Objective: To evaluate pain and mobility improvement in knee osteoarthritis patients after hyaluronic acid viscosupplementation. Method: The cross-sectional, retrospective study was conducted at the Department of Orthopaedics, Aga Khan University Hospital, Karachi, and comprised data from January 2019 to December 2022 of patients having knee osteoarthritis who had received viscosupplementation with hyaluronic acid gel. Western Ontario and McMaster Universities Osteoarthritis Index score was calculated at baseline and on patient follow-up at 12 months. Data was analysed using SPSS 23 Results: Of the 180 patients with mean age 61.1+/-11.4 years, 109(60.6%) were females and 71(39.4%) were males. Mean baseline score was 69.6+/-8.3, which went down to 48.2+/-10.6 post-intervention (p<0.05), with significantly greater improvement in patients with mild to moderate knee osteoarthritis compared to those with advanced osteoarthritis (p<0.05). Conclusion: Viscosupplementation with hyaluronic acid significantly improved outcomes in knee osteoarthritis cases over one year. Benefits were more notable in mild to moderate cases. Key Words: Knee osteoarthritis, Hyaluronic acid gel, WOMAC score, Viscosupplementation, Improvement in pain. Level of Evidence : IV

Objective: To assess the frequency of restoration of mechanical axis deviation (MAD) in patients undergoing primary total knee arthroplasty (TKA) using malalignment test on pre- and postoperative weight-bearing scanograms. Methods: A prospective cohort study was conducted from August 2018 to August 2019 at a tertiary care hospital. A total of 30 patients aged 40–100 years with advanced osteoarthritis were included. Pre- and postoperative MAD was measured on full-length weight-bearing scanograms. Patients with revision TKA, rheumatoid arthritis, tumor surgeries, or failed primary TKAs were excluded. Mechanical axis deviation was assessed on the third postoperative day and correlated with functional outcome. Results: Among 30 patients, 46.7% were male and 53.3% female, with a mean age of 58.3 ± 9.8 years. The mean preoperative MAD was 26.88 ± 43.26 mm (80% medial, 20% lateral), and postoperative MAD was significantly reduced to 10.56 ± 7.31 mm (100% medial). Restoration of neutral alignment was achieved in 80% of cases. No statistically significant association was found between restoration of MAD and variables such as age, gender, BMI, comorbidities, or side of surgery (p > 0.05). Conclusion: Primary total knee arthroplasty effectively restored the mechanical axis in 80% of patients. Malalignment remains a critical factor for long-term prosthesis survival and functional outcomes. Postoperative scanogram is a reliable tool for evaluating limb alignment, although its immediate use may not reflect physiological loading. Further studies with larger cohorts and long-term follow-up are recommended.

Objective: Soft tissue sarcomas can involve major blood vessels, historically leading to amputation as the primary treatment. Advances in surgical and vascular reconstruction techniques, along with multidisciplinary care, now allow for limb preservation in selected cases. However, outcomes data from resource-limited countries remain scarce. Therefore, the aim of this study was to assess the infectious, oncological, and functional outcomes of limb salvage surgery with vascular reconstruction in patients with extremity sarcoma. Methodology: A retrospective review was conducted at Aga Khan University Hospital, Karachi, Pakistan including 29 patients (12 females, 17 males; mean age 34.6 years) who underwent elective sarcoma excision with vascular intervention from 2002 to 2024. All patients had preoperative metastatic screening and MRI to assess tumor extent and vascular involvement. Vascular reconstruction was performed using autologous or synthetic grafts, or primary repair, as appropriate. Outcomes assessed included graft patency, limb perfusion, functional status using Toronto Extremity Salvage Score (TESS), infection and other complications, recurrence and survival Results: Of the 29 patients, 89.6% had lower limb tumors, predominantly soft tissue sarcomas. Vascular reconstruction was required in 69% of cases. Postoperative arterial patency was 93.1%, and limb salvage was achieved in 82.7%. The mean Toronto Extremity Salvage Score (TESS) was 84.2, with 79% of patients achieving good to excellent function. Complications included wound infections (20.6%), graft infections (6.9%), and thrombosis (6.9%). Local recurrence occurred in 13.8% and distant metastasis in 24.1%. The mean follow-up was 55.2 months, with a 20.7% mortality rate due to metastatic disease. Overall mean survival was 8.6 years while five years survival rate was 73%. Conclusion: Limb salvage with vascular reconstruction for extremity sarcomas is feasible and effective, offering good functional outcomes. Although postoperative complications may occur but they are manageable with amputation reserved as a last option.

Objective: This study focuses on assessing the efficacy of intra-articular viscosupplementation, specifically hyaluronic acid (HA), in individuals with mild to moderate knee OA in a Pakistani population. The Knee Society Score (KSS) was employed as an outcome measure to evaluate pain and functional improvement. This study explores the potential of HA injections in providing relief, reducing pain, and improving joint function. Methods: The research methodology involves a single-center, single-arm, prospective observational study conducted at a tertiary care hospital in Karachi. Patients with mild to moderate knee OA received intra-articular HA injections, and their KSS was assessed before and after a 12-month followup. The study aims to contribute pivotal insights to bridge the existing knowledge gap and formulate evidence-based guidelines tailored to the Pakistani population. Results: The study included patients with a mean age of 55.59 ± 13.351, and 14 patients received bilateral knee injections, while 11 opted for unilateral treatment. The mean BMI was 32.2 ± 4.71. Based on Kellgren and Lawrence classification, 46.2% had grade I knee OA, and 53.8% had grade II. Initial Knee Society Score and Knee Society Function Score were 72.28 ± 11.18 and 66.79 ± 15.23, respectively. After twelve months, both scores improved significantly to 81.28 ± 9.7 and 76.54 ± 15.39. The improvement was more pronounced in grade I OA. No significant differences were observed based on gender or BMI. Conclusion: Intra-articular viscosupplementation using HA emerges as a safe and effective treatment for mild to moderate knee OA. The results underscore the potential for HA to offer symptomatic relief and highlight the need for further multicenter studies with substantial sample sizes to establish a standardized treatment algorithm. The study aims to contribute to informed and effective management paradigms for knee osteoarthritis in the Pakistani context

