[Patient-reported outcomes of locally advanced gastric cancer undergoing robotic versus laparoscopic gastrectomy: a randomized controlled study].

Objective: To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer. Methods: This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery,Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher's exact test. Results: A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant (χ2 value were 156.24, 4.08, 36.56, P value were<0.01, 0.043,<0.01). Conclusion: Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Recombinant erythropoietin protective and related effects on brain injury in premature infants.

OBJECTIVE: The aim of this study was to investigate the protective effect of recombinant erythropoietin at different doses on brain injury in premature infants and the related effects on blood routine, liver function, intellectual development, mental development index (MDI), psychomotor development index (PDI), etc. PATIENTS AND METHODS: A total of 120 premature infants were divided into four groups, including experimental group A (n=30), experimental group B (n=30), experimental group C (n=30) and control group (n=30). The experimental group was treated with different doses of recombinant erythropoietin for brain injury protection of premature infants, while the control group with conventional methods. RESULTS: There was no statistical significance in all test indicators of the four groups of patients before the intervention. After the intervention experiment, the S-100B index was p<0.05, and the erythropoietin (EPO) index was p<0.05. In the comparison of IL-6 indicators, the indicators of the experimental group were reduced after the comparison experiment, and there were significant differences, p<0.05. In neonatal behavior evaluation, there was a statistical difference between groups A and B and the control group (p<0.05), and no statistical significance was shown between group C and the control group (p>0.05). In the intelligence test comparison, the F value of the experimental group was 3.113 three months after treatment. After six months, the F value was 3.654. After nine months, the F value was 3.392 with p<0.05. In the comparison of blood routine indicators, the p-values of four indicators between groups were more than 0.05. In the comparison of liver function indexes, the indexes of groups A, B, and C were significantly changed before and after treatment, and the data after treatment were significantly different from those before treatment, p<0.05. In the comparison of development, there were no significant differences observed in the p-values of the two indicators of vigorous exercise and language in the experimental group. CONCLUSIONS: Recombinant erythropoietin has a protective effect on infants with brain injury and can improve the intellectual development of premature infants, but has no significant effect on blood routine indicators. It can effectively improve the MDI, PDI, and related cytokines of premature infants, and has certain significance for the treatment of brain injury.

[Clinical analysis of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma].

Objective: To analyze the incidence and the related risk factors of retropharyngeal lymph node metastasis in patients with hypopharyngeal squamous cell carcinoma, evaluate the accuracy of preoperative enhanced CT in judging retropharyngeal lymph node metastasis, and investigate the impact of retropharyngeal lymph node metastasis on the prognosis. Methods: Retrospective analyses were made on 398 patients with hypopharyngeal squamous cell carcinoma who underwent surgery as the primary therapy and accepted retropharyngeal lymph node exploration and clearance during surgery in Shandong Provincial ENT Hospital from January 2014 to December 2019. Multivariate logistic regression analysis was used to clarify the related risk factors of retropharyngeal lymph node metastasis. Multivariate Cox regression analysis was used to investigate the impact of retropharyngeal lymph node metastasis on prognosis. The retropharyngeal lymph nodes of 218 cases with available preoperative enhanced CT images were evaluated by two experienced radiologists and compared with postoperative pathological results. Results: Retropharyngeal lymph node metastasis were confirmed in 54 of 398 (13.6%) cases according to postoperative pathology. The sensitivity and specificity of preoperative enhanced CT in the diagnosis of retropharyngeal lymph node metastasis were 34.6% and 91.1%, respectively, and the overall accuracy was 84.4%. Multivariate logistic regression analysis showed that the site of the primary lesion and pathological N stage were independent risk factors for retropharyngeal lymph node metastasis in hypopharyngeal squamous cell carcinoma. Patients with primary lesion located in the posterior wall of hypopharynx (OR=4.83, 95% CI: 1.27-18.40), N2 stage (OR=6.30, 95% CI: 2.25-17.67), and N3 stage (OR=26.89, 95% CI: 5.76-125.58) were prone to retropharyngeal lymph node metastasis. The 5-year overall survival rate of the 398 patients was 50.4%, and the 5-year disease-free survival rate was 48.3%. Multivariate Cox regression analysis showed that T stage, N stage, retropharyngeal lymph node metastasis, and radiotherapy were independent influencing factors for overall survival (T stage: HR=1.28, 95% CI: 1.06-1.54; N stage: HR=1.26, 95% CI: 1.14-1.40; retropharyngeal lymph node metastasis: HR=2.13, 95% CI: 1.47-3.08; radiotherapy: HR=0.54, 95% CI: 0.38-0.76) and disease-free survival of patients with hypopharyngeal squamous cell carcinoma (T stage: HR=1.26, 95% CI: 1.06-1.51; N stage: HR=1.25, 95% CI: 1.13-1.37; retropharyngeal lymph node metastasis: HR=2.24, 95% CI: 1.56-3.21; radiotherapy: HR=0.55, 95% CI: 0.40-0.77). Conclusions: Metastasis of retropharyngeal lymph nodes in hypopharyngeal squamous cell carcinoma is not rare. Enhanced CT is of low accuracy and limited value in diagnosing retropharyngeal lymph node metastasis. Primary lesions located in the posterior wall of the hypopharyngx, N2 stage, and N3 stage are independent high-risk factors for retropharyngeal lymph node metastasis. The prognosis of hypopharyngeal cancer patients with retropharyngeal lymph node metastasis is worse, and active surgical exploration and clearance can effectively reduce the mortality caused by retropharyngeal lymph node metastasis.

