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Yitian Zheng,1– 3,* Yu Qi,1,* Samuel Seery,4,5 Jie Yang,2,3 Chen Li,2,3 Wenyao Wang,1 Jun Gao,1 Xiangbin Meng,1 Chunli Shao,1 Yi-Da Tang1 1Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, People’s Republic of China; 2Department of Cardiology, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 3Graduate School of Peking Union Medical College, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China; 4School of Humanities and Social Sciences, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, People’s Republic of China; 5Faculty of Health and Medicine, Division of Health Research, Lancaster University, Lancaster, UK*These authors contributed equally to this workCorrespondence: Yi-Da Tang, Department of Cardiology and Institute of Vascular Medicine, Peking University Third Hospital, NHC Key Laboratory of Cardiovascular Molecular Biology and Regulatory Peptides, Key Laboratory of Molecular Cardiovascular Science, Ministry of Education; Beijing Key Laboratory of Cardiovascular Receptors Research, Beijing, 100191, People’s Republic of China, Email tangyida@bjmu.edu.cnObjective: Anti-inflammatory therapies are reported to have additional benefits beyond lipid control for patients with cardiovascular disease. However, no study has focused on the relationship between inflammation status and long-term outcomes for chronic obstructive pulmonary disease (COPD) patients, after percutaneous coronary intervention (PCI).Methods: 277 COPD-PCI patients were divided into two groups according to hsCRP status upon admission. Major adverse cardiac events (MACE) in high hsCRP patients were compared to patients with low hsCRP. Restricted cubic spline (RCS) analysis was performed using MACE hazard ratios (HR) to investigate interrelations with hsCRP, as a continuous variable.Results: Patients in the high hsCRP group incurred more inflammation activation, in terms of higher white blood cell counts, neutrophil, lymphocytes, and had higher smoking rates, compared to those with lower hsCRPs. A significant increase in MACEs was observed in hsCRP high group, compared to the low hsCRP group (HR: 2.47, 95% CI: 1.22– 5.00; p = 0.012). RCS curves suggest that HRs rise beyond 1.0, after the 0.24 juncture for Lg HsCRP (base 10 logarithm with hsCRP), HR per SD: 1.19 (95% CI: 0.96– 1.48). Further subgroup analysis implies that elevated hsCRP is associated with a higher risk of MACEs across the sub-groups tested.Conclusion: HsCRP could be a useful indicator for COPD-CAD patient prognosis, after PCI. This is because hsCRP highlights inflammation activation. More multi-center research, designed for COPD-CAD patients should be conducted to more accurately determine the cut-off value for hsCRP.Keywords: HsCRP, chronic obstructive pulmonary disease, coronary artery disease, percutaneous coronary intervention, outcomes

Background: Bovine tuberculosis (bTB) is the most important animal health concern in Wales. Annual testing across all cattle herds in Wales commenced in 2010. In 2017, a new geographic division of Wales was conceived, with bespoke cattle controls and eradication milestones reflecting the geographical heterogeneity of bTB distribution., Methods: This observational study uses descriptive analysis and Poisson regression modelling to analyse bTB surveillance data from all herds in Wales., Results: Since 2010, there has been a significant decrease (p < 0.0001) in bTB incidence (8.6%‒6.3%) and plateauing prevalence across Wales. Conversely, there has been an increase in bTB incidence and prevalence in discrete areas. Recurrence and persistence remain important drivers of bTB infection. One of the sharpest declines in bTB incidence was observed in an intensive action area where enhanced cattle control and wildlife vaccination were implemented in an area of high bTB prevalence. Increased herd size, dairy herd type and herd location are important risk factors affecting the rate of bTB incidents in Wales., Limitations: This study includes data from Wales only., Conclusions: Improvements in trends of bTB occurred from 2010 to 2021, but the spatial variations described in this paper support the continued need for regionally adapted surveillance and control measures., (© 2024 The Author(s). Veterinary Record published by John Wiley & Sons Ltd on behalf of British Veterinary Association.)

