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Objective: High disease activity status (HDAS) in patients with systemic lupus erythematosus (SLE) is associated with adverse long-term outcomes. We examined the frequency of lupus low disease activity state (LLDAS) and remission (REM) attainment in HDAS patients and whether their attainment was associated with improved patient outcomes., Methods: Demographic, clinical and outcomes data, collected prospectively from a multinational cohort between 2013 and 2020, were analysed. Disease activity was assessed using SLEDAI-2K. HDAS was defined as SLEDAI-2K ≥ 10. Patients' first visit with SLEDAI-2K ≥ 10 was assigned as baseline. Survival analyses were performed to examine the associations between cumulative and sustained LLDAS and REM attainment in HDAS patients and subsequent organ damage accrual and flare., Results: 1,029 HDAS patients with a median study duration of 2.7 years [IQR: 1.0, 4.8] were studied. LLDAS and REM were attained at least once by 71% (LLDAS-ever, n = 726) and 41% (REM-ever, n = 418) of patients. Approximately one-fifth of patients attained ≥50% cumulative time in LLDAS or REM. 37% (n = 385) of patients attained ≥3months of sustained LLDAS, with progressively lower proportions of patients attaining longer periods of sustained LLDAS. Lower proportions of patients attained sustained REM. Attainment of cumulative and sustained LLDAS or REM provided significant protection against damage accrual and flare in HDAS patients. Sustained periods of LLDAS and REM were difficult to achieve and therefore a more stringent target, but provided the most protection against damage accrual or flare., Conclusion: LLDAS and REM were achievable targets in HDAS patients, and provided significant protection against adverse outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

In many eukaryotic algae, CO2 fixation by Rubisco is enhanced by a CO2-concentrating mechanism, which utilizes a Rubisco-rich organelle called the pyrenoid. The pyrenoid is traversed by a network of thylakoid membranes called pyrenoid tubules, which are proposed to deliver CO2. In the model alga Chlamydomonas (Chlamydomonas reinhardtii), the pyrenoid tubules have been proposed to be tethered to the Rubisco matrix by a bestrophin-like transmembrane protein, BST4. Here, we show that BST4 forms a complex that localizes to the pyrenoid tubules. A Chlamydomonas mutant impaired in the accumulation of BST4 (bst4) formed normal pyrenoid tubules, and heterologous expression of BST4 in Arabidopsis (Arabidopsis thaliana) did not lead to the incorporation of thylakoids into a reconstituted Rubisco condensate. Chlamydomonas bst4 mutants did not show impaired growth under continuous light at air level CO2 but were impaired in their growth under fluctuating light. By quantifying the non-photochemical quenching (NPQ) of chlorophyll fluorescence, we propose that bst4 has a transiently lower thylakoid lumenal pH during dark-to-light transition compared to control strains. We conclude that BST4 is not a tethering protein but is most likely a pyrenoid tubule ion channel involved in the ion homeostasis of the lumen with particular importance during light fluctuations., Competing Interests: Conflict of interest statement. None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

Excitons are key to the optoelectronic applications of van der Waals semiconductors, with the potential for versatile on-demand tuning of properties. Yet, their electrical manipulation remains challenging due to inherent charge neutrality and the additional loss channels induced by electrical doping. We demonstrate the dynamic electrical control of valley polarization in charged excitonic states of monolayer tungsten disulfide, achieving up to a 6-fold increase in the degree of circular polarization under off-resonant excitation. In contrast to the weak direct tuning of excitons typically observed using electrical gating, the charged exciton photoluminescence remains stable, even with increased scattering from electron doping. By exciting at the exciton resonances, we observed the reproducible nonmonotonic switching of the charged state population as the electron doping is varied under gate bias, indicating a resonant interplay between neutral and charged exciton states.

Introduction: To report the long-term outcomes of robot-assisted radical cystectomy (RARC) for the treatment of muscle invasive and high-risk non-muscle invasive bladder cancer., Methods: We reviewed a single tertiary center database of RARC from 2004 to 2020. Concomitant extended pelvic lymph node dissection and extracorporeal urinary diversion were performed. Cox regression analysis and the Kaplan-Meier method were used to identify factors associated with and report time-to-event estimations of recurrence-free survival and overall survival. Clavien-Dindo complications were identified, categorized, and substratified by time from surgery within 90-days and between 90-days and >5-years postoperatively., Results: A total of 510 patients with median follow-up of 57.1 months (IQR 21.8-103.6) were included. Continent diversion was performed in 259 (51%) patients. Of the 340 (67%) ≥cT2 patients, 153 (45%) received cisplatin-based neoadjuvant chemotherapy. Recurrence was identified in 157 (31%) patients, and 118 (23%) died from bladder cancer. The overall complication rate was 52% with 267 (41%) major grade ≥ III events. Infectious (25%) and genitourinary (22%) complications were the most common irrespective of the time interval beyond 90-days. The risk of recurrence or death were increased by extravesical disease (HR 1.91 and 1.97, respectively) and lymph node positivity (HR 4.58 and 2.42, respectively) in multivariable analysis (all, P < 0.001). The estimated 5-, and 10-year recurrence-free and overall survival rates were 69% and 64% and 61% and 44%, respectively., Conclusions: RARC is a durable treatment that optimizes the probability of cure for patients requiring extirpation for bladder cancer. Targeting the modifiable complications of radical surgery may further improve the risk/benefit ratio of RARC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Few studies have attempted to use clinical and laboratory parameters to stratify COVID-19 patients with severe versus non-severe initial disease and evaluate age-specific differences in developing multiple different COVID-19-associated disease outcomes., Methods: A retrospective cohort included patients from the electronic health database of Hong Kong Hospital Authority between 1 January 2022 and 15 August 2022 until 15 November 2022. The cohort was divided into three cohorts by age (≤ 40, 41-64, and ≥ 65 years old). Each age cohort was stratified into four groups: (1) COVID-19 critically exposed group (ICU admission, mechanical ventilation support, CRP > 80 mg/L, or D-dimer > 2 g/mL), (2) severely exposed group (CRP 30-80 mg/L, D-dimer 0.5-2 g/mL, or CT value < 20), (3) mildly-moderately exposed group (COVID-19 positive-tested but not fulfilling the criteria for the aforementioned critically and severely exposed groups), and (4) unexposed group (without COVID-19). The characteristics between groups were adjusted with propensity score-based marginal mean weighting through stratification. Cox regression was conducted to determine the association of COVID-19 disease severity with disease outcomes and mortality in the acute and post-acute phase (< 30 and ≥ 30 days from COVID-19 infection) in each age group., Results: A total of 286,114, 320,304 and 194,227 patients with mild-moderate COVID-19 infection; 18,419, 23,678 and 31,505 patients with severe COVID-19 infection; 1,168, 2,261 and 10,178 patients with critical COVID-19 infection, and 1,143,510, 1,369,365 and 1,012,177 uninfected people were identified in aged ≤ 40, 40-64, and ≥ 65 groups, respectively. Compared to the unexposed group, a general trend tending towards an increase in risks of multiple different disease outcomes as COVID-19 disease severity increases, with advancing age, was identified in both the acute and post-acute phases. Notably, the mildly-moderately exposed group were associated with either insignificant risks (aged ≤ 40) or the lowest risks (aged > 40) for the disease outcomes in the acute phase of infection (e.g., mortality risk HR (aged ≤ 40): 1.0 (95%CI: 0.5,2.0), HR (aged 41-64): 2.1 (95%CI: 1.8, 2.6), HR (aged > 65): 4.8 (95%CI: 4.6, 5.1)); while in the post-acute phase, these risks were largely insignificant in those aged < 65, remaining significant only in the elderly (age ≥ 65) (e.g., mortality risk HR (aged ≤ 40): 0.8 (95%CI: (0.5, 1.0)), HR (aged 41-64): 1.1 (95%CI: 1.0,1.2), HR (aged > 65): 1.5 (95%CI: 1.5,1.6)). Fully vaccinated patients were associated with lower risks of disease outcomes than those receiving less than two doses of vaccination., Conclusions: The risk of multiple different disease outcomes in both acute and post-acute phases increased significantly with the increasing severity of acute COVID-19 illness, specifically among the elderly. Moreover, future studies could improve by risk-stratifying patients based on universally accepted thresholds for clinical parameters, particularly biomarkers, using biological evidence from immunological studies., (© 2024. The Author(s).)

Two-dimensional van der Waals semiconductors are promising for future nanoelectronics. However, integrating high-k gate dielectrics for device applications is challenging as the inert van der Waals material surfaces hinder uniform dielectric growth. Here, we report a liquid metal oxide-assisted approach to integrate ultrathin, high-k HfO 2 dielectric on 2D semiconductors with atomically smooth interfaces. Using this approach, we fabricated 2D WS 2 top-gated transistors with subthreshold swings down to 74.5 mV/dec, gate leakage current density below 10 -6 A/cm 2 , and negligible hysteresis. We further demonstrate a one-step van der Waals integration of contacts and dielectrics on graphene. This can offer a scalable approach toward integrating entire prefabricated device stack arrays with 2D materials. Our work provides a scalable solution to address the crucial dielectric engineering challenge for 2D semiconductor-based electronics.

