Transrectal (TR) ultrasound guided prostate biopsy and transperineal (TP) ultrasound guided prostate biopsy are the two most commonly used methods to detect prostate cancer, the detection rate of the two biopsy approaches may differ in patients with different clinical characteristics. Here we aimed to compare the prostate cancer detection rate and positive rate of biopsy cores between TR and TP prostate biopsy in patients with different clinical characteristics.We retrospectively analyzed and compared the clinical data of 452 patients underwent TR or TP prostate biopsy in our hospital from June 2017 to September 2021. And patients were stratified according to several clinical characteristic , cancer detection rate and positive rate of biopsy cores were compared in different stratified groups.There was no significant difference in age, PSA level, prostate volume, and PSA density between the TR and TP groups. TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30–80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3–T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1–T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade.TR approach may have advantage in patients with prostate volumes 30–80 mL and T3–T4 stages, while TP approach may have advantage in patients with T1–T2 stages. In 2021. , 5. Tran. , 7.Several studies were performed to compare the detection rates and complications of TR and TP approaches. Firstly, TP biopsy significantly reduces infectious complications compared to TR biopsy –10, as w12 cores biopsy was recommended to achieve the balance between the cancer detection rate and adverse events . In our This study collected 452 patients underwent TR or TP prostate biopsy at the Department of Urology, Zhongnan Hospital of Wuhan University from June 2017 to September 2021, Patients with PSA ≥ 100 ng/mL were excluded because their prostate cancer detection rate was close to 100%. All methods used for analysis in this study were carried out in accordance with the approved regulations of the Medical Ethics Committee, Zhongnan Hospital of Wuhan University. The indications for prostate biopsy are based on ‘Chinese diagnosis and treatment of urological diseases Guide’, including patients with: (1) suspicious lesions detected by digital rectal examination (DRE); (2) suspicious lesions on imaging; (3) PSA > 10 ng/mL; (4) 10 ng/mL ≥ PSA > 4 ng/mL and abnormal free/total PSA ratio or PSA density.Almost all prostate biopsies (both TR and TP approaches) in our hospital are performed by using 12 cores systematic biopsies plus 1 core in suspicious area. Biopsies were accomplished in a “fan-like” pattern , an 18-gIn accordance with the same steps reported in the literature , the patThe following clinical data was acquired by retrospective review of medical records and compared between the two groups: age, serum PSA level (ng/mL), prostate volume (mL), prostate cancer diagnosis rate and positive rate of biopsy cores, the prostate volume was calculated using the formula: height × width × length × 0.52 (in cm). Furtherly, patients were stratified according to several clinical characteristic, including: serum PSA level, prostate volume, PSA density, T stage and ISUP  grade, cancer detection rate and positive rate of biopsy cores were compared in different stratified groups.p value < 0.05 was considered significant.Continuous variables were described as averages, ranges and medians. Age was compared by independent t test, while PSA level, prostate volume and PSA density were compared by Mann–Whitney U test as they did not conform to normal distribution. The normal distribution of each dataset was checked by Kolmogorov–Smirnov test. Chi-square test was performed to compare the prostate cancer diagnosis rate and positive rate of biopsy cores among different groups. Cochran–Mantel–Haenszel (CMH) test was performed to compare the cancer detection rate after controlling for confounding variables according to PSA level and PSA density. The results were expressed as odds ratios (ORs) with 95% confidence intervals (CIs). SPSS 22.0 was used to perform all statistical analyses and 2. There was no significant difference in age, PSA level, prostate volume, and PSA density between two groups. The overall detection rate in TR group appeared to be higher than in TP group in our study . To minimize confounding factors of PSA level and PSA density in two groups, CMH test was performed, showing that the cancer detection rate in TR group was still higher than in TP group both when adjusting with PSA level , or when adjusting with PSA density . Similarly, the positive rate of biopsy cores was higher in the TR group than in the TP group .Out of the 452 patients underwent prostate biopsy Table , 230 (50p = 0.010), as well as in the subgroup with > 80 mL prostate volume . However, there was no significant difference between two biopsy approaches in cancer detection rate among the patients with ≤ 30 mL prostate volume. Similarly, cancer detection rates did not significantly differ between TR and TP group according to different PSA density. To minimize confounding factors of PSA level in subgroup analysis with different prostate volume, CMH test was performed, showing that TR group still have a higher cancer detection rate than the TP group with 30–80 mL prostate volume , while there was no significant difference in cancer detection rate in the subgroup with > 80 mL (p = 0.087).Furthermore, to compare the prostate cancer detection rate of two biopsy approaches in patients with different clinical characteristics, subgroup analysis was performed according to serum PSA level, prostate volume and PSA density. As shown in Table p = 0.001), while TP group have a higher rate among the patients with T1 and T2 stages . Additionally, except for 1 patient in TR group diagnosed with neuroendocrine carcinoma, ISUP  grades were obtained according to the highest pathology score core for each individual patient. When stratified by ISUP grade, there were no significant differences in positive rates of biopsy cores between the TR and TP groups for each subgroup.Among 230 patients diagnosed with prostate cancer by biopsy, T stages were assessable in 175 patients . We further analyzed the difference in the positive rates of biopsy cores between the two biopsy approaches in patients with different T stages. As shown in Table p = 0.040). Because of the lower infection rate of TP biopsy according to the current EAU guidelines, TP biopsy is preferentially recommended for patients ever since it was performed in our hospital in May 2020. And for this reason, more than 90% of patients preferred to choose TP biopsy when available, while a few patients chose TR biopsy, which is less expensive with no need for anesthesia. Over the past decades, with the improvement of multiparametric MRI (magnetic resonance imaging) diagnosis, MRI has become more and more sensitive for the detection of prostate cancer [Since TR ultrasound guided biopsy was introduced by Hodge et al. , it has e cancer . MR/ultre cancer , 26. Howp = 0.040). In our study, the overall detection rate in TR group appeared to be higher than in TP group . We speculate that this difference may be due to the average PSA level (22.0 ± 20.6 ng/mL) in our study were significantly higher than in the most previously reported studies[p = 0.280) in our study, which may be caused by the small sample size in the subgroup.Several previous studies were performed to compare the prostate cancer detection rates of TR and TP approaches, indicating no significant difference in overall cancer detection rates between the two approaches , 27–29. d studies, 27–29. p = 0.001) in our study, which suggested that TR approach may have advantage in patients with a probable diagnosis of high-risk prostate cancer . In contrast, TP group seems to have a higher positive rates of biopsy cores among the patients with T1 and T2 stages , and the literature also reported the advantage of the TP approach in patients with PSA levels of 4.01–10.00 ng/mL [In China, the proportion of newly diagnosed prostate cancer patients with high-risk and advanced-stage prostate cancer is higher than in Europe and the United States, which is more prevalent in poorer areas . Among 400 ng/mL , indicatp = 0.023). As we known, the enlargement of prostate volume was mainly due to the hyperplasia of transitional zone, which will cause the peripheral zone (an area with a high incidence of prostate cancer) to be compressed to the back of the gland. When TR biopsy was applied in the hyperplastic prostate, most cores will pass through the peripheral zone because its needles entered the prostate gland from the back of the gland. While the ventral needles  [In our results, TR group had a higher cancer detection rate than TP group in patients with prostate volumes 30–80 mL  . Moreove6 ng/mL) .Our study had some limitations. Firstly, this is a single-center retrospective study with a low level of evidence. Additionally, partial information was missing for some patients in this study, such as T-stage. More research is needed to further verify these opinions.Based on 452 patients underwent prostate biopsy in our hospital, TR group had a higher overall cancer detection rate and positive rate of biopsy cores than TP group. Further subgroup analysis showed that TR group had a higher cancer detection rate in patients with prostate volumes 30–80 mL, and that the TR group had a higher positive rate of biopsy cores among the patients with T3–T4 stages, while TP group had a higher positive rates of biopsy cores among the patients with T1–T2 stages. There were no significant differences between the TR and TP groups for each subgroup when stratified by PSA level, PSA density and ISUP grade.


