A nomogram for predicting 28-day mortality in elderly patients with acute kidney injury receiving continuous renal replacement therapy: a secondary analysis based on a retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a common and serious condition, particularly among elderly patients. It is associated with high morbidity and mortality rates, further compounded by the need for continuous renal replacement therapy in severe cases. To improve clinical decision-making and patient management, there is a need for accurate prediction models that can identify patients at a high risk of mortality. METHODS: Data were extracted from the Dryad Digital Repository. Multivariate analysis was performed using least absolute shrinkage and selection operator (LASSO) logistic regression analysis to identify independent risk factors and construct a predictive nomogram for mortality within 28 days after continuous renal replacement therapy in elderly patients with acute kidney injury. The discrimination of the model was evaluated in the validation cohort using the area under the receiver operating characteristic curve (AUC), and calibration was evaluated using a calibration curve. The clinical utility of the model was assessed using decision curve analysis (DCA). RESULTS: A total of 606 participants were enrolled and randomly divided into two groups: a training cohort (n = 424) and a validation cohort (n = 182) in a 7:3 proportion. A risk prediction model was developed to identify independent predictors of 28-day mortality in elderly patients with AKI. The predictors included age, systolic blood pressure, creatinine, albumin, phosphorus, age-adjusted Charlson Comorbidity Index (CCI), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and sequential organ failure assessment (SOFA) score. These predictors were incorporated into a logistic model and presented in a user-friendly nomogram. In the validation cohort, the model demonstrated good predictive performance with an AUC of 0.799. The calibration curve showed that the model was well calibrated. Additionally, DCA revealed significant net benefits of the nomogram for clinical application. CONCLUSION: The development of a nomogram for predicting 28-day mortality in elderly patients with AKI receiving continuous renal replacement therapy has the potential to improve prognostic accuracy and assist in clinical decision-making.

Comparison of anaesthesia-related outcomes in patients monitored by newly recruited nurse anaesthetists and anaesthesiologists: An observational study.

AIMS: To compare anaesthesia-related outcomes between patients monitored by newly recruited nurse anaesthetists and those monitored by newly recruited anaesthesiologists. DESIGN: This was a retrospective study. METHODS: We conducted a retrospective study that collected demographic information on newly recruited nurse anaesthetists and anaesthesiologists between 2017 and 2022 and recorded information on patients within 6 months of monitoring. Postoperative pain, emergency agitation, nausea, and vomiting were designated anaesthesia-related outcomes. Propensity score matching was used to adjust for covariates. The study adhered to the STROBE guidelines. RESULTS: The study's statistical analysis included 4483 patients monitored by 22 newly recruited nurse anaesthetists and 4959 patients monitored by 23 newly recruited anaesthesiologists. Compared with patients monitored by newly trained anaesthesiologists, the patients monitored by nurse anaesthetists were younger (42.07 ± 20.00 vs. 47.39 ± 18.45 years, p < 0.001) and had a lower body mass index (23.56 ± 4.46 vs. 24.19 ± 4.25, p < 0.001). Patients monitored by anaesthesiologists had a greater proportion of women (61.62% vs. 59.25%, p < 0.001), a high proportion of ASA III and ASA IV (17.1% vs. 8.88%, p < 0.001), and a longer mean surgery duration (78.65 ± 59.01 vs. 70.70 ± 60.65 min, p < 0.001). After propensity score matching was used to adjust for covariates, no statistically significant differences were found in the prevalence of postoperative pain, emergency agitation, or postoperative nausea and vomiting between the two groups (p < 0.05). CONCLUSION: Nurse anaesthetists monitoring alone during anaesthesia maintenance is feasible and safe. The two groups had no significant differences in the incidence of postoperative pain, emergency agitation, or postoperative nausea and vomiting. RELEVANCE TO CLINICAL PRACTICE: The shortage of anaesthesiologists leads to heavy work burden and high incidence of occupational burnout among anaesthesiologists. The study found that it was safe for nurse anaesthetists to perform anaesthetic monitoring alone in the operating room under the supervision of the attending anaesthesiologist and did reduce the burden of anaesthesiologists' work. The results of the current study contribute to the expansion of occupational categories for nurse anaesthetists in countries where anaesthesiologists are in short supply. It provides new ideas for hospital administrators and policy-makers to formulate medical and nursing service policies.