Refractory or relapsed T cell acute lymphoblastic leukemia (r/r T-ALL) patients have poor prognoses, due to the lack of effective salvage therapies. Recently, CD7-targeting chimeric antigen receptor (CAR)-T therapies show efficacy in patients with r/r T-ALL, but relapse with CD7 loss is common. This study evaluates a CD5-gene-edited CAR-T cell therapy targeting CD5 in 19 r/r T-ALL patients, most of whom had previously failed CD7 CAR-T interventions. CAR-T products were derived from previous transplant donors (Cohort A) or newly matched donors (Cohort B). Primary endpoints were dose-limiting toxicity at 21 days and adverse events within 30 days. Secondary endpoints were responses, pharmacokinetics and severe adverse events after 30 days. A total of 16 received infusions, 10 at target dose of 1 × 10 6  kg -1 . All encountered grade 3-4 cytopenias and one had a grade 3 infection within 30 days. All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30. At a median follow-up of 14.3 months, four received transplantation; three were in remission and one died of infection. Of 12 untransplanted patients, 2 were in remission, 3 relapsed, 5 died of infection and 2 of thrombotic microangiopathy. CAR-T cells persisted and cleared CD5 + T cells. CD5 - T cells, mostly CD5-gene-edited, increased but remained below normal levels. These results suggest this CD5-specific CAR-T intervention has a high remission rate for T-ALL patients. Evidence also suggests the risk of late-onset severe infection may be mitigated with consolidative transplantation. This study provides insights that could help to optimize this promising intervention. ClinicalTrials.gov registration: NCT05032599 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: To develop a prognostic model to manage patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) and chemotherapy., Patients and Methods: Clinicopathologic characteristics and survival data were collated from a North American database to develop a model. Genomic and clinicopathologic data were also obtained from European and Asian databases to externally validate the model. Patients were classified as either "primary" or "progressive" MIBC according to non-muscle invasive stage history. Optimized cancer-specific survival (CSS) models, based on MIBC types, were constructed using Cox's proportional hazard regression. Differences of biological function and tumor immunity, between two risk-based groups stratified according to the prognostic model, were estimated., Results: There were 2631 participants in the American cohort, 291 in the European cohort and 142 in the Asian cohort. Under Cox's regression analysis, tumor stage, lymph node stage, age, ethnicity, and MIBC types were independent CSS predictors (all p < 0.05). The constructed nomogram, which integrated these variables, improved the predictive power. This model had good discrimination and calibration. Patients were categorized into high- or low-risk groups according to the total points calculated. Kaplan-Meier curves revealed that patients in the high-risk group had poorer survival (p < 0.001). This was confirmed with two external validation cohorts (both with p < 0.001). Higher stromal scores and increased M0 and M2 macrophage numbers were observed in samples from the high-risk group, whereas regulatory T cells had lower infiltration in these populations (all with p < 0.05)., Conclusions: This MIBC type-based nomogram provides accurate CSS predictions, which could help improve patient management and clinical decision-making., (© 2024. Society of Surgical Oncology.)

Cytokines may related to intrauterine Hepatitis B virus (HBV) transmission. 205 HBsAg(+) pregnant cases and 74 HBsAg(-) women were included. Neonatal blood samples were taken within 24 h of delivery and before HBV vaccinations. Serological HBV biomarkers and cytokines were detected. 21.9 % of the newborns from HBsAg(+) women were intrauterinally transmitted, including 7.3 % with dominant transmission (DBT) and 14.6 % occult transmission (OBT). HBV DNA load (odd ratio [OR], 1.44; 95 % confidence interval [CI], 1.05-1.98), interferon-γ (IFN-γ) (OR, 1.01; 95 %CI, 1.00-1.02) and toll-like receptor 9 (TLR9) (OR, 1.27; 95 %CI, 1.06-1.52) positively correlated with DBT. Only IFN-γ (OR, 1.01; 95 %CI, 1.00-1.01) positively associated with OBT. According to the generated restricted cubic spline, TLR9 was positively correlates with rise of DBT in a log-shape. It may be possible to develop a nomogram which intercalates these factors to predict intrauterine HBV transmissions. Further research should consider immune processes involved in chorioamnionitis., 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. Published by Elsevier Ltd.)