Background: Immunocompromised individuals are at high risk of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and subsequent severe or fatal coronavirus disease 2019 (COVID-19), yet they have suboptimal responses to mRNA and inactivated COVID-19 vaccines. The efficacy of tixagevimab-cilgavimab in reducing symptomatic SARS-CoV-2 infection was demonstrated in phase III clinical trials. Nevertheless, real-world data on the effectiveness and safety of tixagevimab-cilgavimab remain limited., Objective: The aim was to evaluate the effectiveness and safety of tixagevimab-cilgavimab among immunocompromised individuals., Methods: Adults who were immunocompromised or receiving immunosuppressive therapies were included in this target trial emulation using territory-wide electronic health records in Hong Kong. A sequential trial emulation approach was adopted to compare effectiveness and safety outcomes between individuals who received tixagevimab-cilgavimab and individuals who did not., Results: A total of 746 tixagevimab-cilgavimab recipients and 2980 controls were included from 1 May 2022 to 30 November 2022. Tixagevimab-cilgavimab significantly reduced the risk of COVID-19 infection (hazard ratio [HR] 0.708, 95% confidence interval [CI] 0.527-0.951) during a median follow-up of 60 days. No significant difference was observed in the risk of COVID-19-related hospitalisation. Zero versus eight COVID-19 mortality cases and zero versus two severe COVID-19 cases were observed in tixagevimab-cilgavimab recipients and controls, respectively. Notably, significant risk reduction in COVID-19 infection was also observed among immunocompromised individuals who had been previously vaccinated with three or more doses of COVID-19 vaccine, or had no prior COVID-19 infection history., Conclusions: Tixagevimab-cilgavimab was effective in reducing COVID-19 infection among immunocompromised patients during the Omicron wave. Findings were consistent among individuals who previously received three or more doses of COVID-19 vaccine, or had no previous history of COVID-19 infection., (© 2024. The Author(s).)

Objectives: The lupus low disease activity state (LLDAS) allows for certain clinical and/or serological activity of SLE, provided overall disease activity does not exceed predefined cut-offs. This study aimed to evaluate the outcomes of patients who achieved LLDAS with clinical activity, serological activity only or neither clinical nor serological activity., Methods: Patients with SLE enrolled in a prospective multinational cohort from March 2013 to December 2020 who were in LLDAS at least once were included. Visits that fulfilled both LLDAS and Definition of Remission in SLE (DORIS) criteria were excluded., Results: 2099 patients were included, with median follow-up of 3.5 (IQR 1.3-5.8) years. At 6150 visits, patients were in LLDAS but not DORIS criteria; of these 1280 (20.8%) had some clinical activity, 3102 (50.4%) visits had serological activity only and 1768 (28.8%) visits had neither clinical nor serological activity. Multivariable regression analysis showed that compared with non-LLDAS, all three subsets of LLDAS had a protective association with flares in the ensuing 6 months and damage accrual in the ensuing 36 months. LLDAS with no clinical or serological activity had a significantly stronger protective association with severe flares in the ensuing 6 months compared with LLDAS with clinical activity (HR 0.47, 95% CI (0.27 to 0.82), p=0.007)., Conclusions: LLDAS without any clinical activity accounted for almost 80% of LLDAS visits. This study confirms that all subsets of LLDAS are associated with reduced flare and damage accrual. However, LLDAS without any clinical or serological activity has the strongest protective association with severe flares., Competing Interests: Competing interests: SO'N received consulting fees from AstraZeneca, Biogen, Boehringer Ingelheim; lecture/speaker fees from AstraZeneca, Biogen, Boehringer Ingelheim, Pfizer and GSK and research grants from Aurania, Biogen, Idorsia, Novartis. ZL received consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol-Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB and have royalties with Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol-Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB. SS received consulting fees from Pfizer, AstraZeneca, ZP Therapeutics. YK received payment/Honoria from Asahi Kasei, Astellas, AstraZeneca, Chugai, GlaxoSmithKline, Janssen, Mitsubishi Tanabe, Pfizer Japan and Sanofi. MH received speaker’s fee from AbbVie Japan, Ayumi, Boehringer Ingelheim Japan, Bristol-Myers Squibb, Chugai, Eisai, Eli Lilly Japan, GlaxoSmithKline, Kissei Pharmaceutical, Pfizer Japan, Takeda and Teijin; consultant fees from AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Kissei Pharmaceutical and Teijin and research grants from AbbVie Japan GK, Asahi Kasei, Astellas, Ayumi, Bristol-Myers Squibb, Chugai, Daiichi-Sankyo. Eisai, KisseiPharmaceutical, Mitsubishi Tanabe, Nippon Kayaku, Sekisui Medical, Shionogi, Taisho, Takeda and Teijin. TT received grants from Astellas, Asahi Kasei, Chugai, Mitsubishi Tanabe, and consulting fees from Astellas, Chugai. KN received Advisory Board participation fees from AbbVie. YT has received research grants from Eli Lilly, AstraZeneca, AbbVie, Gilead, Chugai, Behringer-Ingelheim, GlaxoSmithKline, Eisai, Taisho, Bristol-Myers, Pfizer and Taiho. AH received research grants from AstraZeneca, and consulting fees from EUSA Pharma (UK), and Speaker/Honoraria from Limbic, Novartis, Moose Republic, AbbVie, Eli Lilly. RK-R received research grants from Novartis and GlaxoSmithKline. EM received research grants and/or consulting fees from AbbVie, AstraZeneca, Biogen, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, Genentech, GlaxoSmithKline, Genentech, Janssen, Novartis, Servier, EMD Serono, Takeda and UCB. MN received research grants and honoraria from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Janssen., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To evaluate the difference between BNT162b2 and CoronaVac in vaccine effectiveness and safety., Methods: This target trial emulation study included individuals aged ≥12 during 2022. Propensity score matching was applied to ensure group balance. The Cox proportional hazard model was used to compare the effectiveness outcomes including COVID-19 infection, severity, 28-day hospitalization, and 28-day mortality after infection. Poisson regression was used for safety outcomes including 32 adverse events of special interests between groups., Results: A total of 639,818 and 1804,388 individuals were identified for the 2-dose and 3-dose comparison, respectively. In 2-dose and 3-dose comparison, the hazard ratios (95% confidence intervals [CI]) were 0.844 [0.833-0.856] and 0.749 [0.743-0.755] for COVID-19 infection, 0.692 [0.656-0.731] and 0.582 [0.559-0.605] for hospitalization, 0.566 [0.417-0.769] and 0.590 [0.458-0.76] for severe COVID-19, and 0.563 [0.456-0.697] and 0.457 [0.372-0.561] for mortality for BNT162b2 recipients versus CoronaVac recipients, respectively. Regarding safety, 2-dose BNT162b2 recipients had a significantly higher incidence of myocarditis (incidence rate ratio [IRR] [95% CI]: 8.999 [1.14-71.017]) versus CoronaVac recipients, but the difference was insignificant in 3-dose comparison (IRR [95% CI]: 2.000 [0.500-7.996])., Conclusion: BNT162b2 has higher effectiveness among individuals aged ≥12 against COVID-19-related outcomes for SARS-CoV-2 omicron compared to CoronaVac, with almost 50% lower mortality risk., Competing Interests: Declarations of competing interest EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, Narcotics Division, Security Bureau of the Government of the Hong Kong SAR, and National Natural Science Foundation of China, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, Hong Kong Research Grant Council, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region; research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Merck Sharp & Dohme; Dohme, unrelated to this work. CKHW has received research grants from the Food and Health Bureau of the Hong Kong Government, the Hong Kong Research Grants Council, and the EuroQol Research Foundation, unrelated to this work. IFNH received speaker fees from MSD. EWYC reports grants from Research Grants Council (RGC, Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region; honorarium from Hospital Authority; outside the submitted work. ICKW reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the National Health and Medical Research Council in Australia, outside the submitted work; and is a nonexecutive director of Jacobson Medical in Hong Kong and a consultant to IQVIA and World Health Organization. All other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Validation of protective associations of the lupus low disease activity state (LLDAS) against flare, irreversible damage, health-related quality of life, and mortality has enabled the adoption of treat-to-target strategies in patients with systemic lupus erythematosus (SLE). Previous validation studies were of short duration, limiting the ability to detect longer term signals in flare rate and irreversible damage. In addition, previous studies have focused on percent time at target, rather than actual periods of time that are more useful in clinical practice and trials. We assessed long-term protective associations of LLDAS and remission, and specifically examined protective thresholds of sustained LLDAS and remission., Methods: Patients aged 18 years or older with SLE were followed up from May 1, 2013, to Dec 31, 2020 in a prospective, multinational, longitudinal cohort study. Patients were recruited from 25 centres in 12 countries. Multi-failure time-to-event analyses were used to assess the effect of sustained LLDAS on irreversible damage accrual (primary outcome; measured with the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index) and flare (key secondary outcome; measured with the SELENA Flare Index), with dose exposure and threshold effects studied. Sustained LLDAS or remission were defined as two or more consecutive visits over at least 3 months in the respective state. This study is registered with ClinicalTrials.gov, NCT03138941., Findings: 3449 patients were followed up for a median of 2·8 years (IQR 1·1-5·6), totalling 37 662 visits. 3180 (92·2%) patients were women, and 3031 (87·9%) were of Asian ethnicity. 2506 (72·7%) patients had sustained LLDAS at least once. Any duration of sustained LLDAS or remission longer than 3 months was associated with reduced damage accrual (LLDAS: hazard ratio 0·60 [95% CI 0·51-0·71], p<0·0001; remission: 0·66 [0·57-0·76], p<0·0001) and flare (LLDAS: 0·56 [0·51-0·63], p<0·0001; remission: 0·66 [0·60-0·73], p<0·0001), and increasing durations of sustained LLDAS corresponded to increased protective associations. Sustained DORIS remission or steroid-free remission were less attainable than LLDAS., Interpretation: We observed significant protective associations of LLDAS and remission against damage accrual and flare, establish a threshold of 3 months sustained LLDAS or remission as protective, and demonstrate deepening protection with longer durations of sustained LLDAS or remission., Funding: The Asia Pacific Lupus Collaboration receives project support grants from AstraZeneca, Bristol Myers Squibb, EMD Sereno, GSK, Janssen, Eli Lilly, and UCB., Competing Interests: Declaration of interests RK-R received grants from GSK and Novartis. SVN received consulting fees from Biogen, Boehringer Ingelheim, Astra Zeneca, Idorsia; payment for lectures from AstraZeneca, Boehringer Ingelheim, GSK, and Roche; participation in advisory board for Biogen; and leadership of societies, unpaid (CEO of Rheumatology Educational Trust Foundation, and Head of the SLE Special Interest Group at the Philippine Rheumatology Association). ZL received consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, and UCB, and has royalties with Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, and UCB. SS received consulting fees from Pfizer, AstraZeneca, and ZP Therapeutics. YK received payment or honoraria from GlaxoSmithKline, AstraZeneca, Sanofi, Pfizer Japan, Janssen Pharmaceutical, Chugai Pharmaceutical, Asahi Kasei Pharma, Astellas Pharma, and Mitsubishi Tanabe Pharma Corporation. MH received institutional research grants from GSK and Novartis; and honoraria for lectures from AstraZeneca and Astellas Pharma. ZZ received payment or honoraria from AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly, GSK, Novartis, Pfizer, Roche, Sanofi, Janssen, and UCB; and participation in advisory board for Beigene. JK received speaker fees from GSK and Asahi Kasei. TT received grants from Astellas, Asahi Kasei, Chugai, and Mitsubishi Tanabe, and consulting fees from Astellas and Chugai. FG is Director of the Board of the Australian Rheumatology Association. KN received Advisory Board participation fees from AbbVie. YT received research grants from Boehringer Ingelheim, Taisho, and Chugai; and speaker fees or honoraria from AbbVie, Eisai, Chugai, Eli Lilly, Boehringer Ingelheim, GSK, Taisho, AstraZeneca, Daiichi-Sankyo, Gilead, Pfizer, UCB, Asahi-kasei, and Astellas. AH received a research grant from AstraZeneca; consulting fees from EUSA Pharma (UK); and speaker fees or honoraria from Limbic, Novartis, Moose Republic, AbbVie, and Eli Lilly. MN received an Investigator Grant from the National Health and Medical Research Council of Australia (NHMRC GNT1176538); research grants from Janssen and Boehringer Ingelheim; consulting fees from AstraZeneca and GSK; honoraria for presentations from AstraZeneca, GSK, and Boehringer Ingelheim; and support for conference attendance from Boehringer Ingelheim. EFM received consulting fees from AstraZeneca, Biogen, Bristol Myers Squibb, Eli Lilly, Genetech, Janssen, Novartis, Servier, and EMD Serono. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To assess whether Lupus Low Disease Activity State (LLDAS) attainment is associated with favorable outcomes in patients with recent onset systemic lupus erythematosus (SLE)., Methods: Data from a 13-country longitudinal SLE cohort were collected prospectively between 2013 and 2020. An inception cohort was defined based on disease duration < 1 year at enrollment. Patient characteristics between inception and noninception cohorts were compared. Survival analyses were performed to examine the association between LLDAS attainment and damage accrual and flare., Results: Of the total 4106 patients, 680 (16.6%) were recruited within 1 year of SLE diagnosis (inception cohort). Compared to the noninception cohort, inception cohort patients were significantly younger, had higher disease activity, and used more glucocorticoids, but had less organ damage at enrollment. Significantly fewer inception cohort patients were in LLDAS at enrollment than the noninception cohort (29.6% vs 52.3%, P < 0.001), but three-quarters of both groups achieved LLDAS at least once during follow-up. Limiting analysis only to patients not in LLDAS at enrollment, inception cohort patients were 60% more likely to attain LLDAS (hazard ratio 1.37, 95% CI 1.16-1.61, P < 0.001) than noninception cohort patients and attained LLDAS significantly faster. LLDAS attainment was significantly protective against flare in both the inception and noninception cohorts. A total of 88 (13.6%) inception cohort patients accrued organ damage during a median 2.2 years of follow-up., Conclusion: LLDAS attainment is protective from flare in recent onset SLE. Significant protection from damage accrual was not observed because of low rates of damage accrual in the first years after SLE diagnosis. (ClinicalTrials.gov: NCT03138941)., (Copyright © 2024 by the Journal of Rheumatology.)

