Prostate Radiotherapy in Low-volume Metastatic Hormone-sensitive Prostate Cancer: A Network Meta-analysis.

BACKGROUND AND OBJECTIVE: The utility of prostate radiotherapy (RT) is unclear in men with metastatic hormone-sensitive prostate cancer (mHSPC) receiving intensified systemic therapy with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPIs). We performed a network meta-analysis of randomized controlled trials (RCTs) to investigate the role of prostate RT in low-volume mHSPC. METHODS: Bibliographic databases and conference proceedings were searched through July 2023 for RCTs evaluating the addition of ARPIs or prostate RT to standard of care (SOC) systemic therapy, defined as ADT or ADT plus docetaxel, for the initial treatment of mHSPC. We focused exclusively on aggregate data from the low-volume mHSPC subpopulation in these trials. We pooled the treatment arms into four groups: SOC, SOC plus ARPI, SOC plus RT, and SOC plus ARPI plus RT. The primary outcome was overall survival (OS). To compare treatment strategies, a fixed-effects Bayesian network meta-analysis was undertaken, while a Bayesian network meta-regression was performed to account for across-trial differences in docetaxel use as part of SOC and in proportions of patients with de novo presentation. KEY FINDINGS AND LIMITATIONS: Ten RCTs comprising 4423 patients were eligible. The Surface Under the Cumulative Ranking Curve scores were 0.0006, 0.45, 0.62, and 0.94 for SOC, SOC plus RT, SOC plus ARPI, and SOC plus ARPI plus RT, respectively. On a meta-regression, in a population with de novo mHSPC and no docetaxel use, we did not find sufficient evidence of a difference in OS between SOC plus ARPI plus RT versus SOC plus ARPI (hazard ratio [HR]: 0.76; 95% credible interval: 0.51-1.16) and SOC plus RT versus SOC plus ARPI (HR: 1.10; 95% credible interval: 0.92-1.42). CONCLUSIONS AND CLINICAL IMPLICATIONS: There was some evidence that SOC plus ARPI plus RT reduced mortality compared with the next best strategy of SOC plus ARPI in patients with low-volume de novo mHSPC. A meta-analysis with individual patient data or an RCT is needed to confirm these findings.

Vitamin D as an intervention for improving quadriceps muscle strength in patients after anterior cruciate ligament reconstruction: study protocol for a randomized double-blinded, placebo-controlled clinical trial.

BACKGROUND: The goal of anterior cruciate ligament reconstruction (ACLR) is to restore the preinjury level of knee function to return to play (RTP). However, even after completing the rehabilitation programme, some patients may have persistent quadriceps muscle weakness affecting knee function which ultimately leads to a failure in returning to play. Vitamin D has been long recognized for its musculoskeletal effects. Vitamin D deficiency may impair muscle strength recovery after ACLR. Correcting vitamin D levels may improve muscle strength. METHODS: This is a double-blinded, randomized controlled trial to investigate the effects of vitamin D supplementation during the post-operative period on quadriceps muscle strength in anterior cruciate ligament (ACL)-injured patients. Patients aged 18-50 with serum vitamin D < 20 ng/ml, unilateral ACL injury, > 90% deficit in total quadriceps muscle volume on the involved leg compared with uninvolved leg, Tegner score 7 + , and no previous knee injury/surgery will be recruited. To assess patient improvement, we will perform isokinetic and isometric muscle assessments, ultrasound imaging for quadriceps thickness, self-reported outcomes, KT-1000 for knee laxity, biomechanical analysis, and Xtreme CT for bone mineral density. To investigate the effect of vitamin D status on quadriceps strength, blood serum samples will be taken before and after intervention. DISCUSSION: Patients with low vitamin D levels had greater quadriceps fibre cross-sectional area loss and impaired muscle strength recovery after ACL. The proposed study will provide scientific support for using vitamin D supplementation to improve quadriceps strength recovery after ACLR. TRIAL REGISTRATION: ClinicalTrials.gov NCT05174611. Registered on 28 November 2021.

Real-World Evaluation of Primary Versus Secondary Prevention of Skeletal-Related Events in Metastatic Castration-Resistant Prostate Cancer.