BACKGROUND:Pain is a common yet underaddressed issue in surgical inpatients. Inadequate pain control in patients with hip fractures can lead to adverse hemodynamic changes, potentially increasing the risk of myocardial ischemia. The authors aim to investigate whether perioperative pain is associated with the development of myocardial ischemic events in patients undergoing hip fracture surgery. METHODS:HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) was a multicenter international randomized controlled trial comparing the effects of accelerated surgical repair of hip fracture versus standard of care. The authors included patients enrolled in the HIP ATTACK trial who had at least one troponin measurement and a pain score measurement. Pain was assessed daily on hospital admission using the 0 to 10 numeric rating scale. The primary analysis included all available pain scores averaged (then categorized as mild [numeric rating scale 0 to 3], moderate [4 to 7], and severe [8 to 10] pain) before and on the day of the first troponin elevation. The primary outcome was troponin elevation from any cause, with secondary outcomes of myocardial injury (due to an ischemic etiology), myocardial infarction, and then a composite of myocardial injury and myocardial infarction. Multivariable regression models adjusting for potential confounders were used to identify an association between pain categories and outcomes. RESULTS:The authors included 2,430 (82%) from the initial HIP ATTACK cohort (n = 2,970). Forty-five percent of patients (1,098) suffered a troponin elevation from any cause. In the adjusted models, moderate (odds ratio, 3.90; 95% CI, 3.02 to 5.05) and severe pain (odds ratio, 29.24; 95% CI, 17.7 to 48.29) were associated with a troponin elevation of any cause. Similarly, moderate (odds ratio, 2.09; 95% CI, 1.71 to 2.57) and severe pain (odds ratio, 6.04, 95% CI, 4.49 to 8.12) were associated with myocardial injury, whereas only severe pain was associated with myocardial infarction (odds ratio, 2.33; 95% CI, 1.35 to 3.99). Both moderate and severe pain were associated with the composite outcome. CONCLUSIONS:Increased pain may be associated with myocardial ischemic events in the perioperative period in hip fracture patients. Future research is needed to confirm and further clarify this relationship and to determine whether analgesic interventions can reduce the risk of perioperative myocardial ischemia.

A case series was conducted between January 2010 and January 2018, which included 17 paediatric patients under the age of 18 years (mean age 13.4 ±3.53), who underwent internal hemipelvectomy. Functional outcomes were assessed based on gait and categorised as either normal or abnormal. The most common diagnosis was Ewings Sarcoma in 14 patients (82.3%). With regards to reconstruction, acetabular reconstruction was necessary in 1 patient (5.9%), and soft tissue coverage with flaps was required in 5 cases (29.4%). Nerve injury was the most common complication noted, i.e. in 5 cases (29.4%). The disease-free survival rate was 12 patients (70.6%) at a median time of 72 months, while the overall mortality rate was 5 patients (29.4%) with metastatic disease being the leading cause. Hence, it was concluded that internal hemipelvectomy is a viable surgical option in the paediatric population particularly when negative margins can be achieved without compromising the neurovascular structures. Keywords: Tumour, Paediatric, Internal hemipelvectomy.

Purpose: Simple bone cysts are among the most prevalent benign cystic tumor-like lesions in children. Proximal femoral simple bone cysts may require specific treatment because of increased fracture risk. With limited literature available on this specific localization, consensus regarding optimal treatment is lacking. We present a large international multicenter retrospective cohort study on proximal femoral simple bone cysts. Methods: All consecutive pediatric patients with proximal femoral simple bone cyst from 10 tertiary referral centers for musculoskeletal oncology were included (2000–2021). Demographics, primary treatment, complications, and re-operations were evaluated. Primary outcomes were time until full weight-bearing and failure-free survival. Results: Overall, 74 simple bone cyst patients were included (median age 9 years (range = 2–16), 56 (76%) male). Median follow-up was 2.9 years (range = 0.5–21). Index procedure was watchful waiting (n = 6), percutaneous procedure (n = 12), open procedure (n = 50), or osteosynthesis alone (n = 6). Median time until full weight-bearing was 8 weeks (95% confidence interval = 0.1–15.9) for watchful waiting, 9.5 (95% confidence interval = 3.7–15.3) for percutaneous procedure, 11 (95% confidence interval = −0.7 to 13.7) for open procedure, and 6.5 (95% confidence interval = 5.9–16.1) for osteosynthesis alone (p = 0.58). Failure rates were 33%, 58%, 29%, and 0%, respectively (p = 0.069). Overall failure-free survival at 1, 2, and 5 years was 77.8% (95% confidence interval = 68.2–87.4), 69.5% (95% confidence interval = 58.5–80.5), and 62.0% (95% confidence interval = 47.9–76.1), respectively. Conclusion: A preferred treatment for proximal femoral simple bone cysts remains unclear, with comparable failure rates and times until full weight-bearing. Watchful waiting may be successful in certain cases. If not feasible, osteosynthesis alone can be considered. Treatment goals should be cyst control, minimizing complications and swift return to normal activities. Therefore, an individualized balance should be made between undertreatment, with potentially higher complication risks versus overtreatment, resulting in possible larger interventions and accompanying complications. Level of evidence: Level IV, retrospective multicentre study

Background Acetabular fractures, a rising concern in developing countries, pose a significant challenge due to their complexity and association with post-operative complications. Often caused by high-energy mechanisms like falls and motor vehicle accidents, these fractures require accurate reduction to prevent long-term issues and the potential need for hip replacement. This study investigates the radiological outcomes of acetabular fracture surgery at six months, focusing on the effectiveness of achieving anatomical reduction using the Matta criteria in a low-and middle-income country (LMIC) setting. Methods and materials This prospective study was conducted at a tertiary care center in Pakistan from May 2023 to December 2023, with ethical approval. Patients with isolated acetabular fractures were recruited. Preoperative X-rays and CT scans classified fractures using the Judet and Letournel Classification. Six-month postoperative X-rays were assessed using Matta radiographic criteria. Appropriate statistical analysis was deployed with a significance level at p < 0.05. Results A total of 33 cases met the study criteria, and the mean average age of patients was 44.18 ±17.2 years. Males constituted 87.9% of the cases. Longer hospital stays were associated with poorer outcomes (p < 0.001). Fracture patterns were significant predictors of outcomes (p < 0.001). Six months post-surgery, 45.5% of patients had excellent results, 24.2% had good results, and 15.2% each had fair and poor results according to the Matta radiographic criteria. Avascular necrosis (AVN) developed in 9.1% of patients. Of the 10 patients with femoral head dislocation, only one developed AVN Conclusion This LMIC-based study investigated factors affecting outcomes in patients with acetabular fractures treated using Open Reduction and Internal Fixation (ORIF). We found a relatively younger patient population, and injury patterns suggested a link to the local environment (e.g., traffic accidents). Optimizing hospital stay and timely surgery improved radiological outcomes as assessed by Matta criteria. While limitations exist, the study supports using Matta criteria in LMICs. Additionally, the use of plain radiographs, rather than CT scans, offers a cost-effective and radiation-reducing alternative for post-operative evaluation in resource-constrained settings.

