Basic Clinical Characteristics Research Articles

Assessment of a multivariable model using MRI-radiomics, age and sex for the classification of hepatocellular adenoma subtypes

ObjectivesNon-invasive subtyping of hepatocellular adenomas (HCA) remains challenging for several subtypes, thus carrying different levels of risks and management. The goal of this study is to devise a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics and to evaluate its diagnostic performance. MethodsThis single-center retrospective case-control study included all consecutive patients with HCA identified within the pathological database from our institution from January 2003 to April 2018 with MRI examination (T2, T1-no injection/injection-arterial-portal); volumes of interest were manually delineated in adenomas and 38 textural features were extracted (LIFEx, v5.10). Qualitative (i.e., visual on MRI) and automatic (computer-assisted) analysis were compared. The prognostic scores of a multivariable diagnostic model based on basic clinical features (age and sex) combined with MRI-radiomics (tumor volume and texture features) were assessed using a cross-validated Random Forest algorithm. ResultsVia visual MR-analysis, HCA subgroups could be classified with balanced accuracies of 80.8 % (I-HCA or ß-I-HCA, the two being indistinguishable), 81.8 % (H-HCA) and 74.4 % (sh-HCA or ß-HCA also indistinguishable). Using a model including age, sex, volume and texture variables, HCA subgroups were predicted (multivariate classification) with an averaged balanced accuracy of 58.6 %, best=73.8 % (sh-HCA) and 71.9 % (ß-HCA). I-HCA and ß-I-HCA could be also distinguished (binary classification) with a balanced accuracy of 73 %. ConclusionMultiple HCA subtyping could be improved using machine-learning algorithms including two clinical features, i.e., age and sex, combined with MRI-radiomics. Future HCA studies enrolling more patients will further test the validity of the model.

Construction of a prognostic model for extensive-stage small cell lung cancer patients undergoing immune therapy in northernmost China and prediction of treatment efficacy based on response status at different time points

Background and purposeRecently, the emergence of immune checkpoint inhibitors has significantly improved the survival of patients with extensive-stage small cell lung cancer. However, not all patients can benefit from immunotherapy; therefore, there is an urgent need for precise predictive markers to screen the population for the benefit of immunotherapy. However, single markers have limited predictive accuracy, so a comprehensive predictive model is needed to better enable precision immunotherapy. The aim of this study was to establish a prognostic model for immunotherapy in ES-SCLC patients using basic clinical characteristics and peripheral hematological indices of the patients, which would provide a strategy for the clinical realization of precision immunotherapy and improve the prognosis of small cell lung cancer patients.MethodsThis research retrospectively collected data from ES-SCLC patients treated with PD-1/PD-L1 inhibitors between March 1, 2019, and October 31, 2022, at Harbin Medical University Cancer Hospital. The study data was randomly split into training and validation sets in a 7:3 ratio. Variables associated with patients’ overall survival were screened and modeled by univariate and multivariate Cox regression analyses. Models were presented visually via Nomogram plots. Model discrimination was evaluated by Harrell’s C index, tROC, and tAUC. The calibration of the model was assessed by calibration curves. In addition, the clinical utility of the model was assessed using a DCA curve. After calculating the total risk score of patients in the training set, patients were stratified by risk using percentile partitioning. The Kaplan–Meier method was used to plot OS and PFS survival curves for different risk groups and response statuses at different milestone time points. Differences in survival time groups were compared using the chi-square test. Statistical analysis software included R 4.1.2 and SPSS 26.ResultsThis study included a total of 113 ES-SCLC patients who received immunotherapy, including 79 in the training set and 34 in the validation set. Six variables associated with poorer OS in patients were screened by Cox regression analysis: liver metastasis (P = 0.001), bone metastasis (P = 0.013), NLR < 2.14 (P = 0.005), LIPI assessed as poor (P < 0.001), PNI < 51.03 (P = 0.002), and LDH ≥ 146.5 (P = 0.037). A prognostic model for immunotherapy in ES-SCLC patients was constructed based on the above variables. The Harrell’s C-index in the training and validation sets of the model was 0.85 (95% CI 0.76–0.93) and 0.88 (95% CI 0.76–0.99), respectively; the AUC values corresponding to 12, 18, and 24 months in the tROC curves of the training set were 0.745, 0.848, and 0.819 in the training set and 0.858, 0.904 and 0.828 in the validation set; the tAUC curves show that the overall tAUC is > 0.7 and does not fluctuate much over time in both the training and validation sets. The calibration plot demonstrated the good calibration of the model, and the DCA curve indicated that the model had practical clinical applications. Patients in the training set were categorized into low, intermediate, and high risk groups based on their predicted risk scores in the Nomogram graphs. In the training set, 52 patients (66%) died with a median OS of 15.0 months and a median PFS of 7.8 months. Compared with the high-risk group (median OS: 12.3 months), the median OS was significantly longer in the intermediate-risk group (median OS: 24.5 months, HR = 0.47, P = 0.038) and the low-risk group (median OS not reached, HR = 0.14, P = 0.007). And, the median PFS was also significantly prolonged in the intermediate-risk group (median PFS: 12.7 months, HR = 0.45, P = 0.026) and low-risk group (median PFS not reached, HR = 0.12, P = 0.004) compared with the high-risk group (median PFS: 6.2 months). Similar results were obtained in the validation set. In addition, we observed that in real-world ES-SCLC patients, at 6 weeks after immunotherapy, the median OS was significantly longer in responders than in non-responders (median OS: 19.5 months vs. 11.9 months, P = 0.033). Similar results were obtained at 12 weeks (median OS: 20.7 months vs 11.9 months, P = 0.044) and 20 weeks (median OS: 20.7 months vs 11.7 months, P = 0.015). Finally, we found that in the real world, ES-SCLC patients without liver metastasis (P = 0.002), bone metastasis (P = 0.001) and a total number of metastatic organs < 2 (P = 0.002) are more likely to become long-term survivors after receiving immunotherapy.ConclusionThis study constructed a new prognostic model based on basic patient clinical characteristics and peripheral blood indices, which can be a good predictor of the prognosis of immunotherapy in ES-SCLC patients; in the real world, the response status at milestone time points (6, 12, and 20 weeks) can be a good indicator of long-term survival in ES-SCLC patients receiving immunotherapy.

