BL-B01D1, a first-in-class EGFR-HER3 bispecific antibody-drug conjugate, in patients with locally advanced or metastatic solid tumours: a first-in-human, open-label, multicentre, phase 1 study.

BACKGROUND: Antibody-drug conjugates have promising clinical activity in the treatment of solid tumours. BL-B01D1 is a first-in-class EGFR-HER3 bispecific antibody-drug conjugate. We aimed to assess the safety and preliminary antitumour activity of BL-B01D1 in patients with locally advanced or metastatic solid tumours. METHODS: This first-in-human, open-label, multicentre, dose-escalation and dose-expansion phase 1 trial was conducted in seven hospitals in China, enrolling patients aged 18-75 years (dose escalation; phase 1a) or older than 18 years (dose expansion; phase 1b), with a life expectancy of at least 3 months, an Eastern Cooperative Oncology Group performance status of 0-1, and histologically or cytologically confirmed locally advanced or metastatic solid tumours that had progressed on current standard treatment. In the phase 1a i3+3 design, patients received intravenous BL-B01D1 at three different schedules: 0·27 mg/kg, 1·5 mg/kg, and 3·0 mg/kg weekly; 2·5 mg/kg, 3·0 mg/kg, and 3·5 mg/kg on days 1 and 8 of each cycle every 3 weeks; or 5·0 mg/kg and 6·0 mg/kg on day 1 of each cycle every 3 weeks. The primary objectives of phase 1a were to identify the safety, maximum tolerated dose, and dose-limiting toxicity. In phase 1b, patients were treated in two schedules: 2·5 and 3·0 mg/kg on days 1 and 8 every 3 weeks, or 4·5, 5·0, and 6·0 mg/kg on day 1 every 3 weeks. The primary objectives of phase 1b were to assess the safety and recommended phase 2 dose of BL-B01D1, and objective response rate was a key secondary endpoint. Safety was analysed in all patients with safety records who received at least one dose of BL-B01D1. Antitumour activity was assessed in the activity analysis set which included all patients who received at least one dose of BL-B01D1 every 3 weeks. This trial is registered with China Drug Trials, CTR20212923, and ClinicalTrials.gov, NCT05194982, and recruitment is ongoing. FINDINGS: Between Dec 8, 2021, and March 13, 2023, 195 patients (133 [65%] men and 62 [32%] women; 25 in phase 1a and 170 in phase 1b) were consecutively enrolled, including 113 with non-small-cell lung cancer, 42 with nasopharyngeal carcinomas, 13 with small-cell lung cancer, 25 with head and neck squamous cell carcinoma, one with thymic squamous cell carcinoma, and one with submandibular lymphoepithelioma-like carcinoma. In phase 1a, four dose-limiting toxicities were observed (two at 3·0 mg/kg weekly and two at 3·5 mg/kg on days 1 and 8 every 3 weeks; all were febrile neutropenia), thus the maximum tolerated dose was reached at 3·0 mg/kg on days 1 and 8 every 3 weeks and 6·0 mg/kg on day 1 every 3 weeks. Grade 3 or worse treatment-related adverse events occurred in 139 (71%) of 195 patients; the most common of which were neutropenia (91 [47%]), anaemia (76 [39%]), leukopenia (76 [39%]), and thrombocytopenia (63 [32%]). 52 (27%) patients had a dose reduction and five (3%) patients discontinued treatment due to treatment-related adverse events. One patient was reported as having interstitial lung disease. Treatment-related deaths occurred in three (2%) patients (one due to pneumonia, one due to septic shock, and one due to myelosuppression). In 174 patients evaluated for activity, median follow-up was 6·9 months (IQR 4·5-8·9) and 60 (34%; 95% CI 27-42) patients had an objective response. INTERPRETATION: Our results suggest that BL-B01D1 has preliminary antitumour activity in extensively and heavily treated advanced solid tumours with an acceptable safety profile. Based on the safety and antitumour activity data from both phase 1a and 1b, 2·5 mg/kg on days 1 and 8 every 3 weeks was selected as the recommended phase 2 dose in Chinese patients. FUNDING: Sichuan Baili Pharmaceutical. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Early change of plasma Epstein-Barr virus DNA load and the viral lytic genome level could positively predict clinical outcome in recurrent or metastatic nasopharyngeal carcinoma receiving anti-programmed cell death 1 monotherapy.

