Chinese Adult Patients Research Articles

Belimumab safety in adult and paediatric Chinese patients with systemic lupus erythematosus: A Phase 4, multicentre, observational study.

Although belimumab has been widely used in patients with systemic lupus erythematosus (SLE) globally, real-world safety data among Chinese patients are limited, particularly for children. This study assessed the safety and tolerability of belimumab in adult and paediatric patients with SLE in China in real-world clinical practice. This Phase 4, multicentre, prospective, observational study enrolled patients prescribed intravenous belimumab by their physicians in tertiary hospitals, independent of a clinical study, during routine clinical visits between May 2021 and May 2022. Patients could have been receiving belimumab prior to enrolment. The primary objective was to describe the incidence of adverse events (AEs), serious AEs (SAEs), adverse drug reactions (ADRs) and AEs of special interest (AESIs) over the 24-week follow-up period. Data were collected at enrolment and approximately 4, 12 and 24weeks post-enrolment, during routine clinical visits. AEs, ADRs and SAEs were collected as independent events. The safety population comprised patients who received ≥1 dose of belimumab and completed ≥1 follow-up visit. Overall, 417 patients were included in the analysis (safety population); 89.2% were female and mean (standard deviation) age was 35.5 (11.9) years. AEs were reported in 158 patients (37.9%) and were mostly mild (79.1%). The most common AEs were upper respiratory tract infections (n = 19, 4.6%) and hypokalaemia (n = 18, 4.3%; all mild). Among 22 patients (5.3%) with SAEs, four patients (1.0%) had drug-related SAEs (pneumonia, respiratory tract infection, gingivitis and decreased white blood cell and neutrophil count). ADRs were experienced by 25 patients (6.0%), most commonly urinary tract infections (n = 5, 1.2%). There were no fatal SAEs. AESIs occurred in 14 patients (3.4%), including infections of interest (n = 5, 1.2% all herpes zoster), serious selected psychiatric events (n = 3, 0.7%) and infusion-related systemic and anaphylactic reactions (n = 7, 1.7%). Of 14 paediatric patients enrolled, six experienced AEs, zero ADRs, two SAEs and one AESI. Belimumab was generally well tolerated in adult and paediatric patients with SLE in this real-world setting in China, with no new safety signals identified. Future assessment of long-term belimumab safety in China beyond 24weeks will extend this current body of evidence.

FISH combined with RT-PCR facilitates classification of Chinese adult patients with B-other ALL through improved identification of ZNF384 rearrangement

ZNF384 gene rearrangements are a distinct subtype of adult B cell acute lymphoblastic leukemia (B-ALL). We screened 46 B-other ALL patients for ZNF384 fusions using fluorescent in situ hybridization (FISH) and reverse transcription-polymerase chain reaction (RT-PCR). Clinical data, treatment response, and minimal residual disease (MRD) status were analyzed. Ten (21.7%) patients were ZNF384-r positive (nine by FISH, nine by RT-PCR, eight by both). FISH showed atypical signals, including 3’ signal gain and 5’ signal deletion. EP300 was the main fusion partner (n = 5). TAF15::ZNF384, SYNRG::ZNF384, CREBBP::ZNF384, and TCF3::ZNF384 fusions were found in one patient each; one case’s partner gene is unknown. One patient was MRD-negative at the end of the first induction, lower than in patients without ZNF384-r. ZNF384-r incidence matched B-other ALL incidence in Chinese patients. Combined FISH and RT-PCR improved detection. ALL with ZNF384-r has unique features, and lower MRD-negative response may indicate a negative impact on traditional treatments.

Sub-Optimal Disease Control and Low Blood Eosinophil Testing Frequency in Chinese Adult Patients with Asthma Receiving GINA Step 4/5 Treatment: A Real-World Study.

To inform effective management strategies for severe asthma in China, this study aimed to comprehensively characterize clinical characteristics, treatment patterns, disease control status, and healthcare resource utilization among patients on GINA Step 4/5 therapies by analyzing data from the Adelphi Asthma Disease Specific Program conducted in China. All information was retrieved from medical records or collected from physicians and patients on the survey date (August-December 2018); no follow-up was conducted. Results were summarized descriptively for patients on GINA Step 4/5 therapies, who were pooled from a consecutive sample (comprising three or more consecutive patients with physician-diagnosed asthma from each participating physician) and an oversample (comprising the next two patients with physician-perceived severe asthma from each participating physician). Of the included patients (n=754), 51.5% had ever had a blood eosinophil measurement taken, 22.1% had available records for their most recent blood eosinophil measurements (68.9% of them had an elevated level ≥150 cells/µL), 39.9% had ever been tested for specific immunoglobulin E or radioallergosorbent, and 8.0% were prescribed maintenance oral corticosteroids. Asthma was not well controlled in 69.2% of patients. In the prior year, 27.1% experienced at least one severe exacerbation and 22.8% experienced at least one hospitalization (emergency visit or overnight stay) due to asthma. In Chinese patients with asthma on GINA Step 4/5 therapies, biomarker testing was underutilized, asthma was not well controlled, and severe exacerbations were not infrequent. These findings highlight the urgent need for optimized asthma management for patients on GINA Step 4/5 therapies in China.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): a prospective, multicenter, randomized controlled trial.

Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings. The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in postinguinal hernia surgery (IHS) patients. The patients were randomly assigned (1:1) to the intervention or control arm. The intervention group used the three-factor model to identify patients at moderate or high risk of VTE for subsequent prophylaxis according to clinical guidelines. Both groups were followed for 4 weeks, with randomization implemented using computer-generated sequences. The primary outcome measured was the rate of VTE prophylaxis. Secondary outcomes included time spent on VTE risk assessment (surgeon self-reported), postoperative D-dimer trends, perioperative VTE occurrence, bleeding events, and the net clinical benefit. Of the 1109 participants, 508 in the experimental group and 601 in the control group completed follow-up. The three-factor model showed higher VTE prophylaxis rates in all patients (pharmacologic prophylaxis: 26.2 vs. 6.00%, P <0.001) and particularly in those at high risk (pharmacologic prophylaxis: 57.3 vs. 9.50%, P <0.001). The experimental group significantly reduced VTE risk assessment time compared to the Caprini score (1.39±0.55min vs. 5.73±1.35min, P <0.001). The experimental group had lower D-dimer levels (0.26±0.73mg/l vs. 0.35±0.55mg/l, P =0.028). In the experimental group, the patients did not experience an increased risk of VTE (0 vs. 1.66%, P =0.268) and bleeding (1.18 vs. 0.67%, P =0.558) compared to the controls. There was no significant difference in net clinical benefit, which combined VTE and bleeding events, between the experimental and control groups (1.18 vs. 0.83%, P =0.559). Applying the simple three-factor model in perioperative VTE management could quickly identify the patient with a high risk of VTE and improve the prophylaxis rate of perioperative VTE.

The recommendation of re-classification of variants of uncertain significance (VUS) in adult genetic disorders patients.

Since variants of uncertain significance (VUS) reported in genetic testing cannot be acted upon clinically, this classification may delay or prohibit precise diagnosis and genetic counseling in adult genetic disorders patients. Large-scale analyses about qualitatively distinct lines of evidence used for VUS can make them re-classification more accurately. We analyzed 458 Chinese adult patients WES data, within 15 pathogenic evidence PS1, PS2, PM1, PM6 and PP4 were not used for VUS pathogenic classification, meanwhile the PP3, BP4, PP2 were used much more frequently. The PM2_Supporting was used most widely for all reported variants. There were also 31 null variants (nonsense, frameshift, canonical ±1 or 2 splice sites) which were probably the disease-causing variants of the patients were classified as VUS. By analyzed the evidence used for all VUS we recommend that appropriate genetic counseling, reliable releasing of in-house data, allele frequency comparison between case and control, expanded verification in patient family, co-segregation analysis and functional assays were urgent need to gather more evidence to reclassify VUS. We also found adult patients with nervous system disease were reported the most phenotype-associated VUS and the lower the phenotypic specificity, the more reported VUS. This result emphasized the importance of pretest genetic counseling which would make less reporting of VUS. Our result revealed the characteristics of the pathogenic classification evidence used for VUS in adult genetic disorders patients for the first time, recommend a rules-based process to evaluate the pathogenicity of VUS which could provide a strong basis for accurately evaluating the pathogenicity and clinical grade information of VUS. Meanwhile, we further expanded the genetic spectrum and improve the diagnostic rate of adult genetic disorders.

