RAGE signalling contributes to oxidative stress and inflammation in knee osteoarthritis patients with metabolic syndrome.

OBJECTIVES: Metabolic factors play significant role in the natural history of knee osteoarthritis (KO). There is a limited understanding of molecular and cellular events that give rise to the disease in patients. This study explored the possible cellular mechanisms by which metabolic syndrome leads to KO. METHODS: This cross-sectional study enrolled 80 subjects with KO who fulfilled the ACR diagnostic criteria and were undergoing total knee replacement surgery. The patients were divided into two groups: KO patients without metabolic syndrome and KO patients with metabolic syndrome. RESULTS: We hypothesised that metabolic syndrome may accelerate pathogenesis of OA by enhanced RAGE axis in articular cartilage and Infrapatellar fat pad of the knee joint. We have found enhanced protein expression of receptor for advanced glycation end products (RAGE) and its ligands AGEs and HMGB-1 in knee joint tissue of KO patients with metabolic syndrome as compared to KO patients without metabolic syndrome. Further downstream, the gene expression of oxidative stress regulators such as NADPH and inflammation, NFĸB were upregulated in KO patients with MetS as compared to KO patients alone. Higher levels of advanced oxidation products and inflammatory marker IL-17 were exhibited in synovial fluid of KO patients with metabolic syndrome. The enhanced levels of these oxidative stress and inflammatory markers were reflected in the serum of KO patients with metabolic syndrome as well. CONCLUSIONS: We conclude that enhanced function of RAGE axis could be one of the mechanisms by which metabolic syndrome leads to KO.

Epidemiology of hip & knee replacement across Pakistan: Multicenter cross-sectional study.

Objective: To know about the predictive prevalence of hip and knee arthroplasty across Pakistan. Methods: It is retrospective cross-sectional study with data collection from Pakistan National Joint Registry (PNJR) of number of hip and knee arthroplasty cases in seven years (2014-2021). Fourteen high volume centers across Pakistan who consented for data publication were included. Stata version 16 was used for data analysis. Mean & standard deviation was reported for quantitative variable & frequency and proportion were reported for qualitative variables. Results: Our results showed a total of 9572 people had total knee replacement in last seven years from 2014-2021 with the rate of 9.57/100,000 population. Mean age of the patient was 61.7±8.95 with 69.5% patients being female and 30.5% being male. Our results showed a total of 2265 people had total hip replacement in last seven years from 2014-2021with the rate of 2.26/100,000 population. Mean age of the patient was 50.7±15.4 with 62% patients being male and 38% being female. Conclusion: This is the first epidemiological study in Pakistan on the rates of hip and knee arthroplasty cases in Pakistan based on registry data, showing that more knee arthroplasty cases are being performed as compared to hip arthroplasty.

Role of stem cells in the treatment of osteoarthritis- a review of literature.

The purpose of this review was to identify and assess the effectiveness of stem cells in the form of injectables in the treatment of joint osteoarthritis as published in the literature. Studies were searched from multiple databases like Pubmed, Embase and Cochrane Library until June 2022 using multiple keywords. Randomized controlled trials of patients with osteoarthritis (OA) were included which compared the pain and functional outcomes for those getting Mesenchymal Stem Cells (MSCs) injectables as compared to those who received no MSCs injection. Twelve randomized controlled trials, assessing a total of 486 participants were identified and studied. Overall, stem cells injection has no significant effect on pain along with physical function. Stem cells injection could be effective in reducing pain and might also help in improving functional outcome in patients with OA. However, the findings are not yet significant and further clinical trials with larger samples are needed to come to a positive conclusion.

The Unusual Cause of Prosthetic Joint Infection: Outcomes of Nontuberculous Mycobacteria Treatment Following Primary Total Knee Arthroplasty.

