Health-related quality of life does not deteriorate while waiting for anterior cruciate reconstruction.

PURPOSE: The aim of this study was to determine how preoperative health-related quality of life (HRQoL) is affected by the duration of the wait time (WT) for anterior cruciate ligament reconstruction (ACLR) once a decision is made to proceed with surgery. METHODS: This was a multi-centre prospective cohort study. One hundred and twenty-two patients 14 years of age and above waiting for ACLR completed the International Knee Documentation Committee (IKDC) demographic, current health assessment and subjective knee evaluation (SKF) forms on the day of decision to operate and the day of surgery. Changes in scores were analyzed for the entire cohort, adjusted for WTs and a subset was compared for patients with isolated anterior cruciate ligament (ACL) tears and ACL tears with concurrent meniscal involvement. Changes in HRQoL scores from the day of the decision to operate to the 9-month postoperative appointments were also assessed. RESULTS: Energy/Fatigue (p < 0.05), Pain (p < 0.05), General Health (p < 0.05) and the IKDC-SKF Score (p < 0.05) significantly increased between the day of the decision to operate and the day of surgery. Only the change in IKDC-SKF score remained significantly higher after adjusting for WT. Baseline HRQoL scores significantly improved by the 9-month postoperative appointment. CONCLUSION: The length of time waiting for ACLR did not adversely influence HRQoL in this study. However, low preoperative HRQoL and the significant improvement in HRQoL of patients followed postoperatively suggest that timely surgery is beneficial for this patient population. LEVEL OF EVIDENCE: Level II.

Predictors of Clinical Benefit with Intra-articular Hyaluronic Acid in Patients with Knee Osteoarthritis - A Narrative Review.

BACKGROUND: There is conflicting evidence regarding the efficacy of viscosupplementation with intra-articular hyaluronic acid injections in knee osteoarthritis. One possible explanation for the inconsistent findings on its efficacy is that only certain subpopulations of patients benefit from this therapy. OBJECTIVE: The purpose of this narrative review is to succinctly summarize the existing data on the predictive factors of clinical response to intra-articular hyaluronic acid to identify the patient profile most likely to benefit from this therapy. METHODS: For this narrative review, a PubMed search was conducted in January 2023, with no date limits, to identify publications reporting predictive factors of response to viscosupplementation using the following terms: hyaluronic acid OR viscosupplem* AND osteoarthritis AND knee AND predict*. Searches were limited to randomized controlled trials, systematic reviews and meta- analyses, or observational studies written in English. Other relevant references were identified by searching the references of retrieved articles. RESULTS: The disease severity was found to reliably predict response to intra-articular hyaluronic acid injections; patients with less severe disease consistently had a more robust therapeutic response than those with more severe disease. Other clinical variables such as level of baseline pain did not reliably predict response. Body mass index, and possibly age, may also be independent predictors of the response. CONCLUSION: A review of the existing literature suggests that patients with less severe clinical symptoms and radiological findings, who are younger, and with a lower or normal body mass index are the best candidates for intra-articular hyaluronic acid therapy.

Arthroscopy Association of Canada Position Statement on Opioid Prescription After Arthroscopic Surgery.

Background: Despite the ongoing opioid epidemic, most patients are still prescribed a significant number of opioid medications for pain management after arthroscopic surgery. There is a need for consensus among orthopaedic surgeons and solutions to aid providers in analgesic strategies that reduce the use of opioid pain medications. Purpose: This position statement was developed with a comprehensive systematic review and meta-analysis of exclusively randomized controlled trials (RCTs) to synthesize the best available evidence for managing acute postoperative pain after arthroscopic surgery. Study Design: Position statement. Methods: The Embase, MEDLINE, PubMed, Scopus, and Web of Science databases were searched from inception until August 10, 2022. Keywords included arthroscopy, opioids, analgesia, and pain, and associated variations. We included exclusively RCTs on adult patients to gather the best available evidence for managing acute postoperative pain after arthroscopic surgery. Patient characteristics, pain, and opioid data were extracted, data were analyzed, and trial bias was evaluated. Results: A total of 21 RCTs were identified related to the prescription of opioid-sparing pain medication after arthroscopic surgery. The following recommendations regarding noninvasive, postoperative pain management strategies were made: (1) multimodal oral nonopioid analgesic regimens-including at least 1 of acetaminophen-a nonsteroidal anti-inflammatory drug-can significantly reduce opioid consumption with no change in pain scores; (2) cryotherapy is likely to help with pain management, although the evidence on the optimal method of application (continuous-flow vs ice pack application) is unclear; (3) and (4) limited RCT evidence supports the efficacy of transcutaneous electrical nerve stimulation and relaxation exercises in reducing opioid consumption after arthroscopy; and (5) limited RCT evidence exists against the efficacy of transdermal lidocaine patches in reducing opioid consumption. Conclusion: A range of nonopioid strategies exist that can reduce postarthroscopic procedural opioid consumption with equivalent vocal pain outcomes. Optimal strategies include multimodal analgesia with education and restricted/reduced opioid prescription.