[Application value of CT examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma].

Objective: To investigate the application value of computed tomography (CT) examination of lymph node short diameter in evaluating cardia-left gastric lymph node metastasis in thoracic esophageal squamous cell carcinoma (ESCC). Methods: A total of 477 patients with primary thoracic ESCC who underwent surgical treatment in the Affiliated Cancer Hospital of Zhengzhou University from January 2013 to December 2017 were collected. All of them underwent McKeown esophagectomy plus complete two-field or three-field lymph node dissection. Picture archiving and communication system were used to measure the largest cardia-left gastric lymph node short diameter in preoperative CT images. The postoperative pathological diagnosis results of cardia-left gastric lymph node were used as the gold standard. Receiver operating characteristic (ROC) curve was used to evaluate the efficacy of CT lymph node short diameter in detecting the metastasis of cardia-left gastric lymph node in thoracic ESCC, and determine the optimal cut-off value. Results: The median short diameter of the largest cardia-left gastric lymph node was 4.1 mm in 477 patients, and the largest cardia-left gastric lymph node short diameter was less than 3 mm in 155 cases (32.5%). Sixty-eight patients had cardia-left gastric lymph node metastases, of which 38 had paracardial node metastases and 41 had left gastric node metastases. The lymph node ratios of paracardial node and left gastric node were 4.0% (60/1 511) and 3.3% (62/1 887), respectively. ROC curve analysis showed that the area under the curve of CT lymph node short diameter for evaluating cardia-left gastric lymph node metastasis was 0.941 (95% CI: 0.904-0.977; P<0.05). The optimal cut-off value of CT examination of the cardia-left gastric lymph node short diameter was 6 mm, and the corresponding sensitivity, specificity and accuracy were 85.3%, 91.7%, and 90.8%, respectively. Conclusion: CT examination of lymph node short diameter can be a good evaluation of cardia-left gastric lymph node metastasis in thoracic ESCC, and the optimal cut-off value is 6 mm.

From association to gist: Some critical tests.

We report the first evidence that the gist mechanism of fuzzy-trace theory and the associative mechanism of activation monitoring theory operate in parallel, in the recall version of the Deese/Roediger/McDermott illusion. In three experiments, we implemented a new methodology that allows their respective empirical indexes, gist strength (GS) and backward associative strength (BAS), to each be manipulated while the other is held constant. In Experiment 1, increasing GS increased false recall of missing words, but increasing BAS did not. In Experiments 2 and 3, however, increasing GS and increasing BAS both increased recall of missing words, and those effects were independent and additive. In all three experiments, GS and BAS affected true recall of list words in qualitatively different ways: (a) Increasing GS always improved true recall, regardless of whether BAS was high or low, but (b) increasing BAS impaired true recall when GS was high and improved true recall when GS was low. To pinpoint the retrieval loci of the two variables' effects, we analyzed the data of all experiments with the dual-retrieval model. Those analyses showed that the variables' respective effects were due to different retrieval processes. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Effect of metformin on Wnt5a in individuals new-onset type 2 diabetes with different body mass indexes: The evidences from the real word research.

Aim: Metformin is a first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM), due to its inhibition of hepatic gluconeogenesis. Wingless family member 5a (Wnt5a) was significantly decreased in newly diagnosed T2DM patients and regulates secretion of ß cells through the Wnt/calcium signalling cascades. This study aims to investigate how metformin works on glucose-lowering effects in diabetes and whether the mechanism underlying it is associated with Wnt5a. Methods: A total of 144 participants were enrolled in this study. Serum Wnt5a levels were measured by an enzyme-linked immunosorbent assay (ELISA). The demographic and clinical parameters were evaluated in normal weight, overweight and obese new-onset T2DM subjects grouped. Results: Wnt5a was increased in overweight T2DM patients and obese T2DM patients compared with the levels in normal Body Mass Index (BMI) T2DM. The level of Wnt5a gradually increased after 3 and 6 months of metformin treatment. Among the three groups, the most significant improvement in blood glucose was observed in the obese type 2 diabetic patients, and the improvement showed a significant correlation with Wnt5a protein after patients received metformin treatment. Pearson correlation showed that there was a significant relationship between △2hOGTT and Wnt5a. After further adjusting for sex and age, a significant association existed only between Wnt5a and 2-h oral glucose tolerance test(2hOGTT), and this association was negative. Conclusion: Our results indicate that Wnt5a may play a role in the mechanism by which metformin improves blood glucose in patients with type 2 diabetes.