Video and phone visit use differed by language preference among U.S. Latino and Chinese adults during the first 9 months of the COVID-19 pandemic: a cross-sectional electronic health record study

BackgroundDuring the first nine months of the COVID-19 emergency, patients were encouraged to use virtual versus clinic visits if in-person care was not deemed necessary by clinical staff. This study examined the association of spoken language preference and ethnicity with use of video versus phone virtual visits by US Latino and Chinese adult patients who got care in the same healthcare system.MethodsWe analyzed electronic health record data for four groups of adults aged 26-85y who had ≥ 1 primary or specialty care outpatient clinician visits during April-December 2020: 80,869 Latino adults preferring Spanish (LEP Latino); 214,765 Latino adults preferring English (non-LEP Latino); 23,430 Chinese adults preferring a Chinese dialect (LEP Chinese); and 49,710 Chinese adults preferring English (non-LEP Chinese). Prevalence of the following utilization outcomes were compared by language preference (LEP/non-LEP) within ethnicity and by ethnicity within language preference for four age subgroups (26-39y, 40-64y, 65-75y, and 76-85y): ≥ 1 virtual (video or phone) visit, ≥ 1 video visit, ≥ 1 phone visit, ≥ 1 clinic visit, video visits only, and phone visits only. We also compared ethnicity x language group differences within age subgroups using absolute difference and adjusted prevalence ratios derived from modified log-Poisson regression models that controlled for age and sex.ResultsAmong virtual users, LEP Latino and Chinese adults were significantly less likely to use video visits and more likely to use phone visits than non-LEP Latino and Chinese adults in the same age strata. The LEP/non-LEP difference in video visit use was significantly larger among Latino than Chinese patients, with no similar ethnic group difference observed for phone visits. Within the LEP and non-LEP language groups, Chinese adults were significantly more likely than Latino adults to use video visits and less likely to use phone visits.ConclusionsDuring the first nine months of the COVID-19 pandemic, uptake of video and phone virtual visits by Latino and Chinese adults significantly differed by LEP/non-LEP status within ethnicity and by ethnicity within LEP/non-LEP language group. These findings underscore the importance of disaggregating data by ethnicity and language preference when attempting to understand and study patient use of different virtual visit modalities.

Relationship between creatinine–cystatin C ratio and all-cause mortality in hospitalized patients with COVID-19: A prospective study in China

BackgroundThis study was conducted to investigate whether baseline creatinine–cystatin C ratio is associated with all-cause mortality in adult Chinese patients hospitalized with coronavirus disease 2019. MethodsThis study included 933 patients with coronavirus disease 2019 who were admitted to The Affiliated Hospital of Guangdong Medical University between December 2022 and March 2023. All-cause mortality was determined by telephone follow-up after 28 days. Multivariate Cox proportional risk models were used to investigate the relationship between baseline creatinine–cystatin C ratio and all-cause mortality. Restricted cubic spline and two-piecewise Cox proportional hazards risk models were used to identify non-linear correlations. ResultsOf the 933 patients, 128 died during the 28 days follow-up. The restricted cubic spline analysis of hospitalized patients with coronavirus disease 2019 revealed an L-shaped association between baseline creatinine–cystatin C ratio and all-cause mortality, with a threshold creatinine–cystatin C ratio of ≤0.93 predicting all-cause mortality. Specifically, a baseline creatinine–cystatin C ratio below this threshold value was negatively correlated with mortality (hazard ratio 0.12, 95 % confidence interval 0.03–0.48), but a creatinine–cystatin C ratio >0.93 was not correlated with mortality (hazard ratio 1.29, 95 % confidence interval 0.65–2.55). ConclusionsIn Chinese adult patients hospitalized with coronavirus disease 2019, an L-shaped relationship was observed between the baseline creatinine–cystatin C ratio and all-cause mortality.

Clinical and genetic characteristics of Chinese pediatric and adult patients with hereditary spherocytosis

ObjectiveThis study aimed to investigate the clinical features, pathogenic gene variants, and potential genotype–phenotype correlations in Chinese patients with hereditary spherocytosis (HS).MethodsRetrospective analysis of clinical data and molecular genetic characteristics was conducted on patients diagnosed with HS at Jiangxi Provincial Children's Hospital, the Second Affiliated Hospital of Nanchang University, Pingxiang People's Hospital and The Third People's Hospital of Jingdezhen between November 2017 and June 2023. Statistical analyses were performed to compare and analyze the red blood cell (RBC), hemoglobin (HB), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) data between and within groups based on different mutations and age groups (< 14 and ≥ 14 years).ResultsA total of 34 HS patients were included in this study, comprising 22 children (64.70%) and 12 adults (35.30%). The probands who underwent genetic testing were derived from 34 unrelated families. Thirty-two variants were tested and 9 of them are novel. Eighteen cases had ANK1 variants, 15 had SPTB variants, and 1 had SLC4A1 variant. 25 patients performed core family members underwent genetic testing, 17 (68.0%, 17/25) were de novo, 5 (20.0%, 5/25) were maternally inherited, and 3 (12.0%, 3/25) were paternally inherited. ANK1-HS patients exhibited more severe anemia compared to cases with SPTB-HS, showing lower levels of RBC and HB (P < 0.05). Anemia was more severe in patients diagnosed in childhood than in those diagnosed in adulthood. Within the ANK1-HS group, MCH levels in adult patients was significantly higher than those in children (P < 0.05), while there were no significant differences in RBC, HB, MCV, and MCHC levels between two groups. Adult patients with SPTB-HS had significantly higher levels of RBC, HB, and MCH than pediatric patients (P < 0.05), while MCV and MCHC levels showed no significant statistical differences.ConclusionThis study conducted a comparative analysis of phenotypic characteristics and molecular genetics in adult and pediatric patients diagnosed with HS, confirming that pediatric ANK1-HS patients exhibit a more severe anemic phenotype compared to SPTB-HS patients, while the severity of HS in adults does not significantly differ between different causative genes.