N = 2662 cooperative students in their first academic year. Our analysis identifies a direct effect of relatedness and subject interest on dropout. Furthermore, indirect effects of satisfying basic psychological needs, specifically, autonomy and relatedness, on dropout via subject interest are noted. We evaluate our results in the context of the current state of research and discuss implications.Student dropout in higher education is a challenge for higher education systems. In recent years, there has been an increasing focus on analyzing motivational aspects in order to counteract dropout. However, the detailed impact mechanisms and processes of motivation on dropout have not been sufficiently researched. For example, there is very little research analyzing the preconditions of motivation and their influence on motivation as well as their eventual influence on dropout. From the background of self-determination theory and the person-object theory of interest, this study analyzes the effects of satisfying the three basic psychological needs on dropout via subject interest. We use data from a cross-sectional design with  Student dropout in higher education is a heavily discussed topic, and no convincing measure has yet been found to effectively counteract it  with 1285 male (48%) and 1377 female (52%) students. At least 42% of the students have an academic family background, meaning at least one parent has a university degree. The distribution to faculty shows that 58% of the students study business administration, 33% are engineering students, and 9% are enrolled in the academic field of social work.The The educational program for the cooperative students in this sample rotates every three months. It varies between academic learning of theoretical frameworks at university and practical experience in companies. From the background of this special situation and based on a high proportion of practice, this bachelor program awards 210 credits over 36 months, according to the European Credit Transfer System  and the lowest performance score of 4 . We recode this measurement in our analysis, so that higher scores indicate better performance.configural, equivalence of model form; (2) metric , equivalence of factor loadings; (3) scalar , equivalence of item intercepts or thresholds; and finally (4) residual (strict or invariant uniqueness), equivalence of items’ residuals or unique variances. (p. 2)We perform analyses of measurement invariance for basic psychological needs and subject interest, in order to assess the (psychometric) equivalence of constructs across dropout and no dropout groups; in addition, we check that a construct has the same meaning in those groups, by following four steps from Putnick and Bornstein :configurCFI ≥ 0.010 and RMSEA ≥ 0.015 or SRMR ≥ 0.010 as indicative of noninvariance (for metric invariance: SRMR ≥ 0.030). The results confirm strict measurement invariance for persons with dropout, compared with persons with no dropout  as statistically significant.We use SPSS (Version 28) to explore data in the chapter preliminary analysis. Pearson’s er Cohen ; values e Cohen, . Skewnese Cohen, . In our DWLS). The criteria by Hu and Bentler , where values < 1.0 have been suggested as indicative of adequate model fit . For 2097 participants (79% of the sample), no missing values exist. We replaced the missing data using multiple imputation by chained equations of the R package “mice,” with 20 imputations  of the continuous variables in our study. There exists a large effect between autonomy and competence (r = 0.58). Autonomy shows a medium effects size with relatedness (r = 0.30) as well as with subject interest (r = 0.34). Competence and relatedness show a medium effects size (r = 0.35) as well. Relatedness has a left-skewed distribution (skew =  − 1.35) and kurtosis = 2.34, which is seen as problematic, given the assumption of a normal distribution.Table t(2660) = 4.23, p ≤ 0.001, Hedges g = 0.34), competence (t(2660) = 5.54, p ≤ 0.001, Hedges g = 0.45), relatedness (t(2660) = 6.17, p ≤ 0.001, Hedges g = 0.50), subject interest (t(2660) = 5.47, p ≤ 0.001, Hedges g = 0.44), and university entrance qualification grades (t(2660) = 4.11, p ≤ 0.001, Hedges g = 0.33).For no dropout compared to dropout, we identify mean level differences see Fig. . Persons2 = 537.231; df = 126; χ2/df = 4.264; p ≤ 0.001; CFI = 0.985; TLI = 0.984; RMSEA = 0.035; SRMR = 0.034; WRMR = 1.700). This result indicates that the theoretical model is accurately and reliably representing the data . Autonomy  and competence  have no significant association with dropout. Autonomy  and relatedness  are associated with subject interest, whereas competence has no significant association with subject interest . There is also a negative significant association between subject interest and dropout . Our results show a high covariance between autonomy and competence  in the model.Our results show that only relatedness has a significant association with dropout . Furthermore, there exists an indirect association from relatedness on dropout via subject interest .Analysis of the 95%-confidence intervals for the indirect effects confirmed mediation. Subject interest mediates the effect of autonomy on dropout  in our SEM is seen as problematic, because of indicating measuring similar constructs, multicollinearity and consequently endangered inference process  or dropout . Here, it seems possible, on the one hand, that the experience of competence actually has a small influence on subject interest and dropout risk, which would require further theoretical explanation; on the other hand, it also seems possible that a better operationalization of the construct is needed to uncover the interrelationships. Therefore, future research should analyze the effect of competence on subject interest as well as dropout in greater detail.Our research has limitations. We are using data from only one university with 12 campuses in one federal state of Germany. Furthermore, the generalizability from our sample to all students is problematic, because we collect data from cooperative students who are chosen from companies; as a consequence, a possible selection bias exists Kupfer, . Thus, oNew research questions arise from our findings. One new research interest is if differential effect sizes for the motivational process of dropout exist, such as gender or domains (Jansen et al., Our work advances research on the role of motivation in student dropout. We found that the satisfaction of BPNs is associated with dropout via subject interest. Arrangements to prevent dropout, such as increasing relatedness through mentoring programs, are discussed here. Further research is needed, as there are various other factors explaining dropout processes.


Pedilanthus tithymaloides is empirically used to treat schistosomiasis, it becomes essential to know its effective action scientifically. This study assessed the cercaricidal and schistosomicidal activity of P. tithymaloides stem barks raffia wine extract (RwPt) and hydroethanolic extract (HePt). Different concentrations of these extracts were tested against cercariae (31.25–1000 μg/mL) and adult worms (62.5–2000 μg/mL) of Schistosoma mansoni. Niclosamide-olamine 5% (1 μg/mL) and praziquantel (10 μg/mL) were used as pharmacological controls. Cercariae viability was determined every 30 min for 180 min, and adult worms' motor activity and viability after 24 and 48 h incubation. In addition, cytotoxicity and phytochemical analysis were performed. HePt was lethal to cercariae and adult worms with LC50 of 73.91 μg/mL after 60 min of incubation and 731.17 μg/mL after 48 h of incubation, respectively. Furthermore, a significant reduction of 94.44% in motor activity was observed in surviving worms at the concentration of 2000 μg/mL. RwPt was less effective on S. mansoni cercariae with an LC50 of 617.86 μg/mL after 180 min and on adult worms with a mortality rate of 9.83% at 2000 μg/mL for 48 h incubation. Both extracts showed a weak cytotoxicity profile with an IC50 of 983.50 μg/mL for HePt and more than 1000 μg/mL for RwPt. The LC-MS analysis of HePt allowed the detection of two annotated diterpenoids. Based on the selectivity index, the hydroethanolic extract of P. tithymaloides stem barks disclosed an intense cercaricidal activity and a moderate schistosomicidal effect with low cytotoxicity. These findings may support the potential use of Pedilanthus tithymaloides as a natural product or a source of natural-derived compounds for interrupting schistosomiasis transmission.Schistosomiasis control remains a public health concern, and there is a need to evaluate new strategies for targeting larval and adult stages of the parasite. As  Schistosoma. Human schistosomiasis is the second most devastating tropical disease after malaria and remains a major public health problem. The World Health Organization estimated that 236 million people in the tropics and subtropics required preventive treatment in 2019, and 90% resided in Africa /[LC50 of the same extract in S. mansoni cercariae (μg/mL)].Selectivity index = + detected at m/z 781.3040  was approximately 50 times greater than 20 μg/mL, indicating the very low cytotoxicity of this extract on mouse hepatoma cell lines. The relative effectiveness of a drug candidate in inhibiting parasite growth compared to inducing cell death is defined as the therapeutic index or selectivity index. Therefore, it is desirable to have a high therapeutic index (>2), giving a maximum anthelmintic activity with minimal toxicity on the cells [P. tithymaloides stem bark was 19.26 for cercaricidal activity and 1.34 for schistosomicidal activity. These findings reveal that this extract is strongly active against S. mansoni cercariae but relatively effective against adult schistosomes.Establishing that a drug candidate cannot induce cytotoxicity at therapeutic concentrations is crucial. The US NCI plant screening program stipulates that a crude extract with and 72 h . Accordihe cells . The selPedilanthus tithymaloides stem bark, with no cytotoxicity on mouse hepatoma cells. Also, we annotated two jatrophane diterpenes from this active extract. These findings may support the potential use of Pedilanthus tithymaloides as a natural product or a source of natural-derived compounds for interrupting schistosomiasis transmission. However, further investigations are in progress to disclose the pharmacological effects of these plant extracts through in vivo models of Schistosoma mansoni infection.The results of the current study provide evidence of the predominant cercaricidal activity and the moderate schistosomicidal activity of the hydroethanolic extract of


Subclinical atherosclerosis detected by increased coronary artery calcium (CAC) or arterial stiffness as reflected by cardio‐ankle vascular index (CAVI) has been associated with major adverse cardiovascular events (MACEs). However, comparative data from these two assessments in the same population are still limited.From 2005 to 2013, patients with stable coronary artery disease (CAD), both asymptomatic and symptomatic who underwent both coronary computed tomography and CAVI were enrolled and followed for occurrence of MACEs  until December 2019. A cause‐specific hazard model was applied to assess the associations of CAC score, and CAVI with long‐term MACEs.A total of 8687 patients participated. Of them, CAC scores were 0, 1–99, 100–399, and ≥400 in 49.7%, 31.9%, 12.3%, and 6.1%, respectively. Arterial stiffness (CAVI ≥ 9.0) was associated with the magnitude of CAC in 23.8%, 36.3%, 44.5%, and 56.2%, respectively. During an average of 9.9 ± 2.4 years follow‐up, MACEs occurred in 8.0%  of subjects. After adjusting for covariables, CAC scores of 100–399 and ≥400, and CAVIs of ≥9.0 were found to independently predict the occurrence of MACEs with the hazard ratios (95% CI) of 1.70 , 1.87 , and 1.27 , respectively. Other risk predictors were hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), aspirin, and statin therapy.A CAC score ≥100 or a CAVI ≥ 9.0 predicts the long‐term occurrence of MACEs in both asymptomatic and symptomatic patients with stable CAD. These two noninvasive tests can be used as screening tools to guide treatment for the prevention of future CV events. Inclusion criteria were: adults aged >18 years; asymptomatic patients with moderate‐to‐high ASCVD risk,2), waist circumference (WC), and prior and current medications. Lab data included fasting plasma glucose (FPG), lipid profile, and serum creatinine. DM was defined as overnight FPG ≥ 126 mg/dl or taking antidiabetic medications. Hypertension was defined as systolic BP (SBP) ≥ 140 mmHg and/or diastolic BP (DBP) ≥ 90 mmHg or taking anti‐hypertensive medications. Smoking was classified as current smoking, ex‐smoking more than 1 month, or never smoked. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2. The eGFR was calculated using the CKD Epidemiology Collaboration (CKD‐EPI) equations.Subject data recorded included age, sex, risk factors , body mass index  x ln(Ps/Pd) x haPWV2}+b, where Ps and Pd are the SBP and DBP, respectively; PWV is the PWV between the heart and ankle; ρ is blood density; ΔP is Ps‐Pd; a and b are scale conversion constants ,2.2The multidetector CT (MDCT) scans done during the study used either a 64‐slice CT scanner  or a 320‐slice CT scanner  before and after 2008, respectively. Two coronary CT scan findings used in this analysis were (i) CAC score and (ii) degree and extent of stenosis by CCTA. The CAC score was calculated according to the Agatston method using a commercially available external workstation . Total CAC score was calculated as the sum of the individual lesion scores in all coronary arteries and then stratified into four groups: 0, no identifiable plaque; 1–99, mild atherosclerotic plaque; 100–399; moderate atherosclerotic plaque; and ≥400, extensive atherosclerotic plaque.Degree of coronary stenosis was evaluated after injecting 70–90 ml of radiocontrast  via the right basilic vein through an 18‐gauge intravenous catheter followed by a 20 ml saline flush at a flow rate of 5 ml/sec. Automated bolus tracking was used to synchronize the arrival of the contrast media and the scan. After a 4‐s delay, images were obtained during an inspiratory breath hold of 5–10 s. Three‐dimensional reconstruction and cross‐sectional imaging measurements were performed; and stenoses were classified as normal (0%), mild (1–<25%), mild‐moderate (25–<50%), moderately severe (50–<75%), or severe (≥75%). In this study, we reclassified into three groups: no CAD (0% stenosis), nonobstructive CAD (1%–49% stenosis), and obstructive CAD ( ≥ 50% stenosis).2.3From each subject, the following data were recorded: age, sex, risk factors , BMI, WC, and prior and current medications during the follow‐up period including aspirin and statin. Also recorded were blood tests , ABI, CAVI, and full report of coronary CT scan. The data were computerized by two independent healthcare personnel . Data were double‐checked for inconsistency and readjusted for accuracy. Finally, electronic databases were exported into Excel spreadsheets for statistical analysis.2.4Patients were scheduled to see a cardiologist or internist with the official report of CCTA , CAVI and baseline data. After completion of this evaluation, patients were managed based upon physician's discretion including aspirin, statin, and risk factor modification. Some patients might have additional tests such as a cardiac stress test, and/or an invasive coronary angiography with possible revascularization (either percutaneous coronary intervention [PCI] or coronary artery bypass surgery [CABG]).2.5Clinical outcomes were retrieved after performing the coronary CT scan until December 2019 by accessing data from three sources: the electronic medical records, Information Technology (IT) division of Ramathibodi Hospital; 43‐file data from the strategy and planning division, Office of the Permanent Secretary Ministry of Public Health; the Information and Communication Technology (ICT) of Ministry of Public Health and Center Office for Healthcare Information.The clinical outcomes of interest were major adverse cardiovascular events (MACEs), including CV death, nonfatal MI, or nonfatal stroke. If a subject had more than one of these CV events, only the first event was counted. CV deaths were classified as either a CAD death or a stroke death, confirmed by death certificates from the National Statistics Office, Ministry of Interior. CAD was defined as the presence of at least one of the following: angina, acute coronary syndrome, acute MI, a significant (>70% diameter stenosis) lesion on coronary angiography, revascularization (PCI or CABG), or documented myocardial ischemia during exercise testing. MI was defined as an increase in cardiac troponin (cTn) plus one of the following: (1) evidence of prolonged ischemia as demonstrated by chest pain longer than 20 min; (2) ischemic ST‐segment changes or new pathological Q waves; (3) angiographic evidence of coronary occlusion or no‐reflow/slow flow; (4) imaging evidence of a new loss of viable myocardium or new regional wall motion abnormality. Stroke was defined as a history of ischemic or hemorrhagic stroke, or a transient ischemic attack (TIA), documented by CT or MRI.2.6χ2 test as appropriate. The incidence of MACE was estimated along with its range estimation . To evaluate the relationships of CAC score and CAVI to MACEs, a competing risk with subdistribution hazard model was applied to estimate a cumulative incidence function (CIF) considering other causes of death as competing risk events. A multivariate cause‐specific Cox hazard (CSH) regression was applied to assess if CAC score, coronary stenosis, CAVI, and/or other significant risk factors were associated with a MACE (and not another cause of death as a competing risk) with the following steps: Frist, a univariate analysis was applied by fitting each of the risk factors in the CSH model. Second, risk factors whose p value was less than .10 from the univariate analysis were simultaneously included in the multivariate CSH model. A backward elimination was applied by eliminating each of the risk factors from the model. A likelihood ratio test was used to keep only significant (p < .05) risk factors, as well as CAC score and CAVI in the final model. Hazard ratio (HR) along with its 95% CI for each risk factor was then estimated and reported.Baseline characteristics were summarized as mean ± standard deviation (SD) and percentage for continuous and categorical variables, respectively. These were then compared among CAC score groups using one‐way analysis of variance, quartile regression, or p values of less than .05 were considered as statistically significant.All analyses were performed using STATA 17.0. . 32. Atherosclerotic risk factors included hypercholesterolemia in 52.5%, hypertension in 42.3%, current or ex‐smoking in 13.8%, DM in 13.7%, and CKD in 7.2%. The mean CAVI was 8.9 ± 2.2, with CAVI ≥ 9 in 36.9%. Baseline blood test results are shown in Supporting Information: Table A total of 8687 patients participated in the study; their mean age at enrolment was 59.0 ± 8.4 years, 63.3% were females, and the mean BMI was 24.9 ± 3.6 kg/mn = 5855 (67.4%)]. Only a minority of them were investigated further with cardiac stress test (n = 35 (0.4%)] and/or underwent coronary angiography (n = 226 [2.6%]), and revascularization (n = 139 [1.6%]). Most patients had never received prior medications, but they were prescribed after CCTA or occurrence of later MACEs, which resulted in percentages of statin and aspirin therapy increased significantly from 9.4% to 67.4% and 0.5% to 31.5%, respectively. During the follow‐up period, almost one‐third and two‐thirds of subjects were being treated with an antiplatelet agent and statin, respectively  of 8.0% . These events comprised of CV death in 0.7%, nonfatal MI in 2.3%, and nonfatal stroke in 6.0%. The magnitude of CAC score was associated in a dose‐dependent manner with the frequency of MACEs . This could be interpreted that after adjusting for these covariables using a multivariate CSH regression model, patients with CAC scores of 100–399 and ≥400 were found to be 1.70  and 1.87  times more likely, respectively, to develop MACEs than patients with a CAC score of zero  CAD was not found to be a significant predictor of MACEs. Other significant risk factors included age ≥60, hypertension, DM, and CKD, and concurrent aspirin and statin therapy. CAC scores of 100–399 and CAVIs ≥9.0 were also significantly associated with other causes of death along with other factors such as CKD, and current or ex‐smoking.4This cohort was one of the largest yet studied with arterial calcification and arterial stiffness assessed by CAC score and CAVI, respectively, as risk predictors of subsequent MACEs in patients with suspected stable CAD. Our findings suggested that patients with CAC scores of 100–399 and ≥400 were at about 1.70‐ and 1.9‐folds higher risk of developing MACEs than patients with a CAC score of zero. Stenosis ≥50% in coronary arteries was found to not be a significant predictor. Patients with CAVIs ≥9.0 were at 1.27‐folds higher risk of developing MACEs than patients with CAVIs <9.We included both asymptomatic patients with moderate to high ASCVD risk and symptomatic stable CAD patients with the following reasons: First, to reflect the real practice situation for serving the need of these patients who want to know whether they have subclinical CAD. Second, to help physicians to reclassify patients' risks and third, to expand the spectrum of disease severity. The uniqueness of our study protocol was to demonstrate the comparative data between CAC and CAVI whether they improve risk prediction of long‐term MACEs in stable CAD patients with all stages of atherosclerosis, from no plaque with endothelial dysfunction to fibrofatty  plaques to calcified plaques. CAC score is well established as a predictor of future MACEs and widely used in risk stratification for primary prevention and treatment.After considering traditional risk factors such as old age, DM, hypertension, CKD, and concurrent aspirin and statin therapy, CAVIs and CAC scores were shown to be independently predictive of long‐term MACEs. We also found that there was a dose‐dependent association between these two measurements, although the existence of calcification was more predictive of MACEs than was arterial stiffness. Both CAC scores ≥100 and CAVIs ≥9.0 were independent risk predictors of long‐term MACEs in asymptomatic patients with risk factors or symptomatic patients with suspected stable CAD.In this study, we used the CAVI as a categorical rather than a continuous variable. From the previous literature, there may be some controversy as to the optimal cut‐off value for discriminating CV risk.Contrary to CAVI, the CAC score is more widely used and studies support its use as a screening test to guide treatment in both symptomatic and asymptomatic patients.The role of aspirin in the primary prevention of ASCVD is still controversial.Even though we found an association between CAC score and the occurrence of future CV events, the role of coronary calcium on the natural history of atherosclerosis remains uncertain. Some researchers suggest that large calcification is a marker of coronary plaque stabilization and thus associated with stable angina (and a reduced risk of acute coronary syndrome events).Interestingly, the degree of coronary stenosis detected by coronary CT angiography (CCTA) was not predictive of MACEs in our study after adjusting for other covariables. This finding was similar to that of Cho and colleagues who reported that there is no further incremental value gained by the addition of CCTA findings to a model incorporating risk factors and CAC score.In summary, the addition of CAC score and CAVI to clinical risk factors should improve the prediction of long‐term occurrence of MACEs and enhance personalized allocation of antiplatelet and statin therapy in primary prevention. The CAC score was a stronger predictor than CAVI and was more reliable than the degree of stenosis as detected by CCTA. CAVI probably is an additional predictor of MACEs, especially in the patients with noncalcified plaques or CAC scores <100. To determine whether they improve the guidance of treatment and prevention of CV events, a future randomized controlled study is needed to evaluate the efficacy of different treatment modalities in each group of patients guided by coronary CT scan findings and/or CAVI.4.1This study had some limitations. First, the analysis did not consider individual patient symptoms at baseline because these data were not completely recorded and unable to adjudicate. Therefore, we could not assess whether predictive values of CAC scores or CAVI on MACEs would be different between asymptomatic and symptom patients. However, most symptoms in our participants  were mild. Second, this study did not aim to analyze the effect of concurrent treatments  on the MACEs. However, to adjust the treatment effect, aspirin and statin therapy were added as covariables and were apparently associated with the higher risk or paradoxical of treatment effects. To clarify this finding, it needs to do propensity score, but this was out of our scope of the study. Other possible explanation of the ineffectiveness of therapy includes discontinuance or no compliance of treatment or including the secondary prevention treatment after CV events occur. Third, follow‐up data were obtained from medical records and government IT data bases, not prospectively planned data collections from patients, and this might have led to some under‐reporting of CV events. Finally, our cohort was not ethically heterogeneous, as all were Asian. Therefore, the discrepancies between studies could be attributed, in part, to ethnic differences.5CAC score and arterial stiffness as reflected by CAVI can enhance risk evaluation beyond that provided by traditional risk factors alone. CAC scores of ≥100 and CAVIs of ≥9.0 predicted the occurrence of long‐term MACEs in both asymptomatic patients with risk factors and symptomatic patients with suspected stable CAD. An advantage of CAVI is that it can be used as a screening tool to predict the CV risk in patients with fibrofatty or noncalcified plaque. However, these two risk predictors must be validated to determine whether they improve the guidance of treatment and prevention of future CV events and prolong survival.The authors declare no conflict of interest.Supplementary information.Click here for additional data file.


