Implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting.

BACKGROUND AND PURPOSE: Length of hospital stay after hip and knee arthroplasty is about 1 day in Denmark with few patients discharged on the day of surgery. Hence, a protocol for multicenter implementation of discharge on day of surgery has been instituted. We aimed to describe the implementation of outpatient hip and knee arthroplasty in a multicenter public healthcare setting. METHODS: We performed a prospective multicenter study from 7 public hospitals across Denmark. Patients were screened using well-defined in- and exclusion criteria and were discharged on day of surgery when fulfilling functional discharge criteria. The study period was from September 2022 to February 2023 with variable start of implementation. Data from the same centers in a 6-month period before the COVID pandemic from July 2019 to December 2019 was used for baseline control. RESULTS: Of 2,756 primary hip and knee arthroplasties, 37% (95% confidence interval [CI] 35-39) were eligible (range 21-50% in centers) and 52% (range 24-62%) of these were discharged on day of surgery. 21% (CI 20-23) of all patients (eligible and non-eligible) were discharged on day of surgery with a range of 10-31% within centers. This was an additional 15% (CI 13-17, P < 0.001) compared with patients discharged in the control period (6% in 2019). CONCLUSION: We found it possible to perform outpatient hip and knee replacement in 21% of patients in a public healthcare setting, probably to be increased with further center experience.

Subretinal AAV delivery of RNAi-therapeutics targeting VEGFA reduces choroidal neovascularization in a large animal model.

Neovascular age-related macular degeneration (nAMD) is a frequent cause of vision loss among the elderly in the Western world. Current disease management with repeated injections of anti-VEGF agents accumulates the risk for adverse events and constitutes a burden for society and the individual patient. Sustained suppression of VEGF using gene therapy is an attractive alternative, which we explored using adeno-associated virus (AAV)-based delivery of novel RNA interference (RNAi) effectors in a porcine model of choroidal neovascularization (CNV). The potency of VEGFA-targeting, Ago2-dependent short hairpin RNAs placed in pri-microRNA scaffolds (miR-agshRNA) was established in vitro and in vivo in mice. Subsequently, AAV serotype 8 (AAV2.8) vectors encoding VEGFA-targeting or irrelevant miR-agshRNAs under the control of a tissue-specific promotor were delivered to the porcine retina via subretinal injection before CNV induction by laser. Notably, VEGFA-targeting miR-agshRNAs resulted in a significant and sizable reduction of CNV compared with the non-targeting control. We also demonstrated that single-stranded and self-complementary AAV2.8 vectors efficiently transduce porcine retinal pigment epithelium cells but differ in their transduction characteristics and retinal safety. Collectively, our data demonstrated a robust anti-angiogenic effect of VEGFA-targeting miR-aghsRNAs in a large translational animal model, thereby suggesting AAV-based delivery of anti-VEGFA RNAi therapeutics as a valuable tool for the management of nAMD.

Protocol for a prospective multicentre cohort study to address the question whether diabetes and its management is still a risk factor in fast-track joint arthroplasty.

INTRODUCTION: Perioperative glycaemic control is important. However, the complexity of guidelines for perioperative diabetes management is complicated due to different and novel antihyperglycaemic medications, limited procedure-specific data and lack of data from implemented fast-track regimens which otherwise are known to reduce morbidity and glucose homeostasis disturbances. Consequently, outcome in patients with diabetes mellitus (DM) after surgery and the influence of perioperative diabetes management on postoperative recovery remains poorly understood. METHODS AND ANALYSIS: A prospective observational multicentre study involving 8 arthroplasty centres across Denmark with a documented implemented fast-track programme (median length of hospitalisation (LOS) 1 day). We will collect detailed perioperative data including preoperative haemoglobin A1c and antidiabetic treatment in 1400 unselected consecutive patients with DM undergoing hip and knee arthroplasty from September 2022 to December 2025, enrolled after consent. Follow-up duration is 90 days after surgery. The primary outcome is the proportion of patients with DM with LOS >4 days and 90-day readmission rate after fast-track total hip arthroplasty (THA), total knee arthroplasty (TKA) and unicompartmental knee arthroplasty (UKA). The secondary outcome is the association between perioperative diabetes treatment and LOS >2 days, 90-day readmission rate, other patient demographics and Comprehensive Complication Index for patients with DM after THA/TKA/UKA in a fast-track regimen. ETHICS AND DISSEMINATION: The study will follow the principles of the Declaration of Helsinki and ICH-Good Clinical Practice guideline. Ethical approval was not necessary as this is a non-interventional observational study on current practice. The trial is registered in the Region of Southern Denmark and on ClinicalTrials.gov. The main results and all substudies of this trial will be published in peer-reviewed international medical journals. TRIAL REGISTRATION NUMBER: NCT05613439.

