Impact of inflammation and anti-inflammatory therapies on the incidence of major cardiovascular events in patients with ankylosing spondylitis: A population-based study.

OBJECTIVE: To examine the independent effect of inflammatory burden and various treatments on the risk of incident major adverse cardiovascular events (MACE) in ankylosing spondylitis (AS) patients. METHODS: AS patients were retrospectively selected from a territory-wide database between 2006 and 2015, and were followed until the end of 2018. The primary outcome was the first occurrence of MACE. Multivariate time-varying Cox proportional hazard models were used to determine the associations between inflammatory burden (measured by c-reactive protein [CRP] and erythrocyte sedimentation rate [ESR]) and different therapies with incident MACE, after adjusting for traditional cardiovascular (CV) risk factors. RESULTS: A total of 3827 patients with AS (mean age: 45.2 ± 15.0 years, male: 2911 [76.1 %]) were recruited. After a follow-up of 23,275 person-years, 135 patients (3.5 %) developed a first MACE. Univariate analyses showed that elevated ESR and CRP levels, and the use of glucocorticoids were associated with a significantly higher risk of MACE, while the use of sulfasalazine (SLZ), biologic DMARDs and non-cyclooxygenase-2 inhibitors (non-COX-IIi) were associated with reduced risk of MACE. After adjusting for CV risk factors in the multivariable models, only ESR (HR: 1.02; ESR ≥30 mm/h, HR:1.94) and CRP level (HR: 1.14; CRP >3 mg/dl HR:5.43) remained significantly associated with increased risk of MACE, while SLZ use (HR: 0.41-0.52) was protective against MACE. CONCLUSION: High inflammatory burden was an independent predictor associated with an increased risk of MACE, while the use of SLZ might reduce risk of incident MACE in patients with AS.

Reference Values for Habitual and Fast Gait Speed in Singapore Adults Aged 21 to 80.

Objectives: Gait speed indicates the individual's functional status and predicts overall health. This study aims to determine (1) the intra- and inter-rater and test-retest reliability of the dynamic 4 m gait speed test protocol; (2) establish the normative reference values of habitual and fast gait speeds in community-dwelling healthy Singaporean adults aged 21 to 80; and (3) explore the association of age, gender, height, weight, and body mass index (BMI) on gait speed. Methods: This prospective cross-sectional study recruited healthy ambulatory community-dwelling Singaporeans aged 21 to 80 who could ambulate independently without aid. Participants were excluded if they required walking aids; were pregnant; or had physical, medical, or cognitive conditions that may affect gait. Each participant completed at least two habitual and fast gait speed test trials via a 4 m walkway with a dynamic start. The data were analysed by descriptive statistics, the Mann-Whitney test, the Spearman coefficient, and the interclass correlation coefficient (ICC). Results: In total, 178 males and 201 females were included in the data analysis. The median age was 45.0 years [interquartile range (IQR) 26.2-59.0], and the median height was 1.64 metres (m) (IQR 1.58-1.70). The median habitual gait speed was 1.08 metre/second (m/s) (IQR 0.97-1.22), and the fast gait speed was 1.55 m/s (IQR 1.40-1.70). The ICC for reliability ranged from 0.84 to 0.99, indicating that the 4 m gait speed test had good-to-excellent reliability. Conclusions: Gait speeds were not influenced by gender but declined with age advancement. Age and height and age and BMI were weakly correlated to habitual and fast gait speed, respectively. We established the norm values for the 4 m gait speeds in Singapore and proved it to be a reliable gait speed assessment ready for immediate community applications.

Repression of PRMT activities sensitize homologous recombination-proficient ovarian and breast cancer cells to PARP inhibitor treatment.