Ibrutinib has revolutionized the treatment of mantle cell lymphoma (MCL). Both ibrutinib monotherapy and ibrutinib‐based combination therapy are important salvage options for patients with relapsed/refractory (R/R) MCL. The real‐world efficacy and safety profile of the two strategies in Chinese patients with R/R MCL remain unclarified.N = 68) or ibrutinib combination therapy (N = 53) in 13 medical centers in China were retrospectively reviewed.In the present study, data of 121 R/R MCL patients who received either ibrutinib monotherapy (p = 0.003), complete remission rate was 16.2% versus 43.4% (p < 0.001), and median progression‐free survival (PFS) was 18.5 months  vs. 30.8 months  , with ibrutinib monotherapy and ibrutinib‐based combination therapy, respectively. Subgroup analysis showed that patients with male gender, no refractory disease, Ki67 <30%, previous line of therapy = 1, non‐blastoid subtype, and the number of extranodal sites involved <2 might benefits more from the combination therapy. Treatment‐emergent adverse events were similar, except for a higher incidence of all grade neutropenia in the ibrutinib combination group .With a median follow‐up of 20.5 months, the overall response rate was 60.3% versus 84.9% (Ibrutinib combination therapy demonstrated potentially superior efficacy and comparable tolerability to ibrutinib monotherapy. Ibrutinib‐based combination therapy could be one of the prominent treatment options for R/R MCL patients. Compared to ibrutinib monotherapy, ibrutinib‐based combination therapy showed potentially superior efficacy for relapsed/refractory mantle cell lymphoma patients, with similar safety profile. Combination therapy based on ibrutinib could be considered as one of the prominent treatment options for this group of patients.  To the best of our knowledge, data on the clinical outcomes and safety profile of ibrutinib in Chinese MCL patients is lacking. This may be attributed to the rarity of the disease and the relatively short period following approval of ibrutinib in China.Although ibrutinib has transformed the treatment of R/R MCL, there are still several limitations when used as a single agent, including a low CR rate, short PFS, and development of resistance due to mutations of BTK or other molecular targets in the B‐cell receptor pathway.Due to the lack of direct comparative data from randomized clinical trials, we conducted a nationwide, multicenter, retrospective analysis comparing the efficacy and toxicity of ibrutinib monotherapy and ibrutinib‐based combination therapy in R/R MCL patients in China.22.1Adult R/R MCL patients initiated on ibrutinib monotherapy or ibrutinib‐based combination therapy between August 2017 and December 2020 were included in this study. Inclusion criteria were as follows: (1) pathologically confirmed MCL according to the 2016 World Health Organization classification of lymphomaThirteen medical centers in China participated in this study, including (1) Sun Yat‐sen University Cancer Center; (2) Peking University Third Hospital; (3) West China Hospital, Sichuan University; (4) Guangdong Provincial People's Hospital; (5) Guangdong Province Traditional Chinese Medical Hospital; (6) Tianjin Medical University Cancer Hospital and Institute; (7) Cancer Center, Union Hospital, Tongji Medical College; (8) The Second Affiliated Hospital of Zhejiang University School of Medicine; (9) The Second Affiliated Hospital of Guangzhou Medical University; (10) Nanfang Hospital of Nanfang Medical University; (11) Second Affiliated Hospital of Dalian Medical University; (12) Hainan General Hospital; and (13) Hainan Cancer Hospital.The study protocol was approved by the institutional review board, and the study was performed in compliance with the Declaration of Helsinki. The included patients provided written informed consent.2.2Data on ORR, CR rate, time to response (TTR), DOR, PFS, overall survival (OS), reasons for ibrutinib discontinuation, and incidence of treatment‐emergent adverse events (TEAEs) were collected. Response to ibrutinib therapy was assessed according to the 2014 Lugano criteria based on medical records in each medical center.2.3Samples were obtained from formalin‐fixed paraffin‐embedded (FFPE) tissue sections after relapse of the last line of therapy before ibrutinib initiation. Tumor samples with >10% tumor cells identified by immunohistochemistry were eligible for next‐generation sequencing (NGS) analysis. Genomic DNA from FFPE samples was extracted using the QIAamp DNA FFPE Tissue kit (Qiagen). Sequencing libraries were prepared using the KAPA Hyper Prep Kit (KAPA Biosystems). Hybridization enrichment was performed using customized xGen lockdown probes (Integrated DNA Technologies) targeting 446 leukemia‐ and lymphoma‐related genes. Dynabeads M‐270 (Life Technologies) and xGen Lockdown hybridization and wash Kit (Integrated DNA Technologies) were used for capture reaction. Captured libraries were amplified by polymerase chain reaction (PCR). The mean depth of coverage sequencing was 1000×.N bases were removed. Then, the paired‐end reads were aligned to the human reference genome (hg19) using Burrows‐Wheeler Aligner. Picard was used to remove PCR duplicates. Genome Analysis Toolkit was used for local realignment around indels and recalibration of base quality score. Matched normal control of the germline DNA was not available due to the retrospective nature of this study. Somatic mutations were first called from each sample (the filtering criteria were a variant frequency of ≥0.5% and ≥5 supporting reads from both directions). Common single‐nucleotide polymorphisms (SNPs) were filtered out if the population frequency was >1% in the 1000 Genomes Project or the Exome Aggregation Consortium 65,000‐ exome database. The mutation list was further filtered by an in‐house list of recurrent artifacts and common SNPs based on blood samples sequenced with the same gene panel in approximately 500 Chinese patients with malignancies. Single‐nucleotide variations/indels were annotated with ANNOVAR, and were manually checked on the Integrative Genomics Viewer. Copy number variations were detected using in‐house‐developed software.Trimmomatic was used for quality control of FASTQ file. The leading and trailing low quality  or 2.4p‐value of <0.05 was set as statistically significant.Baseline characteristics were analyzed by descriptive statistics. Categorical variables were presented as the number and percentage of individuals in each category. Chi‐square test, Fisher exact test, or Wilcoxon rank‐sum tests were used to compare proportions between two treatment groups. All time‐to‐event endpoints, including PFS, OS, TTR, and DOR, were estimated using the Kaplan–Meier survival method and compared by a Log‐rank test. The hazard ratio (HR) for the combination therapy group relative to the monotherapy group and the 95% confidence interval (CI) were calculated using the Cox regression model. Statistical analyses were performed using SAS 9.4. A 33.1p = 0.033) than the monotherapy group. No statistically significant differences were observed in other baseline characteristics between the two groups.A total of 121 R/R MCL patients met the eligibility criteria. There were 68 and 53 patients in ibrutinib monotherapy group and ibrutinib‐based combination therapy group, respectively. A flow diagram of the case selection process is presented in Figure 3.22) . A summary of the regimens in the combination therapy group is presented in Table N = 29), IR (N = 10), rituximab (N = 1), and rituximab + lenalidomide (N = 1).Forty‐five patients (84.9%) of the 53 patients in the combination therapy group received a chemotherapy‐free regimen. Ibrutinib + rituximab (IR)  was the most common combined therapy, followed by ibrutinib + rituximab + lenalidomide . Substantially fewer patients in the combination therapy group achieved SD . In patients who received chemotherapy‐free combination regimens, the ORR and CR rates were 84.4% and 44.4%, respectively. The median TTR for the monotherapy and combination groups were 6.3 months  and 2.6 months , respectively .The treatment response of the entire cohort and the two treatment groups is summarized in Table y Figure . For they Figure . The dif3.3p = 0.025)  , the estimated median PFS of the entire cohort was 21.7 months , with 1‐ and 2‐year PFS of 70.7% and 39.5%, respectively Figure . The med) Figure . However) Figure . Fifty‐n) Figure .We also evaluated the PFS benefit of combination therapy versus monotherapy in different subgroups according to baseline characteristics Figure . Several3.4N = 2; bleeding, N = 3; second malignancies, N = 3; ventricular premature contractions and palpitations, N = 1), physician or patient choice , death unrelated to MCL , and unknown reason .At the last follow‐up, 67 patients had discontinued ibrutinib‐based treatment, principally because of disease progression . Other reasons for ibrutinib discontinuation included: AEs  compared with the monotherapy group. There were no other statistically significant differences in all grade or grade 3–4 TEAEs between the two groups. Of the 15 patients with an electrocardiogram (ECG) abnormality, atrial fibrillation was detected in only two of the patients. Other abnormalities included atrial (N = 11) and ventricular premature contractions (N = 2). No significant difference in incidence of ECG abnormality with ibrutinib dose was observed (p = 0.413) (Table N = 2), grade 3 gastrointestinal hemorrhage (N = 1), and grade 3 subcutaneous hemorrhage (N = 1). There were no new safety signals in this study during ibrutinib treatment.Complete information on TEAEs was recorded in 105 patients from six participating medical centers Table . A signi3) Table . Major bNewly diagnosed secondary malignancies occurred in four patients (two patients in each group) after ibrutinib treatment: acute myeloid leukemia, myelodysplastic syndromes, nasopharyngeal carcinoma, and colorectal carcinoma. All four patients had received cyclophosphamide, anthracycline, vincristine, and prednisone‐based chemotherapy before ibrutinib treatment. The patients who were diagnosed with nasopharyngeal carcinoma had received autologous stem cell transplantation previously.3.5ATM , KMT2D , NSD2 , and SMARCA4 .In the exploratory analysis, 446 leukemia and lymphoma‐relevant genes detected by NGS were analyzed in 21 patients with available tumor samples. The heatmap of gene mutation profiles of the 21 patients is shown in Figure 4In this retrospective study, we analyzed the treatment patterns, efficacy, and toxicity of ibrutinib treatment in Chinese patients with R/R MCL in a real‐world setting. Ibrutinib‐based combination therapy achieved a significantly superior response rate, TTR, DOR, and PFS, and demonstrated an acceptable safety profile compared with ibrutinib monotherapy. The subgroup analysis identified several subgroups of patients that could benefit from the combination therapy.Table The synergistic anti‐tumor effect of ibrutinib with other agents has been demonstrated in several pre‐clinical studies.We conducted a subgroup analysis for PFS according to the baseline characteristics to determine if combination therapy could only benefit a specific group of Chinese MCL patients. Patients with heavily pretreated, more refractory, and highly aggressive diseases failed to show statistically significant PFS benefits with combination therapy. Most of the characteristics identified in our study  were previously reported as inferior prognostic factors for survival in patients who received