Abstract: Lymphocyte to monocyte ratio (LMR) is associated with functional outcome in patients with stroke. But the relationship between the LMR value and the prognosis of cerebral venous sinus thrombosis (CVST) has not been investigated. Methods CVST patients, admitted to the First Affiliated Hospital of Zhengzhou University, were retrospectively identified from November 2010 to January 2017. Functional outcomes of patients were evaluated with the modified Rankin Scale (mRS). Patients were divided into good (mRS 0–2) and poor (mRS 3–6) outcomes groups. Univariate and multivariate Cox regression analyses were used to assess the relationship between LMR and the poor survival outcome. Results A total of 228 patients were included of which 41 had poor outcomes (18.0%). The duration of follow-up was 22 months (6–66 months). LMR (2.3±1.2 vs 3.2±1.8, p 〈 0.01) was significantly lower in the poor outcome group. Multivariate Cox regression analysis showed that LMR (HR 0.726, 95% CI 0.546 to 0.964, p=0.027) was a independent predictor of poor prognosis. Conclusions LMR may be a predictor of poor prognosis in CVST patients.

Abstract: Renal impairment (RI) is associated with worse outcomes in the treatment of intravenous thrombolysis and emergent endovascular treatment (EVT) in anterior circulation stroke. The objective of this study was to investigate the association of RI with short-term and long-term outcomes in patients with vertebrobasilar artery occlusions (VBAO) who received EVT. Methods Consecutive patients with VBAO receiving EVT involving 21 stroke centers were retrospectively included. Multivariate regression analyses were used to evaluate the association of RI with mortality and symptomatic intracranial hemorrhage (sICH) during the hospital stay, and also mortality, favorable functional outcome (modified Rankin Scale (mRS) score of 0–3), and functional improvement (shift in mRS score) at 3 months and 1 year follow-up. The association between RI and the risk of recurrent stroke was evaluated with multivariate competing-risk regression analyses. Results After adjustment for potential confounders, RI was independently associated with sICH (OR 3.30, 95% CI 1.55 to 7.18), as well as mortality (OR 2.54, 95% CI 1.47 to 4.38; OR 3.07, 95% CI 1.72 to 8.08), favorable functional outcome (OR 0.33, 95% CI 0.17 to 0.66; OR 0.25, 95% CI 0.12 to 0.51), and functional improvement (OR 0.45, 95% CI 0.28 to 0.74; OR 0.35, 95% CI 0.21 to 0.60) at 3 months and 1 year follow-up, respectively, but RI was not associated with in-hospital mortality. Additionally, there was no significant association between RI and recurrent stroke within 1 year. Conclusions Our findings suggest that RI is associated with a higher risk of sICH in hospital and a decrease in survival, favorable functional outcome, and functional improvement at 90 days and 1 year follow-up. Trial registration number URL: http://www.chictr.org.cn/ ; Unique identifier: ChiCTR2000033211.

Abstract: In this randomized, double-blind, controlled study, we hypothesized that programmed intermittent bolus infusion (PIBI) of local anesthetic for continuous paravertebral block (PVB), combined with patient-controlled analgesia (PCA), provided better pain control, better patient satisfaction, and decreased in local anesthetic consumption when compared with a continuous infusion (CI) combined with PCA, after video-assisted thoracoscopic unilateral lung resection surgery. Methods Preoperatively, patients undergoing video-assisted thoracoscopic unilateral lung resection surgery received ipsilateral paravertebral catheters inserted at the level of thoracic vertebrae 4 and 5. All the subjects received an initial bolus of 15 mL 0.375% ropivacaine via the catheters. Subjects were randomized to receive 0.2 % ropivacaine 8 mL/h as either PIBI (n=17) or CI (n=17) combined with a PCA pump. The pain scores, frequency of PCA, local anesthetic consumption, patient satisfaction, and the need for rescue analgesia with tramadol were recorded until 48 hours postoperative. Results The numeric rating scale scores in the PIBI group were significantly lower than the CI group at 4, 8, 12 hours and 4, 8, 12, 24 hours postoperatively, at rest, and during coughing, respectively. PCA local anesthetic consumption (30 mg (20–60 mg) vs 120 mg (70–155 mg), p=0.000) and frequency of PCA use over 48 hours (3 (2–6) vs 12 (7–15.5), p=0.000) was lower in the PIBI group as compared with the CI group. Additionally, the PIBI group showed greater patient satisfaction. The need for tramadol rescue was similar in the two groups. Conclusions In PVBs, local anesthetic administered as a PIBI in conjunction with PCA provided superior postoperative analgesia to a CI combined with PCA in patients undergoing video-assisted thoracoscopic unilateral lung resection surgery. Clinical trial registration ChiCTR-IOR-17011253.

