Genotype, cervical intraepithelial neoplasia, and type-specific cervical intraepithelial neoplasia distributions in hrHPV+ cases referred to colposcopy: A multicenter study of Chinese mainland women.

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.

Understanding the influence of cytokines in intrauterine hepatitis B transmission: A cross-sectional study in China.

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.

Cytokine profiles and virological markers highlight distinctive immune statuses, and effectivenesses and limitations of NAs across different courses of chronic HBV infection.

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.

Assessing colposcopy competencies in medically underserved communities: a multi-center study in China.

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.

The impact of hyperkalemia on ICU admission and mortality: a retrospective study of Chinese emergency department data.

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.

Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study.

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 × 106 to 5·0 × 106 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 × 106 per kg (IQR 1·1 × 106 to 3·7 × 106) and CD22-directed CAR T cells at a median dose of 2·2 × 106 per kg (1·1 × 106 to 3·7 × 106), 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.

Improving the Accuracy and Efficiency of Abnormal Cervical Squamous Cell Detection With Cytologist-in-the-Loop Artificial Intelligence.

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.

Developing a predictive nomogram for colposcopists: a retrospective, multicenter study of cervical precancer identification in China.

BACKGROUND: Colposcopic examination with biopsy is the standard procedure for referrals with abnormal cervical cancer screening results; however, the decision to biopsy is controvertible. Having a predictive model may help to improve high-grade squamous intraepithelial lesion or worse (HSIL+) predictions which could reduce unnecessary testing and protecting women from unnecessary harm. METHODS: This retrospective multicenter study involved 5,854 patients identified through colposcopy databases. Cases were randomly assigned to a training set for development or to an internal validation set for performance assessment and comparability testing. Least Absolute Shrinkage and Selection Operator (LASSO) regression was used to reduce the number of candidate predictors and select statistically significant factors. Multivariable logistic regression was then used to establish a predictive model which generates risk scores for developing HSIL+. The predictive model is presented as a nomogram and was assessed for discriminability, and with calibration and decision curves. The model was externally validated with 472 consecutive patients and compared to 422 other patients from two additional hospitals. RESULTS: The final predictive model included age, cytology results, human papillomavirus status, transformation zone types, colposcopic impressions, and size of lesion area. The model had good overall discrimination when predicting HSIL + risk, which was internally validated (Area Under the Curve [AUC] of 0.92 (95%CI 0.90-0.94)). External validation found an AUC of 0.91 (95%CI 0.88-0.94) across the consecutive sample, and 0.88 (95%CI 0.84-0.93) across the comparative sample. Calibration suggested good coherence between predicted and observed probabilities. Decision curve analysis also suggested this model would be clinically useful. CONCLUSION: We developed and validated a nomogram which incorporates multiple clinically relevant variables to better identify HSIL + cases during colposcopic examination. This model may help clinicians determining next steps and in particular, around the need to refer patients for colposcopy-guided biopsies.

Colposcopic accuracy in diagnosing squamous intraepithelial lesions: a systematic review and meta-analysis of the International Federation of Cervical Pathology and Colposcopy 2011 terminology.

BACKGROUND: Colposcopy is an important tool in diagnosing cervical cancer, and the International Federation of Cervical Pathology and Colposcopy (IFCPC) issued the latest version of the guidelines in 2011. This study aims to systematically assess the accuracy of colposcopy in predicting low-grade squamous intraepithelial lesions or worse (LSIL+) / high-grade squamous intraepithelial lesions or worse (HSIL+) under the 2011 IFCPC terminology. METHODS: We performed a systematic review and meta-analysis, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched for studies about the performance of colposcopy in diagnosing cervical intraepithelial neoplasia under the new IFCPC colposcopy terminology from PubMed, Embase, Web of Science and the Cochrane database. Data were independently extracted by two authors and an overall diagnostic performance index was calculated under two colposcopic thresholds. RESULTS: Totally, fifteen articles with 22,764 participants in compliance with the criteria were included in meta-analysis. When colposcopy was used to detect LSIL+, the combined sensitivity and specificity were 0.92 (95% CI 0.88-0.95) and 0.51 (0.43-0.59), respectively. When colposcopy was used to detect HSIL+, the combined sensitivity and specificity were 0.68 (0.58-0.76) and 0.93 (0.88-0.96), respectively. CONCLUSION: In accordance with the 2011 IFCPC terminology, the accuracy of colposcopy has improved in terms of both sensitivity and specificity. Colposcopy is now more sensitive with LSIL+ taken as the cut-off value and is more specific to HSIL+. These findings suggest we are avoiding under- or overdiagnosis both of which impact on patients' well-being.