Objectives: To assess the risk of flare and damage accrual after tapering glucocorticoids (GCs) in modified serologically active clinically quiescent (mSACQ) patients with systemic lupus erythematosus (SLE)., Methods: Data from a 12-country longitudinal SLE cohort, collected prospectively between 2013 and 2020, were analysed. SLE patients with mSACQ defined as the state with serological activity (increased anti-dsDNA and/or hypocomplementemia) but without clinical activity, treated with ≤7.5 mg/day of prednisolone-equivalent GCs and not-considering duration, were studied. The risk of subsequent flare or damage accrual per 1 mg decrease of prednisolone was assessed using Cox proportional hazard models while adjusting for confounders. Observation periods were 2 years and censored if each event occurred., Results: Data from 1850 mSACQ patients were analysed: 742, 271 and 180 patients experienced overall flare, severe flare and damage accrual, respectively. Tapering GCs by 1 mg/day of prednisolone was not associated with increased risk of overall or severe flare: adjusted HRs 1.02 (95% CI, 0.99 to 1.05) and 0.98 (95% CI, 0.96 to 1.004), respectively. Antimalarial use was associated with decreased flare risk. Tapering GCs was associated with decreased risk of damage accrual (adjusted HR 0.96, 95% CI, 0.93 to 0.99) in the patients whose initial prednisolone dosages were >5 mg/day., Conclusions: In mSACQ patients, tapering GCs was not associated with increased flare risk. Antimalarial use was associated with decreased flare risk. Tapering GCs protected mSACQ patients treated with >5 mg/day of prednisolone against damage accrual. These findings suggest that cautious GC tapering is feasible and can reduce GC use in mSACQ patients., Competing Interests: Competing interests: YK received honoraria from Asahi Kasei Pharma, Astellas Pharma, AstraZeneca K.K., Chugai Pharmaceutical, GlaxoSmithKline KK, Janssen Pharmaceutical KK, Mitsubishi Tanabe Pharma Corporation, Pfizer Japan, Sanofi KK. EI received honoraria from Bristol-Myers Squibb KK, Eisai and consulting fees from Nippontect Systems. MH received honoraria from AbbVie GK, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., GlaxoSmithKline K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Pfizer Japan, Takeda Pharmaceutical, Teijin Pharma, consulting fees from AbbVie GK, Bristol-Myers Squibb K.K., Kissei Pharmaceutical, Nippon Boehringer Ingelheim, Teijin Pharma, grant/research support from AbbVie GK, Asahi Kasei Pharma, Astellas Pharma, Ayumi Pharmaceutical, Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Daiichi-Sankyo, Eisai, Kissei Pharmaceutical, Mitsubishi Tanabe Pharma, Nippon Kayaku, Sekisui Medical, Shionogi, Taisho Pharmaceutical, Takeda Pharmaceutical, Teijin Pharma. AH received honoraria from UCB, Janssen, Sandoz, Eli Lilly, consulting fees from AbbVie, GSK and grant/research support from AstraZeneca, GSK, Bristol Myers Squibb, Janssen, Merck Serono. CSL received honoraria from AstraZeneca UK and consulting fee from AstraZeneca Pharmaceuticals LP. ZL received honoraria from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma and consulting fees from Pfizer, Roche, Janssen, Abbott, AbbVie, Bristol Myers Squibb, MSD, Celgene, Eli Lilly, GSK, Novartis, UCB Pharma. SS received consulting fees from Pfizer, AstraZeneca, ZP Therapeutics and grant/research support from Pfizer, AstraZeneca, ZP Therapeutics. SVN received consulting fees from Biogen, Boehringer Ingelheim, AstraZeneca, grant/research support from Jannsen, Novartis, Pfizer, GSK and support for attending meetings from Biogen. SOon received royalty from Venetoclax. KN is on the advisory board for AbbVie. TT received honoraria from AbbVie GK, Chugai Pharmaceutical, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma, consulting fees from AbbVie GK, Chugai Pharmaceutical, Mitsubishi Tanabe Pharma and grant/research support from AbbVie GK, Eli Lilly Japan K.K., Mitsubishi Tanabe Pharma. YT received honoraria from AbbVie GK, Asahi Kasei Pharma, AstraZeneca K.K., Bristol-Myers Squibb K.K., Chugai Pharmaceutical, Eisai, Eli Lilly Japan K.K., Gilead Sciences, GlaxoSmithKline K.K., Nippon Boehringer Ingelheim, Pfizer Japan, Taiho Pharmaceutical, Taisho Pharmaceutical and grant/research support from Asahi Kasei Pharma, Chugai Pharmaceutical, Eisai, Mitsubishi Tanabe Pharma, Taisho Pharmaceutical. MN received honoraria from Actelion, GSK, Janssen, Pfizer, UCB, consulting fees from Boehringer Ingelheim, Certa Therapeutics, Eli Lilly, GSK, Janssen, Pfizer, UCB and grant/research support from Actelion, AstraZeneca, Bristol Myers Squibb, GSK, Janssen, UCB. EFM received honoraria from AstraZeneca, EMD Serono, Gilead, consulting fees from AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Novartis and grant/research support from AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Biogen, Eli Lilly, EMD Serono, Genentech, GSK, Janssen, UCB. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ on behalf of EULAR.)