Biomechanics of a collum-fixated short stem in total hip arthroplasty.

Background: Biomechanical reconstruction of the hip significantly impacts the clinical outcome and implant survival. Our knowledge is limited of the ability of neck-stabilised prostheses to restore hip biomechanics. We hypothesised that hip biomechanics, specifically leg length and global offset (GO), may be restored to an acceptable range using the Primoris™ stem. Methods and material: In this retrospective study, we analysed 152 patients who underwent total hip replacement (THA) using the short collum-fixated stem Primoris™.The primary outcomes were hip parameters measured by x-ray following THA using the Primoris™ stem. After surgery, the biomechanical parameters used were measured at the arthroplasty and the native contralateral side of the same x-ray. The X-rays were taken one year after the patient's surgery.1. GO.2. Leg length discrepancy (LLD).3. Neck shaft angle (NSA). Results: We recorded an average GO of -3.4 mm (standard deviation (SD) 7.2) and an average LLD of +3.8 mm (SD 6.4). Furthermore, we registered an average 14-degree NSA increase (SD 7.4). Conclusion: The Primoris™ neck-stabilised stem enabled hip anatomy restoration to a favourable range with respect to GO and LLD as the average difference fell within ±5 mm. However, the stem tended to be implanted in valgus.

Digital mapping of shoulder pain in patients with shoulder disorders: a reliability study.

INTRODUCTION: Digital body mapping can be used to document and quantify the area and location (distribution) of pain and discomfort and support assessment, monitoring, and treatment in clinical populations. This study determines the test-retest reliability of drawings detailing pain and pins and needles using digital body charts and their relationship to pain intensity and patient-reported shoulder function. METHODS: Sixty-two participants with shoulder disorder completed pain and pins and needles drawings with test-retest interval of 30 minutes. Pain intensity in the last week and the patient-reported shoulder function questionnaires were completed. Area and radiating extent were determined using customized software. To assess relative and absolute test-retest reliability, the intraclass correlation coefficient (ICC3,1), standard error of measurement (SEM) and minimal detectable change (MDC95) were calculated. Regression analysis evaluated relation between area and radiating extent of pain and pins and needles with patient-reported function questionnaires. RESULTS: Relative reliability for pain area and radiating extent was excellent (>0.90). Absolute reliability (SEM and MDC95) values for the pain area and radiating extent were 0.20%/34 pixels and 0.57%/94 pixels. Absolute reliability improves for smaller pain areas. Regression analysis revealed the area and radiation extent for both pain and pins and needles are independent constructs to the patient-reported function outcome when adjusted for pain intensity. CONCLUSIONS: Digital body mapping assessing pain area and radiation extent in patients with shoulder disorders are reliable. The magnitude of absolute reliability suggests other sources of variability on repeat testing in this population. Pain area and radiation extent appear to be independent constructs.

Machine-learning vs. logistic regression for preoperative prediction of medical morbidity after fast-track hip and knee arthroplasty-a comparative study.