Abstract PO5-19-11: A novel portable breast cancer screening method - initial institutional experience

Abstract Background: Breast ultrasound (US) is a remarkable supplementary tool alongside mammography and magnetic resonance imaging (MRI) for the detection of breast lesions. US imaging is a fast, reliable method to identify and localize breast pathology. Innovative technologies that aim to timely identification and prompt diagnosis of suspicious lesions in breast cancer screening remain a clinical need. ATUSA is a B-type rechargeable US, shaped as a wearable device. It uses a linear array of transducers with water acting as a coupling medium that recreates a 3-dimensional image of the scanned breast. The ATUSA portability makes this device a practical breast screening method during a healthcare office visit. We report the initial feasibility of ATUSA to detect breast lesions in an outpatient setting from a trial in progress. Methodology: Interim prospective data from 35 female patients presenting with a mass of equal or greater than 1 cm in size, with a baseline handheld US image and pathology reports that evidenced a cancer diagnosis or a lesion suspicious of malignancy. Breast cancer types included invasive ductal carcinoma (IDC), ductal carcinoma in situ (DCIS) and invasive lobular carcinoma (ILC), invasive mammary carcinoma (IMC) with mixed ductal and lobular features and atypical lobular hyperplasia (ALH). ATUSA and baseline handheld reference US images were cross-referenced from June 2022 to June 2023. Basic demographics, clinical characteristics, mammogram and/or MRI, and pathology reports were included in the analysis. Patients were followed up for a 30-day period to note occurrence of any adverse event (AE). Institutional Review Board (IRB) approved this study (protocol H-42616). Results: The 35 patients had a mean age of 57 years (range: 25 – 79), mean BMI 29.6 kg/m2 (range: 18.1 – 49.3). Mammographic breast density was fibroglandular tissue 15 (42.8%), followed by heterogeneously dense (HD) 13 (3.7%), mixed HD and fibroglandular 1 (2.8%), mildly dense 1 (2.8%), extremely dense 2 (5.7%), and extremely fatty 1 (2.8%). Breast sizes were 1 (2.8 %) A cup, 11 (31.4%) B cups, 1 (2.8%) B – C cups, 5 (14.2%) C cups, 1 (2.8%) C – D cups, 13 (37.1%) D cups, and 3 (8.5%) DD cups. The 35 scanned lesions had a diagnosis (compared with final resected pathology) classified as IDC 18 (51.4 %), DCIS 2 (5.7 %), mixed IDC and DCIS 6 (17.1 %), ILC 3 (8.5 %), IMC with mixed features 2 (5.7 %), IMC with DCIS 1 (2.8 %), ALH 1 (2.8 %), and 2 (5.7 %) benign masses. ATUSA successfully identified 17/35 (48.5 %) lesions from this group as malignant, from which 4 were hard to distinguish due to shadowing artifact and 3 were underestimated in size. A total of 15 (42.8 %) malignant lesions were missed by ATUSA. No AEs related to the ATUSA device were reported. Conclusion: The ATUSA provides the means to produce a good quality US image during a clinic visit or where a facility lacks conventional US imaging. When compared to the handheld US, ATUSA can be safely used in the outpatient setting without the need of trained specialists but requires further development and testing to match conventional breast imaging. Table 1. Basic clinical characteristics &amp; demographics Citation Format: Margarita Riojas-Barrett, Jessica Montalvan, Mary Bajomo, Ivan Marin, Quan Dang Nguyen, Karla A Sepulveda, Elizabeth Bonefas, Alastair Thompson, Stacey Carter. A novel portable breast cancer screening method - initial institutional experience [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-19-11.

Association of obesity and the clinical course of hospitalised COVID-19 survivors.

Obesity is a risk factor for chronic inflammation and severe pulmonary infections. This study aimed to assess the association between obesity and the clinical courses of hospitalised COVID-19 survivors. This cross-sectional study used the Isfahan COVID Cohort (ICC) baseline data. The ICC is an ongoing, 5-year prospective, longitudinal cohort study conducted on hospitalised COVID-19 survivors in affiliated hospitals of the Medical University of Isfahan (MUI), Iran. Patients aged 19 and over throughout Isfahan County were recruited using a consecutive sampling method 1 month after discharge. Demographic and basic characteristics, symptoms and clinical features of these patients were collected and analysed. A total of 3843 hospitalised patients with COVID-19 were included in this study. Regarding the body mass index classification in the general obesity group, the patients with overweight and obesity had more extended hospitalisation and a higher frequency of low O2 saturation compared to the normal weight patients, and the highest frequency of low O2 saturation and more extended hospitalisation was observed in patients with obesity (5.9 ± 3.8 vs. 6.8 ± 5.4 vs. 7.1 ± 5.3, respectively; p = .001 and 59% vs. 64.5% vs. 65.5%; p < .001). Furthermore, individuals with abdominal obesity had a significantly longer duration of hospitalisation compared to the non-abdominal obesity group (6.3 ± 4.6 vs. 7.0 ± 5.3; p < .001). In the fully adjusted model, a significant association was observed between abdominal obesity and an increased occurrence of low oxygen saturation compared to general obesity (odds ratio: 1.25, 95% confidence interval: 1.03-1.44). Obesity was associated with more extended hospitalisation and hypoxia in patients with COVID-19. However, no significant relationship was found between obesity and other clinical courses.