Lupus remains a disease with a low prioritisation in the national agendas of many countries in Latin America, the Middle East, and Asia-Pacific, where there is a dearth of rheumatologists and limited access to new or even standard lupus treatments. There is thus an important need for education, advocacy, and outreach to prioritise lupus in these regions to ensure that patients receive the care they need. This article reviews some of the specific challenges facing the care and management of people with lupus in these regions and suggests strategies for improving patient outcomes. Specifically, we review and discuss (with a focus on the aforementioned regions) the epidemiology of lupus; economic costs, disease burden, and effects on quality of life; barriers to care related to disease assessment; barriers to effective treatment, including limitations of standard treatments, high glucocorticoid use, inadequate access to new treatments, and low adherence to medications; and strategies to improve lupus management and patient outcomes. We hope that this represents a call to action to come together and act now for the lupus community, policymakers, health authorities, and healthcare professionals to improve lupus management and patient outcomes in Latin America, the Middle East, and Asia-Pacific., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Background: Basophil activation tests (BATs) are useful in identifying culprits of perioperative anaphylaxis (PA), but their utility remains limited due to technical limitations, cost, and availability. Being able to prioritize patients with likely higher yields for BAT would be useful in reducing costs and manpower., Objective: We sought to investigate whether tryptase levels and clinical parameters may be useful for selecting patients for BATs., Methods: We performed a 10-year retrospective study in Hong Kong to investigate the performance of BATs associated with tryptase levels (taking during PA) and other clinical parameters., Results: Of 90 patients, 70 (77.8%) showed significant tryptase level elevation and 37 (41.1%) had a positive BAT result. BAT-positive patients presented with significantly higher absolute levels (15.9 μg/L vs 9.1 μg/L; P  = .018), absolute elevation (12.8 μg/L vs 7.1 μg/L; P  = .012), and fold elevation (5.6- vs 4.1-fold; P  = .014) of acute tryptase than did BAT-negative patients. Among patients with positive BAT result, 94.6% (35 of 37) demonstrated elevated acute tryptase, significantly more than the BAT-negative group (66.0%; P  < .001). In regression analysis, tryptase elevation was the sole significant factor correlated to BAT positivity (odds ratio, 10.14; 95% CI, 2.15-47.85; P  = .003). Overall, elevated acute tryptase demonstrated a sensitivity of 94.7% and a negative predictive value of 90.0% in predicting positive results with BATs., Conclusions: We observed that tryptase elevation is a very sensitive predictor of BAT positivity among patients with identified culprits of PA. Acute elevation of tryptase would not only aid in confirming anaphylaxis but may also help guide the decision toward selecting labor-intensive and costly in vitro tests such as BATs., Competing Interests: Disclosure of potential conflict of interest: The authors declare that they have no relevant conflicts of interest., (© 2024 The Author(s).)

Bone regeneration involves multiple factors such as tissue interactions, an inflammatory response, and vessel formation. In the event of diseases, old age, lifestyle, or trauma, bone regeneration can be impaired which could result in a prolonged healing duration or requiring an external intervention for repair. Currently, bone grafts hold the golden standard for bone regeneration. However, several limitations hinder its clinical applications, e.g., donor site morbidity, an insufficient tissue volume, and uncertain post-operative outcomes. Bone tissue engineering, involving stem cells seeded onto scaffolds, has thus been a promising treatment alternative for bone regeneration. Adipose-derived mesenchymal stem cells (AD-MSCs) are known to hold therapeutic value for the treatment of various clinical conditions and have displayed feasibility and significant effectiveness due to their ease of isolation, non-invasive, abundance in quantity, and osteogenic capacity. Notably, in vitro studies showed AD-MSCs holding a high proliferation capacity, multi-differentiation potential through the release of a variety of factors, and extracellular vesicles, allowing them to repair damaged tissues. In vivo and clinical studies showed AD-MSCs favoring better vascularization and the integration of the scaffolds, while the presence of scaffolds has enhanced the osteogenesis potential of AD-MSCs, thus yielding optimal bone formation outcomes. Effective bone regeneration requires the interplay of both AD-MSCs and scaffolds (material, pore size) to improve the osteogenic and vasculogenic capacity. This review presents the advances and applications of AD-MSCs for bone regeneration and bone tissue engineering, focusing on the in vitro, in vivo, and clinical studies involving AD-MSCs for bone tissue engineering.

Assembling two-dimensional van der Waals (vdW)-layered materials into heterostructures is an exciting development that sparked the discovery of rich correlated electronic phenomena. vdW heterostructures also offer possibilities for designer device applications in areas such as optoelectronics, valley- and spintronics, and quantum technology. However, realizing the full potential of these heterostructures requires interfaces with exceptionally low disorder which is challenging to engineer. Here, we show that thermal scanning probes can be used to create pristine interfaces in vdW heterostructures. Our approach is compatible at both the material- and device levels, and monolayer WS 2 transistors show up to an order of magnitude improvement in electrical performance from this technique. We also demonstrate vdW heterostructures with low interface disorder enabling the electrical formation and control of quantum dots that can be tuned from macroscopic current flow to the single-electron tunneling regime.

Importance: Among patients with rheumatoid arthritis (RA) who had an inadequate response to methotrexate, a treatment sequence initiated with biosimilar disease-modifying antirheumatic drugs (DMARDs) provides better clinical efficacy compared with conventional synthetic DMARDs recommended by current treatment guidelines; but its cost-effectiveness evidence remains unclear., Objective: To evaluate the cost-effectiveness of the treatment sequence initiated with biosimilar DMARDs after failure with methotrexate vs leflunomide and inform formulary listing decisions., Design, Setting, and Participants: This economic evaluation's cost-effectiveness analysis was performed at a Hong Kong public institution using the Markov disease transition model to simulate the lifetime disease progression and cost for patients with RA, using monetary value in 2022. Scenario and sensitivity analyses were performed to test the internal validity of the modeling conclusion. Participants included patients diagnosed with RA from 2000 to 2021 who were retrieved retrospectively from local electronic medical records to generate model input parameters. Statistical analysis was performed from January 2023 to March 2024., Interventions: The model assesses 3 competing treatment sequences initiated with biosimilar infliximab (CT-P13), biosimilar adalimumab (ABP-501), and leflunomide; all used in combination with methotrexate., Main Outcomes and Measures: Lifetime health care cost and quality-adjusted life-years (QALYs) of the simulated cohort., Results: In total, 25 099 patients with RA were identified (mean [SD] age, 56 [17] years; 19 469 [72.7%] women). In the base-case analysis, the lifetime health care cost and QALYs for the treatment sequence initiated with leflunomide were US $154 632 and 14.82 QALYs, respectively; for biosimilar infliximab, they were US $152 326 and 15.35 QALYs, respectively; and for biosimilar adalimumab, they were US $145 419 and 15.55 QALYs, respectively. Both biosimilar sequences presented lower costs and greater QALYs than the leflunomide sequence. In the deterministic sensitivity analysis, the incremental cost-effectiveness ratio (US$/QALY) comparing biosimilar infliximab sequence vs leflunomide sequence and biosimilar adalimumab sequence vs leflunomide sequence ranged from -15 797 to -8615 and -9088 to 10 238, respectively, all below the predefined willingness-to-pay threshold (US $48 555/QALY gain). In the probabilistic sensitivity analysis, the probability of treatment sequence initiated with leflunomide, biosimilar infliximab, and biosmilar adalimumab being cost-effective out of 10 000 iterations was 0%, 9%, and 91%, respectively., Conclusions and Relevance: In this economic evaluation study, the treatment sequences initiated with biosimilar DMARDs were cost-effective compared with the treatment sequence initiated with leflunomide in managing patients with RA who experienced failure with the initial methotrexate treatment. These results suggest the need to update clinical treatment guidelines for initiating biosimilars immediately after the failure of methotrexate for patients with RA.

