Validation of the International Myositis Assessment and Clinical Studies Group guideline on cancer risk stratification.

OBJECTIVES: Adult-onset Idiopathic inflammatory myopathies (IIMs) are associated with cancer. Guideline on cancer risk stratifications and screening in IIM patients was recently published, but their external validity remains verified. We evaluated its applicability and reliability among a Hong Kong IIM cohort. METHODS: The longitudinal observational cohort collected data from IIM patients fulfilling relevant classification criteria from 8 rheumatology centres in Hong Kong. Demographic, clinical and laboratory data were reviewed from 2004-2023. IIM patients were stratified into standard, intermediate or high-risk subgroups according to the IMACS guideline. The occurrence of malignancy at or after IIM diagnosis was analyzed. Independent risk factors for cancer were evaluated. RESULTS: 479 patients were included with 327 females (68.3%) and mean age of IIM diagnosis at 54.5 ± 13.6 years. 214 (44.7%) and 238 (49.7%) patients were stratified to high and intermediate risk groups, respectively. Only 5.6% belonged to the standard-risk group. 60 patients (12.5%) had cancer within 3 years of IIM diagnosis. Nasopharyngeal (25%), lung (21.1%) and breast (10.5%) were the top 3 cancers. Significantly more patients (44, 20.6%) in the high-risk group developed cancer within 3 years, compared with intermediate (6.7%, p< 0.001) and standard-risk (0%, p= 0.009) groups. Risk factors for cancer included older age (OR : 1.048, 95%CI : 1.019-1.078), Gottron's rash (OR : 2.453, 95%CI : 1.123-5.356), absence of ILD (OR 2.695, 95% CI : 1.154-6.295), anti-TIF1g positivity (OR : 4.627, 95% CI : 2.046-10.461) and anti-SAE1 positivity (OR : 5.325, 95% CI : 1.271-22.300). CONCLUSIONS: Our real-world study supported the accuracy of cancer risk stratification. Vast majority of IIM patients would be subjected to extensive cancer screening when the guideline was applied.

[Arterial prophylactic occlusion technique in the application of surgery for locally advanced pancreatic cancer with arterial involvement after conversion therapy].

Objective: To investigate and compare the clinical outcomes of the arterial pre-occlusion technique(APOT) and the traditional technique in the surgery of locally advanced pancreatic cancer with arterial involvement after conversion therapy. Methods: This is a retrospective cohort study. The clinical data of 145 patients with locally advanced pancreatic cancer with arterial involvement admitted to the Department of Hepato-Biliary-Pancreatic Surgery of the First Hospital Affiliated to Naval Medical University,from January 2020 to December 2022 were retrospectively analyzed. All patients completed neoadjuvant therapy for tumors, and the feasibility of radical surgical treatment was determined by a multidisciplinary collaborative team evaluation before surgery. According to whether the intraoperative artery was pre-occluded, 145 patients were divided into two groups, including 28 cases in the APOT group(16 males, 12 females, aged (59.0±9.4) years), and 117 cases in the routine surgery group(76 males, 41 females, aged (55.1±8.2) years). To ensure comparability of baseline data between the APOT group and the routine surgery group, a 1∶2 match was performed using the propensity score matching method, and the caliper value was 0.006 45. The t-test,the Mann-Whitney U test, χ2 test or Fisher's exact test were used to compare the data between the two groups,respectively. Results: After matching the propensity score,there were 28 cases in the APOT group and 56 cases in the routine surgery group. There were no significant differences in gender,age,preoperative comorbidities,preoperative body mass index,surgical approaches,chemotherapy regimen,stereotactic body radiation therapy ratio,tumor markers,and type of invaded artery between the two groups (all P>0.05).The arterial occlusion time M(IQR) in the APOT group was 7.0(3.8)minutes(range:3 to 15 minutes),and no ischemic manifestations were observed in the distal target organs that blocked blood vessels after surgery. The operation time was (170.3±57.7)minutes in the APOT group and (235.0±80.2)minutes in the routine surgery group,and the difference was statistically significant (t=-3.800,P<0.01). The APOT group also experienced less intraoperative blood loss(650(588)ml vs. 800(600)ml;U=1 026.500,P=0.021). No significant differences were found between the groups in combined vein resection and reconstruction,celiac trunk resection,early postoperative complications, readmission rates at 30 days,and postoperative length of stay(all P>0.05). Extra-arterial dissection was performed in all patients,with arterial resection and reconstruction in 3 cases: 2 cases in the APOT group(1 case involving the superior mesenteric artery and 1 case involving the common hepatic artery) and 1 case in the routine group(involving the common hepatic artery). Postoperative abdominal bleeding occurred in 4 cases,with 3 cases in the routine group,1 case in the routine group. The R0 resection rate was 85.7%(24/28) in the APOT group and 80.4%(45/56) in the routine group,without significant differences between the groups(P=0.763). The median overall survival time was 27.6 months for the APOT group and 22.5 months for the routine group,while the median disease-free survival was 11.7 months and 16.8 months,respectively,with no significant differences between the two groups(P=0.532,P=0.927). Conclusion: The arterial pre-occlusion technique can be used for extra-arterial dissection in patients with locally advanced pancreatic cancer involving the arteries,reducing surgery time and intraoperative blood loss.

