Development and validation of a nomogram model for predicting distant metastasis of aged ≥50 patients with thyroid carcinoma: a SEER database analysis.

OBJECTIVE: This work aimed to construct and validate a model for predicting distant metastasis (DM) in thyroid carcinoma (TC) patients aged≥50. PATIENTS AND METHODS: The research data were collected from the Surveillance, Epidemiology, and End Results (SEER) program databases via SEER*Stat software (https://seer.cancer.gov/). Logistics regression was used to screen the independent risk factors for TC patients. The nomogram was constructed and validated based on the logistics regression results for predicting DM occurrence in TC patients. Moreover, the characteristic curves (ROC) were used to assess the predictive performance. The decision analysis curve (DCA) and the calibration curve were used to test this nomogram's accuracy and discrimination. Additionally, we analyzed survival and risk scores in TC patients with metastasis using the Kaplan-Meier (KM) method. RESULTS: A total of 11,166 TC patients were divided into a training set and a validation set. The results showed that topography (T), lymph node metastasis (N), and (grade) G were crucial risk factors for predicting DM. ROC analysis showed that the model had a good discriminative ability both in the training and validation set. The DCA curve showed greater net benefits across a range of DM risks for the nomogram in the training and validation set. Survival analyses showed that the metastasis cases with low-risk scores have shown a poorer prognosis in this study, both in the training and validation set. CONCLUSIONS: The nomogram model had excellent predictive performance and net benefit for predicting DM of TC patients aged ≥50. The model can help doctors develop treatment plans for their patients.

Dynamic contrast-enhanced magnetic resonance imaging in cervical cancer: correlation between quantitative parameters and molecular markers hypoxia-inducible factors-1-alpha, vascular endothelial growth factor, and Ki-67.

AIM: To investigate whether dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) has the potential to non-invasively detect microenvironmental condition by quantitatively measuring blood perfusion, vessel wall permeability, and vascularity, and to elucidate the possible correlations between DCE-MRI quantitative parameters and the expression level of hypoxia, vascularity, and cell proliferation related molecular biomarkers. MATERIALS AND METHODS: In this prospective single center clinical study, 58 patients diagnosed with cervical cancer underwent DCE-MRI before anticancer treatment were enrolled. Ktrans, Kep, Ve, and Vp were generated from Extended Toft's model. Then patients conducted colposcopy biopsy within 1 week after DCE-MRI. Pretreatment expression levels of HIF-1α, VEGF and Ki-67 were assessed and scored by immunohistochemistry on colposcopy obtained tumor specimens. RESULTS: In HIF-1α low-expression group, Ktrans (p=0.031) and Kep (p=0.012) values were significantly higher than the high-expression group. In VEGF high-expression group, Ktrans (p=0.044) and Ve values (p=0.021) were significantly higher than the low-expression group. In Ki-67 high-expression group, Ktrans (p=0.026) and Kep (p=0.033) were significantly higher than the low-expression group. Multiple linear regression analyses and Pearson correlation revealed that Ktrans independently negatively correlated with HIF-1α expression, Ve independently positively correlated with VEGF, and Kep independently positively correlated with Ki-67. The area under the ROC curves of Ktrans for HIF-1α, Ve for VEGF, and Kep for Ki-67 were 0.728, 0.743, 0.730, respectively. CONCLUSION: Our results suggest that DCE-MRI quantitative parameters could be potentially used as imaging markers for non-invasively detecting microenvironmental hypoxia, vascularity and proliferation in cervical cancer patients.

[Efficacy analysis of 7 cases of mixed neuroendocrine-nonneuroendocrine neoplasm of the duodenal papilla].

The clinical data of 7 patients diagnosed with mixed neuroendocrine-nonneuroendocrine neoplasm were analyzed in the Department of Hepatobiliary Surgery of Hunan Provincial People's Hospital from January 2016 to December 2022. Among the 7 patients, 5 were male and 2 were female, with an average age of 59.3 years. Its clinical characteristics are similar to malignant ampulla tumors, and it is difficult to differentiate them. The preoperative puncture biopsy positivity rate is low, making it difficult to diagnose preoperatively, and the prognosis is worse.Comprehensive treatment including surgery, chemotherapy, and radiotherapy can be the preferred treatment option for this disease.