Lupus erythematosus (LE) is a heterogeneous, antibody-mediated autoimmune disease. Isolate discoid LE (IDLE) and systematic LE (SLE) are traditionally regarded as the two ends of the spectrum, ranging from skin-limited damage to life-threatening multi-organ involvement. Both belong to LE, but IDLE and SLE differ in appearance of skin lesions, autoantibody panels, pathological changes, treatments, and immunopathogenesis. Is discoid lupus truly a form of LE or is it a completely separate entity? This question has not been fully elucidated. We compared the clinical data of IDLE and SLE from our center, applied multi-omics technology, such as immune repertoire sequencing, high-resolution HLA alleles sequencing and multi-spectrum pathological system to explore cellular and molecular phenotypes in skin and peripheral blood from LE patients. Based on the data from 136 LE patients from 8 hospitals in China, we observed higher damage scores and fewer LE specific autoantibodies in IDLE than SLE patients, more uCDR3 sharing between PBMCs and skin lesion from SLE than IDLE patients, elevated diversity of V-J recombination in IDLE skin lesion and SLE PBMCs, increased SHM frequency and class switch ratio in IDLE skin lesion, decreased SHM frequency but increased class switch ratio in SLE PBMCs, HLA-DRB1*03:01:01:01, HLA-B*58:01:01:01, HLA-C*03:02:02:01, and HLA-DQB1*02:01:01:01 positively associated with SLE patients, and expanded Tfh-like cells with ectopic germinal center structures in IDLE skin lesions. These findings suggest a significant difference in the immunopathogenesis of skin lesions between SLE and IDLE patients. SLE is a B cell-predominate systemic immune disorder, while IDLE appears limited to the skin. Our findings provide novel insights into the pathogenesis of IDLE and other types of LE, which may direct more accurate diagnosis and novel therapeutic strategies., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: This study examines the association of standard-of-care systemic lupus erythematosus (SLE) medications with key outcomes such as low disease activity attainment, flares, damage accrual, and steroid-sparing, for which there is current paucity of data., Methods: The Asia Pacific Lupus Collaboration (APLC) prospectively collects data across numerous sites regarding demographic and disease characteristics, medication use, and lupus outcomes. Using propensity score methods and panel logistic regression models, we determined the association between lupus medications and outcomes., Results: Among 1707 patients followed over 12,689 visits for a median of 2.19 years, 1332 (78.03%) patients achieved the Lupus Low Disease Activity State (LLDAS), 976 (57.18%) experienced flares, and on most visits patients were taking an anti-malarial (69.86%) or immunosuppressive drug (76.37%). Prednisolone, hydroxychloroquine and azathioprine were utilised with similar frequency across all organ domains; methotrexate for musculoskeletal activity. There were differences in medication utilisation between countries, with hydroxychloroquine less frequently, and calcineurin inhibitors more frequently, used in Japan. More patients taking leflunomide, methotrexate, chloroquine/hydroxychloroquine, azathioprine, and mycophenolate mofetil/mycophenolic acid were taking ≤ 7.5 mg/day of prednisolone (compared to > 7.5 mg/day) suggesting a steroid-sparing effect. Patients taking tacrolimus were more likely (Odds Ratio [95% Confidence Interval] 13.58 [2.23-82.78], p = 0.005) to attain LLDAS. Patients taking azathioprine (OR 0.67 [0.53-0.86], p = 0.001) and methotrexate (OR 0.68 [0.47-0.98], p = 0.038) were less likely to attain LLDAS. Patients taking mycophenolate mofetil were less likely to experience a flare (OR 0.79 [0.64-0.97], p = 0.025). None of the drugs was associated with a reduction in damage accrual., Conclusions: This study suggests a steroid-sparing benefit for most commonly used standard of care immunosuppressants used in SLE treatment, some of which were associated with an increased likelihood of attaining LLDAS, or reduced incidence of flares. It also highlights the unmet need for effective treatments in lupus., (© 2024. The Author(s).)

Background: Inborn errors of immunity (IEI) often lack specific disease models and personalized management. Signal transducer and activator of transcription (STAT)-1 gain of function (GoF) is such example of an IEI with diverse clinical phenotype with unclear pathomechanisms and unpredictable response to therapy. Limitations in obtaining fresh samples for functional testing and research further highlights the need for patient-specific ex vivo platforms., Objective: Using STAT1-GoF as an example IEI, we investigated the potential of patient-derived expanded potential stem cells (EPSC) as an ex vivo platform for disease modeling and personalized treatment., Methods: We generated EPSC derived from individual STAT1-GoF patients. STAT1 mutations were confirmed with Sanger sequencing. Functional testing including STAT1 phosphorylation/dephosphorylation and gene expression with or without Janus activating kinase inhibitors were performed. Functional tests were repeated on EPSC lines with GoF mutations repaired by CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) editing., Results: EPSC were successfully reprogrammed from STAT1-GoF patients and expressed the same pluripotent makers as controls, with distinct morphologic differences. Patient-derived EPSC recapitulated the functional abnormalities of index STAT1-GoF patients with STAT1 hyperphosphorylation and increased expression of STAT1 and its downstream genes (IRF1, APOL6, and OAS1) after IFN-γ stimulation. Addition of ruxolitinib and baricitinib inhibited STAT1 hyperactivation in STAT1-GoF EPSC in a dose-dependent manner, which was not observed with tofacitinib. Corrected STAT1 phosphorylation and downstream gene expression were observed among repaired STAT1-GoF EPSC cell lines., Conclusion: This proof-of-concept study demonstrates the potential of our patient-derived EPSC platform to model STAT1-GoF. We propose this platform when researching, recapitulating, and repairing other IEI in the future., (Copyright © 2023 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Background: Consolidative resection or cytoreductive radical prostatectomy (CRP) may benefit men with non-organ confined prostate cancer. We report the safety, feasibility, and outcomes of robot-assisted laparoscopic CRP using a single-port (SP) or multi-port (MP) platform., Methods: We reviewed consecutive men with clinical node positive or metastatic castrate-sensitive prostate cancer who underwent IRB-approved CRP and extended pelvic lymph node dissection using the da Vinci SP or MP Surgical Systems (Intuitive Surgical, Sunnyvale, CA) from 2015-2022. Perioperative data and Clavien-Dindo 90-day complications were recorded., Results: Twenty-four men with a median age of 61 (IQR 56-69) years and prostate-specific antigen of 32.1 (IQR 21.9-62.3) ng/mL were included. Clinical N1, M1, or N1 + M1 disease were detected in 8 (33%), 9 (38%), 7 (29%) patients, respectively. There was no difference in positive margins, 41% vs. 29% (P = 0.67), lymph node yield, 21 (IQR 14-28) vs. 20 (IQR 13.5-21) nodes (P = 0.31), or estimated blood loss, 150 mL (IQR 100-200) vs. 50 mL (IQR 50-125) (P = 0.06), between the MP and SP cohorts, respectively. Hospital length of stay was significantly shorter for the SP group, same-day discharge (IQR 0-0), compared to MP, 1-day (IQR 1-1), P < 0.001. One grade III bowel obstruction and lymphocele occurred in the MP cohort. No major complications occurred in the SP cohort., Conclusion: Robot-assisted laparoscopic CRP is safe and feasible for select men with advanced castrate-sensitive prostate cancer., (© 2024. The Author(s).)

The persisting risk of long-term health consequences of SARS-CoV-2 infection and the protection against such risk conferred by COVID-19 vaccination remains unclear. Here we conducted a retrospective territory-wide cohort study on 1,175,277 patients with SARS-CoV-2 infection stratified by their vaccination status and non-infected controls to evaluate the risk of clinical sequelae, cardiovascular and all-cause mortality using a territory-wide public healthcare database with population-based vaccination records in Hong Kong. A progressive reduction in risk of all-cause mortality was observed over one year between patients with SARS-CoV-2 infection and controls. Patients with complete vaccination or have received booster dose incurred a lower risk of health consequences including major cardiovascular diseases, and all-cause mortality than unvaccinated or patients with incomplete vaccination 30-90 days after infection. Completely vaccinated and patients with booster dose of vaccines did not incur significant higher risk of health consequences from 271 and 91 days of infection onwards, respectively, whilst un-vaccinated and incompletely vaccinated patients continued to incur a greater risk of clinical sequelae for up to a year following SARS-CoV-2 infection. This study provided real-world evidence supporting the effectiveness of COVID-19 vaccines in reducing the risk of long-term health consequences of SARS-CoV-2 infection and its persistence following infection., (© 2024. The Author(s).)

Introduction: Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels., Aim: This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals., Methods: A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory., Results: The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD ( n  = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L ( n  = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L ( n  = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated ( n  = 724), p  < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia., Conclusions: An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population., Competing Interests: WL has received honoraria from Medtronic, Abbott, DKSH, and Novartis, and a research grant from Novartis. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Loh, Soh, Tun, Tan, Lau, Tavintharan, Watts and Aw.)

