Participation in Competitive Sports by Patients With Congenital Heart Disease: AHA/ACC and EAPC/ESC/AEPC Guidelines Comparison.

Sports participation in patients with congenital heart disease is an evolving subject. The American Heart Association/American College of Cardiology released a set of guidelines that advise the type and level of sports participation based primarily on anatomical defects with secondary consideration given to hemodynamic effects. Recently, the European Association of Preventive Cardiology/European Society of Cardiology/Association for European Paediatric and Congenital Cardiology offered a contrasting approach to sports participation that is based on hemodynamic and electrophysiological profiles of each patient, regardless of anatomical consideration. These guidelines are drastically different in their approaches but do have some similarities. In this review, we compare both documents, focusing on the aim, population, classification of sports, and the methodology of making recommendations. This review aims to assist practicing cardiologists in integrating the available published data and recommendations when counseling patients for sports participation.

An Audit on the Pre-operative Fasting Time of Trauma-List Orthopaedic Patients at a District General Hospital in Chichester, United Kingdom.

INTRODUCTION: Pre-operative fasting of patients awaiting non-emergency surgeries has been a common practice to minimise the risk of vomiting and aspiration at the time of induction of anaesthesia. Current standard guidelines recommend that this fasting time be limited to two hours for clear fluids and six hours for solids and semi-solids, as prolonged fasting has been shown to be harmful to the patient. METHODS: A descriptive cross-sectional study of the fasting times of all adult trauma orthopaedic patients who were operated on under anaesthesia between June 1 and 30, 2023. Fifty patients who met the inclusion criteria were included in the study. RESULTS: The minimum and maximum fasting times observed for solids and semi-solids were 9 and 24 hours, respectively. The mean fasting time for solids and semi-solids was 15.8 hours. The minimum and maximum fasting times observed for clear fluids were 2 and 20 hours, respectively. The mean fasting time for clear fluids was 10.5 hours. Elderly patients accounted for a significant portion of the patients, with 64% (n=32) being above the age of 70 years. CONCLUSION: A significant disparity was noted between the current fasting practices and the recommended standards set out by the Royal College of Nursing, the Association of Anaesthetists of Great Britain and Ireland, the European Society of Anaesthesiology, and the American Society of Anaesthesiologists. The knowledge of pre-operative fasting among the orthopaedic team doctors and the ward nursing staff was found to be inadequate.

Pulmonary Complications in Patients With Fontan Circulation: JACC Review Topic of the Week.

The Fontan operation has resulted in significant improvement in survival of patients with single ventricle physiology. As a result, there is a growing population of individuals with Fontan physiology reaching adolescence and adulthood. Despite the improved survival, there are long-term morbidities associated with the Fontan operation. Pulmonary complications are common and may contribute to both circulatory and pulmonary insufficiency, leading ultimately to Fontan failure. These complications include restrictive lung disease, sleep abnormalities, plastic bronchitis, and cyanosis. Cyanosis post-Fontan procedure can be attributed to multiple causes including systemic to pulmonary venous collateral channels and pulmonary arteriovenous malformations. This review presents the unique cardiopulmonary interactions in the Fontan circulation. Understanding the cardiopulmonary interactions along with improved recognition and treatment of pulmonary abnormalities may improve the long-term outcomes in this growing patient population. Interventions focused on improving pulmonary function including inspiratory muscle training and endurance training have shown a promising effect post-Fontan procedure.

NuCLS: A scalable crowdsourcing approach and dataset for nucleus classification and segmentation in breast cancer.