Intracranial vasculopathy: an important organ damage in young adult patients with late-onset Pompe disease

BackgroundLate-onset Pompe disease (LOPD) is mainly characterized by progressive limb-girdle muscle weakness and respiratory impairment, whereas stroke and cerebrovascular abnormalities have been insufficiently studied in LOPD. This study aimed to evaluate the frequency and pattern of intracranial artery and brain parenchyma abnormalities in LOPD patients.ResultsNeuroimaging data from 30 Chinese adult LOPD patients were collected from our center. Seven patients (7/30) had acute cerebral infarction or hemorrhage. Brain magnetic resonance angiography (MRA) or computed tomography angiography (CTA) revealed artery abnormalities in 23 patients (23/30). Dilative arteriopathy was found in 19 patients (19/30), with vertebrobasilar dolichoectasia found in 17 patients and dilatation of the anterior circulation arteries found in 8 patients. The maximum diameter of the basilar artery was correlated with disease duration (p < 0.05). In addition, aneurysms (7/30) and fenestrations (3/30) were discovered. There were 14 patients with arterial stenosis (14/30), and both anterior and posterior circulation involvement occurred in 9 patients (9/14). Stenosis and dilative arteriopathy simultaneously occurred in 10 patients (10/30). White matter hyperintensities were present in 13 patients (13/28). Microbleeds, predominantly located in the cerebellum and brainstem, were detected in 7 patients (7/22) via susceptibility-weighted imaging.ConclusionsIntracranial vasculopathy involving both large arteries and small vessels is an important organ damage in LOPD patients. LOPD should be considered a key differential diagnosis in young adults with cryptogenic stroke, and a series of imaging evaluations of the brain and intracranial blood vessels is recommended as a routine workup in adult LOPD patients.

Do Chinese HIV-infected adult patients with altered renal function need to adjust tenofovir disoproxil fumarate dosage? A population pharmacokinetics analysis

Tenofovir disoproxil fumarate (TDF), a prodrug of tenofovir (TFV), is an effective drug in treating patients infected with human immunodeficiency virus (HIV). Previous population pharmacokinetics (PPK) studies have showed the large variabilities in PK of TFV. Furthermore, limited information was known in Chinese populations. Therefore, the aim of this study was to characterize PPK of TDF in Chinese and identify factors that may affect its PK. TFV concentrations (n = 552) from 30 healthy subjects and 162 HIV-infected Chinese adult patients were pooled for PPK analysis by a nonlinear mixed-effects method. The PK of TFV was adequately described as a two-compartment model with first order absorption and elimination. The typical apparent clearance (CL/F) of TFV in 70-kg adults was 137 L/h, higher than that reported in Caucasians and Blacks (45.8–93 L/h). Estimated glomerular filtration rate was identified to be a significant factor influencing CL/F. Monte Carlo simulation showed that the exposure of standard dosing regimen of TDF 300 mg every 24 h in Chinese people with mild renal impairment (60 to 90 ml/min/1.73 m2) was close to that in individuals with normal renal function (90 mL/min). Dose adjustment is not required for patients with mild renal impairment. Our study might offer new clues for optimal dosing strategies in Chinese patients with HIV-infected.

Effects of Natural Sound Therapy on Pain and Agitation Induced by Endotracheal Suctioning: A Real-World Study.