A novel vitrified cryopreservation approach with stem cell-laden hydrogel microcapsules.

BACKGROUND: Stem cell-laden hydrogel microcapsules construction is important for a wide application in tissue engineering and cell-based medicine, such as building an ideal immune barrier. Challenges are emerging for effectively storing such microcapsules by cryopreservation, and a large proportion of research has been on the cryopreservation of single cells encapsulated into microcapsules without a core-shell structure. OBJECTIVE: To achieve the effective cryopreservation of stem cell-laden hydrogel microcapsules with a core-shell structure. MATERIALS AND METHODS: A novel core-shell alginate hydrogel encapsulation method was used to produce mesenchymal stem cell-laden microcapsules by microfluidic technique. RESULTS: This microcapsule could inhibit ice formation to achieve vitreous cryopreservation with a low concentration (2 M) of penetrating cryoprotectants. CONCLUSION: Cell laden hydrogel microcapsules may have the potential to be the basis of a new strategy of cell cryopreservation and applications. https://doi.org/10.54680/fr24210110212.

[Effect of HBV DNA load on the safety and prognosis of systematic therapy in advanced hepatocellular carcinoma].

Objective: To study the effect of hepatitis B virus (HBV) infection on the occurrence of liver damage, HBV reactivation (HBVr) and the influence of HBVr on the prognosis of patients with advanced hepatocellular carcinoma (HCC) receiving systemic therapy. Methods: The clinical data of 403 patients with HBV-related HCC at the Department of Infectious Diseases, The Third Affiliated Hospital of Sun Yat-Sen University et al, from July 2018 to December 2020 were collected. The incidence of liver damage and HBVr during systematic therapy, and the influence of HBVr on survival prognosis were analyzed. Results: Of the 403 patients, 89.1% were male (n=359), with a median age of 51 years (51.5±12.1). Before propensity score matching (PSM), the proportion of patients with cirrhosis, TNM and advanced BCLC stage was higher in high HBV-DNA (baseline HBV-DNA>1000 U/ml, n=147) group comparing with the low HBV-DNA (baseline HBV DNA≤1000 u/ml, n=256) group (P<0.05). There was no significant difference in baseline indexes between the two groups after PSM. In 290 patients after PSM, there was no significant difference in the incidence of liver damage and HBVr between high HBV-DNA group and low HBV-DNA group (P>0.05). Survival analysis was performed on 169 patients with survival data, the median overall survival (OS) was found to be 11.49 months (95%CI: 7.77-12.89) and 16.65 months (95%CI: 10.54-21.99, P=0.008) in the high and low HBV-DNA groups, respectively. And median progression-free survival (PFS) was 7.41 months (95%CI: 5.06-8.67) and 10.55 months (95%CI: 6.72-13.54, P=0.038), respectively, with a statistically significant difference. There were no differences in overall survival (OS) and progression-free survival (PFS) between patients with and without HBVr and those with or without liver damage (P>0.05). Conclusions: HBV-DNA levels above 1 000 U/ml before systemic therapy do not increase the risk of liver damage or HBVr during systemic therapy in patients with HBV-related hepatocellular carcinoma, and such patients can safely receive systemic therapy.

[Efficacy of combined treatment with pirfenidone and PD-L1 inhibitor in mice bearing ectopic bladder cancer xenograft].