ibrutinib treatment.p = 0.017). However, the neutropenia was manageable, and discontinuation due to neutropenia was not observed. We found no statistically significant difference in other toxicities between the two groups. Most patients reportehan ibrutinib monotherapy (p = 0.017). However, the neutropenia was manageable, and discontinuation due to neutropenia was not observed. We found no statistically significant difference in other toxicities between the two groups. Most patients reported mild to moderate adverse events, and severe (grade 3/4) toxicities were uncommon. Notably, the observed incidence rate of atrial fibrillation in the present study was lower than in previous clinical trials.Ibrutinib‐based combination therapy had a significantly higher rate of all‐grade neutropenia than ibrutinib monotherapy (Baseline characteristics of the two treatment groups were broadly similar except for a relatively younger age (<60 years) in ibrutinib combination group. Ibrutinib monotherapy group showed similar age distribution when compared to previous investigations, mostly with a median age of approximately 65–70 years.ATM, TP53, NSD2, and KMT2D) to this study.This study further explored the correlation between gene alterations and clinical outcomes in MCL patients treated with ibrutinib‐containing therapy. The results showed similarities and differences in the mutation profiles of this study compared with previous reports.The present study has several limitations. First, the retrospective nature of the study might introduce selection bias. Second, the subsequent treatment of patients who failed ibrutinib was not further discussed in this study due to missing treatment details. Third, despite the inclusion of patients from multiple centers, the sample size was still relatively small. For this reason, the results of subgroup analysis and NGS analysis should be interpreted with caution. Last, the maintenance therapy for the combination group was not uniform, which might have affected the results.In conclusion, this multicenter retrospective study illustrated that the efficacy of ibrutinib‐based combination therapy was potentially superior to ibrutinib monotherapy, with comparable toxicity. Ibrutinib‐based combination therapy could be considered as one of the preferred treatment options for R/R MCL patients.The authors have declared no conflicts of interest.Qingqing Cai, Yuchen Zhang, and Panpan Liu were involved in conception and design of the study. Yuchen Zhang, Panpan Liu, and Jun Cai carried out methodology, data analysis, and interpretation. Qingqing Cai was involved in study supervision. All authors carried out acquisition of data, writing, review, and/or revision of the manuscript. They also reviewed the manuscript and approved submitting it.The study was performed in compliance with the Declaration of Helsinki. The study protocol was approved by the institutional review board (B2020‐012‐01).Appendix S1Click here for additional data file.


Malignant peritoneal mesothelioma (MPM) is a rare malignancy, presenting with non‐specific and potentially‐misleading manifestations. It represents a diagnostic pitfall as it mimics ovarian carcinoma. Maintaining a low diagnostic threshold, obtaining a detailed history, and utilizing immunohistochemical markers to diagnose MPM is crucial as early diagnosis and treatment might improve survival. We report a case of multiple primary malignancies involving malignant peritoneal mesothelioma in a 55‐year‐old female with a remote history of radiotherapy for thyroid papillary adenocarcinoma. Her advanced disease made her unfit for chemotherapy and debulking surgery. She died of cardiac arrest 2 days after palliative care referral. She reported an unintentional weight loss of 5 kg within the last 3 months. She denied a history of sick contact, fever, headache, chest pain, palpitations, syncope, joint pain, rectal bleeding, or urinary and bowel changes. Upon admission, she was on Metformin and Insulin Glargine for diabetes mellitus, Amlodipine for hypertension, Atorvastatin for dyslipidemia, Esomeprazole for occasional reflux, and Thyroxine due to her previous history of total thyroidectomy. Her past surgical history was notable for hysteroscopic polypectomy for menorrhagia 2 years ago and total thyroidectomy for papillary adenocarcinoma 15 years ago. Her family history was noncontributory. She is a housewife, and she denied any prolonged exposure to environmental toxins and carcinogens such as cigarette smoking, industrial smoke, and asbestos. On examination, she was ill‐appearing, distressed, and in pain. She was vitally unstable with a blood pressure of 97/83 mmHg and a heart rate of 116 bpm but a normal respiratory rate (20) and body temperature (36.4°C). She was alert, attentive, and oriented to time, place, and person. Her cardiopulmonary examination was unremarkable. Her abdomen was severely‐distended with a positive shifting dullness and fluid thrill, diffusely tender to palpation with a constant pain in the right upper quadrant, audible bowel sounds, and no distended veins or evidence of organomegaly. Both of her lower limbs were diffusely edematous without tenderness. She was admitted under internal medicine for diagnosis and treatment of ascites, and a drainage catheter was placed by the interventional radiology team.Laboratory investigations were remarkable for microcytic hypochromic anemia , thrombocytosis (Platelets: 794 × 10^9/L), leukocytosis with a neutrophilic predominance , mild hyperkalemia (5.3 mmol/L), hyperphosphatemia (1.63 mmol/L), hyponatremia (130 mmol/L), hypoalbuminemia (22 g/L), slightly elevated alkaline phosphatase (189 U/L), and gamma‐glutamyl transferase (41 U/L) without transaminitis , and elevated lactate dehydrogenase (359 U/L), D‐dimer (2.65 mg/L), and inflammatory markers . Coagulation studies were within the normal range. Given her previous history of chronic endometritis, ovarian cyst, and papillary adenocarcinoma of the thyroid and her suspicious presentation of prolonged abdominal pain, unexplained weight loss, anorexia, fatigue, and night sweat, a metastatic gynecologic malignancy was suspected and tumor markers were ordered. Beta‐hCG (30 IU/L), CA 125 (663 U/mL), and CA 15‐3 (229 U/mL) were markedly elevated whereas alpha fetoprotein (<2.0 ng/mL), CEA (2 ng/mL), and CA 19.9 (4 U/mL) were within normal limits. Blood, urine, and ascitic fluid cultures yielded no microbial growth. Her serum‐ascites albumin gradient was 0.5 g/dL, probably reflecting peritoneal carcinomatosis. Ascitic fluid cytologic analysis showed reactive mesothelial cells, histocytes, and lymphocytes intermixed with few highly atypical cells worrisome for adenocarcinoma of ovarian origin.Supine and upright abdominal radiographs were unremarkable. Abdominal CT with contrast showed diffuse omental caking with thick enhancing peritoneal reflections associated with moderate ascites and mesenteric root fluid collection. Also, there were enlarged retrocaval, paraaortic, and internal mammary lymph nodes. In addition, soft tissue thickening of the right adnexa with a poorly defined ovary was noted, which is also suspicious of ovarian malignancy Figure . PET/CT Based on the imaging, histopathological, and immunohistochemical findings, a diagnosis of metastatic malignant peritoneal mesothelioma of biphasic morphology was made. Due to her advanced metastatic disease and overall poor general health, medical and surgical oncology referred her to palliative care as she was unfit for chemotherapy and debulking surgery. She received a high dose of morphine and lorazepam without a significant pain improvement, and 2 days later, she died of cardiac arrest.3Multiple primary malignancies are defined as the occurrence of two or more independent malignancies in the same or different organs. They are classified as synchronous or metachronous based on the time interval between malignancy diagnoses. A metachronous malignancy is a second malignancy occurring at least 6 months after the first malignancy.We believe that this case is interesting due to the following reasons: (1) Malignant peritoneal mesothelioma is a very rare malignancy with a nonspecific clinical presentation. Because of that, this case highlights the importance of keeping it within the differential diagnosis of malignant ascites, especially in patients with previous exposure to radiation as it is a well‐established risk factor for malignant mesothelioma.This case is limited by the absence of genetic testing and the weak association between neck radiation and development of malignant mesothelioma. BRCA1‐associated protein 1 (BAP1) is a tumor suppressor gene and its loss has been reported in malignant mesothelioma.Mesothelioma is an insidious lethal malignancy arising from mesothelial surfaces, with the pleura being the most commonly afflicted (65%–70%), followed by the peritoneum (10%–30%), tunica vaginalis, and pericardium (1%–2%).Although malignant peritoneal mesothelioma and ovarian carcinoma are barely distinguishable morphologically and share many diagnostic markers such as keratins and vimentin, there are some biological and immunohistochemical differences to distinguish both cancers. To begin with, compared to ovarian carcinoma, malignant peritoneal mesothelioma has a higher expression of the nerve growth factor receptors p75 and p‐TrKA and the angiogenic molecules bFGF but lower expression of the laminin receptor 67‐kDa and α6 integrin, the angiogenic molecules VEGF and IL‐8, and the human leukocyte antigen G.In our case, the diagnosis of malignant peritoneal mesothelioma was confirmed by histopathological examination of a core needle biopsy of the omental cacking. The cells came positive for PAN CK, WT1, Calretinin, D2‐40, Podoplanin, and CK5/6. These markers are not 100% specific but have high sensitivities. To emphasize, the most sensitive marker is Calretinin (100%), followed by WT1 (94%), CK5/6 (89%), and D2‐40 (80%).4Malignant peritoneal mesothelioma is an extremely rare but rapidly progressive and highly fatal malignancy. It rarely presents with paraneoplastic syndromes, and it has non‐specific manifestations, which makes it a diagnostic dilemma. Clinicians should maintain a low threshold of its diagnosis, especially among patients with a previous history of radiation or asbestos exposure. Knowledge about malignant peritoneal mesothelioma signs and symptoms, risk factors, and associated paraneoplastic syndromes is crucial as early detection and treatment might improve survival.MSA (MBBS) was responsible for conceiving the report idea and acquiring the patient's data. MSA, RBA, OMW, and AYA (MBBS) were responsible for writing as well as reviewing the original manuscript. MA  and OZA (MD) were responsible for providing the required images/figures. MA , FS, and OZA (MD) critically reviewed the final form of the manuscript and supervised the whole process. All authors contributed to literature search and approved the final form of this paper, and are responsible for its content.No funding was needed for this paper.The authors declare no conflict of interest.This case report does not involve any studies with human subjects or animals, and therefore, it does not need ethical approval. The confidentiality of the patient was protected and no names nor any identifiers were mentioned.A written informed consent was obtained from the patient's son for the purpose of publication as she passed away. The importance of reporting her case for educational purposes was explained, and the patient's son agreed.


