New infundibulopelvic angle measurement method can predict stone-free rates following retrograde intrarenal surgery.

To enhance the accuracy of predicting stone-free rates after retrograde intrarenal surgery, we devised a novel approach to assess the renal infundibulopelvic angle. We conducted a retrospective review of patient records for those who underwent retrograde intrarenal surgery for renal stones between April 2018 and August 2019. Patient demographics, stone characteristics, and perioperative data were recorded. Subsequently, we introduced a modified angle measurement called the pelvic stone angle and evaluated its predictive performance for stone-free rates by comparing it with the traditional method in scoring systems. A total of 43 individuals were included in this study. Notable differences in stone burden and Hounsfield unit measurements were found between stone-free and non-stone-free patients. The pelvic stone angle demonstrated a good model fit when used in scoring systems, performing equally well as the conventional approach. The area under the receiver operating characteristic curve for the R.I.R.S. scoring system using the pelvic stone angle and the conventional approach did not show a significant difference. In conclusion, the predictive ability of the pelvic stone angle for stone-free rates was comparable to the old measurement method. Moreover, scoring systems using the pelvic stone angle exhibited a better model fit than those using the conventional approach.

Development and external validation of a multimodal integrated feature neural network (MIFNN) for the diagnosis of malignancy in small pulmonary nodules (≤10 mm).

Objectives. Current lung cancer screening protocols primarily evaluate pulmonary nodules, yet often neglect the malignancy risk associated with small nodules (≤10 mm). This study endeavors to optimize the management of pulmonary nodules in this population by devising and externally validating a Multimodal Integrated Feature Neural Network (MIFNN). We hypothesize that the fusion of deep learning algorithms with morphological nodule features will significantly enhance diagnostic accuracy.Materials and Methods. Data were retrospectively collected from the Lung Nodule Analysis 2016 (LUNA16) dataset and four local centers in Beijing, China. The study includes patients with small pulmonary nodules (≤10 mm). We developed a neural network, termed MIFNN, that synergistically combines computed tomography (CT) images and morphological characteristics of pulmonary nodules. The network is designed to acquire clinically relevant deep learning features, thereby elevating the diagnostic accuracy of existing models. Importantly, the network's simple architecture and use of standard screening variables enable seamless integration into standard lung cancer screening protocols.Results. In summary, the study analyzed a total of 382 small pulmonary nodules (85 malignant) from the LUNA16 dataset and 101 small pulmonary nodules (33 malignant) obtained from four specialized centers in Beijing, China, for model training and external validation. Both internal and external validation metrics indicate that the MIFNN significantly surpasses extant state-of-the-art models, achieving an internal area under the curve (AUC) of 0.890 (95% CI: 0.848-0.932) and an external AUC of 0.843 (95% CI: 0.784-0.891).Conclusion. The MIFNN model significantly enhances the diagnostic accuracy of small pulmonary nodules, outperforming existing benchmarks by Zhanget alwith a 6.34% improvement for nodules less than 10 mm. Leveraging advanced integration techniques for imaging and clinical data, MIFNN increases the efficiency of lung cancer screenings and optimizes nodule management, potentially reducing false positives and unnecessary biopsies.Clinical relevance statement. The MIFNN enhances lung cancer screening efficiency and patient management for small pulmonary nodules, while seamlessly integrating into existing workflows due to its reliance on standard screening variables.

NTRK3 exhibits a pro-oncogenic function in upper tract urothelial carcinomas.

