New prognostic system specific for epidermal growth factor receptor-mutated lung cancer brain metastasis.

Introduction: Brain metastases (BM) from lung cancer are heterogeneous, and accurate prognosis is required for effective treatment strategies. This study aimed to identify prognostic factors and develop a prognostic system exclusively for epidermal growth factor receptor (EGFR)-mutated lung cancer BM. Methods: In total, 173 patients with EGFR-mutated lung cancer from two hospitals who developed BM and received tyrosine kinase inhibitor (TKI) and brain radiation therapy (RT) were included. Univariate and multivariate analyses were performed to identify significant EGFR-mutated BM prognostic factors to construct a new EGFR recursive partitioning analysis (RPA) prognostic index. The predictive discrimination of five prognostic scoring systems including RPA, diagnosis-specific prognostic factors indexes (DS-GPA), basic score for brain metastases (BS-BM), lung cancer using molecular markers (lung-mol GPA) and EGFR-RPA were analyzed using log-rank test, concordance index (C-index), and receiver operating characteristic curve (ROC). The potential predictive factors in the multivariable analysis to construct a prognostic index included Karnofsky performance status, BM at initial lung cancer diagnosis, BM progression after TKI, EGFR mutation type, uncontrolled primary tumors, and number of BM. Results and discussion: In the log-rank test, indices of RPA, DS-GPA, lung-mol GPA, BS-BM, and EGFR-RPA were all significant predictors of overall survival (OS) (p ≤ 0.05). The C-indices of each prognostic score were 0.603, 0.569, 0.613, 0.595, and 0.671, respectively; The area under the curve (AUC) values predicting 1-year OS were 0.565 (p=0.215), 0.572 (p=0.174), 0.641 (p=0.007), 0.585 (p=0.106), and 0.781 (p=0.000), respectively. Furthermore, EGFR-RPA performed better in terms of calibration than other prognostic indices.BM progression after TKI and EGFR mutation type were specific prognostic factors for EGFR-mutated lung cancer BM. EGFR-RPA was more precise than other models, and useful for personal treatment.

Median nerve block increases the success rate of radial artery cannulation in women with gestational hypertension undergoing cesarean section.

BACKGROUND: The radial artery cannulation helps to maintain the stability of maternal hemodynamics and reduce complications, however, it is difficult for women with gestational hypertension. Ultrasound-guided median nerve block can cause arterial vasodilation, which may improve the success rate of radial artery cannulation. METHODS: Ninety-two women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed ultrasound-guided cannulation were identified and randomized into the median nerve block group and control group. Median nerve block was performed under the guidance of ultrasound in the middle forearm and 5 ml of 0.5% lidocaine was injected. Subcutaneous local block was administered in the control group. The ultrasound-guided radial artery cannulation was performed ten minutes after blocking. Baseline measurements (T1) were performed after 10 minutes of rest. All variables were measured again at 10 (T2) and 30 (T3) minutes after median nerve block or local block. The primary outcome was the success rate of radial artery cannulation within 10 minutes after blocking. The puncture time, number of attempts, the overall complications, and ultrasonographic measurements including radial artery diameter and cross-sectional area were recorded before (T1), 10 minutes (T2) after, and 30 minutes (T3) after block. RESULTS: A total of 92 pregnant women were identified and completed the follow-up. As compared to control group, the first-attempt success rate of radial artery cannulation was significantly higher (95.7% vs78.3%, p = 0.027) and procedure time to success was significantly shorter (118 ± 19 s vs 172 ± 66 s, p < 0.001) in median nerve group. Median nerve group also had a significantly less overall number of attempts (p = 0.024). Compared with control group, the diameter and cross-sectional area of radial artery increased significantly at the T2 and T3 points in median nerve group (p < 0.001), as well as percentage change of radial artery diameter and CSA. No difference was observed in the overall complication at chosen radial artery, which including vasospasm (21.7% vs 28.3%; p = 0.470) and hematoma (4.3% vs 8.7%; p = 0.677). CONCLUSIONS: Ultrasound-guided median nerve block can increase the first-attempt success rate of chosen radial artery cannulation in women with gestational hypertension and risks of intra-operative bleeding undergoing cesarean section following failed radial artery cannulation, and especially for those anesthesiologists with less experienced in radial artery cannulation. TRIAL REGISTRATION: ChiCTR2100052862; http://www.chictr.org.cn , Principal investigator: MEN, Date of registration: 06/11/2021.