Objective: This study assesses the influence of hyperkalemia on both disease severity and the risk of mortality among patients admitted to the emergency room., Methods: This retrospective observational study utilized data from the Chinese Emergency Triage Assessment and Treatment database (CETAT, version 2.0), which was designed to evaluate and optimize management strategies for emergency room (ER) patients. Patients were systematically categorized based on serum potassium levels. Relationships between serum potassium levels, risk of mortality, and the severity of illness were then analyzed using multifactorial logistic regression and through Receiver Operating Characteristic (ROC) analysis. The effectiveness of various treatments at lowering potassium levels was also investigated., Results: 12,799 emergency patients were enrolled, of whom 20.1% (n = 2,577) were hypokalemic and 2.98% (n = 381) were hyperkalemic. Among hyperkalemic patients, the leading reasons for visiting the ER were altered consciousness 23.88% (n = 91), cardiovascular symptoms 22.31% (n = 85), and gastrointestinal symptoms 20.47% (n = 78). Comparative analysis with patients exhibiting normal potassium levels revealed hyperkalemia as an independent factor associated with mortality in the ER. Mortality risk appears to positively correlate with increasing potassium levels, reaching peaks when blood potassium levels ranged between 6.5 and 7.0. Hyperkalemia emerged as a strong predictor of death in the ER, with an Area Under the Curve (AUC) of 0.89. The most frequently prescribed treatment for hyperkalemia patients was diuretics (57.32%, n = 188), followed by intravenous sodium bicarbonate (50.91%, n = 167), IV calcium (37.2%, n = 122), insulin combined with high glucose (27.74%, n = 91), and Continuous Renal Replacement Therapy (CRRT) for 19.82% (n = 65). Among these, CRRT appeared to be the most efficacious at reducing potassium levels. Diuretics appeared relatively ineffective, while high-glucose insulin, sodium bicarbonate, and calcium preparations having no significant effect on the rate of potassium decline., Conclusion: Hyperkalemia is common in emergency situations, especially among patients with altered consciousness. There is a strong positive correlation between the severity of hyperkalemia and mortality risk. CRRT appears to be the most effective potassium reducting strategy, while the use of diuretics should be approached with caution., (© 2024. The Author(s).)

Background: Colposcopy plays an essential role in diagnosing cervical lesions and directing biopsy; however, there are few studies of the capabilities of colposcopists in medically underserved communities in China. This study aims to fill this gap by assessing colposcopists' competencies in medically underserved communities of China., Methods: Colposcopists in medically underserved communities across China were considered eligible to participate. Assessments involved presenting participants with 20 cases, each consisting of several images and various indications. Participants were asked to determine transformation zone (TZ) type, colposcopic diagnoses and to decide whether biopsy was necessary. Participants are categorized according to the number of colposcopic examinations, i.e., above or below 50 per annum., Results: There were 214 participants in this study. TZ determination accuracy was 0.47 (95% CI 0.45,0.49). Accuracy for colposcopic diagnosis was 0.53 (95% CI 0.51,0.55). Decision to perform biopsies was 0.73 accurate (95% CI 0.71,0.74). Participants had 0.61 (95% CI 0.59,0.64) sensitivity and a 0.80 (95% CI 0.79,0.82) specificity for detecting high-grade lesions. Colposcopists who performed more than 50 cases were more accurate than those performed fewer across all indicators, with a higher sensitivity (0.66 vs. 0.57, p = 0.001) for detecting high-grade lesions., Conclusions: In medically underserved communities of China, colposcopists appear to perform poorly at TZ identification, colposcopic diagnosis, and when deciding to biopsy. Colposcopists who undertake more than 50 colposcopies each year performed better than those who perform fewer. Therefore, colposcopic practice does improve through case exposure although there is an urgent need for further pre-professional and clinical training., (© 2024. The Author(s).)

To investigate age and type-specific prevalences of high-risk human papillomavirus (hrHPV) and cervical intraepithelial neoplasia (CIN) in hrHPV+ women referred to colposcopy. This is a retrospective, multicenter study. Participants were women referred to one of seven colposcopy clinics in China after testing positive for hrHPV. Patient characteristics, hrHPV genotyping, colposcopic impressions, and histological diagnoses were abstracted from electronic records. Main outcomes were age-related type-specific prevalences associated with hrHPV and CIN, and colposcopic accuracy. Among 4419 hrHPV+ women referred to colposcopy, HPV 16, 52, and 58 were the most common genotypes. HPV 16 prevalence was 39.96%, decreasing from 42.57% in the youngest group to 30.81% in the eldest group. CIN3+ prevalence was 15.00% and increased with age. As lesion severity increases, HPV16 prevalence increased while the prevalence of HPV 52 and 58 decreased. No age-based trend was identified with HPV16 prevalence among CIN2+, and HPV16-related CIN2+ was less common in women aged 60 and above (44.26%) compared to those younger than 60 years (59.61%). Colposcopy was 0.73 sensitive at detecting CIN2+ (95% confidence interval[CI]: 0.71, 0.75), with higher sensitivity (0.77) observed in HPV16+ women (95% CI: 0.74, 0.80) compared to HPV16- women (0.68, 95% CI: 0.64, 0.71). Distributions of hrHPV genotypes, CIN, and type-specific CIN in Chinese mainland hrHPV+ women referred to colposcopy were investigated for the first time. Distributions were found to be age-dependent and colposcopic performance appears related to HPV genotypes. These findings could be used to improve the management of women referred to colposcopy., (© 2024 Wiley Periodicals LLC.)