Neurotrophic receptor tyrosine kinase 3 (NTRK3) has pleiotropic functions: it acts not only as an oncogene in breast and gastric cancers but also as a dependence receptor in tumor suppressor genes in colon cancer and neuroblastomas. However, the role of NTRK3 in upper tract urothelial carcinoma (UTUC) is not well documented. This study investigated the association between NTRK3 expression and outcomes in UTUC patients and validated the results in tests on UTUC cell lines. A total of 118 UTUC cancer tissue samples were examined to evaluate the expression of NTRK3. Survival curves were generated using Kaplan-Meier estimates, and Cox regression models were used for investigating survival outcomes. Higher NTRK3 expression was correlated with worse progression-free survival, cancer-specific survival, and overall survival. Moreover, the results of an Ingenuity Pathway Analysis suggested that NTRK3 may interact with the PI3K-AKT-mTOR signaling pathway to promote cancer. NTRK3 downregulation in BFTC909 cells through shRNA reduced cellular migration, invasion, and activity in the AKT-mTOR pathway. Furthermore, the overexpression of NTRK3 in UM-UC-14 cells promoted AKT-mTOR pathway activity, cellular migration, and cell invasion. From these observations, we concluded that NTRK3 may contribute to aggressive behaviors in UTUC by facilitating cell migration and invasion through its interaction with the AKT-mTOR pathway and the expression of NTRK3 is a potential predictor of clinical outcomes in cases of UTUC.

Eosinophilic pulmonary disease with ulcerative colitis: A case report.

RATIONALE: Eosinophilic pulmonary disease (EPD) is a general term for a large group of diseases with complex etiology. Ulcerative colitis is an inflammatory bowel disease (IBD). Patients with IBD may have pulmonary involvement. We herein present a case of ulcerative colitis complicated with EPD. PATIENT CONCERNS: A 34-year-old woman with ulcerative colitis presented with dry cough. She had peripheral eosinophilia and apical ground glass opacities on CT (computed tomography) of her chest. Antibiotic treatment was ineffective. DIAGNOSES: Lung biopsy revealed eosinophil infiltration in the alveolar space and interstitial space, so EPD was considered. INTERVENTIONS: After oral administration of prednisone, the lung shadow on CT disappeared when the cough symptoms resolved. However, the symptoms recurred after drug withdrawal, and the lung shadow reappeared on imaging. The cough symptoms and lung shadow disappeared after oral prednisone was given again. Prednisone was slowly discontinued after 6 months of treatment. OUTCOMES: The patient stopped prednisone for half a year. No recurrence or abnormal CT findings were detected during the half-year follow-up. LESSONS: The clinical manifestations of EPD are atypical, laboratory and imaging findings are not specific, and it is difficult to make a definite diagnosis before lung biopsy. The diagnosis depends on pathological examination. Glucocorticoid treatment is effective, but some patients may relapse after drug withdrawal. Active follow-up after glucocorticoid treatment is very important for identifying disease recurrence. Patients with IBD are relatively prone to developing EPD. The etiology of EPD is complex. In clinical practice, we need to make a diagnosis and differential diagnosis to clarify its etiology.

Influence of genetic polymorphisms on imatinib concentration and therapeutic response in patients with chronic-phase chronic myeloid leukemia.

BACKGROUND: Diminished bioavailability of imatinib in leukemic cells contributes to poor clinical response. We examined the impact of genetic polymorphisms of imatinib on the pharmacokinetics and clinical response in 190 patients with chronic myeloid leukaemia (CML). METHODS: Single nucleotide polymorphisms were genotyped using pyrophosphate sequencing. Plasma trough levels of imatinib were measured using liquid chromatography-tandem mass spectrometry. RESULTS: Patients carrying the TT genotype for ABCB1 (rs1045642, rs2032582, and rs1128503), GG genotype for CYP3A5-rs776746 and AA genotype for ABCG2-rs2231142 polymorphisms showed higher concentration of imatinib. Patients with T allele for ABCB1 (rs1045642, rs2032582, and rs1128503), A allele for ABCG2-rs2231142, and G allele for CYP3A5-rs776746 polymorphisms showed better cytogenetic response and molecular response. In multivariate analysis, carriers of the CYP3A5-rs776746 G allele exhibited higher rates of complete cytogenetic response (CCyR) and major molecular response (MMR). Similarly, patients with the T allele of ABCB1-rs1045642 and rs1128503 demonstrated significantly increased CCyR rates. Patients with the A allele of ABCG2-rs2231142 were associated with higher MMR rates. The AA genotype for CYP3A5-rs776746, and the CC genotype for ABCB1-rs104562, and rs1128503 polymorphisms were associated with a higher risk of imatinib failure. Patients with the G allele for CYP3A5-rs776746 exhibited a higher incidence of anemia, and T allele for ABCB1-rs2032582 demonstrated an increased incidence of diarrhea. CONCLUSIONS: Genotyping of ABCB1, ABCG2, and CYP3A5 genes may be considered in the management of patients with CML to tailor therapy and optimize clinical outcomes.