An "induced PARP inhibitor (PARPi) sensitivity by epigenetic modulation" strategy is being evaluated in the clinic to sensitize homologous recombination (HR)-proficient tumors to PARPi treatments. To expand its clinical applications and identify more efficient combinations, we performed a drug screen by combining PARPi with 74 well-characterized epigenetic modulators that target five major classes of epigenetic enzymes. Both type I PRMT inhibitor and PRMT5 inhibitor exhibit high combination and clinical priority scores in our screen. PRMT inhibition significantly enhances PARPi treatment-induced DNA damage in HR-proficient ovarian and breast cancer cells. Mechanistically, PRMTs maintain the expression of genes associated with DNA damage repair and BRCAness and regulate intrinsic innate immune pathways in cancer cells. Analyzing large-scale genomic and functional profiles from TCGA and DepMap further confirms that PRMT1, PRMT4, and PRMT5 are potential therapeutic targets in oncology. Finally, PRMT1 and PRMT5 inhibition act synergistically to enhance PARPi sensitivity. Our studies provide a strong rationale for the clinical application of a combination of PRMT and PARP inhibitors in patients with HR-proficient ovarian or breast cancer.

Kikuchi-Fujimoto disease following SARS-CoV-2 infection: A rare disease with increased incidence during the COVID-19 pandemic?

Kikuchi-Fujimoto Disease (KFD), also known as Kikuchi disease or Kikuchi histiocytic necrotizing lymphadenitis, is a rare and self-limiting condition characterized by cervical lymphadenopathy and fever, primarily affecting young Asian adults. The aetiology of KFD remains unknown, although various infectious agents have been suggested as potential triggers. With the emergence of the COVID-19 pandemic, cases of post-COVID-19 KFD and post-COVID-19 vaccine KFD have been reported. In this article, we present the first case of post-COVID-19 KFD in Hong Kong. A 24-year-old man developed fever and painful neck swelling 1 month after recovering from COVID-19. Diagnostic evaluation, including ultrasound-guided fine needle aspiration cytology (FNAC), confirmed the diagnosis of KFD. The patient's symptoms resolved spontaneously with supportive care. This case underscores the importance of considering KFD as a potential differential diagnosis in patients presenting with cervical lymphadenopathy and fever following COVID-19 recovery or vaccination.

Stereotactic Body Radiotherapy and Liver Transplant for Liver Cancer: A Nonrandomized Controlled Trial.

Importance: Whether stereotactic body radiotherapy (SBRT) as a bridge to liver transplant for hepatocellular carcinoma (HCC) is effective and safe is still unknown. Objective: To investigate the feasibility of SBRT before deceased donor liver transplant (DDLT) for previously untreated unresectable HCC. Design, Setting, and Participants: In this phase 2 nonrandomized controlled trial conducted between June 1, 2015, and October 18, 2019, 32 eligible patients within UCSF (University of California, San Francisco) criteria underwent dual-tracer (18F-fluorodeoxyglucose and 11C-acetate [ACC]) positron emission tomography with computed tomography (PET-CT) and magnetic resonance imaging (MRI) with gadoxetate followed by SBRT of 35 to 50 Gy in 5 fractions, and the same imaging afterward while awaiting DDLT. Statistical analysis was performed on an intention-to-treat basis between October 1 and 31, 2023. Intervention: Patients received SBRT followed by DDLT when matched deceased donor grafts were available. Main Outcomes and Measures: Coprimary end points were progression-free survival (PFS) and objective response rates (ORRs) by the Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1), modified RECIST (mRECIST), and PET Response Criteria in Solid Tumors (PERCIST). Secondary end points were local control rate, overall survival (OS), and safety. Results: A total of 32 patients (median age, 59 years [IQR, 54-63 years]; 22 men [68.8%]) with 56 lesions received SBRT. After a median follow-up of 74.6 months (IQR, 40.1-102.9 months), the median PFS was 17.6 months (95% CI, 6.6-28.6 months), and the median OS was 60.5 months (95% CI, 29.7-91.2 months). The 5-year PFS was 39.9% (95% CI, 19.9%-59.9%), and the 5-year OS was 51.3% (95% CI, 31.7%-70.9%). In terms of number of patients, ORRs were 62.5% ([n = 20] 95% CI, 54.2%-68.7%) by RECIST 1.1, 71.9% ([n = 23] 95% CI, 63.7%-79.0%) by mRECIST, and 78.1% ([n = 25] 95% CI, 73.2%-86.7%) by PERCIST. In terms of number of lesions, ORRs were 75.0% ([n = 42] 95% CI, 61.6%-80.8%) by RECIST 1.1, 83.9% ([n = 47] 95% CI, 74.7%-90.6%) by mRECIST, and 87.5% ([n = 49] 95% CI, 81.3%-98.6%) by PERCIST. Twenty patients with 36 lesions received DDLT, of whom 15 patients (75.0%) with 21 lesions (58.3%) exhibited pathologic complete response. Multivariable analyses revealed that pretreatment metabolic tumor volume (MTV) based on ACC (hazard ratio [HR], 1.06 [95% CI, 1.01-1.10]; P = .01) and complete metabolic response (CMR) by PERCIST (HR, 0.31 [95% CI, 0.10-0.96]; P = .04) were associated with PFS, while pretreatment MTV based on ACC (HR, 1.07 [95% CI, 1.03-1.16]; P = .01), total lesion activity based on ACC (HR, 1.01 [95% CI, 1.00-1.02]; P = .02), and CMR by PERCIST (HR, 0.21 [95% CI, 0.07-0.73]; P = .01) were associated with OS. Toxic effects associated with SBRT were reported for 9 patients (28.1%), with 1 grade 3 event. Conclusions and Relevance: This phase 2 nonrandomized controlled trial demonstrated promising survival and safety outcomes of SBRT before DDLT for unresectable HCC. Future randomized clinical trials are warranted.