Background: The high prevalence of chronic obstructive pulmonary disease (COPD) in coronary artery disease (CAD) has been acknowledged over the past decade, although the cause/s remain uncertain due to differences in diagnoses. COPD has also become a leading CAD comorbidity, although again little is known about its interactions. This meta-analysis explored COPD prevalence in the global CAD population, as well as the influence of COPD on CAD., Methods: PubMed, Web of Science, Embase, and grey literature were searched until 26th November 2021. The prevalence of COPD was calculated, and data were grouped according to COPD diagnostic methods, interventions, region, economic status, etc. Outcomes including all-cause death, cardiac death, myocardial infarction, revascularization, stroke, heart failure, and respiratory failure were analyzed. This study was registered with PROSPERO (CRD No.42021293270)., Results: There was an average prevalence of 14.2% for COPD in CAD patients (95% CI: 13.3-15.1), with diagnostics of COPD through spirometry, International Classification of the Diseases (ICD codes), and self-reported methods. Comorbid COPD-CAD patients were more likely to be smokers and suffer from cardiovascular and respiratory complications (all odds ratios [OR] > 1). COPD-CAD has higher mortality (hazard ratio [HR] 2.81, 95% CI: 2.40-3.29), and myocardial infarction, stroke, and respiratory failure rates (all HR > 1). Coronary artery bypass graft (CABG) reduces the need for revascularization (HR 0.43, 95% CI: 0.20-0.94) compared to percutaneous coronary intervention (PCI), without increasing mortality., Conclusions: The global prevalence of COPD is particularly high in CAD patients. COPD-CAD patients are more likely to encounter cardiovascular and respiratory complications and endure poorer outcomes. Limited evidence suggests that CABG may reduce the need for revascularization without increasing mortality, although further research is required to confirm these observations., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 The Author(s). Published by IMR Press.)

Objective: To assess prognostic differences between primary and progressive muscle-invasive bladder cancer (MIBC) following radical cystectomy., Material and Methods: The Surveillance, Epidemiology, and End Results (SEER) database was used to abstract MIBC data following radical cystectomy from 2000 to 2019. Patients were classified as either 'Primary' MIBC (defined as the presentation of muscle-invasive disease at initial diagnosis) or 'Progressive' MIBC (defined as a non-muscle invasive disease that later progressed to MIBC). Baseline characteristics for the two groups were balanced using a propensity score overlap weight (PSOW) technique. Survival differences between the two groups were analyzed using Kaplan-Meier's plots and log-rank tests. Cox's proportional hazard regression was used to assess risk factors associated with overall survival (OS) and cancer-specific survival (CSS)., Results: Six thousand six hundred thirty-two MIBC patients were identified in the SEER database. Among them, 83.3% ( n =5658) were considered primary MIBC patients, and 16.7% ( n =974) were categorized as progressive MIBC patients. Distribution of baseline covariates, including age, sex, race, T stage, N stage, tumour grade, marital status, and chemotherapy, were well-balanced after PSOWs were applied. After stable PSOW adjustments, Kaplan-Meier survival analysis showed that the CSS for progressive MIBC [hazard ratio (HR)=1.25, 95% confidence interval (CI): 1.12-1.38, P <0.001) was poorer than the primary MIBC group. However, the difference in OS (HR=1.08, 95% CI: 0.99-1.18) was not significant ( P =0.073). Multivariate analysis also suggested that patients with progressive MIBC have significantly poorer CSS (HR=1.24, 95% CI: 1.19-1.38, P <0.001) but not OS (HR=1.08, 95% CI: 0.99-1.18, P =0.089)., Conclusion: CSS for progressive MIBC patients appears worse than for those with primary MIBC. This highlights the need to direct more resources for this patient population and particularly for