Lipid Profiles Impact on the Oncologic Outcome of Upper Tract Urothelial Carcinoma.

Background: The prognosis of upper tract urothelial carcinoma (UTUC) varies, with T3/T4 UTUC having less than 50% 5-year survival post-radical nephroureterectomy (RNU). Lipid profiles including cholesterol (CHOL), low-density lipoprotein (LDL), and triglycerides (TGs), and high-density lipoprotein (HDL) have shown correlations with oncologic outcomes in various cancers. We aimed to investigate the prognostic significance of the lipid profiles in UTUC patients who had received RNU. Methods: In this retrospective study, a total of 217 UTUC patients who underwent RNU were analyzed. Prognostic factors for overall survival (OS), cancer-specific survival (CSS), and progression-free survival (PFS) were assessed using Cox proportional hazards regression model and competing risk analysis. Results: The median follow-up duration was 2.36 years. Fifty-one (23.50%) of the patients experienced tumor progression, 16 (7.37%) died from UTUC, and 41 (18.89%) died from all causes during the follow-up period. Multivariate analysis revealed that elevated CHOL, low HDL, and elevated TG were linked to worse OS (P = 0.0188, 0.0002, and 0.0001, respectively). Higher CHOL, LDL, and TG, as well as lower HDL significantly affected PFS (P < 0.001 for all), and elevated CHOL and TG were associated with poorer CSS (P = 0.0033 and 0.0179). A competing risk model indicated that elevated LDL increased the risk of cancer progression (P = 0.407), with CHOL increasing the risk of UTUC-specific mortality (P = 0.0162). Limitations include retrospective design, limited, single-time sampling and relatively small sample size. Conclusions: Lipid profiles were identified as prognostic indicators for UTUC patients post-RNU. It highlights the potential importance of lipid management in improving tumor-related outcomes.

[Occurrence Characteristics of Microplastics in Multi-environmental Media and Bellamya aeruginosa of Manao River].

Microplastic pollution poses threats to aquatic ecosystems and human health. In this study, in order to investigate the characteristics of microplastic occurrence in different environmental media, the abundance, particle size, shape, color, and composition types of microplastics in the water column, sediment, riparian zone soil, and the benthic snail Bellamya aeruginosa of the Manao River were analyzed using field sampling, microscopic observation, and Fourier infrared spectroscopy. The results showed that the average abundance of microplastics in the surface water of the Manao River was (5.9±0.26) n·L-1; the abundance of microplastics in the upper sediment (by dry weight) was (1.35±0.1) n·g-1, and that in the lower sediment (by dry weight) was (0.93±0.12) n·g-1. The abundance of microplastics in the near riparian zone soil (by dry weight) was (0.68±0.16) n·g-1, and that in the far riparian zone soil (by dry weight) was (0.69±0.14) n·g-1, and the abundance of microplastics in the B. aeruginosa was (2.06±0.25) n·g-1. The analysis results showed that the abundance of microplastics in the upper and lower sediments were positively correlated; the abundance of microplastics in B. aeruginosa was positively correlated with the abundance of microplastics in the upper and lower sediments, respectively; and the abundance of microplastics in the near and far riparian zone soils were also correlated. Most of the microplastics within each environmental medium and B. aeruginosa were <0.1 mm in size, mainly in the form of fibers and fragments, mainly blue and black in color, and mainly composed of polypropylene (PP) and polyethylene (PE). It was found that microplastics in riparian zone soils mainly originated from the fragmentation and decomposition of agricultural plastic films. The results of this study shed light on the accumulation of microplastics in macrobenthic organisms through the investigation of microplastics in multi-environmental media and in the B. aeruginosa, which helps us to understand the potential ecological risk of microplastics in a comprehensive manner.