Inferior Vena Cava Collapsibility Index Can Predict Hypotension and Guide Fluid Management After Spinal Anesthesia.

PURPOSE: We hypothesized that inferior vena cava collapsibility index (IVCCI)-guided fluid management would reduce the incidence of postspinal anesthesia hypotension in patients undergoing non-cardiovascular, non-obstetric surgery. METHODS: A receiver operating characteristic (ROC) curve was used to determine the diagnostic value of IVCCI for predicting hypotension after induction of spinal anesthesia and calculate the cut-off value. Based on the cut-off variation value, the following prospective randomized controlled trial aimed to compare the incidence of postspinal anesthesia hypotension between the IVCCI-guided fluid administration group and the standard fluid administration group. Secondary outcomes included the rate of vasoactive drug administration, the amount of fluid administered, and the incidence of nausea and vomiting. RESULTS: ROC curve analysis revealed that IVCCI had a sensitivity of 83.9%, a specificity of 76.3%, and a positive predictive value of 84% for predicting postspinal anesthesia hypotension at a cut-off point of >42%. The area under the curve (AUC) was 0.834 (95% confidence interval: 0.740-0.904). According to the cut-off variation value of 42%, the IVCCI-guided group exhibited a lower incidence of hypotension than the standard group [9 (15.3%) vs. 20 (31.7%), P = 0.032]. Total fluid administered was lower in the IVCCI-guided group than in the standard group [330 (0-560) mL vs. 345 (285-670) mL, P = 0.030]. CONCLUSIONS: Prespinal ultrasound scanning of the IVCCI provides a reliable predictor of hypotension following spinal anesthesia at a cut-off point of >42%. IVCCI-guided fluid management before spinal anesthesia can reduce the incidence of hypotension following spinal anesthesia.

Effects of combined warmed preoperative forced-air and warmed perioperative intravenous fluids on maternal temperature during cesarean section: a prospective, randomized, controlled clinical trial.

BACKGROUND: Preventing the frequent perioperative hypothermia incidents that occur during elective caesarean deliveries would be beneficial. This trial aimed at evaluating the effect of preoperative forced-air warming alongside perioperative intravenous fluid warming in women undergoing cesarean sections under spinal anesthesia. METHODS: We randomly allocated 135 women undergoing elective cesarean deliveries to either the intervention group (preoperative forced-air and intravenous fluid warming, n = 69) or the control group (no active warming, n = 66). The primary outcome measure was the core temperature change between groups from baseline to the end of the surgical procedure. Secondary outcomes included thermal comfort scores, the incidences of shivering and hypothermia (< 36 °C), the core temperature on arrival at the post-anesthesia care unit, neonatal axillary temperature at birth, and Apgar scores. RESULTS: Two-way repeated measures ANOVA revealed significantly different core temperature changes (from the pre-spinal temperature to that at the end of the procedure) between groups (F = 13.022, P < 0.001). The thermal comfort scores were also higher in the intervention group than in the control group (F = 9.847, P = 0.002). The overall incidence of perioperative hypothermia was significantly lower in the intervention group than in the control group (20.6% vs. 51.6%, P < 0.0001). CONCLUSIONS: Warming preoperative forced-air and perioperative intravenous fluids may prevent maternal hypothermia, reduce maternal shivering, and improve maternal thermal comfort for patients undergoing cesarean sections under spinal anesthesia. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (registration number: ChiCTR1800019117) on October26, 2018.

