Meta-analysis of efficacy and safety of pembrolizumab for the treatment of advanced or recurrent cervical cancer.

BACKGROUND: This meta-analysis seeks to assess the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. METHODS: Databases from PubMed, Embase, and the Cochrane Library were all thoroughly searched for pertinent research. Outcomes include complete response (CR), partial response (PR), stable disease (SD), disease progression (PD), overall response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and adverse events (AEs) were retrieved for further analysis. RESULTS: Ten trials with 721 patients were included in this meta-analysis. The pooled results for patients with cervical cancer receiving pembrolizumab were as follows: CR (0.06, 95%CI: 0.02-0.10), PR (0.15, 95%CI: 0.08-0.22), SD (0.16, 95%CI: 0.13-0.20), PD (0.50, 95%CI: 0.25-0.75), ORR (0.26, 95%CI: 0.11-0.41) and DCR (0.42, 95%CI: 0.13-0.71), respectively. Regarding survival analysis, the pooled mPFS and mOS were 3.81 and 10.15 months. Subgroup analysis showed that pembrolizumab in combination was more beneficial in CR (0.16 vs. 0.03, p = 0.012), PR (0.24 vs. 0.08, p = 0.032), SD (0.11 vs. 0.19, p = 0.043), ORR (0.42 vs. 0.11, p = 0.014), and mPFS (5.54 months vs. 2.27 months, p < 0.001) than as single agent. The three most common AEs were diarrhoea (0.25), anaemia (0.25), and nausea (0.21), and the incidence of grade 3-5 AEs was significantly lower, rarely surpassing 0.10. CONCLUSIONS: For patients with advanced or recurrent cervical cancer, this systematic review and meta-analysis demonstrated that pembrolizumab had a favourable efficacy and tolerability. Future research will primarily focus on optimising customised regiments that optimally integrate pembrolizumab into new therapies and combination strategies. Designed to maximise patient benefit and efficiently control adverse effects while maintaining a high standard of living.

This study demonstrated the efficacy and safety of pembrolizumab in individuals with advanced or recurrent cervical cancer. The study found that an upfront combination of chemotherapy and pembrolizumab immunotherapy appears to be a compelling strategy for these patients. More large-scale and multicentre randomised controlled trials will be required in the future to validate the precise benefits of pembrolizumab in new therapies and combination strategies for the treatment of cervical cancer.

Trends and Preferences of Rhinoplasty Among Chinese Patients: A Social Media Analysis.

BACKGROUND: This study investigated the trends, motivations and preferences of rhinoplasty in China. METHODS: Data on rhinoplasty were collected from Xiaohongshu and analyzed for trends. Text analysis and word frequency statistics were performed on the notes and comments using Python modules. RESULTS: We obtained 1065 notes with 102,153 comments, 239,383 collections and 640,579 likes. The number of rhinoplasty-related publications increased annually, correlating with per capita disposable income of households (DI) growth (r2 = 0.609, P = 0.041 < 0.05). In the Southern provinces, there was a notably higher volume of publications compared to the Northern provinces (P = 0.001). Furthermore, a significant correlation was observed between publication data, population size, and the DI (r2 = 0.786, P < 0.001). The nasal tip (3197) and nasion (1409) were the most mentioned nasal subunits. "Good-looking" (9672) and "natural" (2811) were the most used words to describe the nose shape. The "doctor" (4377), the "hospital" (2182) and "hyaluronic acid" (2106) were the most mentioned rhinoplasty procedure related vocabulary. CONCLUSIONS: Discussions about rhinoplasty in China are increasing, and more people express their desire for rhinoplasty on social networks, related to China's DI growth. The Southern provinces show a higher inclination toward these discussions, a trend that correlates with our findings of a positive association between NOPs and both DI and population size. Netizens pay more attention to the shape of nasal tip and nasion, and prefer the good-looking and natural appearance. Most people consider autologous cartilage or hyaluronic acid injection for rhinoplasty. Doctors are the primary consideration for patients. LEVEL OF EVIDENCE V: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Bioinformatics analysis of the prognostic role of alternative splicing data in lung adenocarcinoma.