Background: Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the physiological stress associated with the hip fracture. This study aimed to determine if accelerated surgery is superior to standard care in terms of the 90-day risk of death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme measurement at hospital arrival. Methods: The HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard care in reducing death or major complications. This substudy is a post-hoc analysis of 1392 patients (from the original study of 2970 patients) who had a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement and thus “troponin” is the term used throughout the paper) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality and non-fatal myocardial infarction, stroke, and congestive heart failure 90 days after randomization. Results: Three hundred and twenty-two (23%) of the 1392 patients had troponin elevation at hospital arrival. Among the patients with troponin elevation, the median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] = 5 to 13) in the accelerated surgery group and 29 hours (IQR = 19 to 52) in the standard care group. Patients with troponin elevation had a lower risk of mortality with accelerated surgery compared with standard care (17 [10%] of 163 versus 36 [23%] of 159; hazard ratio [HR] = 0.43 [95% confidence interval (CI) = 0.24 to 0.77]) and a lower risk of the secondary composite outcome (23 [14%] of 163 versus 47 [30%] of 159; HR = 0.43 [95% CI = 0.26 to 0.72]). Conclusions: One in 5 patients with a hip fracture presented with myocardial injury. Accelerated surgery resulted in a lower mortality risk than standard care for these patients; however, these findings need to be confirmed. Level of Evidence: Therapeutic Level I . See Instructions for Authors for a complete description of levels of evidence.

Background Managing primary bone and soft tissue sarcomas in pediatric patients poses significant challenges, with surgical resection remaining essential for cure. While limb salvage surgery has emerged as the standard approach, concerns persist regarding post-operative complications. Our study aims to evaluate the 30-day morbidity and mortality of limb salvage surgery in pediatric tumor patients, bridging critical knowledge gaps and contributing to enhancing the standard of care in low- and middle-income countries (LMICs). Materials and methods A prospective cohort study was conducted on pediatric patients (aged 18 years or younger) who presented at a tertiary care hospital's orthopedics department and required limb salvage surgery due to various tumors from May 2021 to October 2023. Results Nineteen cases met the inclusion criteria. The average patient age was 12.2 years (SD = 4.71), with 5 (20.8%) females and 14 (79.2%) males. Bone tumors accounted for 12 (63.2%) cases, and soft tissue tumors for 7 (36.8%). Osteosarcoma was the most common tumor (36.8%), followed by Ewing Sarcoma (31.57%) and Synovial Sarcomas (15.8%). Free fibular grafts were used in 6 (31.6%) cases, and Mega prosthesis in 3 (15.8%). Overall, 26.3% of cases experienced post-surgical complications within 30 days, notably including surgical site infections (21.05%) and flap necrosis (10.53%). No significant differences in demographic and clinical variables were observed between patients with and without complications. Conclusion Our study highlights immediate post-operative outcomes and complications of limb salvage surgery in pediatric musculoskeletal tumor patients, particularly in LMIC settings. Despite advancements, early complications remain challenging, with nearly one-quarter of patients experiencing adverse events within 30 days. The prevalence of surgical site infections emphasizes the urgent need for improved infection control measures in LMICs.

INTRODUCTION:Pelvic fractures, encompassing a spectrum from minor to life-threatening injuries, pose challenges in trauma management. This study focuses on short-term outcomes, exploring morbidity and mortality within 30 days postoperative, among pelvic fracture patients at a tertiary care hospital in Karachi, Pakistan. The majority of pelvic injuries result from intense blunt trauma, with associated risks of concomitant injuries. Pelvic fractures are linked to early complications such as hemorrhage, thromboembolism, and infections, influencing mortality rates. METHODOLOGY:A prospective cohort study involving 53 surgically managed pelvic fracture patients was conducted at Aga Khan University Hospital, Karachi. Variables such as age, gender, comorbidities, mechanism of injury, associated injuries, and presenting vitals were documented. Thirty-day morbidity included surgical site infections, hemorrhagic shock, nerve injuries, and others. Statistical analyses assessed associations between patient characteristics and morbidity. RESULTS:The study revealed a median age of 37 years, with 77% male patients. Most fractures result from motor vehicle accidents. Morbidity occurred in 31.6% of cases, primarily associated with the presence of associated injuries. Postoperative complications included neurological deficits (15.1%) and pulmonary complications (9.4%). No 30-day mortality was reported. DISCUSSION:The study highlights the importance of a multidisciplinary approach in managing pelvic fractures, emphasizing the association between associated injuries and postoperative morbidity. Comorbidities did not significantly impact morbidity, emphasizing the traumatic nature's independent contribution. Timely presentation (median 20 hours) and efficient trauma systems are crucial for optimal outcomes. CONCLUSION:This research contributes insights into short-term outcomes following pelvic fracture fixation in a Pakistani tertiary care setting. By exploring a range of parameters, the study emphasizes the need for comprehensive management strategies to minimize complications and improve patient outcomes. Bridging critical knowledge gaps, this research informs clinical decision-making for pelvic fracture patients in this region.

Background: Myocardial injury after a hip fracture is common and has a poor prognosis. Patients with a hip fracture and myocardial injury may benefit from accelerated surgery to remove the physiological stress associated with the hip fracture. This study aimed to determine if accelerated surgery is superior to standard care in terms of the 90-day risk of death in patients with a hip fracture who presented with an elevated cardiac biomarker/enzyme measurement at hospital arrival. Methods: The HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) trial was a randomized controlled trial designed to determine whether accelerated surgery for hip fracture was superior to standard care in reducing death or major complications. This substudy is a post-hoc analysis of 1392 patients (from the original study of 2970 patients) who had a cardiac biomarker/enzyme measurement (>99.9% had a troponin measurement and thus "troponin" is the term used throughout the paper) at hospital arrival. The primary outcome was all-cause mortality. The secondary composite outcome included all-cause mortality and non-fatal myocardial infarction, stroke, and congestive heart failure 90 days after randomization. Results: Three hundred and twenty-two (23%) of the 1392 patients had troponin elevation at hospital arrival. Among the patients with troponin elevation, the median time from hip fracture diagnosis to surgery was 6 hours (interquartile range [IQR] = 5 to 13) in the accelerated surgery group and 29 hours (IQR = 19 to 52) in the standard care group. Patients with troponin elevation had a lower risk of mortality with accelerated surgery compared with standard care (17 [10%] of 163 versus 36 [23%] of 159; hazard ratio [HR] = 0.43 [95% confidence interval (CI) = 0.24 to 0.77]) and a lower risk of the secondary composite outcome (23 [14%] of 163 versus 47 [30%] of 159; HR = 0.43 [95% CI = 0.26 to 0.72]). Conclusions: One in 5 patients with a hip fracture presented with myocardial injury. Accelerated surgery resulted in a lower mortality risk than standard care for these patients; however, these findings need to be confirmed.