high-risk cases of non-MIBC, where timely radical surgery will improve patients prognoses., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The characteristics of cytokine/chemokine(CK) profiles across different courses of chronic hepatitis B virus infection and the effects of NAs antiviral therapy on cytokine profiles remain unclear., Methods: This report provides evidence from 383 patients with chronic HBV infection. The Luminex multiple cytokine detection technology was used to detect CK profiles. The predictive power of CKs across course of disease was assessedusing univariate analyses and with receiver operating characteristic (ROC) curves., Results: Compared to healthy control (HC), expression levels of interleukin 6 (IL)-6, IL-8, IL-21, matrix metalloproteinases (MMP)-2 and tumor necrosis factor receptor (TNFR)-1 showed a significant increasing trend during chronic HBV infection. IL-23 and IL-33 increased respectively in chronic hepatitis B patients (CHB). interferon (IFN)-gamma and TNF-α changed significantly only in liver cirrhosis (LC) patients. Whereas, myeloid-related markers decreased dramatically in those with hepatocellular carcinoma (HCC). The ROC result suggests that combining IL-6, IL-8, CXCL9 and CXCL13 into a nomogram has closely correlation with HCC during chronic HBV infection. In addition, nucleotide analogues (NAs) antiviral treatments are capable of recoveringnormal liver functions and significantly reducing the viral loads, however, they seem to have a limited effect in changing CKs, especially specific antiviral factors., Conclusion: The differential CK and virological markers may serve as potential indicators of distinct immune statuses in chronic HBV infection. They also underscore the varying efficacy and limitations of NAs antiviral therapies. This next step would to break new ground in the optimization of current anti-HBV treatment programs although this requires further research., 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 © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Excessive weight gain and obesity are widely accepted as risk factors for diabetes mellitus, and the age at which obesity onsets may be related to the development of cardiovascular diseases and certain cancers. Here, we aimed to investigate associations between the onset-age of overweight/obesity and risk of developing diabetes mellitus in China., Methods: 42,144 people with the normal weight range and without diabetes at baseline, were enrolled from the Kailuan cohort which began on the 1 st June 2006. All participants were followed-up, biennially, until 31 st December 2017. During follow-up, 11,220 participants had become overweight/obese. For each case, one normal-weight control was matched according to age ( ± 1 year) and sex. Our final analysis included 10,858 case-control pairs. An age-scaled Cox model was implemented to estimate hazard ratios (HR) with corresponding 95% confidence intervals (CI) for diabetes mellitus incidence across age-groups., Results: At a median follow-up of 5.46 years, 1,403 cases of diabetes mellitus were identified. After multivariate adjustments, age-scaled Cox modelling suggested that risk gradually attenuated with every 10 year increase in age of onset of overweight/obesity. Diabetes mellitus adjusted HRs (aHRs) for new-onset overweight/obesity at <45years, 45-54 years, and 55-64 years were 1.47 (95%CI, 1.12-1.93), 1.38 (95%CI, 1.13-1.68), 1.32 (95%CI, 1.09-1.59), respectively. However, new-onset of overweight/obesity at ≥65 years did not relate to diabetes mellitus (aHR, 1.20; 95%CI, 0.92-1.57). This trend was not observed in women or the new-onset obesity subgroup but was evident in men and the new overweight onset subgroup., Conclusion: Participants with early onset of excessive weight gain issues are at considerably higher risk of developing diabetes mellitus compared to those who maintain a normal weight., Competing Interests: The 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., (Copyright © 2023 Fang, Yuan, Li, Seery, Chen, Cai, Huang, Wang, Wu, Chen, Li, Wu and Chen.)