Abstract: Approximately two-thirds of patients with relapsed or refractory large B-cell lymphoma (R/R LBCL) do not respond to or relapse after anti-CD19 chimeric antigen receptor T (CAR T)-cell therapy, leading to poor outcomes. Previous studies have suggested that intensified lymphodepletion and hematological stem cell infusion can promote adoptively transferred T-cell expansion, enhancing antitumor effects. Therefore, we conducted a phase I/II clinical trial in which CNCT19 (an anti-CD19 CAR T-cell) was administered after myeloablative high-dose chemotherapy and autologous stem cell transplantation (HDT/ASCT) in patients with R/R LBCL. Methods Transplant-eligible patients with LBCL who were refractory to first-line immunochemotherapy or experiencing R/R status after salvage chemotherapy were enrolled. The study aimed to evaluate the safety and efficacy of this combinational therapy. Additionally, frozen peripheral blood mononuclear cell samples from this trial and CNCT19 monotherapy studies for R/R LBCL were used to evaluate the impact of the combination therapy on the in vivo behavior of CNCT19 cells. Results A total of 25 patients with R/R LBCL were enrolled in this study. The overall response and complete response rates were 92.0% and 72.0%, respectively. The 2-year progression-free survival rate was 62.3%, and the overall survival was 68.5% after a median follow-up of 27.0 months. No unexpected toxicities were observed. All cases of cytokine release syndrome were of low grade. Two cases (8%) experienced grade 3 or higher CAR T-cell-related encephalopathy syndrome. The comparison of CNCT19 in vivo behavior showed that patients in the combinational therapy group exhibited enhanced in vivo expansion of CNCT19 cells and reduced long-term exhaustion formation, as opposed to those receiving CNCT19 monotherapy. Conclusions The combinational therapy of HDT/ASCT and CNCT19 demonstrates impressive efficacy, improved CNCT19 behavior, and a favorable safety profile. Trial registration numbers ChiCTR1900025419 and NCT04690192 .

Abstract: Gastric adenocarcinoma (GAC) is a lethal disease with limited therapeutic options. Genetic alterations in chromatin remodelling gene AT-rich interactive domain 1A ( ARID1A ) and mTOR pathway activation occur frequently in GAC. Targeting the mechanistic target of rapamycin (mTOR) pathway in unselected patients has failed to show survival benefit. A deeper understanding of GAC might identify a subset that can benefit from mTOR inhibition. Methods Genomic alterations in ARID1A were analysed in GAC. Mouse gastric epithelial cells from CK19-Cre-Arid1A fl/fl and wild-type mice were used to determine the activation of oncogenic genes due to loss of Arid1A. Functional studies were performed to determine the significance of loss of ARID1A and the sensitivity of ARID1A-deficient cancer cells to mTOR inhibition in GAC. Results More than 30% of GAC cases had alterations (mutations or deletions) of ARID1A and ARID1A expression was negatively associated with phosphorylation of S6 and SOX9 in GAC tissues and patient-derived xenografts (PDXs). Activation of mTOR signalling (increased pS6) and SOX9 nuclear expression were strongly increased in Arid1A −/− mouse gastric tissues which could be curtailed by RAD001, an mTOR inhibitor. Knockdown of ARID1A in GAC cell lines increased pS6 and nuclear SOX9 and increased sensitivity to an mTOR inhibitor which was further amplified by its combination with fluorouracil both in vitro and in vivo in PDXs. Conclusions The loss of ARID1A activates pS6 and SOX9 in GAC, which can be effectively targeted by an mTOR inhibitor. Therefore, our studies suggest a new therapeutic strategy of clinically targeting the mTOR pathway in patients with GAC with ARID1A deficiency.