Transthyretin amyloid cardiomyopathy among patients with heart failure and preserved ejection fraction: the AMY score.

Transthyretin 'wild-type' amyloid cardiomyopathy (ATTRwt-CM) is a differential diagnosis of heart failure with preserved ejection fraction (HFpEF). The clinical work-up for ATTRwt-CM is challenging. Considering a combination of clinical variables specific for ATTRwt-CM might aid in identifying patients at risk. Sixty patients (78±6years, 8% female) were diagnosed with ATTRwt-CM by endomyocardial biopsy. Preserved ejection fraction (LVEF >45%) was present in 41 of the patients. Those were 1:1 propensity score age- and sex-matched to a cohort of patients with HFpEF. ATTRwt-CM patients had less obesity (P=0.01) and higher septal thickness (IVSd, P<0.01) as well as more diastolic dysfunction (E/e', P<0.01). On multivariable regression IVSd>14mm, E/e'>14 and absence of obesity (P>0.01 for all) were identified as predictors for ATTRwt-CM. A weighted point-based score was derived with IVSd>14mm=1 point; absence of obesity=2 points; and E/e'>14=3 points. Area under the curve (AUC) for the summation score was 0.91 (0.84-0.97, P<0.01) and a score of more than 3 points predicted ATTRwt-CM with good sensitivity (78%) and specificity (90%). The score was validated in an external cohort of 142 patients with ATTRwt-CM and 419 HFpEF patients showing sufficient accuracy (AUC 0.91, 0.88-0.94, P<0.01). A value greater than 3 points demonstrated a high sensitivity (93%) and a negative predictive value of 97%. A score based on basic clinical and echocardiographic features helps to distinguish ATTRwt-CM from typical HFpEF. This could facilitate the diagnostic work-up for these patients and enable earlier disease screening on a large scale.

Non-O Blood Group Is Associated with High Thrombus Burden and Poor Short- and Long-Term Prognosis in ST-Segment Elevation Myocardial Infarction Patients.

This study investigated how non-O blood groups relate to thrombus burden (TB) and prognosis in ST-segment elevation myocardial infarction (STEMI) patients, aiming to shed light on their association with thrombotic complications in cardiovascular diseases. Retrospectively, 1,180 STEMI patients undergoing primary percutaneous coronary intervention were included. The study population was divided into groups according to TB status and the groups were compared in terms of basic clinical characteristics, laboratory parameters and ABO blood group types. In addition, short-term (30 days) and long-term (12 months) clinical outcomes were assessed to evaluate the prognostic implications. The analysis revealed a significant association between non-O blood groups and increased TB in STEMI patients (p = 0.001). Non-O blood group was independently associated with high TB (OR: 1.726, 95% confidence interval [CI]: 1.279-2.330, p &lt; 0.001). Additionally, patients with non-O blood groups had higher short and long-term mortality rates (hazard ratio [HR]: 2.480, 95% CI: 1.361-4.520, p = 0.003; HR: 2.347, 95% CI: 1.433-3.844, p = 0.001; respectively). This study emphasizes the significance of the ABO blood group system in STEMI outcomes, associating non-O blood groups with higher TB and poorer clinical outcomes. While proposing personalized treatment strategies based on blood group status to improve reperfusion interventions and outcomes, additional trials are needed to comprehensively evaluate their impact.

Microscopy detection and molecular characterisation of Giardia duodenalis infection in outpatients seeking medical care in Egypt.

Giardiosis remains one of the most prevalent enteric parasitic infections globally. Earlier molecular-based studies conducted in Egypt have primarily focused on paediatric clinical populations and most were based on single genotyping markers. As a result, there is limited information on the frequency and genetic diversity of G. duodenalis infections in individuals of all age groups. Individual stool samples (n = 460) from outpatients seeking medical care were collected during January-December 2021 in Kafr El-Sheikh governorate, northern Egypt. Initial screening for the presence of G. duodenalis was conducted by coprological examination. Microscopy-positive samples were further confirmed by real-time PCR. A multilocus sequence typing approach targeted amplification of the glutamate dehydrogenase (gdh), beta-giardin (bg), and triose phosphate isomerase (tpi) genes was used for genotyping purposes. A standardised epidemiological questionnaire was used to gather basic sociodemographic and clinical features of the recruited patients. Giardia duodenalis cysts were observed in 5.4% (25/460, 95% CI: 3.6-7.9) of the stool samples examined by conventional microscopy. The infection was more frequent in children under the age of 10 years and in individuals presenting with diarrhoea but without reaching statistical significance. Stool samples collected during the winter period were more likely to harbour G. duodenalis. All 25 microscopy-positive samples were confirmed by real-time PCR, but genotyping data was only available for 56.0% (14/25) of the isolates. Sequence analyses revealed the presence of assemblages A (78.6%, 11/14) and B (21.4%, 3/14). All assemblage A isolates were identified as sub-assemblage AII, whereas the three assemblage B sequences belonged to the sub-assemblage BIII. Patients with giardiosis presenting with diarrhoea were more frequently infected by the assemblage A of the parasite. This is one of the largest epidemiological studies evaluating G. duodenalis infection in individuals of all age groups in Egypt. Our molecular data suggest that G. duodenalis infections in the surveyed population are primarily of anthropic origin. However, because assemblages A and B are zoonotic, some of the infections identified can have an animal origin. Additional investigations targeting animal (domestic and free-living) and environmental (water) samples are warranted to better understand the epidemiology of giardiosis in Egypt.

