PRaG 3.0 therapy for human epidermal growth factor receptor 2-positive metastatic pancreatic ductal adenocarcinoma: A case report.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.

Trend of research on the medical use of molecular hydrogen: a bibliometric analysis.

The medical use of molecular hydrogen, including hydrogen-rich water and hydrogen gas, has been extensively explored since 2007. This article aimed to demonstrate the trend in medical research on molecular hydrogen. A total of 1126 publications on hydrogen therapy were retrieved from the PubMed database until July 30, 2021. From 2007 to 2020, the number of publications in this field had been on an upward trend. Medical Gas Research, Scientific Report and Shock have contributed the largest number of publications on this topic. Researchers by the name of Xue-Jun Sun, Ke-Liang Xie and Yong-Hao Yu published the most studies in the field. Analysis of the co-occurrence of key words indicated that the key words "molecular hydrogen," "hydrogen-rich water," "oxidative stress," "hydrogen gas," and "inflammation" occurred most frequently in these articles. "Gut microbiota," "pyroptosis," and "COVID-19" occurred the most recently among the keywords. In summary, the therapeutic application of molecular hydrogen had attracted much attention in these years. The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future.

Effects and mechanisms of GSG2 in esophageal cancer progression.

BACKGROUND: Esophageal cancer was recognized as one of the malignant tumors with poor prognosis. Germ cell associated 2 (GSG2) has been reported to be of great significance in cell growth and tumor formation. This study aimed to investigate the biological function and molecular mechanism of GSG2 in esophageal cancer. METHODS: First, relationship between GSG2 expression and tumor characteristics in esophageal cancer patients was analyzed through immunohistochemical (IHC) staining. MTT assay, flow cytometry, cloning formation assay, wound-healing assay and Transwell assay were used to determine proliferation, apoptosis and migration of esophageal cancer cell with GSG2 knockdown in vitro. Expression of apoptosis related proteins and downstream pathway proteins after GSG2 knockdown were detected through Human Apoptosis Antibody Array and western blot analysis. The GSG2 knockdown function in vivo was explored through a xenograft tumor model. RESULTS: GSG2 was highly expressed in tumor tissues, which has clinical significance in predicting the malignant degree of patients with esophageal cancer. In addition, GSG2 knockdown significantly inhibited a variety of malignant biological behaviors of esophageal cancer cells, such as inhibiting proliferation, reducing colony formation, promoting apoptosis, hindering migration. The decrease of GSG2 expression in esophageal cancer cells can inhibit the xenograft tumor growth. CONCLUSIONS: In conclusion, GSG2 was involved in esophageal cancer progression and development, which may provide an effective molecular target for the treatment of esophageal cancer in the future.

Impact of leukoaraiosis in patients with acute ischemic stroke treated with thrombectomy: a post hoc analysis of the DIRECT-MT trial.

BACKGROUND: The influence of leukoaraiosis in patients with acute ischemic stroke (AIS) given intra-arterial treatment (IAT) with or without preceding intravenous thrombolysis (IVT) remains unknown. OBJECTIVE: To assess the clinical and radiological outcomes of IAT in patients with or without leukoaraiosis. METHODS: Patients of the direct mechanical thrombectomy trial (DIRECT-MT) whose leukoaraiosis grade could be assessed were included. DIRECT-MT was a randomized clinical trial performed in China to assess the effect of direct IAT compared with intravenous thrombolysis plus IAT. We employed the Age-Related White Matter Changes Scale for grading leukoaraiosis (ARWMC, 0 indicates no leukoaraiosis, 1-2 indicates mild-to-moderate leukoaraiosis, and 3 indicates severe leukoaraiosis) based on brain CT. The primary outcome was the score on the modified Rankin Scale (mRS) assessed at 90 days. RESULTS: There were 656 patients in the trial, 649 patients who were included, with 432 patients without leukoaraiosis, and 217 (33.4%) patients with leukoaraiosis divided into mild-to-moderate (n=139) and severe groups (n=78). Leukoaraiosis was a predictor of a worse mRS score (adjusted OR (aOR)=0.7 (95% CI 0.5 to 0.8)) and higher mortality (aOR=1.4 (1.1 to 1.9)), but it was not associated with symptomatic intracranial hemorrhage (sICH) (aOR=0.9 (0.5 to 1.5)). IVT preceding IAT did not increase sICH risk for patients with no (aOR=1.4 (0.6 to 3.4)), mild-to-moderate (aOR=1.5 (0.3 to 7.8)), or severe (aOR=1.5 (0.1 to 21.3)) leukoaraiosis. CONCLUSION: Patients with leukoaraiosis with AIS due to large vessel occlusion are at increased risk of a poor functional outcome after IAT but demonstrate similar sICH rates, and IVT preceding IAT does not increase the risk of sICH in Chinese patients with leukoaraiosis.