Methylation of the chromatin modifier KMT2D by SMYD2 contributes to therapeutic response in hormone-dependent breast cancer.

Activating mutations in PIK3CA are frequently found in estrogen-receptor-positive (ER+) breast cancer, and the combination of the phosphatidylinositol 3-kinase (PI3K) inhibitor alpelisib with anti-ER inhibitors is approved for therapy. We have previously demonstrated that the PI3K pathway regulates ER activity through phosphorylation of the chromatin modifier KMT2D. Here, we discovered a methylation site on KMT2D, at K1330 directly adjacent to S1331, catalyzed by the lysine methyltransferase SMYD2. SMYD2 loss attenuates alpelisib-induced KMT2D chromatin binding and alpelisib-mediated changes in gene expression, including ER-dependent transcription. Knockdown or pharmacological inhibition of SMYD2 sensitizes breast cancer cells, patient-derived organoids, and tumors to PI3K/AKT inhibition and endocrine therapy in part through KMT2D K1330 methylation. Together, our findings uncover a regulatory crosstalk between post-translational modifications that fine-tunes KMT2D function at the chromatin. This provides a rationale for the use of SMYD2 inhibitors in combination with PI3Kα/AKT inhibitors in the treatment of ER+/PIK3CA mutant breast cancer.

Transurethral En Bloc Resection Versus Standard Resection of Bladder Tumour: A Randomised, Multicentre, Phase 3 Trial.