Inter-rater Reliability of the Classification of the J-Sign Is Inadequate Among Experts.

OBJECTIVE: The purpose of this study was to determine the inter-rater and intra-rater reliability of the symmetry, classification, and underlying pathoanatomy associated with the J-sign in patients with recurrent lateral patellofemoral instability. STUDY DESIGN: Blinded, inter-rater reliability study. SETTING: N/A. PARTICIPANTS: Thirty patellofemoral joint experts. INTERVENTIONS: Thirty clinicians independently assessed 30 video recordings of patients with recurrent lateral patellofemoral instability performing the J-sign test. MAIN OUTCOME MEASURES: Raters documented J-sign symmetry and graded it according to the quadrant and Donell classifications. Raters indicated the most significant underlying pathoanatomy and presence of sagittal plane maltracking. Intra-rater reliability was assessed by 4 raters repeating the assessments. Mean pairwise simple and/or weighted Cohen's kappa were performed to measure inter-rater and intra-rater reliability, as well as calculation of percent agreement. RESULTS: J-sign symmetry demonstrated fair inter-rater reliability (k = 0.26), whereas intra-rater reliability was moderate (k = 0.48). Inter-rater reliability for the quadrant and Donell classifications indicated moderate agreement, k = 0.51 and k = 0.49, respectively, whereas intra-rater reliability was k = 0.79 and k = 0.72, indicating substantial agreement. Inter-rater reliability of the foremost underlying pathoanatomy produced only slight agreement (k = 0.20); however, intra-rater reliability was substantial (k = 0.68). Sagittal plane maltracking demonstrated slight inter-rater agreement (k = 0.23) but substantial intra-rater agreement (k = 0.64). CONCLUSIONS: The symmetry, classification, and underlying pathoanatomy of the J-sign demonstrated fair to moderate inter-rater reliability and moderate to substantial intra-rater reliability among expert reviewers using video recordings of patients with recurrent lateral patellofemoral instability. These findings suggest individual raters have a consistent standard for assessing the J-sign, but that these standards are not reliable between assessors. LEVEL OF EVIDENCE: III.

Adherence to the OARSI recommendations for designing, conducting, and reporting of clinical trials in knee osteoarthritis: a targeted literature review.

BACKGROUND: The Osteoarthritis Research Society International (OARSI) updated their guideline for clinical trials on knee osteoarthritis (KOA) in 2015, which contains recommendations for the conduct, design, and reporting of clinical trials. The purpose of this study was to assess the quality of clinical trials published between 2010 and 2020 investigating intra-articular interventions in patients with KOA using the OARSI recommendations. METHODS: A targeted literature review was conducted to identify randomized controlled trials in patients with KOA receiving intra-articular interventions, published between 2010 and 2020. Included studies were assessed using the OARSI recommendations. For a comparison between the time periods before and after the introduction of the new OARSI recommendations, the year 2016 was selected as the cut-off. RESULTS: One hundred forty-eight publications, representing 139 unique trials, were included in this review. Included studies adhered to between 9 and 24 recommendations (median: 19). The highest increase in adherence from studies published in 2016 or earlier compared to after 2016 was seen in the reporting and registration of trials and the use of structural outcome measures. Overall, adherence to the recommendations related to the collection of biochemical biomarkers and the use of structural outcome measures remained low. CONCLUSION: An improvement can be made in the conduct, design, and reporting of clinical trials for intra-articular therapies in KOA. Despite proper guidelines, quality of clinical trials varies, and the methodological deficiencies found are preventable and can be corrected. The quality of research should be considered when making treatment decisions for patients with KOA in clinical practice.