Early diagnosis of intracranial atherosclerotic large vascular occlusion: A prediction model based on DIRECT-MT data.

Aims: This study aimed to build a prediction model to early diagnose intracranial atherosclerosis (ICAS)-related large vascular occlusion (LVO) in acute ischemic stroke patients before digital subtractive angiography. Methods: Patients enrolled in the DIRECT-MT trial (NCT03469206) were included in our secondary analysis and distributed into ICAS-LVO and non-ICAS-LVO groups. We also retrieved demographic data, medical histories, clinical characteristics, and pre-operative imaging data. Hypothesis testing was used to compare data of the two groups, and univariate logistic regression was used to identify the predictors of ICAS-LVO primarily. Then, we used multivariate logistic regression to determine the independent predictors and formulate the prediction model. Model efficacy was estimated by the area under the receiver operating characteristic (ROC) curve (AUC) and diagnostic parameters generated from internal and external validations. Results: The subgroup analysis included 45 cases in the ICAS-LVO group and 611 cases in the non-ICAS-LVO group. Variates with p < 0.1 in the comparative analysis were used as inputs in the univariate logistic regression. Next, variates with p < 0.1 in the univariate logistic regression were used as inputs in the multivariate logistic regression. The multivariate logistic regression indicated that the atrial fibrillation history, hypertension and smoking, occlusion located at the proximal M1 and M2, hyperdense artery sign, and clot burden score were related to the diagnosis of ICAS-LVO. Then, we constructed a prediction model based on multivariate logistics regression. The sensitivity and specificity of the model were 84.09 and 74.54% in internal validation and 73.11 and 71.53% in external validation. Conclusion: Our current prediction model based on clinical data of patients from the DIRECT-MT trial might be a promising tool for predicting ICAS-LVO.

Patient-Reported Anxiety/Depression After Endovascular Thrombectomy: A post-hoc Analysis of Direct-MT Trial.

OBJECTIVE: To analyze the effect of endovascular thrombectomy (EVT) alone vs. EVT after an intravenous (IV) alteplase of ischemic stroke on a patient-reported anxiety/depression, and to identify predictors of patient-reported anxiety/depression by analyzing data from Direct Intraarterial Thrombectomy in Order to Revascularize the patients with Acute Ischemic Stroke with a Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals: a Multicenter Randomized Clinical Trial (DIRECT-MT). METHODS: Patients with acute ischemic stroke (AIS), triggered by a large-vessel occlusion in the anterior circulation, were randomly allocated to undergo an EVT after IV alteplase (combination-therapy group) or an EVT alone (EVT-alone group) at a 1:1 ratio in DIRECT-MT. Patients in both groups were followed up for 90 days (±14 days) after stroke using a structured modified Ranking Scale (mRS), a Barthel Index (BI), and a 5-Dimensional European Quality of Life Scale (EQ-5D-5L). Patients who returned EQ-5D-5L were included. The EQ-5D-5L anxiety/depression dimension was used to analyze the patient-reported anxiety/depression. First, differences in patient-reported anxiety/depression were compared between the combination-therapy group and the EVT-alone group. Then, the baseline and influencing factors between the anxiety/depression group and no anxiety/depression group were analyzed using univariate regression analysis. Finally, variables with p < 0.1 in univariate regression were subjected to multivariable binary regression analysis to screen independent predictors for patient-reported anxiety /depression after ischemic stroke. RESULTS: : Five hundred fifteen patients returned the EQ-5D-5L in Direct-MT. Of these patients, 226 (43.88%) reported a level of anxiety/depression, and about 7% reported a severe or extremely severe anxiety/depression. The patient-reported anxiety/depression in the EVT-alone group was significantly higher than that in the combination-therapy group (48.26% vs. 39.45%, p = 0.04). The clinical outcomes were significantly different between the no Anxiety/Depression Group and the anxiety/depression group (mRS at 90 days:2 vs 3, p < 0.001; BI of 95 or 100 at 90 days: 73.36% vs 42.04%, p < 0.001; EQ-5D-5l utility indexes at 90 days:0.96 vs.57, p < 0.001). Logistic regression analysis showed that allocation to thrombolysis before EVT strategy was inversely associated with anxiety/depression [0.61(0.40, 0.94), p = 0.03], an insular cortex ischemia, and National Institute of Health Strocke Scale (NIHSS) at 7 days were positively associated with anxiety/depression [2.04(1.07, 3.90), p = 0.03; 1.07(1.03, 1.12), p < 0.001]. CONCLUSIONS: Patient-reported anxiety/depression may suggest that there is a benefit to administering intravenous alteplase before EVT. It may also indicate that it is better to provide IV alteplase before EVT, rather than EVT alone according to patient-reported anxiety/depression. Future research should consider not only the motor function impairments but also the patient-reported mental problems as measures of treatment efficacy in patients with stroke (DIRECT-MT ClinicalTrials.gov number, NCT03469206).