Enhancing colposcopy training using a widely accessible digital education tool in China.

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.

A Retrospective, Nested Case-Control Study to Develop a Biomarker-Based Model for ARDS Diagnostics.

BACKGROUND: Several biomarkers could be intercalated with traditional measures to improve ARDS diagnostics. METHODS: There were 211 ICU patients enrolled in this retrospective, nested case-control study. Participants were divided into an ARDS (n = 79) and non-ARDS (n = 132) groups, according to the Berlin criteria. Patient characteristics, vital signs, and laboratory tests were collected within three hours of admission. CC16, Ang-2, sRAGE, HMGB1, and SPD were measured within three hours and again at 24 hours, after admission to ICU. Receiver Operating Characteristic curves and multivariate logistic regression analyses were applied for predictive purposes. RESULTS: C-reactive protein (CRP), NT-proBNP, and pH values were intercalated with five established ARDS indicators, and the PaO2/FiO2 ratio. Only four potential indicators were analyzed, with CRP having high diagnostic value. Areas under curve (AUC) were as follows: CC16 (AUC: 0.752; 95% CI 0.680 - 0.824), Ang-2 (AUC: 0.695; 95% CI 0.620 - 0.770), HMGB1 (AUC: 0.668; 95% CI 0.592 - 0.744), sRAGE (AUC: 0.665; 95% CI 0.588 - 0.743), CRP (AUC: 0.701; 95% CI 0.627 - 0.776). No single indicator improved upon the PaO2/FiO2 ratio which had an AUC: 0.844 (95% CI 0.789 - 0.898). However, when the binary logistic model was transformed and the model was constructed, the AUC increased from 0.647 (95% CI 0.568 - 0.726) to 0.911 (95% CI 0.864 - 0.946). Among the combinations tested, PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1 resulted in the highest AUC of 0.910 (95% CI 0.863 - 0.945), although there are other factors which must be considered. CONCLUSIONS: A combination of biomarkers could enhance ARDS diagnostics, which has obvious ramifications for patient care and prognosis. It may be possible to develop a predictive ARDS nomogram; however, of the combinations tested here, we tentatively recommend PaO2/FiO2 + CRP + Ang-2 + CC16 + HMGB1. This is because of the cost implications in contrast with benefit involved in utilizing the more elaborate model. Further health economics research is required to consider the opportunity cost for emergency care policy.

Assessing artificial intelligence enabled liquid-based cytology for triaging HPV-positive women: a population-based cross-sectional study.

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.

Endocervical curettage for diagnosing high-grade squamous intraepithelial lesions or worse in women with type 3 transformation zone lesions: a retrospective, observational study.

