Abstract Background CD19 chimeric antigen receptor T cells (CAR-T cells) have demonstrated impressive response rates in relapse and refractory B acute lymphoblastic leukemia (r/r B-ALL). However, a high rate of patients suffered a CD19-negative (CD19 − ) relapse, and confers dismal outcomes. Dual targets approaches are proved to optimize the response rate and prevent antigen negative relapse. While for r/r B-ALL patients, whether it would show better outcome than CD19 CAR-T, is still not clear. Methods We conducted an open label, single center clinical trial at the First Affiliated Hospital of Soochow University to investigate the efficacy and safety of tandem CD19/CD22 dual targets CAR-T cells for r/r B-ALL. Results A total of 47 r/r B-ALL patients with high-risk cytogenetics, such as TP53 alteration, Philadelphia Chromosome positive ( Ph + ) ALL with T315I mutation and Ph-like ALL, received CD19/CD22 CAR-T therapy from 2017 October to 2021 June. Severe cytokine release syndrome occurred in 8 of 47 patients (17.02%). The immune effector cell-associated neurotoxicity syndrome (ICANS) and macrophage release syndrome (MAS) were rare observed. Hematologic complete remission (CR) was observed in 47/47 (100%) and 40/47 (85.1%) patients achieved minimal residual disease negative (MRD - ) CR. At a median follow up of 24.83 months (range, 2.57 to 50.67), overall survival was 93.56% (95% CI, 81.36–97.8%) at 6 months, 80.51% (95% CI, 65.88–89.35%) at 1 year. Twelve patients relapsed post CAR-T infusion and only 2 of 12 had CD19 - recurrence. The leukemia free survival (LFS) rate and cumulative incidence of relapse at 1 year was 74.47% (95% CI, 59.44–84.61%) and 19.66% (95% CI, 4.36–42.68%), respectively. High-risk cytogenetics did not affect the long long-term survival. The multivariable Cox regression analyses showed that better long-term LFS was associated with MRD - CR status post CAR-T, as well as bridging hematopoietic stem cell transplantation (HSCT). Conclusions Tandem CD19/CD22 CAR-T cells are safety and effective for patients with high-risk cytogenetics. Allo-HSCT can provide long-term durable disease control in these patients. Trial Registration: ClinicalTrials.gov identifier: NCT 03614858
Percutaneous interventions are gaining rapid acceptance in cardiology and revolutionizing the treatment of structural heart disease (SHD). As new percutaneous procedures of SHD are being developed, their associated complexity and anatomical variability demand a high-resolution special understanding for intraprocedural image guidance. During the last decade, three-dimensional (3D) transesophageal echocardiography (TEE) has become one of the most accessed imaging methods for structural interventions. Although 3D-TEE can assess cardiac structures and functions in real-time, its limitations (e.g., limited field of view, image quality at a large depth, etc.) must be addressed for its universal adaptation, as well as to improve the quality of its imaging and interventions. This review aims to present the role of TEE in the intraprocedural guidance of percutaneous structural interventions. We also focus on the current and future developments required in a multimodal image integration process when using TEE to enhance the management of congenital and SHD treatments.
Objective: To compare the surgery and survival outcomes between neoadjuvant chemotherapy and primary debulking surgery in patients with advanced ovarian yolk sac tumor (OYST).Methods: In this retrospective cohort analysis, patients with stage III to IV OYST or mixed germ cell tumor containing yolk sac tumor elements and underwent surgery at Peking Union Medical College Hospital between 2010 and 2021 were identified. Nineteen cases were treated with neoadjuvant chemotherapy (NACT) followed by interval surgery. Twenty-one cases were treated with primary debulking surgery (PDS). Data on patient characteristics, treatment and survival were analyzed between the two groups.Results: After NACT, the physical status of patients were significantly improved and tumor burden were decreased, with an optimal cytoreduction rate of 100% at interval surgery. No statistical difference was found in 3-year disease-free survival (DFS) and overall survival (OS) between NACT group and PDS group (Log Rank p=0.461 and 0.935). Patients suffered less blood loss, lower rate of transfusion, shorter operation time, and less severe peri-operative complications at the debulking surgery after NACT, as compared to patients who underwent PDS.Conclusion: For patients with advanced stage OYST, NACT followed by interval surgery might be an alternative option, especially for those who could not tolerate the primary debulking surgery because of high tumor burden and vulnerable status.Funding: This study was supported by the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (CIFMS) [2022-I2M-C&T-B-023].Declaration of Interest: The authors have declared no conflict of interest.Ethical Approval: The Peking Union Medical College Hospital (PUMCH) Institution Review Board approved this retrospective cohort study (IRB number: I-23PJ272).