PURPOSE: Patients with recurrent or metastatic nasopharyngeal carcinoma (RM-NPC) have proven benefit from anti-programmed cell death 1 (anti-PD-1) monotherapy. Here, we retrospectively analyze the association of plasma Epstein-Barr virus (EBV) DNA load and tumor viral lytic genome with clinical outcome from 2 registered phase I trials. METHODS: Patients with RM-NPC from Checkmate 077 (nivolumab phase I trial in China) and Camrelizumab phase I trial between March 2016 and January 2018 were enrolled. Baseline EBV DNA titers were tested in 68 patients and EBV assessment was performed in 60 patients who had at least 3 post-baseline timepoints of EBV data and at least 1 post-baseline timepoint of radiographic assessment. We defined "EBV response" as 3 consecutive timepoints of load below 50% of baseline, and "EBV progression" as 3 consecutive timepoints of load above 150% of baseline. Whole-exome sequencing was performed in 60 patients with available tumor samples. RESULTS: We found that the baseline EBV DNA load was positively correlated with tumor size (spearman p < 0.001). Both partial response (PR) and stable disease (SD) patients had significantly lower EBV load than progression disease (PD) patients. EBV assessment was highly consistent with radiographic evaluation. Patients with EBV response had significantly improved overall survival (OS) than patients with EBV progression (log-rank p = 0.004, HR = 0.351 [95% CI: 0.171-0.720], median 22.5 vs. 11.9 months). The median time to initial EBV response and progression were 25 and 36 days prior to initial radiographic response and progression, respectively. Patients with high levels of EBV lytic genomes at baseline, including BKRF2, BKRF3 and BKRF4, had better progression-free survival (PFS) and OS. CONCLUSION: In summary, early clearance of plasma EBV DNA load and high levels of lytic EBV genes were associated with better clinical outcome in patients with RM-NPC receiving anti-PD-1 monotherapy.

Comparison of aprepitant versus desloratadine for EGFR-TKI-induced pruritus: A randomized phase 2 clinical trial.

BACKGROUND: Pruritus is one of the most common and challenging side effects of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) and has impaired patients' quality of life and treatment compliance. Our study evaluated the efficacy and safety of aprepitant in managing EGFR-TKIs-related pruritus. METHODS: This randomized, double-blind, placebo-controlled study was conducted between December 2016 and August 2020 in China. Patients were eligible if they were 18 years or older and had histologically confirmed locally advanced or metastatic non-small cell lung cancer (NSCLC) with first onset of moderate to severe pruritus during EGFR-TKI treatment. RESULTS: A total of 130 eligible patients were randomly assigned to aprepitant (n = 65) or desloratadine (n = 65) groups. The median (interquartile range [Q1, Q3]) age was 63 (54, 70) years, and 79 (60.8%) were women. Mean visual analog scale scores at baseline were 6.35 (95% confidence interval [CI], 5.89-6.82) in the aprepitant group and 5.94 (95% CI, 5.56-6.32) in the desloratadine group. After 1 week of treatment, 33 (53.2%) patients responded to aprepitant, which was significantly higher than that of 14 (23.7%) patients responded to desloratadine (p = .001). Moreover, patients in the aprepitant group had a significantly shorter response time than patients in the desloratadine group (mean [days], 13.39 [95% CI, 11.08-15.70] vs. 16.67 [95% CI, 14.19-19.13], p = .04). The most frequent drug-related adverse events in aprepitant group and desloratadine were constipation and dry mouth, and all adverse events were grade 1-2. CONCLUSIONS: To the authors' knowledge, this is the first study to prospectively present that aprepitant elicited a better and faster response and mild toxicity for managing EGFR-TKI induced pruritus than desloratadine. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02646020.

The perception gap of chemotherapy-induced adverse events between doctors and cancer patients: an observational study in China.