BACKGROUND: Machine-learning models may improve prediction of length of stay (LOS) and morbidity after surgery. However, few studies include fast-track programs, and most rely on administrative coding with limited follow-up and information on perioperative care. This study investigates potential benefits of a machine-learning model for prediction of postoperative morbidity in fast-track total hip (THA) and knee arthroplasty (TKA). METHODS: Cohort study in consecutive unselected primary THA/TKA between 2014-2017 from seven Danish centers with established fast-track protocols. Preoperative comorbidity and prescribed medication were recorded prospectively and information on length of stay and readmissions was obtained through the Danish National Patient Registry and medical records. We used a machine-learning model (Boosted Decision Trees) based on boosted decision trees with 33 preoperative variables for predicting "medical" morbidity leading to LOS > 4 days or 90-days readmissions and compared to a logistical regression model based on the same variables. We also evaluated two parsimonious models, using the ten most important variables in the full machine-learning and logistic regression models. Data collected between 2014-2016 (n:18,013) was used for model training and data from 2017 (n:3913) was used for testing. Model performances were analyzed using precision, area under receiver operating (AUROC) and precision recall curves (AUPRC), as well as the Mathews Correlation Coefficient. Variable importance was analyzed using Shapley Additive Explanations values. RESULTS: Using a threshold of 20% "risk-patients" (n:782), precision, AUROC and AUPRC were 13.6%, 76.3% and 15.5% vs. 12.4%, 74.7% and 15.6% for the machine-learning and logistic regression model, respectively. The parsimonious machine-learning model performed better than the full logistic regression model. Of the top ten variables, eight were shared between the machine-learning and logistic regression models, but with a considerable age-related variation in importance of specific types of medication. CONCLUSION: A machine-learning model using preoperative characteristics and prescriptions slightly improved identification of patients in high-risk of "medical" complications after fast-track THA and TKA compared to a logistic regression model. Such algorithms could help find a manageable population of patients who may benefit most from intensified perioperative care.

Engineered lentivirus-derived nanoparticles (LVNPs) for delivery of CRISPR/Cas ribonucleoprotein complexes supporting base editing, prime editing and in vivo gene modification.

Implementation of therapeutic in vivo gene editing using CRISPR/Cas relies on potent delivery of gene editing tools. Administration of ribonucleoprotein (RNP) complexes consisting of Cas protein and single guide RNA (sgRNA) offers short-lived editing activity and safety advantages over conventional viral and non-viral gene and RNA delivery approaches. By engineering lentivirus-derived nanoparticles (LVNPs) to facilitate RNP delivery, we demonstrate effective administration of SpCas9 as well as SpCas9-derived base and prime editors (BE/PE) leading to gene editing in recipient cells. Unique Gag/GagPol protein fusion strategies facilitate RNP packaging in LVNPs, and refinement of LVNP stoichiometry supports optimized LVNP yield and incorporation of therapeutic payload. We demonstrate near instantaneous target DNA cleavage and complete RNP turnover within 4 days. As a result, LVNPs provide high on-target DNA cleavage and lower levels of off-target cleavage activity compared to standard RNP nucleofection in cultured cells. LVNPs accommodate BE/sgRNA and PE/epegRNA RNPs leading to base editing with reduced bystander editing and prime editing without detectable indel formation. Notably, in the mouse eye, we provide the first proof-of-concept for LVNP-directed in vivo gene disruption. Our findings establish LVNPs as promising vehicles for delivery of RNPs facilitating donor-free base and prime editing without formation of double-stranded DNA breaks.

25 years of maturation: A systematic review of RNAi in the clinic.

The year 2023 marks the 25th anniversary of the discovery of RNAi. RNAi-based therapeutics enable sequence-specific gene knockdown by eliminating target RNA molecules through complementary base-pairing. A systematic review of published and ongoing clinical trials was performed. Web of Science, PubMed, and Embase were searched from January 1, 1998, to December 30, 2022 for clinical trials using RNAi. Following inclusion, data from the articles were extracted according to a predefined protocol. A total of 90 trials published in 81 articles were included. In addition, ongoing clinical trials were retrieved from ClinicalTrials.gov, resulting in the inclusion of 48 trials. We investigated how maturation of RNAi-based therapeutics and developments in delivery platforms, administration routes, and potential targets shape the current landscape of clinically applied RNAi. Notably, most contemporary clinical trials used either N-acetylgalactosamine delivery and subcutaneous administration or lipid nanoparticle delivery and intravenous administration. In conclusion, RNAi therapeutics have gained great momentum during the past decade, resulting in five approved therapeutics targeting the liver for treatment of severe diseases, and the trajectory depicted by the ongoing trials emphasizes that even more RNAi-based medicines also targeting extra-hepatic tissues are likely to be available in the years to come.

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial].