OBJECTIVE: To assess the efficacy of pirfenidone combined with PD-L1 inhibitor for treatment of bladder cancer in a mouse model and its effect on tumor immune microenvironment modulation. METHODS: Forty C57BL/6 mouse models bearing ectopic human bladder cancer xenografts were randomized into control group, PD-L1 inhibitor group, pirfenidone group and combined treatment group (n=10). After successful modeling, PD-L1 inhibitor treatment was administered via intraperitoneal injection at 12.5 mg/kg every 3 days, and oral pirfenidone (500 mg/kg) was given on a daily basis. The survival rate of the mice and tumor growth rate were compared among the 4 groups. The expressions of CD3, CD8, CD45, E-cadherin and N-cadherin in the tumor tissues were detected with immunohistochemistry after the 21-day treatment, and bone marrow-derived suppressor cells (MDSCs) were observed with immunofluorescence staining; serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), creatinine (CRE) and lactate dehydrogenase (LDH-L) were analyzed using an automated biochemical analyzer. RESULTS: Treatment with PD-L1 inhibitor and pirfenidone alone both significantly decreased tumor growth rate and tumor volume at 21 days (P < 0.05), but the combined treatment produced an obviously stronger inhibitory effect (P < 0.05). PD-L1 inhibitor and pirfenidone alone significantly increased E- cadherin expression and decreased N-cadherin expression in the tumor tissue (P < 0.05). The two treatments both significantly increased the percentage of CD3+, CD8 and CD45+ T cells and decreased the percentage of Ly-6G+CD11b+MDSCs in the tumor tissue, and these changes were more obvious in the combined treatment group (P < 0.05). No significant differences were found in serum ALT, AST, BUN, CRE or LDH-L levels among the 4 groups (P>0.05). CONCLUSION: Combined treatment with pirfenidone and PD-L1 inhibitor significantly inhibits the progression of bladder cancer in mice possibly by regulating tumor immune microenvironment and inhibiting epithelial-mesenchymal transition of the tumor cells.

Excitation functions for fast neutron induced reactions on iron and lead.

Cross sections of the 54Fe(n,p)54Mn, 54Fe(n,α)51Cr, 56Fe(n,p)56Mn and 204Pb (n,2n)203Pb reactions induced by D-T neutrons were obtained with activation method and γ-ray spectrometry technique. Experimental values measured in this work are consistent with most of the previous literature data. These reactions cross sections were theoretically calculated by using the TALYS-1.96 and EMPIRE-3.2.3 codes from threshold up to 20 MeV, and significant discrepancies were found between calculated results and experiment data. In addition, experimental values are compared with evaluated nuclear data of the CENDL-3.2, ENDF/B-VIII.0, JENDL-5, BROND-3.1 and JEFF-3.3 libraries, and significant difference was found for the 54Fe(n,α)51Cr reaction in ENDF/B-VIII.0 library but not for other reactions.

Dai gen. nov., a new genus of Gnaphosinae (Araneae: Gnaphosidae) from Yunnan, China, with descriptions of two new species.

A new ground spider genus Dai gen. nov. of subfamily Gnaphosinae is described with the type species D. jinchii sp. nov. () and D. jijiao sp. nov. () from Yunnan Province, China.

[The role of NLRP3 inflammasome pathway in silicosis-induced pulmonary fibrosis and its prospect as a therapeutic target].

Inhalation of crystalline silicon dioxide particles can induce silicosis, and the development of silicosis is closely related to the occurrence and development of pulmonary inflammation and pulmonary fibrosis. NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome has been established as a major proinflammatory receptor for sensing environmental danger signals. Activation of NLRP3 inflammasomes after phagocytosis of silicon dioxide particles by pulmonary macrophages may be an important mechanism to induce oxidative stress and sustained inflammatory response in the lung. This article summarizes the role of NLRP3 inflammasome in the inflammatory response and pulmonary fibrosis in silicosis, and analyzes it as a potential target for silicosis treatment.

[Comparison among different flushing media for intracoronary imaging with optical coherence tomography].