Comparison of the Efficacy Among Nilotinib, Dasatinib, Flumatinib and Imatinib in Newly Diagnosed Chronic-Phase Chronic Myeloid Leukemia Patients: A Real-World Multi-Center Retrospective Study.

BACKGROUND: There are limited data comprehensively comparing therapy responses and outcomes among nilotinib, dasatinib, flumatinib and imatinib for newly diagnosed chronic-phase chronic myeloid leukemia in a real-world setting. PATIENTS AND METHODS: Data from patients with chronic-phase CML receiving initial a second-generation tyrosine-kinase inhibitor (2G-TKI, nilotinib, dasatinib or flumatinib) or imatinib therapy from 77 Chinese centers were retrospectively interrogated. Propensity-score matching (PSM) analyses were performed to to compare therapy responses and outcomes among these 4 TKIs. RESULTS: 2,496 patients receiving initial nilotinib (n = 512), dasatinib (n = 134), flumatinib (n = 411) or imatinib (n = 1,439) therapy were retrospectively interrogated in this study. PSM analyses indicated that patients receiving initial nilotinib, dasatinib or flumatinib therapy had comparable cytogenetic and molecular responses (p = .28-.91) and survival outcomes including failure-free survival (FFS, p = .28-.43), progression-free survival (PFS, p = .19-.93) and overall survival (OS) (p values = .76-.78) but had significantly higher cumulative incidences of cytogenetic and molecular responses (all p values < .001) and higher probabilities of FFS (p < .001-.01) than those receiving imatinib therapy, despite comparable PFS (p = .18-.89) and OS (p = .23-.30). CONCLUSION: Nilotinib, dasatinib and flumatinib had comparable efficacy, and significantly higher therapy responses and higher FFS rates than imatinib in newly diagnosed CML patients. However, there were no significant differences in PFS and OS among these 4 TKIs. These real-world data may provide additional evidence for routine clinical assessments to identify more appropriate therapies.

The factors impacting on Gleason score upgrading in prostate cancer with initial low Gleason scores.

BACKGROUND: This study aims to investigate the factors contributing to the discrepancy in between biopsy Gleason score (GS) and radical prostatectomy GS in patients diagnosed with prostate cancer. METHODS: 341 patients who underwent radical prostatectomy from 2011/04 to 2020/12 were identified. 102 Patients with initial GS of six after biopsy were enrolled. Preoperative clinical variables and pathological variables were also obtained and assessed. The optimal cut-off points for significant continuous variables were identified by the area under the receiver operating characteristic curve. RESULTS: Upgrading was observed in 63 patients and non-upgrading in 39 patients. In the multiple variables assessed, smaller prostate volume (PV) (p value = 0.0007), prostate specific antigen density (PSAD) (p value = 0.0055), positive surgical margins (p value = 0.0062) and pathological perineural invasion (p value = 0.0038) were significant predictors of GS upgrading. To further explore preclinical variables, a cut-off value for PV (≤ 38 ml, p value = 0.0017) and PSAD (≥ 0.26 ng/ml2, p value = 0.0013) were identified to be associated with GS upgrading. CONCLUSIONS: Smaller PV and elevated PSAD are associated with increased risk of GS upgrading, whereas lead-time bias is not. A cut-off value of PV < 38 ml and PSAD > 0.26 ng/ml2 were further identified to be associated with pathological GS upgrading.