Music therapy has been used as a complementary intervention to provide synergistic analgesia for various procedures. To evaluate the effects of natural sound therapy on pain intensity and agitation scores in intubated adult Chinese patients who received endotracheal suctioning in a critical care unit. A prospective, real-world, randomized, double-blind, controlled study was conducted from July 2021 through February 2022 among intubated surgical intensive care unit patients in a Chinese hospital. Patients were randomly assigned to a control group receiving conventional treatment or an intervention group receiving natural sound therapy plus conventional treatment (50 patients in each group). Patients' pain intensity and agitation levels were analyzed before, during, immediately after, 5 minutes after, and 15 minutes after completion of endotracheal suctioning. Pain intensity was assessed with the Critical-Care Pain Observation Tool (CPOT); agitation was assessed with the Richmond Agitation-Sedation Scale (RASS). According to CPOT scores, patients in the intervention group had significant relief of pain intensity during, immediately after, and 5 minutes after endotracheal suctioning compared with patients in the control group (all P < .001). The RASS scores showed that agitation levels were significant lower in the intervention group than in the control group during (P = .002) and immediately after (P < .001) endotracheal suctioning. In this real-world study, natural sound therapy was part of a holistic bundle of interventions used to reduce pain and agitation in surgical intensive care unit patients during endotracheal suctioning.

Prevalence and co-prevalence of comorbidities among Chinese adult patients with type 2 diabetes mellitus: a cross-sectional, multicenter, retrospective, observational study based on 3B study database.

This study aimed to investigate the prevalence and co-prevalence of comorbidities among Chinese individuals with type 2 diabetes (T2DM). Medical records were retrospectively retrieved from the 3B Study database, which provided a comprehensive assessment of comorbid conditions in Chinese adult outpatients with T2DM. Patient characteristics, laboratory measures, and comorbidities were summarized via descriptive analyses, overall and by subgroups of age (<65, 65-74, 75 years) and gender. Among 25,454 eligible patients, 53% were female, and the median age was 63 years. The median time of diabetes duration was 6.18 years. A total of 20,309 (79.8%) patients had at least one comorbid condition alongside T2DM. The prevalence of patients with one, two, three, and four or more comorbid conditions was 28.0%, 24.6%, 15.6%, and 11.6%, respectively. Comorbidity burden increased with longer T2DM duration. Older age groups also exhibited higher comorbidity burden. Females with T2DM had a higher overall percentage of comorbidities compared to males (42.7% vs. 37.1%). The most common comorbid conditions in T2DM patients were hypertension (HTN) in 59.9%, overweight/obesity in 58.3%, hyperlipidemia in 42.0%, retinopathy in 16.5%, neuropathy in 15.2%, cardiovascular disease (CVD) in 14.9%, and renal disease in 14.4%. The highest co-prevalence was observed for overweight/obesity and HTN (37.6%), followed by HTN and hyperlipidemia (29.8%), overweight/obesity and hyperlipidemia (27.3%), HTN and CVD (12.6%), HTN and retinopathy (12.1%), and HTN and renal disease (11.3%). The majority of T2DM patients exhibit multiple comorbidities. Considering the presence of multimorbidity is crucial in clinical decision-making. https://clinicaltrials.gov/, identifier NCT01128205.

Neglected Mendelian causes of stroke in adult Chinese patients who had an ischaemic stroke or transient ischaemic attack

Background and purposeMultiple factors play important roles in the occurrence and prognosis of stroke. However, the roles of monogenic variants in all-cause ischaemic stroke have not been systematically investigated. We...

Clinical Characteristics of 427 Unvaccinated Chinese Adult Patients with Maintenance Hemodialysis Infected with the SARS-CoV-2 Omicron Variant: A Retrospective Study

Background: Maintenance hemodialysis (MHD) patients constitute a distinctive population characterized by unique traits, such as hemodialysis-related immune disturbances, and increased vulnerability to infections, heart failure, particularly severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite considerable research on MHD patients with coronavirus disease 2019 (COVID-19), there is limited information available on the clinical characteristics and outcomes of unvaccinated adult MHD patients infected with the SARS-CoV-2 Omicron variant. Methods: A retrospective investigation was conducted in a cohort of 427 unvaccinated MHD patients diagnosed with SARS-CoV-2 Omicron infection. The clinical symptoms, laboratory results, and treatment regimens were comprehensively examined. Multivariate regression identified independent risk factors for disease severity, and two-month follow-up assessments were conducted. Results: The cohort exhibited a spectrum of disease severity, with 37.5% classified as mild, 35.3% as common, 22.5% as severe, and 4.7% as critical. Serum C-reactive protein level, procalcitonin level, and bicarbonate concentration are related to the severity of the disease. Tailored treatment strategies—including nutritional support, hemodialysis management, anti-bacterial interventions, and more—were implemented. There was a 5.6% mortality rate, with a higher prevalence of deaths in the critical subtype. Independent risk factors for disease severity included fever, age, cycle threshold values (Ct values) of ORF1ab gene, and arterial oxygen partial pressure. Follow-up assessments revealed a median duration of 11 days for the negative nucleic acid of SARS-CoV-2. Twelve patients presented a second positive ORF1ab gene during follow-up but remained asymptomatic. Conclusion: These findings suggest the intricate clinical characteristics and outcomes of MHD patients with the SARS-CoV-2 Omicron infection. Tailored treatment strategies, continuous surveillance, and understanding prognostic factors are imperative for managing this high-risk population. Further research is warranted to validate these findings.