[Efficacy and feasibility of catheter-based adrenal ablation on Cushing's syndrome associated hypertension].

Objective: To explore the value of catheter-based adrenal ablation in treating Cushing's syndrome (CS)-associated hypertension. Methods: A clinical study was conducted in patients with CS, who received catheter-based adrenal ablation between March 2018 and July 2023 in Daping Hospital. Parameters monitored were blood pressure (outpatient and 24-hour ambulatory), body weight, clinical characteristics, serum cortisol and adrenocorticotropic hormone (ACTH) at 8 am, 24-hour urinary free cortisol (24 h UFC), fasting blood glucose and postoperative complications. Procedure effectiveness was defined as blood pressure returning to normal levels (systolic blood pressure<140 mmHg (1 mmHg=0.133 kPa) and diastolic blood pressure<90 mmHg), cortisol and 24 h UFC returning to normal and improvement of clinical characteristics. The parameters were monitored during follow up in the outpatient department at 1, 3, 6, and 12 months after catheter-based adrenal ablation. Results: A total of 12 patients (aged (40.0±13.2) years) were reviewed. There were 5 males, with 5 cases of adenoma and 7 with hyperplasia from imaging studies. Catheter-based adrenal ablation was successful in all without interruption or surgical conversion. No postoperative complication including bleeding, puncture site infection, adrenal artery rupture or adrenal bleeding was observed. The mean follow up was 28 months. Compared to baseline values, body weight declined to (59.48±11.65) kg from (64.81±10.75) kg (P=0.008), fasting blood glucose declined to (4.54±0.83) mmol from (5.53±0.99) mmol (P=0.044), outpatient systolic blood pressure declined to (128±21) mmHg from (140±19) mmHg (P=0.005), diastolic blood pressure declined to (78±10) mmHg from (86±11) mmHg (P=0.041), and the mean ambulatory daytime diastolic blood pressure declined to (79±12) mmHg from (89±8) mmHg (P=0.034). Catheter-based adrenal ablation in 8 patients was defined as effective with their 24 h UFC significantly reduced after the procedure (1 338.41±448.06) mmol/L from (633.66±315.94) mmol/L, P=0.011). The change of 24 h UFC between the effective treatment group and ineffective group was statistically significant (P=0.020). The postoperative systolic blood pressure in the treated adenoma group was significantly lower than those of hyperplasia group (112±13) mmHg vs. (139±20) mmHg, P=0.026). Conclusions: For patients with CS-associated hypertension who are unwilling or unable to undergo surgical treatment, catheter-based adrenal ablation could improve the blood pressure and cortisol level. Catheter-based adrenal ablation could be a safe, effective, and minimally invasive therapy. However, our results still need to be validated in further large-scale studies.

[The correlation between burst suppression on electroencephalogram during laparoscopic surgery and emergence delirium in elderly patients].

Objective: To investigate the relationship between intraoperative electroencephalogram burst suppression (BS) and emergence delirium (ED) in elderly patients undergoing elective laparoscopic surgery under total intravenous anesthesia (TIVA). Methods: From October 2017 to September 2019, a total of 358 elderly patients who underwent elective laparoscopic surgery under TIVA at Xiangya Hospital, Central South University, were included. Patients were divided into two groups based on the confusion assessment method for the intensive care unit (CAM-ICU) assessment conducted before leaving the post-anesthesia care unit (PACU): the ED group [n=63, 46 males, 17 females, average age of (70.8±0.6) years] and the non-ED group [n=295, 220 males, 75 females, average age of (69.7±0.2) years]. Preoperative general information, intraoperative conditions, and intraoperative electroencephalogram BS status were collected. A multivariate logistic regression model was employed to identify risk factors associated with ED. Results: In the ED group, the duration of surgery, intraoperative blood loss, the burst suppression ratio (BSR)>10% lasting for more than 1 minute were (224.4±9.6) min, (240.8±33.9) ml, 36.5% (23/63), respectively, which were higher than those of the non-ED group [(204.7±3.6) min, (150.5±9.2) ml, 21.7% (64/295), all P<0.05]. Multivariate logistic regression analysis revealed that a longer duration of education was a protective factor for ED (OR=0.904, 95%CI: 0.833-0.982,P=0.016), whereas increased intraoperative blood loss (OR=1.002, 95%CI: 1.000-1.003, P=0.013) and BSR>10% lasting for more than 1 minute (OR=2.131, 95%CI: 1.004-4.524,P=0.049) were identified as risk factors for ED. Conclusion: In elderly patients undergoing laparoscopic surgery under TIVA, intraoperative electroencephalogram BS may be a risk factor for ED.

A comprehensive analysis of LINC00958 as a prognostic biomarker for head and neck squamous cell carcinomaLi et al.