BACKGROUND: Deep learning enables accurate high-resolution mapping of cells and tissue structures that can serve as the foundation of interpretable machine-learning models for computational pathology. However, generating adequate labels for these structures is a critical barrier, given the time and effort required from pathologists. RESULTS: This article describes a novel collaborative framework for engaging crowds of medical students and pathologists to produce quality labels for cell nuclei. We used this approach to produce the NuCLS dataset, containing >220,000 annotations of cell nuclei in breast cancers. This builds on prior work labeling tissue regions to produce an integrated tissue region- and cell-level annotation dataset for training that is the largest such resource for multi-scale analysis of breast cancer histology. This article presents data and analysis results for single and multi-rater annotations from both non-experts and pathologists. We present a novel workflow that uses algorithmic suggestions to collect accurate segmentation data without the need for laborious manual tracing of nuclei. Our results indicate that even noisy algorithmic suggestions do not adversely affect pathologist accuracy and can help non-experts improve annotation quality. We also present a new approach for inferring truth from multiple raters and show that non-experts can produce accurate annotations for visually distinctive classes. CONCLUSIONS: This study is the most extensive systematic exploration of the large-scale use of wisdom-of-the-crowd approaches to generate data for computational pathology applications.

Cambridge Protocol for Management of Segmental Bone Loss.

INTRODUCTION: Segmental long bone defects are some of the most challenging to surgically reconstruct; however, there is no clear guidance on which of the myriad of techniques is superior in a given clinical context. We describe three cases of segmental bone loss presenting to a major trauma center and have use these to develop a treatment algorithm for the sub-acute management of such fractures. CASE REPORT: Case 1 - Acute shortening and delayed lengthening using lengthening intramedullary (IM) nail to treat diaphyseal non-union of the femur with associated 3 cm shortening. Case 2 - 15 cm traumatic bone loss of femur, failed Masquelet, treated with IM nail, monolateral external-fixation and cable with a mean lengthening rate of 46 days/cm. Case 3 - 12 cm tibial traumatic bone loss, failed Masquelet, treated with fine wire frame with a mean lengthening rate of 49 days/cm. CONCLUSION: As our cases illustrate; attempting complicated, definitive management in the acute phase generates complications and necessitates re-intervention. As such, we have developed a treatment algorithm for traumatic segmental bone loss. We recommend waiting 6 weeks and reimaging to check for evidence of spontaneous bone formation before deciding on definitive treatment. First-line treatment for femoral defects <4 cm is acute limb shortening with delayed lengthening using lengthening IM nail. First-line treatment for femoral defects >4 cm is lengthening over nail with monolateral external fixator. First-line treatment of tibial segmental bone defects in our hands is fine wire circular frames which provide excellent scope for soft tissue coverage and deformity correction. Treatment times of over 2 years in a frame are not uncommon and patients must diligently comply with pin sites management and lengthening protocols. This is the first paper providing an algorithm to guide surgeons in choosing the best lower limb reconstruction options in the sub-acute setting; considering the skill set and resources of the center in which one works.

The Influence of Patellofemoral Degenerative Changes on the Outcome of the Unicompartmental Knee Replacement: A Prospective Study.

Unicompartmental knee arthroplasty (UKA) is a recognized procedure for treatment of medial compartment osteoarthritis. Patellofemoral (PF) joint degeneration is widely considered to be a contraindication to medial compartment UKA. We examined the validity of this preconception using information gathered prospectively on 147 consecutive patients who underwent the Repicci II UKA for medial compartment osteoarthritis between July 1999 and September 2000 by the same surgeon. The status of the PF joint was assessed intraoperatively in all patients, and accordingly patients were divided into two groups. Among them, 69 had associated PF osteoarthritis (group A), while 78 patients had a normal PF compartment (group B). Variables measured included the International Knee Society (IKS) score, limb alignment, and range of motion. Radiographs, demographic data, length of hospital stay, perioperative complications were also measured. All subsequent surgery and survivorship at 10 years were recorded. The mean follow-up was 9.4 years (range: 5-10.7 years) and results of the two groups were compared. We found no significant differences in terms of IKS scores, alignment, and flexion between the two groups. However, measured extension was significantly increased postoperatively in those patients with minimal or no PF joint degenerative disease (p < 0.05).

Beyond p-Hexaphenylenes: Synthesis of Unsubstituted p-Nonaphenylene by a Precursor Protocol.