INTRODUCTION: Anti-osteoclast treatment with denosumab or zoledronate is known to effectively reduce the need for radiotherapy to bone and other skeletal-related events (SREs) in patients with metastatic castration-resistant prostate cancer (mCRPC). In this study, we analyze primary versus secondary initiation of bone-targeting agents (BTAs) relative to first palliative bone radiotherapy in patients dying of mCRPC. METHODS: Provincial administrative databases from Ontario, Canada identified patients with prostate cancer (2007-2018, n = 98 646) who received continuous androgen deprivation therapy (n = 29 453), died of prostate cancer (2013-2018, n = 3864), and received life-prolonging therapy for mCRPC (n = 1850). Variables were collected looking back 3 years from death. Multivariable analysis explored the relationship between clinical variables and BTAs. RESULTS: Of the 58% (1066/1850) patients with mCRPC who received BTA, only 289 (25.4%) started BTA prior to first palliative bone radiotherapy as primary prevention. Eight hundred and forty-eight (74.6%) patients either never received BTA before death (n = 447) or started BTA only after first bone radiotherapy (n = 401). More patients received denosumab (n = 825, 77%) than zoledronic acid (n = 241, 23%). 51.2% (582/1137) of palliative bone radiotherapy was initiated in the last 12 months of life. Factors associated with the use of BTA included elevated alkaline phosphatase (OR = 1.0, P = .023), de novo metastases (OR = 1.4, P = .005), medical oncologist involvement (OR = 2.0, P = .007), diagnosis 2012-2017 versus 2007-2011 (OR = 0.75, P = .034), and academic center (OR = 0.061, P = .007). CONCLUSION: A majority of patients with mCRPC never receive BTAs prior to first SRE, despite universal access and availability of these agents in Ontario. These results highlight an opportunity to improve outcomes by emphasizing early introduction of BTA in patients with mCRPC being started on systemic therapy.

Variation in Access to Palliative Radiotherapy in Prostate Cancer: A Population-Based Study in Canada.

BACKGROUND: As a result of improvements in cancer therapies, patients with metastatic malignancies are living longer, and the role of palliative radiotherapy has become increasingly recognized. However, access to adequate palliative radiotherapy may continue to be a challenge, as is evident from the high proportion of patients dying of prostate cancer who never receive palliative radiotherapy. The main objective of this investigation is to identify and describe the factors associated with the receipt of palliative radiation treatment in a decedent cohort of prostate cancer patients in Ontario. METHODOLOGY:  Population-based administrative databases from Ontario, Canada, were used to identify prostate cancer decedents, 65 years or older who received androgen deprivation therapy between January 1, 2013, and December 31, 2018. Baseline and treatment characteristics were analyzed using univariate and multivariate logistic regression models for association with receipt of radiotherapy in a two-year observation period before death. RESULTS: We identified 3,788 prostate cancer decedents between 2013 and 2018; among these, 49.9% received radiotherapy in the two years preceding death. There were statistically significant positive associations between receipt of radiotherapy and younger age at diagnosis (odds ratio [OR] 1.6, 95% confidence interval [CI] 1.1-2.3); higher stage at diagnosis (OR 1.3, 95% CI 1.1-1.7); receipt of care at a regional cancer center (OR 1.8, 95% CI 1.3-2.4); and involvement of radiation oncologists (OR 155.1, 95% CI 83.3-288.7) or medical oncologists (OR 1.4, 95% CI 1.1-1.8). However, there were no associations between receipt of radiotherapy and income, distance to the nearest cancer center, involvement of urologists in cancer care, healthcare administrative region, home-care involvement, or number of hospitalizations in the observation period. CONCLUSIONS: We found the utilization of palliative radiotherapy for prostate cancer patients in Ontario varies depending on age, stage at diagnosis, number of comorbidities, registration at regional cancer centers, and involvement of oncologists. There were no differences detected based on income or distance from a cancer center. The findings of this study represent an important opportunity to facilitate better access to palliative radiotherapy and referrals to multidisciplinary regional cancer centers, to improve the quality of life of this patient population.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Deep-WET: a deep learning-based approach for predicting DNA-binding proteins using word embedding techniques with weighted features.