Background: Relapses frequently occur following CD19-directed chimeric antigen receptor (CAR) T-cell treatment for relapsed or refractory B-cell acute lymphocytic leukaemia in children. We aimed to assess the activity and safety of sequential CD19-directed and CD22-directed CAR T-cell treatments., Methods: This single-centre, single-arm, phase 2 trial, done at Beijing GoBroad Boren Hospital, Beijing, China, included patients aged 1-18 years who had relapsed or refractory B-cell acute lymphocytic leukaemia with CD19 and CD22 positivity greater than 95% and an Eastern Cooperative Oncology Group performance status of 0-2. Patients were initially infused with CD19-directed CAR T cells intravenously, followed by CD22-directed CAR T-cell infusion after minimal residual disease-negative complete remission (or complete remission with incomplete haematological recovery) was reached and all adverse events (except haematological adverse events) were grade 2 or better. The target dose for each infusion was 0·5 × 10 6 to 5·0 × 10 6 cells per kg. The primary endpoint was objective response rate at 3 months after the first infusion. Secondary endpoints were duration of remission, event-free survival, disease-free survival, overall survival, safety, pharmacokinetics, and B-cell quantification. The prespecified activity analysis included patients who received the target dose and the safety analysis included all treated patients. This study is registered with ClinicalTrials.gov, NCT04340154, and enrolment has ended., Findings: Between May 28, 2020, and Aug 16, 2022, 81 participants were enrolled, of whom 31 (38%) were female and 50 (62%) were male. Median age was 8 years (IQR 6-10), all patients were Asian. All 81 patients received the first infusion and 79 (98%) patients received sequential infusions, CD19-directed CAR T cells at a median dose of 2·7 × 10 6 per kg (IQR 1·1 × 10 6 to 3·7 × 10 6 ) and CD22-directed CAR T cells at a median dose of 2·2 × 10 6 per kg (1·1 × 10 6 to 3·7 × 10 6 ), with a median interval of 39 days (37-41) between the two infusions. 62 (77%) patients received the target dose, including two patients who did not receive CD22 CAR T cells. At 3 months, 60 (97%, 95% CI 89-100) of the 62 patients who received the target dose had an objective response. Median follow-up was 17·7 months (IQR 11·4-20·9). 18-month event-free survival for patients who received the target dose was 79% (95% CI 66-91), duration of remission was 80% (68-92), and disease-free survival was 80% (68-92) with transplantation censoring; overall survival was 96% (91-100). Common adverse events of grade 3 or 4 between CD19-directed CAR T-cell infusion and 30 days after CD22-directed CAR T-cell infusion included cytopenias (64 [79%] of 81 patients), cytokine release syndrome (15 [19%]), neurotoxicity (four [5%]), and infections (five [6%]). Non-haematological adverse events of grade 3 or worse more than 30 days after CD22-directed CAR T-cell infusion occurred in six (8%) of 79 patients. No treatment-related deaths occurred. CAR T-cell expansion was observed in all patients, with a median peak at 9 days (IQR 7-14) after CD19-directed and 12 days (10-15) after CD22-directed CAR T-cell infusion. At data cutoff, 35 (45%) of 77 evaluable patients had CAR transgenes and 59 (77%) had B-cell aplasia., Interpretation: This sequential strategy induced deep and sustained responses with an acceptable toxicity profile, and thus potentially provides long-term benefits for children with this condition., Funding: The National Key Research & Development Program of China, the CAMS Innovation Fund for Medical Sciences (CIFMS), and the Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests AHC is employed by, holds leadership in, and has stock and other ownership interests in Shanghai YaKe Biotechnology. XF has a consulting or advisory role for Beijing Health-Biotech Biotechnology. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Colposcopy is a cornerstone of cervical cancer prevention; however, there is a global shortage of colposcopists. It is challenging to train a sufficient number of colposcopists through in-person methods, which hinders our ability to adequately diagnose and manage positive cases. A digital platform is needed to make colposcopy training more efficient, scalable, and sustainable; however, current online training programs are generally based on didactic curricula that do not incorporate image analysis training. In addition, long-term assessments of online training are not readily available. Therefore, innovative digital training and an assessment of its effectiveness are needed., Objective: This study aimed to