Background: As a post-transcriptional regulatory mechanism, alternative splicing (AS) is engaged in a variety of pathophysiological processes, and it has been widely reported in connection with the occurrence, progression, metastasis, and drug resistance of cancer. However, the research on AS in lung adenocarcinoma (LUAD) is very limited. In addition, the prognostic effect of AS event (ASE) on LUAD and its related mechanism are not clear. This study aimed to explore the role and potential prognostic value of ASE in LUAD. Methods: Relevant data and ASE datasets of the sample were acquired from The Cancer Genome Atlas (TCGA) and TCGASpliceSeq databases. We constructed a new prognostic criterion based on ASEs. Then, Cox regression and least absolute shrinkage and selection operator (LASSO) regression analysis were used to construct the model. Based on this model, the risk score of each ASE was calculated, and the reliability of this model was evaluated by Kaplan-Meier survival and receiver operating characteristic (ROC) curve analyses. Finally, these results were verified on different network platforms. Results: We identified seven types of ASEs related to survival. The prognostic risk model for ASEs was established. The Kaplan-Meier curve showed that compared to the low-risk group, the overall survival (OS) rate of LUAD patients in the high-risk group was lower. ROC curve analysis showed that the prognostic risk model of LUAD patients was well predicted, and the area under the curve (AUC) also confirmed this. Conclusions: This study screened the ASE related to the prognosis of LUAD patients, and provided a theoretical basis for further study of the correlation between ASE and the prognosis of LUAD patients. It has provided new ideas for developing new biomarkers and therapeutic targets for LUAD patients.

221S-1a inhibits endothelial proliferation in pathological angiogenesis through ERK/c-Myc signaling.

Pathological angiogenesis plays a major role in many disease processes, including cancer and diabetic retinopathy. Antiangiogenic therapy is a potential management for pathologic angiogenesis. The novel synthetic compound 221S-1a, derived from captopril, tanshinol and borneol, may have antiangiogenic properties. On the basis of MS, NMR and HPLC analysis, the structure of 221S-1a was identified. The cellular uptake and metabolism of this compound was also observed. Next, the antiangiogenic properties of 221S-1a were evaluated in tumor-xenograft and OIR models in vivo. The inhibitory properties of 221S-1a on endothelial cell proliferation, migration, tube formation and sprouting were detected in vitro. Furthermore, 221S-1a induced G1/S phase arrest was detected by PI staining flow cytometry analysis and Cyclin D, Cyclin E expression. 221S-1a inhibited ERK1/2 activation and nuclear translocation, in addition to downregulation of c-Myc, a transcription factor that regulates cell cycle progression. Molecular docking indicated the interaction of 221S-1a with the ATP-binding site of ERK2, leading to the inhibition of ERK2 phosphorylation and a concomitant inhibition of ERK1 phosphorylation. In conclusion, 221S-1a inhibited the G1/S phase transition by blocking the ERK1/2/c-Myc pathway to reduce tumor and OIR retinal angiogenesis. These novel findings suggest that 221S-1a is a potential pharmacologic candidate for treating pathological angiogenesis.

Intraoperative body temperature and emergence delirium in elderly patients after non-cardiac surgery: A secondary analysis of a prospective observational study.

BACKGROUND: Emergence delirium (ED) is a kind of delirium that occured in the immediate post-anesthesia period. Lower body temperature on post-anesthesia care unit (PACU) admission was an independent risk factor of ED. The present study was designed to investigate the association between intraoperative body temperature and ED in elderly patients undergoing non-cardiac surgery. METHODS: This study was a secondary analysis of a prospective observational study. Taking baseline body temperature as a reference, intraoperative absolute and relative temperature changes were calculated. The relative change was defined as the amplitude between intraoperative lowest/highest temperature and baseline reference. ED was assessed with the confusion assessment method for intensive care unit at 10 and 30 min after PACU admission and before PACU discharge. RESULTS: A total of 874 patients were analyzed with a mean age of 71.8 ±â€Š5.3 years. The incidence of ED was 38.4% (336/874). When taking 36.0°C, 35.5°C, and 35.0°C as thresholds, the incidences of absolute hypothermia were 76.7% (670/874), 38.4% (336/874), and 17.5% (153/874), respectively. In multivariable logistic regression analysis, absolute hypothermia (lowest value <35.5°C) and its cumulative duration were respectively associated with an increased risk of ED after adjusting for confounders including age, education, preoperative mild cognitive impairment, American Society of Anesthesiologists grade, duration of surgery, site of surgery, and pain intensity. Relative hypothermia (decrement >1.0°C from baseline) and its cumulative duration were also associated with an increased risk of ED, respectively. When taking the relative increment >0.5°C as a threshold, the incidence of relative hyperthermia was 21.7% (190/874) and it was associated with a decreased risk of ED after adjusting above confounders. CONCLUSIONS: In the present study, we found that intraoperative hypothermia, defined as either absolute or relative hypothermia, was associated with an increased risk of ED in elderly patients after non-cardiac surgery. Relative hyperthermia, but not absolute hyperthermia, was associated with a decreased risk of ED. REGISTRATION: Chinese Clinical Trial Registry (No. ChiCTR-OOC-17012734).

