Real-World Efficacy of 5-Azacytidine as Salvage Chemotherapy for Angioimmunoblastic T-cell Lymphoma

BackgroundBased on specific epigenetic mutation in AITL such as TET2, DNMT3A, IDH2, and RHOA, hypomethylating agents are emerging as a promising treatment option for AITL.MethodThe efficacy and safety of 5-azacytidine as salvage chemotherapy were retrospectively analyzed in 15 patients with RR-AITL from 2019 to 2022.ResultsDuring the median 6.0 months of follow-up, the overall response rate (ORR) was 40% (n = 6/15) with 2 CRs and 4 PRs. The patients who previously had received ≤2 prior chemotherapies showed higher ORR than subjects with >2 prior chemotherapies (80% vs. 20%). The 10 patients who received 5-azacitidine at the late chemotherapy lines (>2 prior chemotherapy lines) usually received less dose 5-azacitidine. And these patients discontinued treatment due to disease progression (n = 6/10, 60%) or neutropenic fever (n = 4/10, 40%). The patients who received a full dose (75 mg/m² for 7 days) of 5-azacitidine seemed to show better ORR than subjects (100 mg for 7 days) who did not receive an optimal dose (60.0% vs. 30.0%). The median progression-free survival (PFS) was 1.6 months, and the patients who previously had undergone ≤2 chemotherapies had better PFS compared with subjects who previously received >2 chemotherapies (P-value = .04).Conclusion5-azacitidine shows reasonable efficacy and manageable toxicities for patients with RR-AITL, especially those who previously received ≤2 chemotherapy lines.     

Development and validation of artificial intelligence models for preoperative prediction of inferior mesenteric artery lymph nodes metastasis in left colon and rectal cancer

BackgroundDissection of lymph nodes at the roots of the inferior mesenteric artery (IMAN) should be offered only to selected patients at a major risk of developing IMAN involvement. The aim of this study is to present the first artificial intelligence (AI) models to predict IMAN metastasis risk in the left colon and rectal cancer patients.MethodsA total of 2891 patients with descending colon including splenic flexure, sigmoid colon and rectal cancer undergoing major primary surgery and IMAN dissection were included as a study cohort, which was then split into a training set (67%) and a testing set (33%). Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO) regression model. Seven AI algorithms, namely Support Vector Machine (SVM), Logistic Regression (LR), Extreme Gradient Boosting (XGB), Light Gradient Boosting (LGB), Decision Tree Classifier (DTC), Random Forest (RF) classifier, and Multilayer Perceptron (MLP), as well as traditional multivariate LR model were employed to construct predictive models. The optimal hyperparameters were determined with 5 fold cross-validation. The predictive performance of models and the expert surgeon was assessed and compared in the testing set independently.ResultsThe IMAN involvement incidence was 4.6%. The optimal set of features selected by LASSO included 10 characteristics: neoadjuvant treatment, age, synchronous liver metastasis, synchronous lung metastasis, signet ring adenocarcinoma, neural invasion, lymphovascular invasion, CA199, endoscopic obstruction, T stage evaluated by MRI. The most accurate model derived from MLP showed excellent prediction power with area under the receiver operating characteristic curve (AUROC) of 0.873 and produced 81.0% recognition sensitivity and 82.5% specificity in the testing set independently. In contrast, the judgment of IMAN metastasis by expert surgeon yield rather imprecise and unreliable results with a significantly lower AUROC of 0.509. Additionally, the proposed MLP had the highest net benefits and the largest reduction of unnecessary IMAN dissection without the cost of additional involved IMAN missed.ConclusionMLP model was able to maintain its prediction accuracy in the testing set better than other models and expert surgeons. Our MLP model could be used to help identify IMA nodal metastasis and to select candidates for individual IMAN dissection.     

Go-Ichi-Ni-San 2: A potential biomarker and therapeutic target in human cancers

Cancer incidence and mortality are increasing globally, leading to its rising status as a leading cause of death. The Go-Ichi-Ni-San (GINS) complex plays a crucial role in DNA replication and the cell cycle. The GINS complex consists of four subunits encoded by the GINS1, GINS2, GINS3, and GINS4 genes. Recent findings have shown that GINS2 expression is upregulated in many diseases, particularly tumors. For example, increased GINS2 expression has been found in cervical cancer, gastric adenocarcinoma, glioma, non-small cell lung cancer, and pancreatic cancer. It correlates with the clinicopathological characteristics of the tumors. In addition, high GINS2 expression plays a pro-carcinogenic role in tumor development by promoting tumor cell proliferation and migration, inhibiting tumor cell apoptosis, and blocking the cell cycle. This review describes the upregulation of GINS2 expression in most human tumors and the pathway of GINS2 in tumor development. GINS2 may serve as a new marker for tumor diagnosis and a new biological target for therapy.     