BACKGROUND: This study aimed to assess the value of endocervical curettage (ECC) in detecting high-grade squamous intraepithelial lesion or worse (HSIL+) in women with type 3 transformation zone (TZ3) lesions, and to identify the clinical characteristics of patients with TZ3 lesions who benefit most from ECC. METHODS: This retrospective, multicenter study included 1,905 women with TZ3 lesions who attended cervical screening in one of seven tertiary hospitals in China between January 2020 and November 2021. All participants had received abnormal results and had been referred to colposcopy. Risk factors were identified through univariate and multifactorial logistic analyses. RESULTS: In total, 20.5% (n = 391) of HSIL+ cases with TZ3 lesions had been diagnosed with biopsy and ECC. ECC detected 0.8% (n = 15) HSIL+ cases otherwise missed by biopsy alone. Multivariate analysis identified four factors which influenced detection performance. The probability of detecting HSIL+ with ECC is 2.653 (95% confidence interval [CI] 1.009-6.977) times greater in women aged 40-49 years and 2.545 (95% CI 0.965-6.716) times greater for those aged 50 years and older compared to those younger than 30 years. The probability of ASC-H (atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion) and HSIL cytologies were respectively 2.415 (95% CI 1.213-4.808) and 2.933 (95% CI 1.648-5.220) times higher than for NILM (negative for intraepithelial lesion or malignancy). Women with human papillomavirus 16/18 infections were 2.299 (95% CI 0.942-5.613) times more likely to be HSIL+. Precancerous lesions were 35.884 (95% CI 12.214-105.426) times more likely in women who had high-grade colposcopic impressions compared to those with normal impressions. CONCLUSIONS: ECC should be performed for patients with ASC-H or HSIL cytologies, human papillomavirus 16/18 infections, and for those with high-grade colposcopic impressions. This will increase the number of HSIL+ cases identified using biopsy by reducing the number of false negatives.

Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

BACKGROUND: A number of publications have demonstrated that deep learning (DL) algorithms matched or outperformed clinicians in image-based cancer diagnostics, but these algorithms are frequently considered as opponents rather than partners. Despite the clinicians-in-the-loop DL approach having great potential, no study has systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. OBJECTIVE: We systematically quantified the diagnostic accuracy of clinicians with and without the assistance of DL in image-based cancer identification. METHODS: PubMed, Embase, IEEEXplore, and the Cochrane Library were searched for studies published between January 1, 2012, and December 7, 2021. Any type of study design was permitted that focused on comparing unassisted clinicians and DL-assisted clinicians in cancer identification using medical imaging. Studies using medical waveform-data graphics material and those investigating image segmentation rather than classification were excluded. Studies providing binary diagnostic accuracy data and contingency tables were included for further meta-analysis. Two subgroups were defined and analyzed, including cancer type and imaging modality. RESULTS: In total, 9796 studies were identified, of which 48 were deemed eligible for systematic review. Twenty-five of these studies made comparisons between unassisted clinicians and DL-assisted clinicians and provided sufficient data for statistical synthesis. We found a pooled sensitivity of 83% (95% CI 80%-86%) for unassisted clinicians and 88% (95% CI 86%-90%) for DL-assisted clinicians. Pooled specificity was 86% (95% CI 83%-88%) for unassisted clinicians and 88% (95% CI 85%-90%) for DL-assisted clinicians. The pooled sensitivity and specificity values for DL-assisted clinicians were higher than for unassisted clinicians, at ratios of 1.07 (95% CI 1.05-1.09) and 1.03 (95% CI 1.02-1.05), respectively. Similar diagnostic performance by DL-assisted clinicians was also observed across the predefined subgroups. CONCLUSIONS: The diagnostic performance of DL-assisted clinicians appears better than unassisted clinicians in image-based cancer identification. However, caution should be exercised, because the evidence provided in the reviewed studies does not cover all the minutiae involved in real-world clinical practice. Combining qualitative insights from clinical practice with data-science approaches may improve DL-assisted practice, although further research is required. TRIAL REGISTRATION: PROSPERO CRD42021281372; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=281372.

Correction: Unassisted Clinicians Versus Deep Learning-Assisted Clinicians in Image-Based Cancer Diagnostics: Systematic Review With Meta-analysis.

[This corrects the article DOI: 10.2196/43832.].

Atherogenic index of plasma for non-diabetic, coronary artery disease patients after percutaneous coronary intervention: a prospective study of the long-term outcomes in China.