Tra2ß silencing suppresses cell proliferation in laryngeal squamous cell carcinoma via inhibiting PI3K/AKT signaling.

OBJECTIVES/HYPOTHESIS: Transformer-2 protein homolog beta (Tra2ß) generally plays an important role in various human cancers, but its role and the underlying mechanisms in laryngeal squamous cell carcinoma (LSCC) remained unknown. So this study aimed to assess the clinical significance and regulatory mechanisms of Tra2ß in LSCC. STUDY DESIGN: Laboratory analysis. METHODS: Expression of Tra2ß was compared in human LSCC tissue samples and paired adjacent normal tissue samples. The in vitro effects of Tra2ß expression in Hep-2 cells on their proliferation, invasion, and migration were assessed by CCK-8 assays, Matrigel invasion, and transwell migration assays. In addition, the effects of downregulation of Tra2ß on the activation of PI3K/AKT signaling pathway were measured using Western blot analysis. The effect of Tra2ß on the growth of tumors was detected in the Hep-2-injected xenograft models in vivo. RESULTS: Reverse-transcription quantitative polymerase chain reaction analysis and immunochemistry analysis indicated that the increased expression of Tra2ß in LSCC was significantly associated with poor differentiation, lymph node metastasis, and advanced clinical stage. In vitro knockdown of Tra2ß caused a significant decrease in the proliferation, invasion, and migration of Hep-2 cells. Tra2ß silencing decreased the expression of Bcl-2 but increased Bax and Caspase-3 both in mRNA and protein levels. Furthermore, knockdown of Tra2ß eliminated the suppressive effects of activation of PI3K/AKT signaling. In vivo knockdown of Tra2ß significantly inhibited the tumor growth of Hep-2-injected xenograft mice. CONCLUSIONS: The results of the present study demonstrated that knockdown of Tra2ß inhibits the proliferation and invasion of LSCC cells, at least partly via inhibiting PI3K/AKT signaling. LEVEL OF EVIDENCE: NA Laryngoscope, 129:E318-E328, 2019.

Diabetes mellitus might be a protective factor of glioma.

AIMS: Several studies suggested that diabetes mellitus (DM) was associated with the risk of glioma. However, other studies did not confirm the result. Therefore, I conducted this meta-analysis. MATERIALS AND METHODS: I retrieved the PubMed, Embase, and Web of Science database, by adopting keywords "glioma," and "diabetes," "DM." The strength of the associations between DM and the risk of glioma was measured by odds ratios (ORs) with 95% confidence intervals (95% CIs). RESULTS: Ten relevant studies were identified in the final analysis. A statistically significant association between DM and glioma risk was fond (OR = 0.84; 95% CI, 0.73-0.97; P = 0.02). In the subgroup analysis of age group, young population with DM showed decreased glioma risk (OR = 0.83; 95% CI, 0.70-0.98; P = 0.02), whereas old population with DM did not show a significant association (OR = 0.87; 95% CI, 0.65-1.16; P = 0.34). In the subgroup analysis of gender, male patients with DM showed decreased glioma risk (OR = 0.82; 95% CI, 0.68-0.99; P = 0.04), whereas female population with DM did not show a significant association (OR = 0.93; 95% CI, 0.70-1.24; P = 0.63). CONCLUSIONS: This meta-analysis suggested that DM may be associated with the reduced glioma risk.

Intra-abdominal pressure, vertebral column length, and spread of spinal anesthesia in parturients undergoing cesarean section: An observational study.