INTRODUCTION: Patient-reported outcomes (PROs) have been widely accepted in western countries. However, limited attention has been given to PROs in China due to a lack of research on the agreement between doctors' and patients' reports of adverse events. This study aims to reveal the perception gap of chemotherapy-induced adverse events between doctors and cancer patients in China. METHODS: An observational study was administered at Sun Yat-Sen University Cancer Center (SYSUCC). Totally, 200 adult cancer patients undergoing chemotherapy participated. Patient reports were collected by nurses via telephone. Doctor reports were collected by nurses based on their medical records. The agreement between doctors and patients was analyzed by Cohen's κ. RESULTS: Agreement between doctors and patients varied among different symptoms: 0.26 for nausea/vomiting, 0.49 for constipation, 0.63 for diarrhea, 0.65 for general pain, and 0.76 for rash. Doctors' underreporting rates were 70% for nausea/vomiting, 50% for diarrhea, 38% for rash, 33% for constipation, and 29% for general pain. CONCLUSIONS: The perception gap of chemotherapy-induced adverse events between doctors and patients exists in China, especially regarding subjective symptoms. Introduction of PROs in both clinical trials and routine clinical practice should be considered in China.

Intratumor heterogeneity comparison among different subtypes of non-small-cell lung cancer through multi-region tissue and matched ctDNA sequencing.

Understanding of intratumor heterogeneity (ITH) among different non-small cell lung cancer (NSCLC) subtypes is necessary. Whether circulating tumor DNA (ctDNA) profile could represent these ITH is still an open question. We performed 181 multi-region tumor tissues sequencing and matched ctDNA sequencing from 32 operative NSCLC to compare ITH among different NSCLC subtypes, including EGFR-mutant lung adenocarcinoma (LUAD), KRAS-mutant LUAD, EGFR&KRAS-wild-type LUAD, and lung squamous cell carcinoma (LUSC), and examine potential value of ctDNA for ITH analysis. ITH is evaluated by ITH index (ITHi). If the somatic genetic alteration is shared by all the tissue regions, it is defined as trunk mutation. Otherwise, it is called branch mutation. The ITHi will be higher, if the tumor has less trunk mutations. We found EGFR-mutant LUAD showed significantly higher ITHi than KRAS-mutant LUAD/wild-type LUAD (P = 0.03) and numerically higher ITH than LUSC. For trunk mutations, driver mutations were identified at a higher proportion than passenger mutations (60% vs. 40%, P = 0.0023) in overall, especially in EGFR-mutant LUAD (86% vs. 14%, P = 0.0004), while it was opposite in KRAS-mutant LUAD (40% vs. 60%, P = 0.18). For branch mutations, the proportions of driver mutations and passenger mutations were similar for each NSCLC subtype. ctDNA analysis showed unsatisfactory detections of tumor-derived trunk and branch mutations (43% vs. 23%, P = 4.53e-6) among all NSCLC subtypes. In summary, EGFR-mutant LUAD has the highest ITH than other NSCLC subtypes, offering further understanding of tumorigenesis mechanisms among different NSCLC subtypes. Besides, ctDNA maybe not an appropriate method to reflect ITH.

Cause-specific death assessment of patients with stage I small-cell lung cancer: a competing risk analysis.

Aim: Stage I small-cell lung cancer (SCLC) is a potentially curable disease that needs timely and multidisciplinary management. The aim of this study was to evaluate the probability of cause-specific mortality for patients with stage I SCLC. Material & methods: We identified patients in the SEER database and constructed a proportional subdistribution hazard model to evaluate cancer-specific mortality. A nomogram was built based on Fine and Gray competing risk regression model. Results: A total of 864 stage I SCLC patients were identified. The 5-year cumulative incidence of SCLC-specific mortality was 56.2%, while that for other causes of death was 17.3%. The c-index for the prognostic prediction model was 0.66. Besides, the nomogram was well calibrated. Conclusion: Our nomogram might serve as a reference for clinicians when evaluating the prognosis of stage I SCLC.

Impact of prior cancer history on the overall survival of patients newly diagnosed with cancer: A pan-cancer analysis of the SEER database.