Non‐small cell lung cancer (NSCLC) comprises the majority (~85%) of all lung tumors, with lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) being the most frequently diagnosed histological subtypes. Multi‐modal omics profiling has been carried out in NSCLC, but no studies have yet reported a unique metabolite‐related gene signature and altered metabolic pathways associated with LUAD and LUSC.We integrated transcriptomics and metabolomics to analyze 30 human lung tumors and adjacent noncancerous tissues. Differential co‐expression was used to identify modules of metabolites that were altered between normal and tumor.We identified unique metabolite‐related gene signatures specific for LUAD and LUSC and key pathways aberrantly regulated at both transcriptional and metabolic levels. Differential co‐expression analysis revealed that loss of coherence between metabolites in tumors is a major characteristic in both LUAD and LUSC. We identified one metabolic onco‐module gained in LUAD, characterized by nine metabolites and 57 metabolic genes. Multi‐omics integrative analysis revealed a 28 metabolic gene signature associated with poor survival in LUAD, with six metabolite‐related genes as individual prognostic markers.We demonstrated the clinical utility of this integrated metabolic gene signature in LUAD by using it to guide repurposing of AZD‐6482, a PI3Kβ inhibitor which significantly inhibited three genes from the 28‐gene signature. Overall, we have integrated metabolomics and transcriptomics analyses to show that LUAD and LUSC have distinct profiles, inferred gene signatures with prognostic value for patient survival, and identified therapeutic targets and repurposed drugs for potential use in NSCLC treatment. Integrated metabolomic and transcriptomic strategies in lung adenocarcinoma (LUAD) and squamous cell carcinoma (LUSC) tumors. The transcriptomic and metabolomic data were integrated and enriched pathways were inferred. Integrated gene signatures were evaluated for tumor prognosis and drug repurposing. As outlined in Figure 22.1LUAD and LUSC tissue samples (15 each) for both with adjacent normal tissues (60) were obtained from the Houston Methodist biorepository under an IRB‐approved protocol. All patients signed an informed consent for the use of their tissues in research studies.2.2After measuring concentrations using Thermo Scientific's Nanodrop, RNA was sent to the Sequencing and Gene Editing Core at the University of Houston for: RNA quality analysis using the Agilent 2100 Bioanalyzer; sequencing library preparation using the Illumina Truseq stranded total RNA kit, with 1000 ng of RNA per sample with a RIN value >8.4; and sequencing using the NextSeq 500 (Illumina).2.3t‐test with the Benjamini‐Hochberg correction, with significance achieved at FDR < 0.05 and fold change exceeding 1.25X. Enriched pathways were inferred using the hypergeometric test, with significance achieved for FDR < 0.05.RNA‐seq data were mapped onto the human genome UCSC hg19 using hisat2 ,2.4Metabolites were extracted from homogenized frozen lung tissue samples (25 mg) using the liquid–liquid extraction procedure described previously.2.5t‐test followed by Benjamini‐Hochberg correction, with significance achieved at an FDR‐adjusted p < 0.25. Volcano plots were generated using the R statistical system.Metabolomics data were normalized to internal standards on a per‐sample, per‐method basis, then log2‐transformed. Differentially expressed metabolites (DEMs) were detected using the unequal variance two‐sided Student's 2.6p < 0.2.We determined genes associated with metabolomic signatures using the Human Metabolome Database .Differentially co‐expressed modules were detected using the DiffCoEx method.We used the LUAD integrated transcriptomic/metabolomics signature data to query the Library of Integrated Network‐Based Cellular Signatures (LINCS) for repurposable chemical compounds .2.7survivalp < 0.05. Distribution of gene signature score across tumor stages was assessed using the ANOVA test, with significance achieved at p < 0.05.We determined gene signatures association with patient survival using the TCGA LUAD Cohort. Specimens were stratified and survival association was determined using the R package 2.850 values were calculated using GraphPad Prism software version 8.02 . All data in the viability curves are reported as mean ± standard error of the mean.Normal human bronchial epithelial cells (Beas‐2B) and human LUAD cells (NCI‐H2342) were purchased from ATCC . Both cell lines were authenticated from ATCC. Beas‐2B cells were grown in a special media, Bronchial Epithelial Cell Growth Medium Bullet Kit (CC‐3170‐Lonza). H2342 cells were cultured in DMEM:F12 supplemented with 10% fetal bovine serum, 1% penicillin–streptomycin, and 1% glutamine. Cells were seeded at 5000 cells/well in 96‐well plates and grown for 24 h before treatment with various concentrations of AZD‐6482 and PI‐828  for up to 48 h. Cell viability was assessed using the XTT assay.2.9p‐value) that measures the overlap of observed and predicted regulated gene sets, and a Z‐score assessing the match of observed and predicted up/down‐regulation patterns.We used Ingenuity pathway analysis (IPA) network analysis  to identify interactions with other genes. We used an ‘enrichment’ score  method, with significance achieved at FDR < 0.05 and fold change exceeding 1.25X. We utilized unequal variance two‐sided parametric t‐test to assess significance of metabolomics changes, followed by Benjamini‐Hochberg correction, with significance achieved for FDR < 0.25. We utilized unequal variance two‐sided parametric t‐test with three replicates for Real‐Time PCR analysis, with significance achieved for p < 0.05.We utilized unequal variance two‐sided parametric 33.1The LUAD and LUSC tumors and adjacent normal tissue samples were obtained from both males and females with an age range of 54–80. After removing samples with low‐quality RNA sequencing data, the final analysis included 12 tumors and 13 normal tissues for LUAD and 13 tumors and 12 normal tissues for LUSC as outlined in . Of these pathways, 24 were highly interconnected and related to the synthesis of amino acids, namely lysine, cysteine, methionine, arginine, proline, tryptophan, and alanine as well as glycolysis, lipid metabolism, and fatty acids  analysis. The number and direction of DEMs associated with each DiffCoEx module are presented in Figure 3.3p < 0.02). Because the LUSC 13‐gene signature was not associated with prognosis in the TCGA LUSC cohort, we elected to proceed with further analysis only in the LUAD cohort. Survival analysis in LUAD, based on individual genes, identified six upregulated genes  significantly associated with survival   Figure . Togethe3.4clinicaltrials.gov), and seven of those have been used for NSCLC. Of the eight PI3K inhibitors, only one had been used in a NSCLC clinical trial (GDC‐0941/pictilisib) and four others had been used in clinical trials for other diseases. We selected two drugs, AZD‐6482 (PI3Kβ inhibitor) and PI‐828 (PI3K inhibitor), for further study. AZD‐6482 has been used in two clinical trials to test an anti‐platelet effect, while PI‐828 has not been used in humans. In a cytotoxicity assay, PI‐828 inhibited both H2342 lung cancer cells and Beas‐2B normal lung epithelial cells similarly, with IC50 values of 71 and 50 μM respectively , we proceeded with this drug for further experiments. To determine potential therapeutic targets, we selected six genes with differences in LUAD survival, along with a few other genes from the 28 gene signature and six cell cycle‐specific genes from the RNA‐Seq data   Figure . Notably) Figure . Our dat4The rapid development of omics technology has facilitated molecular insights into NSCLC. These studies have revealed transcriptomic expression signatures associated with clinical outcomes in NSCLC,Previous studies identified individual metabolism‐associated genes associated with survival, such as ATIC and ADSL, which are associated with purine metabolism.Recent studies and ongoing trials have aimed to identify novel metabolism‐targeting drugs. To determine whether the LUAD‐specific 28‐gene signature could contain novel therapeutic targets, we used LINCS/Connectivity Map analysisIPA analysis identified that LDHA interacts with the PLK1‐AURKB‐CENPA axis. PPAT is also strongly correlated with malignancy, particularly in neuroendocrine cancer including small cell lung cancer (SCLC), and its depletion suppresses the growth of SCLC lines.Integration of transcriptomic and metabolomic data can reveal metabolic reprogramming signatures and significantly enriched metabolic pathways associated with LUSC and LUAD, as was recently reported in a weighted gene co‐expression network analysis.In conclusion, for the first time, multi‐omics integration of transcriptomics and metabolomics was used to identify unique metabolite gene signatures specifically for LUAD and LUSC, and prognostic markers and therapeutic targets for LUAD. We further provided a proof of concept that repurposed drugs targeting transcriptional programs associated with metabolic dysregulation may have anti‐tumor effects in LUAD. Ultimately, the metabolite‐related gene signatures and altered metabolic pathways may offer novel insights into the prognosis and innovative treatment of NSCLC.All authors of this research paper have directly participated in the planning, execution, and/or analysis of this study. Conceptualization, Jose Thaiparambil, Cristian Coarfa, and Randa El‐Zein; Data curation, Jose Thaiparambil, Jianrong Dong, Sandra L. Grimm, Dimuthu Perera, Matthew J. Robertson, Brandon Mistretta, Preethi H. Gunaratne, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein; Formal analysis, Jianrong Dong, Sandra L. Grimm, Dimuthu Perera, Tajhal D. Patel, Nagireddy Putluri; Funding acquisition, Preethi H. Gunaratne, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein; Investigation, all authors; Methodology, all authors; Project administration, Jose Thaiparambil, Cristian Coarfa, Randa El‐Zein; Resources, Jose Thaiparambil, Jianrong Dong, Sandra L. Grimm, Dimuthu Perera, Matthew J. Robertson, Preethi H. Gunaratne, Min P. Kim, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein; Software, Jianrong Dong, Dimuthu Perera, Matthew J. Robertson, Cristian Coarfa; Supervision, Jose Thaiparambil, Preethi H. Gunaratne, Jason T. Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein; Validation, Jose Thaiparambil, Jianrong Dong, Sandra L. Grimm, Dimuthu Perera, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein; Visualization, Jose Thaiparambil, Jianrong Dong, Sandra L. Grimm, Dimuthu Perera, Cristian Coarfa, Randa El‐Zein; Writing—original draft preparation, Jose Thaiparambil, Sandra L. Grimm, Cristian Coarfa, Randa El‐Zein; Writing—review and editing, Jose Thaiparambil, Sandra L. Grimm, Preethi H. Gunaratne, Jason T. Yustein, Nagireddy Putluri, Cristian Coarfa, Randa El‐Zein.This project was partially supported by The Cancer Prevention Institute of Texas (CPRIT) grants RP170005, RP210227, and RP200504, NIH P30 shared resource grant CA125123, and NIEHS grants P30 ES030285 and P42 ES027725.The authors declare no conflicts of interest.The study protocol was approved by the institutional Review Board of the Houston Methodist Research Institute (Pro00014471).All analyses and conclusions in this manuscript are the sole responsibility of the authors and do not necessarily reflect the opinions or views of CPRIT, NIH, NIEHS, or the authors' institutions.Written informed consent was obtained from all patients before enrollment.Figure S1–S8Click here for additional data file.