Background: Nontuberculous mycobacterium (NTM) is a rare cause of prosthetic joint infection (PJI) following primary total knee arthroplasty (TKA). NTM causes a variety of infections, mainly divided into pulmonary and extrapulmonary infections. In Pakistan, there was a 7.7-fold increase in NTM infections from 21 cases in 2012 to 163 cases in 2018. An earlier study evaluating the distribution of NTM species across Pakistan suggested geographical variation across different regions, every area having its own distribution spectrum. There are no data available especially in developing countries such as Pakistan regarding PJI due to NTM following primary TKA. The purpose of our study was to determine treatment outcomes of two-stage revision surgery following NTM infection. Methods: This is a retrospective study. Patients who underwent TKA between June 2008 and December 2018 were included in the study. NTM was defined as the presence of traditional criteria for diagnosing PJI plus growth of NTM cultured from a joint aspirate or deep periprosthetic tissue specimen using Löwenstein-Jensen medium and Mycobacteria Growth Indicator Tube medium. All patients were female with a mean age of 62.8 ± 7.9 years. The mean body mass index was 25.6 ± 2.8 kg/m2. Treatment outcomes were categorized into favorable and unfavorable. Results: We found rapid-growing mycobacterium in 6 patients whereas slow-growing mycobacterium was found in 2 patients only. Generally, clarithromycin was the standard antibiotic used in all cases of NTM infections. All patients underwent revision surgery. Conclusions: Meticulous surgical debridement and prolonged antibiotic treatment course were the only hope of cure to combat the unusual cause of PJI following primary TKA.

Clinical Response of Nuberol Forte® for Pain Management With Musculoskeletal Conditions in Routine Pakistani Practice (NFORTE-EFFECT).

Background Musculoskeletal pain is the most common complaint presented to the health practitioner. It is well-known that untreated or under-treated pain can have a significant negative impact on an individual's quality of life (QoL). Objectives The current study aimed to assess the clinical response of Nuberol Forte® (paracetamol 650 mg + orphenadrine 50 mg) to musculoskeletal pain in routine Pakistani practice and its impact on improving the patient's QoL. Methods A prospective, observational multicenter study (NFORT-EFFECT: Safety & Efficacy of Nuberol Forte in Pain Management). Three hundred ninety-nine patients with known prescreened musculoskeletal pain were recruited from 10 major healthcare facilities across six (6) major cities of Pakistan, as per the inclusion/exclusion criteria. After the baseline visit (Visit 1), the patients were followed up one to two weeks (Visit 2) after the treatment as per the physician's discretion. Data were collected using the Case Report Form (CRF) designed for the study, and adverse events (AEs) were also monitored to assess drug safety. Pain intensity was assessed through a visual analog scale (VAS), and QoL was assessed using the Muscle and Joint Measure (MJM) scale. Results Out of 399 enrolled patients, 49.4% were males and 50.6% were females with a mean age of 47.24 ± 14.20 years. Most patients were presented with knee osteoarthritis (OA), i.e., 148 (38%), followed by backache 70 (18.2%). A significant reduction in the mean pain score was observed after treatment with the combination of paracetamol and orphenadrine (p<0.05). Furthermore, an overall improvement in the patient's QoL was also observed. During the study, only 10 patients reported mild adverse events (AEs), namely, dryness of the mouth, dizziness, gastric irritation, tachycardia, restlessness, etc. Conclusion The combination of paracetamol and orphenadrine (Nuberol Forte) exhibited effective pain management among patients with musculoskeletal conditions and improved their QoL.

Mid-term results and survival rates following a single-design rotating hinge knee arthroplasty in non-tumor conditions in a Pakistani population.

BACKGROUND: Information regarding the use of hinged implants in non-oncological conditions is limited in our region due to a lack of adequate data collection and follow-up. The purpose of this study is to evaluate mid-term results and risk factors affecting the survivorship of third-generation rotating hinge knee (RHK) patients in non-oncological conditions. METHODS: We retrospectively reviewed 41 single, third-generation, rotating hinge prostheses in three complex primary knee procedures and 38 revision knee surgeries in between 2007 to 2014. Implant survival was assessed using the Kaplan-Meier method. Factors influencing implant survival were identified using the log-rank test. During the study period, clinical results along with complications were assessed. Clinical outcomes were assessed by using the Knee Society Score (KSS). RESULTS: RHK arthroplasty was used in 41 patients. Out of 41 patients, a RHK was used in three patients with a complex primary deformed knee whereas in 38 patients, a RHK was used in revision arthroplasty surgery. The cumulative implant survival rate with re-revision due to any cause was found to be 87.8% (95% CI 69.2-90.1) at 5-7 years. Prosthetic joint infection, peri-prosthetic fracture and extensor mechanism complications were the commonest mode of failure. The P value was found to be significant when comparing KSS pre-operatively and post-operatively. CONCLUSION: The cumulative implant survival rate was found to be 87.8%. Prosthetic joint infection was the commonest mode of failure in patients who underwent third-generation RHK surgery for variable indications. Being a patient with a high Charlson comorbidity index is the main risk factor associated with failure of the rotating hinge implant.