Prognostic Value of Neutrophil/Lymphocyte Ratio for Pulmonary Embolism: A Meta-Analysis and External Validation

BackgroundPrognostic value of neutrophil/lymphocyte ratio (NLR) for pulmonary embolism (PE) has been reported in several retrospective studies. The purpose of this investigation was to perform a pooled analysis and external validation of predictive value of NLR. Material and methodPubMed, Embase, and Cochrane databases were searched from inception to November 5, 2022. A random effects model was used. Grade was used to evaluate the certainty of evidence. External validation was conducted in clinical cohorts before and after a propensity scoring matching (PSM). Covariates include basic clinical characteristics, such as age, gender, etc. The value of NLR in prediction model was also evaluated. ResultsA total of 15 studies comprising 5,874 patients were included. Pooled risk ratio (RR) of NLR was 2.33 [95% confidence interval (CI):1.97-2.75], with an area under the curve (AUC) of 0.78 (95% CI:0.74-0.81), a sensitivity of 0.75 (95% CI:0.71-0.79), a specificity of 0.67 (95% CI:0.61-0.73), and a median cut-off value of 5.7. GRADE certainty analysis showed the quality of the evidence was moderate. Before (n=336) and after (n=152) PSM, RR of NLR was 2.69 (95% CI:1.04-6.97) and 6.58 (95% CI:1.99-17.75). A prediction model consisting of NLR, age, D-dimer and simplified pulmonary embolism severity index (sPESI) had an AUC of 0.809 (95% CI:0.738-0.88), a sensitivity of 0.638 (95% CI:0.511,0.745), and a specificity of 0.851 (95% CI:0.709,0.917). Net reclassification index (NRI) (12%, p=0.035) and integrated discrimination improvement (17%, p=0.022) indicated an improvement caused by NLR. ConclusionPrognostic value of NLR for PE was confirmed by meta-analysis and validated in an independent cohort, deserving further clinical application.

Discordant responses of bone formation and absorption markers in Japanese infants with vitamin D deficiency: a comprehensive matched case-control study.

Vitamin D deficiency during infancy has been associated with increased bone turnover rate and bone mineral loss. However, few studies have examined bone turnover markers (BTMs) for both bone formation and resorption in infants with vitamin D deficiency. Here, we analyzed serum concentrations of 25OHD, intact parathormone (iPTH), and BTMs including total alkaline phosphatase (ALP), tartrate-resistant acid phosphatase isoform 5b (TRACP-5b), and serum type I collagen N-telopeptide (NTx) as well as basic clinical characteristics of 456 infants (626 samples) aged less than 12mo born at Saitama City Hospital, Japan (latitude 35.9° North) between January 2021 and December 2022. One hundred sixteen infants (147 samples) were classified as having vitamin D deficiency (25OHD < 12.0ng/mL), and 340 infants (479 samples) had sufficient vitamin D levels (25OHD ≥ 12.0ng/mL). In addition to 25OHD and ALP, both TRACP-5b and sNTx were measured in 331 infants (418 samples), while 90 infants (105 samples) had only TRACP-5b measured and 101 infants (103 samples) had only sNTx measured. Statistical comparison of 104 subjects each in the vitamin D deficiency and sufficiency groups after matching for the background characteristics revealed that the vitamin D deficiency group had significantly higher levels of ALP and iPTH compared with the sufficiency group (P = <.0001, .0012, respectively). However, no significant differences were found in TRACP-5b and NTx levels between the 2 groups (P = .19, .08, respectively). Our findings suggest discordant responses between bone formation and resorption markers in subclinical vitamin D deficiency during infancy.

MRI brain structural and functional networks changes in Parkinson disease with REM sleep behavior disorders.

Rapid eye movement sleep behavior disorder (RBD) is common in individuals with Parkinson's disease (PD). In spite of that, the precise mechanism underlying the pathophysiology of RBD among PD remains unclear. The aim of the present study was to analyze gray matter volumes (GMVs) as well as the changes of functional connectivity (FC) among PD patients with RBD (PD-RBD) by employing a combination of voxel-based morphometry (VBM) and FC methods. A total of 65 PD patients and 21 healthy control (HC) subjects were included in this study. VBM analyses were performed on all subjects. Subsequently, regions with significant different GMVs between PD patients with and without RBD (PD-nRBD) were selected for further analysis of FC. Correlations between altered GMVs and FC values with RBD scores were also investigated. Additionally, receiver operating characteristic (ROC) curves were employed for the evaluation of the predictive value of GMVs and FC in identifying RBD in PD. PD-RBD patients exhibited lower GMVs in the left middle temporal gyrus (MTG) and bilateral cuneus. Furthermore, we observed higher FC between the left MTG and the right postcentral gyrus (PoCG), as well as lower FC between the bilateral cuneus (CUN) and the right middle frontal gyrus (MFG) among PD-RBD patients in contrast with PD-nRBD patients. Moreover, the GMVs of MTG (extending to the right PoCG) was positively correlated with RBD severity [as measured by REM Sleep Behavior Disorder Screening Questionnaire (RBDSQ) score]. Conversely, the FC value between the bilateral CUN and the right MTG in PD-RBD patients was negatively correlated with RBDSQ score. This study revealed the presence replace with GMV and FC changes among PD-RBD patients, which were closely linked to the severity of RBD symptoms. Furthermore, the combination of basic clinical characteristics, GMVs and FC values effectively predicted RBD for individuals with PD.

Systemic immune-inflammation index as a novel hematological marker for predicting the recurrence of deep venous thrombosis.