Purpose: To systemically investigate the prognostic value of pre-ablation stimulated thyroglobulin (s-Tg) in children and adolescents with differentiated thyroid cancer. Methods: Clinical records from 118 children and adolescents were retrospectively reviewed. Results: The median age was 16 years, and the majority were female (79.7%). All children and adolescents underwent total thyroidectomy and received radioactive iodine therapy. After a median follow-up of 5.3 years, 68 (57.6%) patients were disease free, while 50 patients (42.4%) had persistent/recurrent disease. In multivariate analysis, pre-ablation s-Tg and M1 were the independent predictive factors for persistent/recurrent disease. According to the receiver operating curve analysis, the best pre-ablation s-Tg cutoff to predict disease-free status was 17.8 ng/mL with a negative predictive value of 96.8%. Integration of pre-ablation s-Tg into American Thyroid Association pediatric risk categories indicated that the presence of pre-ablation s-Tg ≤17.8 ng/mL was associated with a decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (22.6% to 2.6% in intermediate-risk patients, and 64.4% to 5.6% in high-risk patients). Conclusions: Our findings suggest that pre-ablation s-Tg has the capability of predicting the clinical outcomes in children and adolescents with thyroid cancer.
Ammonia volatilization (NH3) and nitrous oxide (N2O) emission are the main underliers of nitrogen loss in farmlands, which can decrease nitrogen use efficiency and trigger environmental problems regarding greenhouse effects. Previous studies have regional limitations and lack universal guiding significance, as they are primarily based on individual experiments related to the effects of applying nitrogen fertilizer on maize. In this study, we performed a meta-analysis on a regional scale to investigate the overall impact of nitrogen fertilizer application on maize yield, N2O, and NH3 in Northeast China. The database included 85 studies and 1147 pairs of experimental data that were analyzed. The results showed that applying nitrogen fertilizer significantly increased maize yield, N2O emissions, and NH3 volatilization effects, and the growth rates (E) were 50.64%, 64.39%, and 69.25%, respectively. In Northeast China, the average emission factors of N2O and NH3 were 0.72% and 8.21%, respectively. The optimum nitrogen application rate for maize in Northeast China was 205 kg ha−1, resulting in 8.37% nitrogen loss (through N2O and NH3). Soil texture, alkaline nitrogen (AN) content in the soil, mean annual precipitation (MAP), nitrogen application rate, and fertilizer type were the key influential factors affecting changes in maize yield and N loss (N2O and NH3). Yield-scaled N2O and NH3 were found to be the significant emission reduction parameters that ensured maize yield. However, there was a remarkable ‘seesaw effect’ between yield-scaled N2O and NH3 under the same natural conditions (MAP and soil texture). Therefore, human activities such as reducing N surplus in soil, and N fertilizer application rate, along with selecting suitable fertilizer types should be given more attention to reduce yield-scaled N2O and NH3. Moreover, minimizing NH3 and N2O dual emission should be the main objective for green agriculture in Northeast China, rather than over-emphasizing on single emission reduction.
Abstract Context The risk of persistent and recurrent disease in patients with differentiated thyroid cancer (DTC) is a continuum that ranges from very low to very high, even within the 3 primary risk categories. It is important to identify independent clinicopathological parameters to accurately predict clinical outcomes. Objective To examine the association between pre-ablation stimulated thyroglobulin (ps-Tg) and persistent and recurrent disease in DTC patients and investigate whether incorporation of ps-Tg could provide a more individualized estimate of clinical outcomes. Design, Setting, and Participants Medical records of 2524 DTC patients who underwent total thyroidectomy and radioiodine ablation between 2006 and 2018 were retrospectively reviewed. Main Outcome Measure Ps-Tg was measured under thyroid hormone withdrawal before remnant ablation. Association of ps-Tg and clinical outcomes. Results In multivariate analysis, age, American Thyroid Association (ATA) risk stratification, distant metastasis, ps-Tg, and cumulative administered activities were the independent predictive factors for persistent/recurrent disease. Receiver operating characteristic analysis identified ps-Tg cutoff (≤10.1 ng/mL) to predict disease-free status with a negative predictive value of 95%, and validated for all ATA categories. Integration of ps-Tg into ATA risk categories indicated that the presence of ps-Tg ≤ 10.1 ng/mL was associated with a significantly decreased chance of having persistent/recurrent disease in intermediate- and high-risk patients (9.9% to 4.1% in intermediate-risk patients, and 33.1% to 8.5% in high-risk patients). Conclusion The ps-Tg (≤10.1 ng/mL) was a key predictor of clinical outcomes in DTC patients. Its incorporation as a variable in the ATA risk stratification system could more accurately predict clinical outcomes.