#1723 Genetic landscape of polycystic kidney disease in a Chinese cohort – experience using whole genome sequencing in a tertiary renal unit

Abstract Background and Aims Genetic testing has increasingly been employed to provide definitive diagnoses and prognostic information in patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD). We aim to explore the genetic landscape of ADPKD in a Chinese cohort utilizing whole genome sequencing and study its real-world clinical utility. Method From 1st January 2022 to 31st March 2023, we recruited 50 adult Chinese patients who had the clinical diagnosis of ADPKD followed up at Queen Mary Hospital and consented to the study protocol. The study was approved by the University Institution Review Board and local ethics committees. Genomic DNA was isolated from samples obtained from patients per standard protocol. Whole-genome sequencing was performed and analysed through the germline analysis pipeline. Diagnostic analysis was performed per American College of Medical Genetics (ACMG) guidelines and ClinGen variant curation expert panel specifications. Diagnostic variants were defined as those classified as ‘pathogenic’ or ‘likely pathogenic’. Potential clinical utility of genetic findings were studied case-by-case based on the Kidney Disease Improving Global Outcomes (KDIGO) 2023 Clinical Practice Guideline for the Evaluation, Management and Treatment of ADPKD. Results Among the 50 unrelated probands with ADPKD, half were males and the mean age at presentation was 38. 38% patients had incidental finding of kidney cysts on abdominal imaging performed for unrelated symptoms or health screening, 32% presented for screening due to positive family history and only 30% presented with typical symptoms of ADPKD. Cystic complications were present in 30%, with cyst haemorrhage being the most common, followed by kidney stones, cyst rupture and infection. 80% patients also had liver cysts and none had a history of cerebral aneurysms. The majority of our cohort (72%) had a family history of ADPKD. We identified diagnostic variants in 35 individuals, reaching a diagnostic yield of 70%. Diagnostic variants were identified in PKD1 (20/35), PKD2 (11/35), IFT140 (3/35) and ALG9 (1/35). The majority of diagnostic variants were protein-truncating (32/35), while non-truncating variants consisted of 1 in-frame deletion and 2 missense variants in PKD1. We identified 3 copy number variation:NC_000016.10:g.2110587_2111851del,NC_000016.10:g.2132339_2137621del,NC_000016.10:g.2036427_2101117del. The genetic findings allowed physicians to make definitive diagnosis in 9 patients with negative family history of ADPKD. The genetic findings provided important prognostic information as protein-truncating variants in PKD1 or PKD2 were associated with more severe disease compared to non-truncating variants. For the 3 patients harbouring heterozygous pathogenic variants in IFT140 (NM_014714.4:c.2659G&amp;gt;T, NM_014714.4:c.3780del, NM_014714.4:c.1035_1036del), they demonstrated a milder PKD phenotype with stable kidney function, normal kidneys size and absence of liver cysts 10 years after the diagnosis. The patient with heterozygous likely pathogenic ALG9 variant (NM_024740.2:c.1225del) also had milder PKD phenotype with normal kidney function and normal sized kidneys on USG 5 years after the diagnosis. In another male patient with young hypertension who was classified as Mayo Class 1C according to kidney imaging, identifying the pathogenic protein-truncating variant in PKD1 (NM_001009944.3:c.7288C&amp;gt;T) would render him eligible to tolvaptan treatment in view of the high PROPKD score (7). Furthermore, the genetic findings enabled an earlier diagnosis in a number of family members by cascade testing and genetic results were important to identify suitable living-related kidney donors. Conclusion Genetic testing utilizing whole genome sequencing has multiple clinical utility in ADPKD patients. It could provide a definitive diagnosis in those with atypical presentation or without family history, inform prognosis, guide treatment, determine living-related donor suitability and allow earlier diagnosis in other family members.

Development and validation of a nomogram for predicting poor operative visibility during FESS in Chinese adult patients with CRS.