Objective: To explore the effects and safety of saline mixed 1∶1 with contrast medium (mixed medium) and pure heparinized saline as alternative media for optimal Optical Coherence Tomography (OCT) guided percutaneous coronary intervention (PCI). Methods: This single-center, prospective cohort study enrolled patients who underwent PCI with OCT guidance for chronic stable angina or acute coronary syndrome at the Department of Cardiology, the Second Hospital of Jilin University from October 2021 to August 2022. The target vessels were examined using OCT with three different flushing media at the same anatomical positions: contrast agent, mixed medium, and pure heparinized saline. An independent observer analyzed all imaging results and evaluated the lumen imaging quality, using the proportion of the clear imaging field (CIF%) as a quantitative measure for analysis. The average luminal diameter was compared among different flushing media. The study also assessed the image quality of the luminal anatomical structures, lesion pathologies, and stents. Results: A total of 105 patients were enrolled in the study, including 110 target vessels. The age of the enrolled patients was (60.5±8.4) years, with 60 male patients (57.1%). OCT examinations were successfully completed using all three media, and no related complications were observed in any groups. The three flushing media presented with the same image quality in terms of depicting the lumen anatomical structures, lesion characteristics, and stent-related features. The mixed medium group achieved a comparable CIF% to the contrast group with both right and left coronary arteries (right coronary 100.0% (100.0%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05; left coronary 100.0% (95.9%, 100.0%) vs. 100.0% (100.0%, 100.0%), P>0.05). While the saline group reached a comparable CIF% to the contrast group with right coronary arteries (100.0% (97.6%, 100.0%) vs. 100.0% (95.9%, 100.0%), P>0.05) but showed a significantly lower CIF% with left coronary arteries (84.9% (75.9%, 93.4%) vs. 100.0% (100.0%, 100.0%), P<0.05). For the average diameter of the coronary lumen, there was no statistically significant difference between the mixed medium group and the saline group compared to the contrast group with both right and left coronary arteries (P>0.05). Conclusions: A 1∶1 heparinized saline and contrast mixture can serve as a substitute flushing medium for OCT examination during PCI procedure. Pure saline can also yield good results in OCT examination of the right coronary artery, and both alternatives are safe for use as flushing medium in OCT imaging.

[Research progress on the role of resveratrol in wound healing].

The difficulty of wound healing in patients is a difficult problem that doctors in all clinical departments may encounter, and there is still no good solution. Resveratrol is a kind of natural active substance, which has anti-inflammatory, antioxidant, antibacterial, and angiogenesis promoting effects, and is a potential drug to promote wound healing. However, the clinical application of resveratrol is limited due to its low bioavailability. In this review, the molecular mechanism of resveratrol in promoting wound healing and its administration methods in wound treatment were reviewed to provide ideas for the redevelopment of resveratrol.

[The cases of tracing the source of patients infected with Omicron variant of SARS-CoV-2 based on wastewater-based epidemiology in Shenzhen].

Wastewater-based epidemiology (WBE) is an emerging discipline, which has been applied to drug abuse tracking and infectious disease pathogen surveillance. During the COVID-19 epidemic, WBE has been applied to monitor the epidemic trend and SARS-CoV-2 variants etc. In order to detect hidden COVID-19 cases and prevent transmission in the community, wastewater surveillance system for monitoring SARS-CoV-2 RNA was developed in Shenzhen. The sewage sampling sites were set up in key places such as the port areas, urban villages and residential communities of Futian, Nanshan, Luohu and Yantian districts. From July 26 to November 30, 2022, a total of 369 sewage sampling sites were set up, covering 1.93 million people. Continuous sampling was carried out for 3 hours in the peak period of water use every day. Sewage virus enrichment and SARS-CoV-2 nucleic acid detection were carried out by polyethylene glycol precipitation method and RT-qPCR, and a positive water sample disposal process was molded. This article aims to introduce the case of source tracing of COVID-19 infected patients based on urban sewage in Shenzhen. The sewage monitoring of Honghu water treatment plant in Luohu District played an early warning role, and the source of infection was traced. In the disposal of positive water samples in Futian South Road, Futian District, the important experience of monitoring point layout was obtained. In the sewage monitoring of Nanshan village, Nanshan District, the existence of occult infection was revealed. Sharing the experience of tracing the source of COVID-19 patients to avoid the spread of COVID-19 in the community based on wastewater surveillance of SARS-CoV-2 RNA in Shenzhen, and summarizing the advantages and application prospects of sewage surveillance can provide new ideas for monitoring emerging or re-emerging pathogens that are known to exhibit gastrointestinal excretion in the future.