Objective: Disease activity monitoring in SLE includes serial measurement of anti-double stranded-DNA (dsDNA) antibodies, but in patients who are persistently anti-dsDNA positive, the utility of repeated measurement is unclear. We investigated the usefulness of serial anti-dsDNA testing in predicting flare in SLE patients who are persistently anti-dsDNA positive., Methods: Data were analysed from patients in a multinational longitudinal cohort with known anti-dsDNA results from 2013 to 2021. Patients were categorized based on their anti-dsDNA results as persistently negative, fluctuating or persistently positive. Cox regression models were used to examine longitudinal associations of anti-dsDNA results with flare., Results: Data from 37 582 visits of 3484 patients were analysed. Of the patients 1029 (29.5%) had persistently positive anti-dsDNA and 1195 (34.3%) had fluctuating results. Anti-dsDNA expressed as a ratio to the normal cut-off was associated with the risk of subsequent flare, including in the persistently positive cohort (adjusted hazard ratio [HR] 1.56; 95% CI: 1.30, 1.87; P < 0.001) and fluctuating cohort (adjusted HR 1.46; 95% CI: 1.28, 1.66), both for a ratio >3. Both increases and decreases in anti-dsDNA more than 2-fold compared with the previous visit were associated with increased risk of flare in the fluctuating cohort (adjusted HR 1.33; 95% CI: 1.08, 1.65; P = 0.008) and the persistently positive cohort (adjusted HR 1.36; 95% CI: 1.08, 1.71; P = 0.009)., Conclusion: Absolute value and change in anti-dsDNA titres predict flares, including in persistently anti-dsDNA positive patients. This indicates that repeat monitoring of dsDNA has value in routine testing., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

The widespread occurrence of sulfonamides raises significant concerns about the evolution and spread of antibiotic resistance genes. Biodegradation represents not only a resistance mechanism but also a clean-up strategy. Meanwhile, dynamic and diverse environments could influence the cellular function of individual sulfonamide-degrading strains. Here, we present Paenarthrobacter from different origins that demonstrated diverse growth patterns and sulfonamide-degrading abilities. Generally, the degradation performance was largely associated with the number of sadA gene copies and also relied on its genotype. Based on the survey of sad genes in the public database, an independent mobilization of transposon-borne genes between chromosome and plasmid was observed. Insertions of multiple sadA genes could greatly enhance sulfonamide-degrading performance. Moreover, the sad gene cluster and sadA transposable element showed phylogenetic conservation currently, being identified only in two genera of Paenarthrobacter (Micrococcaceae) and Microbacterium (Microbacteriaceae). Meanwhile, Paenarthrobacter exhibited a high capacity for genome editing to adapt to the specific environmental niche, opening up new opportunities for bioremediation applications., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Society for Microbial Ecology.)

Background and Objective: Approximately two-thirds of men who undergo primary treatment for prostate cancer (PC) will experience biochemical recurrence (BCR). Salvage robot-assisted radical prostatectomy (sRARP) offers curative treatment in this disease setting and men who choose this option may avoid palliative androgen deprivation therapy (ADT). The purpose of this study was to describe long-term outcomes and patient feedback following sRARP., Methods: We reviewed data for consecutive men with biopsy-proven localized BCR who underwent sRARP and pelvic lymph node dissection at a single tertiary referral center between 2004 and 2021. Perioperative data, Clavien-Dindo complications, and functional outcomes were recorded . The Kaplan-Meier method was used to estimate prostate-specific antigen-free (≥0.2 ng/ml) survival (PSAFS) and metastasis-free survival (MFS). Three Likert-type items (score 1-5) from the validated Surgical Satisfaction Questionnaire-8 were distributed to patients postoperatively., Key Findings and Limitations: We included 78 men, of whom 72 (92%) had undergone primary radiotherapy and six (8%) had received primary prostate ablation. Median follow-up was 10.1 yr (interquartile range 5.8-12.4). Final pathology identified ≥pT3N0M0 in 35 patients (45%) and positive margins in 23 (29%). The overall complication rate was 50%. Of the 26 (33%) major (grade ≥III) complications, anastomotic stricture (32%) was most common. The estimated 3-, 5-, and 10-yr survival rates were 85.6% and 80.2%, 83.5% for PSAFS ( n  = 11), and 74.1%, 83.5%, and 70.5% for MFS ( n  = 23), respectively. At last follow-up, postoperative ADT had been administered to 17 patients (22%), and 39 men (50%) remained alive a decade after sRARP. Continence and potency were maintained in 33/62 (53%) and 1/16 (6%) patients, respectively. Thirty-five respondents (45%) reported median questionnaire scores (≥4) in favor of sRARP. Limitations include the small single-center series and a single query point for patient feedback., Conclusions and Clinical Implications: Long-term outcomes of sRARP suggest that the technical challenges and morbidity of the procedure are qualified by patient feedback and the opportunity to evade the morbidity and mortality of biochemically recurrent PC., Patient Summary: We reviewed the cancer outcomes and side effects of robot-assisted surgical removal of the prostate after treatment failure with radiation or ablation for prostate cancer. We found that this type of treatment has substantial risks and long-term side effects, but the surgery provides an opportunity to cure prostate cancer and/or avoid the consequences of indefinite hormonal treatment. Overall, most men who underwent this surgery were not disappointed with their decision despite the higher risks and consequences., (© 2023 The Author(s).)

Background: This study aims to evaluate waning effectiveness against severe and fatal COVID-19 with two to three doses of CoronaVac/BNT162b2, where data are limited., Methods: A case-control study included individuals aged ≥18 years, unvaccinated or received two to three doses of CoronaVac/BNT162b2, using electronic healthcare databases in Hong Kong. Those with first COVID-19-related hospitalization, severe complications, or mortality between 1 January and 15 August 2022 were defined as cases and matched with up-to-10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness (VE) against COVID-19-related outcomes was estimated at different time intervals from second and third-dose vaccination (0-13 up-to 210-240 days) using conditional logistic regression adjusted for comorbidities and medications., Results: By 211-240 days after second dose, VE against COVID-19-related hospitalization reduced to 46.6% (40.7-51.8%) for BNT162b2 and 36.2% (28.0-43.4%) for CoronaVac, and VE against COVID-19-related mortality were 73.8% (55.9-84.4%) and 76.6% (60.8-86.0%). After third dose, VE against COVID-19-related hospitalization decreased from 91.2% (89.5-92.6%) for BNT162b2 and 76.7% (73.7-79.4%) for CoronaVac at 0-13 days, to 67.1% (60.4-72.6%) and 51.3% (44.2-57.5%) at 91-120 days. VE against COVID-19-related mortality for BNT162b2 remained high from 0-13 days [98.2% (95.0-99.3%)] to 91-120 days [94.6% (77.7-98.7%)], and for CoronaVac reduced from 0-13 days [96.7% (93.2-98.4%)] to 91-120 days [86.4% (73.3-93.1%)]., Conclusions: Significant risk reduction against COVID-19-related hospitalization and mortality after CoronaVac or BNT162b2 vaccination was observed for >240 and >120 days after second and third doses compared to unvaccinated, despite significant waning over time. Timely administration of booster doses could provide higher levels of protection.

Background: Conducting a systematic review is a time- and resource-intensive multi-step process. Enhancing efficiency without sacrificing accuracy and rigor during the screening phase of a systematic review is of interest among the scientific community., Methods: This case study compares the screening performance of a title-only (Ti/O) screening approach to the more conventional title-plus-abstract (Ti + Ab) screening approach. Both Ti/O and Ti + Ab screening approaches were performed simultaneously during first-level screening of a systematic review investigating the relationship between dietary patterns and risk factors and incidence of sarcopenia. The qualitative and quantitative performance of each screening approach was compared against the final results of studies included in the systematic review, published elsewhere, which used the standard Ti + Ab approach. A statistical analysis was conducted, and contingency tables were used to compare each screening approach in terms of false inclusions and false exclusions and subsequent sensitivity, specificity, accuracy, and positive predictive power., Results: Thirty-eight citations were included in the final analysis, published elsewhere. The current case study found that the Ti/O first-level screening approach correctly identified 22 citations and falsely excluded 16 citations, most often due to titles lacking a clear indicator of study design or outcomes relevant to the systematic review eligibility criteria. The Ti + Ab approach correctly identified 36 citations and falsely excluded 2 citations due to limited population and intervention descriptions in the abstract. Our analysis revealed that the performance of the Ti + Ab first-level screening was statistically different compared to the average performance of both approaches (Chi-squared: 5.21, p value 0.0225) while the Ti/O approach was not (chi-squared: 2.92, p value 0.0874). The predictive power of the first-level screening was 14.3% and 25.5% for the Ti/O and Ti + Ab approaches, respectively. In terms of sensitivity, 57.9% of studies were correctly identified at the first-level screening stage using the Ti/O approach versus 94.7% by the Ti + Ab approach., Conclusions: In the current case study comparing two screening approaches, the Ti + Ab screening approach captured more relevant studies compared to the Ti/O approach by including a higher number of accurately eligible citations. Ti/O screening may increase the likelihood of missing evidence leading to evidence selection bias., Systematic Review Registration: PROSPERO Protocol Number: CRD42020172655., (© 2023. The Author(s).)