INTRODUCTION: A feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is no consensus on the dosages and current recommendations are based on a low evidence level. The objective is to compare the effect of a single versus multiple doses of prophylactic antibiotics administered within 24 hours on PJI. METHODS AND ANALYSIS: The study is designed as a cross-over, cluster randomised, non-inferiority trial. All clinical centres use both antibiotic practices (1 year of each intervention). All Danish orthopaedic surgery departments will be involved: Based on quality databases, 2-year cohorts of approximately 20 000 primary THAs conducted at 39 public and private hospitals, will be included. INCLUSION CRITERIA: age ≥18 years, all indications for THA except patients operated due to acute or sequelae from proximal femoral or pelvic fractures or bone tumour or metastasis. The primary outcome is PJI within 90 days after primary THA. Secondary outcomes include (1) serious adverse events, (2) potential PJI, (3) length of hospitalisation stay, (4) cardiovascular events, (5) hospital-treated infections, (6) community-based antibiotic use, (7) opioid use and (8) use of acetaminophen and non-steroidal anti-inflammatory drugs. All outcome measures will be extracted from national databases. Analyses will be based on the intention-to-treat population. Non-inferiority will be shown if the upper limit of the two-sided 95% CI for the OR is less than 1.32 for the single dose as compared with multiple doses. The results will establish best practice on antibiotic prophylaxis dosages in the future. ETHICS AND DISSEMINATION: This study has been approved by Committees on Health Research Ethics for The Capital Region of Denmark (21069108) and The Danish Medicines Agency (2021091723). All results will be presented in peer-reviewed medical journals and international conferences. TRIAL REGISTRATION NUMBER: NCT05530551.

Porcine models of choroidal neovascularization: A systematic review.

Animal models of choroidal neovascularization (CNV) are extensively used in translational studies of CNV formation and to evaluate angiostatic treatment strategies. However, the current paucity of large animal models compared with rodent models constitutes a knowledge gap regarding the clinical translation of findings. Ocular anatomical and physiological similarities to humans suggest the pig as a relevant model animal. Thus, a systematic survey of porcine CNV models was performed to identify pertinent model parameters and suggest avenues for model standardization and optimization. A systematic search was performed in PubMed and EMBASE on November 28, 2022 for porcine models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. A total of 14 articles, representing 19 independent porcine CNV models were included. The included models were almost equally divided between laser-induced (53%) and surgically-induced (47%) models. Different specified breeds of domestic pigs (71%) were most commonly used in the studies. All studies used normal animals. Female pigs were reported used in 43% of the studies, while 43% did not report on sex of the animals. Younger pigs were typically used. The surgical models reported consistent CNV induction following mechanical Bruch's membrane rupture. The laser models used variants of the infrared diode laser (40%) or the frequency-doubled Nd:YAG laser (50%). Both lasers enabled successful CNV induction with reported induction rates ranging from 60 to 100%. Collateral damage to the neuroretina was reported for the infrared diode laser. CNV evaluation varied across studies with fluorescein angiography (50%) as the most used in vivo method and retinal sections (71%) as the most used ex vivo method. In interventional studies, quantification of lesions was in general performed between 7 and 14 days. The field of porcine CNV models is relatively small and heterogeneous and almost equally divided between surgically-induced and laser-induced models. Both methods have allowed successful modeling of CNV formation with induction rates comparable to those of non-human primates. However, the field would benefit from standardization of model parameters and reporting. This includes laser parameters and validation of CNV formation as well as methods of CNV evaluation and statistical analysis.

Sortilin Inhibition Protects Neurons From Degeneration in the Diabetic Retina.

Purpose: To investigate the level and localization of the multifunctional receptor sortilin in the diabetic retina, as well as the effect of sortilin inhibition on retinal neurodegeneration in experimental diabetes. Methods: The localization of sortilin and colocalization with the p75 neurotrophin receptor (p75NTR) and Müller cell (MC) markers were determined using immunofluorescence on retinal sections from human patients with diabetes and streptozotocin-induced diabetic C57BL/6J male mice. In the diabetic mice, levels were further quantified using Western blot and quantitative PCR. Therapeutic studies were performed on diabetic mice using intravitreally injected anti-sortilin antibodies. Neuroprotection was evaluated in vivo by optical coherence tomography and by quantification of retinal ganglion cells (RGCs) in flat mounts. Results: Increased levels of sortilin were observed in human and murine diabetic retinas compared with nondiabetic control retinas. Sortilin was highly localized to retinal MCs, and, notably, colocalization with p75NTR was only seen in diabetic retinas. A remarkable protective effect of sortilin inhibition on inner retinal cells was observed in diabetic mice. At eight weeks after diabetes induction, inner retinal thickness was reduced by 9.7% (-12.7%, -6.6%; P < 0.0001; n = 11-12) in the PBS-injected control group compared with the anti-sortilin injected group. Similarly, the count of RGCs was reduced by 20.5% (-30.8%, -10.2%; P = 0.0009) in the PBS-injected control group compared with the anti-sortilin-injected group. Conclusions: Sortilin is upregulated in the diabetic retina, and sortilin inhibition effectively protects against neuronal loss. Thus sortilin emerges as a novel pharmacological target in diabetic retinal neurodegeneration-an important early event in the pathogenesis of diabetic retinopathy.