This work focused on exploring whether the long intergenic non-protein coding RNA LINC00958 is associated with the prognosis of head and neck squamous cell carcinoma (HNSCC). Associations of the LINC00958 expression level with clinicopathological features of HNSCC were investigated by logistic regression and Wilcoxon signed-rank test. The Kaplan-Meier method was applied to evaluate patient survival. Clinical data and expression profiles were obtained from The Cancer Genome Atlas (TCGA). Associations of patient clinical characteristics with overall survival (OS), progression-free interval (PFI), and disease-specific survival (DSS) were assessed by univariate and multivariate analysis using the Cox proportional hazard model. Immune cell infiltration analysis and gene set enrichment analysis (GSEA) were applied to determine any significant effects of LINC00958. High LINC00958 expression was related to early pT stage (P < 0.01), primary therapy outcome (P < 0.01), HPV status (P < 0.001), lymphovascular invasion (P < 0.001), and perineural invasion (P < 0.01). The receiver operating characteristic curve showed strong prognostic power for LINC00958 (area under curve = 0.886). High LINC00958 expression predicted poor OS (P = 0.007), DSS (P = 0.036), and PFI (P = 0.040). LINC00958 was related to signalling pathways and the infiltration of certain immune cells. miR-27b-5p was significantly associated with LINC00958, and downstream NT5E predicted poor survival in HNSCC cases. LINC00958 may affect the prognosis by regulating NT5E via miR-27b-5p, and could serve as a possible factor to predict the prognosis of HNSCC, especially oral squamous cell carcinoma.

The effect of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in STEMI patients after PCI.

OBJECTIVE: This study aimed to investigate the effects of ticagrelor on myocardial microcirculation, cardiac function, and adverse cardiovascular events in ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). PATIENTS AND METHODS: A total of 80 STEMI patients admitted to our hospital from February 2020 to March 2023 were selected and included in the retrospective study, all receiving PCI treatment. They were randomly and retrospectively divided into a control group (40 cases) and an observation group (40 cases), and treated with clopidogrel and ticagrelor, respectively. The clinical effects were compared. RESULTS: The starting perfusion time of the contrast agent in the myocardial infarction area in the observation group was 2.22±0.27 s, and the peak perfusion time was 2.62±0.27 s, which was lower than those in the control group (2.51±0.29 s and 3.21±0.39 s, t=4.629, 7.867, p=0.000). The ratio of peak perfusion intensity between the two groups was significantly different (t=2.363, p=0.021). Left ventricular ejection fraction, stroke volume index, and cardiac index in the observation group were higher than those in the control group (55.03±6.03 vs. 52.33±5.13; 57.39±6.81 vs. 51.11±6.31 L/min·m-2; 3.49±0.45 vs. 3.12±0.38 mL/m2, t=2.157, 4.278, 3.973, p<0.05). The observation group had lower levels of brain natriuretic peptide and C-reactive protein compared to the control group (425.35±55.71 vs. 589.36±70.24 pg/mL; 15.13±1.03 vs. 21.64±2.74 mg/L; t=11.570, 14.066, p=0.000). There was no statistical significance in the incidence of adverse cardiovascular events between the two groups (2.50% vs. 7.50%, χ2=1.920, p=0.166). CONCLUSIONS: The use of ticagrelor can regulate myocardial microcirculation and improve cardiac function in STEMI patients undergoing PCI.

The effect of the enhanced recovery after surgery protocol and the reduced use of opioids on postoperative outcomes in elderly patients with colorectal cancer.

OBJECTIVE: The study aimed to assess the impact of the enhanced recovery after surgery (ERAS) pathways and the reduced use of opioids on postoperative outcomes in elderly colorectal cancer (CRC) patients who underwent laparoscopic surgery under general anesthesia (GA). PATIENTS AND METHODS: Clinical data from 99 elderly patients who underwent laparoscopic CRC surgery in the First Affiliated Hospital of Hebei North University from April 2021 to April 2023 were retrospectively analyzed and grouped based on the method of pain control measures received. Of 99 patients, 51 received conventional doses of opioid drugs (conventional group), and 48 patients were treated with reduced doses of opioids based on the principles of ERAS (low-dose group). Perioperative characteristics, postoperative pain level, cognitive function, serum biochemical index levels, and adverse reactions were compared between the two groups. RESULTS: The first exhaust time, defecation time, and bedtime activity time of the low-dose group were compared to the conventional group (p<0.05). On the first day after the surgery, the mini-mental state examination (MMSE) score of the low-dose group was higher than the conventional group (p<0.05). After the surgery, the levels of serum brain-derived neurotrophic factor (BDNF) decreased in both groups, while the levels of neuron-specific enolase (NSE) and 5-hydroxytryptamine (5-HT) increased. However, compared to the conventional group, the low-dose group had higher levels of BDNF and lower levels of NSE and 5-HT (p<0.05). The incidence of adverse reactions in the low-dose group was lower than that in the conventional group (p<0.05). CONCLUSIONS: ERAS protocol and the reduced use of opioid drugs in CRC patients who underwent surgery under GA is associated with an analgesic effect that is comparable to that of conventional opioid use. Reduced dosage of opioid drugs lessened cognitive impairment and lowered the incidence of adverse reactions in surgical patients with CRC.

A DNA Replication Stress-Based Prognostic Model for Lung Adenocarcinoma.