Comparison of intravenous and oral administration of acetaminophen in adults undergoing general anesthesia.

BACKGROUND: Acetaminophen is a widely clinically used analgesic. However, the clinical effect of the route of administration on postoperative analgesia as well as on postoperative nausea and vomiting in patients undergoing general anesthesia remains unclear. This study aimed to explore whether the route of administration of acetaminophen affects postoperative analgesia, nausea, and vomiting in patients undergoing general anesthesia. METHODS: We included all randomized controlled trials investigating the effects of the route of administration of acetaminophen on postoperative pain, nausea, and vomiting in patients undergoing general anesthesia. Independent examiners reviewed the literature and extracted data, with disagreements resolved through negotiation or the involvement of a third party. The Cochrane risk assessment tool was used to evaluate the quality of the included randomized controlled trials. A narrative synthesis was conducted to summarize the qualitative information from the included studies. A meta-integration of quantitative data was performed using RevMan 5.4. RESULTS: Ten studies met the inclusion criteria. Eight studies assessed postoperative pain, whereas two assessed postoperative nausea and vomiting. Data from the eight studies assessing postoperative pain confirmed that there was no difference between intravenously and orally administered acetaminophen in adults (OR = -0.13; 95% CI, -0.36 to 0.11; p = 0.3). Data from the two studies assessing postoperative nausea and vomiting revealed no difference between intravenously and orally administered acetaminophen in adults (OR = 0.89; 95% CI, 0.64-1.25; p = 0.51). The included studies were of poor quality, with a heterogeneity of 68%. CONCLUSIONS: No differences in postoperative analgesia or postoperative nausea and vomiting were observed between the routes of administration (intravenous vs. oral) of acetaminophen in adult patients undergoing general anesthesia. There is a need for future large sample studies to increase the reliability of the results.

Landscape of associations between long non-coding RNAs and infiltrating immune cells in liver hepatocellular carcinoma.

Liver hepatocellular carcinoma (LIHC) can be detected by the immune system; however, it acquires features for evasion of immune surveillance during its origin and development. Long non-coding RNAs (lncRNAs) are critical as immune regulators in cancers; nevertheless, the biological functions and mechanisms of lncRNAs in evasion of immune system by LIHC remain unclear. In this study, an integrated and computational approach was developed to identify immune-related lncRNAs and to divide LIHC patients into diverse immune-related risk groups based on the expression profiles of coding genes and lncRNAs. LIHC-specific genes and lncRNAs in 17 immune cell populations were identified and analysed. Gene and lncRNA co-expressing networks for diverse immune cell populations were constructed and analysed. Some imported immune-related lncRNAs, such as MIR9-3HG, were also identified. The LIHC patients comprised three different groups based on immune-related risk. LIHC patients possessing a greater diversity of immune cell populations had better survival prognosis. The collective data are evidence of a credible computational model that can prioritize novel immune-related lncRNAs and depict the atlas of immune-related lncRNAs in LIHC. These findings will further the understanding of lncRNA function and advance the identification of immunotherapy targets in LIHC.

Clinical characteristics, treatment patterns and survival outcome of hepatocellular carcinoma patients aged 70 years or older: a single-center retrospective study from China.