evaluate the short- and long-term effects of DECO (an online Digital Education Tool for Colposcopy) on trainees' colposcopy competencies and confidence., Study Design: DECO can be used both on laptops and smartphones and comprises 4 training modules (image interpretation; terminology learning; video teaching; and collection of guidelines and typical cases) and 2 test modules. DECO was tested through a pre-post study between September and November 2022. Participants were recruited in China, and DECO training lasted 12 days. Trainees initially learned basic theory before completing training using 200 image-based cases. Pretest, posttest, and follow-up testing included 20 distinct image-based questions, and was conducted on Days 0, 13, and 60. Primary outcomes were competence and confidence scores. Secondary measures were response distributions for colposcopic diagnoses, biopsies, and DECO training satisfaction. Multilevel modeling was used to determine improvement from baseline to posttraining and follow-up for the outcomes of interest., Results: Among 402 participants recruited, 96.8% (n=389) completed pretesting, 84.1% (n=338) posttesting, and 75.1% (n=302) follow-up testing. Colposcopic competence and confidence increased across this study. Diagnostic scores improved on average from 55.3 (53.7-56.9) to 70.4 (68.9-71.9). The diagnostic accuracy for normal/benign lesions, low-grade squamous intraepithelial lesions, and high-grade squamous intraepithelial lesions or worse increased by 16.9%, 13.1%, and 16.9%, respectively. Mean confidence scores increased from 48.1 (45.6-50.6) to 56.2 (54.5-57.9). These improvements remained evident 2 months after training. Trainees were also satisfied with DECO overall. Most found DECO to be scientific (82.5%), easy to use (75.2%), and clinically useful (98.4%), and would recommend it to colleagues (93.2%)., Conclusion: DECO is a useful, acceptable digital education tool that improves colposcopy competencies and confidence. DECO could make colposcopy training more efficient, scalable, and sustainable because there are no geographic or time limitations. Therefore, DECO could be used to alleviate the shortage of trained colposcopists around the world., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Individual responses to behavioural weight loss interventions can vary significantly, and a better understanding of the factors associated with successful treatment might help to target interventions for those who will benefit the most. We sought to identify demographic and clinical characteristics that predicted intervention "success" (defined as ≥5% weight loss) and other health gains in patients with severe obesity attending a ten-week structured lifestyle modification programme., Methods: We conducted a prospective cohort study of all 1122 patients (751 (66.9%) female, mean age 47.3 ± 11.9 years, mean body mass index (BMI) 46.7 ± 7.8 kgm -2 ) referred from our hospital-based obesity clinic, who started the structured lifestyle programme between 2012-2019. We compared routine clinical measures such as weight, fitness, blood pressure, lipids and HbA1c at baseline and follow-up. We also used validated questionnaires to quantify anxiety, depression and health-related quality of life., Results: Of 1122 patients who started, 877 (78.2%) completed the programme and attended for follow up. Of these, 12.8% lost ≥5% body weight. The amount of weight lost was a strong and consistent predictor of improvements in metabolic, cardiovascular, and mental health, even after adjusting for age, sex, programme attendance and baseline fitness. Older age, male sex, being physically active and having lower anxiety and depression scores at baseline predicted greater weight loss. Younger age, depression and longer wait time to start the intervention were associated with drop-out., Conclusions: In adults with severe obesity completing a structured lifestyle modification programme, older age and good mental health were associated with programme completion and attaining ≥5% weight loss. The magnitude of weight lost was a strong predictor of improvements in cardiovascular, metabolic and mental health associated with programme completion., Competing Interests: FF has served on Data Safety Monitoring Boards for the LEAP and LEGEND randomised controlled trials of low carbohydrate dietary interventions, run by the University of Michigan, and as a paid grant reviewer for the Danish Diabetes Academy. 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., (Copyright © 2023 Finucane, Gibson, Hughes, Murphy, Hynes, Harris, McGuire, Hynes, Collins, Cradock, Seery, Jones, O’Brien and O’Donnell.)