The synthesis of unsubstituted oligo-para-phenylenes (OPP) exceeding para-hexaphenylene-in the literature often referred to as p-sexiphenyl-has long remained elusive due to their insolubility. We report the first preparation of unsubstituted para-nonaphenylenes (9PPs) by extending our precursor route to poly-para-phenylenes (PPP) to a discrete oligomer. Two geometric isomers of methoxylated syn- and anti-cyclohexadienylenes were synthesized, from which 9PP was obtained via thermal aromatization in thin films. 9PP was characterized via optical, infrared and solid-state 13 C NMR spectroscopy as well as atomic force microscopy and mass spectrometry, and compared to polymeric analogues. Due to the lack of substitution, para-nonaphenylene, irrespective of the precursor isomer employed, displays pronounced aggregation in the solid state. Intermolecular excitonic coupling leads to formation of H-type aggregates, red-shifting emission of the films to greenish. 9PP allows to study the structure-property relationship of para-phenylene oligomers and polymers, especially since the optical properties of PPP depend on the molecular shape of the precursor.

Atraumatic Bilateral Acute Compartment Syndrome of the Lower Legs: A Review of the Literature.

Bilateral acute compartment syndrome of the legs is a very rare presentation that requires emergency surgical intervention. Atraumatic bilateral cases are almost unheard of in medicine. There is currently no link between compartment syndrome and cognitive impairment or mental health. A systematic literature search was performed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines using the following keywords in multiple databases: compartment syndrome, atraumatic, spontaneous, bilateral, both, lower leg, acute, compartmental pressure, and fasciotomy. Atraumatic, bilateral, acute, and confirmed compartment syndrome cases were included. In total, 33 cases of atraumatic bilateral acute compartment syndrome (ABACS) were identified, of those 72.7% of cases were males. A form of cognitive impairment was found in 66% of cases. The medical history of the cases included substance abuse (nine patients), mental health illness (seven patients), and hypothyroidism (four patients). Within the reports, there was evidence of a misdiagnosis or delayed management in 19 cases (57.6%). Creatinine kinase (CK) was measured in 28 cases with a mean CK of 110,893 IU/L. Compartment pressure measurements were used in only 12 cases. A total of 29 cases were managed with bilateral four-compartment fasciotomy. This review highlights that ABACS is a condition with high rates of misdiagnosis or delay in treatment. Associations found included patients with cognitive impairment on presentation, mental health conditions, substance misuse, and elevated levels of CK. In addition, this review demonstrates that this condition is less rare than previously thought with serious morbidity and mortality.

A health economic analysis of the management of open lower limb fractures in the elderly.

AIM: The aim of this study was to investigate the financial implications of the inpatient management of open lower limb fractures in adults over 65 years old. Further, the study compares the calculated cost to the income received by the hospital for these patients and to the existing body of literature. METHODS: This study employed direct inpatient costing analysis to estimate the cost of treating the open lower limb fractures incurred by 58 patients over the age of 65 years treated in our centre (Addenbrooke's Hospital, Cambridge University Hospitals NHS Trust) between March 2014 and March 2019. RESULTS: The median cost of inpatient care calculated in this study was £20,398 per patient, resulting in a financial loss to the hospital of £5113 per patient. When the results were disaggregated by sex, the median cost for an open lower limb fracture in a male patient was £20,886 compared to £19,304 in a female patient. Data were also disaggregated by the site of injury, which produced a median cost for an open femur fracture of £23,949, and £24,549 and £15,362 for open tibia and ankle fractures, respectively. CONCLUSION: This study provides a valuable estimate of the expense of treating open lower limb fractures in patients over the age of 65 years in a Major Trauma Centre in England. The study highlights the large losses incurred by hospitals in treating these cases, and supports revision of the remuneration structures in the National Health Service to adequately cover their cost.

Cambridge experience in spontaneous bone regeneration after traumatic segmental bone defect: a case series and review of literature.