BACKGROUND AND AIMS: The information about clinical presentation and outcome of elderly hepatocellular carcinoma (HCC) patients is limited. We performed this study to assess the impact of age on potential differences in clinical characteristics, treatment patterns and outcome in HCC patients. METHODS: Clinical data of 164 "elderly" (≥70 years old) and 531 "younger" (<70 years old) HCC patients treated at a Chinese tertiary university-affiliated medical center between April 2004 and April 2012 were collected and compared using various parameters. RESULTS: Compared with younger patients, the elderly patients had a higher proportion of females (32.9 % vs. 18.1 %, p < 0.001), less hepatitis B virus (HBV) infection (40.9 % vs. 76.6 %, p < 0.001), more hepatitis C virus (HCV) infection (23.8 % vs. 5.6 %, p < 0.001), less liver cirrhosis (68.3 % vs. 76.8 %, p = 0.03) and massive tumors (12.8 % vs. 21.8 %, p = 0.01). There was no significant difference between the two groups in Child-Pugh class and tumor stages. The elderly patients received less surgical resection (14.6 % vs. 29.6 %, p < 0.001) and more supportive care (48.8 % vs. 37.9 %, p = 0.01) than younger patients. The overall survival was not significantly different between the two groups (26.2 mo. vs. 28.3 mo., p = 0.75). CONCLUSION: Characteristics that distinguish elderly from younger HCC patients included more female, less HBV infection, more HCV infection, less liver cirrhosis and massive tumors. Significant differences were observed in therapeutic strategies utilized with the two groups, but the overall survival was not significantly different.

Non-linear relationship between baseline fasting blood glucose and mortality in peritoneal dialysis patients, a retrospective cohort study.

Background: The relationship between baseline fasting blood glucose (bFBG) and mortality in peritoneal dialysis (PD) patients has been the subject of debate, with limited exploration of the non-linear relationship between bFBG and death in these patients. Methods: This retrospective study categorized patients into four groups based on their bFBG using quartiles. Baseline clinical data at the initiation of dialysis were compared. Survival curves were plotted, and subgroup analyses were stratified by relevant covariates. To address the non-linear relationship, curve fitting and a threshold effect analysis were performed. Results: The study included 379 PD patients with a median follow-up of 41.8 (22.6, 60.1) months. The COX proportional hazards model showed an association between bFBG and the risk of death after adjusting for confounding factors [hazard ratio (HR): 1.22, 95% CI: 1.05-1.41, P = 0.009]. Stratified analyses indicated a stable correlation between bFBG and mortality. The Kaplan-Meier curve analysis revealed significant differences in survival rates among different groups based on bFBG levels (P < 0.01). The curve fitting analysis revealed a U-shaped relationship between bFBG and mortality, with an inflection point at approximately 5.1 mmol/L. Conclusion: Our study has demonstrated a non-linear relationship between bFBG and mortality in PD patients. Additionally, we have found that the optimal bFBG value associated with the lowest risk of mortality is approximately 5.1 mmol/L.

Waist-to-height ratio is a better predictor of hypertension in women during recovery from anesthesia compared to BMI, waist-to-hip ratio, and waist circumference.

This was an observational study of patients with benign breast tumors intended to investigate and compare the predictive value of body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), and waist-to-height ratio (WHtR) for hypertension in the recovery room. Logistic regression analysis was used to determine the association between these body fat anthropometric indices and hypertension. Receiver operating characteristic curve (ROC) analysis was performed to assess the comparative predictive ability. A total of 689 women were evaluated. Patients with BMI ≥28 (kg/m2), WC > 85 cm, WHR ≥0.82, and WHtR ≥0.5 had a significantly higher probability of increased systolic blood pressure (SBP) and diastolic blood pressure (DBP) than patients with less than threshold values (all P < 0.05). The areas under the ROC curve (AUC) of BMI, WC, and WHtR where all modestly significant (all AUC ≥0.65) and nearly identical at 0.6592, 0.65, and 0.6724, respectively. Conclusion: body fat anthropometric indices are useful predicting hypertension during recovery from general anesthesia in patients with benign breast tumors undergoing day surgery; WHtR outperformed the other indices and nearly identical.

Breast cancer clinical outcomes and tumor immune microenvironment: cross-dialogue of multiple epigenetic modification profiles.