The population of cancer survivors with prior cancer is rapidly growing. Whether a prior cancer diagnosis interferes with outcome is unknown. We conducted a pan-cancer analysis to determine the impact of prior cancer history for patients newly diagnosed with cancer. We identified 20 types of primary solid tumors between 2004 and 2008 in the Surveillance, Epidemiology, and End Results database. Demographic and clinicopathologic variables were compared by χ2 test and t-test as appropriate. The propensity score-adjusted Kaplan-Meier method and Cox proportional hazards models were used to evaluate the impact of prior cancer on overall survival (OS). Among 1,557,663 eligible patients, 261,474 (16.79%) had a history of prior cancer. More than 65% of prior cancers were diagnosed within 5 years. We classified 20 cancer sites into two groups (PCI and PCS) according to the different impacts of prior cancer on OS. PCI patients with a prior cancer history, which involved the colon and rectum, bone and soft tissues, melanoma, breast, cervix uteri, corpus and uterus, prostate, urinary bladder, kidney and renal pelvis, eye and orbits, thyroid, had inferior OS. The PCS patients (nasopharynx, esophagus, stomach, liver, gallbladder, pancreas, lung, ovary and brain) with a prior cancer history showed similar OS to that of patients without prior cancer. Our pan-cancer study presents the landscape for the survival impact of prior cancer across 20 cancer types. Compared to the patients without prior cancer, the PCI group had inferior OS, while the PCS group had similar OS. Further studies are still needed.

Integrated Analysis of Expression Profile Based on Differentially Expressed Genes in Middle Cerebral Artery Occlusion Animal Models.

Stroke is one of the most common causes of death, only second to heart disease. Molecular investigations about stroke are in acute shortage nowadays. This study is intended to explore a gene expression profile after brain ischemia reperfusion. Meta-analysis, differential expression analysis, and integrated analysis were employed on an eight microarray series. We explored the functions and pathways of target genes in gene ontology (GO) enrichment analysis and constructed a protein-protein interaction network. Meta-analysis identified 360 differentially expressed genes (DEGs) for Mus musculus and 255 for Rattus norvegicus. Differential expression analysis identified 44 DEGs for Mus musculus and 21 for Rattus norvegicus. Timp1 and Lcn2 were overexpressed in both species. The cytokine-cytokine receptor interaction and chemokine signaling pathway were highly enriched for the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. We have exhibited a global view of the potential molecular differences between middle cerebral artery occlusion (MCAO) animal model and sham for Mus musculus or Rattus norvegicus, including the biological process and enriched pathways in DEGs. This research helps contribute to a clearer understanding of the inflammation process and accurate identification of ischemic infarction stages, which might be transformed into a therapeutic approach.

Implementation of paste backfill mining technology in Chinese coal mines.

Implementation of clean mining technology at coal mines is crucial to protect the environment and maintain balance among energy resources, consumption, and ecology. After reviewing present coal clean mining technology, we introduce the technology principles and technological process of paste backfill mining in coal mines and discuss the components and features of backfill materials, the constitution of the backfill system, and the backfill process. Specific implementation of this technology and its application are analyzed for paste backfill mining in Daizhuang Coal Mine; a practical implementation shows that paste backfill mining can improve the safety and excavation rate of coal mining, which can effectively resolve surface subsidence problems caused by underground mining activities, by utilizing solid waste such as coal gangues as a resource. Therefore, paste backfill mining is an effective clean coal mining technology, which has widespread application.

A cross-sectional study of the relationship between premenstrual syndrome and missed nursing care among female nursing staff.

Purpose: Premenstrual syndrome (PMS) is a cyclical psychosomatic disorder prevalent among women of reproductive age. However, research on the potential impact of PMS on routine nursing schedules and activities is limited. This study aims to identify the prevalence of PMS among female nursing staff and to examine the relationship between PMS and missed nursing care (MNC). Method: Between November 1, 2022, and April 30, 2023, this study was conducted among female nursing staff working in nine inpatient departments at Sun Yat-sen University Cancer Center. This study used a cross-sectional design. The participants were recruited through convenience sampling. Data were collected using the standardized Menstrual Distress Questionnaire, the Oncology Missed Nursing Care self-rating scale, and a sociodemographic questionnaire. One-way analysis of variance, Fisher's least significant difference test for post-hoc comparisons, and Spearman's correlation coefficient were utilized for data analysis. A trend test was also performed to explore patterns in the severity of PMS and MNC over time. Results: We collected a total of 224 questionnaires, with 154 (68.7%) female nursing staff reporting PMS. The most common symptoms were low back pain (91.1%), abdominal discomfort (90.6%), cold hands and feet (87.1%), and lethargy (87.1%). Moreover, 91.5% of the 224 female nursing staff reported at least one MNC activity. The nursing activities most frequently missed or left incomplete were liquid intake and output monitoring as ordered (43.3%), medication administration within 30 min before or after the scheduled time (43.3%), and electrocardiogram monitoring as ordered (42.9%). "Abdominal discomfort" from the Menstrual Distress Questionnaire was significantly correlated with the majority of MNC activities (p < 0.001). Conclusions: This study provides evidence for a strong association between PMS and MNC among female nursing staff, suggesting that administrators should take the premenstrual conditions of female nursing staff into consideration. It is necessary to provide appropriate understanding and support to mitigate the impact on patient care and safety.