Background Total knee arthroplasty has become very popular globally as a safe surgical modality for relieving pain and improving functional outcomes in patients who fail to respond to conservative treatments; however, it may be associated with postoperative complications. The aim of this study is to determine the incidence of postoperative complications occurring within the first 30 days after total knee replacement (TKR). Materials and methods This is a prospective cross-sectional study. All consecutive patients who underwent primary unilateral or bilateral total knee arthroplasty between November 2020 and July 2021 were included in the study. Patients were followed for a period of 30 days, and postoperative complications (if any) were documented. Continuous variables were expressed as means ± standard deviations. Categorical variables were expressed as frequency and percentages, and chi-square test was used to compare the qualitative variables. Univariate and multiple logistic regression analyses were done to analyze the magnitude of associations of the complication with other predictor variables keeping a level of significance of <0.05. Results The overall complication rate within the 30-day window was 7.0%. Postoperative surgical site infections (SSI) were noted in three patients (2.6%). Thromboembolic complications were seen in only one patient (0.9%). One patient (0.9%) was readmitted within the one-month period after initial discharge, and one patient (0.9%) expired within 12 hours postoperatively. Conclusion TKR renders satisfactory results with a low incidence of complications in general; however, wound infections, thromboembolic complications, and cardiovascular complications do occur postoperatively. Male gender, obesity, and bilateral TKRs remain the notable risk factors for the development of complications post-procedure.

Due to its high prevalence, we aimed to create postmenopausal osteoporosis clinical practice guideline via GRADE-ADOLOPMENT for Pakistan. We recommend a higher dose (2000–4000 IU) of vitamin D for osteoporotic patients who are old, have malabsorption, or are obese. The guideline will help standardize care provision and improve health care outcomes for osteoporosis. Postmenopausal osteoporosis affects one in every five postmenopausal women in Pakistan. An evidence-based clinical practice guideline (CPG) is needed to standardize care provision to optimize health outcomes. Hence, we aimed to develop CPG for the management of postmenopausal osteoporosis in Pakistan. The GRADE-ADOLOPMENT process was used to adopt (as is or with minor changes), exclude (omit), or adapt (modify based on local context) recommendations to the source guideline (SG)—clinical practice guidelines for the diagnosis and treatment of postmenopausal osteoporosis—2020 update from American Association of Clinical Endocrinology (AACE). The SG was “adoloped” to cater to the local context. The SG consisted of 51 recommendations. Forty-five recommendations were adopted as is. Due to unavailability of drugs, 4 recommendations were adopted with minor changes, and one was excluded, while one recommendation was adopted with the inclusion of use of a surrogate FRAX tool specific for Pakistan. One recommendation regarding vitamin D dosage was adapted to recommend a dose of 2000–4000 IU of vitamin D in patients with obesity, malabsorption, and old age. The developed Pakistani postmenopausal osteoporosis guideline consists of 50 recommendations. The guideline created recommends a higher dose (2000–4000 IU) of vitamin D for patients who are old, have malabsorption, or are obese, which is an adaptation from the SG by the AACE. This higher dose is justified as lower doses prove to be suboptimal in these groups and should be complemented with baseline vitamin D and calcium levels.

Abstract Background Giant cell tumor (GCT) of bone is a benign lesion which is characterized by presence of multinucleated osteoclasts type giant cells. Nuclear factor kappa B (RANKL) serves as the trigger factor for osteoclasts cells formation. Although surgery is the primary treatment for GCT of bone but recurrence remains the concern. Therefore, the development of denosumab, a monoclonal antibody for treating GCT for both primary and recurrent disease cases. The present study aims to show the role of denosumab along with surgery when given as neo-adjuvant drug to patients of GCT for their treatment.Methodology:A total of 23 patients diagnosed with GCT were included in this study from January 2016- December 2019 and all of these patients had received neo adjuvant denosumab dose of 120 mg SC on day 0, 15, 30 & 45. All patients were treated at the section of Orthopedics, department of surgery, Aga Khan University hospital, Karachi. Other benign lesions were excluded from the study.Results Out of 23 patients we had 12 (52.2%) males and 11 (47.8%) females. The mean age of our patients was 34 13.8 years and mean follow up duration of all patients was 20.5±10.7 months. There were 15 (65.2%) primary cases of GCT while 8 (34.8%) were recurrent cases. In 8 (34.8%) of the cases primary site of lesion was distal femur followed by 7(30.4%). In surgical procedure 20 (87%) patients underwent wide margin excision and only 3 (13%) had intralesional curettage. Reconstruction was performed in 21 patients which consist of bone grafting in 9 patients and mega prosthesis insertion in 12 patients. Only two patients had no reconstruction. On final histopathology, there was no residual GCT and we observed no denosumab induced adverse effects. Post-operative complications included wound infection and peri prosthetic infection in 3 patients. On follow-up we had 4(17.4%) cases of recurrence that were offered revision surgery while 19 (82.6%) were disease free.Conclusion:Denosumab has shown successful results in treating patients with GCT along with surgical intervention and it can be a best option for treating recurrent disease as well.Research registration no: researchregistry4695