The discovery of RNA methylation alterations associated with cancer holds promise for their utilization as potential biomarkers in cancer diagnosis, prognosis, and prediction. RNA methylation has been found to impact the immunological microenvironment of tumors, but the specific role of methylation-related genes (MRGs), particularly in breast cancer (BC), the most common cancer among women globally, within the tumor microenvironment remains unknown. In this study, we obtained data from TCGA and GEO databases to investigate the expression patterns of MRGs in both genomic and transcriptional domains in BC. By analyzing the data, we identified two distinct genetic groupings that were correlated with clinicopathological characteristics, prognosis, degree of TME cell infiltration, and other abnormalities in MRGs among patients. Subsequently, an MRG model was developed to predict overall survival (OS) and its accuracy was evaluated in BC patients. Additionally, a highly precise nomogram was created to enhance the practical usability of the MRG model. In low-risk groups, we observed lower TBM values and higher TIDE scores. We further explored how MRGs influence a patient's prognosis, clinically significant characteristics, response to therapy, and the TME. These risk signatures have the potential to improve treatment strategies for BC patients and could be applied in future clinical settings. Moreover, they may also be utilized to determine prognosis and biological features in these patients.

Design and Control of the Magnetically Actuated Micro/Nanorobot Swarm toward Biomedical Applications.

Recently, magnetically actuated micro/nanorobots hold extensive promises in biomedical applications due to their advantages of noninvasiveness, fuel-free operation, and programmable nature. While effectively promised in various fields such as targeted delivery, most past investigations are mainly displayed in magnetic control of individual micro/nanorobots. Facing practical medical use, the micro/nanorobots are required for the development of swarm control in a closed-loop control manner. This review outlines the recent developments in magnetic micro/nanorobot swarms, including their actuating fundamentals, designs, controls, and biomedical applications. The fundamental principles and interactions involved in the formation of magnetic micro/nanorobot swarms are discussed first. The recent advances in the design of artificial and biohybrid micro/nanorobot swarms, along with the control devices and methods used for swarm manipulation, are presented. Furthermore, biomedical applications that have the potential to achieve clinical application are introduced, such as imaging-guided therapy, targeted delivery, embolization, and biofilm eradication. By addressing the potential challenges discussed toward the end of this review, magnetic micro/nanorobot swarms hold promise for clinical treatments in the future.

Peripheral T-cell subsets in radiofrequency ablation for tumors from different origins.

BACKGROUNDS: Radiofrequency ablation (RFA) is known to destroy tumoral tissue and activate immune cells. This study aimed to investigate the impact of RFA on peripheral T-cell responses and its relationship with tumor origin and hepatitis status. METHODS: A retrospective analysis was conducted on 62 patients with various types of tumors, including hepatocellular carcinoma, colorectal cancer, lung cancer, breast cancer, and others, who underwent RFA treatment between June 2017 and December 2018. Blood samples were collected before and one day after RFA treatment. The peripheral T-cell subsets were measured by flow cytometry, and their changes were analyzed. RESULTS: The study found a decrease in the CD4+CD8-and CD4-CD8+ T-cell subsets after RFA, but no significant changes were observed in the populations of CD4+CD8+ and the CD4+CD8-/CD4-CD8+ ratio. Furthermore, no significant differences were observed in peripheral T-cell subsets concerning tumor type or hepatitis status. CONCLUSIONS: The study suggests that RFA treatment may have a short-term impact on peripheral T-cell responses, characterized by a decrease in certain T-cell subsets. However, these changes do not seem to be related to the tumor type or hepatitis status of the patients.

The association between common genetic variant of microRNA-499 and cancer susceptibility: a meta-analysis.