Higher Baseline Cortical Score Predicts Good Outcome in Patients With Low Alberta Stroke Program Early Computed Tomography Score Treated with Endovascular Treatment.

BACKGROUND: Patients with large vessel occlusion and noncontrast computed tomography (CT) Alberta Stroke Program Early CT Score (ASPECTS) <6 may benefit from endovascular treatment (EVT). There is uncertainty about who will benefit from it. OBJECTIVE: To explore the predicting factors for good outcome in patients with ASPECTS <6 treated with EVT. METHODS: We retrospectively reviewed 60 patients with ASPECTS <6 treated with EVT in our center between March 2018 and June 2019. Patients were divided into 2 groups because of the modified Rankin Score (mRS) at 90 d: good outcome group (mRS 0-2) and poor outcome group (mRS ≥3). Baseline and procedural characteristics were collected for unilateral variate and multivariate regression analyses to explore the influent variates for good outcome. RESULTS: Good outcome (mRS 0-2) was achieved in 24 (40%) patients after EVT and mortality was 20% for 90 d. Compared with the poor outcome group, higher baseline cortical ASPECTS (c-ASPECTS), lower intracranial hemorrhage, and malignant brain edema after thrombectomy were noted in the good outcome group (all P < .01). Multivariate logistic regression showed that only baseline c-ASPECTS (≥3) was positive factor for good outcome (odds ratio = 4.29; 95% CI, 1.21-15.20; P = .024). The receiver operating characteristics curve indicated a moderate value of c-ASPECTS for predicting good outcome, with the area under receiver operating characteristics curve 0.70 (95% CI, 0.56-0.83; P = .011). CONCLUSION: Higher baseline c-ASPECTS was a predictor for good clinical outcome in patients with ASPECTS <6 treated with EVT, which could be helpful to treatment decision.

The "distal-to-proximal" strategy for the treatment of posterior circulation tandem occlusions: a single-centre experience.

PURPOSE: Data on posterior circulation tandem occlusions in acute ischemic stroke are scarce: recognition may be challenging and little is known about optimal treatment strategy. We report our endovascular treatment strategy for posterior circulation tandem occlusion. METHODS: Consecutive patients with posterior circulation tandem occlusions in our centre were enrolled retrospectively. The preferred strategy was "distal-to-proximal" strategy, which means opening the distal occlusion first followed by treatment of the proximal pathology. The imaging characteristics, treatment strategy, clinical outcomes, and complications of patients with posterior circulation tandem occlusions were analyzed. RESULTS: In total, 21 patients with posterior circulation tandem occlusions were enrolled in the study, which accounted for 23.6% of patients with posterior circulation stroke in our centre. The mean age was 60 years (range 32 to 80), and median pre-procedure NIHSS score was 28 (interquartile range: 13-31). Eighteen patients (85.7%) had vertebrobasilar artery tandem occlusions and 3 (14.3%) had basilar artery to basilar artery tandem occlusions. All distal occlusions were successfully recanalized (modified TICI 2b/3). Two (9.5%) of the proximal lesions were not treated. A total of 57.1% of the patients had stents implanted on the proximal occlusions. The rate of mRS 0-3 at 3 months was 57.1% and the mortality rate was 19.0%. CONCLUSION: In patients with acute ischaemic stroke caused by posterior circulation tandem occlusions, we favor "distal-to-proximal" strategy based on the positive results in this small series. Nevertheless, a more extensive study is required to explore the optimal treatment strategy further.