BACKGROUND: In parturients with increased physiologically intra-abdominal pressure (IAP) and a short stature, a greater cephalad spread of spinal anesthesia is often observed after a fixed amount of plain bupivacaine is administered. Therefore, we designed this prospective study to test whether IAP and vertebral column length (VCL) were predictors of spinal spread in parturients undergoing a cesarean section. METHODS: A total of 113 parturients, all undergoing elective cesarean sections with single-shot spinal anesthesia, were enrolled. The L3-L4 interspace was entered, and 2 mL of 0.5% plain bupivacaine was injected into the subarachnoid space. Upon loss of temperature sensation at the T4 level, IAP was measured through a bladder catheter while the patient was in the supine position with a 10°left lateral tilt. Parturient demographic variables, including age, height, weight, IAP, and VCL were recorded. Linear regressions and multiple regressions were performed to analyze the relationships between parturient variables and the spread of spinal anesthesia. RESULTS: A total of 109 parturients were included in the analysis. Linear regression analysis showed a significant univariate correlation of height, weight, body mass index (BMI), IAP, and VCL with cephalad spread (all P< 0.004). Multiple linear regression analysis showed that IAP and VCL were the key determinants of spinal spread (both P < 0.0001), where as exclusion of age, weight, and height did not change the result (all P> 0.209). CONCLUSIONS: Our data indicated that IAP and VCL were significant predictors of intrathecal spread of plain bupivacaine, and there was a positive association between IAP and abdominal girth in term parturients.

Knockdown of microRNA-1323 restores sensitivity to radiation by suppression of PRKDC activity in radiation-resistant lung cancer cells.

Resistance to radiation is a major problem in cancer treatment. The mechanisms of radioresistance remain poorly understood; however, mounting evidence supports a role for microRNAs (miRNAs) in the modulation of key cellular pathways mediating the response to radiation. The present study aimed to identify specific miRNAs and their effect on radioresistant cells. The global miRNA profile of an established radioresistant lung cancer cell line and the corresponding control cells was determined. Differential expression of the miRNAs was confirmed by quantitative real-time PCR (qRT-PCR). The binding effect of identical novel miRNAs and target mRNAs was determined by luciferase assay. Lung cancer cells were transfected with miRNA-specific mimics or inhibitors. The DNA-dependent protein kinase (DNA-PKcs) protein level was tested by western blot analysis. Radiosensitivity of cancer cells was determined using colony formation assay. Among the differentially expressed miRNAs, 25 miRNAs were overexpressed while 18 were suppressed in the radioresistant cells, both basally and in response to radiation compared to their control. An miRNA signature miR-1323 exhibited a >5-fold increase in the radioresistant cells. miR-1323 was demonstrated to bind to PRKDC 3'UTR, which is involved in DNA repair. Ectopic expression of miR-1323 significantly increased the survival fraction of irradiated cancer cells. Inhibition of miR-1323 reversed the radioresistance of cancer cells and subsequently suppressed the expression of miR-1323-regulated DNA-PKcs protein. The present study indicated that miRNAs are involved in the radioresistance of human lung cancer cells. A possible mechanism for resistance to radiation was via enhanced DNA repair. The present study demonstrated a role for miR-1323 in modulating radioresistance and highlights the need for further study investigating the potential role of miR-1323 as both a predictive marker of response and a novel therapeutic agent with which to enhance the efficacy of radiotherapy.

MicroRNA-204 targets signal transducer and activator of transcription 5 expression and inhibits proliferation of B-cell lymphoma cells.

The function of microRNAs (miRNAs) in tumorigenesis has been extensively investigated. In the present study, the aim was to investigate the expression and role of miR­204 in B­cell lymphoma. The present study demonstrated that miR­204 is downregulated in B­cell lymphoma. Using in vitro studies, overexpression of miR­204 was shown to inhibit growth in Daudi and Raji B­cell lymphoma cell lines. Furthermore, miR­204 could bind the 3'­untranslated region of signal transducer activator of transcription 5 (STAT5), a transcription factor that promotes B­cell lymphoma oncogenesis. Re­introduction of STAT5 reversed the antiproliferative roles of miR­204, confirming the specific importance of STAT5 for miR­204 action in cell proliferation. The present study suggests a novel mechanism for dysregulated miRNAs in the progression of B­cell lymphoma.