to the development of extensive peri-articular soft tissue damage. Monitoring may include serum or whole blood metal levels and metal artifact reduction sequence magnetic resonance imaging (MARS-MRI) depending on the patient's signs and symptoms and the track record of the implanted device. While there currently is a lack of high quality evidence-based guidelines on the management of patients with either symptomatic or asymptomatic metal-on-metal total hip replacements, professional organizations have issued consensus-based algorithms to guide the practitioner in management. Ultimately, the decision for revision surgery should not be based on a single diagnostic test but on the entire clinical scenario

TKA is one of the most common orthopaedic operations performed worldwide and it is largely successful in pain relief and functional recovery. However, when pain persists post-operatively the thorough evaluation must be instituted. Extra-articular causes of knee pain include; hip pathology, lumbar spine degenerative disease or radicular symptoms, focal neuropathy, vascular disease, and chronic regional pain syndrome. Intra-articular causes of knee pain: infection, crepitation/ clunk, patella osteonecrosis, patella mal-tracking, soft tissue imbalance, malalignment, arthrofibrosis, component loosening, implant wear, ilio-tibial band irritation, and bursitis. Other causes of pain to rule out are component overhang with soft tissue irritation, recurrent hemarthrosis secondary to synovial impingement or entrapment, non-resurfaced patella, and metal sensitivity. A careful history may reveal previous knee surgeries with delayed healing or prolonged drainage, chronology of sign and symptoms, co-morbid medical conditions, jewel or metal sensitivity. Physical exam should help with specific signs in the operated knee. Targeted local anesthetic blocks are helpful and response to lumbar sympathetic blocks determines presence of CRPS. Lab tests are important: ESR, CRP, WBC, aspiration with manual cell count and diff, leukocyte esterase dipstick, RA titers, metal derm patch testing, nuclear scans, CT best for rotational malalignment,, and MARS MRI. More recently patient satisfaction as an outcome measure has shown TKA results not satisfactory in 11 – 18% of patients. A discordance of patient vs. surgeon satisfaction exists so the following factors may help improve this: correct patient selection, establishing and correlating surgeon-patient expectations, peri-operative optimisation of patient comorbidities to help avoid preventable complications, use of pre- and post-operative pathways. Satisfaction rates can best be improved by addressing the previous points with patients prior to TKA surgery

Carpal tunnel syndrome is the most frequent form of median nerve entrapment, accounting for 90% of all entrapment neuropathies. Routinely nerve conduction study (NCS) tests are ordered to confirm the diagnosis however; there are issues of long waiting periods and costs with it. We aimed to compare carpal tunnel questionnaire score (CTQS) by Kamath and Stothard (2003) to nerve conduction study result in the diagnosis of carpal tunnel syndrome. This prospective study involved analysis of data from all the patients referred to NHS Tayside (Dundee) hand clinic with signs and symptoms of Carpal tunnel syndrome (CTS) from September 2016 to February 2017. Statistical analysis was done using SPSS and sensitivity and specificity was calculated. The questionnaires were filled in by a team of specialist physiotherapists. Nerve conduction study tests were done by a team of consultant neurophysiologists. Both the groups were blinded to each other's assessment. We analysed 88 patients who filled in CTQS and also underwent NCS. We noted that CTQS of less than 3 correlated 100% to negative nerve conduction result. When the carpal tunnel questionnaire score was more than or equal to 5, 54 patients had positive NCS result and 6 patients had negative NCS result, giving a 90% predictability of a positive NCS result. Mean waiting period of carpal tunnel patients for NCS was 141 days. We noted from this prospective study that CTQS was sensitive enough to exclude carpal tunnel syndrome when the questionnaire score was less than 3. In addition, the questionnaire revealed a 90% probability of having carpal tunnel syndrome when CTQS was more than or equal to 5. Based on the present study, we would recommend that patients in grey zone of 3 to 4 on questionnaire should undergo NCS, resulting in only 20% of patients (based on the figures from the current study) being referred for NCS. The questionnaire can be used in primary health care or specialist physiotherapy screening clinic as a tool for diagnosing CTS with implications of cost saving and avoiding long waiting periods

Report of a case of migrating periprosthetic infection from a hip replacement to a contralateral knee joint undergoing a total knee replacement. We present a 74-year old female patient who underwent a total hip arthroplasty of the left hip after a subcapital fracture of the femur. Four months after the index procedure the patient presented with signs and symptoms of infection of the operated joint. Staph aureus and Enterococcus faecalis were recognized as the infecting bacteria. The implants were removed, cement spacers were placed and a total hip arthroplasty was performed again after three months. Unfortunately, infection ensued again and the patient underwent three more procedures until the joint was considered clean and t he hip remained flail without implants. The patient elected to undergo a total knee arthroplasty due to severe osteoarthritis of right knee. Intraoperatively tissue samples were taken and sent for cultures which identified Enterococcus faecalis present in the knee joint. Enterococcus migrated from the infected hip to nonoperated knee joint. Intravenous antibiotics were administered for three weeks but the knee presented with infection of the arthroplasty ten months after its insertion. The implants were removed the joint was debrided and cement spacers were inserted. The patient decided not to proceed with another procedure and she remains with the cement spacers in her knee. Rare report of migrating periprosthetic infection. Nosocomial enterococci acquired resistance cannot be ruled out. Unique characteristics in enterococci antibiotic resistance and biofilm formation