The role of perfluoroalkyl and polyfluoroalkyl substances (PFAS) as thyroid carcinogens is unclear. Therefore, we intended to identify associations between each PFAS congener and their mixture with thyroid cancer risk. This case-control study of thyroid cancer was conducted in Shijiazhuang, Hebei Province, China. Three hundred participants were recruited from January to May 2022 and were matched according to sex and age. Twelve PFAS were assessed using ultra-high-performance liquid chromatography-tandem mass spectrometry. Associations between PFAS congeners and thyroid cancer risk were considered under conditional logistic regression analysis and a restricted cubic spline model. Mixture effects were also assessed with quantile g-computation and a Bayesian kernel machine regression model. Compared to the first tertile, third tertile PFOA, PFNA, PFHxS, PFDA, and PFUnDA concentrations were associated with lower thyroid cancer risk (OR PFOA : 0.32, 95% confidence interval (CI): 0.15-0.69; OR PFNA : 0.18, 95% CI: 0.07-0.46; OR PFHxS : 0.37, 95% CI: 0.15-0.92; OR PFDA : 0.07, 95% CI: 0.02-0.23; OR PFUnDA : 0.12, 95% CI: 0.05-0.30) after adjusting for confounding factors. PFNA, PFDA, and PFUnDA had a negative dose-response relationship with thyroid cancer risk. Mixture analysis also showed that thyroid cancer risk is negatively associated with the overall mixture and carboxylates. In the overall mixture, PFOS and PFDA contributed most to positive and negative changes in thyroid cancer risk, respectively. However, PFOS, PFNA, PFDA, and PFUnDA were of equally high importance. This study is the first to confirm the effects of the PFAS mixture on thyroid cancer, and further large-scale prospective studies are still warranted to test these inverse associations., 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 © 2023 Elsevier Ltd. All rights reserved.)

Population-based cervical cytology screening techniques are demanding and laborious and have relatively poor diagnostic accuracy. In this study, we present a cytologist-in-the-loop artificial intelligence (CITL-AI) system to improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening. The artificial intelligence (AI) system was developed using 8000 digitalized whole slide images, including 5713 negative and 2287 positive cases. External validation was performed using an independent, multicenter, real-world data set of 3514 women, who were screened for cervical cancer between 2021 and 2022. Each slide was assessed using the AI system, which generated risk scores. These scores were then used to optimize the triaging of true negative cases. The remaining slides were interpreted by cytologists who had varying degrees of experience and were categorized as either junior or senior specialists. Stand-alone AI had a sensitivity of 89.4% and a specificity of 66.4%. These data points were used to establish the lowest AI-based risk score (ie, 0.35) to optimize the triage configuration. A total of 1319 slides were triaged without missing any abnormal squamous cases. This also reduced the cytology workload by 37.5%. Reader analysis found CITL-AI had superior sensitivity and specificity compared with junior cytologists (81.6% vs 53.1% and 78.9% vs 66.2%, respectively; both with P < .001). For senior cytologists, CITL-AI specificity increased slightly from 89.9% to 91.5% (P = .029); however, sensitivity did not significantly increase (P = .450). Therefore, CITL-AI could reduce cytologists' workload by more than one-third while simultaneously improving diagnostic accuracy, especially compared with less experienced cytologists. This approach could improve the accuracy and efficiency of abnormal cervical squamous cell detection in cervical cancer screening programs worldwide., (Copyright © 2023. Published by Elsevier Inc.)

Introduction: Cytology-based triaging is commonly used to manage the care of women with positive human papillomavirus (HPV) results, but it suffers from subjectivity and a lack of sensitivity and reproducibility. The diagnostic performance of an artificial intelligence-enabled liquid-based cytology (AI-LBC) triage approach remains unclear. Here, we compared the clinical performance of AI-LBC, human cytologists and HPV16/18 genotyping at triaging HPV-positive women., Material and Methods: HPV-positive women were triaged using AI-LBC, human cytologists and HPV16/18 genotyping. Histologically confirmed cervical intraepithelial neoplasia grade 2/3 or higher (CIN2+/CIN3+) were accepted as thresholds for clinical performance assessments., Results: Of the 3514 women included, 13.9% (n = 489) were HPV-positive. The sensitivity of AI-LBC was comparable to that of cytologists (86.49% vs 83.78%, P = 0.744) but substantially higher than HPV16/18 typing at detecting CIN2+ (86.49% vs 54.05%, P = 0.002). While the specificity of AI-LBC was significantly lower than HPV16/18 typing (51.33% vs 87.17%, P < 0.001), it was significantly higher than cytologists at detecting CIN2+ (51.33% vs 40.93%, P < 0.001). AI-LBC reduced referrals to colposcopy by approximately 10%, compared with cytologists (51.53% vs 60.94%, P = 0.003). Similar patterns were also observed for CIN3+., Conclusions: AI-LBC has equivalent sensitivity and higher specificity compared with cytologists, with more efficient colposcopy referrals for HPV-positive women. AI-LBC could be particularly useful in regions where experienced cytologists are few in number. Further investigations are needed to determine triaging performance through prospective designs., (© 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).)