Published data on the association between microRNA-499 (miR-499) rs3746444 T>C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of this relationship, a comprehensive meta-analysis was performed on nine published studies, with a total sample of 4,794 cases and 5,971 controls. Overall, no significant association was found between miR-499 polymorphism and cancer risk after all studies were pooled into the meta-analysis. However, in the subgroup analysis by ethnicity, significant association with an increased risk was found in Asian (CC vs. TT: OR = 1.439, 95 % CI = 1.118-1.852, P = 0.005, p-heterogeneity = 0.116). Moreover, in the the subgroup analysis by cancer type, this SNP was associated with an increased risk of breast cancer in the recessive model (OR = 1.077, 95 % CI = 1.008-1.151, P = 0.028, p-heterogeneity = 0.125). Our findings support the view that miR-499 rs3746444 T>C polymorphism is associated with breast cancer and the C allele can increase cancer susceptibility in Asian.

Unplanned Post-Anesthesia Care Unit to ICU Transfer Following Cerebral Surgery: A Retrospective Study.

Background: Unplanned transfer to intensive care unit (ICU) lead to reduced trust of patients and their families in medical staff and challenge medical staff to allocate scarce ICU resources. This study aimed to explore the incidence and risk factors of unplanned transfer to ICU during emergence from general anesthesia after cerebral surgery, and to provide guidelines for preventing unplanned transfer from post-anesthesia care unit (PACU) to ICU following cerebral surgery. Methods: This was a retrospective case-control study and included patients with unplanned transfer from PACU to ICU following cerebral surgery between January 2016 and December 2020. The control group comprised patients matched (2:1) for age (±5 years), sex, and operation date (±48 hours) as those in the case group. Stata14.0 was used for statistical analysis, and p < .05 indicated statistical significance. Results: A total of 11,807 patients following cerebral surgery operations were cared in PACU during the study period. Of the 11,807 operations, 81 unscheduled ICU transfer occurred (0.686%). Finally, 76 patients were included in the case group, and 152 in the control group. The following factors were identified as independent risk factors for unplanned ICU admission after neurosurgery: low mean blood oxygen (OR = 1.57, 95%CI: 1.20-2.04), low mean albumin (OR = 1.14, 95%CI: 1.03-1.25), slow mean heart rate (OR = 1.04, 95%CI: 1.00-1.08), blood transfusion (OR = 2.78, 95%CI: 1.02-7.58), emergency surgery (OR = 3.08, 95%CI: 1.07-8.87), lung disease (OR = 2.64, 95%CI: 1.06-6.60), and high mean blood glucose (OR = 1.71, 95%CI: 1.21-2.41). Conclusion: We identified independent risk factors for unplanned transfer from PACU to ICU after cerebral surgery based on electronic medical records. Early identification of patients who may undergo unplanned ICU transfer after cerebral surgery is important to provide guidance for accurately implementing a patient's level of care.

[Investigation of Methods and Influencing Factors to Increase the Positive Rate of 
Cytological Pathology of Cerebrospinal Fluid from Lung Cancer Leptomeningeal Metastases].