High-energy traumatic long bone defects are some of the most challenging to reconstruct. Although cases of spontaneous bone regeneration in these defects have been reported, we are aware of no management guidelines or recommendations for when spontaneous bone regeneration should be considered a viable management option. We aim to identify how certain patient characteristics and surgical factors may help predict spontaneous bone regeneration. A total of 26 cases with traumatic segmental defects were treated at our institution, with eight cases (30.8%) undergoing spontaneous regeneration. We discuss four in detail. Six (75%) reported a degree of periosteal preservation, four (50%) were associated with traumatic brain injury and none were complicated by infection. The average time to spontaneous bone regeneration was 2.06 months. According to our cases, patients with favourable characteristics may benefit from delaying surgical treatment by 6 weeks to monitor for any signs of spontaneous bone formation.

Systematic review on the outcomes of poller screw augmentation in intramedullary nailing of long bone fracture.

Various technical tips have been described on the placement of poller screws during intramedullary (IM) nailing; however studies reporting outcomes are limited. Overall there is no consistent conclusion about whether intramedullary nailing alone, or intramedullary nails augmented with poller screws is more advantageous.We conducted a systematic review of PubMed, EMBASE, and Cochrane databases. Seventy-five records were identified, of which 13 met our inclusion criteria. In a systematic review we asked: (1) What is the proportion of nonunions with poller screw usage? (2) What is the proportion of malalignment, infection and secondary surgical procedures with poller screw usage? The overall outcome proportion across the studies was computed using the inverse variance method for pooling.Thirteen studies with a total of 371 participants and 376 fractures were included. Mean follow-up time was 21.1 months. Mean age of included patients was 40.0 years. Seven studies had heterogenous populations of nonunions and acute fractures. Four studies included only acute fractures and two studies examined nonunions only.The results of the present systematic review show a low complication rate of IM nailing augmented with poller screws in terms of nonunion (4%, CI: 0.03-0.07), coronal plane malunion (5%, CI: 0.03-0.08), deep (5%, CI: 0.03-0.11) and superficial (6%, CI: 0.03-0.11) infections, and secondary procedures (8%, CI: 0.04-0.18).When compared with the existing literature our review suggests intramedullary nailing with poller screws has lower rates of nonunion and coronal malalignment when compared with nailing alone. Prospective randomized control trial is necessary to fully determine outcome benefits. Cite this article: EFORT Open Rev 2020;5:189-203. DOI: 10.1302/2058-5241.5.190040.

Improving radiographic imaging for circular frames: the Cambridge experience.

INTRODUCTION: Limb reconstruction using circular frames requires complex accurate measurements to achieve correction of mechanical bone axis. Inadequate imaging could ultimately lead to poor clinical outcome. Therefore, radiographs should be obtained in a standardised manner to yield accurate results. Our aim is to improve the effectiveness of post-operative imaging by obtaining precise examinations and improving the accuracy of frame correction; therefore, reducing technical repeats, radiation exposure, time waste in clinic, and achieving cost effectiveness. METHODS: We implemented a simple technique for obtaining adequate imaging using standard X-ray equipment. This technique was introduced to the radiographers in the radiology department to image patients with circular frames. Images were taken by obtaining a field of view using the X-ray machine cone of light that is orthogonal to the location of interest in both the antero-posterior (AP) and lateral planes. We compared the quality of radiographs, number of repeated X-rays and radiation dose both before and after implementing our protocol RESULTS: We assessed 54 consultations before and 63 consultations after the implementation of our protocol. The results showed a reduction in inadequate radiographs from 78% to 13% department at Addenbrooke's Hospital at a statistical significance of p < 0.00001. In addition, we found a potential radiation dose reduction of 2.7-0.32mSev between the two cohorts. Our results indicate that there would also be a reduction in the cost to the department as well as time spent repeating inaccurate radiographs. CONCLUSION: We have been able to achieve a significant improvement in the quality of post-operative radiographic imaging and have expanded its use to adult frame patients with a background of traumatic or infectious aetiologies.

