Metastatic stomach lymphoepithelioma-like carcinoma and immune checkpoint inhibitor therapy: A case report.

BACKGROUND: Pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare type of non-small-cell lung cancer. Stomach lymphoepithelioma-like carcinoma (LELC) metastasis secondary to PLELC has not been reported recently. CASE SUMMARY: A 64-year-old female was admitted to our hospital for a regular gastroscopy examination with a 6-year history of surgical resection for left PLELC. Positron emission tomography/computed tomography suggested high accumulation of 18F-fludeoxyglucose in the gastric cardia region. Upper gastrointestinal endoscopy confirmed a large mass at the stomach fundus. Immunohistochemistry (IHC) of the biopsy suggested metastatic stomach LELC. Proximal gastrectomy showed that this 6.5 cm × 5.0 cm mass was located in the stomach fundus near the cardia. Histopathological examination showed a poorly differentiated carcinoma with prominent lymphoplasmacytic infiltration. IHC demonstrated that the tumor was positive for CK (AE1/AE3), p63, p40, p53, Ki-67 (70%), and EGFR (3+) and negative for CK7, CK20, Her2, and CD10. In situ hybridization analysis showed positive staining Epstein-Barr virus-encoded RNA. Tumor programmed cell death ligand 1 (PD-L1) expression score was 98%, and the combined positive score was 100, with no evidence of microsatellite instability. Thus, the patient was unequivocally diagnosed with metastatic stomach LELC secondary to pulmonary LELC. After discharge, this patient underwent PD-1 inhibitor treatment (toripalimab, 240 mg) every 3 wk for ten cycles, and she has had no tumor recurrence. CONCLUSION: For gastric LELC metastasis, PD-1 inhibitor therapy could become a new therapeutic approach, though there is still no evidence from large data sets to support this.

Pre-Operative Immunonutrition Enhances Postoperative Outcomes and Elevates Tumor-Infiltrating Lymphocyte Counts in Colorectal Cancer Patients: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: This study (CRD42023464989) aimed to explore the effects of pre-operation immunonutrition on safety and immune related factors in colorectal cancer patients undergoing surgery. METHODS: We systematically searched PubMed, Embase, and Wanfang databases to collect all clinical randomized controlled trials of the application of pre-operation immunonutrition for patients with colorectal cancer, published until July 2023. The primary outcomes were safety and immune related factors. RESULTS: A total of 16 studies were finally included. Preoperative immunonutrition could reduce the postoperative infection rate (risk ratio (RR) = 0.56, 95% confidence interval (CI): 0.36, 0.88; p = .01), and wound infection rate (RR = 0.44, 95% CI: 0.27, 0.70; p < .001) in patients with colorectal cancer. For length of stay (mean difference (MD) = -1.10, 95% CI: -2.70, 0.49; p = .17), it was similar between groups. Meanwhile, patients in the pre-operation immune nutrition group also had significantly increased infiltrative lymphocytes CD16+ (MD = 0.04, 95% CI: 0.02, 0.06; p < .001), and CD56+ (MD = 0.05, 95% CI: 0.03, 0.06; p < .001) cells in the tumor tissues, compared to the control group. CONCLUSION: Immunonutrition intervention has the potential to reduce postoperative infectious complications and improve tumor infiltrative lymphocytes in patients with colorectal cancer undergoing surgery.

Coumarin-embedded [5]helicene derivatives: synthesis, X-ray analysis and photoconducting properties.

Two novel coumarin-embedded π-extended [5]helicene derivatives (3a and 6a) have been strategically synthesized and characterized, and the structure of 3a was determined via single crystal X-ray analysis. Both of them exhibit green fluorescence in dichloromethane. In addition, molecule 3a can aggregate to form a large quantity of nanowires through the re-precipitation method. More importantly, the photoelectric conversion properties of 3a nanowire-C60 based films are much better than those of the thin film of bulk 3a-C60, indicating that the ordered nanostructures are a crucial factor for enhancing device performance.