BACKGROUND: In advanced non-small cell lung cancer (NSCLC), leptomeningeal metastases (LM) is a common consequence with rapid progression and a poor prognosis. LM affects roughly 3% to 5% of NSCLC patients, and it affects as many as 9.4% of individuals with epidermal growth factor receptor (EGFR) mutations. Cerebrospinal fluid cytology is the gold standard for diagnosing LM, while conventional cytopathology has a positive detection rate of less than 50%, resulting in a delay in diagnosis and treatment of LM. The fixation treatment of cerebrospinal fluid samples has a significant impact on the positive cytology detection rate, and how to improve the positive cytopathology detection rate of cerebrospinal fluid is a hot topic in clinical research. METHODS: From June 2019 to November 2021, 105 cases diagnosed with LM based on clinical symptoms and positive imaging were collected and retrospectively evaluated in the second ward of the Department of Oncology of The Second Affiliated Hospital of Harbin Medical University. The effect of different fixation methods on the positive rate of cerebrospinal fluid cytopathology was investigated, and specimens of cerebrospinal fluid were collected and sent for examination using different delivery methods, including the application of the TIB cell preservation solution kit (experimental group) and the routine application of sterile plastic tubes in lumbar puncture bags (control group). Biochemical assays (glucose and total protein) were performed on the cerebrospinal fluid fluid, and Logistic regression analysis and receiver operating characteristic (ROC) curve were used to evaluate the supplementary diagnostic value for LM patients with lung cancer. The relevance of chemical indexes in the assessment of therapeutic efficacy was examined, and biochemical (glucose, total protein) indices and cytological changes in cerebrospinal fluid fluid after pemetrexed intrathecal injection therapy were dynamically monitored. RESULTS: In the control group, 24 (45.28%) patients were positive for the first time, while 42 (80.77%) patients were positive for the first time and 10 (19.23%) patients were negative for the first time in the experimental group. Significant differences existed between the two groups (P<0.001). The results of Logistic regression analysis of patients with the first cerebrospinal fluid biochemical test showed that the risk of positive cerebrospinal fluid biochemical pathology with less than 2.5 mmol/L was 2.456 times greater than 2.5 mmol/L of cerebrospinal fluid glucose (OR=2.456, P<0.05), and total cerebrospinal fluid biochemical protein greater than 430 mg/L was 2.647 times less than 430 mg/L (OR=2.647, P>0.05). The ROC curve showed glucose sensitivity of 76.9% in cerebrospinal fluid, the specificity of 54.5%, Youden index of 0.315 and area under the curve (AUC) of 0.620, total protein sensitivity in cerebrospinal fluid of 44.4%, 90.6%, Youden index of 0.350 and AUC of 0.671. After 2 cycles of pemetrexed intrathecal treatment with complete cerebrospinal fluid cytology and cerebrospinal fluid biochemical (glucose, total protein) tests in 73 and 50 patients, respectively, the rate of cerebrospinal fluid cytology turning negative was gradually increased. Cerebrospinal fluid glucose levels increased after 2 cycles of treatment compared with the first time, with a statistically significant difference (P<0.001). CONCLUSIONS: The use of a cell preservation solution kit to immediately fix cerebrospinal fluid samples following isolation in patients with clinical symptoms and positive imaging greatly enhances the rate of positive cerebrospinal fluid cytology detection. The effect of treatment can be assessed and predicted by continuous dynamic monitoring of cerebrospinal fluid biochemistry and cytology.

Concordance Study of a 520-Gene Next-Generation Sequencing-Based Genomic Profiling Assay of Tissue and Plasma Samples.

INTRODUCTION: Next-generation sequencing (NGS) enables simultaneous detection of actionable somatic variants and estimation of genomic signatures such as tumor mutational burden (TMB) or microsatellite instability (MSI) status, which empowers therapeutic decisions in clinical oncology. OBJECTIVE: Our retrospective study investigated the clinical performance of somatic variant detection in paired tissue and blood samples using a large targeted gene panel, the OncoScreen Plus, which interrogates 520 cancer-related genes. METHODS: We analyzed sequencing data derived from paired tissue and blood samples of 3005 patients spanning 20 solid tumor types, including lung (n = 1971), gastrointestinal (n = 625), breast (n = 120) and gynecological (n = 110), genitourinary (n = 38), and other cancers (n = 141). RESULTS: Across tumor types, the OncoScreen Plus panel achieved a high tissue detection rate, with an average of 97.9%. The average plasma detection rate was 72.2%, with an average tissue concordance rate of 36.6%. Considering all variant types, the plasma assay yielded an average sensitivity/true positive rate of 45.7%, with a positive predictive value of 64.7% relative to tissue assay. Pearson correlation analysis revealed a strong correlation in TMB estimated from blood and tissue samples (correlation coefficient 0.845, R2 = 0.756). MSI-high status was identified in five tumor types, including endometrial cancer (28.6%), colorectal cancer (2.5%), ovarian cancer (2.0%), gastric cancer (1.5%), and lung adenocarcinoma (0.2%). CONCLUSION: Paired tumor and blood samples from a large cohort of patients spanning 20 tumor types demonstrated that the OncoScreen Plus is a reliable pan-cancer panel for the accurate detection of somatic variants and genomic signatures that could guide individualized treatment strategies to improve the care of patients with advanced cancer.