Epidemiology and outcomes of geriatric and non-geriatric patients with drug allergy labels in Hong Kong.

INTRODUCTION: Adverse drug reactions are more common in geriatric patients than in younger patients, but there have been insufficient studies concerning the epidemiology or burden of drug allergy labels in geriatric patients. We prospectively investigated the prevalence and outcomes of geriatric patients with drug allergy labels in a cohort of hospitalised patients. METHODS: Patients admitted to a regional hospital over a 6-month period were recruited for this study. All patients with drug allergy labels were prospectively followed until discharge; clinical data were anonymously extracted for analyses. Patients were categorised into either geriatric (aged ≥65 years) or non-geriatric (aged <65 years) groups. Demographic characteristics, clinical outcomes, and prevalences of drug allergy labels were compared between groups. RESULTS: There were 4361 admissions involving 3641 patients during the 6-month study period. Overall, 492 patients (13.5%) had drug allergy labels, consisting of 151 non-geriatric patients (30.7%) and 341 geriatric patients (69.3%). The prevalence of drug allergy labels did not significantly differ between geriatric and non-geriatric patients (13.5% vs 13.5%, P=0.976). Significantly more patients in the geriatric group had drug allergy labels to cardiovascular system drugs (15.5% vs 4.6%, P=0.001). Geriatric patients had a significantly lower rate of direct discharge from the hospital (73.0% vs 88.1%, P<0.001) and required transfers to convalescent or rehabilitation care for further management. CONCLUSIONS: More than 13% of hospitalised geriatric patients had drug allergy labels. The leading causes of drug allergy labels were similar between geriatric and non-geriatric patients. Geriatric patients with drug allergy labels had significantly more labelled allergies to cardiovascular system drugs and adverse clinical outcomes.

[Clinical characteristics of anti-CV2 antibody-associated neurological diseases].

This study reviewed the clinical data of patients who were hospitalized in the Department of Neurology of Henan Provincial People's Hospital from January 2017 to October 2020. A total of 46 patients with positive serum anti-CV2 antibody were included. The average age of the patients was (54±15) years old, with a male to female ratio of 1.88∶1. Twenty-six patients were diagnosed with paraneoplastic neurological syndrome (PNS). The most malignant tumors were thymoma, small cell lung cancer, and prostate cancer. The most common PNS included myasthenia gravis, subacute cerebellar degeneration, and subacute/chronic sensorimotor neuropathies. Twenty non-PNS patients exhibited subacute/old cerebral infarction, Parkinson's disease, Alzheimer's disease, and so on. Among them, brain magnetic resonance imaging (MRI) of 10 cases showed different degrees of white matter demyelination, some of which were accompanied by brain atrophy. The current study found that the positive predictive value of anti-CV2 antibody for the diagnosis of PNS was 56.5%, which was relatively weak. As an accompanying antibody, it may be a coincidence, and it may also be related to the involvement of family members in the pathological process of the diseases.

[Research on the relationship between environmental chemical pollutant exposure and epigenetics].

Environmental chemical pollutants are increasing, which brings various harms to human health. Epigenetics may be an important medium between exposure to environmental chemical contaminants and adverse health effects. Many environmental chemical pollutant exposures can regulate gene expression and promote disease occurrence and development through epigenetic mechanisms. This review outlines the mechanisms of epigenetics and the latest research advances in exposure and epigenetics of several environmental chemical substances (heavy metal arsenic, bisphenol A, dioctyl phthalate and benzene). To further understand and study the relationship between environmental chemical pollutant exposures and epigenetics in order to elucidate the mechanisms of disease occurrence and development.

Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients.

Vaccination of egg-allergic individuals has been a historical concern, particularly for influenza and measles-mumps-rubella-varicella vaccines that are developed in chicken egg embryos or chicken cell fibroblasts. The egg proteins in these vaccines were believed to trigger an immediate allergic reaction in egg-allergic individuals. However, recently published international guidelines have updated their recommendations and now state that these vaccines can be safely administered to egg-allergic individuals. This joint consensus statement by the Hong Kong Institute of Allergy and the Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases summarises the updates and provides recommendations for local general practitioners and paediatricians. Hong Kong Institute of Allergy and Hong Kong Society for Paediatric Immunology Allergy & Infectious Diseases joint consensus statement 2018 on vaccination in egg-allergic patients Background.

Identification of new single nucleotide polymorphisms affecting total number born and candidate genes related to ovulation rate in Chinese Erhualian pigs.

The Chinese Erhualian pig has the highest record for litter size in the world. However, the genetic mechanism of its high prolificacy remains poorly understood. In our study, large phenotypic variations in litter size were found among Erhualian sows. Significant differences in total number born (TNB) and corpora lutea numbers were observed between sows with high and low estimated breeding values (EBVs) for TNB. To identify single nucleotide polymorphisms (SNPs) associated with TNB, a selective genomic scan was conducted on 18 sows representing the top 10% and 18 sows representing the bottom 10% of EBVs of 177 sows using Illumina Porcine SNP60 genotype data. Genome-wide fixation coefficient (FST ) values were calculated for each SNP between the high- and low-EBV groups. A total of 154 SNPs were significantly differentiated loci between the two groups. Of the top 10 highest FST SNPs, rs81399474, rs81400131 and rs81405013 on SSC8 and rs81434499 and rs81434489 on SSC 12 corresponded to previously reported QTL for litter size. The other five SNPs, rs81367039 on SSC2, rs80891106 on SSC7, rs81477883 on SSC12 and rs80938898 and rs80971725 on SSC14, appeared to be novel QTL for TNB. Significant associations between rs81399474 on SSC8 and TNB were confirmed in 313 Erhualian sows. Forty genes were identified around the top 10 highest FST SNPs, of which UCHL1, adjacent to rs81399474, and RPS6KB1 and CLTC, adjacent to rs81434499, have been reported to affect the ovulation rate in pig. The findings can advance understanding of the genetic variations in litter size of pigs.

Immunoglobulin G4-related disease in Hong Kong: clinical features, treatment practices, and its association with multisystem disease.

INTRODUCTION: Immunoglobulin G4-related disease remains an under-recognised and evolving disease. Local data are sparse and previous publications have been limited to individual case reports or case series only. We conducted this study to review the clinical features, treatment practices, and factors associated with multisystem involvement in Hong Kong. We described the clinical features and treatment modalities of the largest cohort of immunoglobulin G4-related disease in our locality thus far. METHODS: We retrospectively evaluated all patients with immunoglobulin G4-related disease between January 2003 and December 2015 in Queen Mary Hospital and combined this with patient data extracted from previous local publications. We analysed the clinical features, treatment practices, and factors associated with the number of organ systems involved. RESULTS: A total of 104 patients (55 from Queen Mary Hospital and 49 from literature review) were identified. Patients were predominantly older men (mean [standard deviation] age, 61.9 [12.7] years; male-to-female ratio=3:1) and 94.4% had elevated pre-treatment serum immunoglobulin G4 levels. Hepatobiliary and pancreatic system (40.4%), salivary gland (33.7%), lymph node (29.8%), and eye (19.2%) were the most common organ systems involved. Lymphadenopathy was associated with glucocorticoid use (odds ratio=2.65; 95% confidence interval, 1.08-6.54; P=0.034). Pre-treatment serum immunoglobulin G4 levels correlated with the number of organ systems involved (ß=0.347; P=0.004) and, specifically, more associated with patients having salivary gland involvement than those without (mean, 1109 mg/dL vs 599 mg/dL; P=0.012). CONCLUSION: We identified pre-treatment serum immunoglobulin G4 to be associated with multisystem disease, especially with salivary gland involvement, highlighting its potential for disease prognostication and monitoring. Increased physician awareness and multidisciplinary efforts are required for early diagnosis and optimal management of this masquerading disease.