A report of two infant cases operated for jejunal duplication cyst associated with malrotation and volvulus.

INTRODUCTION: Both Enteric duplication and intestinal malrotation are concerning causes for intestinal obstruction in the pediatric age group and they very rarely coexist in the same patient. PRESENTATION OF CASES: We present 2 cases of previously healthy children, the first is a 4-month-old infant and the second is a 1.5-year-old boy, both presented with recurrent attacks of bilious vomiting that proved to be due to acute midgut volvulus caused by an enteric duplication cyst associated with intestinal malrotation. DISCUSSION: Enteric duplication and intestinal malrotation are two of the concerning causes of billious vomiting in the pediatric age group. They could be encountered at any level of the alimentary tract from the tongue to the anus. The term malrotation refers to all abnormalities of intestinal position. The coincidence of intestinal malrotation and an enteric duplication cyst (EDC) is very rare and has been described only in a few case reports. CONCLUSION: The concomitance of EDC and intestinal malrotation is extremely rare and should be kept in mind in a child presenting with bilious vomiting especially in a child preoperatively diagnosed with a duplication cyst.

Rotating-hinge knee prosthesis as a viable option in primary surgery: Literature review & meta-analysis.

BACKGROUND: Rotating-hinge knee replacements are usually reserved for revision surgeries, when the extent of soft tissue loss makes a constrained implant more suitable. They remain an uncommon choice in primary surgery when the soft tissue loss is not as extensive. METHODS: We completed a systematic review and meta-analysis to assess patients who underwent a Total Knee Replacement (TKR) with the rotating-hinge prosthesis in the primary setting. We searched PubMed and Embase for articles published in the ten years prior June 2017: Prosthesis survival rates, causes of failure, and clinical/functional scores were the primary outcomes. Twenty-one articles met the inclusion criteria for meta-analysis. Articles were grouped into (1) non-tumour (n=11) and (2) tumour indications (n=10). Survival data was summarized in forest plots, generated using Stata. RESULTS: We found that for certain indications the prosthesis has impressive survival rates and functional outcomes. Short-term (1-5 year) prosthesis survival in non-tumour cases was 92% (95% CI, 87-98%) and 77% (95% CI, 68-87%) in tumour cases. Mid-term (6-10 year) survival was 82% (95% CI, 74-89%) and 69% (95% CI, 57-81%) in non-tumour and tumour studies respectively. In analysis of clinical scores, patients showed a significant improvement in their pain score. Infection was the most commonly cited cause of prosthesis failure in both non-tumour and tumour studies, attributing to 31.5% and 37.6% of failures respectively. Aseptic loosening, dislocation and fracture were also commonly cited complications. CONCLUSION: We concluded that the rotating-hinge knee prosthesis is a viable option in primary surgery when there is extensive soft tissue destruction surrounding the joint. LEVEL OF EVIDENCE: I.

Sliding hip screws versus cancellous screws for femoral neck fractures: a systematic review and meta-analysis.

PURPOSE: Both sliding hip screws (SHS) and cancellous screws are used in the surgical management of intracapsular femoral neck fracture. However, there is paucity of information as to which is the superior treatment modality. We performed this systematic review and meta-analysis study to compare the clinical outcomes of SHS and cancellous screws for the treatment of femoral neck fractures in adult patients. METHODS: We searched PubMed, Scopus, Web of Science, and Cochrane CENTRAL, up to December 2017. Randomized controlled trials (RCTs) directly comparing the clinical outcomes of SHS and cancellous screws for femoral neck fractures were retrieved with no language or publication year restrictions. Data retrieved included operative details, nonunion rate, avascular necrosis, reoperation, infection and mortality, hip pain, functional hip scores, and medical complications. These were pooled as risk ratio or mean difference (MD) with their corresponding 95% confidence interval (CI). Heterogeneity was assessed by Chi-square test. RESULTS: Ten RCTs involving 1934 patients were included in the final analysis. The pooled estimate showed that the SHS group was associated with more intraoperative blood loss (MD = 110.01 ml, 95% CI [52.42, 167.60], p = 0.00002) than the cancellous screws. There was no significant difference in terms of operative time, postoperative hip function, nonunion, avascular necrosis, reoperation rate, infection, fracture healing, hip pain, medical complications, and mortality rate. CONCLUSION: Based on our study, the cancellous screws group was associated with less intraoperative blood loss in comparison with the SHS group. No other significant differences were found between the two interventions.