DNA-binding proteins (DBPs) play a significant role in all phases of genetic processes, including DNA recombination, repair, and modification. They are often utilized in drug discovery as fundamental elements of steroids, antibiotics, and anticancer drugs. Predicting them poses the most challenging task in proteomics research. Conventional experimental methods for DBP identification are costly and sometimes biased toward prediction. Therefore, developing powerful computational methods that can accurately and rapidly identify DBPs from sequence information is an urgent need. In this study, we propose a novel deep learning-based method called Deep-WET to accurately identify DBPs from primary sequence information. In Deep-WET, we employed three powerful feature encoding schemes containing Global Vectors, Word2Vec, and fastText to encode the protein sequence. Subsequently, these three features were sequentially combined and weighted using the weights obtained from the elements learned through the differential evolution (DE) algorithm. To enhance the predictive performance of Deep-WET, we applied the SHapley Additive exPlanations approach to remove irrelevant features. Finally, the optimal feature subset was input into convolutional neural networks to construct the Deep-WET predictor. Both cross-validation and independent tests indicated that Deep-WET achieved superior predictive performance compared to conventional machine learning classifiers. In addition, in extensive independent test, Deep-WET was effective and outperformed than several state-of-the-art methods for DBP prediction, with accuracy of 78.08%, MCC of 0.559, and AUC of 0.805. This superior performance shows that Deep-WET has a tremendous predictive capacity to predict DBPs. The web server of Deep-WET and curated datasets in this study are available at https://deepwet-dna.monarcatechnical.com/ . The proposed Deep-WET is anticipated to serve the community-wide effort for large-scale identification of potential DBPs.

Reconsidering "Critical" Bone Loss in Shoulder Instability: 17-Year Follow-Up Study following Arthroscopic Bankart Repair.

Background: Glenoid bone loss is a risk factor leading to the failure of arthroscopic Bankart repair. While 20-25% glenoid bone loss has long been considered the level to necessitate bony augmentation, recent studies indicate that 13.5% has a "subcritical" glenoid bone loss level, which is associated with decreased short- and medium-term functional scores. Few researchers worked on the long-term effect of "subcritical" or even less severe degrees of glenoid bone loss on redislocation rates and functional outcomes after arthroscopic Bankart repair. This study aimed to evaluate the effect of subcritical or less severe glenoid bone loss on redislocation rates and function after arthroscopic Bankart repair. Methods: A patient cohort who had undergone computed tomography (CT) of glenoid bone loss and arthroscopic Bankart repair over 15 years ago was reviewed. Western Ontario Shoulder Instability (WOSI) score, Single Assessment Numeric Evaluation (SANE) score, redislocation after operation, mechanism of recurrence, and revision details were reviewed. Results: Seventy-five patients were reassessed 17.6 ± 1.9 years following initial surgery. The age at enrolment was 26.8 ± 8.3 years. Twenty-two (29%) patients of the 75 patients had a redislocation on long-term follow-up, though this was not related to glenoid bone loss severity. The impaired functional score was found in patients with initial glenoid bone loss of 7% or more on long-term follow-up: WOSI (physical symptoms): 0.98 ± 2.00 vs 2.25 ± 4.01, p=0.04 and WOSI (total): 0.79 ± 1.43 vs 1.88 ± 3.56, p=0.04. Conclusions: At a mean of 17.5 years following arthroscopic Bankart repair, redislocation occurs in over a quarter of 75 patients, and they are not related to initial glenoid bone loss severity. Impaired functional outcome is apparent in patients with initial glenoid bone loss of >7%, though this impairment does not seem sufficiently severe to warrant an alternative treatment approach.

In Vivo Effect of Single Intra-Articular Injection of Tranexamic Acid on Articular Cartilage and Meniscus: Study in a Rat Model.