Stent Angioplasty for Acute Intracranial Atherosclerotic Occlusion After Failed Thrombectomy: A Single-Institution Series of 55 Patients.

INTRODUCTION: Analysis of safety and effectiveness of stent angioplasty for failure of thrombectomy in patients with acute intracranial atherosclerotic occlusion. METHODS: Retrospective continuous analysis of the clinical data of 458 patients with acute stroke undergoing endovascular artery thrombectomy in Changhai Hospital of Second Military Medical University from May 2013 to February 2018. Patients with acute intracranial atherosclerotic occlusion treating with stent implantation were included and the safety and effectiveness of stent angioplasty was evaluated. RESULTS: There was successful stent release in 55 patients. There were 36 cases (65.5%) with occlusion located in the anterior circulation and 19 cases (34.5%) in the posterior circulation. Twenty patients underwent intravenous thrombolysis before surgery, and the time of admission to intravenous thrombolysis was (39.9 ± 13.2) minutes. Fifty-four patients (98.2%) achieved modified thrombolysis in cerebral infarction 2b-3 recanalization. The National Institutes of Health Stroke Scale score 2.0 (0.0,6.0) 7 days after surgery was significantly improved compared with the preoperative National Institutes of Health Stroke Scale score 12.5 (6.0-20.0) (Z = -4.073, P < 0.05). Intracranial hemorrhage occurred in 7 patients (12.7%) after surgery, among them, symptomatic intracranial hemorrhage occurred in 2 cases (3.6%). CTP examination of the skull 3-5 days after operation showed: Among 39 cases (70.9%): 33 cases (84.6%) were patency, 4 cases (10.3%) were occlusion, 2 cases (5.1%) were moderate stenosis, and 16 cases (29.1%) were not examined by computed tomography perfusion. Ninety-day follow-up showed that a total of 43 cases were followed up, and 12 cases were lost to follow-up. Thirty-four patients (79.1%) had a good prognosis 90 days after surgery (modified Rankin scale score 0-2) and 9 patients died (20.9%). CONCLUSION: When thrombectomy in patients with acute intracranial atherosclerotic occlusion fails, stent angioplasty is safe and effective; however, short-term stent reocclusion after surgery cannot be ignored. Because of the small sample size, larger multicenter clinical studies are needed to confirm this result.

Association of CYP2J2 gene polymorphisms with ischemic stroke and stroke subtypes in Chinese population.

BACKGROUND AND PURPOSE: Ischemic stroke (IS) is the main cause of mortality and disability among the old people in China and is a multifactorial disease influenced by many factors including genetic factors like the allele for CYP 2J2. It has been demonstrated that CYP2J2 polymorphisms alter the transcriptional activity. However, studies on the association between CYP2J2-50G/T polymorphism and IS have reported conflicting results. Thus, our study aimed to examine the association between 4 variants in the CYP2J2 gene and the risk of IS and its subtypes, in the Chinese population. MATERIALS AND METHODS: In this study, genotyping was performed by using polymerase chain reaction (PCR) sequencing for 202 IS patients and 206 age- and sex-matched controls. Odds ratios (ORs) and confidence interval (CI) were estimated by multivariate logistic regression and PCR results were confirmed by DNA sequencing. A meta-analysis was conducted to evaluate the association of CYP2J2-50G>T polymorphism with the risk of IS in Chinese population by calculating pooled OR. RESULTS: We found this polymorphism was significantly associated with IS (17.82% vs. 10.68%, P = 0.039). Multiple logistic regression analysis revealed that GT genotype was associated with a significantly high risk of IS (OR = 2.32, 95% CI: 1.21-4.45, P = 0. 011) after adjustment for other confounding factors such as hypertension, diabetes, heart disease, smoking habit, family history, triglyceride and low-density lipoprotein levels. We also found a significant association of GT genotype with small artery occlusion (SAA) (P < 0.05; OR = 2.22; 95% CI: 1.043-4.72). Meta-analysis results also showed that the GT genotype carriers had a negative effect on the risk of IS in Chinese population with overall OR of 1.40 (95% CI: 1.06-1.84). CONCLUSION: The findings of the present study suggested that polymorphism in -50G/T position of CYP2J2 gene might be a risk factor for IS in Chinese population. Further large prospective studies were required to confirm these findings.