[Analysis of the clinical characteristics of acute myeloid leukemia related to the treatment of hematological and solid tumors].

Objective: To compare and analyze the clinical characteristics of acute myeloid leukemia (AML) related to the treatment of hematological tumors and solid tumors. Methods: The laboratory and clinical data of 41 patients with treatment-related AML (t-AML) in the Department of Hematology, Henan Cancer Hospital from January 2014 to December 2021 were retrospectively analyzed, and they were divided into hematological tumor group and solid tumor group. Survival analysis was performed using the Kaplan-Meier method and Log rank test. Results: The median interval from the first tumor diagnosis to t-AML in 41 patients was 21.0 (16.5-46.0) months; 24 (58.5%) had abnormal expression of lymphoid antigen, 28 (68.3%) had abnormal karyotype, 18 cases (43.9%) were positive for fusion gene, and 28 cases (68.3%) were positive for gene mutation; the median recurrence-free survival (RFS) was 11.0 months, and the median overall survival (OS) was 11.5 months. The proportion of acute promyelocytic leukemia ([APL], 0.0, 0/13), complete response ([CR],18.2%, 2/11), median OS (4.5 months) and median RFS (2.5 months) of t-AML patients in the hematological tumor group were significantly lower than those in the solid tumor group (35.7%, 10/28; 68.0%, 17/25; not reach; not reach), but the proportion of M4 /M5 (93.2%,12/13) was significantly higher than that in the solid tumor group (53.6%,15/18; all P values<0.05). Through subgroup analysis, the proportion of patients with positive PML-RARa and good prognosis karyotypes in the solid tumor group (35.7%, 10/28; 46.4%, 13/28) was significantly higher than that in the hematological tumor group (0.0, 0/13; 0.0, 0/13; P<0.05), while the proportion of patients with intermediate karyotypes (42.9%, 12/28) was significantly lower than that in the hematological tumor group (84.6%, 11/13; P<0.05), the difference was statistically significant. The CR rate (90.0%, 9/10), median OS (not reach) and median RFS (not reach) in the t-APL group were higher than those in the t-AML (without t-APL) group (38.5%, 10/26; 6 months; 8 months; P<0.05). After excluding the effect of t-APL patients, there was no significant difference in the CR rate, median OS and median RFS between the solid tumor group (8; 9 months; not reach) and the hematological tumor group (2; 4 months; 2 months; P>0.05). Univariate analysis showed that the primary tumor belongs to hematological tumor was a common risk factor for OS and RFS in t-AML patients (P<0.10). Conclusions: Compared with patients with t-AML secondary to solid tumors, patients with t-AML secondary to hematological tumors have poorer treatment effects and poorer prognosis. After excluding the effect of t-APL patients, there are no significant differences in the treatment efficacy and prognosis between the two types of t-AML patients.

Toripalimab plus axitinib versus sunitinib as first-line treatment for advanced renal cell carcinoma: RENOTORCH, a randomized, open-label, phase III study.