Impact of Tibial Tubercle Osteotomy on Final Outcome in Revision Total Knee Arthroplasty: Our Experience and Technique in Pakistan.

BACKGROUD: Due to extensive fibrosis during revision surgery, adequate exposure is essential and it can be achieved with several extensile approach options, such as tibial tubercle osteotomy. Information regarding surgical exposure during revision arthroplasty is limited in developing countries, such as Pakistan, due to the lack of adequate data collection and follow-up. Therefore, the purpose of this study was to evaluate the impact of tibial tubercle osteotomy on final outcome of revision total knee arthroplasty (TKA). METHODS: A total of 231 revision TKAs were performed between January 2008 and December 2017. Twenty-nine patients underwent tibial tubercle osteotomy for adequate exposure during revision surgery. Of these, 27 patients with complete follow-up were included in our study. Factors examined include age at the time of revision surgery, gender, comorbidities, arthroplasty site (right or left), body mass index (BMI), and primary indications for the tibial tubercle osteotomy during revision TKA. Functional outcome was measured by using Knee Society score (KSS) at 3 months and the final follow-up. All statistical analysis was done using SPSS version 20.0 with a p-value < 0.05 considered significant. RESULTS: Out of 27 patients, 6 patients (22.2%) were men and 21 patients (77.7%) were women. Right knee revision arthroplasty was performed in 15 patients (55.5%), left knee revision arthroplasty was performed in 12 patients (44.4%), and bilateral revision surgery was performed in only 1 patient (3.7%). The mean BMI was 29.2 kg/m2. We used a constrained condylar knee in 20 patients (74%), a rotating hinge knee in 5 patients (18.5%), and mobile bearing tray plus metaphyseal sleeves in 2 patients (7.4%). The KSS was 52.21 ± 4.05 preoperatively, and 79.42 ± 2.2 and 80.12 ± 1.33 at 3 months and 12 months, respectively. Radiological union was achieved in all patients at 3 months. Of 27 patients, only 1 patient (3.7%) had proximal migration of the osteotomy site at 6 months: the patient was asymptomatic and union was also achieved and, therefore, no surgical intervention was performed. CONCLUSIONS: Tibial tubercle osteotomy during revision TKA can be a safe and reliable technique with superior outcomes and minimal complication rates.

Management of early and late presenting tibial stress fracture with advanced osteoarthritis of the knee: A dilemma among arthroplasty surgeons in developing countries.

BACKGROUND: Single-stage total knee arthroplasty (TKA) with long-stem is a viable option to treat proximal tibial stress fracture in advance knee osteoarthritis. However, in patients with old mal-united or non-united tibial fractures, treatment becomes complicated. Therefore, our aim in this study was to monitor clinical and radiological outcome in patients presenting early or late managed by single-stage long-stem TKA. METHODS: This retrospective study included 24 consecutive patients; all were female. Patients with recent and mobile stress fracture (Group A) were treated with close reduction and long-stem tibial component. However, in patients with old, sclerotic or mal-united fractures (Group B), open reduction, partial fibulectomy and plating with bone grafting was also performed. Outcome was monitored by tibiofemoral angle, functional Knee Society score and time taken for union. RESULTS: The mean age of patients was 62.34 years. There were 13 patients in Group A and 11 in Group B. The mean follow up was 42.79 months (range, 18-72 months). Knee Society score improved from 29.83 ± 6.10 to 91.57 ± 4.89 in Group A and from 27.21 ± 3.32 to 89.87 ± 3.89 in Group B. Tibiofemoral angle improved from 20.57 ± 3.00° to 0.80 ± 0.46° in 21 varus knees, whereas it improved from 22.33 ± 4.61° to 0.83 ± 0.28° in three valgus knees. Iatrogenic perforation of tibial cortex occurred in one case. Union of stress fracture was achieved in all cases with a mean duration of 4.70 months. CONCLUSION: Excellent results were obtained in both groups but were slightly lower in patients presenting late, therefore all efforts must be made to treat such cases as early as possible.

Bilateral severe heterotopic ossification following primary total knee arthroplasty: a case report in Pakistan.