[Contribution of different sources of exposure to particulate matter in an elderly community in Tianjin].

OBJECTIVE: To determine the pollution sources that influence the level of exposure to particulate matter 2.5 (PM2.5) in the elderly, and calculate the quantitative contributions of difference sources. METHODS: Personal exposure PM samples were collected in the summer and winter of 2011 from 101 elderly men in a Tianjin community. Chemical species (elements, water-soluble ions and carbonaceous species) were analyzed in PM samples to determine PM2.5 concentrations and chemical compositions. The Positive Matrix Factorization (PMF) model, which is recommended by the US Environmental Protection Agency, was employed to quantitatively analyze the contribution of each potential sources to personal levels of PM2.5 exposure. RESULTS: In both summer and winter, the model identified the same six sources of personal exposure to PM2.5 in the elderly: fugitive dust (marker species: Si, Al, Ca, Mg, Fe etc.), coal combustion emissions (marker species: organic carbon (OC) and SO4(2-)), vehicle exhausts (marker species: inorganic carbon and NO3-), secondary sulfates and nitrates (marker species: NO3-, SO42- and NH4(+)), industrial emissions (marker species: Mn, Ni, Cu, Zn, Pb etc.), and indoor sources (marker species: OC, K, Si, Al etc.). Among these six potential sources, vehicle exhausts (summer: 33.6%, winter: 24.2%), secondary sulfates and nitrates (summer: 27.4%, winter: 29.1%), as well as coal combustion emissions (summer: 19.9%, winter: 24.1%) were the greatest contributors. CONCLUSIONS: Coal combustion and vehicle exhaust emissions were the major sources of personal exposure to PM2.5 in the elderly, suggesting that these two sources were the key contributors to the precursor gases of secondary sulfate and nitrate.

Association of CD247 with systemic lupus erythematosus in Asian populations.

OBJECTIVE: Systemic lupus erythematosus (SLE) is a prototypic autoimmune disease with complex genetic inheritance. CD247 (CD3Z, TCRZ) plays a vital role in antigen recognition and signal transduction in antigen-specific immune responses, and is known to be involved in SLE pathogenesis. Weak disease association was reported for genetic variants in this gene in Caucasian studies for SLE, Crohn's disease and systemic sclerosis, but its role as a genetic risk factor was never firmly established. METHODS: In this study, using a collection of 612 SLE patients and 2193 controls of Chinese ethnicity living in Hong Kong in a genome-wide study, single nucleotide polymorphisms (SNPs) in and around CD247 were identified as being associated with SLE. The two most significant SNPs in this locus were selected for further replication using TaqMan genotyping assay in 3339 Asian patients from Hong Kong, Mainland China, and Thailand, as well as 4737 ethnically and geographically matched controls. RESULTS: The association of CD247 with SLE in Asian populations was confirmed (rs704853: odds ratio [OR] = 0. 81, p = 2.47 × 10(-7); rs858543: OR = 1.10, p = 0.0048). Patient-only analysis suggested that rs704853 is also linked to oral ulcers, hematologic disorders and anti-double-stranded DNA (dsDNA) antibody production. CONCLUSION: A significant association between variants in CD247 and SLE was demonstrated in Asian populations. Understanding the involvement of CD247 in SLE may shed new light on disease mechanisms and development of new treatment paradigms.

SARS CoV subunit vaccine: antibody-mediated neutralisation and enhancement.

1. A SARS vaccine was produced based on recombinant native full-length Spike-protein trimers (triSpike) and efficient establishment of a vaccination procedure in rodents. 2. Antibody-mediated enhancement of SARS-CoV infection with anti-SARS-CoV Spike immune-serum was observed in vitro. 3. Antibody-mediated infection of SARS-CoV triggers entry into human haematopoietic cells via an FcγR-dependent and ACE2-, pH-, cysteine-protease-independent pathways. 4. The antibody-mediated enhancement phenomenon is not a mandatory component of the humoral immune response elicited by SARS vaccines, as pure neutralising antibody only could be obtained. 5. Occurrence of immune-mediated enhancement of SARS-CoV infection raises safety concerns regarding the use of SARS-CoV vaccine in humans and enables new ways to investigate SARS pathogenesis (tropism and immune response deregulation).