Epithelioid Hemangioendothelioma: Incidence, Mortality, Prognostic Factors, and Survival Analysis Using the Surveillance, Epidemiology, and End Results Database.

Background: Although epithelioid hemangioendothelioma (EHE) is a rare and aggressive vascular tumor, its demographic characteristics remain unclear. We used the surveillance, epidemiology, and end results (SEER) database to determine the clinical features, incidence, and prognostic factors associated with overall survival in patients with EHE. Methods: The demographic and clinical data of patients with EHE were extracted from the SEER database (1975-2019) to calculate the incidence of EHE and survival rate in these patients. The Cox proportional hazards model and Kaplan-Meier method were used to analyze the prognostic factors of overall survival in these patients. A nomogram and time-dependent receiver operating characteristic (ROC) curve were employed to predict the 3- and 5-year survival rate. Results: The overall incidence rate (IR) of EHE was 0.230 (95%confidence interval [CI] = 0.201-0.263) per 1,000,000 person-years. According to the age-stratified IR, the highest age-adjusted IR was observed in patients aged 60-79 years (0.524 per 1,000,000 person-years, 95%CI = 0.406-0.665). The majority (30.8%) of the tumors were located in the soft tissue and skin, followed by lesions in the abdomen (28%), respiratory system (19%), bone and joint (8.6%), and others. The 5-year overall survival rate was 55.6% (95%CI = 32.8-73.5%). Multiple Cox regression analysis revealed that age >80 years (hazard ratio [HR] = 8.57, 95%CI = 2.32-31.63, P < 0.001), African-American race (HR = 2.52, 95%CI = 1.31-4.85, P < 0.01), "American Indian/Alaska Native" or "Asian or Pacific Islander" (HR = 2.99, 95%CI = 1.5-5.96, P < 0.01) race, and respiratory tumors (HR = 2.55, 95%CI = 1.37-4.75, P < 0.01) were distinctly related to worse overall survival. The calibration plots demonstrated good consistency between nomogram-predicted and actual survival. The area under the time-dependent ROC curve was 0.721 (95%CI = 0.63-0.81) and 0.719 (95%CI = 0.63-0.81) for the 3- and 5-year survival, respectively. For the convenience of researchers and clinicians, we designed an online dynamics nomogram to predict the survival rate. Conclusion: EHE is a relatively rare vascular tumor, which principally occurs in the soft tissue and skin. It most commonly occurs in patients aged 60-79 years and its incidence has increased in recent years. Age at diagnosis, race, and tumor location may affect the overall survival outcomes.

Therapeutic Effect of Ultrasound-Guided Peripherally Inserted Central Catheter Combined with Predictive Nursing in Patients with Large-Area Severe Burns.

This study was aimed to explore the application value of ultrasound-guided peripherally inserted central catheter (PICC) combined with predictive nursing in the treatment of large-area severe burns. 88 patients with large-area severe burns who visited hospital were chosen as the research objects. They were randomly divided into the observation group and the control group, with 44 cases in each. The patients in the observation group were treated with ultrasound-guided PICC combined with predictive nursing, while those in the control group were treated with traditional PICC and nursing methods. Then, the anxiety of patients was compared between groups by the Self-rating Anxiety Scale (SAS), while the depression was compared by the Self-rating Depression Scale (SDS). The pain of the patients was analyzed by the McGill Pain Questionnaire (MPQ), and a self-made nursing satisfaction questionnaire was adopted to evaluate the nursing satisfaction. The surgery-related indicators of the patients were detected and recorded (the success rate of one-time puncture, the success rate of one-time catheter placement, incidence of complications, heart rate, blood pressure, etc.). The success rates of one-time puncture (93% vs. 86%) and of catheter placement (95% vs. 81%) in the observation group were significantly higher than those in the control group, P < 0.05. The pain scores of the observation group were much lower than those of the control group at each time period, P < 0.05. The number of patients with negative emotions such as anxiety and depression in the observation group was markedly less than that in the control group. The incidence of complications in the observation group was notably lower than that in the control group (4.5% vs 18%), P < 0.05. The nursing satisfaction of the observation group was significantly higher than that of the control group (93% vs 79.5%), P < 0.05. In conclusion, ultrasound-guided PICC and predictive nursing had high clinical application values in the treatment of patients with large-area severe burns.