Trends in pain undertreatment among lung cancer patients at the EOL: Analysis of urban city medical insurance data in China.

BACKGROUND: Cancer-related pain is one of the common priority symptoms in advanced lung cancer patients at the end-of-life (EOL). Alleviating pain is undoubtedly a critical component of palliative care in lung cancer. Our study was initiated to examined trends in opioid prescription-level outcomes as potential indicators of undertreated pain in China. METHODS: This study used data on 1330 patients diagnosed with lung cancer of urban city medical insurance in China who died between 2014 and 2017. Opioid prescription-level outcomes were determined by annual trends of the proportion of patients filling an opioid prescription, the total dose of opioids filled by decedents, and morphine milligram equivalents per day (MMED) at the EOL (defined as the 60 days before death). We further analyzed monthly changes in the number of opioid prescriptions filled, MMED, and mean daily dose of opioids per prescription (MDDP) of the last 60 days of life by year at death and age, respectively. RESULTS: A total of 959 patients with exact dates of death were included, with 432 cases (45.06%; 95% CI: 44.36%-45.77%) receiving at least one opioid prescription at the EOL. The declining trends were shown in the proportion of patients filling any opioid prescription, the total dose of opioids filled by decedents and MMED, with an annual decrease of 0.341% (p = 0.01), 104.23 mg (p = 0.011) and 2.84 mg (p = 0.014), respectively. Within the 31-60 days to the 0-30 days of life, the MMED declined 6.08 mg (95% CI: -7.14 to -5.03; p = 0.000351), while the number of opioid prescriptions rose 0.66 (95% CI: 0.160-1.16; p = 0.025). Like the MMED, the MDDP fell 4.11 mg (95% CI: -5.86 to -2.37; p = 0.005) within the last month before death compared to the previous month. CONCLUSION: Terminal lung cancer populations in urban China have experienced reduced access to opioids at the EOL. The clinicians did not prescribe a satisfactory dose of opioids per prescription, while the patients suffered increasing pain in the last 30 days of life. Sufficient opioid analgesic administration should be advocated for lung cancer patients during the EOL period.

Rare SMARCA4-deficient thoracic tumor: Insights into molecular characterization and optimal therapeutics methods.

INTRODUCTIONS: The 2021 WHO Classification of Thoracic Tumors recognized SMARCA4-deficient undifferentiated thoracic tumors (SMARCA4-dUT) as a distinct entity that shows a striking overlap in demographic and molecular profiles with SMARCA4-deficient non-small lung cancer (SMARCA4-dNSCLC). The implications of SMARCA4 deficiency based on immunohistochemistry remain unclear. We aimed to investigate molecular characteristics of SMARCA4-deficient thoracic tumors (SDTT) and explore optimal therapeutics. METHODS: From June.15, 2018, to Nov.15, 2023, a large cohort including patients diagnosed with SMARCA4-deficient (N = 196) and SMARCA4-intact (N = 438) thoracic tumors confirmed by immunohistochemistry at SYSUCC were screened. Clinicopathologic and molecular characteristics were identified and compared. External SRRSH cohort (N = 34) was combined into a pooled cohort to compare clinical outcome of first-line therapy efficacy. RESULTS: SDTT is male predominance with smoking history, high tumor burden, and adrenal metastases. The relationship between SMARCA4 mutation and protein expression is not completely parallel. The majority of SMARCA4-deficient patients harbor truncating (Class-I) SMARCA4 mutations, whereas class-II alterations and wild-type also exist. Compared with SMARCA4-intact thoracic tumors, patients with SDTT displayed a higher tumor mutation burden (TMB) and associated with a shorter median OS (16.8 months vs. Not reached; P < 0.001). Notably, SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in these differences. SDTT is generally resistant to chemotherapy, while sensitive to chemoimmunotherapy (median PFS: 7.5 vs. 3.5 months, P < 0.001). In particular, patients with SMARCA4 deficient thoracic tumors treated with paclitaxel-based chemoimmunotherapy achieved a longer median PFS than those with pemetrexed-based chemoimmunotherapy (10.0 vs. 7.3 months, P = 0.028). CONCLUSIONS: SMARCA4 protein deficiency, rather than genetic mutations, played a decisive role in its characteristics of higher TMB and poor prognosis. Chemoimmunotherapy serves as the optimal option in the current treatment regimen. Paclitaxel-based chemoimmunotherapy performed better than those with pemetrexed-based chemoimmunotherapy.