A novel AML1-ETO/FTO positive feedback loop promotes leukemogenesis and Ara-C resistance via stabilizing IGFBP2 in t(8;21) acute myeloid leukemia.

BACKGROUND: t(8;21)(q22;q22) is one of the most frequent chromosomal abnormalities in acute myeloid leukemia (AML), leading to the generation of the fusion protein AML1-ETO. Despite t(8;21) AML being considered as a subtype with a favorable prognosis, approximately 30-50% of patients experience drug resistance and subsequent relapse. N6-methyladenosine (m6A) is demonstrated to be involved in the development of AML. However, the regulatory mechanisms between AML1-ETO and m6A-related enzymes and the roles of dysregulated m6A modifications in the t(8;21)-leukemogenesis and chemoresistance remain elusive. METHODS: Chromatin immunoprecipitation, dual-luciferase reporter assay, m6A-qPCR, RNA immunoprecipitation, and RNA stability assay were used to investigate a regulatory loop between AML1-ETO and FTO, an m6A demethylase. Gain- and loss-of-function experiments both in vitro and in vivo were further performed. Transcriptome-wide RNA sequencing and m6A sequencing were conducted to identify the potential targets of FTO. RESULTS: Here we show that FTO is highly expressed in t(8;21) AML, especially in patients with primary refractory disease. The expression of FTO is positively correlated with AML1-ETO, which is attributed to a positive regulatory loop between the AML1-ETO and FTO. Mechanistically, AML1-ETO upregulates FTO expression through inhibiting the transcriptional repression of FTO mediated by PU.1. Meanwhile, FTO promotes the expression of AML1-ETO by inhibiting YTHDF2-mediated AML1-ETO mRNA decay. Inactivation of FTO significantly suppresses cell proliferation, promotes cell differentiation and renders resistant t(8;21) AML cells sensitive to Ara-C. FTO exerts functions by regulating its mRNA targets, especially IGFBP2, in an m6A-dependent manner. Regain of Ara-C tolerance is observed when IGFBP2 is overexpressed in FTO-knockdown t(8;21) AML cells. CONCLUSION: Our work reveals a therapeutic potential of targeting AML1-ETO/FTO/IGFBP2 minicircuitry in the treatment for t(8;21) patients with resistance to Ara-C.

Structure-based design of potent FABP4 inhibitors with high selectivity against FABP3.

Fatty-acid binding protein 4 (FABP4) presents an attractive target for therapeutic intervention in metabolic and inflammatory diseases in recent years. However, highly similar three-dimensional structures and fatty acid binding ability of multiple FABP family members pose a significant challenge in design of FABP4-selective inhibitors. Particularly, inhibition of FABP3 raises safety concerns such as cardiac dysfunction and exercise intolerance. Here, we reported the discovery of new FABP4 inhibitors with high selectivity over FABP3 by exploiting the little structural difference in the ligand binding pockets of FABP4 and FABP3. On the basis of our previously reported FABP4 inhibitors with nanomolar potency, different substituents were further introduced to perfectly occupy two sub-pockets of FABP4 that are distinct from those of FABP3. Remarkably, a single methyl group introduction leads to the discovery of compound C3 that impressively exhibits a 601-fold selectivity over FABP3 when maintained nanomolar binding affinity for FABP4. Moreover, C3 also shows good metabolic stability and potent cellular anti-inflammatory activity, making it a promising inhibitor for further development. Therefore, the present study highlights the utility of the structure-based rational design strategy for seeking highly selective and potent inhibitors of FABP4 and the importance of identifying the appropriate subsite as well as substituent for gaining the desired selectivity.

The effects of treating GERD on the outcomes of otitis media with effusion: A systematic review and meta-analysis.