Abstract: To explore diabetes-related behaviours and their influencing factors among elderly individuals with pre-diabetes in rural areas of China. Design, setting and participants A cross-sectional survey was conducted among elderly individuals (≥60 years) in rural communities in Yiyang City of China. Multistaged cluster random sampling was carried out to select 42 areas, and interviews were conducted among 434 elderly individuals with pre-diabetes (fasting plasma glucose 6.1–7.0 mmol/L and/or 2-hour post-glucose load of 7.8–11.1 mmol/L) using questionnaires on diabetes-related behaviours. The diabetes-related behaviours included eight categories: average daily sedentary time; frequency of physical activities per week; regular or irregular diet; whether paying attention to diet control or not; daily dietary preferences; frequency of physical examinations per year; current smoking status; and current consumption of alcohol. Each of the risky behaviours was scored −1 and each of the healthy behaviours was scored +1. Each individual’s score of diabetes-related behaviours was the sum of the score for all behaviours. Main outcome measures Participants were asked about general information (age, gender, marital status, history of hyperglycaemia, family history of diabetes mellitus, presence of other diseases, body mass index, waist-to-hip ratio and education) and their diabetes-related behaviours. Multivariate linear regression analysis was performed to identify the risk factors for diabetes-related behaviour among elderly individuals with pre-diabetes. Results The average score of diabetes-related behaviours of elderly individuals with pre-diabetes in rural China was 2.7. The prevalences of risky diabetes-related behaviours were as follows: 〈 1 physical examination per year (57.6%), insufficient physical activities (55.3%), lack of attention paid to diet control (51.4%), high-salt and high-fat diets (41.0%), sedentary lifestyle (35.9%), smoking (22.8%), regular alcohol uptake (15.0%) and irregular diet (3.9%). Gender and a history of hyperglycaemia were found to be influencing factors of the diabetes-related behaviour score. Conclusions The prevalence of risky diabetes-related behaviours was high among pre-diabetic elderly individuals in rural China. More effort should be made to promote the prevention and control of diabetes in rural China. Future studies should be undertaken on diabetes prevention strategies tailored specially for this population. Trial registration number ChiCTR-IOR-15007033; Results.

Abstract: To examine the association between diabetes-specific health literacy (DSHL) and health-related quality of life (HRQoL) among elderly individuals with pre-diabetes in rural China. Design, setting and participants This cross-sectional study included 434 elderly individuals with pre-diabetes from 42 villages in rural China. Main outcome measures HRQoL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey. DSHL was measured by a validated questionnaire in China. Differences in HRQoL between groups with and without high DSHL were tested by multivariate analysis of covariance (MANCOVA). Results The prevalence of pre-diabetes was 21.5%. The average age of participants (n=434) was 69.4±6.4 years, and 58.5% were female. Bivariate analysis showed that those with high DSHL had increases of 2.9 points in the physical health component score and 4.4 points in the mental health component score (MCS) compared with those without. After adjustment for potential confounders, a significant MANCOVA model (Wilks’ λ=0.974, F=5.63, p=0.004) indicated that individuals with pre-diabetes who had high DSHL reported higher MCS (M diff =3.5, 95% CI 1.8 to 6.3, effect size=0.38). This remained significant across subscales: general health (p=0.028), vitality (p=0.014), social functioning (p=0.017) and mental health (p=0.005). Conclusions Low DSHL was associated with worsening HRQoL among elderly individuals with pre-diabetes in rural China, particularly in the mental health components. Trial registration number ChiCTR-IOR-15007033.