Gastrointestinal complications after fast-track total hip and knee replacement: an observational study in a consecutive 36,932 patient cohort.

INTRODUCTION: Gastrointestinal complications after total hip (THA) and knee arthroplasty (TKA) have been reported to be between 0.3 and 2.6% with bleeding and C. difficile infection in 0-1%, and 0.1-1.7%, respectively. The use of enhanced recovery or "fast-track" protocols have focused on optimizing all aspects of perioperative care resulting in reduced length of hospital stay (LOS) and potentially also gastrointestinal complications. This study is a detailed analysis on the occurrence of postoperative gastrointestinal complications resulting in increased hospital stay or readmissions in a large consecutive cohort of fast-track THA and TKA with complete 90 days follow-up. MATERIALS AND METHODS: This is an observational study on a consecutive cohort of primary unilateral THAs and TKAs performed between January 2010 and August 2017 in nine Danish high-volume fast-track centers. Discharge summaries and relevant patient records were reviewed in patients with readmissions within 90 days or LOS > 4 days caused by gastrointestinal complications. RESULTS: The cohort included 36,932 patients with 58.3% females and 54.1% THAs. Mean age and BMI were 68 years and 28. Median postoperative LOS was 2 days. Only n: 276 (0.75 %) had a LOS > 4 days or a readmission within 90 days due to a gastrointestinal complication (CI 0.67%-0.84%). Of these, only 34 (0.09%) were graded as severe ileus or gastrointestinal bleeding. CONCLUSIONS: The risk of GI-complications within the first 90 postoperative days after fast-track THA and TKA was low (0.75%).

Hip precautions after posterior-approach total hip arthroplasty among patients with primary hip osteoarthritis do not influence early recovery: a systematic review and meta-analysis of randomized and non-randomized studies with 8,835 patients.

BACKGROUND AND PURPOSE: Hip precautions are routinely prescribed to patients with osteoarthritis to decrease dislocation rates after total hip arthroplasty (THA) using a posterior approach. However, recommendations have been based on very low certainty of evidence. We updated the evidence on the influence of hip precautions on early recovery following THA by this systematic review. MATERIALS AND METHODS: We performed systematic searches for randomized controlled trials (RCT) and non-randomized (NRS) studies in MEDLINE, Embase, PEDro, and CINAHL published from 2016 to July 2022. 2 reviewers independently included studies comparing postoperative precautions with minimal or no precautions, extracted data, and assessed the risk of bias. Random effects meta-analyses were used to synthesize the results. The certainty of the evidence was rated by the Grading of Recommendations Assessment and Evaluation approach. The critical outcome was the risk of hip dislocations within 3 months of surgery. Other outcomes were long-term risk of dislocation and reoperation, self-reported and performance-based assessment of function, quality of life, pain, and time to return to work. RESULTS: 4 RCTs and 5 NRSs, including 8,835 participants, were included. There may be no or negligible difference in early hip dislocations (RCTs: risk ratio [RR] 1.8, 95% confidence interval [CI] 0.6-5.2; NRS: RR 0.9, CI 0.3-2.5). Certainty in the evidence was low for RCTs and very low for NRSs. Finally, precautions may reduce the performance-based assessment of function slightly, but the evidence was very uncertain. For all other outcomes, no differences were found (moderate to very low certainty evidence). CONCLUSION: The current evidence does not support routinely prescribing hip precautions post-surgically for patients undergoing THA to prevent hip dislocations. However, the results might change with high-quality studies.

Study protocol for discharge on day of surgery after hip and knee arthroplasty from the Center for Fast-track Hip and Knee Replacement.