Tumor cells endure continuous DNA replication stress, which opens the way to cancer development. Despite previous research, the prognostic implications of DNA replication stress on lung adenocarcinoma (LUAD) have yet to be investigated. Here, we aimed to investigate the potential of DNA replication stress-related genes (DNARSs) in predicting the prognosis of individuals with LUAD. Differentially expressed genes (DEGs) originated from the TCGA-LUAD dataset, and we constructed a 10-gene LUAD prognostic model based on DNARSs-related DEGs (DRSDs) using Cox regression analysis. The receiver operating characteristic (ROC) curve demonstrated excellent predictive capability for the LUAD prognostic model, while the Kaplan-Meier survival curve indicated a poorer prognosis in a high-risk (HR) group. Combined with clinical data, the Riskscore was found to be an independent predictor of LUAD prognosis. By incorporating Riskscore and clinical data, we developed a nomogram that demonstrated a capacity to predict overall survival and exhibited clinical utility, which was validated through the calibration curve, ROC curve, and decision curve analysis curve tests, confirming its effectiveness in prognostic evaluation. Immune analysis revealed that individuals belonging to the low-risk (LR) group exhibited a greater abundance of immune cell infiltration and higher levels of immune function. We calculated the immunopheno score and TIDE scores and tested them on the IMvigor210 and GSE78220 cohorts and found that individuals categorized in the LR group exhibited a higher likelihood of deriving therapeutic benefits from immunotherapy intervention. Additionally, we predicted that patients classified in the HR group would demonstrate enhanced sensitivity to Docetaxel using anti-tumor drugs. To summarize, we successfully developed and validated a prognostic model for LUAD by incorporating DNA replication stress as a key factor.

Value of spectral CT parameters in predicting the efficacy of neoadjuvant chemotherapy for gastric cancer.

AIM: To investigate the value of pre-chemotherapy spectral computed tomography (CT) parameters in predicting neoadjuvant chemotherapy (NAC) response in gastric cancer (GC). MATERIALS AND METHODS: Sixty patients with GC who received NAC and underwent spectral CT examination before chemotherapy were enrolled retrospectively and divided into a responsive group and a non-responsive group according to the postoperative pathological tumour regression grade. Clinical characteristics were collected. The iodine concentration (IC), water concentration (WC), and effective atomic number (Eff-Z) of the portal venous phases were measured before chemotherapy, and IC was normalised to that of the aorta to provide the normalised IC (NIC). An independent samples t-test, Mann-Whitney U-test, or chi-square test was used to analyse the differences between the two groups, and the receiver operating curve (ROC) was used to evaluate the predictive performance of different variables. RESULTS: The neutrophil-to-lymphocyte ratio (NLR) was lower in the responsive group than in the non-responsive group (p<0.05). IC, NIC, and Eff-Z values were significantly higher in the responsive group than in the non-responsive group (p<0.01). The areas under the ROC curves for the NLR, IC, NIC, and Eff-Z were 0.694, 0.688, 0.799, and 0.690, respectively. The combination of NIC, Eff-Z, and NLR values showed good diagnostic performance in predicting response to NAC in GC, with an area under the ROC curve of 0.857, 76.92% sensitivity, 80% accuracy, and 85.71% specificity. CONCLUSION: Spectral CT parameters may serve as non-invasive tools for predicting the response to NAC in patients with GC.

[Safety and effectiveness of emergency stenting for acute anterior circulation large artery disease].