Clinical pharmacokinetics and drug-drug interactions of tyrosine-kinase inhibitors in chronic myeloid leukemia: A clinical perspective.

In the past decade, numerous tyrosine kinase inhibitors (TKIs) have been introduced in the treatment of chronic myeloid leukemia. Given the significant interpatient variability in TKIs pharmacokinetics, potential drug-drug interactions (DDIs) can greatly impact patient therapy. This review aims to discuss the pharmacokinetic characteristics of TKIs, specifically focusing on their absorption, distribution, metabolism, and excretion profiles. Additionally, it provides a comprehensive overview of the utilization of TKIs in special populations such as the elderly, children, and patients with liver or kidney dysfunction. We also highlight known or suspected DDIs between TKIs and other drugs, highlighting various clinically relevant interactions. Moreover, specific recommendations are provided to guide haemato-oncologists, oncologists, and clinical pharmacists in managing DDIs during TKI treatment in daily clinical practice.

Prognostic factors of intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: To evaluate predictive factors of increasing intravesical recurrence (IVR) rate in patients with upper tract urothelial carcinoma (UTUC) after receiving radical nephroureterectomy (RNUx) with bladder cuff excision (BCE). MATERIALS AND METHODS: A total of 2114 patients were included from the updated data of the Taiwan UTUC Collaboration Group. It was divided into two groups: IVR-free and IVR after RNUx, with 1527 and 587 patients, respectively. To determine the factors affecting IVR, TNM stage, the usage of pre-operative ureteroscopy, and pathological outcomes were evaluated. The Kaplan-Meier estimator was used to estimate the rates of prognostic outcomes in overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and bladder recurrence-free survival (BRFS), and the survival curves were compared using the stratified log-rank test. RESULTS: Based on our research, ureter tumor, female, smoking history, age (< 70 years old), multifocal tumor, history of bladder cancer were determined to increase the risk of IVR after univariate analysis. The multivariable analysis revealed that female (BRFS for male: HR 0.566, 95% CI 0.469-0.681, p < 0.001), ureter tumor (BRFS: HR 1.359, 95% CI 1.133-1.631, p = 0.001), multifocal (BRFS: HR 1.200, 95% CI 1.001-1.439, p = 0.049), history of bladder cancer (BRFS: HR 1.480, 95% CI 1.118-1.959, p = 0.006) were the prognostic factors for IVR. Patients who ever received ureterorenoscopy (URS) did not increase the risk of IVR. CONCLUSION: Patients with ureter tumor and previous bladder UC history are important factors to increase the risk of IVR after RNUx. Pre-operative URS manipulation is not associated with higher risk of IVR and diagnostic URS is feasible especially for insufficient information of image study. More frequent surveillance regimen may be needed for these patients.

Construction and optimization of a polygenic risk model for venous thromboembolism in the Chinese population.

BACKGROUND: Venous thromboembolism (VTE) has both environmental and genetic risk factors. It is regulated by polygenes and multisites. The polygenic risk score (PRS) has been widely used because any single genetic biomarker failed to accurately predict the genetic risk of VTE. However, no polygenic risk model has been proposed for VTE in the Chinese population. Thus, we aimed to construct a PRS model for the first episode of VTE in the Chinese population. METHODS: First, single nucleotide polymorphisms (SNPs) associated with VTE in genome-wide association studies, meta-analyses, and candidate gene studies were screened as variables for the PRS. The logarithm of the odds ratio was used to weight the variables. Second, a training set with simulated data from 1000 cases of VTE and 1000 controls was created with different genotypes and frequencies. Finally, we calculated the area under the receiver operating characteristic curve (AUC) to evaluate the discriminatory ability of the PRS model. RESULTS: We screened 53 SNPs potentially associated with the first episode of VTE in the Chinese population. The AUC of the PRS-53 model (containing 53 SNPs) was 0.748 (95% confidence interval, 0.727-0.770) in the training set. From the largest weight to the smallest weight, SNPs were incrementally added to the model to calculate the AUC for model optimization. The AUC of the PRS-10 model (containing 10 SNPs) was 0.718 (95% confidence interval, 0.696-0.740), with no statistically significant difference from the AUC for the PRS-53 model. CONCLUSIONS: The PRS-10 and PRS-53 models showed similar predictive abilities and satisfactory discriminatory power and can be used to predict the genetic risk of the first episode of VTE in the Chinese population. The simplified PRS-10 model is more efficient in clinical practice.