Development of succinimide-based inhibitors for the mitochondrial rhomboid protease PARL.

While the biochemistry of rhomboid proteases has been extensively studied since their discovery two decades ago, efforts to define the physiological roles of these enzymes are ongoing and would benefit from chemical probes that can be used to manipulate the functions of these proteins in their native settings. Here, we describe the use of activity-based protein profiling (ABPP) technology to conduct a targeted screen for small-molecule inhibitors of the mitochondrial rhomboid protease PARL, which plays a critical role in regulating mitophagy and cell death. We synthesized a series of succinimide-containing sulfonyl esters and sulfonamides and discovered that these compounds serve as inhibitors of PARL with the most potent sulfonamides having submicromolar affinity for the enzyme. A counterscreen against the bacterial rhomboid protease GlpG demonstrates that several of these compounds display selectivity for PARL over GlpG by as much as two orders of magnitude. Both the sulfonyl ester and sulfonamide scaffolds exhibit reversible binding and are able to engage PARL in mammalian cells. Collectively, our findings provide encouraging precedent for the development of PARL-selective inhibitors and establish N-[(arylsulfonyl)oxy]succinimides and N-arylsulfonylsuccinimides as new molecular scaffolds for inhibiting members of the rhomboid protease family.

Arthroscopy Association of Canada Position Statement on Exercise for Knee Osteoarthritis: A Systematic Review of Guidelines.

BACKGROUND: Exercise is widely regarded to improve pain and function in patients with knee osteoarthritis (OA) through building supportive muscle mass, facilitating weight loss, and through the other beneficial effects associated with it. PURPOSE: To explore literature that presents clinical guidelines for the use of exercise in the treatment of knee OA to inform an evidence-based position statement for the Arthroscopy Association of Canada. STUDY DESIGN: Position statement. METHODS: PubMed, MEDLINE, Embase, and Cochrane databases were searched for guidelines commenting on the role of exercise for knee OA. The search was limited to guidelines published in the last 10 years. Articles were screened for relevance, focusing on recently published research with clinical guidelines. Inclusion criteria involved all articles providing clinical guidelines for exercise and knee OA. RESULTS: Eight guidelines were identified. All eight recommended exercise as an important component of treatment for knee OA, with 6/8 strongly recommending it. CONCLUSION: Exercise is an effective and important component of the non-pharmacological management of knee OA. The Arthroscopy Association of Canada strongly recommends the use of exercise in the management of knee OA.

ATG9A regulates proteostasis through reticulophagy receptors FAM134B and SEC62 and folding chaperones CALR and HSPB1.

The acetylation of ATG9A within the endoplasmic reticulum (ER) lumen regulates the induction of reticulophagy. ER acetylation is ensured by AT-1/SLC33A1, a membrane transporter that maintains the cytosol-to-ER flux of acetyl-CoA. Defective AT-1 activity, as caused by heterozygous/homozygous mutations and gene duplication events, results in severe disease phenotypes. Here, we show that although the acetylation of ATG9A occurs in the ER lumen, the induction of reticulophagy requires ATG9A to engage FAM134B and SEC62 on the cytosolic side of the ER. To address this conundrum, we resolved the ATG9A interactome in two mouse models of AT-1 dysregulation: AT-1 sTg, a model of systemic AT-1 overexpression with hyperacetylation of ATG9A, and AT-1S113R/+, a model of AT-1 haploinsufficiency with hypoacetylation of ATG9A. We identified CALR and HSPB1 as two ATG9A partners that regulate the induction of reticulophagy as a function of ATG9A acetylation and discovered that ATG9A associates with several proteins that maintain ER proteostasis.

Efficacy and Safety of Hylan G-F 20 Versus Intra-Articular Corticosteroids in People with Knee Osteoarthritis: A Systematic Review and Network Meta-Analysis.