Remodeling the tumor-immune microenvironment by anti-CTLA4 blockade enhanced subsequent anti-PD-1 efficacy in advanced nasopharyngeal carcinoma.

Sequential immunotherapy has shown certain advantages in malignancy. Here, we aim to evaluate the efficacy of sequential anti-CTLA-4 and anti-PD-1 treatment for recurrent or metastatic nasopharyngeal carcinoma patients (R/M NPC). We retrospectively analysis 2 phase I trial of ipilimumab and camrelizumab in Chinese R/M NPC patients. These patients were initially treated with ipilimumab, a CTLA4 blockade, followed by anti-PD-1 treatment. We observed a durable tumor remission in these patients (mPFS: 12.3 months; mDoR: 20.9 months). Multimodal investigations of biopsy samples disclosed remodeling of tumor-immune microenvironment triggered by ipilimumab. In responders, we found increased tumoral PD-L1/PD-L2 expression and T-cell infiltration after ipilimumab treatment, accompanied by reduced stroma and malignant cell components. In contrast, non-responders exhibited increased B-cell infiltration and increased peripheral CD19 + B cells, suggesting a defective transition from memory B cells to plasma cells. This study proposes that sequential therapy can potentially enhance treatment efficacy in chemotherapy-resistant NPC patients and provides insights into how preexisting anti-CTLA4 blockade can influence subsequent anti-PD-1 efficacy by remodeling the TME. Additionally, our results highlight the need for therapeutic strategies targeting naïve/memory B cells.

Phase 1b trial of anti-HER2 antibody inetetamab and pan-HER inhibitor pyrotinib in HER2-positive advanced lung cancer.

There remains an unmet need for targeted therapies against advanced non-small-cell lung cancer (NSCLC) with HER2 mutations. To improve the antitumor activity of single anti-HER2 agent, this prospective, single-arm clinical trial (NCT05016544) examined the safety profile and efficacy of anti-HER2 antibody inetetamab and pan-HER TKI pyrotinib in HER2-posivite advanced NSCLC patients. Enrolled patients received inetetamab every 3 weeks and pyrotinib once per day (pyrotinib, dose-escalation part, 240 mg, 320 mg; dose-expansion part, 320 mg). Primary endpoints were dose-limiting toxicity (DLT) dosage and safety. Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). A total of 48 patients were enrolled. During the dose-escalation period, no DLT occurred. Diarrhea was the most commonly reported treatment-related adverse event (TRAE). Grade 3 TRAEs occurred in seven patients. The median PFS (mPFS) was 5.5 months [95% confidence interval (CI): 4.4-8.6 months]. The confirmed ORR and DCR reached 25% (11/44) and 84.1% (37/44), respectively. Responses were shown in patients with distinct HER2 aberrations. In summary, inetetamab in combination with pyrotinib demonstrated acceptable safety and antitumor activity among patients with advanced HER2-mutant NSCLC.

Complications of Unilateral Biportal Endoscopic Spinal Surgery for Lumbar Spinal Stenosis: A Meta-Analysis and Systematic Review.