MicroRNA-299-3p inhibits cell proliferation, motility, invasion and angiogenesis via VEGFA in upper tract urothelial carcinoma.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) is a rare tumor with extraordinarily different features between Eastern and Western countries. Vascular endothelial growth factor-A (VEGFA) was originally identified as a secreted signaling protein and regulator of vascular development and cancer progression. In this study, we aimed to elucidate the molecular mechanisms underlying the regulation of VEGFA by microRNA in UTUC. METHODS: VEGFA expression was evaluated by immunohistochemistry in 140 human UTUC tissue samples. Next, we assessed the regulatory relationship between VEGFA and miR-299-3p by real-time PCR, western blotting, ELISA and dual-luciferase reporter assays using two UTUC cell lines. The role of miR-299-3p/VEGFA in cell proliferation, motility, invasion, and tube formation was analyzed in vitro. RESULTS: High VEGFA expression was significantly associated with tumor stage, grade, distant metastasis and cancer-related death and correlated with poor progression-free and cancer-specific survival. VEGFA knockdown repressed proliferation, migration, invasion and angiogenesis in UTUC cell lines. miR-299-3p significantly reduced VEGFA protein expression and miR-299-3p overexpression inhibited VEGFA mRNA and protein expression by directly targeting its 3'-UTR. Functional studies indicated that VEGFA overexpression reversed the miR-299-3p-mediated suppression of tumor cell proliferation, migration, invasion and angiogenesis. In addition, miR-299-3p/VEGFA suppressed cellular functions in UTUC by modulating the expression of P18 and cyclin E2. CONCLUSIONS: Our findings suggest that miR-299-3p possibly suppresses UTUC cell proliferation, motility, invasion and angiogenesis via VEGFA. VEGFA may act as a prognostic predictor, and both VEGFA and miR-299-3p could be potential therapeutic targets for UTUC.

Machine Learning Model of ResNet50-Ensemble Voting for Malignant-Benign Small Pulmonary Nodule Classification on Computed Tomography Images.

BACKGROUND: The early detection of benign and malignant lung tumors enabled patients to diagnose lesions and implement appropriate health measures earlier, dramatically improving lung cancer patients' quality of living. Machine learning methods performed admirably when recognizing small benign and malignant lung nodules. However, exploration and investigation are required to fully leverage the potential of machine learning in distinguishing between benign and malignant small lung nodules. OBJECTIVE: The aim of this study was to develop and evaluate the ResNet50-Ensemble Voting model for detecting the benign and malignant nature of small pulmonary nodules (<20 mm) based on CT images. METHODS: In this study, 834 CT imaging data from 396 patients with small pulmonary nodules were gathered and randomly assigned to the training and validation sets in an 8:2 ratio. ResNet50 and VGG16 algorithms were utilized to extract CT image features, followed by XGBoost, SVM, and Ensemble Voting techniques for classification, for a total of ten different classes of machine learning combinatorial classifiers. Indicators such as accuracy, sensitivity, and specificity were used to assess the models. The collected features are also shown to investigate the contrasts between them. RESULTS: The algorithm we presented, ResNet50-Ensemble Voting, performed best in the test set, with an accuracy of 0.943 (0.938, 0.948) and sensitivity and specificity of 0.964 and 0.911, respectively. VGG16-Ensemble Voting had an accuracy of 0.887 (0.880, 0.894), with a sensitivity and specificity of 0.952 and 0.784, respectively. CONCLUSION: Machine learning models that were implemented and integrated ResNet50-Ensemble Voting performed exceptionally well in identifying benign and malignant small pulmonary nodules (<20 mm) from various sites, which might help doctors in accurately diagnosing the nature of early-stage lung nodules in clinical practice.