To determine whether there was a possible predictive relationship between systemic immune-inflammation index (SII) and recurrence of deep venous thrombosis (DVT). A total of 231 patients with DVT who met the study criteria and whose data could be accessed were enrolled to this retrospective single-centered cross-sectional study. Of them 26 patients with DVT recurrence consisted of the study group (Group 1) while remaining 205 cases without recurrence were considered as the control population (Group 2). The patients' basic clinical features and laboratory results from the complete blood count (CBC) test were recorded and compared between groups. Following univariate analyses, a multivariate logistic regression analysis was performed to identify the independent predictors of the recurrence of DVT. Additionally, a receiver-operating characteristic (ROC) curve analysis was performed to detect the cut-off values of the predictors with sensitivity and specificity rates. There were no significant differences between the groups for basic clinical features, except for diabetes mellitus, pulmonary embolism, and atrial fibrillation. Although the univariate analysis revealed that the median values of NLR, PLR, and SII were significantly higher in the DVT recurrence group, only SII was determined to be a significant and independent predictor of DVT recurrence in the multivariate logistic regression analysis. According to ROC curve analysis, SII of 1685 × 103/mm3 constituted the cut-off value for predicting DVT recurrence with 61.5% sensitivity and 76.6% specificity (AUC = 0.686, p = .001). The present study demonstrated for the first time in the literature that SII significantly predicted the recurrence of DVT.

Whole-tumor histogram analysis of synthetic magnetic resonance imaging predicts isocitrate dehydrogenase mutation status in gliomas.

An accurate assessment of isocitrate dehydrogenase (IDH) status in patients with glioma is crucial for treatment planning and is a key factor in predicting patient outcomes. In this study, we investigated the potential value of whole-tumor histogram metrics derived from synthetic magnetic resonance imaging (MRI) in distinguishing IDH mutation status between astrocytoma and glioblastoma. In this prospective study, 80 glioma patients were enrolled from September 2019 to June 2022. All patients underwent pre- and post-contrast synthetic MRI scan protocol. Immunohistochemistry (IHC) staining or gene sequencing were used to assess IDH mutation status in tumor tissue samples. Whole-tumor histogram metrics, including T1, T2, proton density (PD), etc., were extracted from the quantitative maps, while radiological features were assessed by synthetic contrast-weighted maps. Basic clinical features of the patients were also evaluated. Differences in clinical, radiological, and histogram metrics between IDH-mutant astrocytoma and IDH-wildtype glioblastoma were analyzed using univariate analyses. Variables with statistical significance in univariate analysis were included in multivariate logistic regression analysis to develop the combined model. Receiver operating characteristic (ROC) and area under the curve (AUC) were used to assess the diagnostic performance of metrics and models. The histopathologic analysis revealed that of the 80 cases, 41 were classified as IDH-mutant astrocytoma and 39 as IDH-wildtype glioblastoma. Compared to IDH-wildtype glioblastoma, IDH-mutant astrocytoma showed significantly lower T1 [10th percentile (10th), mean, and median] and post-contrast PD (10th, 90th percentile, mean, median, and maximum) values as well as higher post-contrast T1 (cT1) (10th, mean, median, and minimum) values (all P<0.05). The combined model (T1-10th + cT1-10th + age) was developed by integrating the independent influencing factors of IDH-mutant astrocytoma using the multivariate logistic regression. The diagnostic performance of this model [AUC =0.872 (0.778-0.936), sensitivity =75.61%, and specificity =89.74%] was superior to the clinicoradiological model, which was constructed using age and enhancement degree (AUC =0.822 (0.870-0.898), P=0.035). The combined model constructed using histogram metrics derived from synthetic MRI could be a valuable preoperative tool to distinguish IDH mutation status between astrocytoma and glioblastoma, and subsequently, could assist in the decision-making process of pretreatment.

Angiographic characteristics of coronary artery disease in patients undergoing diagnostic coronary angiography at a tertiary hospital in Tanzania

BackgroundCoronary artery disease (CAD) is an important cause of global burden of disease. There is a paucity of data on the burden and risk factors for CAD in sub-Saharan Africa (SSA), despite the rising trends in the shared risk factors across regions. The recent introduction of cardiac catheterization laboratory services in SSA could shed light on the burden of CAD in the region. We aimed to assess the angiographic characteristics among patients undergoing diagnostic coronary angiography (CAG) at a single tertiary care hospital in Tanzania.MethodsThis study was a retrospective chart review. A total of 728 patients ≥ 18 years of age who underwent CAG from January 2020 to December 2022 were recruited into the study. Basic demographic variables, risk factors and clinical characteristics including CAG findings were obtained from the registry. In addition, CAG images were retrieved for assessment of angiographic features. The luminal vessel stenosis was assessed based on eyeballing and the degree of obstruction was agreed by two independent and experienced cardiologists. The coronary stenosis of ≥ 50% was considered significant for obstructive CAD. The study was approved by the local ethics committee.ResultsOf patients who were recruited into the study, 384 (52.23%) were female. The study participants had a mean age of 59.46 ± 10.83 standard deviation (SD) and mean body mass index (BMI) of 31.18 kg/m2. The prevalence of CAD of any degree was estimated at 24.43% (34.18% in male, 15.50% in female), while that of obstructive CAD was 18.27%. Forty six percent of those with obstructive CAD had multiple vessel disease (MVD). Nearly 77% of patients were found to have ≥ 50–70% luminal stenosis and while those with ≥ 70% luminal coronary artery stenosis constituted 56.65%. Right coronary artery (RCA) was the most commonly affected vessel, accounting for 36.84% when any vessel disease or 56% when single vessel disease were considered. Being 65 years or older and comorbidity with type 2 diabetes (T2D) were independent risk factors for developing CAD.ConclusionThere is a high prevalence of obstructive CAD among patients undergoing diagnostic CAG in Tanzania, with male gender preponderance and increasingly higher in older age, often with severe disease. A large, prospective study is needed to provide epidemiological and clinical data for developing a locally-relevant cardio-preventive strategy for CAD intervention in Tanzania.