AbstractBackgroundOver or sub-optimal analgesic treatment leads to undesired consequences and patient dissatisfaction. The study aims to assess the sub-optimal or optimal pain relief and safety of routinely prescribed oral analgesic(s) at discharge and 1-week post-discharge in ankle and foot fracture surgeries.MethodsThe ongoing prospective cohort study data on 54 ankle and hindfoot trauma fracture adult patients enrolled between June 2022 to July 2023 was analyzed. Post-surgery oral analgesics prescribed at hospital discharge and 1-week follow-up were stratified for assessing adverse events and pain (Visual Analogue Scale) at 1- and 2 weeks post-discharge. The relationship of age, gender, and comorbidity was analyzed by multiple logistic regression for adverse events and multiple linear regression for pain score.ResultsMedian pain scores at 1- and 2-week follow-ups were 3.2 (IQR=3.0) and 2 (IQR=2.0) respectively. Combinations of tramadol, acetaminophen with naproxen or diclofenac or orphenadrine; and naproxen, pregabalin, with acetaminophen seemed toxic with sub-optimal pain control. Similar results were for celecoxib combined with pregabalin and etoricoxib combined with diclofenac or tramadol. Acetaminophen alone was safe but occasionally showed intolerance. Etoricoxib or diclofenac alone or with acetaminophen was safe and showed better pain control in this cohort. A regression model was non-significant for a relationship between covariates and pain scores or adverse events.ConclusionCurrent data suggests that certain oral analgesics or their combinations are harmful with sub-optimal pain control while some are safe and effective. Choosing suitable analgesics or their combinations in specific fractures might reduce patient harm with optimal pain management.

Background: Aneurysmal bone cysts (ABC) are rare benign cystic bone tumors, generally diagnosed in children and adolescents. Proximal femoral ABCs may require specific treatment strategies because of an increased pathologic fracture risk. As few reports are published on ABCs, specifically for this localization, consensus regarding optimal treatment is lacking. We present a large retrospective study on the treatment of pediatric proximal femoral ABCs. Methods: All eligible pediatric patients with proximal femoral ABC were included, from 11 tertiary referral centers for musculo-skeletal oncology (2000-2021). Patient demographics, diagnostics, treatments, and complications were evaluated. Index procedures were categorized as percutaneous/open procedures and osteosynthesis alone. Primary outcomes were: time until full weight-bearing and failure-free survival. Failure was defined as open procedure after primary surgery, >3 percutaneous procedures, recurrence, and/or fracture. Risk factors for failure were evaluated. Results: Seventy-nine patients with ABC were included [mean age, 10.2 (±SD4.0) y, n=56 male]. The median follow-up was 5.1 years (interquartile ranges=2.5 to 8.8). Index procedure was percutaneous procedure (n=22), open procedure (n=35), or osteosynthesis alone (n=22). The median time until full weight-bearing was 13 weeks [95% confidence interval (CI)=7.9-18.1] for open procedures, 9 weeks (95% CI=1.4-16.6) for percutaneous, and 6 weeks (95% CI=4.3-7.7) for osteosynthesis alone (P=0.1). Failure rates were 41%, 43%, and 36%, respectively. Overall, 2 and 5-year failure-free survival was 69.6% (95% CI=59.2-80.0) and 54.5% (95% CI=41.6-67.4), respectively. Risk factors associated with failure were age younger than 10 years [hazard ratios (HR)=2.9, 95% CI=1.4-5.8], cyst volume >55 cm3 (HR=1.7, 95% CI=0.8-2.5), and fracture at diagnosis (HR=1.4, 95% CI=0.7-3.3). Conclusions: As both open and percutaneous procedures along with osteosynthesis alone seem viable treatment options in this weight-bearing location, optimal treatment for proximal femoral ABCs remains unclear. The aim of the treatment was to achieve local cyst control while minimizing complications and ensuring that children can continue their normal activities as soon as possible. A personalized balance should be maintained between undertreatment, with potentially higher risks of pathologic fractures, prolonged periods of partial weight-bearing, or recurrences, versus overtreatment with large surgical procedures, and associated risks. Level of Evidence: Level IV, therapeutic study.

Introduction: Sarcomas are tumors that are mesenchymal in origin involving bone and soft tissues occurring in all age groups. Giant cell tumor, although benign, is locally aggressive and can also destroy the bone. Amputation was once considered primary treatment but now with advancements in diagnostic imaging modalities, surgical procedures and adjuvant therapies, limb salvage surgeries have become the preferred treatment modality. The primary objective of our study was to determine the incidence of early complications occurring within the first thirty days in patients who underwent limb salvage surgery at our hospital. The secondary objective was to assess the association of these complications with patient-related factors, surgical modality, tumor characteristics and neoadjuvant therapy. Methodology: All the patients with bone or soft tissue sarcoma and aggressive giant cell tumors of the extremities who underwent wide excision and limb salvage surgery from February 2020 to December 2021 were included in this study. Data were collected prospectively on follow-up visits in the clinic for one month. Data were compiled and analyzed using SPSS version 22. A p-value of <0.05 was considered significant throughout the study. Results: A total of 60 patients were included in this study. The mean age of the patients was 39.90 years. Bone and soft tissue tumors were found in 35 and 25 patients respectively. A total of 13 patients experienced postoperative complications within 30 days of surgery. The association of these postoperative complications with gender distribution, prior comorbid conditions, type of tumor, anatomical location of the tumor and neoadjuvant therapy was found to be statistically insignificant. Conclusion: The most frequently occurring postoperative complications are wound-related and the incidence of these complications is independent of the proposed risk factors.