It is challenging to manage inflammatory diseases using traditional anti-inflammatory drugs due to their limited efficacy and systemic side effects, which are a result of their lack of selectivity, poor stability, and low solubility. Herein, it reports the development of a novel nanoparticle system, called ROS-CA-NPs, which is formed using polymer-cinnamaldehyde (CA) conjugates and is responsive to reactive oxygen species (ROS). ROS-CA-NPs exhibit excellent drug stability, tissue selectivity, and controlled drug release upon oxidative stress activation. Using mouse models of chronic rheumatoid arthritis and acute ulcerative colitis, this study demonstrates that the systemic administration of ROS-CA-NPs results in their accumulation at inflamed lesions and leads to greater therapeutic efficacy compared to traditional drugs. Furthermore, ROS-CA-NPs present excellent biocompatibility. The findings suggest that ROS-CA-NPs have the potential to be developed as safe and effective nanotherapeutic agents for a broad range of inflammatory diseases., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

It is unknown if vaccination affects the risk of post-COVID-19 cardiovascular diseases (CVDs). Therefore, this retrospective cohort study examines the short-term and long-term risks of post-infection CVD among COVID-19 patients with different vaccination status utilizing data from electronic health databases in Hong Kong. Cox proportional hazards regression adjusted with inverse probability of treatment weighting is used to evaluate the risks of incident CVD (coronary heart disease, stroke, heart failure) and all-cause mortality in COVID-19 patients. Compared with unvaccinated patients, vaccinated patients have a lower risk of CVD and all-cause mortality, and the lowest risk is observed in those who completed three doses of vaccine. Similar patterns in the subgroups of different vaccine platforms, age, gender, Charlson comorbidity index, and disease severity are observed. These findings highlight a positive dose-response relationship between overall CVD risk reduction and the number of vaccine doses received., Competing Interests: Declaration of interests E.Y.F.W. has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region and the Hong Kong Research Grants Council (RGC) outside the submitted work. F.T.T.L. has been supported by the RGC Postdoctoral Fellowship under the Hong Kong RGC and has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region outside the submitted work. C.S.L.C. has received grants from the Health Bureau of the Hong Kong Government, Hong Kong RGC, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, and Amgen and personal fees from PrimeVigilance outside the submitted work. X.L. has received research grants from the Health Bureau of the Government of the Hong Kong Special Administrative Region, research and educational grants from Janssen and Pfizer, internal funding from the University of Hong Kong, and consultancy fees from Merck Sharp & Dohme unrelated to this work. I.C.K.W. reports grants from Amgen, Bristol-Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong RGC, the Hong Kong Health and Medical Research Fund in Hong Kong, National Institute for Health Research in the United Kingdom, the European Commission, and the National Health and Medical Research Council in Australia; consulting fees from IQVIA and World Health Organization; payment for expert testimony for Appeal Court of Hong Kong; and is a non-executive director of Jacobson Medical in Hong Kong and Therakind in the United Kingdom outside of the submitted work. E.W.C. reports grants from RGC (Hong Kong), Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, and the Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region and a honorarium from Hospital Authority outside the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Targets of treatment for systemic lupus erythematosus (SLE) include the Lupus Low Disease Activity State (LLDAS), remission, and complete remission. Whether treatment can be tapered after attaining these targets and whether tapering is safer in patients in complete remission compared with LLDAS are unknown. We aimed to assess the odds of disease flares after treatment tapering in stable disease, versus continuing the same therapy. We also aimed to examine whether tapering in complete remission resulted in fewer flares or longer time to flare compared with tapering in LLDAS or remission., Methods: This multinational cohort study was conducted at 25 sites across 13 Asia-Pacific countries. We included adult patients aged 18 years or older with stable SLE who were receiving routine clinical care, had two or more visits and had attained stable disease at one or more visits. We categorised stable disease into: LLDAS (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K] score ≤4, Physician Global Assessment [PGA] ≤1, and prednisolone ≤7·5 mg/day); Definitions of Remission in SLE (DORIS) remission (clinical SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day); or complete remission on therapy (SLEDAI-2K score 0, PGA <0·5, and prednisolone ≤5 mg/day). Stable disease categories were mutually exclusive. Tapering was defined as any decrease in dose of corticosteroids or immunosuppressive therapy (mycophenolate mofetil, calcineurin inhibitors, azathioprine, leflunomide, or methotrexate). Using multivariable generalised estimating equations, we compared flares (SELENA-SLEDAI Flare Index) at the subsequent visit after drug tapering. We used generalised estimating equations and Cox proportional hazard models to compare tapering attempts that had begun in LLDAS, remission, and complete remission., Findings: Between May 1, 2013, and Dec 31, 2020, 4106 patients were recruited to the cohort, 3002 (73·1%) of whom were included in our analysis. 2769 (92·2%) participants were female, 233 (7·8%) were male, and 2636 (88·1%) of 2993 with ethnicity data available were Asian. The median age was 39·5 years (IQR 29·0-50·0). There were 14 808 patient visits for patients in LLDAS, or remission or complete remission, of which 13 140 (88·7%) entered the final multivariable model after excluding missing data. Among the 9863 visits at which patients continued the same therapy, 1121 (11·4%) flared at the next visit, of which 221 (19·7%) were severe flares. Of the 3277 visits at which a patient received a tapering of therapy, 557 (17·0%) flared at the next visit, of which 120 (21·5%) were severe flares. Tapering was associated with higher odds of flare compared with continuing the same therapy (odds ratio [OR] 1·24 [95% CI 1·10-1·39]; p=0·0005). Of 2095 continuous tapering attempts, 860 (41·1%) were initiated in LLDAS, 596 (28·4%) in remission, and 639 (30·5%) in complete remission. Tapering initiated in LLDAS (OR 1·37 [95% CI 1·03-1·81]; p=0·029) or remission (1·45 [1·08-1·94]; p=0·013) had higher odds of flare in 1 year compared with complete remission. Tapering in LLDAS (hazard ratio 1·24 [95% CI 1·04-1·48]; p=0·016) or remission (1·30 [1·08-1·56]; p=0·0054) had a significantly shorter time to first flare than tapering initiated in complete remission. Attaining sustained LLDAS, remission, or complete remission for at least 6 months just before the time of taper was associated with lower odds of flare at next visit, flares in 1 year, and longer time to flare., Interpretation: Tapering of corticosteroids or immunosuppressive therapy in patients with stable SLE was associated with excess flares. Our findings suggest that drug tapering should be carefully considered, weighing the risks and benefits, and is best exercised in complete (clinical and serological) remission and after maintaining stable disease for at least 6 months., Funding: AstraZeneca, BMS, Eli Lily, Janssen, Merck Serono, GSK, and UCB., Competing Interests: Declaration of interests YK received honoraria from GSK, AstraZeneca, Sanofi, Pfizer Japan, Janssen Pharmaceutical, Chugai Pharmaceutical, Asahi Kasei Pharma, Astellas Pharma, and Mitsubishi Tanabe Pharma Corporation. MHa received payment for post-marketing surveillance from GSK; research grants from Novartis; and honoraria from GSK, AstraZeneca, and Astella Pharma. TT received research grants from Astellas Pharma, Asahi Kasei, Chugai, and Mitsubishi Tanabe, as well as consulting fees from Astellas Pharma and Chugai. KPKN is on the advisory board for AbbVie. SVN received consulting fees from Biogen and Boehringer Ingelheim; honoraria from Janssen, Novartis, Pfizer, and GSK; support for attending meetings from Pfizer; and is on the advisory board for Biogen. EFM received consulting fees from AstraZeneca, Biogen, Bristol Myers Squibb, Genentech, Janssen, Novartis, Servier, EMD, Serono, and Eli Lily. MN received research grants from Janssen; consulting fees from AstraZeneca, Boehringer Ingelheim, GSK, and Janssen; and honoraria from Janssen, Boehringer Ingelheim, and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Competing Interests: I declare no competing interests.

Introduction: Various cutaneous manifestations have been reported as symptoms of coronavirus disease 2019 (COVID-19), which may facilitate early clinical diagnosis and management. This study explored the incidence of cutaneous manifestations among hospitalised patients with COVID-19 and investigated its relationships with viral load, co-morbidities, and outcomes., Methods: This retrospective study included adult patients admitted to a tertiary hospital for COVID-19 from July to September 2020. Clinical information, co-morbidities, viral load (cycle threshold [Ct] value), and outcomes were analysed., Results: In total, 219 patients with confirmed COVID-19 were included. Twenty patients presented with new onset of rash. The incidence of new rash was 9.1% (95% confidence interval=6.25%-14.4%). The most common manifestations were maculopapular exanthem (n=6, 42.9%, median Ct value: 24.8), followed by livedo reticularis (n=4, 28.6%, median Ct value: 21.3), varicella-like lesions (n=2, 14.3%, median Ct value: 19.3), urticaria (n=1, 7.1%, median Ct value: 14.4), and acral chilblain and petechiae (n=1, 7.1%, median Ct value: 33.1). The median Ct values for patients with and without rash were 22.9 and 24.1, respectively (P=0.58). There were no significant differences in mortality or hospital stay between patients with and without rash. Patients with rash were more likely to display fever on admission (P<0.01). Regardless of cutaneous manifestations, patients with older age, hypertension, and chronic kidney disease stage ≥3 had significantly higher viral load and mortality (P<0.05)., Conclusion: This study revealed no associations between cutaneous manifestation and viral load or clinical outcomes. Older patients with multiple co-morbidities have risks of high viral load and mortality; they should be closely monitored., Competing Interests: All authors declare no conflicts of interest.