OBJECTIVE: Gastroesophageal reflux disease (GERD) may cause otitis media with effusion (OME). However, whether treating GERD can benefit patients with OME has not been well studied. METHODS: We systematically searched PubMed, Embase, Cochrane Library, and Wanfang databases. The search period was from the establishment of the databases until December 31, 2022. Clinical studies related to GERD treatment on the outcomes of OME were included. Two reviewers independently conducted literature screening and data extraction according to the inclusion and exclusion criteria. To evaluate the quality of the included studies, we used the NOS assessment tool and the RevMan 5.4. Subgroup analysis was conducted to reduce the risk of heterogeneity, and Egger and Begg funnel plots were used to evaluate publication bias. Meta-analysis was performed using Stata14.0 and Review Manager 5.4 software. RESULTS: Finally, 21,744 patients from 16 studies were included. The results showed that the rate of GERD in OME patients was 0.56 (95 % confidence interval (CI): 0.33, 0.79), while it was 0.04 (95 % CI: 0.03, 0.05) in the adult GERD population. The combined risk ratio (RR) of OME in patients with versus without GERD was 1.58 (95 % CI: 1.35, 1.85; p < 0.01). The efficacy rate of GERD treatment in OME patients was 0.59 (95 % CI: 0.44, 0.74), especially for those with chronic OME (0.64, 95 % CI: 0.36, 0.92). Compared to the control group, treatment with GERD improved the symptoms and efficacy of OME (OR = 1.65; 95 % CI: 0.95, 2.85; p > 0.05). The hearing loss cure rate was 0.70 (95 % CI: 0.57, 0.82). CONCLUSION: GERD has been suggested to be a high-risk factor for OME. Treatment of GERD can improve the symptoms of OME. However, further studies are required to verify these findings.

Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Positive t(8;21) Acute Myeloid Leukemia.

BACKGROUND In t(8;21) acute myeloid leukemia (AML), patients with extramedullary infiltration (EMI) tend to have worse survival outcomes than those without EMI. However, it is still unclear whether allogeneic hematopoietic stem cell transplantation (allo-HSCT) benefits EMI-positive t(8;21) AML patients. MATERIAL AND METHODS This study retrospectively enrolled 651 t(8;21) AML patients, and analyzed 51 patients with EMI at diagnosis. Among the 51 patients, 15 patients received allo-HSCT. RESULTS The incidence of EMI in t(8;21) AML was 10.0%, and the first complete remission rate was 78.5% in EMI-positive t(8;21) AML patients. The central nervous system was the most frequently involved site (29.4%), followed by bones (15.7%), and skin (9.8%). In terms of karyotype, 19 (37.3%) patients were t(8;21) alone, 12 (23.5%) had additional loss of a sex chromosome, and 5 (9.8%) had complex karyotype. Significantly better overall survival was observed in patients with allo-HSCT compared to patients without allo-HSCT in both multivariable models (HR=0.32; P=0.0122) and the Kaplan-Meier curves (P=0.0157). CONCLUSIONS Allo-HSCT improved the survival of EMI-positive t(8;21) AML.

Drug repurposing and structure-based discovery of new PDE4 and PDE5 inhibitors.

Phosphodiesterase-4 (PDE4) and PDE5 responsible for the hydrolysis of intracellular cAMP and cGMP, respectively, are promising targets for therapeutic intervention in a wide variety of diseases. Here, we report the discovery of novel, drug-like PDE4 inhibitors by performing a high-throughput drug repurposing screening of 2560 approved drugs and drug candidates in clinical trial studies. It allowed us to identify eight potent PDE4 inhibitors with IC50 values ranging from 0.41 to 2.46 µM. Crystal structures of PDE4 in complex with four compounds, namely ethaverine hydrochloride (EH), benzbromarone (BBR), CX-4945, and CVT-313, were further solved to elucidate molecular mechanisms of action of these new inhibitors, providing a solid foundation for optimizing the inhibitors to improve their potency as well as selectivity. Unexpectedly, selectivity profiling of other PDE subfamilies followed by crystal structure determination revealed that CVT-313 was also a potent PDE5 inhibitor with a binding mode similar to that of tadalafil, a marketed PDE5 inhibitor, but distinctively different from the binding mode of CVT-313 with PDE4. Structure-guided modification of CVT-313 led to the discovery of a new inhibitor, compound 2, with significantly improved inhibitory activity as well as selectivity towards PDE5 over PDE4. Together, these results highlight the utility of the drug repurposing in combination with structure-based drug design in identifying novel inhibitors of PDE4 and PDE5, which provides a prime example for efficient discovery of drug-like hits towards a given target protein.