Objective: To explore the safety and effectiveness of early stent implantation in patients with acute anterior circulation large artery disease. Methods: Patients were recruited from the RESCUE-RE study (a registration study for Critical Care of Acute Ischemic Stroke After Recanalization). Patients who were diagnosed with acute ischemic stroke within 24 hours of onset and given endovascular treatment after consultation from July 2018 to May 2019 from 18 sub-centers nationwide were retrospectively enrolled. According to whether the stents were placed during the operation, the patients were divided into two groups: stenting group and non-stenting group. The baseline between the two groups was matched by propensity score. The matching variables included age, sex, baseline National Institutes of Health Stroke Scale (NIHSS) score, baseline Glasgow Coma Scale (GCS) score, history of stroke, smoking and onset to hospital time. The primary clinical outcome was 90-day good neurological outcome [defined as modified Rankin score (mRS) 0-2]. Secondary outcomes include 90-day mortality, 24-hour re-occlusion of the responsible artery, and symptomatic intracranial hemorrhage. The differences in clinical endpoints between the two groups were compared. Result: A total of 899 patients with acute anterior circulation artery stenosis or occlusion were included in the study, with a mean age of(66±12)years,and 532(59.18%) were male. There were 193 patients in the stenting group and 706 patients in the non-stenting group. After the baseline data between the two groups were matched by propensity score, 169 patients were enrolled in each of two groups respectively. After matching, the proportion of patients in the stenting group with etiological diagnosis of large atherosclerosis [82.53% (137/166) vs 55.69% (93/167)] and the proportion of patients with previous history of hypertension [63.31% (107/169) vs 47.93% (81/169)] in the stenting group were higher than those in the non-stenting group (both P<0.05). While the proportion of patients in the non-stenting group with cardiogenic embolism [37.73%(63/167) vs 11.45%(19/166)]and the proportion of patients with atrial fibrillation [18.93% (32/169) vs 10.65%(18/169)]was higher(all P<0.05). In the stenting group, the time from onset to recanalization was longer[519 (408, 620)min vs 469 (365, 690)min], and the proportion of general anesthesia [50.89% (86/169) vs 35.50% (60/169)] was higher in the stenting group(both P<0.05). In addition, in the stenting group, the proportion of patients receiving mechanical thrombectomy[67.46% (114/169) vs 88.76% (150/169)] and arterial thrombolysis [2.37% (4/169) vs 18.93% (32/169)] was lower than non-stenting group during the operation, while the proportion of patients receiving balloon dilation [53.85% (91/169) vs 13.61% (23/169)]was higher(both P<0.05). The proportion of patients in stent group receiving antiplatelet drugs before operation was higher [13.46% (21/169) vs 8.70% (14/169)](both P<0.05). In terms of clinical outcome, compared with the non-stenting group, the proportion of patients in the stenting group with good neurological function in 90 days was lower [44.79% (73/169) vs 56.36% (93/169)], and the proportion of death at 90 days was higher[15.98% (27/169) vs 8.88% (15/169)] (both P<0.05). There was no significant difference between the two groups in 24-hour re-occlusion[8.88% (15/169) vs 9.47% (16/169)] and symptomatic intracranial hemorrhage[5.92% (10/169) vs 4.76% (8/169)](both P>0.05). Conclusion: For patients with acute anterior circulation artery disease, early stent therapy may increase the proportion of patients with adverse neurological outcomes.

[Chinese expert guidance on overall application of lenvatinib in hepatocellular carcinoma].

Lenvatinib mesylate is an oral receptor tyrosine kinase inhibitor against targets of vascular endothelial growth factor receptors 1-3, fibroblast growth factor receptors 1-4, platelet-derived growth factor receptor α, stem cell growth factor receptor, and rearranged during transfection, et al. Lenvatinib has been approved by the National Medical Products Administration of China on September 4, 2018, for the first-line treatment of patients with unresectable hepatocellular carcinoma who have not received systematic treatment before. Up to February 2023, Lenvatinib has been listed in China for more than 4 years, accumulating a series of post-marketing clinical research evidences. Based on the clinical practice before and after the launch of lenvatinib and referring to the clinical experience of other anti-angiogenesis inhibitors, domestic multidisciplinary experts and scholars adopt the Delphi method to formulate the Chinese Expert Guidance on Overall Application of Lenvatinib in Hepatocellular Carcinoma after repeated discussions and revisions, in order to provide reference for reasonable and effective clinical application of lenvatinib for clinicians.

Clinical Outcomes Following Postoperative Cavity Stereotactic Radiosurgery for Brain Metastases.

PURPOSE/OBJECTIVE(S): We evaluated outcomes of patients with brain metastases (BM) treated with surgical resection and postoperative cavity stereotactic radiosurgery (SRS) to identify which baseline characteristics and treatment factors may increase risk for local recurrence (LR). MATERIALS/METHODS: From June 2017 to December 2021, 68 patients underwent surgical resection for BM followed by single-fraction SRS (n = 15) or fractionated SRS (FSRS) in 3 (n = 24) or 5 (n = 29) fractions to the postoperative cavity using frameless LINAC-based technique. Patients treated with surgery alone or surgery with postoperative whole brain radiotherapy (WBRT) were excluded. Median prescription doses were 1600 cGy (range: 1440-1875) in 1 fraction, 2400 cGy (range: 2100-2700) in 3 fractions, and 3000 cGy (range: 2500-3000) in 5 fractions. Local control (LC) and overall survival (OS) were estimated by the Kaplan-Meier method. Cox proportional hazards models were used to compare groups. RESULTS: Median follow-up was 19.5 months (IQR: 9.0-34.7). Median patient age was 62.5 years (range: 24-80), and 38 (55.9%) patients were male. Primary tumors were lung (n = 29), including NSCLC (n = 28) and SCLC (n = 1), melanoma (n = 12), breast (n = 11), and other (n = 16). Median preoperative tumor maximal dimension was 3.5cm (range: 1.1-6.3). Median planning treatment volume (PTV) was larger in the FSRS group (26.2cc (range: 6.5-151.8)) than in the SRS group (7.7cc (range: 1.1-11.5)) (p<0.001). Median number of concurrently treated intact lesions was 0 (range: 0-13). Median time from surgery to SRS was 32 days (range: 14-77). Forty-eight (70.6%) patients were treated with immunotherapy or targeted therapy. Median OS was 22.3 months (95% CI: 14.4-30.9). The 1-year and 2-year OS rates were 70% and 48%, respectively. The 1-year and 2-year LC rates were 86% and 73%, respectively. Median time to LR was 8.4 months (95% CI: 4.4-11.0). Among the 14 patients with LR, 11 had undergone salvage therapy at last follow-up which included repeat SRS (n = 4), WBRT (n = 3), palliative local radiotherapy (n = 2), surgery followed by repeat SRS (n = 1), and systemic therapy (n = 1). Eleven (16.2%) patients ultimately underwent WBRT post-SRS for local and/or distant failure. No difference in LC was observed based on primary tumor, time interval between resection and SRS, PTV volume, prescription dose, or fractionation regimen (SRS v. FSRS). However, all LR in the 3-fraction group occurred in patients who received less than 2700 cGy. CONCLUSION: Favorable LC and OS outcomes were observed following postoperative cavity SRS for resected BM in a modern cohort with a large percentage of patients receiving immunotherapy or targeted therapy. No prognostic factors were identified for LC which may be attributable to the cohort size and small number of events observed. However, our findings suggest that patients who undergo 3-fraction FSRS should be treated to a total dose of 2700 cGy to maximize LC.