BACKGROUND: Conventionally, standard resection (SR) is performed by resecting the bladder tumour in a piecemeal manner. En bloc resection of the bladder tumour (ERBT) has been proposed as an alternative technique in treating non-muscle-invasive bladder cancer (NMIBC). OBJECTIVE: To investigate whether ERBT could improve the 1-yr recurrence rate of NMIBC, as compared with SR. DESIGN, SETTING, AND PARTICIPANTS: A multicentre, randomised, phase 3 trial was conducted in Hong Kong. Adults with bladder tumour(s) of ≤3 cm were enrolled from April 2017 to December 2020, and followed up until 1 yr after surgery. INTERVENTION: Patients were randomly assigned to receive either ERBT or SR in a 1:1 ratio. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was 1-yr recurrence rate. A modified intention-to-treat analysis on patients with histologically confirmed NMIBC was performed. The main secondary outcomes included detrusor muscle sampling rate, operative time, hospital stay, 30-d complications, any residual or upstaging of disease upon second-look transurethral resection, and 1-yr progression rate. RESULTS AND LIMITATIONS: A total of 350 patients underwent randomisation, and 276 patients were histologically confirmed to have NMIBC. At 1 yr, 31 patients in the ERBT group and 46 in the SR group developed recurrence; the Kaplan-Meier estimate of 1-yr recurrence rates were 29% (95% confidence interval, 18-37) in the ERBT group and 38% (95% confidence interval, 28-46) in the SR group (p = 0.007). Upon a subgroup analysis, patients with 1-3 cm tumour, single tumour, Ta disease, or intermediate-risk NMIBC had a significant benefit from ERBT. None of the patients in the ERBT group and three patients in the SR group developed progression to muscle-invasive bladder cancer; the Kaplan-Meier estimates of 1-yr progression rates were 0% in the ERBT group and 2.6% (95% confidence interval, 0-5.5) in the SR group (p = 0.065). The median operative time was 28 min (interquartile range, 20-45) in the ERBT group and 22 min (interquartile range, 15-30) in the SR group (p < 0.001). All other secondary outcomes were similar in the two groups. CONCLUSIONS: In patients with NMIBC of ≤3 cm, ERBT resulted in a significant reduction in the 1-yr recurrence rate when compared with SR (funded by GRF/ECS, RGC, reference no.: 24116518; ClinicalTrials.gov number, NCT02993211). PATIENT SUMMARY: Conventionally, non-muscle-invasive bladder cancer is treated by resecting the bladder tumour in a piecemeal manner. In this study, we found that en bloc resection, that is, removal of the bladder tumour in one piece, could reduce the 1-yr recurrence rate of non-muscle-invasive bladder cancer.

The Provision and Perceptions of Telemedicine Services Among Traditional Chinese Medicine Practitioners During COVID-19: A Cross-Sectional Study in Hong Kong, China.

Objectives: Telemedicine has been widely used during the COVID-19 pandemic. Among other health care professionals, Chinese medicine practitioners (CMPs) face practical challenges in providing telemedicine consultations. This study aims to explore CMPs' experience and perceptions of telemedicine service provision before and during the pandemic. Methods: A territory-wide cross-sectional online survey was conducted in Hong Kong between April and May 2022. A structured questionnaire with open-ended questions was used to investigate the provision of and perception on telemedicine service, as well as usability of telemedicine among CMPs. Results: A total of 195 CMPs participated the survey. Before COVID-19, 42% (81/195) had been providing telemedicine services, and the proportion doubled during COVID-19. CMPs in the private sector are the main providers. Mobile apps including WhatsApp, WeChat, and Zoom were commonly used for consultations (75%, 120/161). Barriers in providing telemedicine included inability of conducting physical examination on patients (69%, 134/195), legal and ethical concerns over medical negligence (61%, 118/195), and patients' incompetence on e-literacy (50%, 98/195). Respondents urged professional and regulatory bodies to provide an explicit clinical guideline that demonstrate best practice in traditional Chinese medicine telemedicine, and to clarify legal and ethical implications of such practice. Conclusions: CMPs demonstrated their competency in telemedicine, and most of them provided telemedicine during COVID-19. Development of appropriate guidelines on the provision of telemedicine would support CMPs to continue provision after the pandemic, whereas a user-friendly and comprehensive telemedicine e-platform would enhance quality of such service. Facilitating patients with lower e-literacy to access telemedicine is key to reduce disparities.

Combination therapy of beta-blockers and digoxin is associated with increased risk of major adverse cardiovascular events and all-cause mortality in patients with atrial fibrillation: a report from the GLORIA-AF registry.