The purpose of this study is to develop and evaluate a nomogram that is capable of predicting poor operative visibility during functional endoscopic sinus surgery. To identify potential risk factors, patients with chronic rhinosinusitis who underwent functional endoscopic sinus surgery (FESS) between January 2019 and December 2022 were selected from our hospital's electronic medical record system. Data on general patient information, clinical manifestations, clotting-related test indices, Lund-Machay score of sinuses CT scanning, Lund-kennedy score of nasal endoscopies, anesthesia methods, intraoperative blood pressure and heart rate, and Boezaart bleeding score were collected. Minimum absolute convergence and selection operator (LASSO) regression, as well as multivariate logistic regression, were used to determine the risk factors. A nomogram was developed in order to predict poor operating visibility during FESS, and its performance was evaluated utilizing both the training and verification datasets via various measures including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC), Hosmer-Lemeshow goodness-of-fit test, calibration curve, and decision curve analysis. Of the 369 patients who met the inclusion criteria, 88 of them exhibited POV during FESS. By deploying LASSO and multivariate logistic regression analyses, six risk factors were identified and used to construct a nomogram for predicting POV during FESS. These factors include prothrombin time (PT), prothrombin activity (PTA), Lund-Mackay score (LMS), Lund-Kennedy score (LKS), anesthetic method, and intraoperative hypertension. The AUC of the training set was found to be 0.820 while that of the verification set was 0.852. The Hosmer-Lemeshow goodness-of-fit test and calibration curve analysis revealed good consistency between predicted and actual probabilities. Also, the decision curve demonstrated that the nomogram had a high degree of clinical usefulness and net benefit. The constructed nomogram has a strong ability to predict the poor intraoperative field in patients with chronic rhinosinusitis, which can help preoperative judgment of high-risk patients and provide evidence for perioperative management and preoperative plan formulation.

Impact of LDLR polymorphisms on lipid levels and atorvastatin’s efficacy in a northern Chinese adult Han cohort with dyslipidemia

BackgroundDyslipidemia, a significant risk factor for atherosclerotic cardiovascular disease (ASCVD), is influenced by genetic variations, particularly those in the low-density lipoprotein receptor (LDLR) gene. This study aimed to elucidate the effects of LDLR polymorphisms on baseline serum lipid levels and the therapeutic efficacy of atorvastatin in an adult Han population in northern China with dyslipidemia.MethodsIn this study, 255 Han Chinese adults receiving atorvastatin therapy were examined and followed up. The 3’ untranslated region (UTR) of the LDLR gene was sequenced to identify polymorphisms. The associations between gene polymorphisms and serum lipid levels, as well as changes in lipid levels after intervention, were evaluated using the Wilcoxon rank sum test, with a P < 0.05 indicating statistical significance. Assessment of linkage disequilibrium patterns and haplotype structures was conducted utilizing Haploview.ResultsEleven distinct polymorphisms at LDLR 3’ UTR were identified. Seven polymorphisms (rs1433099, rs14158, rs2738466, rs5742911, rs17249057, rs55971831, and rs568219285) were correlated with the baseline serum lipid levels (P < 0.05). In particular, four polymorphisms (rs14158, rs2738466, rs5742911, and rs17249057) were in strong linkage disequilibrium (r2 = 1), and patients with the AGGC haplotype had higher TC and LDL-C levels at baseline. Three polymorphisms (rs1433099, rs2738467, and rs7254521) were correlated with the therapeutic efficacy of atorvastatin (P < 0.05). Furthermore, carriers of the rs2738467 T allele demonstrated a significantly greater reduction in low-density lipoprotein cholesterol (LDL-C) levels post-atorvastatin treatment (P = 0.03), indicating a potentially crucial genetic influence on therapeutic outcomes. Two polymorphisms (rs751672818 and rs566918949) were neither correlated with the baseline serum lipid levels nor atorvastatin’s efficacy.ConclusionsThis research outlined the complex genetic architecture surrounding LDLR 3’ UTR polymorphisms and their role in lipid metabolism and the response to atorvastatin treatment in adult Han Chinese patients with dyslipidemia, highlighting the importance of genetic profiling in enhancing tailored therapeutic strategies. Furthermore, this investigation advocates for the integration of genetic testing into the management of dyslipidemia, paving the way for customized therapeutic approaches that could significantly improve patient care.Trial registrationThis multicenter study was approved by the Ethics Committee of Xiangya Hospital Central South University (ethics number K22144). It was a general ethic. In addition, this study was approved by The First Hospital of Hebei Medical University (ethics number 20220418).

Association of lactate/albumin ratio with 3-month readmission risk in heart failure patients: a retrospective study.