BACKGROUND: In recent years, unilateral biportal endoscopic spinal surgery has been used for the treatment of lumbar spinal stenosis with good results. Some investigators counted the total incidence of complications in unilateral biportal endoscopic surgery for lumbar spinal stenosis, but none have analyzed the incidence of specific complications. The present study further counted the incidence of specific complications and gave the possible causes of the complications. METHODS: English databases including PubMed were searched to collect relevant literature on unilateral biportal endoscopic spinal surgery for lumbar spinal stenosis. The inquiry period is from January 1, 2015, to July 1, 2022. The literature was screened, information extracted, and risk of bias evaluated by the researchers, followed by Meta analysis using R4.2.1 and RStudio statistical software. RESULTS: In total, we included 14 studies involving 707 patients. The included studies were retrospective case series, The results of the single-arm rate meta-analysis showed that the total complication rate of unilateral biportal endoscopic surgery treatment of lumbar spinal stenosis was 8.1% (95% confidence interval [CI] [0.060; 0.103]); of which, the highest incidence of dural tear was 4.5% (95% CI [0.030; 0.064]), the incidence of symptomatic postoperative spinal epidural hematoma was approximately 1.1% (95% CI [0.001; 0.027]), the incidence of incomplete decompression was 2.0% (95% CI [0.007; 0.038]), the incidence of transient palsy was 2.6% (95% CI [0.005; 0.057]). CONCLUSIONS: The incidence of total complications of unilateral biportal endoscopic surgery for lumbar spinal stenosis was 8.1%, dural tear remained a major complication with an incidence of 4.5%, incomplete decompression was 2.0%, transient palsy was 2.6%, and, unexpectedly, symptomatic postoperative spinal epidural hematoma was only 1.1%.

LncRNA HEIH expression in cancer prognosis: A review and meta-analysis.

BACKGROUND: As a newly discovered lncRNA, lncRNA High expression in hepatocellular carcinoma (HEIH) has been reported to correlate with poor clinical outcomes in several different cancers, In addition, studies have shown that HEIH is overexpressed in a variety of cancers and plays an oncogenic role. The present meta-analysis aims to elucidate the relationship between HEIH expression and prognosis and clinicopathological features among cancer patients. METHODS: PubMed, Web of Science, Cochrane Library, and EMBASE database were comprehensively and systematically searched. pooled odds ratios (ORs) and hazard ratios (HRs) with 95% confidence interval (CI) were employed to assess the relationship between HEIH expression and clinical outcomes and clinicopathological features in cancer patients. CONCLUSION: The present study finally enrolled 11 studies which included 1227 cancer patients. The combined results indicated that HEIH overexpression was significantly associated with shorter overall survival (OS) (pooled HR = 2.03, 95% CI 1.74-2.38, P < .00001).Meanwhile, regarding clinicopathology of cancer patients, upregulated HEIH expression was closely related to larger tumor size (OR = 2.65, 95% CI: 1.52-4.65, P = .0006), advanced tumor T stage (OR = 2.41, 95 % CI: 1.54-3.77, P = .0001), advanced TNM stage (OR = 4.76, 95% CI: 2.73-8.29, P < .00001), distant metastasis (OR = 2.94, 95% CI: 1.75-4.96, P < .0001) and lymph node metastasis (OR = 2.07, 95% CI: 1.05-4.07, P = .04), respectively. CONCLUSIONS: High expression of HEIH in some cancers predicts shorter overall survival and higher clinical stage as well as larger tumor size. HEIH has great potential to become a prognostic marker for cancer patients.

The role and mechanism of JAK2/STAT3 signaling pathway regulated by m6A methyltransferase KIAA1429 in osteosarcoma.

Osteosarcoma (OS) is the most malignant bone tumor which mainly occurs in childhood or adolescence. The previous studies indicated that OS is difficult to treat. KIAA1429 is one of the components of m6A complex that regulating the process of m6A modification, which plays a crucial role in tumorigenesis. But the mechanism of KIAA1429 regulating OS cell identity was not entirely clear, which needs further investigate. RT-qPCR and western blotting were applied to determine KIAA1429 expression station in OS cells and tissues. To further detect the KIAA1429 function in OS cells, the ability of proliferation, migration and invasion were analyzed by Edu, wound-healing and transwell experiments respectively. Besides, RNA sequencing was also used to further find the downstream of KIAA1429 regulation and small molecule inhibitor was added to explore the specific role of signaling pathway. Our data found that KIAA1429 is up-regulated in human OS cell lines compared to the human osteoblast cells. Meanwhile, the deletion of KIAA1429 significantly decreased cell proliferation, migration, and invasion. Interestingly, the JAK2/STAT3 signal pathway was involved in KIAA1429 regulation on OS cell characters. The KIAA1429 eliminated OS cells exhibited a decreased activity of JAK2/STAT3 signal. And the addition of JAK2/STAT3 stimulator (colivelin) could distinctly rescue the decreased OS cells' proliferation, migration, and invasion upon KIAA1429 knockdown. In summary, these data demonstrated that KIAA1429/JAK2/STAT3 axis may a new target for OS therapy.