BACKGROUND: Tranexamic acid (TXA) has been increasingly used in arthroscopic surgery to prevent hemarthrosis. Despite its effectiveness, safety concerns have been raised regarding its potential cytotoxicity to articular cartilage and meniscus following intra-articular injection. METHODS: To evaluate the impact of TXA on cartilage and meniscus, a rat model of knee instability was utilized wherein anterior cruciate ligament (ACL) transection surgery was followed by a single intra-articular injection of TXA at varying concentrations (0, 20, 50, 100, and 150 mg/mL) in saline solution. Cell viability assessment of the cartilage and meniscus (n = 6 per group) was conducted at 24 hours, and gross observation and histological analysis of the medial tibial plateau and medial meniscus were conducted at 2, 4, and 8 weeks (n = 6 per group and time point). RESULTS: The chondrocyte viability was significantly decreased in the 50, 100, and 150 mg/mL TXA groups compared with the specimens injected with saline solution only (saline group) (p = 0.001, p < 0.001, p < 0.001, respectively), as was meniscal cell viability (p = 0.042, p < 0.001, p < 0.001, respectively). At week 8, the saline and 20 and 50 mg/mL groups showed relatively normal appearances, whereas the 100 and 150 mg/mL groups exhibited increased and varying severity of cartilage and meniscal degeneration. In the 150 mg/mL group, the mean Osteoarthritis Research Society International score was significantly higher than that in the saline and 20 mg/mL groups (p = 0.010 and p = 0.007). Additionally, the mean meniscus score in the 150 mg/mL group was significantly higher than that in the saline, 20 mg/mL, and 50 mg/mL groups (p = 0.020, p = 0.021, p = 0.031, respectively). CONCLUSIONS: Our findings indicate that concentrations of TXA at or above 100 mg/mL can lead to decreased cell viability in both cartilage and meniscus, resulting in significant cartilage degeneration in rats with ACL transection. Furthermore, the use of 150 mg/mL of TXA led to significant meniscal degeneration. CLINICAL RELEVANCE: It is prudent to avoid using concentrations of TXA at or above 100 mg/mL for intra-articular injection, as such concentrations may result in adverse effects on the cartilage and meniscus.

Unsupervised domain adaptation for automated knee osteoarthritis phenotype classification.

Background: Osteoarthritis (OA) is a global healthcare problem. The increasing population of OA patients demands a greater bandwidth of imaging and diagnostics. It is important to provide automatic and objective diagnostic techniques to address this challenge. This study demonstrates the utility of unsupervised domain adaptation (UDA) for automated OA phenotype classification. Methods: We collected 318 and 960 three-dimensional double-echo steady-state magnetic resonance images from the Osteoarthritis Initiative (OAI) dataset as the source dataset for phenotype cartilage/meniscus and subchondral bone, respectively. Fifty three-dimensional turbo spin echo (TSE)/fast spin echo (FSE) MR images from our institute were collected as the target datasets. For each patient, the degree of knee OA was initially graded according to the MRI Knee Osteoarthritis Knee Score before being converted to binary OA phenotype labels. The proposed four-step UDA pipeline included (I) pre-processing, which involved automatic segmentation and region-of-interest cropping; (II) source classifier training, which involved pre-training a convolutional neural network (CNN) encoder for phenotype classification using the source dataset; (III) target encoder adaptation, which involved unsupervised adjustment of the source encoder to the target encoder using both the source and target datasets; and (IV) target classifier validation, which involved statistical analysis of the classification performance evaluated by the area under the receiver operating characteristic curve (AUROC), sensitivity, specificity and accuracy. We compared our model on the target data with the source pre-trained model and the model trained with the target data from scratch. Results: For phenotype cartilage/meniscus, our model has the best performance out of the three models, giving 0.90 [95% confidence interval (CI): 0.79-1.02] of the AUROC score, while the other two model show 0.52 (95% CI: 0.13-0.90) and 0.76 (95% CI: 0.53-0.98). For phenotype subchondral bone, our model gave 0.75 (95% CI: 0.56-0.94) at AUROC, which has a close performance of the source pre-trained model (0.76, 95% CI: 0.55-0.98), and better than the model trained from scratch on the target dataset only (0.53, 95% CI: 0.33-0.73). Conclusions: By utilising a large, high-quality source dataset for training, the proposed UDA approach enhances the performance of automated OA phenotype classification for small target datasets. As a result, our technique enables improved downstream analysis of locally collected datasets with a small sample size.

Effectiveness of a theory-driven mHealth intervention in promoting post-surgery rehabilitation adherence in patients who had anterior cruciate ligament reconstruction: A randomized clinical trial.