Acute kidney injury (AKI) is a lesser-known complication of hip fracture that may come about owing to decreased kidney perfusion and heightened inflammation from trauma, pain, bleeding, and fasting.1Sharfuddin A.A. Molitoris B.A. Pathophysiology of ischemic acute kidney injury.Nat Rev Nephrol. 2011; 7: 189-200Crossref PubMed Scopus (549) Google Scholar,2Kinsey G.R. Li L. Okusa M.D. Inflammation in acute kidney injury.Nephron Exp Nephrol. 2008; 109: e102-e107Crossref PubMed Scopus (320) Google Scholar Approximately 15%-20% of patients undergoing surgery for a hip fracture develop AKI, with 0.5%-1.8% receiving dialysis.3Bennet S.J. Berry O.M.B. Goddard J. Keating J.F. Acute renal dysfunction following hip fracture.Injury. 2010; 41: 335-338Abstract Full Text Full Text PDF PubMed Scopus (72) Google Scholar, 4Ulucay C. Eren Z. Kaspar E.C. et al.Risk factors for acute kidney injury after hip fracture surgery in the elderly individuals.Geriatr Orthop Surg Rehabil. 2012; 3: 150-156Crossref PubMed Scopus (52) Google Scholar, 5Hong S.E. Kim T.-Y. Yoo J.-H. et al.Acute kidney injury can predict in-hospital and long-term mortality in elderly patients undergoing hip fracture surgery.PLoS One. 2017; 12e0176259Crossref Scopus (26) Google Scholar A strategy of accelerating the time to surgery after a hip fracture was recently compared with standard care in HIP ATTACK-1 (ClinicalTrials.gov identifier NCT02027896), a multinational randomized clinical trial.6Borges F.K. Bhandari M. Patel A. et al.Rationale and design of the HIP fracture Accelerated surgical TreaTment And Care tracK (HIP ATTACK) Trial: a protocol for an international randomised controlled trial evaluating early surgery for hip fracture patients.BMJ Open. 2019; 9e028537Crossref Scopus (18) Google Scholar,7Borges F.K. Bhandari M. Guerra-Farfan E. et al.Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial.Lancet. 2020; 395: 698-708Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar Enrollment occurred March 2014 through May 2019, and 2,970 patients from 69 hospitals in 17 countries were randomized. Compared with standard care, accelerated medical assessment and surgical repair did not significantly lower the risk of the 2 co–primary outcomes (mortality and major perioperative complications), although it did decrease the risk of delirium, moderate-to-severe pain, and urinary tract infection, and resulted in faster mobilization and a shorter hospital stay.7Borges F.K. Bhandari M. Guerra-Farfan E. et al.Accelerated surgery versus standard care in hip fracture (HIP ATTACK): an international, randomised, controlled trial.Lancet. 2020; 395: 698-708Abstract Full Text Full Text PDF PubMed Scopus (137) Google Scholar We conducted a prespecified kidney substudy of HIP ATTACK-1 to examine the effect of accelerated surgical treatment versus standard care on AKI in patients with a hip fracture.8Borges F.K. Devereaux P.J. Cuerden M. et al.Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture: a substudy protocol of the hip fracture Accelerated surgical TreaTment and Care tracK (HIP ATTACK) international randomised controlled trial.BMJ Open. 2019; 9e033150Google Scholar Eligibility criteria for the main trial and the kidney substudy are provided in Table S1, and substudy methods are detailed in Item S1; minor changes in substudy execution compared to the published protocol8Borges F.K. Devereaux P.J. Cuerden M. et al.Effects of accelerated versus standard care surgery on the risk of acute kidney injury in patients with a hip fracture: a substudy protocol of the hip fracture Accelerated surgical TreaTment and Care tracK (HIP ATTACK) international randomised controlled trial.BMJ Open. 2019; 9e033150Google Scholar are summarized in Table S2. Briefly, eligible patients aged ≥45 years who presented to the emergency department with a hip fracture were randomly allocated (1:1) to receive accelerated surgical repair or standard care. The primary outcome of the substudy was AKI, defined as an Scr increase (from the prerandomization value) of ≥0.3 mg/dL (26.5 μmol/L) within 48 hours after randomization, or an increase of ≥50% within 7 days after randomization.9Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work GroupKDIGO clinical practice guideline for acute kidney injury.Kidney Int Suppl. 2012; 2: 1-138Google Scholar Six secondary definitions of AKI (listed in Item S1) were also examined. Of 2,970 patients randomized in HIP ATTACK-1, 2,445 (82%) were included in the substudy (Figure S1). Baseline characteristics of patients in the substudy are shown in Table 1 (corresponding data for the main trial are in Table S3). The baseline, prerandomization Scr was obtained at the time of hospital admission for 99% of patients and before the hospital admission for 1%. The accelerated surgery group had surgery earlier than the standard care group and the mean between-group difference in the time from hip fracture diagnosis to surgery was 18 (95% CI, 15-20) hours.Table 1Baseline Characteristics and Surgical DetailsAccelerated Surgery (n = 1,216)Standard Care (n = 1,229)Sociodemographic characteristicsAge, y79 ± 1279 ± 11Female sex852 (70%)852 (69%)Ethnicity White755 (62%)767 (62%) Asian363 (30%)360 (29%) Hispanic/Latino50 (4%)60 (5%) Black/African descent39 (3%)38 (3%) Other9 (1%)4 (<1%)Health history before hip fractureHistory of tobacco use in 5 years before randomization338 (28%)294 (24%)Residing in a nursing home219 (18%)234 (19%)Comorbidities Hypertension736 (61%)750 (61%) Needing assistance with activities of daily living392 (32%)431 (35%) Diabetes271 (22%)250 (20%) Dementia210 (17%)226 (18%) Osteoporosis201 (17%)200 (16%) Chronic obstructive pulmonary disease127 (10%)106 (9%) Stroke107 (9%)95 (8%) Myocardial infarction103 (8%)93 (8%) Hip fracture80 (7%)104 (8%) Congestive heart failure86 (7%)61 (5%) Coronary revascularization77 (6%)72 (6%) Chronic atrial fibrillation63 (5%)65 (5%) Active canceraA patient with a diagnosis of cancer who is receiving, or has received, active cancer treatment (eg, chemotherapy, radiation, or surgery) in the previous 6 months.62 (5%)61 (5%) Transient ischemic attack60 (5%)67 (5%) Peripheral vascular disease37 (3%)44 (4%) Aortic stenosis29 (2%)25 (2%) Deep venous thrombosis21 (2%)26 (2%) Subarachnoid hemorrhage15 (1%)7 (1%) Pulmonary embolism13 (1%)8 (1%) Kidney failure receiving dialysis0 (0%)0 (0%) Coronary artery bypass graft42 (3%)37 (3%) Percutaneous coronary intervention47 (4%)41 (3%)New diagnoses from time of hip fracture until randomizationInfection27 (2%)27 (2%)Atrial fibrillation8 (1%)9 (1%)Significant hyponatremia or hypernatremia8 (1%)9 (1%)Significant hypokalemia or hyperkalemia9 (1%)4 (<1%)Non-ST-elevation MI without mechanical complicationbMechanical complication included acute papillary muscle rupture or ventricular septal defect.10 (1%)4 (<1%)MI