Efficacy of continuous gastric artery infusion chemotherapy in relieving digestive obstruction in advanced gastric cancer.

BACKGROUND: Obstruction or fullness after feeding is common in gastric cancer (GC) patients, affecting their nutritional status and quality of life. Patients with digestive obstruction are generally in a more advanced stage. Existing methods, including palliative gastrectomy, gastrojejunostomy, endoluminal stent, jejunal nutrition tube and intravenous chemotherapy, have limitations in treating these symptoms. AIM: To analyze the efficacy of continuous gastric artery infusion chemotherapy (cGAIC) in relieving digestive obstruction in patients with advanced GC. METHODS: This study was a retrospective study. Twenty-nine patients with digestive obstruction of advanced GC who underwent at least one cycle of treatment were reviewed at The Second Affiliated Hospital of Zhejiang University School of Medicine. The oxaliplatin-based intra-arterial infusion regimen was applied in all patients. Mild systemic chemotherapy was used in combination with local treatment. The clinical response was evaluated by contrast-enhanced computed tomography using Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Digestive tract symptoms and toxic effects were analyzed regularly. A comparison of the Karnofsky Performance Status (KPS) score and Stooler's Dysphagia Score before and after therapy was made. Univariate survival analysis and multivariate survival analysis were also performed to explore the key factors affecting patient survival. RESULTS: All patients finished cGAIC successfully without microcatheter displacement, as confirmed by arteriography. The median follow-up time was 24 mo (95%CI: 20.24-27.76 mo). The overall response rate was 89.7% after cGAIC according to the RECIST criteria. The postoperative Stooler's Dysphagia Score was significantly improved. Twenty-two (75.9%) of the 29 patients experienced relief of digestive obstruction after the first two cycles, and 13 (44.8%) initially unresectable patients were then considered radically resectable. The median overall survival time (mOS) was 16 mo (95%CI: 9.32-22.68 mo). Patients who received radical surgery had a significantly longer mOS than other patients (P value < 0.001). Multivariate Cox regression analysis indicated that radical resection after cGAIC, intravenous chemotherapy after cGAIC, and immunotherapy after cGAIC were independent predictors of mOS. None of the patients stopped treatment because of adverse events. CONCLUSION: cGAIC was effective and safe in relieving digestive obstruction in advanced GC, and it could improve surgical conversion possibility and survival time.

Distinct on-treatment HCC risks associated with different decompensation events in HBV patients with cirrhosis.

OBJECTIVES: Long-term treatment with nucleoside analog (NA) reduces the risks for decompensation and hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients with compensated cirrhosis (CC). However, whether antiviral therapy has differential efficacy on the risks for decompensation and HCC is insufficiently elucidated. Therefore, we investigated the disease state transition, focusing on decompensation event-specific HCC risk in NA-treated CHB patients with CC. METHODS: We prospectively followed up on 1163 NA-treated CHB patients with CC every six months for up to seven years. The cumulative incidence and risk of HCC were analyzed by the Kaplan-Meier method and competing risk model. The multistate model was used to estimate the transition probabilities to HCC from different disease states. RESULTS: HCC predominated the first liver-related events, with a 5-year cumulative incidence of 9.0%, followed by decompensation (8.3%, including 7.9% nonbleeding decompensation and 2.4% variceal bleeding) and 0.2% death. The decompensation stage had a significantly higher 5-year cumulative HCC incidence than the CC stage (27.6% vs. 9.1%; HR = 2.42, 95% CI: 1.24, 4.71). Furthermore, nonbleeding decompensation events had a higher 5-year transition probability to HCC than bleeding (27.6% vs. 15.8%; HR = 2.69, 95% CI: 1.41, 4.17). Viral suppression modified the on-treatment transition risk to HCC (1-year: HR = 0.45, 95% CI: 0.28, 0.73; 3-year: HR = 0.23, 95% CI: 0.14, 0.38). An online calculator was developed to facilitate HCC risk stratification. CONCLUSIONS: In NA-treated CHB patients with compensated cirrhosis, the risk was higher for HCC than for decompensation; more importantly, different decompensation events conferred distinct HCC risks.