RATIONALE: Patients with anterior cruciate ligament (ACL) reconstruction often have poor adherence to post-surgery rehabilitation. OBJECTIVE: This study applied the integrated model of self-determination theory and the theory of planned behavior to examine the effects of a smartphone-delivered intervention on the recovery outcomes of patients with an ACL rupture during post-surgery rehabilitation period. Additionally, we explored the effects of the intervention on participants with different beliefs toward rehabilitation at baseline. METHODS: The randomized control trial recruited 96 eligible participants (M age = 27.82 years, SD = 8.73; female = 39%) who underwent ACL reconstruction surgery. Participants were randomly assigned to an intervention group (n = 41), which received standard post-surgical treatment (usual-care) and smartphone application ("ACL-Well"), or a usual-care control group (n = 55). The primary outcomes were recovery outcomes from ACL surgery measured by knee muscle strength and laxity, and subjective knee evaluation completed 4-month post-intervention. Secondary outcomes were the psychological and behavioral outcomes measured at baseline, at 2- and 4-month post-intervention. RESULTS: ANCOVA indicated no significant between-group differences in primary outcomes: knee muscle strength, knee laxity and subjective knee evaluation, Fs(1, 27 to 55) = 0.01 to 1.36, p = .25 to .99, η2 = 0.01 to 0.03. For the secondary outcomes, growth mixture modelling revealed self-determined treatment motivation declined significantly over the intervention period in the control group (M slope = -0.39 to -0.12, p = .01 to .04), but not in the intervention group (M slope = -0.19 to -0.08, p = .06 to .38). CONCLUSIONS: The smartphone application fell short in promoting orthopedic outpatients' recovery outcomes. Yet, it shows some promises as a mean to maintain patients' motivation and adherence to treatment.

Surgical accuracy of image-free versus image-based robotic-assisted total knee arthroplasty.

BACKGROUND: This study investigated the accuracy in achieving proper lower limb alignment and component positions after total knee replacement (TKR) with image-free and image-based robotic-assisted TKR. METHODS: A total of 129 patients (166 knees) suffering from end-stage knee arthritis who underwent TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Radiological outcomes were compared between image-free and image-based robotic-assisted surgical systems. RESULTS: There were significant differences between the two robotic systems when comparing the mean planned component alignment and the mean measured alignment on radiographs, in which the image-free robotic-assisted system was more varus, whereas the image-based robotic-assisted system was more valgus for both the mean femoral and tibial component coronal alignment (p < 0.001). For tibial component sagittal alignment, the image-based group had a larger deviation from the planned posterior slope (p < 0.001). CONCLUSION: Image-free and image-based robotic assisted TKR had differing accuracy in femoral and tibial alignment.

Geographic Variation in the Quality of Heart Failure Care Among U.S. Veterans.

BACKGROUND: The burden of heart failure is growing. Guideline-directed medical therapies (GDMT) reduce adverse outcomes in heart failure with reduced ejection fraction (HFrEF). Whether there is geographic variation in HFrEF quality of care is not well described. OBJECTIVES: This study evaluated variation nationally for prescription of GDMT within the Veterans Health Administration. METHODS: A cohort of Veterans with HFrEF had their address linked to hospital referral regions (HRRs). GDMT prescription was defined using pharmacy data between July 1, 2020, and July 1, 2021. Within HRRs, we calculated the percentage of Veterans prescribed GDMT and a composite GDMT z-score. National choropleth maps were created to evaluate prescription variation. Associations between GDMT performance and demographic characteristics were evaluated using linear regression. RESULTS: Maps demonstrated significant variation in the HRR composite score and GDMT prescriptions. Within HRRs, the prescription of beta-blockers to Veterans was highest with a median of 80% (IQR: 77.3%-82.2%) followed by angiotensin-converting enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitors (69.3%; IQR: 66.4%-72.1%), sodium-glucose cotransporter-2 inhibitors (10.3%; IQR: 7.7%-12.8%), mineralocorticoid receptor antagonists (29.2%; IQR: 25.8%-33.9%), and angiotensin receptor-neprilysin inhibitors (12.2%; IQR: 8.6%-15.3%). HRR composite GDMT z-scores were inversely associated with the HRR median Gini coefficient (R = -0.13; P = 0.0218) and the percentage of low-income residents (R = -0.117; P = 0.0413). CONCLUSIONS: Wide geographic differences exist for HFrEF care. Targeted strategies may be required to increase GDMT prescription for Veterans in lower-performing regions, including those affected by income inequality and poverty.

Genetic testing practices among specialist physicians who treat prostate cancer A Canadian, cross-sectional survey.