Pristine Poly( para-phenylene): Relating Semiconducting Behavior to Kinetics of Precursor Conversion.

We investigated unsubstituted poly( para-phenylene) (PPP), a long-desired prototype of a conjugated polymer semiconductor. PPP was accessed via thermal aromatization of a precursor polymer bearing kinked, solubility-inducing dimethoxycyclohexadienylene moieties. IR spectroscopy and Vis ellipsometry studies revealed that the rate of conversion of the precursor to PPP increases with temperature and decreases with film density, indicating a process with high activation volume. The obtained PPP films were analyzed in thin-film transistors to gain insights into the interplay between the degree of conversion and the resulting p-type semiconducting properties. The semiconducting behavior of PPP was further unambiguously proven through IR and transistor measurements of molybdenum trioxide p-doped films.

Structured crowdsourcing enables convolutional segmentation of histology images.

MOTIVATION: While deep-learning algorithms have demonstrated outstanding performance in semantic image segmentation tasks, large annotation datasets are needed to create accurate models. Annotation of histology images is challenging due to the effort and experience required to carefully delineate tissue structures, and difficulties related to sharing and markup of whole-slide images. RESULTS: We recruited 25 participants, ranging in experience from senior pathologists to medical students, to delineate tissue regions in 151 breast cancer slides using the Digital Slide Archive. Inter-participant discordance was systematically evaluated, revealing low discordance for tumor and stroma, and higher discordance for more subjectively defined or rare tissue classes. Feedback provided by senior participants enabled the generation and curation of 20 000+ annotated tissue regions. Fully convolutional networks trained using these annotations were highly accurate (mean AUC=0.945), and the scale of annotation data provided notable improvements in image classification accuracy. AVAILABILITY AND IMPLEMENTATION: Dataset is freely available at: https://goo.gl/cNM4EL. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Does Tourniquet Use in TKA Increase Postoperative Pain? A Systematic Review and Meta-analysis.