Background: Molnupiravir and nirmatrelvir-ritonavir have emerged as promising options for COVID-19 treatment, but direct comparisons of their effectiveness have been limited. This study aimed to compare the effectiveness of these two oral antiviral drugs in non-hospitalised and hospitalised patients with COVID-19., Methods: In this target trial emulation study, we used data from a territory-wide electronic health records database on eligible patients aged ≥18 years infected with COVID-19 who were prescribed either molnupiravir or nirmatrelvir-ritonavir within five days of infection between 16 March 2022 and 31 December 2022 in the non-hospitalised and hospitalised settings in Hong Kong. A sequence trial approach and 1:1 propensity score matching was applied based on age, sex, number of COVID-19 vaccine doses received, Charlson comorbidity index, comorbidities, and drug use within past 90 days. Cox regression adjusted with patients' characteristics was used to compare the risk of effectiveness outcomes (all-cause mortality, intensive care unit (ICU) admission or ventilatory support and hospitalisation) between groups. Subgroup analyses included age (<70; ≥70 years); sex, Charlson comorbidity index (<4; ≥4), and number of COVID-19 vaccine doses received (0-1; ≥2 doses)., Findings: A total of 63,522 non-hospitalised (nirmatrelvir-ritonavir: 31,761; molnupiravir: 31,761) and 11,784 hospitalised (nirmatrelvir-ritonavir: 5892; molnupiravir: 5892) patients were included. In non-hospitalised setting, 336 events of all-cause mortality (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 265, 0.83%), 162 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 71, 0.22%; molnupiravir: 91, 0.29%), and 4890 events of hospitalisation (nirmatrelvir-ritonavir: 1853, 5.83%; molnupiravir: 3037, 9.56%) were observed. Lower risks of all-cause mortality (absolute risk reduction (ARR) at 28 days: 0.61%, 95% CI: 0.50-0.72; HR: 0.43, 95% CI: 0.33-0.56) and hospital admission (ARR at 28 days: 3.73%, 95% CI: 3.31-4.14; HR: 0.72, 95% CI: 0.67-0.76) were observed in nirmatrelvir-ritonavir users compared to molnupiravir users. In hospitalised setting, 509 events of all-cause mortality (nirmatrelvir-ritonavir: 176, 2.99%; molnupiravir: 333, 5.65%), and 50 events of ICU admission or ventilatory support (nirmatrelvir-ritonavir: 26, 0.44%; molnupiravir: 24, 0.41%) were observed. Risk of all-cause mortality was lower for nirmatrelvir-ritonavir users than for molnupiravir users (ARR at 28 days: 2.66%, 95% CI: 1.93-3.40; HR: 0.59, 95% CI: 0.49-0.71). In both settings, there was no difference in the risk of intensive care unit admission or ventilatory support between groups. The findings were consistent across all subgroup's analyses., Interpretation: Our analyses suggest that nirmatrelvir-ritonavir was more effective than molnupiravir in reducing the risk of all-cause mortality in both non-hospitalised and hospitalised patients. When neither drug is contraindicated, nirmatrelvir-ritonavir may be considered the more effective option., Funding: HMRF Research on COVID-19, The Hong Kong Special Administrative Region (HKSAR) Government; Collaborative Research Fund, University Grants Committee, the HKSAR Government; and Research Grant from the Food and Health Bureau, the HKSAR Government; the Laboratory of Data Discovery for Health (D 2 4H) funded by the AIR@InnoHK administered by Innovation and Technology Commission., Competing Interests: EYFW has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, Narcotics Division, Security Bureau of the Government of the Hong Kong SAR, and National Natural Science Foundation of China, outside the submitted work. FTTL has been supported by the RGC Postdoctoral Fellowship under the Hong Kong Research Grants Council and has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, outside the submitted work. CSLC has received grants from the Food and Health Bureau of the Hong Kong Government, the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, Hong Kong Innovation and Technology Commission, Pfizer, IQVIA, MSD, and Amgen; and personal fees from PrimeVigilance; outside the submitted work. XL has received research grants from the Food and Health Bureau of the Government of the Hong Kong Special Administrative Region; research grants from the Hong Kong Research Grants Council (Early Career Scheme, and Research Impact Fund) of the Government of the Hong Kong SAR; research and educational grants from Janssen and Pfizer; internal funding from the University of Hong Kong; and consultancy fees from Pfizer, and Merck Sharp & Dohme; Dohme, unrelated to this work. CKHW has received research grants from the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, the EuroQol Group Research Foundation, AstraZeneca, and Boehringer Ingelheim, unrelated to this work. IFNH received payments as member of Advisory Board for Pfizer, MSD, Moderna, GSK, and Gilead. ICKW reports research funding from Amgen, Bristol Myers Squibb, Pfizer, Janssen, Bayer, GSK, Novartis, the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, the Hong Kong Health and Medical Research Fund, the National Institute for Health Research in England, the European Commission, and the National Health and Medical Research Council in Australia, consulting fees from IQVIA and World Health Organization, payment for expert testimony for Appeal Court of Hong Kong and is a non-executive director of Jacobson Medical in Hong Kong and Therakind in England, outside of the submitted work. ICKW reports role as member of Pharmacy and Poisons Board in Hong Kong, the Expert Committee on Clinical Events Assessment Following COVID-19 Immunization, and the Advisory Panel on COVID-19 Vaccines of the Hong Kong Government. EWYC reports grants from the Hong Kong Research Grants Council of the Government of the Hong Kong SAR, Research Fund Secretariat of the Food and Health Bureau, National Natural Science Fund of China, Wellcome Trust, Bayer, Bristol-Myers Squibb, Pfizer, Janssen, Amgen, Takeda, RGA Reinsurance Company, AstraZeneca, Narcotics Division of the Security Bureau of the Hong Kong Special Administrative Region, Innovation and Technology Commission of the Government of the Hong Kong Special Administrative Region, Novartis, National Health and Medical Research Council Australia; honorarium from Hospital Authority; outside the submitted work. EWYC reports unpaid role of president of International Society for Pharmacoeconomics and Outcomes Research (ISPOR), Hong Kong Regional Chapter. All other authors declare no competing interests., (© 2023 The Authors.)

We thank the authors [...].

Introduction: Evidence on long-term associations between coronavirus disease 2019 (COVID-19) and risks of multi-organ complications and mortality in older population is limited. This study evaluates these associations., Research Design and Methods: The cohorts included patients aged ≥60 year diagnosed with COVID-19 infection (cases), between 16 March 2020 and 31 May 2021 from the UK Biobank; and between 01 April 2020 and 31 May 2022 from the electronic health records in Hong Kong. Each patient was randomly matched with individuals without COVID-19 infection based on year of birth and sex and were followed for up to 18 months until 31 August 2021 for UKB, and up to 28 months until 15 August 2022 for HK cohort. Patients with COVID-19 infection over 6 months after the date of last dose of vaccination and their corresponding controls were excluded from our study. Characteristics between cohorts were further adjusted with Inverse Probability Treatment Weighting. For evaluating long-term association of COVID-19 with multi-organ disease complications and mortality after 21-days of diagnosis, Cox regression was employed., Result: 10,759 (UKB) and 165,259 (HK) older adults with COVID-19 infection with matched 291,077 (UKB) and 1,100,394 (HK) non-COVID-19-diagnosed older adults were recruited. Older adults with COVID-19 were associated with a significantly higher risk of cardiovascular outcomes [major cardiovascular disease (stroke, heart failure and coronary heart disease): hazard ratio(UKB): 1.4 (95% Confidence interval: 1.1,1.6), HK:1.2 (95% CI: 1.1,1.3)]; myocardial infarction: HR(UKB): 1.8 (95% CI: 1.3,2.4), HK:1.2 (95% CI: 1.0,1.4)]; respiratory outcomes [interstitial lung disease: HR(UKB: 3.4 (95% CI: 2.5,4.5), HK: 4.0 (95% CI: 1.3,12.8); chronic pulmonary disease: HR(UKB): 1.7 (95% CI: 1.3,2.2), HK:1.6 (95% CI: 1.3,2.1)]; neuropsychiatric outcomes [seizure: HR(UKB): 2.6 (95% CI: 1.7,4.1), HK: 1.6 (95% CI: 1.2,2.1)]; and renal outcomes [acute kidney disease: HR(UKB): 1.4 (95% CI: 1.1,1.6), HK:1.6 (95% CI: 1.3,2.1)]; and all-cause mortality [HR(UKB): 4.9 (95% CI: 4.4,5.4), HK:2.5 (95% CI: 2.5,2.6)]., Conclusion: COVID-19 is associated with long-term risks of multi-organ complications in older adults (aged ≥ 60). Infected patients in this age-group may benefit from appropriate monitoring of signs/symptoms for developing these complications., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)