INTRODUCTION: In patients with prostate cancer (PCa), the identification of an alteration in genes associated with homologous recombination repair (HRR) has implications for prognostication, optimization of therapy, and familial risk mitigation. The aim of this study was to assess the genomic testing landscape of PCa in Canada and to recommend an approach to offering germline and tumor testing for HRR-associated genes. METHODS: The Canadian Genitourinary Research Consortium (GURC) administered a cross-sectional survey to a largely academic, multidisciplinary group of investigators across 22 GURC sites between January and June 2022. RESULTS: Thirty-eight investigators from all 22 sites responded to the survey. Germline genetic testing was initiated by 34%, while 45% required a referral to a genetic specialist. Most investigators (82%) reported that both germline and tumor testing were needed, with 92% currently offering germline and 72% offering tissue testing to patients with advanced PCa. The most cited reasons for not offering testing were an access gap (50%), uncertainties around who to test and which genes to test, (33%) and interpreting results (17%). A majority reported that patients with advanced PCa (74-80%) should be tested, with few investigators testing patients with localized disease except when there is a family history of PCa (45-55%). CONCLUSIONS: Canadian physicians with academic subspecialist backgrounds in genitourinary malignancies recognize the benefits of both germline and somatic testing in PCa; however, there are challenges in accessing testing across practices and specialties. An algorithm to reduce uncertainty for providers when ordering genetic testing for patients with PCa is proposed.

Assessments of early patellofemoral joint osteoarthritis features after anterior cruciate ligament reconstruction: a cross-sectional study.

BACKGROUND: Persistent anterior knee pain and subsequent patellofemoral joint (PFJ) osteoarthritis (OA) are common symptoms after anterior cruciate ligament reconstruction (ACLR). Quadriceps weakness and atrophy is also common after ACLR. This can be contributed by arthrogenic muscle inhibition and disuse, caused by joint swelling, pain, and inflammation after surgery. With quadriceps atrophy and weakness are associated with PFJ pain, this can cause further disuse exacerbating muscle atrophy. Herein, this study aims to identify early changes in musculoskeletal, functional and quality of health parameters for knee OA after 5 years of ACLR. METHODS: Patients treated with arthroscopically assisted single-bundle ACLR using hamstrings graft for more than 5 years were identified and recruited from our clinic registry. Those with persistent anterior knee pain were invited back for our follow-up study. For all participants, basic clinical demography and standard knee X-ray were taken. Likewise, clinical history, symptomatology, and physical examination were performed to confirm isolated PFJ pain. Outcome measures including leg quadriceps quality using ultrasound, functional performance using pressure mat and pain using self-reported questionnaires (KOOS, Kujala and IKDC) were assessed. Interobserver reproducibility was assessed by two reviewers. RESULTS: A total of 19 patients with unilateral injury who had undergone ACLR 5-years ago with persistent anterior knee pain participated in this present study. Toward the muscle quality, thinner vastus medialis and more stiffness in vastus lateralis were found in post-ACLR knees (p < 0.05). Functionally, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb with increasing knee flexion. In accordance, rectus femoris muscle stiffness in the ACLR knee was significantly correlated with pain (p < 0.05). CONCLUSION: In this study, it was found that patients having higher degree of anterior knee pain were associated with higher vastus medialis muscle stiffness and thinner vastus lateralis muscle thickness. Similarly, patients with more anterior knee pain tended to shift more of their body weight towards the non-injured limb leading to an abnormal PFJ loading. Taken together, this current study helped to indicate that persistent quadriceps muscle weakness is potential contributing factor to the early development of PFJ pain.

Single use Negative Pressure Wound Therapy (NPWT) system in the management of knee arthroplasty.