The effect of digoxin and beta-blockers on cardiovascular outcomes and mortality remains unclear. The study aimed to determine differences in cardiovascular (CV) outcomes and death rates among patients with atrial fibrillation (AF) who were prescribed with beta-blockers, digoxin or combination therapy. Data from phase II/III of the prospective Global Registry on Long-Term Oral Anti-thrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) were analysed. The risk of major cardiovascular events (MACE) and death among patients with different prescriptions using COX proportional hazard regression was considered. Propensity score (PS) matching and weighting were further used to adjust for potential confounders of prescription use. A total of 14,201 patients [median age: 71.0 (IQR 64.0-77.0) years; 46.2% female] were recruited. After a median follow-up of 3.0 (IQR 2.4-3.1) years, 864 MACE, and 988 all-cause deaths were recorded. The incidence rate (IR) of MACE was 22.4 (95%CI 21.0-24.0) per 1000 person-years, while the IR of all-cause death was 25.4 (95%CI 23.8-27.0) per 1000 person-years. After multivariate adjustment with Cox regression, the risk of MACE (HR 1.35, 95% CI 1.09-1.68) and the risk of all-cause death (HR 1.28, 95%CI 1.04-1.57) were significantly higher in the combination therapy group, compared to the beta-blockers alone group. The risks of MACE and all-cause death remained significant in both PS matched and PS weighted cohort Among AF patients, combination therapy of beta-blockers and digoxin was associated with higher risks of MACE and all-cause death compared to beta-blockers alone.

Development of porcine skeletal muscle extracellular matrix-derived hydrogels with improved properties and low immunogenicity.

Hydrogels derived from decellularized extracellular matrices (ECM) of animal origin show immense potential for regenerative applications due to their excellent cytocompatibility and biomimetic properties. Despite these benefits, the impact of decellularization protocols on the properties and immunogenicity of these hydrogels remains relatively unexplored. In this study, porcine skeletal muscle ECM (smECM) underwent decellularization using mechanical disruption (MD) and two commonly employed decellularization detergents, sodium deoxycholate (SDC) or Triton X-100. To mitigate immunogenicity associated with animal-derived ECM, all decellularized tissues were enzymatically treated with α-galactosidase to cleave the primary xenoantigen-the α-Gal antigen. Subsequently, the impact of the different decellularization protocols on the resultant hydrogels was thoroughly investigated. All methods significantly reduced total DNA content in hydrogels. Moreover, α-galactosidase treatment was crucial for cleaving α-Gal antigens, suggesting that conventional decellularization methods alone are insufficient. MD preserved total protein, collagen, sulfated glycosaminoglycan, laminin, fibronectin, and growth factors more efficiently than other protocols. The decellularization method impacted hydrogel gelation kinetics and ultrastructure, as confirmed by turbidimetric and scanning electron microscopy analyses. MD hydrogels demonstrated high cytocompatibility, supporting satellite stem cell recruitment, growth, and differentiation into multinucleated myofibers. In contrast, the SDC and Triton X-100 protocols exhibited cytotoxicity. Comprehensive in vivo immunogenicity assessments in a subcutaneous xenotransplantation model revealed MD hydrogels' biocompatibility and low immunogenicity. These findings highlight the significant influence of the decellularization protocol on hydrogel properties. Our results suggest that combining MD with α-galactosidase treatment is an efficient method for preparing low-immunogenic smECM-derived hydrogels with enhanced properties for skeletal muscle regenerative engineering and clinical applications.

Do Forgiveness Campaign Activities Improve Forgiveness, Mental Health, and Flourishing?

Objectives: To evaluate the effectiveness of a forgiveness public health intervention at promoting forgiveness, mental health, and flourishing. Methods: Colombian students (N = 2,878) at a private, nonreligious university were exposed to a 4-week forgiveness community campaign and were assessed pre- and post-campaign. Results: Forgiveness, mental health, and flourishing outcomes showed improvements after the campaign. On average, participants reported engaging in 7.18 (SD = 3.99) of the 16 types of campaign activities. The number of types of campaign activities that participants engaged in evidenced a positive linear association with forgiveness, although some activities were more popular than others and some activities were more strongly associated with increased forgiveness. For depression, anxiety, and flourishing, engaging in more activities was generally associated with greater improvements, but the patterns were less consistent relative to forgiveness. Conclusion: This forgiveness public health intervention effectively promoted forgiveness, mental health, and flourishing. Effective campaigns in diverse communities involve promoting mental and physical health through forgiveness. However, recent conflict may hinder acceptance, necessitating political capital for leadership advocating forgiveness initiatives.