Abstract: Colorectal cancer is a heterogeneous disease with complicated genetic alterations. Right colon and left colon have different features while right colon cancer displays an even worse prognosis. The randomized phase III FOxTROT trial demonstrated better downstaging effect with neoadjuvant plus adjuvant chemotherapy compared with adjuvant chemotherapy alone (P=0.04). 1 Moreover, 2-year relapse rate was improved with neoadjuvant therapy, though the difference was not statistically significant. The NICHE study of neoadjuvant immunotherapy (maximum 6 weeks) showed that the pathological response was observed in 20/20 mismatch repair-deficient (dMMR) resectable colon cancers, with 19 major pathological responses and 12 pathological complete responses (pCRs). 2 Recently, KEYNOTE-177 study showed improved progression-free survival with PD-1 inhibitor over chemotherapy (16.5 months vs. 8.2 months) in untreated microsatellite instability-high (MSI-H)/dMMR colon cancer patients, including 68% of right colon cancers. 3 In addition, camrelizumab (PD-1 inhibitor) plus apatinib (vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor) demonstrated favorable antitumor effects and a manageable safety profile in advanced hepatocellular carcinoma and gastric cancer. 4 5 This phase II trial aims to explore whether the combination of camrelizumab, apatinib and chemotherapy (mFOLFOX6) could significantly improve the pathological regression rate in locally advanced right colon cancer so as to bring considerable survival benefit for patients. Methods Eligible patients are aged 18–75 years, with locally advanced (T4 or T3 with extramural depth ≥5 mm, N0-2, M0, AJCC 8th) adenocarcinoma of right colon (including ileocecal area, ascending colon, and transverse colon to splenic flexion), and without prior systemic chemotherapy or immunotherapy. All patients will receive 5 cycles of camrelizumab (200 mg once every 2 weeks) plus mFOLFOX6 and 2 months of apatinib (250 mg orally once a day), followed by surgery and 7 cycles of adjuvant camrelizumab plus mFOLFOX6. The primary endpoint is the proportion of patients with tumor regression grade (TRG) 2–4 according to the Dworak criteria (TRG2: dominantly fibrotic changes with few tumor cells or groups; TRG3: very few tumor cells in fibrotic tissue; TRG4: no tumor cells). Secondary endpoints include downstaging rate, pCR rate, R0 resection rate, 2-year disease-free survival rate, 2-year event-free survival, overall survival, quality of life, and safety. Results To date, three of planned 64 patients have been enrolled. Two patients have completed surgery. According to Dworak criteria, TRG ranked 4 (pathologic complete response) for the first patient and 3 (very few tumor cells in fibrotic tissue) for the second patient. No severe adverse events have been observed for all patients. Trial Registration This trial has been registered at ClinicalTrials.gov ( NCT04625803 ). References G. Foxtrot Collaborative. Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial. Lancet Oncol 13 (11) (2012):1152–60. Chalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med 26 (4) (2020):566–576. André T, Shiu KK, Kim TW, Jensen BV, Jensen LH, Punt C, Smith D, Garcia-Carbonero R, Benavides M, Gibbs P, de la Fouchardiere C, Rivera F, Elez E, Bendell J, Le DT, Yoshino T, Van Cutsem E, Yang P, Farooqui MZH, Marinello P, Diaz Jr LA. Pembrolizumab in microsatellite-instability-high advanced colorectal cancer. N Engl J Med 383 (23) (2020):2207–2218. Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial. Clin Cancer Res 27 (4) (2021):1003–1011. Xu J, Shen J, Gu S, Zhang Y, Wu L, Wu J, Shao G, Zhang Y, Xu L, Yin T, Liu J, Ren Z, Xiong J, Mao X, Zhang L, Yang J, Li L, Chen X, Wang Z, Gu K, Chen X, Pan Z, Ma K, Zhou X, Yu Z, Li E, Yin G, Zhang X, Wang S, Wang Q, Xu J, Zhang Y, Jia R, Yue C, Chang L, Liu R, Zhang G, Zhao C, Zhang Y, Chen C, Wang Y, Yi X, Hu Z, Zou J, Wang Q. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res 27 (4) (2021):1003–1011. Ethics Approval Study protocol was approved by the Clinical Research Ethics Committee of the First Affiliated Hospital, College of Medicine, Zhejiang University (2020–119) Consent Written informed consent was obtained from the patient for publication of this abstract and any accompanying images. A copy of the written consent is available for review by the Editor of this journal.

Abstract: To determine the correspondence between GNAQ R183Q (c.548G＞A) mutation in abnormal scleral tissue of patients with Sturge-Weber syndrome (SWS) secondary glaucoma and explore the role of GNAQ R183Q in glaucoma pathogenesis. Methods Episcleral tissues were obtained from 8 patients: SWS secondary glaucoma (n=5) and primary congenital glaucoma (PCG, n=3). Scleral tissues were obtained from 7 patients: SWS secondary glaucoma (n=2), PCG (n=1) and juvenile open-angle glaucoma (n=4). GNAQ R183Q mutation was detected in scleral tissue by droplet digital PCR. Tissue sections from SWS were examined by immunohistochemistry to determine the expression of p-ERK. Results The GNAQ R183Q mutation was present in 100% of the SWS abnormal sclera. Five cases were SWS patient-derived episcleral tissue, and the mutant allelic frequencies range from 6.9% to 12.5%. The other two were deep scleral tissues and the mutant frequencies were 1.5% and 5.3%. No mutations in GNAQ R183 codon were found in the sclera of PCG and juvenile open-angle glaucoma. Increased expression of p-ERK and p-JNK was detected in the endothelial cells of SWS abnormal scleral blood vessels. Conclusions GNAQ R183Q occurred in all abnormal scleral tissue of SWS secondary glaucoma. Increased expression of p-ERK and p-JNK in endothelial cells of blood vessels was detected in the abnormal scleral tissue. This study suggests GNAQ R183Q may regulate episcleral vessels of patients with SWS through abnormal activation of ERK and JNK, providing new genetic evidence of pathogenesis of glaucoma in SWS, and the dysplasia of scleral tissue in anterior segment may be used as an early diagnostic method or treatment targets to prevent the development and progression of glaucoma in patients with SWS.