BACKGROUND: Although tourniquets are commonly used during TKA, that practice has long been surrounded by controversy. Quantifying the case for or against tourniquet use in TKA, in terms of patient-reported outcomes such as postoperative pain, is a priority. QUESTIONS/PURPOSES: The purpose of this study was to meta-analyze the available randomized trials on tourniquet use during TKA to determine whether use of a tourniquet during TKA (either for the entire procedure or some portion of it) is associated with (1) increased postoperative pain; (2) decreased ROM; and (3) longer lengths of hospital stay (LOS) compared with TKAs performed without a tourniquet. METHODS: We completed a systematic review and meta-analysis using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines to assess the impact of tourniquet use on patients after TKA. We searched the following databases from inception to February 1, 2015, for randomized controlled trials meeting prespecified inclusion criteria: PubMed, Embase, and Cochrane Central Register of Controlled Trials. Postoperative pain was the primary outcome. Secondary outcomes were postoperative ROM and LOS. The initial search yielded 218 studies, of which 14 met the inclusion criteria. For our primary analysis on pain and ROM, a total of eight studies (221 patients in the tourniquet group, 219 patients in the no-tourniquet group) were meta-analyzed. We also performed a subgroup meta-analysis on two studies that used the tourniquet only for a portion of the procedure (from osteotomy until the leg was wrapped with bandages) and defined this as half-course tourniquet use (n = 62 in this analysis). The Jadad scale was used to ascertain methodological quality, which ranged from 3 to 5 with a maximum possible score of 5. Statistical heterogeneity was tested with I and chi-square tests. A fixed-effects (inverse variance) model was used when the effects were homogenous, which was only the case for postoperative pain; the other endpoints had moderate or high levels of heterogeneity. Publication bias was assessed using a funnel plot, and postoperative pain showed no evidence of publication bias, but the endpoint of LOS may have suffered from publication bias or poor methodological quality. We defined the minimum clinically important difference (MCID) in pain as 20 mm on the 100-mm visual analog scale (VAS). RESULTS: We found no clinically important difference in mean pain scores between patients treated with a tourniquet and those treated without one (5.23 ± 1.94 cm versus 3.78 ± 1.61 cm; standardized [STD] mean difference 0.88 cm; 95% confidence interval [CI], 0.54-1.23; p < 0.001). None of the studies met the MCID of 20 mm in VAS pain scores. There was also no clinically important difference in ROM based on degrees of flexion between the two groups (49 ± 21 versus 56 ± 22; STD mean difference 0.8; 95% CI, 0.4-1.1; p < 0.001). Similarly, we found no difference in mean LOS between groups (5.8 ± 4.4 versus 5.9 ± 4.6; STD mean difference -0.2; 95% CI, -0.4 to 0.1; p = 0.25). A subgroup meta-analysis also showed no clinically important difference in pain between the full-course and half-course tourniquet groups (5.17 ± 0.98 cm versus 4.09 ± 1.08 cm; STD mean difference 1.31 cm; 95% CI, -0.16 to 2.78; p = 0.08). CONCLUSIONS: We found no clinically important differences in pain or ROM between patients treated with and without tourniquets during TKA and no differences between the groups in terms of LOS. In the absence of short-term benefits of avoiding tourniquets, long-term harms must be considered; it is possible that use of a tourniquet improves a surgeon's visualization of the operative field and the quality of the cement technique, either of which may improve the long-term survivorship or patient function, but those endpoints could not be assessed here. We recommend that the randomized trials discussed in this meta-analysis follow patients from the original series to determine if there might be any long-term differences in pain or ROM after tourniquet use. LEVEL OF EVIDENCE: Level I, therapeutic study.

Denosumab versus bisphosphonates in patients with advanced cancers-related bone metastasis: systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Bone metastasis is reported to be associated with poor quality of life, and increased risk of hospitalization. We aim to synthesize evidence from published randomized controlled trials (RCTs) which compared the efficacy of denosumab versus bisphosphonates in patients with advanced cancers. METHODS: We searched for all published RCTs in the following electronic databases: PubMed, Scopus, Web of Science, and Cochrane Central. Retrieved records were screened for eligibility. Time-to-event data were pooled as hazard ratio (HR) using the generic inverse-variance method and dichotomous data were pooled as relative risk (RR) in a random-effect model. We used Review Manager 5.3 for windows. RESULTS: Six unique RCTs with a total of 7722 patients were included. Overall effect estimates favored denosumab group in comparison to intravenous (IV) bisphosphonates in the following terms: time to first skeletal-related events (HR 0.92, 95% CI [0.86, 0.98], p = 0.01), time to subsequent skeletal-related event (RR 0.92, 95% CI [0.86, 0.99], p = 0.03), and radiation to bone (RR 0.81, 95% CI [0.71, 0.92], p = 0.02). Denosumab group was associated with increased risk of grade 3 or 4 hypocalcaemia (RR 1.99, 95% CI [1.11, 3.54], p = 0.02) and reduced risk of renal impairment or toxicity (RR 0.75, 95% CI [0.61, 0.91], p = 0.003) in comparison to IV bisphosphonates group. Pooled studies were homogenous. CONCLUSION: Denosumab showed a favorable significant impact on delaying the time to first skeletal-related event and reducing the incidence of radiation to the bone event in comparison to bisphosphonates, with similar efficacy regarding overall survival and time to disease progression. Further large-scale and long-term studies are needed to clarify the long-term efficacy and safety of both regimens.