Making Sense: Treating Patients with Opioid Use Disorder through the Lens of Game Theory.

The opioid epidemic continues to influence the field of medicine, creating new challenges and obstacles to quality care. Patients with injection drug use are marginalized individuals who received poor quality of care and often discharged without safe recovery plan. Cooperation between physicians and patients allow the best outcomes for the patient, the physician, and society, however we often see patient-directed discharges and inadequate care. We believe that this result is due to an incentive model in the decision-making process that ultimately makes cooperation difficult. We use different game theory models (assurance model, prisoner's dilemma, centipede model, conflicting interest coordination) in this paper to describe common scenarios within a hospitalization when caring for patient with opioid use disorder, from admission through discharge. When physician and patient are driven away from cooperation, the outcome is the worst and most harmful for society. In today's worsening opioid crisis, game theory can help physician provide high quality care to a complex high-risk population.

Osteo-inductive effect of piezoelectric stimulation from the poly(l-lactic acid) scaffolds.

Piezoelectric biomaterials can generate piezoelectrical charges in response to mechanical activation. These generated charges can directly stimulate bone regeneration by triggering signaling pathway that is important for regulating osteogenesis of cells seeded on the materials. On the other hand, mechanical forces applied to the biomaterials play an important role in bone regeneration through the process called mechanotransduction. While mechanical force and electrical charges are both important contributing factors to bone tissue regeneration, they operate through different underlying mechanisms. The utilizations of piezoelectric biomaterials have been explored to serve as self-charged scaffolds which can promote stem cell differentiation and the formation of functional bone tissues. However, it is still not clear how mechanical activation and electrical charge act together on such a scaffold and which factors play more important role in the piezoelectric stimulation to induce osteogenesis. In our study, we found Poly(l-lactic acid) (PLLA)-based piezoelectric scaffolds with higher piezoelectric charges had a more pronounced osteoinductive effect than those with lower charges. This provided a new mechanistic insight that the observed osteoinductive effect of the piezoelectric PLLA scaffolds is likely due to the piezoelectric stimulation they provide, rather than mechanical stimulation alone. Our findings provide a crucial guide for the optimization of piezoelectric material design and usage.

Clinical Outcomes of 111 Patients with Early Onset Idiopathic Scoliosis (EOIS) Receiving Brace Treatment: A Longitudinal Retrospective Cohort Study.

Introduction: Bracing is one of the first-line treatment for early-onset idiopathic scoliosis (EOIS) to control curves from progression. This study aimed to explore the determinants that govern bracing effectiveness in EOIS. Methods: One hundred and eleven patients with EOIS (mean age of 8.6 ± 1.25 at diagnosis) received bracing treatment and had a final follow-up beyond skeletal maturity were identified from records between 1988 and 2021. Demographic data and clinical features of spinal curvature were obtained for correlation analyses to determine the associations between curve outcomes and clinical features. Results: Most patients were female (85.6%) and had a major curve on the left side (67%). The mean baseline Cobb angle of major curves was 21.73 ± 7.92°, with a mean Cobb angle progression of 18.05 ± 19.11°. The average bracing duration was 5.3 ± 1.9 years. Only 26 (23.4%) of them underwent surgery. The final Cobb angle and curve progression at the final follow-up with a Cobb angle of ≥50° were positively correlated with the initial Cobb angle (r = 0.206 and r = 0.313, respectively) and negatively correlated with maturity parameters. The lumbar curve type was found to correlate with a smaller final Cobb angle. Conclusions: The majority of patients had a final Cobb angle < 50°, which was considered a successful bracing outcome. The final Cobb angle correlated with the initial Cobb angle and curve types observed in EOIS.