BACKGROUND: Wound complication, skin blister formation in particular, causes devastating consequences after total knee arthroplasty (TKA). Negative Pressure Wound Therapy (NPWT) tries to improve wound management leading to decrease length of hospital stay and better clinical outcomes. Low body mass index (BMI) could play a part in wound recovery management although lacking evidence. This study compared length of hospital stay and clinical outcomes between NPWT and Conventional groups, and factors affected and how BMI affected. METHODS: This was a retrospective clinical record review of 255 (160 NPWT and 95 Conventional) patients between 2018 and 2022. Patient demographics including body mass index (BMI), surgical details (unilateral or bilateral), length of hospital stay, clinical outcomes including skin blisters occurrence, and major wound complications were investigated. RESULTS: Mean age of patients at surgery was 69.95 (66.3% were female). Patients treated with NPWT stayed significantly longer in the hospital after joint replacement (5.18 days vs. 4.55 days; p = 0.01). Significantly fewer patients treated with NPWT found to have blisters (No blisters: 95.0% vs. 87.4%; p = 0.05). In patients with BMI < 30, percentage of patients requiring dressing change was significantly lower when treated with NPWT than conventional (0.8% vs. 33.3%). CONCLUSION: Percentage of blisters occurrence in patients who underwent joint replacement surgery is significantly lower using NPWT. Patients using NPWT stayed significantly longer in the hospital after surgery because significant proportion received bilateral surgery. NPWT patients with BMI < 30 were significantly less likely to change wound dressing.

Triplet Therapy in Metastatic Castrate Sensitive Prostate Cancer (mCSPC)-A Potential New Standard of Care.

The treatment paradigm for metastatic castrate-sensitive prostate cancer (mCSPC) has evolved rapidly in the past decade with the approval of several life-prolonging therapies including docetaxel chemotherapy and multiple androgen receptor pathway inhibitors (ARPI) in combination with androgen deprivation therapy (ADT). Recently reported phase-three trials have demonstrated a survival benefit of upfront triplet therapy with ADT, docetaxel plus either abiraterone acetate or darolutamide when compared to ADT plus docetaxel alone. However, multiple questions including the incremental benefit of docetaxel to a combination of ADT and ARPI, the timing of ARPI, optimal patient selection for triplet therapy and clinical and genomic biomarkers still remain to be answered. Moreover, real-world data suggest suboptimal treatment intensification with many patients treated with ADT alone highlighting challenges in implementation. In this article, we review the phase-three data associated with triplet therapy in mCSPC. We also discuss the knowledge gaps that exist despite the completion of these studies and how ongoing studies are likely to change the paradigm in the near future. Finally, we provide a simple algorithm based on current data that clinicians can use in daily practice to select patients for appropriate treatment strategies.

Long-term survivorship and results in lower limb arthroplasty: a registry-based comparison study.

INTRODUCTION: Popularity of joint replacement surgery due to ever aging population surges the demand for a proper national joint registry. Our Chinese University of Hong Kong - Prince of Wales Hospital (CUHK-PWH) joint registry has passed the 30th year. The aims of this study are 1) summarize our territory-wide joint registry which has passed the 30th year since establishment and 2) compare our statistics with other major joint registries. METHODS: Part 1 was to review the CUHK-PWH registry. Demographic characteristics of our patients who underwent knee and hip replacements had been summarized. Part 2 was a series of comparisons with registries from Sweden, UK, Australia and New Zealand. RESULTS: CUHK-PWH registry captured 2889 primary total knee replacements (TKR) (110 (3.81%) revision) and 879 primary total hip replacements (THR) (107 (12.17%) revision). Median Surgery time of TKR was shorter than THR. Clinical outcome scores were much improved after surgery in both. Uncemented of hybrid in TKR were most popular in Australia (33.4%) and 40% in Sweden and UK. More than half of TKR and THR patients showed the highest percentage with ASA grade 2. New Zealand reflected the best cumulative percentage survival 20 years after surgery of 92.2%, 76.0%, 84.2% survivorship 20 years after TKR, unicompartmental knee replacement (UKR) and Hip. CONCLUSION: A worldwide accepted patient-reported outcome measure (PROM) is recommended to develop to make comparisons among registries and studies feasible. Completeness of registry data is important and useful to improve surgical performance through data comparisons from different regions. Funding from government on sustaining registries is reflected. Registries from Asian countries have yet to be grown and reported.

Smoking Cessation, Version 3.2022, NCCN Clinical Practice Guidelines in Oncology.