What Should We Focus on in Sepsis Fluid Resuscitation?--A Research Based on Scientometrics and Visual Analysis

Sepsis is a life-threatening condition and a global disease burden.Heterogeneous syndrome is defined as severe organ dysfunction caused by a dysregulated host response to infection,with renewed emphasis on the immune pathophysiology.Researchers worldwide constantly update the diagnostic criteria of sepsis and have introduced concepts such as“sepsis-3”“Surviving Sepsis Campaign(SSC)”“Early Goal-Directed Therapy(EGDT)”,the 3-h and 6-h bundles to an hour-1 bundle[1],“limited ventilation”“the best PEEP[2]”,and“Lung Protective-Ventilation”.Despite all efforts of experimental and clinical research during the last three decades,the ability to positively influence the course and outcome of the syndrome remains limited.     

Anisodamine affects the pigmentation,mineral density,craniofacial area,and eye development in zebrafish embryos

Anisodamine is one of the major components of the tropine alkaloid family and is widely used in the treatment of pain, motion sickness, pupil dilatation, and detoxification of organophosphorus poisoning. As a muscarinic receptor antagonist, the low toxicity and moderate drug effect of anisodamine often result in high doses for clinical use, making it important to fully investigate its toxicity. In this study, zebrafish embryos were exposed to 1.3-, 2.6-, and 5.2-mM anisodamine for 7 days to study the toxic effects of drug exposure on pigmentation, mineral density, craniofacial area, and eye development. The results showed that exposure to anisodamine at 1.3 mM resulted in cranial malformations and abnormal pigmentation in zebrafish embryos; 2.6- and 5.2-mM anisodamine resulted in significant eye development defects and reduced bone density in zebrafish embryos. The associated toxicities were correlated with functional development of neural crest cells through gene expression (col1a2, ddb1, dicer1, mab21l1, mab21l2, sox10, tyrp1b, and mitfa) in the dose of 5.2-mM exposed group. In conclusion, this study provides new evidence of the developmental toxicity of high doses of anisodamine in aqueous solutions to organisms and provides a warning for the safe use of this drug.     

Evaluation of Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) for the prevention of breast cancer-related lymphedema after axillary lymph node dissection using bioimpedance spectroscopy

BackgroundLymphedema is a serious complication of axillary lymph node dissection (ALND) with an incidence rate of 20%. Simplified Lymphatic Microsurgical Preventing Healing Approach (SLYMPHA) is a safe and relatively simple method, which decreases incidence of lymphedema dramatically. Our initial study showed an 88% decrease in clinical lymphedema rate. In the initial study, we used arm circumference measurement for the diagnosis of lymphedema and median follow up was 15 months. The aim of this study was to confirm these results after a long-term follow up period and by using bioimpedance spectroscopy (L-Dex) technology in detecting lymphedema.Study designAll patients, undergoing ALND with or without SLYMPHA between January 2014 and November 2020 were included in the study. Patients with no postoperative L-Dex measurements were excluded. A L-Dex score outside the normal range (±10 L-Dex unit) or ≥10 L-Dex unit increase above patient's baseline was considered as lymphedema. The incidence of lymphedema was compared between patients with and without SLYMPHA.Results194 patients were included in the study. 57% of cohort underwent SLYMPHA. Mean follow-up time was 47 ± 37 months. Patients, who underwent SLYMPHA, had a significantly lower rate of lymphedema (16% vs 32%; p = 0.01; OR 0.4 [0.2–0.8]).ConclusionSLYMPHA is a safe and relatively simple method, which continued its efficacy after a long-term follow up period. It should be considered as an adjunct procedure to ALND for all patients during initial surgery.     

涎腺导管内癌的病理诊断及新进展

涎腺导管内癌(intraductal carcinoma,IDC)是一种主要发生在腮腺,在导管内或囊内生长为主的罕见肿瘤,但也可伴浸润性生长,生物学行为相对惰性。具有独特的形态学、免疫表型及分子遗传学特征。主要包括4种亚型:闰管型、顶浆分泌型、闰管-顶浆分泌混合型和嗜酸型。闰管型多数存在NCOA4-RET融合,个别存在STRN-ALK融合;混合型存在TRIM27-RET融合,顶浆分泌型具有PIK3CA和HRAS突变或TP53缺失;嗜酸型具有TRIM33-RET融合或BRAF V600E突变。目前多数观点认为与涎腺导管癌不同,即使存在浸润,仍具有良好的预后,罕见复发和淋巴结转移,无远处转移。因此精准诊断对于临床治疗的选择极其重要。