HistoEM: A Pathologist-Guided and Explainable Workflow Using Histogram Embedding for Gland Classification.

Pathologists have, over several decades, developed criteria for diagnosing and grading prostate cancer. However, this knowledge has not, so far, been included in the design of convolutional neural networks (CNN) for prostate cancer detection and grading. Further, it is not known whether the features learned by machine-learning algorithms coincide with diagnostic features used by pathologists. We propose a framework that enforces algorithms to learn the cellular and subcellular differences between benign and cancerous prostate glands in digital slides from hematoxylin and eosin-stained tissue sections. After accurate gland segmentation and exclusion of the stroma, the central component of the pipeline, named HistoEM, utilizes a histogram embedding of features from the latent space of the CNN encoder. Each gland is represented by 128 feature-wise histograms that provide the input into a second network for benign vs cancer classification of the whole gland. Cancer glands are further processed by a U-Net structured network to separate low-grade from high-grade cancer. Our model demonstrates similar performance compared with other state-of-the-art prostate cancer grading models with gland-level resolution. To understand the features learned by HistoEM, we first rank features based on the distance between benign and cancer histograms and visualize the tissue origins of the 2 most important features. A heatmap of pixel activation by each feature is generated using Grad-CAM and overlaid on nuclear segmentation outlines. We conclude that HistoEM, similar to pathologists, uses nuclear features for the detection of prostate cancer. Altogether, this novel approach can be broadly deployed to visualize computer-learned features in histopathology images.

A prospective cohort of men with localized prostate cancer on active surveillance protocol in Hong Kong, China: what did we learn?

This study aimed to report the outcomes of active surveillance (AS) in the management of low-risk prostate cancer (PCa). It recruited 87 men who were prospectively followed up according to the Prostate Cancer Research International Active Surveillance (PRIAS) protocol with local adaptation at SH Ho Urology Centre, Prince of Wales Hospital, Hong Kong, China. We investigated the predictors of disease progression and found that baseline prostate-specific antigen density (PSAD) and the presence of the highest Prostate Imaging-Reporting and Data System (PI-RADS) score 5 lesion on magnetic resonance imaging (MRI) are significantly correlated with disease progression. Moreover, men with PSAD >0.2 ng ml-2 or PI-RADS 4 or 5 lesions had significantly worse upgrading-free survival compared to those with PSAD ≤0.2 ng ml-2 and PI-RADS 2 or 3 lesions. The study concludes that AS is a safe and effective management strategy for selected patients to defer radical treatment and that most disease progression can be detected after the first repeated biopsy. The combination of PSAD >0.2 ng ml-2 and PI-RADS 4 or 5 lesions may serve as a useful predictor of early disease progression and provide a guide to optimize follow-up protocols for men in different risk groups.

The effects of Chinese proprietary medicine and vaccination on patients with COVID-19: a retrospective study in Macao.