A nomogram for predicting liver metastasis in patients with gastric gastrointestinal stromal tumor

BackgroundLiver metastasis (LIM) is an important factor in the diagnosis, treatment, follow-up, and prognosis of patients with gastric gastrointestinal stromal tumor (GIST). There is no simple tool to assess the risk of LIM in patients with gastric GIST. Our aim was to develop and validate a nomogram to identify patients with gastric GIST at high risk of LIM. MethodsPatient data diagnosed as having gastric GIST between 2010 and 2019 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database and randomly divided into training cohort and internal validation cohort in a 7:3 ratio. For external validation, retrospective data collection was performed on patients diagnosed as having gastric GIST at Yunnan Cancer Center (YNCC) between January 2015 and May 2023. Univariate and multivariate logistic regression analyses were used to identify independent risk factors associated with LIM in patients with gastric GIST. An individualized LIM nomogram specific for gastric GIST was formulated based on the multivariate logistic model; its discriminative performance, calibration, and clinical utility were evaluated. ResultsIn the SEER database, a cohort of 2341 patients with gastric GIST was analyzed, of which 173 cases (7.39%) were found to have LIM; 239 patients with gastric GIST from the YNCC database were included, of which 25 (10.46%) had LIM. Multivariate analysis showed tumor size, tumor site, and sex were independent risk factors for LIM (P < .05). The nomogram based on the basic clinical characteristics of tumor size, tumor site, sex, and age demonstrated significant discrimination, with an area under the curve of 0.753 (95% CI, 0.692–0.814) and 0.836 (95% CI, 0.743–0.930) in the internal and external validation cohort, respectively. The Hosmer-Lemeshow test showed that the nomogram was well calibrated, whereas the decision curve analysis and the clinical impact plot demonstrated its clinical utility. ConclusionTumor size, tumor subsite, and sex were significantly correlated with the risk of LIM in gastric GIST. The nomogram for patients with GIST can effectively predict the individualized risk of LIM and contribute to the planning and decision making related to metastasis management in clinical practice.

Analysis of efficacy and safety of daratumumab-containing regimen in relapsed and refractory multiple myeloma patients

Objective: To investigate the efficacy and safety in relapsed and refractory multiple myeloma (RRMM) patients with combination regimen of daratumumab. Methods: The clinical data of 42 RRMM patients admitted to Qingdao Municipal Hospital from December 2020 to November 2023 were retrospectively analyzed, which included 26 males and 16 females, with a median age of 59 (47, 82) years old. According to the number of courses of treatment with Daratumumab, patients were divided into three groups: long course group (≥9 courses, n=21), medium course group (7-8 courses, n=12), and short course group (≤6 courses, n=9). The deadline for follow-up was November 10, 2023, and the follow-up period was 15.6 (6.0, 34.0) months. After completing at least 2 courses of treatment, patients were evaluated for efficacy, including stringent complete response (sCR), complete response (CR), very good partial response (VGPR), partial response (PR), minimal response (MR), stable disease (SD), and progressive disease (PD). Basic clinical characteristics of patients, overall response rate of treatment, and adverse reactions were statistically analyzed. Kaplan-Meier method was used to compare the differences of progression-free survival (PFS) in patients with different courses of treatment. Results: Among the 42 patients, 15 (35.7%) had extramedullary disease or plasmacytic leukemia, 7 (16.6%) had amyloidosis, and 18 (42.9%) had renal insufficiency. In Mayo stage, 25 patients (59.5%) were at high risk of myeloma cytogenetic stratification, 8 patients (19%) were standard risk, 9 patients (21.4%) had no cytogenetic data. There were 16 patients with second-line treatment (38.0%), 13 patients with third-line treatment (31%), and 13 patients with more than fourth-line treatment (31%). All patients received at least 2 courses of treatment, achieving the best degree of disease response in 4 cases of sCR (9.5%), 3 cases of CR (7.1%), 10 cases of VGPR (23.8%), 11 cases of PR (26.2%), and 6 cases of MR (14.2%). The overall response rate (ORR) was 80.9% (34/42). The overall response rate was 100% (21/21) in the long course group, 91.6% (11/12) in the medium course group and 22.2% (2/9) in the short course group. Kaplan-Meier survival analysis showed that the duration of PFS was 5.0 (95%CI: 3.1-6.9) months in the short course group,>8.0 months in the medium course group, and>38.0 months in the long course group, the difference was statistically significant (P<0.05). Grade≥3 adverse reactions were mainly neutropenia (3 cases) and thrombocytopenia (1 case). None of the patients discontinued treatment due to adverse reactions. Conclusion: Treatment of RRMM with a regimen containing Daratumumab requires a longer course of treatment to achieve maximum efficacy and the adverse reactions can be controlled.