Comparison of Supraclavicular Surgery plus Radiotherapy vs. Radiotherapy Alone in Breast Cancer Patients with Synchronous Ipsilateral Supraclavicular Lymph Node Metastasis: A Multicenter Retrospective Study.

PURPOSE/OBJECTIVE(S): To evaluate and compare the outcomes of supraclavicular lymph node dissection (SLND) plus radiotherapy (RT) and RT alone for patients with synchronous ipsilateral supraclavicular lymph node metastasis (sISLM). MATERIALS/METHODS: In all, 293 patients with sISLM across three centers were included. Of these, 85 (29.0%) received SLND plus RT and 208 (71.0%) received RT alone. All patients received preoperative systemic therapy followed by mastectomy or lumpectomy and axillary dissection. Supraclavicular recurrence-free survival (SCRFS), locoregional recurrence-free survival (LRRFS), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) were evaluated by using the Kaplan-Meier method and multivariate Cox models. Multiple imputation was used for missing data. RESULTS: The median follow-up duration of the RT and SLND+RT groups were 53.7 and 63.5 months, respectively. For the RT and SLND+RT groups, the 5-year SCRFS rates were 91.7% vs. 85.5% (P = 0.522), LRRFS rates were 79.1% vs. 73.1% (P = 0.412), DMFS rates were 60.4 vs. 58.8% (P = 0.708), DFS rates were 57.6% vs. 49.7% (P = 0.291), and OS rates were 71.9% vs. 62.2% (P = 0.272), respectively. There was no significant effect on any outcome when comparing SLND+RT versus RT alone in the multivariate analysis. Based on four risk factors of DFS, patients were classified into three risk groups: the intermediate- and high-risk groups had significantly lower survival outcomes than the low-risk group. SLND+RT did not improve outcomes of any risk group compared with RT alone. CONCLUSION: Patients with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups with sISLM may not benefit from SLND. Distant metastasis remained the major failure pattern, especially for intermediate- and high-risk groups.

Study of DNA Damage-Induced MSI1 Serine-347 Phosphorylation in Regulation of Radiosensitivity in Glioblastoma Multiforme.

PURPOSE/OBJECTIVE(S): Despite the growing therapeutic techniques, Glioblastoma Multiforme (GBM) patients have limited survival due to the location and malignancies of tumor burdens. Radiotherapy is one of the common treatments with maximal surgery and chemotherapy. However, the often radioresistance occurred in GBM results in recurrence and marginal disease control. Therefore, the medical need remains unmet to treat GBM efficiently. Musashi-1 (MSI1) is one of the RNA-binding proteins known for its high oncogenicity in many cancers, including GBM. MSI1 is highly expressed in tumors and abundant in tumorigenic cancer cells. However, the relationship between MSI1 and GBM radioresistance is still largely unknown. MATERIALS/METHODS: Three human GBM cell lines, U87-MG, 05MG, and S1R1, were used in vitro, and an orthotopic nude mouse GBM model was employed in vivo. Phos-Tag blotting and phospho-MSI1 (Ser 347) antibody helped to detect the phosphorylation level of MSI1. Ultra-low attachment dishes and 3D cell culture were performed for the tumor initiation study. Flow cytometry, immunohistochemistry staining, and confocal microscope with immunofluorescent staining provide respective biomarker expressions. RESULTS: We initiated our study by inducing DNA damage on GBM cell lines using ionizing radiation and an alkylating agent. With Phos-Tag and NetPhos3.1 prediction, we hypothesized that a novel phosphorylation site on MSI1 serine-347 (S347) may sense DNA damage events. To unveil the molecular mechanism, we found DNA-dependent protein kinase catalytic subunits (DNA-PKcs), one of the DNA damage repair components, physically interacted with MSI1 in the role of a kinase. We suggest that activated DNA-PKcs may phosphorylate MSI1-S347, leading to enhanced oncogenicity and subsequent malignancies. Wild-type MSI1-overexpressing GBM cells (MSI1-WT) showed better colony and sphere-forming ability, whereas loss-of-function mutation S347A deprived the oncogenic behaviors. Besides, S347A limited the cancer initiation in the orthotopic animal model compared with MSI1-WT, suggesting that phosphorylation of MSI1-S347 promotes GBM tumorigenicity both in vitro and in vivo. In addition, we noticed that CD133 (Prominin-1), a well-characterized cancer stem-like cell marker, accompanied MSI1-WT introduction but was not seen in S347A cells. Intriguingly, we identified a few members of the let-7 microRNA family, including let-7b, 7e, and 7i, who were rescued by the S347A mutation and correspondingly expressed with CD133 levels and tumorigenic abilities. CONCLUSION: This study explains a vital relationship between GBM radioresistance and a novel oncogenic post-translational modification on MSI1 S347. IR-induced DNA damage triggers DNA-PKcs activation that subsequently phosphorylates MSI1-S347, enhancing GBM tumorigenicity via let-7 pathway. Further studies on the potential regulators, either inhibiting DNA-PKcs or antagonizing agents, may provide GBM patients with an optimistic outcome.