with ST elevation or mechanical complicationbMechanical complication included acute papillary muscle rupture or ventricular septal defect.2 (<1%)2 (<1%)Congestive heart failure0 (0%)2 (<1%)Glasgow Coma Scale <12 of unknown origin2 (<1%)1 (<1%)Subarachnoid hemorrhage1 (<1%)2 (<1%)Stroke0 (0%)1 (<1%)Expanded acute medical conditioncOccurred after the hip fracture but before randomization (eg, cardiac or central nervous system conditions; full details in Item S2).66 (5%)56 (5%)Prerandomization physiological measurementsBody mass index, kg/m224 [21, 27]24 [21, 27]Obesity: body mass index ≥30 kg/m2129 (11%)110 (10%)Systolic blood pressure, mm Hg141 [130, 160]141 [126, 160]Diastolic blood pressure, mm Hg78 [70, 86]77 [69, 85]Heart rate, beats per minute80 [71, 89]80 [70, 90]Prerandomization laboratory measurementsHemoglobin, g/L121 ± 18121 ± 18Scr, mg/dL0.95 ± 0.400.96 ± 0.41eGFR, mL/min/1.73 m269 ± 2368 ± 22 <30 mL/min/1.73 m259 (5%)60 (5%) 30-44 mL/min/1.73 m2143 (12%)156 (13%) 45-59 mL/min/1.73 m2212 (17%)248 (20%) 60-89 mL/min/1.73 m2596 (49%)582 (47%) ≥90 mL/min/1.73 m2206 (17%)183 (15%)Medications taken at least once 7 days to 24 h before surgeryACEI/ARB412 (34%)410 (33%)Antiplatelet agent351 (29%)322 (26%)Statin310 (25%)327 (27%)β-blocker286 (24%)274 (22%)Prophylactic antithrombotic59 (5%)156 (13%)Therapeutic dose vitamin K antagonist37 (3%)43 (4%)Therapeutic non–vitamin K antagonist anticoagulant25 (2%)28 (2%)Prothrombin complex concentrate3 (<1%)2 (<1%)Medications taken ≤24 h before surgeryACEI/ARB288 (24%)244 (20%)Antiplatelet agent201 (17%)130 (11%)Statin223 (18%)226 (18%)β-blocker215 (18%)216 (18%)Prophylactic antithrombotic123 (10%)325 (26%)Therapeutic dose vitamin K antagonist19 (2%)4 (<1%)Therapeutic non–vitamin K antagonist anticoagulant22 (2%)29 (2%)Prothrombin complex concentrate16 (1%)8 (1%)Type of fracturedSome patients had more than 1 type of fracture.Intertrochanteric631 (52%)638 (52%)Femoral neck527 (43%)528 (43%)Subtrochanteric76 (6%)71 (6%)Other2 (<1%)1 (<1%)Intraoperative anestheticNeuraxial766 (63%)782 (64%)General406 (34%)395 (33%)General and neuraxial36 (3%)36 (3%)Type of hip surgery performedOpen reduction and internal fixation779 (64%)777 (63%)Arthroplasty427 (35%)434 (35%) Hemiarthroplasty351 (29%)356 (29%) Total hip arthroplasty71 (6%)77 (6%) Other arthroplasty5 (<1%)1 (<1%)Other3 (<1%)1 (<1%)Data presented as mean ± SD, median [25th, 75th percentile], or number (percentage). Body mass index was missing in 137 participants (6% in accelerated surgery group and 6% in standard care group); missing data on other variables was <2%. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker; eGFR, estimated glomerular filtration rate (calculated with CKD-EPI equation10Levey A.S. Stevens L.A. Schmid C.H. et al.A New Equation to Estimate Glomerular Filtration Rate.Ann Intern Med. 2009; 150: 604-612Crossref PubMed Scopus (16605) Google Scholar); MI, myocardial infarction; Scr, serum creatinine concentration.a A patient with a diagnosis of cancer who is receiving, or has received, active cancer treatment (eg, chemotherapy, radiation, or surgery) in the previous 6 months.b Mechanical complication included acute papillary muscle rupture or ventricular septal defect.c Occurred after the hip fracture but before randomization (eg, cardiac or central nervous system conditions; full details in Item S2).d Some patients had more than 1 type of fracture. Open table in a new tab Data presented as mean ± SD, median [25th, 75th percentile], or number (percentage). Body mass index was missing in 137 participants (6% in accelerated surgery group and 6% in standard care group); missing data on other variables was <2%. Abbreviations: ACEI/ARB, angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker; eGFR, estimated glomerular filtration rate (calculated with CKD-EPI equation10Levey A.S. Stevens L.A. Schmid C.H. et al.A New Equation to Estimate Glomerular Filtration Rate.Ann Intern Med. 2009; 150: 604-612Crossref PubMed Scopus (16605) Google Scholar); MI, myocardial infarction; Scr, serum creatinine concentration. AKI occurred in 13.5% (163/1,204) in the accelerated surgery group and in 14.9% (179/1,203) in the standard care group (postrandomization Scr was missing in 38 [1.6%] patients and was imputed using fully conditional specification for the primary analysis as described in Item S1). The relative risk (RR) was 0.91 (95% CI, 0.74-1.13), and the absolute risk difference was 1.3% (95% CI, −1.5% to 4.1%; Table 2). Results were similar in sensitivity analyses (Tables S4-S5). The mean between-group difference in the percentage and absolute change in Scr to the peak value was −1.5 (95% CI, −5.2 to 2.2) and −1.9 (95% CI, −5.1 to 1.3), respectively. The time to AKI after randomization in each group is shown in Figure S2. Pre-existing chronic kidney disease (CKD) did not significantly modify the effect of the accelerated surgery intervention versus standard care on AKI (Table S6), nor did prerandomization eGFR considered as a continuous variable (P = 0.1 for the interaction between the group allocation and eGFR).Table 2Accelerated Hip-Repair Surgery Versus Standard Care and the Risk of AKINo. (%) of eventsaBased on all participants with at least 1 postrandomization Scr in the first 7 days after randomization.RR (95% CI)bA modified Poisson regression model that accounts for the treating center and planned surgery type (open reduction and internal fixation or arthroplasty) was used to estimate the RR and 95% CI for AKI comparing the randomized groups. A missing outcome variable was imputed using multiple imputation; standard methods were used to combine estimates from each imputed dataset, as detailed in Item S2. For the outcomes of AKI or death, stage 2 AKI or higher, and stage 3 AKI, complete-case analysis was used, since<2 patients had missing outcome status.PcCalculated for the primary outcome only; for this analysis, missing data on postrandomization Scr (12 [1.0%] in the accelerated surgery group; 26 [2.1%] in the standard care group) were imputed using fully conditional specification (detailed in Item S2).Accelerated Surgery Group (n = 1,216)Standard Care Group (n = 1,229)AKI163/1,204 (13.5%)179/1,203 (14.9%)0.91 (0.74-1.13)0.4AKI or deathdA composite of AKI (primary outcome definition) or death within 48 hours after randomization. For patients with at least 48 hours of follow-up postrandomization (to assess the death outcome) who were missing all postrandomization Scr, a value of 0 (no AKI or death within 48 hours) was imputed.166/1,216 (13.7%)180/1,229 (14.7%)0.93 (0.77-1.12)--Stage 2 AKI or highereDefined as a postrandomization increase in Scr of≥100% from the prerandomization value within 7 days after randomization or an increase to an absolute value of≥4.0mg/dL (353.6μmol/L) within 7 days after randomization (when the primary outcome definition of AKI was met) or receipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if≥1 Scr was provided within 7 days after randomization or the patient was followed for≥30 days after randomization to assess dialysis status.35/1,215 (2.9%)38/1,228 (3.1%)0.93 (0.65-1.33)--Stage 3 AKIfDefined as a postrandomization increase in Scr of≥200% from the prerandomization value within 7 days after randomization or an increase to an absolute value of≥4.0mg/dL (353.6μmol/L) within 7 days after randomization or receipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if≥1 Scr was provided within 7 days after randomization or the patient was followed for≥30 days after randomization to assess dialysis status.5/1,215 (0.4%)12/1,228 (1.0%)0.42 (0.20-0.91)--Receipt of dialysisgReceipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if the patient was followed for≥30 days after randomization to assess dialysis status.0/1,213 (0.0%)1/1,226 (0.1%)----a Based on all participants with at least 1 postrandomization Scr in the first 7 days after randomization.b A modified Poisson regression model that accounts for the treating center and planned surgery type (open reduction and internal fixation or arthroplasty) was used to estimate the RR and 95% CI for AKI comparing the randomized groups. A missing outcome variable was imputed using multiple imputation; standard methods were used to combine estimates from each imputed dataset, as detailed in Item S2. For the outcomes of AKI or death, stage 2 AKI or higher, and stage 3 AKI, complete-case analysis was used, since <2 patients had missing outcome status.c Calculated for the primary outcome only; for this analysis, missing data on postrandomization Scr (12 [1.0%] in the accelerated surgery group; 26 [2.1%] in the standard care group) were imputed using fully conditional specification (detailed in Item S2).d A composite of AKI (primary outcome definition) or death within 48 hours after randomization. For patients with at least 48 hours of follow-up postrandomization (to assess the death outcome) who were missing all postrandomization Scr, a value of 0 (no AKI or death within 48 hours) was imputed.e Defined as a postrandomization increase in Scr of ≥100% from the prerandomization value within 7 days after randomization or an increase to an absolute value of ≥4.0 mg/dL (353.6 μmol/L) within 7 days after randomization (when the primary outcome definition of AKI was met) or receipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if ≥1 Scr was provided within 7 days after randomization or the patient was followed for ≥30 days after randomization to assess dialysis status.f Defined as a postrandomization increase in Scr of ≥200% from the prerandomization value within 7 days after randomization or an increase to an absolute value of ≥4.0 mg/dL (353.6 μmol/L) within 7 days after randomization or receipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if ≥1 Scr was provided within 7 days after randomization or the patient was followed for ≥30 days after randomization to assess dialysis status.g Receipt of dialysis within 30 days after randomization. A patient was considered to have observed outcome data if the patient was followed for ≥30 days after randomization to assess dialysis status. Open table in a new tab The strengths of this substudy include its randomized concealed allocation, recruitment from 69 hospitals in 17 countries, and standardized collection of postrandomization Scr. Three limitations merit discussion. First, baseline Scr was obtained at the time of hospital admission for 99% of patients. Depending on the circumstances of the fracture, instability in the baseline measurement could complicate detecting an acute rise in postrandomization Scr, which is needed to identify AKI. That said, the average baseline Scr was 0.96 mg/dL, a level considered normal. Second, urine output data were not collected, given challenges with accurate measurement in an international setting. Third, we were underpowered to detect an RR reduction <30% for the primary AKI outcome. Therefore, we conducted prespecified analyses of the percentage change and the absolute change to the peak postrandomization Scr; however, no statistically significant between-group differences were observed. In summary, the risk of perioperative AKI was not significantly different in patients allocated to accelerated surgery versus standard care for hip fracture. AKI occurred nearly twice as often in patients with versus without CKD (21% vs 11%); however, regardless of CKD status, the risk of AKI was not significantly lower with accelerated surgery versus standard care. Research idea and study design: AXG, FKB, JMS, PJD; data acquisition: ANN, AO, AP, ARL, AS, AXG, BMB, CYW, EGF, FKB, GCAW, GS, JN, JSM, JTH, JV, KB, MB, MBC, MT, MTR, MU, PJD, PSancheti, PŚlęczka, RJ, RJF, SP, VH, VT, WS; data analysis/interpretation: AXG, FKB, JMS, KB, MC, PJD; statistical analysis: KB, MC; supervision or mentorship: AXG, FKB, JMD, PJD. Each author contributed important intellectual content during manuscript drafting or revision and agrees to be personally accountable for their own contributions and to ensure that questions pertaining to the accuracy or integrity of any portion of the work, even one in which the author was not directly involved, are appropriately investigated and resolved, including with documentation in the literature if appropriate. A list of the HIP ATTACK-1 collaborators is in Item S3. This work was supported by the Canadian Institutes of Health Research (CIHR) Foundation Award, CIHR's Strategy for Patient-Oriented Research (SPOR), through the Ontario SPOR Support Unit (OSSU), as well as the Ontario Ministry of Health and Long-Term Care, and a grant from Smith & Nephew to recruit 300 patients in Spain. Grants to support this substudy were provided by the Department of Medicine at Western University. FKB holds a McMaster University Department of Medicine Career Research Award. PJD was supported by a Tier 1 Canada Research Chair in Perioperative Medicine. AXG was supported by the Dr Adam Linton Chair in Kidney Health Analytics and a CIHR Clinician Investigator Award. No funding entity had a role in data collection, statistical analysis, manuscript writing, or the decision to publish. The authors declare that they have no other relevant financial interests. The conduct, trial analyses, the composing of this manuscript, and its final contents are solely the authors' incumbency. Received August 12, 2021. Evaluated by 2 external peer reviewers, with direct editorial input from a Statistics/Methods Editor, an Associate Editor, and the Editor-in-Chief. Accepted in revised form January 14, 2022. Download .pdf (.42 MB) Help with pdf files Supplementary File (PDF)Figures S1-S2; Items S1-S3; Tables S1-S6.