The predictive value of the lactate/albumin ratio (LAR) in mortality is established in various conditions, yet its relevance to 3-month readmission risk in Chinese adults with heart failure (HF) remains unclear. Analysing data from 957 patients with HF at Zigong Fourth People's Hospital, Sichuan, China (December 2016 to June 2019), we assessed baseline characteristics, vital signs, comorbidities, and prescriptions. LAR demonstrated a linear correlation with 3-month readmission risk (HR=1.60, 95% CI: 1.19-2.16). Tertile 3 (≥-0.48) exhibited higher risk than tertile 1 (<-0.83) and tertile 2 [-0.83, -0.48), with HRs and 95% CI of 1.49 (1.06-2.10), 1.43 (1.01-2.02), 1.48 (1.03-2.12), respectively. Subgroup and sensitivity analyses affirmed consistent influence of LAR on 3-month readmission risk for HF. Higher LAR significantly correlates with increased 3-month readmission risk in Chinese adult patients with HF, suggesting LAR is a valuable predictor for early readmission.

Prevalence and related factors of first-time suicide attempts in the past 14 days in Chinese adult patients with first-episode drug-naïve major depressive disorder.

This study aimed to identify socio-demographic, physiologic, and psychologic related factors of the first-time suicide attempt (FSA) in the past 14 days in Chinese adult patients with first-episode drug-naïve (FEDN) major depressive disorder (MDD). A total of 1718 adult patients with FEDN MDD were enrolled in this cross-sectional survey. Depression, anxiety symptoms, and suicide attempts were assessed. Additionally, biological samples were collected and measured, while Logistic regression analysis was employed to explore the risk factors for FSA in the past 14 days among FEDN MDD patients. Among suicide attempters, 12.11% (208 out of 1718) reported experiencing FSA in the past 14 days. Logistic regression analysis showed that the risk factors for FSA included more severe anxiety symptoms (OR=1.37, 95%CI: 1.28-1.48, p<0.001), higher levels of total cholesterol (TC) (OR=1.42, 95%CI: 1.13-1.77, p=0.003), and elevated thyroid-stimulating hormone (TSH) (OR=1.13, 95%CI: 1.03-1.25, p=0.01). The regression model exhibited good discriminatory power for FSA with an area under the curve (AUC) of 0.82. FEDN MDD patients with more severe anxiety and higher levels of TSH and TC are more likely to develop FSA in the past 14 days. These factors are risk factors for short-term (in the past 14 days) FSA and may serve as indicators for early intervention.

Abstract 3548: OKAIN: A comprehensive oncology knowledgebase for the interpretation of clinically actionable alterations

Abstract Background: The increased use of Next-Generation Sequencing (NGS) in clinical genetic testing has resulted in the identification of several genetic variations with possible therapeutic implications. Several knowledgebases, such as OncoKB, have been curated to better understand the clinical implications of somatic mutations in cancer. While thorough annotation of gene variations of Chinese pharmaceuticals is not recorded in the majority of those databases. As a result, we developed OKAIN (https://szcube.origimed.com), an algorithm tool that assesses clinically actionable mutations using a precision oncology knowledge database. Methods: OKAIN employs a weighted evidence analysis system to deliver final clinical annotation outcomes for intricate variations. This process commences with a weighted analysis of all therapeutic efficacy evidence for a specific genomic variant related to a particular drug, to determine the highest degree of efficacy for that drug. The top efficacy level is then assessed against numerous variants of the gene, resulting in efficacy data for all variants of the gene in relation to the medication. Results: To date, OKAIN has collected 15,654 pieces of evidence on 471 genes associated with cancer. This comprises 2,600 pieces of Level A evidence (included in FDA/NMPA labeling or clinical professional guidelines) on 66 genes, 180 Level B evidence (included in extensive retrospective studies or prospective investigations) on 31 genes, 676 Level C evidence (included in small-scale retrospective studies or early-stage prospective studies) on 81 genes, and 5,562 Level D evidence (included in case reports and preclinical studies) on 188 genes. For Level A evidence, 864 pieces of evidence were derived from either the NMPA label or CSCO guidelines. As an illustration, Befotertinib was approved by NMPA as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC) in adult patients with either EGFR exon 19 deletion or L858R mutation. This indicates that adult Chinese patients with locally advanced or metastatic NSCLC who have EGFR exon 19 deletion or L858R mutation can potentially experience benefits from administering Befotertinib. Conclusion: OKAIN acts as a precision oncology knowledgebase for the assessment of clinically actionable alterations, integrating exhaustive data related to cancer-associated genomic variants and therapeutic efficacy. It is a beneficial tool for medical professionals and patients, providing an enhanced means of understanding and approaching precision oncology. Citation Format: Zhenhua Yang, Mingmin Wang, Hongli Qin, Yanfei Yu, Yufeng Zheng, Ziang Li, Xinxiu Meng, Xiaowei Dong, Liwei Wang, Kai Wang, Aodi Wang. OKAIN: A comprehensive oncology knowledgebase for the interpretation of clinically actionable alterations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3548.