BACKGROUND AND PURPOSE: Limited data exists on the implementation process and safety of discharge on the day of surgery after primary hip and knee arthroplasty in a multicenter setting. We report our study protocol on the investigation of the feasibility, safety, and socioeconomic aspects following discharge on day of surgery after hip and knee arthroplasty across 8 fast-track centers. PATIENTS AND METHODS: This is a study protocol for a prospective cohort study on discharge on day of surgery from the Center for Fast-track Hip and Knee Replacement. The collaboration includes 8 centers covering 40% of the primary hip and knee arthroplasty procedures undertaken in Denmark. All patients scheduled for surgery are screened for eligibility using well-defined inclusion and exclusion criteria. Eligible patients fulfilling discharge criteria will be discharged on day of surgery. We expect to screen 9,000 patients annually. Duration and outcome: Patients will be enrolled over a 3-year period from September 2022 and reporting of results will run continuously until December 2025. We shall report the proportion of eligible patients and patients discharged on day of surgery as well as limiting factors. Readmissions and complications within 30 days are recorded with real-time follow-up by research staff. Furthermore, patient-reported information on willingness to repeat discharge on day of surgery, contacts with the healthcare system, complications, and workability is registered 30 days postoperatively. EQ-5D, Oxford Knee Score, and Oxford Hip Score are completed preoperatively and after 3 months and 1 year. Finally, outcome data will be used in the development of a prediction model for successful discharge on the day of surgery.

Peripheral nerve-blocks and associations with length of stay and readmissions in fast-track total hip and knee arthroplasty.

BACKGROUND: Peripheral nerve blocks (PNB) have recently been recommended in total hip (THA) and knee (TKA) arthroplasty as they may reduce pain, morphine consumption, length of stay (LOS) and complications. However, whether PNBs are associated with early discharge within an enhanced recovery protocol including multimodal analgesia is uncertain. METHODS: An observational multicenter study from January to August 2017 in six Danish Arthroplasty Centers with established fast-track protocols. Prospective recording of preoperative characteristics and information on PNB, LOS and readmissions through the Danish National Patient Registry and medical records. Multiple logistic regression was used to investigate associations between PNB and a LOS >1 day, LOS >4 days, and 30-days readmissions. We also reported on mobilization, pain, opioid and fall-related complications leading to LOS >4 days or readmissions. RESULTS: A total of 2027 (58.6%) THA and 1432 (41.4%) TKAs with a median LOS of 1 day (IQR 1-2) and 5.3% (CI:4.6-6.1) 30-days readmission rate were identified. PNB was used in 40.7% (CI:38.2-43.3) of TKA and 2.7% (CI:2.0-3.5) of THA, but with considerable interdepartmental variation (0.0-89.0% for TKA). There was no association between PNB and LOS >1 day (OR:1.19 CI:0.82-1.72; p = .354), LOS >4 days (OR:1.4 CI:0.68-2.89; p = .359) or 30-days readmissions (OR:1.02 CI:0.63-1.65; p = .935) in TKA. Logistic regression in THA was not possible due to limited use of PNB. In TKA there were 12 (2.1% CI:1.2-3.6) with and 1 (0.1% CI:0.02-0.7) without a PNB, who had mobilization, pain or opioid-related complications, and 5 (0.9% CI:0.4-2.0) versus 4 (0.5% CI:0.2-1.2) who fell. Correspondingly, 2 (3.7% CI:1.0-12.6) and 11 (0.6% CI:0.3-1.0) of THA patients had these complications, while 0 (0.0% CI:0.0-6.6) and 17 (0.8% CI:0.5-1.3) fell. CONCLUSION: Routine use of peripheral nerve blocks was not associated with early discharge or 30-days readmissions in fast-track THA and TKA. Future studies should focus on benefits of PNB in high-risk patients.

Projection of primary and revision hip arthroplasty surgery in Denmark from 2020 to 2050.