Comparison of Two Malnutrition Assessment Scales in Predicting Postoperative Complications in Elderly Patients Undergoing Noncardiac Surgery.

Background: The present study was designed to investigate the relationship between two malnutrition assessment scales, perioperative nutrition screen (PONS) and Nutritional Risk Screening 2002 (NRS2002), with postoperative complications in elderly patients after noncardiac surgery. Methods: This was a secondary analysis of a prospective cohort study. Elderly patients (65-90 years) undergoing noncardiac surgery were enrolled in Peking University First Hospital. Malnutrition was screened by PONS and NRS2002 at the day before surgery. Multivariable analysis was employed to analyze the relationship between PONS and NRS2002 and postoperative 30-day complications. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive value of PONS and NRS2002 in predicting postoperative complications. Results: A total of 915 patients with mean age of 71.6 ± 5.2 years were consecutively enrolled from September 21, 2017, to April 10, 2019. The incidence of malnutrition was 27.3% (250/915) by PONS ≥ 1 and 53.6% (490/915) by NRS2002 ≥ 3. The overall incidence of complications within postoperative 30 days was 45.8% (419/915). After confounders were adjusted, malnutrition by PONS ≥ 1 (OR 2.308, 95% CI 1.676-3.178, P < 0.001), but not NRS2002 ≥ 3 (OR 1.313, 95% CI 0.973-1.771, P = 0.075), was related with an increased risk of postoperative complications. ROC curve analysis showed that the performances of PONS [area under the ROC curve (AUC) 0.595, 95% CI 0.558-0.633] showed very weak improvement in predicting postoperative complications than NRS2002 score (AUC 0.577, 95% CI 0.540-0.614). Conclusion: The present study found that malnutrition diagnosed by PONS was related with an increased risk of postoperative complications. The performances of PONS and NRS2002 were poor in predicting overall postoperative complications. Clinical Trial Registration: www.chictr.org.cn, identifier: ChiCTR-OOC-17012734.

Malnutrition is not related with emergence delirium in older patients after noncardiac surgery.

BACKGROUND: Delirium is one of the most common complications in older surgical patients. Although previous studies reported that preoperative malnutrition was related with postoperative delirium (POD), there was lack of evidence to illustrate the relationship between malnutrition and emergency delirium (ED). The objective of this study was to investigate the relationship between preoperative malnutrition and ED in older patients undergoing noncardiac surgery. METHODS: The study was carried out in accordance with STROBE guidelines. This was a secondary analysis of a prospective cohort study. Older patients (65-90 years) who underwent noncardiac surgery under general anesthesia were enrolled in Peking University First Hospital. RESULTS: 915 patients were enrolled. The incidence of malnutrition was 53.6 % (490/915). The incidence of emergency delirium was 41.8 % (205/490) in malnutrition group and 31.5 % (134/425) in control group, P < 0.001. After adjusting confounding factors (i.e., age, cognitive impairment, American Society of Anesthesiologists classification (ASA), duration of surgery, pain score, low body temperature and allogeneic blood transfusion), malnutrition was not associated with increased risk of emergency delirium (OR = 1.055, 95 % CI 0.767-1.452, P = 0.742). CONCLUSIONS: Malnutrition was common in older patients undergoing non-cardiac surgery, but it's not related with emergence delirium after adjusted for confounders. TRIAL REGISTRATION: Chinese Clinical Trial Registry ( http://www.chictr.org.cn ) ( ChiCTR-OOC-17,012,734 ).

Comparison of Surgical Resection and Stereotactic Radiosurgery in the Initial Treatment of Brain Metastasis.