BACKGROUND: Non-diabetic coronary artery disease (CAD) patients are thought to encounter metabolic dysfunction and while these changes may be imperceptible to the patient they probably influence outcomes. At present, there is no system to support patients sensing these subtle changes, nor is there an established model for prognoses. The Atherogenic Index of Plasma (AIP) index has already proven useful for atherosclerosis although further research is needed, especially for those without hyperglycemia. METHODS: This is a prospective study of 5538 non-diabetic CAD patients who had received percutaneous coronary intervention (PCI). Participants were assigned to one of three groups according to their AIP index. High AIP index cases were then compared to low index patients according to major adverse cardiac events (MACE). Restricted cubic spline (RCS) analysis was also conducted to investigate interrelations between AIP index levels and hazard ratios (HR) for MACEs. RESULTS: Patients with a high AIP index encountered metabolic dysfunction compared to those with a low AIP index i.e., higher Body Mass Index (BMI), Total Cholesterol (TC), Triglycerides (TG), and uric acid as well as lower HDL-C. Each of the aforementioned interrelations were significant with p values of less than 0.001. There was also a significant increase in the number of MACEs in the high AIP index group compared to the low AIP index group (HR: 1.37, 95% CI 1.04-1.81; p = 0.025). A J-shaped RCS curve highlighted a change in the HR after the 0.18 juncture (HR per SD: 1.20, 95% CI 0.96-1.50). Further subgroup analysis supported the main findings, all with HRs greater than one. CONCLUSION: The AIP index could be used in prognostics for non-diabetic CAD patients 2 years after PCI. The relationship between hazard ratio and the AIP index appears to be J-shaped. Although, further multi-center studies designed for non-diabetic patients with potential metabolic dysfunction should be conducted to determine the value of the AIP index.

Improving colposcopic accuracy for cervical precancer detection: a retrospective multicenter study in China.

BACKGROUND: Colposcopy alone can result in misidentification of high-grade squamous intraepithelial or worse lesions (HSIL +), especially for women with Type 3 transformation zone (TZ) lesions, where colposcopic assessment is particularly imprecise. This study aimed to improve HSIL + case identification by supplementing referral screening results to colposcopic findings. METHODS: This is an observational multicenter study of 2,417 women, referred to colposcopy after receiving cervical cancer screening results. Logistic regression analysis was conducted under uni- and multivariate models to identify factors which could be used to improve HSIL + case identification. Histological diagnosis was established as the gold standard and is used to assess accuracy, sensitivity, and specificity, as well as to incrementally improve colposcopy. RESULTS: Multivariate analysis highlighted age, TZ types, referral screening, and colposcopists' skills as independent factors. Across this sample population, diagnostic accuracies for detecting HSIL + increased from 72.9% (95%CI 71.1-74.7%) for colposcopy alone to 82.1% (95%CI 80.6-83.6%) after supplementing colposcopy with screening results. A significant increase in colposcopic accuracy was observed across all subgroups. Although, the highest increase was observed in women with a TZ3 lesion, and for those diagnosed by junior colposcopists. CONCLUSION: It appears possible to supplement colposcopic examinations with screening results to improve HSIL + detection, especially for women with TZ3 lesions. It may also be possible to improve junior colposcopists' diagnoses although, further psychological research is necessary. We need to understand how levels of uncertainty influence diagnostic decisions and what the concept of "experience" actually is and what it means for colposcopic practice.

Assessing colposcopic accuracy for high-grade squamous intraepithelial lesion detection: a retrospective, cohort study.

BACKGROUND: Inappropriate management of high-grade squamous intraepithelial lesions (HSIL) may be the result of an inaccurate colposcopic diagnosis. The aim of this study was to assess colposcopic performance in identifying HSIL+ cases and to analyze the associated clinical factors. METHODS: Records from 1130 patients admitted to Shenzhen Maternal and Child Healthcare Hospital from 12th January, 2018 up until 30th December, 2018 were retrospectively collected, and included demographics, cytological results, HPV status, transformation zone type, number of cervical biopsy sites, colposcopists' competencies, colposcopic impressions, as well as histopathological results. Colposcopy was carried out using 2011 colposcopic terminology from the International Federation of Cervical Pathology and Colposcopy. Logistic regression modelling was implemented for uni- and multivariate analyses. A forward stepwise approach was adopted in order to identify variables associated with colposcopic accuracy. Histopathologic results were taken as the comparative gold standard. RESULTS: Data from 1130 patient records were collated and analyzed. Colposcopy was 69.7% accurate in identifying HSIL+ cases. Positive predictive value, negative predictive value, sensitivity and specificity of detecting HSIL or more (HSIL+) were 35.53%, 64.47%, 42.35% and 77.60%, respectively. Multivariate analysis highlighted the number of biopsies, cytology, and transformation zone type as independent factors. Age and HPV subtype did not appear to statistically correlate with high-grade lesion/carcinoma. CONCLUSION: Evidence presented here suggests that colposcopy is only 69.7% accurate at diagnosing HSIL. Even though not all HSIL will progress into cancer it is considered pre-cancerous and therefore early identification will save lives. The number of biopsies, cytology and transformation zone type appear to be predictors of misdiagnosis and therefore should be considered during clinical consultations and by way of further research.