The incidence of unilateral minor heterotopic ossification after primary total knee arthroplasty is still unknown, but bilateral severe heterotopic ossification is rare and has not been reported before. Presented in this report is a 60-year-old female patient who developed bilateral knee pain and stiffness 2 weeks after primary total knee arthroplasty. Her weight was 70 kg and body mass index was 32.2. Preoperatively, she had bilateral varus deformity of both knees. X-rays taken 3 months after surgery revealed bilateral severe heterotopic ossification. The patient had been on non-operative treatment (including anti-inflammatory drugs and physiotherapy). There was a marked improvement 6 months after surgery. This case report showed the non-operative treatment may produce acceptable results for patients with severe bilateral heterotopic ossification after primary total knee arthroplasty, and exerted no influence on the final clinical outcome.

Economic Burden of Periprosthetic Joint Infection Following Primary Total Knee Replacement in a Developing Country.

BACKGROUND: Periprosthetic joint infection is one of the devastating complications after primary total knee arthroplasty, which increases the financial burden on patients and affects their quality of life as well. The financial burden of periprosthetic joint infection after joint replacement in developed countries is well known. There is a need to evaluate the economic burden in developing countries such as Pakistan. METHODS: This is a single-center, retrospective, case-control study conducted at the Department of Orthopedic Surgery, Liaquat National Hospital Karachi. Cases of primary total knee arthroplasty performed during this study were divided into 2 groups: uneventful primary total knee arthroplasty and periprosthetic joint infection treated with 2-stage revision. To calculate the final cost, we divided the total hospital cost into the hospital stay cost and operating room cost. RESULTS: During study period, 32 patients were diagnosed with periprosthetic joint infection. The total cost of revision surgery for periprosthetic joint infection considering 2 hospitalizations was 1,780,222 ± 313,686 Pakistani rupee (PKR). The total cost of uneventful arthroplasty was 390,172 ± 51,460 PKR. We observed significant difference with respect to economic details between the 2 groups. CONCLUSIONS: Management of periprosthetic joint infection was 4.5 times more expensive than uneventful primary total knee arthroplasty. Measures should be undertaken to reduce the prevalence of periprosthetic joint infection, thereby reducing patients' economic burden.

Management of the bone loss by metaphyseal sleeves in primary and revision knee arthroplasty: clinical experience and outcome after forty three cases.

AIM OF THE STUDY: Management of metaphyseal bone loss in complex primary and revision TKA is a challenge for surgeons. Out of various types of bony defects, large metaphyseal bone loss (AORI types IIB and III) requires special augments in the form of cones or sleeves. The aim of this study is to assess the reliability of metaphyseal sleeves, in dealing with massive bone defects to provide stability for immediate weight bearing and also to check short to mid-term survivorship of metaphyseal sleeves in Asian population by assessing various parameters and complications. METHODS: This is a retrospective study that includes 36 patients (43 knees), operated from 2011 to 2019. Patients with AORI type IIB (large metaphyseal bone defect) and AORI type III (metaphyseal defect with compromised collateral ligaments) were included. We included both the primary and revision knee arthroplasties in our study. Our interest in this study was to look for incidence of intra-operative iatrogenic fracture on the one hand, and post-operative complications in the form of peri-prosthetic joint infection and aseptic loosening on the other hand. Knee Society Score (KSS) was used to assess improvement in patient's clinical outcome. SPSS version 23 was used to process data. RESULTS: The average age of patients in our study was 59.4 (SD 9.78) years. Male to female ratio was 21:15. The average follow-up was 5.42 (SD 2.24) years with the longest follow up of nine years. Metaphyseal sleeves were used in 12 primary TKA and 31 revision TKA. During surgery, iatrogenic fracture of tibial condyle was encountered in three patients (6.9%), all were managed without any intervention and union was achieved in all cases. There was not a single case with aseptic loosening as per radiological criteria in our study. Peri-prosthetic joint infection (PJI) was encountered in a single case (2.3%). Pre-op Knee Society Score (KSS) was 36.21 (SD 7.43) where as it improved to 92.00 (SD 5.66), six months after surgery. Also the range of flexion was increased from 76.83o (SD 14.07o) to 122.91o (SD 4.84o). CONCLUSION: In our study, metaphyseal sleeves showed excellent short to mid-term survivorship in AORI types IIB and III boneloss in Asian population. These results are comparable to various studies conducted on North American and European population. Metaphyseal sleeve is a reliable tool in the armamentarium of the arthroplasty surgeon. It is user friendly implant and provides immediate stability to allow full weight-bearing mobilization.

Fate of the Retained Acetabular Component During Revision Total Hip Arthroplasty: A Meta-Analysis and Systematic Review.