BACKGROUND: Brain metastasis (BM) is the most common brain malignancy and a common cause of death in cancer patients. However, the relative outcome-related advantages and disadvantages of surgical resection (SR) and stereotactic radiosurgery (SRS) in the initial treatment of BM are controversial. METHOD: We systematically reviewed the English language literature up to March 2020 to compare the efficacy of SR and SRS in the initial treatment of BM. We identified cohort studies from the Cochrane Library, PubMed, and EMBASE databases and conducted a meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Twenty cohort studies involving 1,809 patients were included. Local control did not significantly differ between the SR and SRS groups overall (hazard ratio [HR] 1.02, 95% confidence interval (CI) 0.64-1.64, p = 0.92; I2 = 54%, p = 0.03) or in subgroup analyses of SR plus SRS vs. SRS alone, SR plus whole brain radiation therapy (WBRT) versus SRS plus WBRT, or SR plus WBRT versus SRS alone. Distant intracranial control did not significantly differ between the SR and SRS groups overall (HR 0.78, 95% CI 0.38-1.60, p = 0.49; I2 = 61%, p = 0.03) or in subgroup analyses of SR plus SRS versus SRS alone or SR plus WBRT versus SRS alone. In addition, overall survival (OS) did not significantly differ in the SR and SRS groups (HR 0.91, 95% CI 0.65-1.27, p = 0.57; I2 = 47%, p = 0.09) or in subgroup analyses of SR plus SRS versus SRS alone, SR plus WBRT versus SRS alone or SR plus WBRT versus SRS plus WBRT. CONCLUSION: Initial treatment of BM with SRS may offer comparable local and distant intracranial control to SR in patients with single or solitary BM. OS did not significantly differ between the SR and SRS groups in people with single or solitary BM.

Emergence delirium is associated with increased postoperative delirium in elderly: a prospective observational study.

BACKGROUND: The clinical significance of emergence delirium remains unclear. The purpose of this study was to investigate the association between emergence delirium and postoperative delirium in elderly after general anesthesia and surgery. METHODS: This prospective observational study was done in a tertiary hospital in Beijing, China. Elderly patients (65-90 years) who underwent major noncardiac surgery under general anesthesia and admitted to the postanesthesia care unit (PACU) after surgery were enrolled. Emergence delirium was assessed with the Confusion Assessment Method for the Intensive Care Unit during PACU stay. Postoperative delirium was assessed with the Confusion Assessment Method during the first 5 postoperative days. The association between emergence delirium and postoperative delirium was analyzed with a multivariable logistic regression model. RESULTS: A total of 942 patients were enrolled and 915 completed the study. Emergence delirium developed in 37.0% (339/915) of patients during PACU stay; and postoperative delirium developed in 11.4% (104/915) of patients within the first 5 postoperative days. After adjusted confounding factors, the occurrence of emergence delirium is independently associated with an increased risk of postoperative delirium (OR 1.717, 95% CI 1.078-2.735, P = 0.023). Patients with emergence delirium stayed longer in PACU and hospital after surgery, and developed more non-delirium complications within 30 days. CONCLUSIONS: Emergence delirium in elderly admitted to the PACU after general anesthesia and major surgery is independently associated with an increased risk of postoperative delirium. Patients with emergence delirium had worse perioperative outcomes. Chinese Clinical Trial Registry (chictr.org.cn) ChiCTR-OOC-17012734.

General Anesthesia versus Local Anesthesia for Deep Brain Stimulation in Parkinson's Disease: A Meta-Analysis.

BACKGROUND: Deep brain stimulation (DBS) implantation under general anesthesia (GA) is of great importance for patients with disabling off-medication symptoms or medical comorbidities. However, the relative advantages/disadvantages of routine local anesthesia (LA) surgery versus GA regarding clinical outcomes are controversial, and the safety of DBS implantation under GA is debatable. SUMMARY: We systematically reviewed the literature to compare the efficacy and safety of awake and asleep DBS surgery. We identified cohort studies from the Cochrane library, MEDLINE, and EMBASE (January 1970 to August 2019) by using Review Manager 5.3 software to conduct a meta-analysis following the PRISMA guidelines. Fourteen cohort studies involving 1,523 patients were included. The meta-analysis results showed that there were no significant differences between the GA and LA groups in UPDRSIII score improvement (standard mean difference [SMD] 0.06; 95% CI -0.16 to 0.28; p = 0.60), postoperative LEDD requirement (SMD -0.17; 95% CI -0.44 to 0.12; p = 0.23), or operation time (SMD 0.18; 95% CI -0.31 to 0.67; p = 0.47). Additionally, there was no significant difference in the incidence of adverse events (OR 0.98; 95% CI 0.53-1.80; p = 0.94), including postoperative speech disturbance and intracranial hemorrhage. However, the volume of intracranial air was significantly lower in the GA group than that in the LA group. In a subgroup analysis, there was no significant difference in clinical efficacy between the microelectrode recording (MER) and non-MER groups. We demonstrated equivalent clinical outcomes of DBS surgery between GA and LA in terms of improvement of symptoms and the incidence of adverse events. Key Messages: MER might not be necessary for DBS implantation. For patients who cannot tolerate DBS surgery while being awake, GA should be an appropriate alternative.