BACKGROUND: Immune checkpoint inhibitors in combination with tyrosine kinase inhibitors are standard treatments for advanced clear cell renal cell carcinoma (RCC). This phase III RENOTORCH study compared the efficacy and safety of toripalimab plus axitinib versus sunitinib for the first-line treatment of patients with intermediate-/poor-risk advanced RCC. PATIENTS AND METHODS: Patients with intermediate-/poor-risk unresectable or metastatic RCC were randomized in a ratio of 1 : 1 to receive toripalimab (240 mg intravenously once every 3 weeks) plus axitinib (5 mg orally twice daily) or sunitinib [50 mg orally once daily for 4 weeks (6-week cycle) or 2 weeks (3-week cycle)]. The primary endpoint was progression-free survival (PFS) assessed by an independent review committee (IRC). The secondary endpoints were investigator-assessed PFS, overall response rate (ORR), overall survival (OS), and safety. RESULTS: A total of 421 patients were randomized to receive toripalimab plus axitinib (n = 210) or sunitinib (n = 211). With a median follow-up of 14.6 months, toripalimab plus axitinib significantly reduced the risk of disease progression or death by 35% compared with sunitinib as assessed by an IRC [hazard ratio (HR) 0.65, 95% confidence interval (CI) 0.49-0.86; P = 0.0028]. The median PFS was 18.0 months in the toripalimab-axitinib group, whereas it was 9.8 months in the sunitinib group. The IRC-assessed ORR was significantly higher in the toripalimab-axitinib group compared with the sunitinib group (56.7% versus 30.8%; P < 0.0001). An OS trend favoring toripalimab plus axitinib was also observed (HR 0.61, 95% CI 0.40-0.92). Treatment-related grade ≥3 adverse events occurred in 61.5% of patients in the toripalimab-axitinib group and 58.6% of patients in the sunitinib group. CONCLUSION: In patients with previously untreated intermediate-/poor-risk advanced RCC, toripalimab plus axitinib provided significantly longer PFS and higher ORR than sunitinib and had a manageable safety profile TRIAL REGISTRATION: ClinicalTrials.gov NCT04394975.

Fast neutron induced reaction cross sections on natural manganese and tantalum.

The cross sections for the 55Mn(n,2n)54Mn, 181Ta(n,2n)180gTa, and 181Ta(n,p)181Hf reactions were measured to be 705.1 ± 26.1 mb at 14.0 MeV, 1362.7 ± 87.2 mb at 13.6 MeV, and 2.31 ± 0.09 mb at 13.6 MeV, respectively, by using an off-line γ-ray spectroscopic technique. The neutrons were produced via the 3H(d,n)4He reaction. The monitor reactions 27Al(n,α)24Na and 93Nb(n,2n)92mNb were used for neutron flux determination. The results from the present work were compared with those of the literature and the evaluated data from ENDF/B-VIII.0, JEFF-3.3, JENDL-5, CENDL-3.2, and BROND-3.1 libraries. Besides, the cross sections were also estimated with the TALYS-1.96 nuclear model code using different level density models for a better description of the present work and literature data. The present experimental results were found to be in good agreement with most of the available literature data and with the evaluated data.

Clinical service evaluation of the feasibility and reproducibility of novel artificial intelligence based-echocardiographic quantification of global longitudinal strain and left ventricular ejection fraction in trastuzumab-treated patients.

Introduction: Cardiotoxicity is a potential prognostically important complication of certain chemotherapeutic agents that may result in preclinical or overt clinical heart failure. In some cases, chemotherapy must be withheld when left ventricular (LV) systolic function becomes significantly impaired, to protect cardiac function at the expense of a change in the oncological treatment plan, leading to associated changes in oncological prognosis. Accordingly, patients receiving potentially cardiotoxic chemotherapy undergo routine surveillance before, during and following completion of therapy, usually with transthoracic echocardiography (TTE). Recent advancements in AI-based cardiac imaging reveal areas of promise but key challenges remain. There are ongoing questions as to whether the ability of AI to detect subtle changes in individual patients is at a level equivalent to manual analysis. This raises the question as to whether AI-based left ventricular strain analysis could provide a potential solution to left ventricular systolic function analysis in a manner equivocal to or superior to conventional assessment, in a real-world clinical service. AI based automated analyses may represent a potential solution for addressing the pressure of increasing echocardiographic demands within limited service-capacity healthcare systems, in addition to facilitating more accurate diagnoses. Methods: This clinical service evaluation aims to establish whether AI-automated analysis compared to conventional methods (1) is a feasible method for assessing LV-GLS and LVEF, (2) yields moderate to good correlation between the two approaches, and (3) would lead to different clinical recommendations with serial surveillance in a real-world clinical population. Results and Discussion: We observed a moderate correlation (r = 0.541) in GLS between AI automated assessment compared to conventional methods. The LVEF quantification between methods demonstrated a strong correlation (r = 0.895). AI-generated GLS and LVEF values compared reasonably well with conventional methods, demonstrating a similar temporal pattern throughout echocardiographic surveillance. The apical-three chamber view demonstrated the lowest correlation (r = 0.423) and revealed to be least successful for acquisition of GLS and LVEF. Compared to conventional methodology, AI-automated analysis has a significantly lower feasibility rate, demonstrating a success rate of 14% (GLS) and 51% (LVEF).