Alectinib as first-line treatment for advanced ALK-positive non-small cell lung cancer in the real-world setting: preliminary analysis in a Chinese cohort.

Background: Tyrosine kinase inhibitors (TKIs) have been a major advance in the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) which have been substantiated in clinical trials. However, real-world data on first-line alectinib in a Chinese patient population are limited. Methods: We enrolled patients diagnosed with advanced ALK-positive NSCLC treated with first-line alectinib at 8 centers in China, including cases with symptomatic or active CNS metastases. Continuation of alectinib was permitted after local or gradual progression at the treating clinician's discretion. Time-to-treatment failure (TTF) was defined as the period from the start of alectinib to discontinuation for any cause including disease progression, death, adverse events and patient's preference. We defined longer EML4-ALK variants as containing EML4 fusions to at least exon 13 and shorter variants had EML4 fusions up to exon 6. Results: Of the 110 patients included, 26.4% had Eastern Cooperative Oncology Group Performance Status (ECOG) ≥2 points. The objective response rate (ORR) was 88.5% [95% confidence interval (CI): 79.9-94.3%] and median tumor shrinkage rate was 60% (range, 0-100%) in patients with target lesions. For patients with measurable central nervous system (CNS) metastases, the CNS-ORR was 92.9% (95% CI: 66.1-99.8%), additionally, 80% (8/10) of patients experienced significant improvement in CNS-related symptoms following alectinib treatment. With a median follow-up of 18.3 months, the estimated 2-year progression-free survival (PFS) rate and 2-year treatment failure-free rate were 81.1% (95% CI: 71.5-87.7%) and 81.0% (95% CI: 70.6-88.0%) respectively. Grade 3-4 adverse events occurred in 6.4% and only 2 patients (1.8%) permanently discontinued alectinib due to adverse events. Multivariate analysis indicated that patients with metastases in ≥3 distant organs and a tumor reduction rate ≤50% demonstrated more unfavorable mPFS than their counterparts. Furthermore, patients carrying longer variants showed superior mPFS to those with shorter variants (not reached vs. 24.2 months, hazard ratio =0.17, 95% CI: 0.04-0.68, P=0.004). Conclusions: Alectinib showed substantial efficacy and an excellent safety profile in a real-world setting of Chinese patients. Clinical outcomes and long-term survival still require longer follow-up. Tumors with shorter EML4 fusion variants, more extensive metastases and less reduction in tumor lesions may require more aggressive strategies.

Efficacy and Safety of Intrathecal Pemetrexed Combined With Dexamethasone for Treating Tyrosine Kinase Inhibitor-Failed Leptomeningeal Metastases From EGFR-Mutant NSCLC-a Prospective, Open-Label, Single-Arm Phase 1/2 Clinical Trial (Unique Identifier: ChiCTR1800016615).

INTRODUCTION: We aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating EGFR-mutant leptomeningeal metastases (LMs) from EGFR-mutant NSCLC. METHODS: Patients with EGFR-mutant NSCLC with LM who had failed tyrosine kinase inhibitors were recruited. The dose of IP was escalated from 15 mg to 80 mg using an accelerated titration design in a phase 1 study. The recommended dose (RD) determined in phase 1 was used in the phase 2 study. The primary end point was treatment efficacy measured as the clinical response rate. Overall survival and adverse events (AEs) were evaluated as secondary end points. RESULTS: The RD observed in the phase 1 study was 50 mg pemetrexed. A total of 30 cases of LM-NSCLC were enrolled in the phase 2 study, including 14 males and 16 females. Four patients did not survive for 4 weeks and could not be evaluated for efficacy. The clinical response rate was 84.6% (22 of 26). The median overall survival of all patients was 9.0 months (n = 30, 95% confidence interval: 6.6-11.4 mo). Most AEs were mild, and the most frequent AE of any grade was myelosuppression (n = 9, 30%), which returned to normal after symptomatic treatment. CONCLUSIONS: This study revealed that 50 mg pemetrexed is the RD which results in few AEs and a good response rate. IP is an effective treatment for patients with EGFR-mutant NSCLC-LM who had failed on tyrosine kinase inhibitor.