BACKGROUND: The aim of this meta-analysis and systematic review is to estimate re-revision rates due to aseptic loosening of retained acetabular components after revision total hip arthroplasty. METHODS: PubMed, EMBASE, Cochrane Library, and Web of Science were searched until June 11, 2018. Data were extracted by 2 independent investigators and consensus was reached with the involvement of a third investigator. Rates of re-revision due to aseptic loosening from 6 studies were aggregated using random effects model after a logit transformation and were grouped by study and population level characteristics. RESULTS: An assessment of the re-revision rates of retained acetabular components due to aseptic loosening in revision total hip arthroplasty was reported in 6 studies involving 669 cases. The pooled re-revision rate was 12.6% (95% confidence interval 8.4-18.4) with a mean study follow-up of 8.6 years. The rate of re-revision due to aseptic loosening of retained acetabular components was 6.8% (95% confidence interval 3.4-13.3). In the univariate meta-regression analysis, mean age at index revision surgery was significantly associated with the rate of re-revision due to aseptic loosening (R2 = 99.98%, P < .0001). CONCLUSION: Based on this exploratory analysis, revision hip procedures with retentions of well-fixed acetabular components generally have a low risk of failure during mid-term to long-term follow-ups.

Knee dislocations and popliteal artery injury: A single centre experience from Karachi.

OBJECTIVE: To determine the association of popliteal artery injury with simple knee dislocations or knee fracture dislocations, and to evaluate the role of clinical assessment and colour Doppler ultrasound examination in diagnosing these injuries. METHODS: The prospective case series study was done at the Liaquat National Hospital, Karachi, and comprised patients with simple knee dislocations or knee fracture dislocations presenting between February 2013 and April 2014. All patients underwent clinical assessment including distal pulse examination and signs of vascular trauma. Following reduction of dislocation, repeat clinical examination and assessment of limb with colour Doppler ultrasound was carried out. RESULTS: Out of 9 patients in the study, 6(66.7%)had simple dislocations, while 3(33.3%) sustained fracture dislocations of the knee. Two (22%) patients sustained injury to the popliteal artery which was effectively managed via surgical treatment. Clinical examination of the affected extremities effortlessly revealed the 2(22%) vascular trauma cases. Doppler ultrasound was carried out in 8(89%) cases and it successfully excluded 7(78%) cases for vascular trauma and identified 1(11%) injury with reduced flow. This case underwent computed angiography scan and later surgery revealed popliteal artery trauma. Doppler ultrasound was not carried out in 1(11%) case which was a spontaneously relocated knee with hard signs of vascular injury. CONCLUSIONS: Popliteal artery injury can be a limb-threatening complication following trauma to the knee. Carefully performed clinical examination and colour Doppler ultrasound are effective tools for identification of such cases.

Serum alkaline phosphatase screening for vitamin D deficiency states.

OBJECTIVE: To determine whether serum vitamin D levels are correlated with serum levels of alkaline phosphatase or not. STUDY DESIGN: Cross-sectional, observational study. PLACE AND DURATION OF STUDY: Multi-centre study, conducted at Liaquat National Hospital and Medical College, National Medical Centre and Medicare Hospital, Karachi, from January to October 2009. METHODOLOGY: Patients attending the Orthopaedic OPDs with complaints of pain in different body regions and serum vitamin D3 levels of ² 30 ng/ml were included in the study. Patients with vitamin D deficiency were further categorized into mild deficiency or insufficiency (vit. D3 = 20-29 ng/ml), moderate deficiency (vit. D3 = 5 - 19 ng/ml) and severe deficiency forms (vit. D3 < 5 ng/ml). Pearson correlation was applied to test the correlation of serum alkaline phosphatase levels with serum vitamin D3 levels. P-value < 0.05 was considered to be significant. RESULTS: Out of 110 samples, 26 had mild (23%), 61 had moderate (55%) and 21 had severe (19.1%) vitamin D deficiencies. All of the patients in the three groups had alkaline phosphatase with in normal limits and the total mean value of the enzyme was 135.97 ± 68.141 U/L. The inter group comparison showed highest values of alkaline phosphatase in the moderate vitamin D deficiency group. The correlation coefficient of alkaline phosphatase and serum vitamin D3 levels was r =0.05 (p =0.593). CONCLUSION: Serum vitamin D3 levels may not be correlated with increased serum alkaline phosphatase levels. Therefore, alkaline phosphatase may not be used as a screening test to rule out vitamin D deficiency.