[Interpretation of the Implant Dentistry Core Outcome Set and Measurement international consensus report].

Selection and measurement of clinical outcome are key components of clinical research in implant dentistry. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine took the lead and collaborated with multiple internationally renowned colleges of stomatology to develop an international consensus on the core outcome set and measurement in implant dentistry, which took two years and was published in May, 2023 in Journal of Clinical Periodontology and Clinical Oral Implants Research simultaneously. The consensus, aiming at identifying the full spectrum of benefits and harms of interventions, provides a comprehensive, agreed, and standardized set of outcomes that should be measured and reported as a minimum in clinical trials relating with implant dentistry, bone augmentation, and soft tissue augmentation. The present review describes the methodology and key elements of the consensus to help Chinese clinical researchers fully understand and appropriately apply the core outcome set and improve the overall quality of Chinese clinical research in implant dentistry.

[To compare the efficacy and incidence of severe hematological adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia].

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.

[Humanized anti-CD25 monoclonal antibody as a salvage therapy for steroid-refractory acute graft-versus-host disease after hematopoietic stem cell transplantation].

Objective: To investigate the efficacy of humanized anti-CD25 monoclonal antibody for steroid-refractory acute graft-versus-host disease (SR-aGVHD) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Methods: A total of 64 patients with SR-aGVHD between June 2019 and October 2020 in Suchow Hopes Hematology Hospital were enrolled in this study. Humanized anti-CD25 monoclonal antibodies 1 mg·kg(-1)·d(-1) were administered on days 1, 3, and 8, and then once per week according to the disease progression. Efficacy was assessed at days 7, 14, and 28 after humanized anti-CD 25 treatment. Results: Of the 64 patients with a median age of 31 (15-63) years, 38 (59.4%) were male and 26 (40.6%) were female. The overall response (OR) rate of the humanized CD25 monoclonal antibody in 64 patients with SR-aGVHD on days 7, 14, and 28 were 48.4% (31/64), 53.1% (34/64), and 79.7% (51/64), respectively. Liver involvement is an independent risk factor for poor efficacy of humanized CD25 monoclonal antibody for SR-aGVHD at day 28 (OR=9.588, 95% CI 0.004-0.291, P=0.002). The median follow-up time for all patients was 17.1 (0.2-50.8) months from the start of humanized CD25 monoclonal antibody therapy. The 1- and 2-year OS rates were 63.2% (95% CI 57.1% -69.3%) and 52.6% (95% CI 46.1% -59.1%), respectively. The 1- and 2-year DFS rates were 58.4% (95% CI 52.1% -64.7%) and 49.8% (95% CI 43.4% -56.2%), respectively. The 1- and 2-year NRM rates were 28.8% (95% CI 23.1% -34.5%) and 32.9% (95% CI 26.8% -39.0%), respectively. The results of the multifactorial analysis showed that liver involvement (OR=0.308, 95% CI 0.108-0.876, P=0.027) and GVHD grade Ⅲ/Ⅳ (OR=9.438, 95% CI 1.211-73.577, P=0.032) were independent risk factors for OS. Conclusion: Humanized CD25 monoclonal antibody has good efficacy and safety for SR-aGVHD. This study shows that SR-aGVHD with pretreatment grade Ⅲ/Ⅳ GVHD and GVHD involving the liver has poor efficacy and prognosis and requires early intervention.