Exploring the characteristics of gut microbiome in patients of Southern Fujian with hypocitraturia urolithiasis and constructing clinical diagnostic models.

PURPOSE: Hypocitraturia is an important cause of urolithiasis. Exploring the characteristics of the gut microbiome (GMB) of hypocitriuria urolithiasis (HCU) patients can provide new ideas for the treatment and prevention of urolithiasis. METHODS: The 24 h urinary citric acid excretion of 19 urolithiasis patients was measured, and patients were divided into the HCU group and the normal citrate urolithiasis (NCU) group. The 16 s ribosomal RNA (rRNA) was used to detect GMB composition differences and construct operational taxonomic units (OTUs) coexistence networks. The key bacterial community was determined by Lefse analysis, Metastats analysis and RandomForest analysis. Redundancy analysis (RDA) and Pearson correlation analysis visualized the correlation between key OTUs and clinical features and then established the disease diagnosis model of microbial-clinical indicators. Finally, PICRUSt2 was used to explore the metabolic pathway of related GMB in HCU patients. RESULTS: The alpha diversity of GMB in HCU group was increased and Beta diversity analysis suggested significant differences between HCU and NCU groups, which was related to renal function damage and urinary tract infection. Ruminococcaceae_ge and Turicibacter are the characteristic bacterial groups of HCU. Correlation analysis showed that the characteristic bacterial groups were significantly associated with various clinical features. Based on this, the diagnostic models of microbiome-clinical indicators in HCU patients were constructed with the areas under the curve (AUC) of 0.923 and 0.897, respectively. Genetic and metabolic processes of HCU are affected by changes in GMB abundance. CONCLUSION: GMB disorder may be involved in the occurrence and clinical characteristics of HCU by influencing genetic and metabolic pathways. The new microbiome-clinical indicator diagnostic model is effective.

Hepatocellular carcinoma prediction model performance decreases with long-term antiviral therapy in chronic hepatitis B patients.

BACKGROUND/AIMS: Existing hepatocellular carcinoma (HCC) prediction models are derived mainly from pretreatment or early on-treatment parameters. We reassessed the dynamic changes in the performance of 17 HCC models in patients with chronic hepatitis B (CHB) during long-term antiviral therapy (AVT). METHODS: Among 987 CHB patients administered long-term entecavir therapy, 660 patients had 8 years of follow-up data. Model scores were calculated using on-treatment values at 2.5, 3, 3.5, 4, 4.5, and 5 years of AVT to predict threeyear HCC occurrence. Model performance was assessed with the area under the receiver operating curve (AUROC). The original model cutoffs to distinguish different levels of HCC risk were evaluated by the log-rank test. RESULTS: The AUROCs of the 17 HCC models varied from 0.51 to 0.78 when using on-treatment scores from years 2.5 to 5. Models with a cirrhosis variable showed numerically higher AUROCs (pooled at 0.65-0.73 for treated, untreated, or mixed treatment models) than models without (treated or mixed models: 0.61-0.68; untreated models: 0.51-0.59). Stratification into low, intermediate, and high-risk levels using the original cutoff values could no longer reflect the true HCC incidence using scores after 3.5 years of AVT for models without cirrhosis and after 4 years of AVT for models with cirrhosis. CONCLUSION: The performance of existing HCC prediction models, especially models without the cirrhosis variable, decreased in CHB patients on long-term AVT. The optimization of existing models or the development of novel models for better HCC prediction during long-term AVT is warranted.