Downregulation of CRTAC1 in Urothelial Carcinoma Promotes Tumor Aggressiveness and Confers Poor Prognosis.

BACKGROUND: Cartilage acidic protein 1 (CRTAC1) is a glycosylated calcium-binding extracellular matrix protein. The oncological functions of CRTAC1 in urothelial carcinoma (UC) of the urinary bladder (UB) and upper urinary tract (UT) have not yet been elucidated. Based on the published UBUC transcriptome data, we re-evaluated the differential expression profile of calcium ion binding-related genes (GO:0005509), and we found that CRTAC1 was the most significantly downregulated gene in UBUC progression. Therefore, we analyzed the prognostic value and biological significance of CRTAC1 expression in UC. METHODS: We used immunohistochemistry to determine the CRTAC1 expression levels in 340 patients with UTUC and 295 patients with UBUC. The CRTAC1 expression was compared with the clinicopathological characteristics, and the prognostic impact of CRTAC1 on metastasis-free survival (MFS) and disease-specific survival (DSS) was evaluated. To study the biological functions of CRTAC1, the proliferation, migration, invasion, and tube formation abilities of UC-derived cells were evaluated. RESULTS: A low CRTAC1 expression significantly correlated with high tumor stage, high histological grade, perineural invasion, vascular invasion, nodal metastasis, and high mitotic rate (all p < 0.01). Moreover, the CRTAC1 immunoexpression status was an independent prognostic factor for MFS and DSS in UBUC and UTUC patients (all p < 0.001) in the multivariate analysis. The exogenous expression of CRTAC1 suppressed the cell proliferation, invasion, and angiogenesis, and downregulated the matrix metallopeptidase 2 (MMP2) level in BFTC909 and T24 cells. CONCLUSIONS: CRTAC1 may participate in progression of UC and serve as a prognostic marker for metastasis. Low CRTAC1 expression was significantly associated with aggressive UC characteristics and worse clinical outcomes. The inclusion of CRTAC1 immunoexpression in the standard pathological variables may optimize the risk stratification of patients.

The efficacy and safety of eltrombopag in treating TKI-induced thrombocytopenia in patients with chronic myeloid leukemia.

ABSTRACTThrombocytopenia is one of the most common hematological adverse reactions in chronic myeloid leukemia (CML) patients receiving tyrosine kinase inhibitors (TKI) therapy, causing life-threatening bleeding cases. However, there are fewer therapeutic drugs for TKI-induced thrombocytopenia. Eltrombopag is a non-peptide thrombopoietin receptor agonist used for the treatment of immune thrombocytopenia， aplastic anemia, and hepatitis C-associated thrombocytopenia. Nevertheless, studies of eltrombopag for TKI-induced thrombocytopenia are still lacking. This study retrospectively analyzed the clinical and test data of 21 CML patients with TKI-related thrombocytopenia. The results demonstrated that the median baseline value of thrombocytopenia in the 21 CML patients was 15.57 × 109/L [2-28 × 109/L]. Following treatment with eltrombopag, 16 patients had a significant increase in their platelet levels. The peak median for platelet increase in effective responders was 145.12 × 109/L (51-460 × 109/L). However, 5 patients failed to respond to eltrombopag. Moreover, 4 of the 21 patients enrolled had adverse reactions, including reversible liver function impairment, palpitation, headache, insomnia, and loss of appetite. Nonetheless, no cases of disease progression, thrombotic events, or myelofibrosis were observed. Hence, eltrombopag may be a useful adjunctive therapy for relieving TKI-related thrombocytopenia in patients with CML.