Ureter tissue engineering with vessel extracellular matrix and differentiated urine-derived stem cells.

OBJECTIVE: To assess the possibility of ureter tissue engineering using vessel extracellular matrix (VECM) and differentiated urine-derived stem cells (USCs) in a rabbit model. METHODS: VECM was prepared by a modified technique. USCs were isolated from human urine samples and cultured with an induction medium for the differentiation of the cells into urothelium and smooth muscle phenotypes. For contractile phenotype conversion, the induced smooth muscle cells were transfected with the miR-199a-5p plasmid. The differentiated cells were seeded onto VECM and cultured under dynamic conditions in vitro for 2 weeks. The graft was tubularized and wrapped by two layers of the omentum of a rabbit for vascularization. Then, the maturated graft was used for ureter reconstruction in vivo. RESULTS: VECM has microporous structures that allow cell infiltration and exhibit adequate biocompatibility with seeding cells. USCs were isolated and identified by flow cytometry. After induction, the urothelium phenotype gene was confirmed at mRNA and protein levels. With the combined induction by TGF-ß1 and miR-199a-5p, the differentiated cells can express the smooth muscle phenotype gene and convert to the contractile phenotype. After seeding cells onto VECM, the induced urothelium cells formed a single epithelial layer, and the induced smooth muscle cells formed a few cell layers during dynamic culture. After 3 weeks of omental maturation, tubular graft was vascularized. At 2 months post ureter reconstruction, histological evaluation showed a clearly layered structure of ureter with multilayered urothelium over the organized smooth muscle tissue. CONCLUSION: By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. STATEMENT OF SIGNIFICANCE: Cell-based tissue engineering offers an alternative technique for urinary tract reconstruction. In this work, we describe a novel strategy for ureter tissue engineering. We modified the techniques of vessel extracellular matrix (VECM) preparation and used a dynamic culture system for seeding cells onto VECM. We found that VECM had the trait of containing VEGF and exhibited blood vessel formation potential. Urine-derived stem cells (USCs) could be differentiated into urothelial cells and functional contractile phenotype smooth muscle cells in vitro. By seeding differentiated USCs onto VECM, a tissue-engineered graft could form multilayered urothelium and organized smooth muscle tissue after ureteral reconstruction in vivo. This strategy might be applied in clinical research for the treatment of long-segment ureteral defect.

Comparison of efficacy and toxicity of bevacizumab, endostar and apatinib in transgenic and human lung cancer xenograftzebrafish model.

The poor prognosis in non-small-cell lung cancer has driven the development of novel targeted therapies. Vascular endothelial growth factor is the most potent force in mediating tumor angiogenesis, and many angiogenesis inhibitors have been developed for oncology treatment. We performed a study to characterize the efficacy, safety and tumor suppression of three lung cancer related anti-angiogenic drugs (bevacizumab, endostar and apatinib) using transgenic zebrafish embryo and human lung cancer xenotransplantation model. All three drugs demonstrated remarkable angiogenesis and tumor inhibition effect in the zebrafish model, within the nonlethal dose range. Endostar and bevacizumab showed competitive anti-tumor efficacy. The anti-tumor performance of apatinib was hamstrung by its elevated toxicity at 35 °C. The addition of pemetrexed to anti-angiogenesis therapy had no obvious additional benefit in tumors.