Systemic lupus erythematosus is a complex and potentially fatal autoimmune disease, characterized by autoantibody production and multi-organ damage. By a genome-wide association study (320 patients and 1,500 controls) and subsequent replication altogether involving a total of 3,300 Asian SLE patients from Hong Kong, Mainland China, and Thailand, as well as 4,200 ethnically and geographically matched controls, genetic variants in ETS1 and WDFY4 were found to be associated with SLE (ETS1: rs1128334, P = 2.33×10−11, OR = 1.29; WDFY4: rs7097397, P = 8.15×10−12, OR = 1.30). ETS1 encodes for a transcription factor known to be involved in a wide range of immune functions, including Th17 cell development and terminal differentiation of B lymphocytes. SNP rs1128334 is located in the 3′-UTR of ETS1, and allelic expression analysis from peripheral blood mononuclear cells showed significantly lower expression level from the risk allele. WDFY4 is a conserved protein with unknown function, but is predominantly expressed in primary and secondary immune tissues, and rs7097397 in WDFY4 changes an arginine residue to glutamine (R1816Q) in this protein. Our study also confirmed association of the HLA locus, STAT4, TNFSF4, BLK, BANK1, IRF5, and TNFAIP3 with SLE in Asians. These new genetic findings may help us to gain a better understanding of the disease and the functions of the genes involved.
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IntroductionBeta-lactams (BL) are the most frequently reported drug allergy, but the vast majority of patients are found not to be genuinely allergic after evaluation. Few studies have investigated the clinical predictors of genuine BL allergy, and the prevalence in hospitalized Chinese patients is unknown.MethodsPatients admitted to a tertiary hospital in Hong Kong (HK) were analyzed to identify the prevalence and factors associated with the presence of BL allergy labels among hospitalized Chinese patients. A combined cohort of patients having completed allergy investigation for suspected BL allergies in the United Kingdom (UK) and HK were analyzed to identify predictors of genuine allergy.ResultsThe prevalence of BL allergy labels in hospitalized HK Chinese was 5%, which was associated with female gender and concomitant non-BL antibiotic allergy labels. The rate of genuine BL allergy patients referred for suspected allergies in the UK and HK cohort was only 14%. History of anaphylaxis and interval of less than a year since the index reaction were independent clinical predictors of genuine BL allergy. The negative predictive value of penicillin skin testing was 90%, confirming the need for drug provocation testing after negative skin testing. There was a high rate of confirmed piperacillin-tazobactam allergy.DiscussionThe estimated true prevalence of genuine BL allergy in hospitalized HK Chinese is around 0.5%. This high rate of BL mislabeling highlights the need for comprehensive allergy evaluation and screening. History of anaphylaxis and duration since the index reaction are important predictors of genuine allergy. Piperacillin-tazobactam allergy may pose a unique challenge in this population with a high prevalence of suspected allergies, surging antibiotic resistance, and lack of testing available.
Data regarding protection against mortality and severe complications after Omicron BA.2 infection with CoronaVac and BNT162b2 vaccines remains limited. We conducted a case–control study to evaluate the risk of severe complications and mortality following 1–3 doses of CoronaVac and BNT162b2 using electronic health records database. Cases were adults with their first COVID-19-related mortality or severe complications between 1 January and 31 March 2022, matched with up-to 10 controls by age, sex, index date, and Charlson Comorbidity Index. Vaccine effectiveness against COVID-19-related mortality and severe complications by type and number of doses was estimated using conditional logistic regression adjusted for comorbidities and medications. Vaccine effectiveness (95% CI) against COVID-19-related mortality after two doses of BNT162b2 and CoronaVac were 90.7% (88.6–92.3) and 74.8% (72.5–76.9) in those aged ≥65, 87.6% (81.4–91.8) and 80.7% (72.8–86.3) in those aged 50–64, 86.6% (71.0–93.8) and 82.7% (56.5–93.1) in those aged 18–50. Vaccine effectiveness against severe complications after two doses of BNT162b2 and CoronaVac were 82.1% (74.6–87.3) and 58.9% (50.3–66.1) in those aged ≥65, 83.0% (69.6–90.5) and 67.1% (47.1–79.6) in those aged 50–64, 78.3% (60.8–88.0) and 77.8% (49.6–90.2) in those aged 18–50. Further risk reduction with the third dose was observed especially in those aged ≥65 years, with vaccine effectiveness of 98.0% (96.5–98.9) for BNT162b2 and 95.5% (93.7–96.8) for CoronaVac against mortality, 90.8% (83.4–94.9) and 88.0% (80.8–92.5) against severe complications. Both CoronaVac and BNT162b2 vaccination were effective against COVID-19-related mortality and severe complications amidst the Omicron BA.2 pandemic, and risks decreased further with the third dose.
♦ BACKGROUND: spp. is an important cause of peritoneal dialysis (PD)-related peritonitis, but studies on peritonitis have been scarce. In view of the rising concern of carbapenem-resistant (CRA) and multidrug-resistant (MDRA) infections, we conducted this study on the incidence of peritonitis and the impact of CRA and MDRA on its outcome. ♦ METHODS: We retrospectively evaluated the clinical characteristics, prevalence, antibiotic sensitivity patterns, outcomes, and factors associated with treatment failure over the past 16 years in our patients with PD-related peritonitis. ♦ RESULTS: Out of 2,389 episodes of peritonitis, there were 66 episodes (3%) of peritonitis occurring in 59 patients. Twelve episodes were caused by MDRA (18%), of which 5 were CRA (8%). There was a progressive increase in the incidence of MDRA and CRA infections over the study period. Most isolates were sensitive to sulbactam combinations (ampicillin-sulbactam [95.4%] and cefoperazone-sulbactam [93.9%]), aminoglycosides (amikacin [92.4%], tobramycin [90.9%], and gentamicin [89.4%]), and carbapenems (imipenem [92.2%]). There was 1 case of relapse. Fifteen episodes resulted in catheter removal (23%), and 7 patients died (11%). Hypoalbuminemia (odds ratio [OR] = 0.85, = 0.006) and carbapenem resistance (OR = 18.2, = 0.049) were significantly associated with higher rates of treatment failure. ♦ CONCLUSION: Both carbapenem resistance and hypoalbuminemia were significantly associated with treatment failure. Up to 80% of peritonitis episodes by CRA resulted in catheter loss or mortality. Sulbactam combinations and/or aminoglycosides remained effective for the majority of isolates. There seemed to be an increasing relative incidence of MDRA and CRA infections over the past 16 years.
We conclude that autoantibody clustering and clinical subsets exist in SLE patients of our locality. These clusters may be viewed as a bipolar spectrum of related autoantibody and clinical manifestations. At one end are patients with over-representation of anti-dsDNA and renal disorder, while at the other end are two distinct autoantibody clusters (anti-Sm/anti-RNP/aPL and anti-Ro/anti-La) with overlapping of other clinical manifestations.
IMPORTANCE Allergy to β-lactam antibiotics is one of the most frequently reported drug reactions, but epidemiological data in Chinese populations are lacking. Ethnic-and region-specific sensitization patterns of skin testing for β-lactam antibiotic allergy are also unknown. OBJECTIVE To identify the prevalence, 1-year incidence, and sensitization patterns of β-lactam antibiotic allergy in patients in Hong Kong. DESIGN, SETTING, AND PARTICIPANTS This cross-sectional study obtained territorywide, anonymized electronic patient data from the Clinical Management Systems of the Hospital Authority, the sole publicly funded health care system in Hong Kong with facilities in 7 regions (
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