Klotho is a hormone that emerges as an antiaging biomarker. However, the influence of the dietary pattern’s inflammatory potential on serum Klotho levels in human populations, especially in a general adult population, remains unknown. This study aimed to evaluate the relationship between the dietary inflammatory index (DII) and serum Klotho concentrations in individuals living in the United States. From the 2007–2016 National Health and Nutrition Examination Survey database, data of participants who completed the full 24-h dietary history and underwent serum Klotho testing were analyzed. The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models. We also conducted segmented regression model to examine the threshold effect of DII on serum Klotho concentrations.P for trend = 0.036). The segmented regression showed that the turning point value of DII was − 1.82 . A 1-unit increase in DII was significantly associated with lower Klotho levels by − 33.05  when DII ranges from − 5.18 to − 1.82; however, the relationship was not significant when DII ranges from − 1.82 to 5.42 (P > 0.05). Furthermore, stratified analyses indicated that the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, those with normal weight, and those without chronic kidney disease .A total of 10,928 participants were included, with a median serum Klotho concentration of 805.20 pg/mL (IQR: 657.58 − 1001.12) and a median DII of 1.43 (IQR: − 0.16 − 2.82). Multivariable regression showed that participants with high DII scores were associated with low serum Klotho concentrations; when classifying DII into quartiles, after full adjustment, participants in DII quartiles 3 and 4 showed a decrease in Klotho levels  compared with those in the lowest quartile (quartile 1) (95% CI: − 41.80, − 8.73 and − 29.83, 4.95, respectively; In summary, we indicated that there was a dose–response relationship between DII and serum Klotho concentrations, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration.The online version contains supplementary material available at 10.1186/s12877-022-03228-8. klotho deficiency linked to multiple premature-aging syndromes and a short lifespanProinflammatory cytokines, including TNF-α, IFN-γ, and IL-6, downregulate α-Klotho gene expressionDietary Inflammatory Index was developed as a tool to determine the inflammatory potential of dietWe found that there was a dose–response relationship between DII and circulating concentrations of klotho in a nationally representative population of American adults.The online version contains supplementary material available at 10.1186/s12877-022-03228-8. It is highly expressed in the distal convoluted tubules of the kidney and acts as an obligate coreceptor for fibroblast growth factor 23 (FGF23) [klotho gene expression defects resulting in multiple premature-aging syndromes and a short lifespan [klotho gene also suppress aging in mammals, and its overexpression is related to an extended lifespan of up to 30% in transgenic mice [Alpha-Klotho (Klotho) is a single-pass transmembrane protein encoded by the  FGF23) , 2. Kuro3 , 2. Kulifespan . Conversnic mice . Klotho nic mice –7. Recennic mice .klotho gene expression [klotho gene expression [Currently, dietary patterns play an important role in life expectancy and reduce the risk of overall mortality and morbidity , 10. Propression . Throughpression . Diets hpression . In a prpression . Thus, apression ; such repression . It was pression –19. In apression –23. Howepression  but negapression .Therefore, the insight into whether the inflammatory potential of the dietary pattern could influence serum Klotho levels in human populations, especially in a general adult population, remains unknown. Therefore, this study aimed to evaluate the association between dietary inflammatory potential and serum Klotho concentrations in a nationally representative sample of adults in the United States. We hypothesized that individuals with a high proinflammatory diet would have a lower Klotho level than those with a high anti-inflammatory diet.https://www.cdc.gov/nchs/nhanes/about_nhanes.htm). This study obtained written informed consent in all participants and was approved by the NCHS Ethics Review Board.The National Health and Nutrition Examination Survey (NHANES) is a major ongoing program of the National Center for Health Statistics (NCHS) at the Centers for Disease Control and Prevention. NHANES is designed to assess the health and nutritional status of noninstitutionalized residents in the United States. It uses a complex, stratified, multistage, probability sampling design to identify participants representative of the target population. It is unique in such a way that it not only collects questionnaire data through in-person interviews but also performs health examinations in a mobile examination center and collects specimens for laboratory tests. More details about NHANES can be found on their website  and serum klotho . We also excluded participants who were diagnosed with cancer or stroke. Ultimately, 10,928 participants were included in the final analyses . Serum klotho was only measured among those aged 40–79 years who consented to surplus serum collection for future research. Thus, participants who completed the full 24-h dietary history and underwent serum Klotho testing were included. We excluded those with incomplete data on dietary recall assessments , moderate active (< 150 min/week MVPA), and vigorous active (≥ 150 min/week MVPA) [2 had CKD [Potential confounders were selected a priori according to a literature review , 28, 29.ek MVPA) . In accoek MVPA) . Alcoholek MVPA) . Furtherek MVPA) . The urihttps://wwwn.cdc.gov/nchs/nhanes/analyticguidelines.aspx). Continuous variables are presented as the mean ± SD or median and interquartile range (IQR) when appropriate, whereas categorical variables are expressed as percentages. The differences between the DII quartile groups were compared using the Student’s-t test or Mann–Whitney U test for the continuous variables and the chi-square or Fisher’s exact test for the categorical variables.We used the appropriate survey procedures to account for the complex sampling design and weights in NHANES (The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models including the nonadjusted model (model I), minimally adjusted model II , and fully adjusted model III . DII was treated as both a continuous independent variable and a categorical variable (divided into quartiles), with the lowest quartile used as the reference. Linear trend tests were performed by entering the median value of each DII category as a continuous variable in the models. We further applied smooth curve fitting and segmented regression  model to examine the threshold effect of DII on serum Klotho concentrations. Log-likelihood ratio test that compares one-line (non-segmented) model with segmented regression model was also conducted. To explore whether the association was modified by age, sex, BMI, physical activity, and CKD, we conducted interaction analyses and stratified analyses. Moreover, the effects of outliers (serum Klotho and DII) on our results were assessed by sensitivity analysis. We tested the stability of our results after excluding those with Klotho levels > 2500 pg/ml, those with Klotho levels > 2000 pg/ml, and those with Klotho levels > 2000 pg/ml and DII > 5.http://www.R-project.org, The R Foundation) and Empower (R) . A two-tailed P value < 0.05 was considered statistically significant.All statistical data were analyzed using the software packages R .Table P = 0.002; model 3: 95% CI: − 7.49, − 1.28, P = 0.006). Moreover, the significant association persisted when classifying DII into quartiles. After adjustment for age, sex, and race, the DII was negatively associated with serum Klotho concentration (P for trend = 0.015). Compared with those at quartile 1, those at quartiles 2 and 3 had significantly decreased klotho levels (15.17 and 32.62 pg/ml) . In the fully adjusted model, participants in the highest DII quartile had a 12.44 pg/ml decrease in Klotho levels compared with those in the lowest quartile . Additionally, the β values for serum Klotho concentration among participants in DII quartiles 2 and 3 were 9.75 and 25.27 pg/ml, respectively, compared with those in the lowest quartile. . A nonlinear relationship between DII and serum Klotho concentrations was observed by smoothing curve fitting after fully adjustment.  when DII ranges from − 5.18 to − 1.82; however, the relationship was not significant when DII ranges from − 1.82 to 5.42 (P > 0.05).  (Table P for trend < 0.001). A 1-unit increase in the DII was also associated with lower serum Klotho concentrations among individuals with normal weight (P for trend = 0.015), and the β was − 25.79 , − 60.43 , − 49.89 for quartiles 2, 3, and 4, respectively. Similar results were observed in individuals without CKD . Those in DII quartiles 3 and 4 had a 31.21 and 16.99 pg/ml decrease in serum Klotho level, respectively, compared with those in quartile 1. . However, the association between DII and serum klotho was not significantly modified by sex or BMI.In stratified analyses, the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, normal weight, and without CKD. (This study demonstrated there was a dose–response relationship between DII and serum Klotho concentrations; higher DII score was associated with a decreased concentration of serum Klotho on the left side of the turning point; however, the relationship was not significant on the right side of the turning point. Furthermore, stratified analyses showed that the observed association of DII and serum Klotho concentration was stronger and significantly differed by age, BMI, and CKD status.Klotho is a transmembrane protein with important antiaging functions and anti-inflammatory effects , 13. RecIn our study, DII was negatively associated with serum Klotho on the left side of the turning point in a general population sample. Aging was also a potential modifier that influenced this negative association. This association was stronger in the older group, possible because natural aging results in a decrease in nephron number, causing the serum Klotho level to decrease; Klotho is an important factor involved in the aging process . In otheklotho gene expression secondary to inflammatory bowel disease, which was further potentiated by IFN-γ; in addition, an anti-TNF-α antibody attenuated inflammation and reversed the repression of Klotho expression [Fgf23 and induces its transcription [klotho gene, thereby decreasing the Klotho level, especially in people who were above 60 years, have less than moderate physical activity, and have no CKD.The possible mechanisms for our findings may be through the effect of diet on inflammatory markers. Recent research has identified that both systemic and local inflammations decrease Klotho expression in the kidneys . Moreno pression . Klotho pression , 43. Indpression . Proinflpression , 45, 46.cription . TherefoThis is the first to evaluate the dietary potential of inflammation in relation to serum Klotho concentration using a nationally representative US population. We conducted the threshold effect analysis, and a dose–response relationship was found between DII and serum Klotho concentrations. However, it also has some limitations. First, the cross-sectional nature precluded the establishment of causality. Second, the NHANES database only included participants aged 40–80 years old who were tested for Klotho level measurement; therefore, we do not know whether our results can be applied to younger age groups. Third, dietary information was only evaluated once at a 24-h period, not taking into account the variability of day-to-day diet. Fourth, the distribution of serum Klotho was not normalized. However, considering the small sample size of outliers, the results were stable after the sensitivity analysis, which we excluded participants with Klotho levels > 2500 pg/ml, those with Klotho level > 2000 pg/ml, and those with Klotho level > 2000 pg/ml and DII > 5. Finally, although we adjusted for as many confounders as possible, some unmeasured confounders were still found.In conclusion, there was a dose–response relationship between DII and serum Klotho concentrations in a nationally representative population of American adults, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration. Future human research is warranted to determine the causal relationship between DII and serum Klotho concentration.Additional file 1: Supplementary figure 1. Participants selection flowchart. Additional file 2: Supplementary figure 2. Association between Dietary Inflammatory index and serum klotho concentrations among adults in NHANES 2007-2016.Additional file 3: Supplementary Material. The method of the calculation of Dietary Inflammatory Index.


Primary osseous sarcoma of the pelvis is rare and has a particularly sinister outcome. This study aims to identify independent prognostic factors of cancer‐specific survival (CSS) in patients with primary pelvic sarcoma (PS) and develop a nomogram to predict 3‐, 5‐, and 10‐year probability of CSS in these patients.The Surveillance, Epidemiology, and End Results (SEER) database was used to identify 416 patients with primary PS, who were divided into two groups: a training cohort and a validation cohort. Univariate and multivariate Cox analyses were used to screen independent prognostic factors in patients with primary PS. Based on these independent prognostic factors, a prognostic nomogram was developed to predict 3‐, 5‐, and 10‐year probability of CSS. The nomogram's predictive performance and clinical value were evaluated using the calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA). Finally, a mortality risk stratification system was developed.Tumor size, tumor stage, histological type, surgery, and chemotherapy were identified as independent prognostic factors for the CSS of primary PS patients. Based on these factors, a nomogram was created to predict the 3‐, 5‐, and 10‐year probability of CSS in these patients. The calibration curve, ROC, and DCA indicated that the nomogram performed well and was appropriate for clinical use, with 3‐, 5‐, and 10‐year areas under ROC curve all higher than 0.800. Furthermore, the nomogram‐based mortality risk stratification system could effectively divide these patients into three risk subgroups.The nomogram constructed in this study could accurately predict 3‐, 5‐, and 10‐year probability of CSS in patients with primary PS. Clinicians can use the nomogram to categorize these patients into risk subgroups and provide personalized treatment plans. Four hundred and sixteen patients with primary pelvic sarcomas were collected from the SEER database, consisting of 18 cancer registries and covering 30% of the US population. Tumor size, tumor stage, histological type, surgery, and chemotherapy were identified as independent prognostic factors for the cancer‐specific survival (CSS) of patients with primary pelvic sarcomas. Nomograms for predicting 3‐, 5‐, and 10‐year CSS for patients with primary pelvic sarcomas were constructed based on identified prognostic factors. The mortality risk stratification system based on the nomogram could effectively divide patients with primary pelvic sarcomas into three risk subgroups. This study adhered to .2.2The following were the inclusion criteria: 1) Bones and joints were the site recode ICD‐O‐3/WHO 2008; (2) diagnostic confirmation by positive histology; (3) the primary site of the tumor was the pelvis ; (4) the designated histologic ICD‐O‐3 codes identified sarcomas for chondrosarcoma , osteosarcoma , Ewing sarcoma (9260/3), chordoma (9370–2/3), and others ; (5) primary tumor; and (6) complete follow‐up information. The following were the exclusion criteria: (1) Life expectancy less than 1 month; (2) no information about patients' demographics , tumor features , Derived American Joint Committee on Cancer (AJCC) T/N stage‐6th ed (T/N stage), and tumor grade), and treatment information . Finally, 416 patients met the study's criteria and were enrolled , tumor characteristics , and treatment information  were analyzed in this study. According to X‐tile software, the best cut‐off values for age and tumor size were 51 and 64 years old and 78 and 115 mm, respectively  and 95% confidence intervals (CI). Then, to control for confounding variables, the risk variables (p < 0.05) identified by univariate Cox regression analysis were explored further in multivariate Cox regression analysis to identify CSS‐related independent prognostic factors for patients with primary PS. We created a nomogram based on these CSS‐related independent prognostic factors to predict 3‐, 5‐, and 10‐year CSS probability in patients with primary PS. Meanwhile, this nomogram assigned a point to each CSS‐related independent prognostic factor , R (version 4.0.3), and SPSS (version 22.0) software. A 33.1Based on inclusion and exclusion criteria, this study enrolled 416 individuals with primary PS from SEER database between 2000 and 2015. These patients were divided into two groups: a training cohort  and a validation cohort . All patients' demographic and clinicopathologic features are summarized in Table 3.2p < 0.05, Figure Tumor size, histological type, tumor grade, tumor stage, T stage, N stage, surgery, radiotherapy, and chemotherapy were identified as risk‐related variables for CSS using Kaplan–Meier method and univariate Cox regression analysis , formulating treatment strategies adapted to the risk of death, enabling clinicians to achieve patient risk stratification management and targeted treatment to maximize patient benefit.Tumor size is an independent prognostic predictor of CSS in patients with primary PS. The larger the tumor, the worse the patient's prognosis. The larger the tumor, the more likely it is to compress the visceral and neurovascular bundles surrounding the tumor in the pelvis, causing more obvious signs and symptoms, thus affecting the patient's quality of life. Furthermore, a large tumor size within the complex pelvic structures would cause significant challenges for surgeons attempting to achieve adequate or negative margins during surgical resection. The probability of tumor recurrence and metastasis will also increase, which reduces the survival time of patients.Surgery, chemotherapy, and radiotherapy are currently used to treat primary PS. In the current study, the multivariate Cox regression analysis revealed that surgery and chemotherapy were independent predictive variables for CSS in individuals with primary PS. Patients who received chemotherapy had a significantly lower survival rate than those who did not. Although neoadjuvant chemotherapy combined with surgery is considered the standard of care for osteosarcoma, it should be noted that chemotherapy does not work for all patients with osteosarcoma. Chemotherapy was previously ineffective in elderly patients and those with pelvic osteosarcoma.p < 0.001, Table Surgery is the most preferred option for PS treatment. In our study, 313 75.24%) patients received surgery. Surgical resection of the tumor was significantly associated with CSS in univariate and multivariate Cox regression analyses , and the 1·3·5 Project for Disciplines of Excellence, West China Hospital, Sichuan University (grant number: ZYJC18039).https://seer.cancer.gov/seerstat/. We obtained access to the SEER database after obtaining permission to access research data files with the reference number 16336‐Nov2020.All methods were carried out in accordance with relevant guidelines and regulations. Data extraction and usage has been approved by SEER Program. All the data can be found in the SEER dataset: All data collected in this study have consent for publication.The authors declare no competing interests.File S1Click here for additional data file.File S2Click here for additional data file.