Although the harmful effects of smoking after a cancer diagnosis have been clearly demonstrated, many patients continue to smoke cigarettes during treatment and beyond. The NCCN Guidelines for Smoking Cessation emphasize the importance of smoking cessation in all patients with cancer and seek to establish evidence-based recommendations tailored to the unique needs and concerns of patients with cancer. The recommendations contained herein describe interventions for cessation of all combustible tobacco products (eg, cigarettes, cigars, hookah), including smokeless tobacco products. However, recommendations are based on studies of cigarette smoking. The NCCN Smoking Cessation Panel recommends that treatment plans for all patients with cancer who smoke include the following 3 tenets that should be done concurrently: (1) evidence-based motivational strategies and behavior therapy (counseling), which can be brief; (2) evidence-based pharmacotherapy; and (3) close follow-up with retreatment as needed.

Surgical accuracy and clinical outcomes of image-free robotic-assisted total knee arthroplasty.

BACKGROUND: The development of total knee arthroplasty (TKA) for knee osteoarthritis (OA) has a good reputation for its effectiveness in reducing joint pain and improving range of motion. We aimed to review our early results using the image-free robotic-assisted technology in knee arthroplasty. METHODS: A total of 71 patients suffering from end-stage OA knee receiving TKA operated by robotic-assisted surgery between the years 2018 and mid-2021 were recruited. Clinical and radiological outcomes were compared with age and sex-matched control group (conventional TKA). RESULTS: The radiological outcome showed significantly more postoperative lower limb alignment outliers in conventional side than robotic-assisted sides. Postoperative knee scores were similar among both groups. Robotic-assisted TKA required a longer implantation time but a shorter hospital stay. CONCLUSION: Robotic-assisted TKA achieved a lower rate of mechanical axis Outlier in the coronal and sagittal plane with a shorter hospital stay. Yet both methods achieve a similar functional outcome.

Doxycycline Promotes Graft Healing and Attenuates Posttraumatic Osteoarthritis After Anterior Cruciate Ligament Reconstruction in a Rat Model.

BACKGROUND: Doxycycline (Doxy) has been shown to facilitate tendon healing by reducing on-site matrix metalloproteinase (MMP) activity, but its effect on graft healing after anterior cruciate ligament reconstruction (ACLR) has not been investigated, and the therapeutic effect of Doxy in preventing ACLR-induced posttraumatic osteoarthritis (PTOA) is unclear. HYPOTHESIS: Doxy promotes graft healing and alleviates the progression of PTOA after ACLR. STUDY DESIGN: Controlled laboratory study. METHODS: Sprague Dawley rats (n = 74; age, 12-13 weeks; male) that underwent ACLR were divided into untreated control and Doxy treatment (50 mg/kg/d orally until sacrifice) groups. At 2 and 6 weeks after surgery, graft healing was assessed by biomechanical testing, histology, immunohistochemical staining, and micro-computed tomography (µCT). The progression of PTOA was evaluated at 6 weeks by histology, the Mankin score, and immunofluorescence staining of the tibial plateau, and osteophyte formation was evaluated by µCT. Hindlimb weight distribution was evaluated at 6 weeks, and gait patterns were evaluated at 2 and 6 weeks. Intra-articular MMP activity was evaluated at 6 weeks in vivo using an MMP-activatable near-infrared fluorescent probe. RESULTS: Graft healing was enhanced by Doxy treatment, and the ultimate failure load (P = .002) and stiffness of the graft (P = .007) were significantly higher in the Doxy group at week 2. Bone mineral density and bone volume/total volume for both the tibial and the femoral tunnels at week 6 in the Doxy group were significantly higher compared with in the control group (P < .05). The overall graft healing scores were significantly higher in the Doxy group. Doxy treatment enhanced graft integration, intratunnel graft integrity, and collagen birefringence; more collagen types 1 and 10 and less MMP-13 were found at the graft-bone interface. At week 6, the Doxy group had a lower modified Mankin score (P = .033) and showed fewer MMP 13-positive chondrocytes at the articular cartilage surface (P = .002), indicating moderate joint cartilage damage. µCT revealed less osteophyte formation, and gait analysis revealed more symmetric weightbearing and gait patterns, after Doxy treatment at week 6 (P < .05). In vivo imaging with the near-infrared fluorescent probe identified significantly lower intra-articular MMP activity in the Doxy group at week 6 (P = .016). CONCLUSION: The oral administration of Doxy was able to synchronously promote graft healing and attenuate PTOA in an ACLR rat model. CLINICAL RELEVANCE: Our results indicated that Doxy, a widely used drug, is potentially beneficial to patients after ACLR.