BACKGROUND AND PURPOSE: The incidence of primary and revision total hip arthroplasty (THA) has increased over the last decades. Previous forecasts from different healthcare systems have predicted a continuous increase. We present a forecast of both primary and revision surgery from 2020 to 2050 based on 25 years data from the healthcare system in Denmark. PATIENTS AND METHODS: We retrieved data from the Danish Hip Arthroplasty Register on 198,835 primary and 29,456 revision surgeries. Historical censuses and population forecasts were retrieved from Statistics Denmark. Logistic and Gompertz regression analysis was used to forecast incidence rates (IR) and total numbers in the next 30 years. RESULTS: Our forecast predicts an increase in IR of 3-9% and an increase in total numbers of primary THA of between 12% and 19% in 2050. For revision THA the IRs have reached a plateau but total numbers are predicted to increase by 19% in 2050. CONCLUSION: Our forecast shows that both primary and revision THA will increase in total numbers in the next decades, but the IR for primary THA is near its plateau and for revision THA the plateau has already been reached. The forecast may aid in healthcare resource planning for the decades to come.

Blood flow restriction added to usual care exercise in patients with early weight bearing restrictions after cartilage or meniscus repair in the knee joint: a feasibility study.

PURPOSE: Blood flow restriction - low load strength training (BFR-LLST) is theoretically superior to traditional heavy strength training when rehabilitating patients who cannot heavily load tissues following surgery. The main purpose of this study was to examine the feasibility of BFR-LLST added to usual care exercise early after cartilage or meniscus repair in the knee joint. METHODS: We included 42 patients with cartilage (n = 21) or meniscus repair (n = 21) of the knee joint. They attended 9 weeks of BFR-LLST added to a usual care exercise program at an outpatient rehabilitation center. Outcome measures were assessed at different time points from four (baseline) to 26 weeks postoperatively and included adherence, harms, knee joint and thigh pain, perceived exertion, thigh circumference (muscle size proxy), isometric knee-extension strength, self-reported disability and quality of life. RESULTS: On average, patients with cartilage or meniscus repair completed > 84% of the total BFR-LLST supervised sessions. Thirty-eight patients reported 146 adverse events of which none were considered serious. No decrease in thigh circumference or exacerbation of knee joint or quadriceps muscle pain of the operated leg was found in either group during the intervention period. CONCLUSIONS: BFR-LLST added to usual care exercise initiated early after cartilage or meniscus repair seems feasible and may prevent disuse thigh muscle atrophy during a period of weight bearing restrictions. Harms were reported, but no serious adverse events were found. Our findings are promising but need replication using a RCT-design. TRIAL REGISTRATION: NCT03371901 , preprint (open access):  https://www.medrxiv.org/content/10.1101/2022.03.31.22272398v1.

[Bisphosphonate-induced ocular and orbital inflammation].

The inflammatory side effects of bisphosphonates are well-known. We report a case of orbital and ocular inflammation secondary to the use of intravenous zoledronic acid and a case of scleritis secondary to oral alendronate. Bisphosphonate-induced inflammation can present as uveitis, (epi)scleritis, and orbital inflammation. The course is typically self-limiting after cessation of bisphosphonate therapy, but resolution can be further promoted by steroid therapy. The ocular side effects of bisphosphonates should be duly considered.

Animal Models of Choroidal Neovascularization: A Systematic Review.

Purpose: Animal models of choroidal neovascularization (CNV) are extensively used to characterize the pathophysiology of chorioretinal diseases with CNV formation and to evaluate novel treatment strategies. This systematic review aims to give a detailed overview of contemporary animal models of CNV. Methods: A systematic search was performed in PubMed and EMBASE from November 20, 2015, to November 20, 2020, for mammalian animal models of CNV. Following inclusion by two investigators, data from the articles were extracted according to a predefined protocol. Results: A total of 380 full articles, representing 409 independent animal models, were included. Mice were by far the most utilized animal (76%) followed by rats and non-human primates. The median age of rodents was 8 weeks but with a wide range. Male animals were used in 44% of the studies, but 32% did not report the sex. CNV was laser induced in 89% of the studies, but only 44% of these reported sufficiently on standard laser parameters. Surprisingly, 28% of the studies did not report a sample size for quantitative CNV evaluation. Less than half of the studies performed quantitative in vivo evaluation, and 73% evaluated CNV quantitatively ex vivo. Both in vivo and ex vivo evaluations were conducted primarily at day 7 and/or day 14. Conclusions: The laser-induced mouse model is the predominant model for experimental CNV. The widespread use of young, healthy male animals may complicate clinical translation, and inadequate reporting challenges reproducibility. Definition and implementation of standardized methodologic and reporting guidelines are attractive.