Multiphase MRI-Based Radiomics for Predicting Histological Grade of Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a highly heterogeneous cancer. Accurate preoperative prediction of histological grade holds potential for improving clinical management and disease prognostication. To evaluate the performance of a radiomics signature based on multiphase MRI in assessing histological grade in solitary HCC. Retrospective. A total of 405 patients with histopathologically confirmed solitary HCC and with liver gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced MRI within 1 month of surgery. Contrast-enhanced T1-weighted spoiled gradient echo sequence (LAVA) at 1.5 or 3.0 T. Tumors were graded (low/high) according to results of histopathology. Basic clinical characteristics (including age, gender, serum alpha-fetoprotein (AFP) level, history of hepatitis B, and cirrhosis) were collected and tumor size measured. Radiomics features were extracted from Gd-EOB-DTPA-enhanced MRI data. Three feature selection strategies were employed sequentially to identify the optimal features: SelectFromModel (SFM), SelectPercentile (SP), and recursive feature elimination with cross-validation (RFECV). Probabilities of five single-phase radiomics-based models were averaged to generate a radiomics signature. A combined model was built by combining the radiomics signature and clinical predictors. Pearson χ2 test/Fisher exact test, Wilcoxon rank sum test, interclass correlation coefficient (ICC), univariable/multivariable logistic regression analysis, area under the receiver operating characteristic (ROC) curve (AUC), DeLong test, calibration curve, Brier score, decision curve, Kaplan-Meier curve, and log-rank test. A P-value <0.05 was considered statistically significant. High-grade HCCs were present in 33.8% of cases. AFP levels (odds ratio [OR] 1.89) and tumor size (>5 cm; OR 2.33) were significantly associated with HCC grade. The combined model had excellent performance in assessing HCC grade in the test dataset (AUC: 0.801), and demonstrated satisfactory calibration and clinical utility. A model that combined a radiomics signature derived from preoperative multiphase Gd-EOB-DTPA-enhanced MRI and clinical predictors showed good performance in assessing HCC grade. 3 TECHNICAL EFFICACY: Stage 5.

Establishment and efficiency test of a clinical prediction model of bronchopulmonary dysplasia associated pulmonary hypertension in very premature infants

Objective: To develop a risk prediction model for identifying bronchopulmonary dysplasia (BPD) associated pulmonary hypertension (PH) in very premature infants. Methods: This was a retrospective cohort study. The clinical data of 626 very premature infants whose gestational age <32 weeks and who suffered from BPD were collected from October 1st, 2015 to December 31st, 2021 of the Seventh Medical Center of the People's Liberation Army General Hospital as a modeling set. The clinical data of 229 very premature infants with BPD of Hunan Children's Hospital from January 1 st, 2020 to December 31st, 2021 were collected as a validation set for external verification. The very premature infants with BPD were divided into PH group and non PH group based on the echocardiogram after 36 weeks' corrected age in the modeling set and validation set, respectively. Univariate analysis was used to compare the basic clinical characteristics between groups, and collinearity exclusion was carried out between variables. The risk factors of BPD associated PH were further screened out by multivariate Logistic regression, and the risk assessment model was established based on these variables. The receiver operating characteristic (ROC) area under curve (AUC) and Hosmer-Lemeshow goodness-of-fit test were used to evaluate the model's discrimination and calibration power, respectively. And the calibration curve was used to evaluate the accuracy of the model and draw the nomogram. The bootstrap repeated sampling method was used for internal verification. Finally, decision curve analysis (DCA) to evaluate the clinical practicability of the model was used. Results: A total of 626 very premature infants with BPD were included for modeling set, including 85 very premature infants in the PH group and 541 very premature infants in the non PH group. A total of 229 very premature infants with BPD were included for validation set, including 24 very premature infants in the PH group and 205 very premature infants in the non PH group. Univariate analysis of the modeling set found that 22 variables, such as artificial conception, fetal distress, gestational age, birth weight, small for gestational age, 1 minute Apgar score ≤7, antenatal corticosteroids, placental abruption, oligohydramnios, multiple pulmonary surfactant, neonatal respiratory distress syndrome (NRDS)>stage Ⅱ, early pulmonary hypertension, moderate-severe BPD, and hemodynamically significant patent ductus arteriosus (hsPDA) all had statistically significant influence between the PH group and the non PH group (all P<0.05). Antenatal corticosteroids, fetal distress, NRDS >stage Ⅱ, hsPDA, pneumonia and days of invasive mechanical ventilation were identified as predictive variables and finally included to establish the Logistic regression model. The AUC of this model was 0.86 (95%CI 0.82-0.90), the cut-off value was 0.17, the sensitivity was 0.77, and the specificity was 0.84. Hosmer-Lemeshow goodness-of-fit test showed that P>0.05. The AUC for external validation was 0.88, and the Hosmer-Lemeshow goodness-of-fit test suggested P>0.05. Conclusions: A high sensitivity and specificity risk prediction model of PBD associated PH in very premature infants was established. This predictive model is useful for early clinical identification of infants at high risk of BPD associated PH.

Risk factors for recurrence of common bile duct stones after surgical treatment and effect of ursodeoxycholic acid intervention.

Endoscopic retrograde cholangiopancreatography (ERCP) is an accurate diagnostic method for choledocholithiasis and treatment option for stone removal. Additionally, ursodeoxycholic acid (UDCA) can dissolve cholesterol stones and prevent their development and reappearance by lowering the cholesterol concentration in bile. Despite these treatment options, there are still patients who experience stone recurrence. To analyze the risk factors for choledocholithiasis recurrence after ERCP retrograde cholangiopancreatography and the effect of UDCA intervention. The clinical data of 100 patients with choledochal stones who were hospitalized at the Yixing People's Hospital and underwent ERCP for successful stone extraction between June 2020 and December 2022 were retrospectively collected. According to the post-ERCP treatment plan, 100 patients were classified into UDCA (n = 47) and control (n = 53) groups. We aimed to assess the clinical efficacy and rate of relapse in the two patient populations. We then collected information (basic demographic data, clinical characteristics, and serum biochemical indicators) and determined the factors contributing to relapse using logistic regression analysis. Our secondary goal was to determine the effects of UDCA on liver function after ERCP. Compared to the control group, the UDCA group demonstrated a higher clinical effectiveness rate of 92.45% vs 78.72% (P < 0.05). No significant differences were observed in liver function indices, including total bilirubin, direct bilirubin, gamma-glutamyl transpeptidase, alanine aminotransferase, alkaline phosphatase, and aspartate aminotransferase, between the two groups before treatment. After treatment, all liver function indices were significantly reduced. Comparing the control vs UDCA groups, the UDCA group exhibited significantly lower levels of all indices (55.39 ± 6.53 vs 77.31 ± 8.52, 32.10 ± 4.62 vs 45.39 ± 5.69, 142.32 ± 14.21 vs 189.63 ± 16.87, 112.52 ± 14.25 vs 149.36 ± 15.36, 122.61 ± 16.00 vs 171.33 ± 22.09, 96.98 ± 10.44 vs 121.35 ± 11.57, respectively, all P < 0.05). The stone recurrence rate was lower in the UDCA group (13.21%) in contrast with the control group (44.68%). Periampullary diverticula (OR: 6.00, 95%CI: 1.69-21.30), maximum stone diameter (OR: 1.69, 95%CI: 1.01-2.85), stone quantity >3 (OR: 4.23, 95%CI: 1.17-15.26), and positive bile culture (OR: 7.61, 95%CI: 2.07-27.91) were independent factors that influenced the relapse of common bile duct stones after ERCP (P < 0.05). Furthermore, postoperative UDCA was identified as a preventive factor (OR: 0.07; 95%CI: 0.08-0.09). The intervention effect of UDCA after ERCP for common bile duct stones is adequate, providing new research directions and references for the prevention and treatment of stone recurrence.