Unilateral biportal endoscopy versus microscopic decompression in the treatment of lumbar spinal stenosis: A meta-analysis.

BACKGROUND: The aim of this study was to evaluate whether there is a superior clinical effect of unilateral biportal endoscopy compared with microscopic decompression in the treatment of lumbar spinal stenosis. METHODS: We searched CNKI, WANFANG, CQVIP, CBM, PubMed, and Web of Science up to January 2022, and selected studies that met our inclusion criteria. RESULTS: The results of this meta-analysis indicated that unilateral biportal endoscopy was demonstrated to be more beneficial for patients compared with microscopic decompression for the following outcomes: Operation time [standardized mean difference (SMD) = -0.943, 95% confidence interval (CI) (-1.856, -0.031), P = .043], hospital stays [SMD = -2.652, 95% CI (-4.390, -0.914), P = .003], EuroQol 5-Dimension questionnaire [SMD = 0.354, 95% CI (0.070, 0.638), P = .014], back pain visual analogue score [SMD = -0.506, 95% CI (-0.861, -0.151), P = .005], leg pain visual analogue score [SMD = -0.241, 95% CI (-0.371, -.0112), P = .000], the C-reactive protein level [SMD = -1.492,95% CI (-2.432, -0.552), P = .002]. Other outcomes demonstrated no significant differences between the 2 groups. CONCLUSION: For patients with lumbar spinal stenosis, unilateral biportal endoscopy was found to be more superior than microscopic decompression in terms of operation time, hospital stays, EuroQol 5-Dimension questionnaire, back visual analogue score, leg visual analogue score and the C-reactive protein level. There was no significant difference between the 2 groups in other outcome indicators.

The maximum tumor growth rate predicts clinical outcomes of patients with small-cell lung cancer undergoing first-line chemotherapy plus immune-checkpoint inhibitor therapy.

BACKGROUND: Currently, no biomarkers can accurately predict survival outcomes in patients with SCLC undergoing treatment. Tumor growth rate (TGR; percent size change per month [%/m]) is suggested as an imaging predictor of response to anti-cancer treatment. We aimed to evaluate the predictive role of the maximum TGR (TGRmax) for outcomes of small-cell lung cancer (SCLC) patients undergoing first-line chemotherapy plus immune-checkpoint inhibitor (ICI) treatment. METHODS: Patients with SCLC receiving first-line chemotherapy plus immunotherapy were analyzed within this retrospective study. The X-tile program was used to identify the cut-off value of TGRmax based on maximum progression-free survival (PFS) stratification. The Kaplan-Meier methods and Cox regression models were used to evaluate the effect of the presence of TGRmax on PFS and overall survival (OS). RESULTS: In total, 104 patients were evaluated. Median (range) TGRmax was -33.9 (-65.2 to 21.6) %/m and the optimal cut-off value of TGRmax was -34.3%/m. Multivariate Cox regression analysis revealed that patients with TGRmax > -34.3%/m was associated with shorter PFS (hazard ratio [HR], 2.81; 95% CI, 1.71-4.63; p < 0.001) and OS (HR, 3.17; 95% CI, 1.41-7.08; p = 0.005). In patients who received partial response (PR), Kaplan-Meier survival analyses showed that superior PFS and OS (p = 0.005 and p = 0.009, respectively) benefit was observed when TGRmax ≤-34.3%/m. CONCLUSIONS: SCLC patients with TGRmax > -34.3%/m had worse PFS and OS in first-line ICI plus platin-based chemotherapy. TGRmax could independently serve as an early biomarker to predict the benefit from chemoimmunotherapy.