BACKGROUND: Direct injection of corticosteroids into the joint is a standard treatment for knee osteoarthritis (OA). However, the treatment is somewhat controversial with regard to the benefit of both single and repeated injections; evidence that they are beneficial comes from small studies that show only modest improvements. The aim of this study was to estimate the short- and long-term clinical efficacy and safety of hylan G-F 20 versus intra-articular corticosteroids (IACS) for the treatment of pain in knee OA using Bayesian network meta-analysis. METHODS: Based on a pre-specified protocol, MEDLINE, Embase, and CENTRAL were searched from inception to June 2018 to identify randomized controlled trials. The Cochrane Collaboration's tool for assessing risk of bias in randomized trials was used to assess the included studies. Hylan G-F 20 and IACS were compared using Bayesian network meta-analysis. Efficacy was evaluated at 1, 3, and 6 months, and at the final follow-up for safety outcomes. A pain hierarchy was used to select 1 pain outcome per study. RESULTS: Forty-two trials were included for analysis. The network meta-analysis of pain showed that hylan G-F 20 may be equivalent to IACS in the short-term, but by 6 months the benefit relative to IACS was statistically significant, standardized mean difference (95% credible interval): -0.13 (-0.26, -0.01). There were no statistical differences in adverse events. CONCLUSIONS: Hylan G-F 20 may perform better in relieving pain at 6 months post-injection compared to IACS. Both agents were relatively well tolerated, with no clear differences in safety.

Osteoarthritis, mobility-related comorbidities and mortality: an overview of meta-analyses.

AIMS: The objective of this review was to examine the relationship between osteoarthritis (OA) and mobility-related comorbidities, specifically diabetes mellitus (DM) and cardiovascular disease (CVD). It also investigated the relationship between OA and mortality. METHODS: An overview of meta-analyses was conducted by performing two targeted searches from inception to June 2020. The association between OA and (i) DM or CVD (via PubMed and Embase); and (ii) mortality (via PubMed) was investigated. Meta-analyses were selected if they included studies that examined adults with OA at any site and reported associations between OA and DM, CVD, or mortality. Evidence was synthesized qualitatively. RESULTS: Six meta-analyses met inclusion criteria. One meta-analysis of 20 studies demonstrated a statistically significant association between OA and DM, with pooled odds ratio of 1.41 (95% confidence interval: 1.21, 1.65; n = 1,040,175 patients). One meta-analysis of 15 studies demonstrated significantly increased risk of CVD among OA patients, with a pooled risk ratio of 1.24 (1.12, 1.37, n = 358,944 patients). Stratified by type of CVD, OA was shown to be associated with increased heart failure (HF) and ischemic heart disease (IHD) and reduced transient ischemic attack (TIA). There was no association reported for stroke or myocardial infarction (MI). Three meta-analyses did not find a significant association between OA (any site) and all-cause mortality. However, OA was found to be significantly associated with cardiovascular-related death across two meta-analyses. CONCLUSION: The identified meta-analyses reported significantly increased risk of both DM and CVD (particularly, HF and IHD) among OA patients. It was not possible to confirm consistent directional or causal relationships. OA was found to be associated with increased mortality, but mostly in relation to CVD-related mortality, suggesting that further study is warranted in this area.

Chemical comparison of Prunus africana bark and pygeum products marketed for prostate health.

The bark of Prunus africana may contain atranorin, atraric acid, beta-sitosterol and its esters, ferulic acid and its esters, and N-butylbenzene sulfonamide, compounds that have been shown to improve the conditions of benign prostatic hyperplasia, enlarged prostate. An analytical scheme, involving liquid-solid extractions, saponifications, and LC-APCI-MS (triple quadrupole) analysis, was developed, optimized, and validated to determine the compounds at µg/g levels. Limits of quantification were in the low ng/mL range except for beta-sitosterol. All of the compounds plus two internal standards eluted in under 10 min on a phenyl-hexyl column with gradient elution involving water-methanol and acetonitrile. The mass fraction of the compounds in Prunus africana bark (four samples) and commercial pygeum products (seven samples), derived from bark, were compared. Bark and pygeum were similar in their content of atranorin and atraric acid, found at low µg/g levels, and in the fact that ferulic acid was almost totally (> 90%) in the form of esters. In contrast, the total amount of ferulic acid was on average four times higher in bark (450 µg/g) than in pygeum while the opposite was true for total beta-sitosterol. Some pygeum samples had levels of total beta-sitosterol above 10,000 µg/g while the compound in bark was relatively invariant at about 680 µg/g. The fraction of free beta-sitosterol varied significantly between bark (33%) and pygeum (nearly all). In pygeum, the measured total beta-sitosterol concentration generally followed the labeled values for phytosterol content. No N-butylbenzene sulfonamide was found in any of the bark and pygeum samples.