BACKGROUND: COVID-19 is continuing to ravage globally and has resulted in a huge health and financial burden. Chinese proprietary medicines, such as Lianhua Qingwen (LHQW) and Huoxiang Zhengqi (HXZQ) capsules, have been recommended for non-high-risk patients with COVID-19 in China. Based on this, we described the baseline information, using status of LHQW and HXZQ capsules and inoculation history of quarantined patients in the second half of 2022 in Macao. Additionally, we analyzed the underlying association among medicines administration, vaccination and COVID-19 indices, in order to explore novel clues for the regular control and prevention of local epidemic situation in the future. METHODS: A total of 976 patients in Macao quarantine hotels from June to August 2022 were included in the present study, of which, 857 subjects were followed-up for prognosis evaluation. During quarantine, the baseline demographic information, including sex, age, BMI, occupation and personal habits were collected. Additionally, the inoculation history, medicine employment status and cycle threshold (Ct) values were also reported. We interviewed the patients for collection of their symptoms at the beginning and end of quarantine, as well as prognostic ones. Basic statistical description of baseline information, vaccination history and medication were displayed. Chi-squared test or with continuous correction test was employed for comparison of dichotomous data between two or multiple groups. Binary logistic regression was applied to reveal the correlation between potential risk factors and Ct values or prognosis symptoms. We also used Cox regression model to identify the effect of different types of vaccine products on Ct value altering rate. RESULTS: Patients who were female (52.0%), engaged in service industry (31.8%), from Macao native (65.8%), never took physical exercises (33.6%) and preferred irritated diet (59.5%) enjoyed more dominant proportions. Over 80% of participants were inoculated and 74.6% of them chose inactivated COVID-19 vaccine produced by China National Biotech Group (CNBG). Participants used LHQW capsules accounted for 92.1% and the duration of medicating lasted for one to two weeks. All of the reported symptoms were significantly ameliorated after quarantine and the duration of quarantine was concentrated on 21 days. People with different age, sex, occupation and region had different choices of HXZQ administration and vaccination. Additionally, middle dose (4-5 boxes) of LHQW capsules exhibited evidently negative association with positive Ct values (adjusted, - 0.037 ± 0.19, p = 0.04). Two doses of CNBG and one dose of mRNA vaccine had obvious protective effect on reducing Ct positive rate (p = 0.041). Meanwhile, symptoms after quarantine were significantly positive correlated with those in prognosis (adjusted, 1.38 ± 0.18, p < 0.0001). CONCLUSION: Our study found that the administration of LHQW capsules was beneficial for Ct value turning negative, meanwhile, certain mixed inoculation may be the promoting factor to reduce the positive rate of Ct value. These findings provide data basis for the Chinese proprietary medicine treatment and mixed vaccination applying for prevention and control of local COVID-19 epidemic in the future.

Effect of Real-Time Computer-Aided Polyp Detection System (ENDO-AID) on Adenoma Detection in Endoscopists-in-Training: A Randomized Trial.

BACKGROUND: The effect of computer-aided polyp detection (CADe) on adenoma detection rate (ADR) among endoscopists-in-training remains unknown. METHODS: We performed a single-blind, parallel-group, randomized controlled trial in Hong Kong between April 2021 and July 2022 (NCT04838951). Eligible subjects undergoing screening/surveillance/diagnostic colonoscopies were randomized 1:1 to receive colonoscopies with CADe (ENDO-AID[OIP-1]) or not (control) during withdrawal. Procedures were performed by endoscopists-in-training with <500 procedures and <3 years' experience. Randomization was stratified by patient age, sex, and endoscopist experience (beginner vs intermediate level, <200 vs 200-500 procedures). Image enhancement and distal attachment devices were disallowed. Subjects with incomplete colonoscopies or inadequate bowel preparation were excluded. Treatment allocation was blinded to outcome assessors. The primary outcome was ADR. Secondary outcomes were ADR for different adenoma sizes and locations, mean number of adenomas, and non-neoplastic resection rate. RESULTS: A total of 386 and 380 subjects were randomized to CADe and control groups, respectively. The overall ADR was significantly higher in the CADe group than in the control group (57.5% vs 44.5%; adjusted relative risk, 1.41; 95% CI, 1.17-1.72; P < .001). The ADRs for <5 mm (40.4% vs 25.0%) and 5- to 10-mm adenomas (36.8% vs 29.2%) were higher in the CADe group. The ADRs were higher in the CADe group in both the right colon (42.0% vs 30.8%) and left colon (34.5% vs 27.6%), but there was no significant difference in advanced ADR. The ADRs were higher in the CADe group among beginner (60.0% vs 41.9%) and intermediate-level (56.5% vs 45.5%) endoscopists. Mean number of adenomas (1.48 vs 0.86) and non-neoplastic resection rate (52.1% vs 35.0%) were higher in the CADe group. CONCLUSIONS: Among endoscopists-in-training, the use of CADe during colonoscopies was associated with increased overall ADR. (ClinicalTrials.gov, Number: NCT04838951).