Structure-Based Design of Potent Peptidomimetic Inhibitors Covalently Targeting SARS-CoV-2 Papain-like Protease.

The papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) plays a critical role in the proteolytic processing of viral polyproteins and the dysregulation of the host immune response, providing a promising therapeutic target. Here, we report the structure-guide design of novel peptidomimetic inhibitors covalently targeting SARS-CoV-2 PLpro. The resulting inhibitors demonstrate submicromolar potency in the enzymatic assay (IC50 = 0.23 µM) and significant inhibition of SARS-CoV-2 PLpro in the HEK293T cells using a cell-based protease assay (EC50 = 3.61 µM). Moreover, an X-ray crystal structure of SARS-CoV-2 PLpro in complex with compound 2 confirms the covalent binding of the inhibitor to the catalytic residue cysteine 111 (C111) and emphasizes the importance of interactions with tyrosine 268 (Y268). Together, our findings reveal a new scaffold of SARS-CoV-2 PLpro inhibitors and provide an attractive starting point for further optimization.

A Liquid Metal Temperature Detection System Based on Multi-Node Sapphire Fiber Sensor.

In order to accurately detect the temperature of molten aluminum and overcome the adverse influence of high temperature and corrosiveness on the sensing results, a temperature detection system based on a multi-node sapphire fiber sensor was proposed and developed. Through the structural parameter design of the fiber sensor, the scheme of utilizing the 0.7 mm diameter fiber and 0.5 mm groove was formulated. Simulation and analysis were carried out to determine the ultrasonic response distribution of the signal passing through the whole fiber sensor. The results indicate that the system is capable of distinguishing test signals from various positions and temperatures. Following the completion of the static calibration, the temperature of the molten aluminum was observed in real-time, and the data of the temperature measurements conducted at the two groove locations were compared. According to the obtained results, the test accuracy was greater than 1 degree Celsius and the temperature test stability was good, laying a solid foundation for the potential development of temperature measurement devices.

A Space Expander of Laparoscopic Rectal Cancer Surgery for Overweight or Obese Patients.

BACKGROUND/NEED: Laparoscopic rectal cancer surgery (LRCS) has become a preferred approach for its minimal invasion and fast postoperative recovery. But it is challenging for the tumors of the middle and lower rectum, especially for overweight or obese patients. METHODOLOGY: We present a space expander of laparoscopic rectal cancer surgery, which is a simple tool to widen the perirectal space, as to facilitate the procedure of total mesorectal excision (TME) during the rectal cancer surgery. It has several advantages of lower demand for an assistant, less risk of surgical complications and good feasibility. DEVICE DESCRIPTION: It is designed as a cylindrical shape, and it is the first invented device to help surgeons safely perform accurate TME on overweight or obese patients during LRCS. With this method, we are able to dissect the rectal wall circumferentially in a safe and quick way. PRELIMINARY RESULTS: Our previous pig experiments indicated that the learning curve for this technique was as short as 10 minutes. CURRENT STATUS: Further clinical trials will be conducted on its efficacy and safety in the future.

Single-Cell Profiling of Tumor Immune Microenvironment Reveals Immune Irresponsiveness in Gastric Signet-Ring Cell Carcinoma.