Among the extra pulmonary forms of tuberculosis (TB), the osteoarticular localization has been detached in 1–2% of cases. In 30% of these children either a pulmonary and extra-pulmonary localization was found. The diagnosis of skeletal TB is often insidious due to variable signs and symptoms. The medical records of children admitted to our center between 2006 and 2013 due to skeletal TB were evaluated. All patient underwent TB skin test, IGRA test, chest X-ray and focused imaging tests. In the complicated forms of osteoarthritis the infected material drained spontaneously or surgically was analyzed for Mycobacterium Tuberculosis (MT) detection and culture. In patients with pulmonary localization gastric aspirates or sputum analysis was performed. Nine patients met the inclusion criteria. The median age at diagnosis was 7 (range 2–13) years. All patients presented with local osteoarticular symptoms and 4 of them had fever. In five cases there was a preceding history of minor trauma. Three patients had a case of TB in the family. Four patients had a spinal localization, three hips and two ankles. ERS and CRP values were altered in 7 and 4 patients respectively. All patient underwent radiography, bone three phase scintigraphy and a MRI. The diagnosis of tuberculosis was confirmed by histopathological examination of bone biopsy in 6 (66%) cases. The skin test and the IGRA test were positive in all patients. The chest X-ray showed a pulmonary localization in 3 cases that had positive gastric aspirate or sputum. All patients were treated with isoniazid, rifampicin pyrazinamide and ethambutol. In 3 patients Linezolid or Ciprofloxacin was also associated. The follow-up had an average value of 34 months. Sequelae were reported in 7 patients (limping in 5 cases, severe kyphosis in 2 cases). Owing to its low incidence in developed countries, the diagnosis ot TB is often delayed for months to years. Additionally, we highly recommend taking a biopsy of the site of suspected infection because an early diagnosis is the key to successful treatment

INTRODUCTION. Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease, and is considered one of the most successful surgical interventions in the history of medicine. However, infection of these implants, called Periprosthetic Joint Infection (PJI), remains one of the biggest challenges facing orthopaedics today. PJI can lead to additional surgeries, revision, fusion and amputation. Diagnosis of PJI. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. These include the erythrocyte sedimentation rate (ESR), the serum C-reactive protein (CRP), the synovial fluid white blood cell count and the leukocyte differential. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The Synovasure® Test for Periprosthetic Joint Infection (PJI). The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. These biomarkers include inflammatory proteins, cytokines, and microbicidal peptides / proteins that are known to be involved in the host response to infection. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. DISCUSSION. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. CONCLUSIONS. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

Total joint arthroplasty continues to gain acceptance as the standard of care for the treatment of severe degenerative joint disease. However, the Periprosthetic Joint Infection (PJI) remains one of the biggest challenges facing orthopaedics today. It is important to accurately diagnose PJI because its management differs from that of other causes of arthroplasty failure. The most common symptom of PJI is pain. In acute infection, the local signs and symptoms (e.g., severe pain, swelling, erythema, and warmth at the infected joint) of inflammation are generally present. On the other hand, chronic infection usually has a more subtle presentation, with pain alone, and is often accompanied by loosening of the prosthesis at the bone-implant interface. The diagnosis of PJI has proven quite challenging, as both acute and chronic infections can be difficult to differentiate from other forms of inflammation. The reported literature on the diagnosis of PJI has focused on evaluated laboratory tests that were never developed specifically for the diagnosis of PJI. Because these tests were not made for the purpose of diagnosing PJI, it has been the responsibility of the orthopaedic community to evaluate and recommend their interpretation. This has resulted in significant confusion regarding the appropriate thresholds and optimal combination of these tests. These difficulties were the motivation for the development of a specific test for the detection of PJI. The promising diagnostic capabilities of synovial fluid biomarkers for PJI have already been reported in the literature. Studies have demonstrated that the alpha-defensin microbicidal peptide present in human neutrophils is an ideal biomarker for PJI due to the distinct separation it achieves between positive and negative results. A specific test allowing to measure the concentration of the alpha-defensin in the synovial fluid has been developed. The specificity and the sensitivity of this test for the detection of a PJI are respectively 96% and 97%. This test has been proven to have also a high reproducibility, its results not being influenced by antibiotics. A lateral flow version of this test (Synovasure PJI, distributed exclusively in Europe by Zimmer GmbH) has been recently developed. It allows reading the results in 10 minutes and it doesn't require any laboratories for its interpretation. Currently, this test device is in clinical evaluation in more than 200 European hospitals. In case that the clinical evaluation of this test device is positive, this method will be a new paradigm for the diagnosis of periprosthetic joint infection