Management of chronic myelogenous leukemia with COVID-19 and hepatitis B.

The application of immunosuppressive agents and targeted drugs has opened a novel approach for the treatment of hematological tumors, and the application of tyrosine kinase inhibitors for the treatment of chronic myeloid leukemia is one of the landmark breakthroughs that has considerably improved the prognosis of CML patients. However, with the extensive use of TKI, the co-infection of CML patients has become increasingly apparent, especially regarding infectious diseases such as hepatitis B and COVID-19. The underlying mechanism may be related to the inhibition of the immune function by TKI. Poor management, including disease progression due to the infectious disease or TKI dose reduction or discontinuation, may lead to adverse clinical outcomes and can even be life-threatening. Therefore, this review principally provides an overview of the pathogenesis and standardized management principles of CML patients with comorbid COVID-19 or hepatitis B in order to improve clinicians' awareness of the risks so as to more effectively diagnose and treat CML and improve the survival rate and quality of life of patients. In the past two decades, owing to the advent of imatinib, chronic myeloid leukemia (CML) has transformed into a chronic controllable disease, and even treatment-free remission can be anticipated. Earlier studies have indicated that tyrosine kinase inhibitor (TKI) exerts a peculiar inhibitory effect on the body's immune function. Therefore, with the widespread application of TKI, more and more attention has been paid to the comorbidity of infectious diseases in CML patients, especially in patients with progressive disease or non-remission. Despite some studies revealing that the proportion and severity of SARS-CoV-2 infection in CML patients receiving TKI treatment are lower than in patients with other hematological malignancies, CML patients with stable disease are still recommended to be vaccinated against SARS-CoV-2, while TKI may or may not be discontinued. Meanwhile, the management of CML patients during the epidemic of coronavirus disease 2019 (COVID-19) still necessitates further discussion. This article also provides an overview of TKI-related hepatitis B reactivation. If not managed, patients may face adverse consequences such as hepatitis B reactivation-related hepatitis, liver failure, and progression of CML after forced withdrawal of medication. Therefore, this review aimed to comprehensively describe the management of CML patients with comorbid COVID-19, the pathogenesis of hepatitis B reactivation, the indicated population for prophylactic antiviral therapy, the time of antiviral drug discontinuation, and drug selection.

Adherence to tyrosine kinase inhibitor and clinical outcomes in patients with chronic myeloid leukemia.

PURPOSE: To ensure optimal care for patients with chronic myeloid leukemia (CML), adherence to tyrosine kinase inhibitors (TKIs) has emerged as a critical component. The objective of this study was to assess the impact of TKIs adherence on clinical outcomes in a cohort of Chinese CML patients who received treatment with TKIs. METHODS: This retrospective study employed a cross-sectional design utilizing questionnaires to assess adherence to TKIs in a sample of 398 patients diagnosed with CML. Adherence was measured using the Morisky Medication Adherence Scale (MMAS-8), which dichotomizes patients into low, medium, and high adherence groups. RESULTS: Of the patients included in this study, 34.2% were classified as highly adherent, with 43.2% and 22.6% of patients categorized as having medium and low adherence, respectively. Compared to the low-adherence group, patients in the medium- and high-adherence groups exhibited significantly higher rates of achieving major molecular response (MMR) and lower rates of switching TKIs. Moreover, patients who failed to adhere to TKIs treatment demonstrated significantly lower event-free survival and failure-free survival compared to those in the high-adherence group. Notably, regular molecular monitoring and utilization of the "CML Academy" mobile application were positively associated with increased TKI adherence. On the other hand, patients receiving third-generation or above first-line TKIs treatment displayed reduced adherence. CONCLUSION: The findings suggest that high adherence to TKIs treatment confers clinical benefits to patients with CML. Accordingly, the implementation of effective guidance and intervention measures aimed at promoting adherence to TKIs therapy in real-world settings is imperative.