Presence of secondary bladder cancer following radical nephroureterectomy for upper tract urothelial carcinoma: characteristics, risk factors, and predictive value.

BACKGROUND: To assess the characteristics, predictive risk factors, and prognostic effect of secondary bladder cancer (SBCa) following radical nephroureterectomy (RNU) in upper tract urothelial carcinoma (UTUC). METHODS: Using the Surveillance, Epidemiology, and End Results database, the authors analyzed clinicopathologic characteristics and survival data from 472 UTUC patients with SBCa after RNU, between 2004 and 2017. Cox's proportional hazard regression model was implemented to identify independent predictors associated with post-recurrence outcomes. The threshold for statistical significance was p < 0.05. RESULTS: In total, 200 Ta-3N0M0 localized UTUC patients with complete data were finally included. With a median follow-up of 71.0 months (interquartile ranges [IQR] 36.0 -103.8 months), 52.5% (n = 105) had died, with 30.5% (n = 61) dying of UTUC. The median time interval from UTUC to SBCa was 13.5 months (IQR 6.0-40.8 months). According to multivariable Cox regression analysis, patients with SBCa located at multiple sites, advanced SBCa stage, higher SBCa grade, elderly age and a shorter recurrence time, encountered worse cancer-specific survival (CSS), all p < 0.05. CONCLUSION: For primary UTUC patients with SBCa after radical surgery, advanced age, multiple SBCa sites, shorter recurrence time, higher SBCa stage, and grade proved to be significant independent prognostic factors of CSS. We ought to pay more attention to SBCa prevention as well as to earlier signs which may increase the likelihood of early detection. Having the ability to manage what may be seen as the superficial SBCa signs may enable us to improve survival but further research is required.

Development and validation of a predictive model for endocervical curettage in patients referred for colposcopy: A multicenter retrospective diagnostic study in China.

Objective: This study aimed to develop a nomogram that can predict occult high-grade squamous intraepithelial lesions or worse (HSIL+) and determine the need for endocervical curettage (ECC) in patients referred for colposcopy. Methods: This retrospective multicenter study included 4,149 patients who were referred to any one of six tertiary hospitals in China for colposcopy between January 2020 and November 2021 because of abnormal screening results. ECC data were extracted from the medical records. Univariate and multivariate logistic regression analyses were performed to identify factors that could predict HSIL+ on ECC. Patients were randomly assigned to a training set or to an internal validation set for performance and comparability testing. The model was externally validated and tested in patients from two additional hospitals. The nomogram was assessed in terms of discrimination and calibration and subjected to decision curve analysis. Results: HSIL+ was found on ECC in 38.8% (n=388) of cases. Our predictive nomogram included age group, cytology, human papillomavirus (HPV) status, visibility of the cervix and colposcopic impression. The nomogram had good overall discrimination, which was internally validated [area under the receiver-operator characteristic (AUC), 0.839; 95% confidence interval (95% CI), 0.773-0.904]. In terms of external validation, the AUC was 0.843 (95% CI, 0.773-0.912) for the consecutive sample and 0.843 (95% CI, 0.783-0.902) for the comparative sample. Calibration analysis suggested good consistency between predicted and observed probabilities. Decision curve analysis suggested this nomogram would be clinically useful with almost the entire range of threshold probabilities. Conclusions: This internally and externally validated nomogram can be easily applied and incorporates multiple clinically relevant variables that can be used to identify patients with occult HSIL+ who need ECC.