Objective. To investigate the relationship between the pattern of pelvic or acetabular fracture, and bladder injuries. Methods. A total of 173 patients admitted at our Academic Hospital from January 2006 to March 2012 with cystograms done for pelvic or acetabular fractures were studied retrospectively. Records of pelvic X-Rays, CT scans and cystograms were reviewed. Tile's classification and Young & Burgess classification were used for pelvic fractures and Judet & Letournel classification system for acetabular fractures. Results. Out of 173 patients 16% had bladder injuries of which 22% were intra-peritoneal and 70% were extra-peritoneal. The bladder injuries mostly occurred among male patients; 16 males compared to 9 female patients. Out of the 21 fractures of the acetabulum only 2 sustained bladder injury and they were secondary to gunshot wounds. Lateral compression fractures accounted for 67% of bladder injuries. Motor vehicle accidents were the leading mechanism of injury accounting for 117 patients in total and 81% of those with bladder injuries. Among the patients with bladder rupture 55% had at least 3 rami involved and only one patient (4%) with 1 ramus involved had a bladder injury. Overall 44 (34%) of patients with 3 or more rami fractured had bladder injury. Conclusion. Bladder injury appears to be related to the mechanism of injury. We recommend that a cystogram be done routinely when a patient presents with a type III lateral compression fracture. In isolated acetabulum fractures, single ramus fractures and lateral compression type I fractures, request for cystogram should be correlated with clinical signs and symptoms, and not done routinely. NO DISCLOSURES

Background:. Early diagnosis of septic arthritis and osteomyelitis in children is essential to prevent long term sequelae. The diagnosis for these orthopaedic emergencies can be difficult and challenging especially in infants. Standard blood tests used for diagnosis have a low specificity. Procalcitonin (PCT) is significantly elevated in bacterial infections and remains low in viral infections and inflammatory conditions. Good positive predictive values for PCT have been obtained in various studies used in paediatric infections, but limited studies have examined the role in orthopaedic infections. Aims:. To introduce PCT testing in the work up of Septic Arthritis (SA) and Acute Osteomyelitis (OM) and to see if the test is useful in the diagnosis. Also to determine whether 0.2 ng/ml is a suitable cutoff level as indicated by previous studies. Method:. All children under 14 years presenting with signs and symptoms of SA/OM from 1 June 2009 to 31 June 2010 were subjected to standard blood tests with addition of PCT and compared to a control group. The definitive diagnosis was made by microbiologic examination obtained in theatre. A PCT cut-off level of 0.2 ng/mL was used. Results:. A total number of 33 patients were included in the study. Eight patients were diagnosed as OM, 4 as SA and 21 had another diagnosis. Staphylococcus aureus was the most common organism isolated in this series with no resistant organisms seen. In the SA/OM Group 11 of the 12 patients had an increased PCT level and 4 in the other diagnosis group had raised PCT. The calculated sensitivity of PCT was 92% with a confidence interval of 62–100% and the specificity was 81% with a confidence interval of 58–95%. In this study the sensitivity of CRP was 100% while the specificity 26%. The positive predictive value for PCT in this study was 73% and the negative predictive value was 94%. The accuracy for PCT in Septic Arthritis and Osteomyelitis in this study was 85%. Conclusions:. The calculated sensitivity and specificity in this study has shown that PCT testing can aid in the diagnosis of SA/OM in children using 0.2 ng/ml as cut-off level. PCT was more specific for bacterial infections in this study than CRP. Further research is needed with larger numbers to conclusively prove that this specific cut-off for PCT is significant

Aims. A new therapy, based on the intra-articular injection of autologous conditioned serum (ACS), is used in several European countries for osteoarthritis (OA) treatment. ACS is generated by incubating venous blood with medical grade glass beads. Peripheral blood leukocytes produce elevated amounts of endogenous anti-inflammatory cytokines such as interleukin-1 receptor antagonist (IL-1Ra) and growth factors that are recovered in the serum(1). ACS has been shown to improve the clinical lameness in horses significantly to enhance the healing of muscle injuries in animal models, and in human athletes. In the present study, the efficacy and safety of ACS was compared to intra-articular hyaluronan (HA), and saline in patients with confirmed knee OA. Methods. In a prospective, randomised, patient- and observer-blind trial with three parallel groups, 376 patients with knee OA were included in an intention to treat (ITT-) analysis. Efficacy was assessed by patient-administered outcome instruments (WOMAC, VAS, SF-8, GPA) after 7, 13 and 26 weeks (blinded) and Two-years (non-blinded). The frequency and severity of adverse events were used as safety parameters. Results. In all treatment groups, intra-articular injections produced a significant reduction in WOMAC-scores and weight-bearing pain (VAS). However, responses to ACS were stronger. The superiority of ACS and either HA or saline was statistically significant for all outcome measures and time points. No significant differences between HA treatment and saline injections (p>0.05, at all time points and outcome measures) were recorded. Frequency of adverse advents (AE) was comparable in the ACS- and the saline-group (p>0.05). Conclusion. The results demonstrate that ACS is effective, long-lasting and well tolerated in the management of chronic, idiopathic OA of the knee. So far, the efficacy of ACS is defined through improvement in clinical signs and symptoms, particularly pain. It remains to be determined whether they are disease-modifying, chondroprotective, or even chondroregenerative, sequelae