P219 Prognostic potential of mucosal proteins in Ulcerative Colitis

Abstract Background Better prognostic measures for ulcerative colitis (UC) could significantly advance patient care. While the prognostic capacity of circulating proteins in UC has been explored, the role of mucosal proteins remains largely unknown. We examined mucosal protein markers in patients with incident ulcerative colitis and evaluated their prognostic value. Methods Biopsies from macroscopically inflamed colonic/rectal mucosa of adult patients in the Swedish inception cohort of IBD (SIC IBD) were obtained at diagnosis of UC. Patients were followed prospectively, and clinical data were recorded after 3 and 12 months. Disease course was categorised as indolent or aggressive at 12 months, based on a composite outcome of colectomy, hospital admission for active disease, treatment refractoriness towards ≥2 biological agents; the use of &amp;gt;2 courses of corticosteroids, or a cumulative dose of &amp;gt;2.5 g. Relative estimates of 162 protein markers were assessed in homogenised tissue supernatants, using proximity extension assay technology (Olink Proteomics, Uppsala, Inflammation and Oncology II panel). Mann-Whitney U test, with Benjamini-Hochberg correction was used to identify differentially regulated mucosal proteins in aggressive vs indolent disease course, with a 5% false discovery rate (FDR). Smoothly clipped absolute deviation regularised logistic regression models were used to identify prognostic signatures distinguishing aggressive from indolent disease course. Performance was estimated in a leave-one-out cross-validation and reported as the area under the receiver operating characteristic (ROC) curve (AUC). Results 117 patients provided a macroscopically inflamed colonic/rectal biopsy at diagnosis of UC. Basic demographics and clinical characteristics are presented in Table 1. Relative protein levels of WFdc2 and CCL20 were significantly lower in lysates from patients developing an aggressive course vs patients developing an indolent course, while estimates of MMP1, CCL11, WISP-1, OPG, RSPO3 and VEGFR2 were higher (Figure 1A). Regularized logistic regression identified signatures restricted to 28 proteins, distinguishing aggressive from indolent UC courses, yielding an AUC of 0.68 (95% confidence interval (CI): 0.56-0.80) for left-out samples (Figure 1B). Incorporating extent of inflammation at diagnosis in the model improved the AUC to 0.71 (95% CI: 0.60-0.83). Conclusion We identified prognostic mucosal protein signatures associated with future course of ulcerative colitis by analysing inflamed mucosal biopsies that were obtained at diagnosis. These protein markers may highlight pathways of relevance for ulcerative colitis outcomes.

Transformation to small cell lung cancer is irrespective of EGFR and accelerated by SMAD4-mediated ASCL1 transcription independently of RB1 in non-small cell lung cancer

ObjectivesHistological transformation to small cell lung cancer (SCLC) has been identified as a mechanism of TKIs resistance in EGFR-mutant non-small cell lung cancer (NSCLC). We aim to explore the prevalence of transformation in EGFR-wildtype NSCLC and the mechanism of SCLC transformation, which are rarely understood.MethodsWe reviewed 1474 NSCLC patients to investigate the NSCLC-to-SCLC transformed cases and the basic clinical characteristics, driver gene status and disease course of them. To explore the potential functional genes in SCLC transformation, we obtained pre- and post-transformation specimens and subjected them to a multigene NGS panel involving 416 cancer-related genes. To validate the putative gene function, we established knocked-out models by CRISPR-Cas 9 in HCC827 and A549-TP53-/- cells and investigated the effects on tumor growth, drug sensitivity and neuroendocrine phenotype in vitro and in vivo. We also detected the expression level of protein and mRNA to explore the molecular mechanism involved.ResultsWe firstly reported an incidence rate of 9.73% (11/113) of SCLC transformation in EGFR-wildtype NSCLC and demonstrated that SCLC transformation is irrespective of EGFR mutation status (P = 0.16). We sequenced 8 paired tumors and identified a series of mutant genes specially in transformed SCLC such as SMAD4, RICTOR and RET. We firstly demonstrated that SMAD4 deficiency can accelerate SCLC transition by inducing neuroendocrine phenotype regardless of RB1 status in TP53-deficient NSCLC cells. Further mechanical experiments identified the SMAD4 can regulate ASCL1 transcription competitively with Myc in NSCLC cells and Myc inhibitor acts as a potential subsequent treatment agent.ConclusionsTransformation to SCLC is irrespective of EFGR status and can be accelerated by SMAD4 in non-small cell lung cancer. Myc inhibitor acts as a potential therapeutic drug for SMAD4-mediated resistant lung cancer.9vNWjpNbo9djtsBQF6k7BHVideo