Development of a simple multidisciplinary arthroplasty wound-assessment instrument: the SMArt Wound Tool

Background: There are currently no validated instruments in the orthopedic literature for assessing the healing of acute surgical wounds. The creation of a simple wound-assessment tool would provide a standardized method of reporting wound outcomes. The objective of this study was to systematically develop a wound-assessment tool that can be used to assess the early healing of arthroplasty incisions. Methods: The databases MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cochrane reviews and CINAHL were searched. Articles that described objective assessment of acute incisional wounds were included. Items for the wound-assessment tool were then extracted from eligible studies based on the frequency of reporting. A multidisciplinary panel of wound experts compiled the items into an initial tool to assess key domains of wound healing. The items were reduced through several iterations of panel discussion. Results: Our search strategy yielded 3743 results, which were screened by title and abstract. Thirty-four studies were included in the systematic review for the development of the wound-assessment tool, and 10 domains were extracted based on frequency of reporting. After item reduction, the final version of the wound-assessment tool, the SMArt Wound Tool, contained 3 major domains: blistering, peri-incisional skin colour and exudate type. Conclusion: There is currently a need for a standardized tool to assess the healing of orthopedic surgical incisions. The SMArt Wound Tool provides a simple, objective method of assessing arthroplasty incisions for the presence of early complications.

Contexte: Il n'existe actuellement aucun instrument validé dans la littérature orthopédique pour évaluer la cicatrisation des plaies chirurgicales récentes. La création d'un outil d'évaluation simple des plaies offrirait une méthode standard pour suivre leur évolution. L'objectif de cette étude était de concevoir un outil d'évaluation systématique des plaies pouvant être utilisé pour vérifier la bonne cicatrisation des incisions d'arthroplastie. Méthodes: Les bases de données MEDLINE, Embase, CINAHL, le registre central Cochrane des essais contrôlés et la base de données Cochrane des revues systématiques ont été interrogés. Les articles qui décrivaient une évaluation objective des plaies d'incision récentes ont été inclus. Les paramètres d'évaluation des plaies ont ensuite été extraits à partir des études retenues en fonction de la fréquence à laquelle ils étaient rapportés. Un comité multidisciplinaire d'experts des plaies a compilé les paramètres pour créer un outil initial d'évaluation des domaines clés de la cicatrisation des plaies. Des discussions successives du comité ont ensuite permis de réduire le nombre de paramètres d'évaluation. Résultats: Notre stratégie d'interrogation a généré 3743 résultats qui ont été triés par titre et résumé. Trente-quatre études ont été retenues pour la revue systématique en vue de la création de l'outil d'évaluation des plaies et 10 domaines ont été extraits en fonction de la fréquence à laquelle ils étaient rapportés. Après la réduction du nombre de paramètres, la version finale de l'outil d'évaluation des plaies, appelé SMArt Wound Tool, comprenait 3 domaines principaux : formation de vésicules, couleur de la peau au pourtour de l'incision et type d'exsudat. Conclusion: On déplore actuellement l'absence d'outils standards pour évaluer la cicatrisation des plaies en chirurgie orthopédique. L'outil SMArt offre une méthode simple et objective d'évaluation des incisions d'arthroplastie pour déceler rapidement la moindre complication, le cas échéant.

Does it really spin? Intra-medullary nailing of segmental tibial fractures--a cadaveric study.