Objective Boundary Generation for Gross Target Volume and Organs at Risk Using 3D Multi-Modal Medical Images.

PURPOSE/OBJECTIVE(S): Accurate delineation of Gross Target Volume (GTV) and Organs at Risk (OARs) in medical images is an essential but challenging step in radiotherapy. Deep-learning based automated delineation methods, which learn from manual annotations, are currently prevalent in academic research. However, the limited resolution of medical images and the fuzzy boundaries of lesions and organs present a challenge to the precision of manual annotations. By leveraging the complementary information from multi-modal medical images, this study proposed a novel method to generate objective boundaries of GTV and OARs. MATERIALS/METHODS: We present a novel method of objective boundary generation, inspired by image matting primarily used for 2D RGB natural images, to process 3D grayscale medical images. The proposed method has the following advantages. 1) It allows for flexible input modalities and assigns weights to each modality according to their relative significance when computing information flows in the matting algorithm. 2) It computes 3D spatial information flow among voxels, which has more advantages over its 2D counterpart. 3) It has a closed-form solution that generates deterministic results. To evaluate the characteristics of the generated boundaries, patients with stage I nasopharyngeal carcinoma (NPC) were studied, with CT images and multi-modal MR images (T1, T1C, T2) aligned using deformable registration. Region of Interests (ROIs), i.e., GTV and parotid gland, were used, with a rough trimap marking extremely few foreground voxels, many background voxels, and a large unknown region. The proposed algorithm leverages the connection between each voxel and its nearest neighbors in the feature space, to propagate the opacity information. RESULTS: We evaluated the results by employing both qualitative and quantitative methods. Using qualitative evaluation, experienced clinicians confirmed that the results were in agreement with the input data, especially for areas where borders were visible in most modalities (e.g., between air and tumor). For more challenging regions, where boundaries were unclear in the images, the results displayed fine-grained opacity transitions indicating the confidence of each voxel belonging to the ROI. When compared to the delineations made by clinicians, we found our results are usually more compact. We define a precision metric that evaluates the ratio of the matted foreground inside clinicians' delineations versus the entire matted foreground. Using a threshold of 0.4, our binarized result scored 0.95 for GTV and 0.92 for parotid gland. CONCLUSION: The proposed method demonstrated satisfactory results on challenging ROIs. The objective boundaries generated by this method have advantages in many aspects, including improvement of delineation protocols, enhancement of manual annotation consistency, and increase of deep-learning based automated delineation accuracy.

Association of Treatment Disparities and Primary Sites with the Survival of Non-Gastric Early-Stage MALT Lymphoma.

PURPOSE/OBJECTIVE(S): To investigate the association between utilization of radiotherapy and differences in survival among patients with non-gastric early-stage mucosa-associated lymphoid tissue (MALT) lymphoma at different primary sites. MATERIALS/METHODS: A total of 5,995 patients with non-gastric early-stage MALT lymphoma in the Surveillance, Epidemiology, and End Results (SEER) database treated between 2000-2015 were extracted and analyzed. Mediation analyses were conducted to quantitatively determine the proportion of the relationship between OS and primary sites mediated by radiotherapy. Inverse probability of treatment weighting (IPTW) was conducted to control confounding factors affecting treatment choice. RESULTS: After controlling for confounding factors, pulmonary MALT lymphoma was found to have the highest rate of omitted radiotherapy compared to other primary sites, including ocular adnexa, salivary gland, skin and other sites. Multivariate Cox analyses showed that lung MALT lymphoma patients had the lowest 10-year OS rate of 58.3%, while skin MALT lymphoma patients had the highest 10-year OS rate of 81.6%. After balancing confounding factors that potentially affected the choice of radiotherapy using IPTW, differences in utilization of radiotherapy explained a significant portion of the poor prognosis of lung MALT lymphoma (35.6%, P = 0.002) and the favorable prognosis of skin MALT lymphoma (6.1%, P <0.001). CONCLUSION: Differences in survival among patients with non-gastric early-stage MALT lymphoma at different primary sites are associated with disparities in the utilization of radiotherapy.