BACKGROUND & AIMS: Gastric cancer (GC) is a major cancer type characterized by high heterogeneity in both tumor cells and the tumor immune microenvironment (TIME). One intractable GC subtype is gastric signet-ring cell carcinoma (GSRCC), which is associated with poor prognosis. However, it remains unclear what the GSRCC TIME characteristics are and how these characteristics may contribute to clinical outcomes. METHODS: We enrolled 32 patients with advanced GC of diverse subtypes and profiled their TIME using an immune-targeted single-cell profiling strategy, including (1) immune-targeted single-cell RNA sequencing (n = 20 patients) and (2) protein expression profiling by a targeted antibody panel for mass cytometry (n = 12 patients). We also generated matched V(D)J (variable, diversity, and joining gene segments) sequencing of T and B cells along CD45+ immunocytes. RESULTS: We found that compared to non-GSRCC, the GSRCC TIME appears to be quiescent, where both CD4+ and CD8+ T cells are difficult to be mobilized, which further impairs the proper functions of B cells. CXCL13, mainly produced by follicular helper T cells, T helper type 17, and exhausted CD8+ T cells, is a central coordinator of this transformation. We show that CXCL13 expression can predict the response to immune checkpoint blockade in GC patients, which may be related to its effects on tertiary lymphoid structures. CONCLUSIONS: Our study provides a comprehensive molecular portrait of immune cell compositions and cell states in advanced GC patients, highlighting adaptive immune irresponsiveness in GSRCC and a mediator role of CXCL13 in TIME. Our targeted single-cell transcriptomic and proteomic profiling represents a powerful approach for TIME-oriented translational research.

Risk factors for post-transplant relapse and survival in younger adult patients with t(8;21)(q22;q22) acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: A multicenter retrospective study.

Background: Outcomes of patients with t(8;21)(q22;q22) acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain heterogeneous. Methods: To identify the risk factors for relapse and survival after allo-HSCT in t(8;21) AML patients, we retrospectively evaluated the clinical and prognostic information of 142 patients with t(8;21) AML undergoing allo-HSCT between January 2002 and September 2018 at 15 hematology research centers in China. Results: Twenty-nine patients (20%) relapsed after undergoing allo-HSCT. A > 1-log reduction in RUNX1/RUNX1T1-based minimal residual disease (MRD) directly before allo-HSCT and a > 3-log reduction within the first 3 months after allo-HSCT were associated with a significantly lower post-transplant 3-year cumulative incidence of relapse (CIR, 9% vs. 62% and 10% vs. 47%,all P < 0.001), whereas transplantation during the second complete remission (CR2, 39% vs. 17% during CR1, P = 0.022), during relapse (62% vs. 17% during CR1, P < 0.001) and KIT D816 mutations at diagnosis (49% vs. 18%, P = 0.039) were related to a significantly higher 3-year CIR. Multivariate analysis demonstrated that a > 1-log reduction in MRD directly before transplantation (CIR: hazard ratio(HR), 0.21 [0.03-0.71], P = 0.029; overall survival (OS): HR = 0.27 [0.08-0.93], P = 0.038) and a > 3-log reduction in post-transplant MRD within the first 3 months (CIR: HR = 0.25 [0.07-0.89], P = 0.019; OS: HR = 0.38 [0.15-0.96], P = 0.040) were independent favorable prognostic factors, and transplantation during relapse (CIR: HR = 5.55 [1.23-11.56], P = 0.041; OS: HR = 4.07 [1.82-20.12], P = 0.045) were independent adverse prognostic factors for post-transplant relapse and survival in patients with t(8;21) AML. Conclusion: Our study suggests that for patients with t(8;21) AML undergoing allo-HSCT, it would be better to receive transplantation during CR1 with a MRD directly before transplantation achieving at least 1-log reduction. MRD monitoring in the first 3 months after allo-HSCT might be robust in predicting relapse and adverse survival after allo-HSCT.

Comparison of short-term surgical outcomes and long-term survival between emergency and elective surgery for colorectal cancer: a systematic review and meta-analysis.