Background Fruquintinib and regorafenib have been approved for the third-line therapy of metastatic colorectal cancer (mCRC) in China. However, at present, there is a lack of head-to-head clinical trials on the comparison of efficacy and safety between the two drugs. Materials and methods The data of patients with mCRC who were treated with fruquintinib or regorafenib after the standard chemotherapy in Zhejiang Provincial People’s Hospital from October 2018 to November 2021 were collected and analyzed. The primary endpoints were overall survival (OS), progression-free survival (PFS) and adverse events. The secondary endpoints were the appropriate sequence, objective remission rate (ORR) and disease control rate (DCR) of fruquintinib and regorafenib. Results A total of 105 patients were enrolled in this study. The ORR of fruquintinib group (n=55) and regorafenib group (n=50) were 6.1% and 2.0%; the DCR were 65.3% and 54.2%, respectively. There was no significant difference in median OS (mOS) and PFS (mPFS) between the two groups (mOS:14.2 vs12.0 months, p=0.057; mPFS:4.4 vs 3.5 months, p=0.150). Combined immunotherapy showed a synergistic effect. The mPFS and mOS of fruquintinib combined with anti-PD-1 therapy were longer than those of fruquintinib monotherapy (mPFS:5.9 vs 3.0 months, p=0.009; mOS:17.5 vs 11.3 months, p=0.008). The mOS of patients treated with regorafenib combined with anti-PD-1 therapy was 14.8 months higher than that of regorafenib monotherapy (p=0.045). When combined with anti-PD-1 therapy, the mPFS and mOS of fruquintinib was significantly longer than regorafenib (mPFS:5.9 vs 3.8 months, p=0.018; mOS:17.5 vs 14.8 months, p=0.044). In the treatment sequence, the OS of patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence (15.0 vs 8.3 months, p=0.019). The adverse reactions were generally similar, but the incidence of hand-foot syndrome of regorafenib was higher than that of fruquintinib, while fruquintinib was more prone to grade 3 hypertension. Conclusion Fruquintinib monotherapy showed better disease control rate and objective remission rate in the post-line therapy of metastasis colorectal cancer. Notably, the combination of PD-1 immunotherapy brought the additional effect, especially in the fruquintinib combined with anti-PD-1 therapy. Patients treated with regorafenib and then fruquintinib was significantly longer than that of the reverse treatment sequence. The toxicity of fruquintinib and regorafenib are similar.
Abstract Purpose The 2019 novel coronavirus(COVID-19) mainly transmitted by person-to-person through inhalation of respiratory droplets. We report the laboratory results of conjunctival PCR-tests and some clinical features of these patients in shenyang China. Design This is a cross-sectional non-randomized study Subjects The study include 14 confirmly diagnosed cases, 16 suspected cases and some medical observed patients. Methods All patients with diagnosed and suspected COVID-19 were admitted to a designated hospital in Shenyang, China. We collected conjunctival samples of these patients to do the laboratory tests by real time RT-PCR. Medical observed patients were enrolled if they had clinical symptoms. Then we analysed the PCR results and clinical data from eletronic medical records in order to find some relationships. Main Outcome Measures Clinical condition and PCR results. of conjunctival swabs compared with other specimens Results One of the identified case coverted from suspected case without typical clinical symptoms. Twenty-two medical observed cases were removed because none of them converted to identified cases. One of the suspected converted to identified case recently. The included cases in our study are imported cases with less underlying diseases and the severity of their infection was relatively moderate. All the conjunctival results of PCR-test were negative. Two cases had typical clinical symptoms but were finally confirmed by repeated pharynxswabtests. Conclusion Conjunctiva may be a transmission way of COVID-19. And ocular conjunctival swabs in combination with PCR test could be a non-invasive, convenient and feasible diagnostic method for identifying the infection of COVID-19. Emphasis on the false-negative results is vital.
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