This study aims to quantify the effect of intra-medullary reaming on rotational displacement of both long diaphyseal segmental tibial fractures (Melis Type III) and short (Melis Type IV) in a cadaveric model with differing degrees of soft tissue stripping. Eighteen fresh-frozen cadaveric specimens (9 matched pairs), median age at death was 85 years (68-92) were used to perform a standardized reaming procedure for an intra-medullary tibial nail and the rotational displacement of the segmental fracture fragment (long and short diaphyseal fractures) was recorded. Rotational displacement was recorded using a goniometer and K-wires positioned in the proximal, segmental and distal fracture fragments. Type III fractures rotate more than Type IV fractures (p<0.0001). In Type III fractures reaming to fit with 0%, 50% and 100% soft tissue stripping resulted in rotational displacement of 11.7 SD 12), 13 (SD 16.5) and 307.3 (SD 118.1) degrees respectively. In Type IV fractures reaming to fit with 0%, 50% and 100% soft tissue stripping resulted in rotational displacement of 8.5 (SD 5.5), 12.7 (SD 9.9) and 135.3 (SD 147.1) degrees respectively. The use of a pointed reduction clamp or unicortical plate eliminated rotational displacement. Reaming is a major risk factor for rotational displacement of segmental tibial fractures irrespective of the degree of soft tissue stripping. Long diaphyseal segmental fractures rotate more than shorter segmental fractures. We recommend always clamping the fracture during reaming to avoid rotational displacement.

Minimally invasive reduction and fixation of displaced calcaneal fractures: surgical technique and radiographic analysis.

PURPOSE: The optimal treatment of calcaneal fractures is controversial. A specific subgroup of healthy patients has good outcomes with open reduction and internal fixation using an extensile lateral approach. However, there are many patients who do not fit into this category. Consequently, they are either denied surgical intervention or put at significant risk of developing complications as a result of open surgical intervention. Minimally invasive reduction and fixation (MIRF) of calcaneal fractures can restore the height, width, length and shape of the hindfoot in addition to restoring the orientation of the posterior facet of the calcaneus (Böhler's angle). METHODS: We present a series of 31 patients treated with minimally invasive reduction and fixation technique using threaded K wires and Steinmann pins as an alternative treatment method in patients who are not suitable for open reduction and internal fixation. RESULTS: The mean time to surgery from injury was six days (range one to ten days). The mean duration of surgery was 35 minutes (range 11-52 minutes). The mean followup was 14.9 months (range of seven to 30 months). The mean change in Böhler's angle and length of the calcaneus from intra-operative fixation to final followup were 18.7° and 4.7 mm, respectively. The complication rate was low and there was one case of a superficial wound infection and no cases of deep infection or peroneal impingement in this series. CONCLUSION: The MIRF technique with the use of threaded K wires has not been previously described in the literature. In our experience, the operative time is short and can be safely performed even in the presence of extensive soft tissue swelling in the immediate period following injury. The infection risk is low and calcaneal morphology was improved and maintained in terms of Böhler's angle. This technique is suitable to be considered in patients who have significant medical co-morbidities (smokers, diabetics, peripheral vascular disease) and in those patients who are not suitable for an extensile lateral approach and internal fixation.

A relation based measure of semantic similarity for Gene Ontology annotations.

BACKGROUND: Various measures of semantic similarity of terms in bio-ontologies such as the Gene Ontology (GO) have been used to compare gene products. Such measures of similarity have been used to annotate uncharacterized gene products and group gene products into functional groups. There are various ways to measure semantic similarity, either using the topological structure of the ontology, the instances (gene products) associated with terms or a mixture of both. We focus on an instance level definition of semantic similarity while using the information contained in the ontology, both in the graphical structure of the ontology and the semantics of relations between terms, to provide constraints on our instance level description.Semantic similarity of terms is extended to annotations by various approaches, either though aggregation operations such as min, max and average or through an extrapolative method. These approaches introduce assumptions about how semantic similarity of terms relates to the semantic similarity of annotations that do not necessarily reflect how terms relate to each other. RESULTS: We exploit the semantics of relations in the GO to construct an algorithm called SSA that provides the basis of a framework that naturally extends instance based methods of semantic similarity of terms, such as Resnik's measure, to describing annotations and not just terms. Our measure attempts to correctly interpret how terms combine via their relationships in the ontological hierarchy. SSA uses these relationships to identify the most specific common ancestors between terms. We outline the set of cases in which terms can combine and associate partial order constraints with each case that order the specificity of terms. These cases form the basis for the SSA algorithm. The set of associated constraints also provide a set of principles that any improvement on our method should seek to satisfy. CONCLUSION: We derive a measure of semantic similarity between annotations that exploits all available information without introducing assumptions about the nature of the ontology or data. We preserve the principles underlying instance based methods of semantic similarity of terms at the annotation level. As a result our measure better describes the information contained in annotations associated with gene products and as a result is better suited to characterizing and classifying gene products through their annotations.