OBJECTIVE: The objective of this study was to summarize relevant data from previous reports and perform a meta-analysis to compare short-term surgical outcomes and long-term oncological outcomes between emergency and elective surgery for colorectal cancer (CRC). METHODS: A systematic literature search was performed using PubMed and Embase databases, and relevant data were extracted. Postoperative morbidity, hospital mortality within 30 days, postoperative recovery, overall survival (OS), and relapse-free survival (RFS) were compared using a fixed or random-effect model. RESULTS: A total of 28 studies involving 353,686 participants were enrolled for this systematic review and meta-analysis, and 23.5% (83,054/353,686) of CRC patients underwent emergency surgery. The incidence of emergency presentations in CRC patients ranged from 2.7 to 38.8%. The lymph node yield of emergency surgery was comparable to that of elective surgery (WMD:0.70, 95%CI: - 0.74,2.14, P = 0.340; I2 = 80.6%). Emergency surgery had a higher risk of postoperative complications (OR:1.83, 95%CI:1.62-2.07, P < 0.001; I2 = 10.6%) and hospital mortality within 30 days (OR:4.62, 95%CI:4.18-5.10, P < 0.001; I2 = 42.9%) than elective surgery for CRC. In terms of long-term oncological outcomes, emergency surgery was significantly associated with poorer RFS (HR: 1.51, 95%CI:1.24-1.83, P < 0.001; I2 = 58.9%) and OS(HR:1.60, 95%CI: 1.47-1.73, P < 0.001; I2 = 63.4%) of CRC patients. In addition, the subgroup analysis for colon cancer patients revealed a pooled HR of 1.73 for OS (95%CI:1.52-1.96, P < 0.001), without the evidence of significant heterogeneity (I2 = 21.2%). CONCLUSION: Emergency surgery for CRC had an adverse impact on short-term surgical outcomes and long-term survival. A focus on early screening programs and health education was warranted to reduce emergency presentations of CRC patients.

Development and validation of a machine learning-based model for varices screening in compensated cirrhosis (CHESS2001): an international multicenter study.

BACKGROUND AND AIMS: The prevalence of high-risk varices (HRV) is low among compensated cirrhotic patients undergoing EGD. Our study aimed to identify a novel machine learning (ML)-based model, named ML EGD, for ruling out HRV and avoiding unnecessary EGDs in patients with compensated cirrhosis. METHODS: An international cohort from 17 institutions from China, Singapore, and India were enrolled (CHESS2001). The variables with the top 3 importance scores (liver stiffness, platelet count, and total bilirubin) were selected by the Shapley additive explanation and input into a light gradient-boosting machine algorithm to develop ML EGD for identification of HRV. Furthermore, we built a web-based calculator for ML EGD, which is free with open access (http://www.pan-chess.cn/calculator/MLEGD_score). Unnecessary EGDs that were not performed and the rates of missed HRV were used to assess the efficacy and safety for varices screening. RESULTS: Of 2794 enrolled patients, 1283 patients formed a real-world cohort from 1 university hospital in China used to develop and internally validate the performance of ML EGD for varices screening. They were randomly assigned into the training (n = 1154) and validation (n = 129) cohorts with a ratio of 9:1. In the training cohort, ML EGD spared 607 (52.6%) unnecessary EGDs with a missed HRV rate of 3.6%. In the validation cohort, ML EGD spared 75 (58.1%) EGDs with a missed HRV rate of 1.4%. To externally test the performance of ML EGD, 966 patients from 14 university hospitals in China (test cohort 1) and 545 from 2 hospitals in Singapore and India (test cohort 2) comprised the 2 test cohorts. In test cohort 1, ML EGD spared 506 (52.4%) EGDs with a missed HRV rate of 2.8%. In test cohort 2, ML EGD spared 224 (41.1%) EGDs with a missed HRV rate of 3.1%. When compared with the Baveno VI criteria, ML EGD spared more screening EGDs in all cohorts (training cohort, 52.6% vs 29.4%; validation cohort, 58.1% vs 44.2%; test cohort 1, 52.4% vs 26.5%; test cohort 2, 41.1% vs 21.1%, respectively; P < .001). CONCLUSIONS: We identified a novel model based on liver stiffness, platelet count, and total bilirubin, named ML EGD, as a free web-based calculator. ML EGD could efficiently help rule out HRV and avoid unnecessary EGDs in patients with compensated cirrhosis. (Clinical trial registration number: NCT04307264.).