scholarly journals A cohort study and meta-analysis of the evidence for consideration of Lauren subtype when prescribing adjuvant or palliative chemotherapy for gastric cancer

2020 ◽  
Vol 12 ◽  
pp. 175883592093035 ◽  
Author(s):  
Kunning Wang ◽  
Enxiao Li ◽  
Rita A. Busuttil ◽  
Joseph C. Kong ◽  
Sharon Pattison ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Systemic Chemotherapy ◽  
Meta Analysis ◽  
Sensitivity Analyses ◽  
Diffuse Gastric Cancer ◽  
Lauren Classification ◽  
Significant Difference ◽  
Laurén Classification ◽  
Better Than

Background: The association between the survival or efficacy of chemotherapy and the Lauren subtype of gastric cancer (GC) remains unclear. We aimed to clarify whether patients with different Lauren subtypes have different survival after treatment with systemic chemotherapy: intestinal gastric cancer (IGC) patients survived better than patients with mixed type gastric cancer (MGC) or diffuse gastric cancer (DGC) after treatment with systemic chemotherapy. Patients & methods: Relevant studies for the meta-analysis were identified through searching Pubmed, Embase, Cochrane and Ovid up to March 2020. We also included our own prospectively collected cohort of patients that were followed over a 10-year period. Sub-group and sensitivity analyses were also performed. Results: In our prospective cohort, the overall survival (OS) of IGC patients receiving systemic chemotherapy (chemoIGC) [median OS 5.01 years, interquartile range (IQR) 2.63–6.71] was significantly higher than that of DGC patients receiving the same chemotherapy (chemoDGC) (median OS 1.33 years, IQR 0.78–3.33, p = 0.0001). After adjusting for age, gender and cancer stage, there was a significant difference in OS in patients treated with chemotherapy based on the Lauren classification of GC {hazard ratio (HR) for OS of the IGC versus DGC 0.33, [95% confidence interval (CI), 0.17–0.65; p < 0.001]}. In the IGC patients, the adjusted HR associated with chemotherapy was 0.26 (95% CI, 0.12–0.56; p = 0.001), whereas the association was 0.64 (95% CI, 0.30–1.33; p = 0.23) in the DGC patient group. In our meta-analysis, 33 studies comprising 10,246 patients treated with systemic chemotherapy (chemoIGC n = 4888, chemoDGC n = 5358) met all the selection criteria. While we accounted for much of the heterogeneity in these studies, we found that chemoIGC patients showed significantly improved OS [HR, 0.76 (95% CI, 0.71–0.82); p < 0.00001] when compared with similarly treated chemoDGC patients. Conclusion: Our results support the consideration of Lauren subtype when prescribing systemic chemotherapy for GC, particularly for MGC or DGC, which may not benefit from chemotherapy. Lauren classification should be considered to stratify chemotherapy regimens to GC patients in future clinical trials, with particular relevance to MGC or DGC, which is more difficult to treat with current regimens.

scholarly journals 1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S639-S640
Author(s):  
L W Preston Church
Keyword(s):  
Plasmodium Falciparum ◽  
Random Effects ◽  
Normal Saline ◽  
Meta Analysis ◽  
Laboratory Data ◽  
Plasmodium Falciparum Malaria ◽  
Sub Saharan Africa ◽  
Sensitivity Analyses ◽  
Double Blind ◽  
Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age &gt; 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

scholarly journals Centromere Protein I (CENP-I) Is Upregulated in Gastric Cancer, Predicts Poor Prognosis, and Promotes Tumor Cell Proliferation and Migration

2021 ◽  
Vol 20 ◽  
pp. 153303382110455
Author(s):  
Jiahui Wang ◽  
Xin Liu ◽  
Hong-jin Chu ◽  
Ning Li ◽  
Liu-ye Huang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Poor Prognosis ◽  
Cellular Function ◽  
Mesenchymal Transition ◽  
Qrt Pcr ◽  
Lauren Classification ◽  
Centromere Protein ◽  
Laurén Classification ◽  
And Migration

This study aimed to investigate the expression and cellular function of the centromeric family of proteins (CENPs), especially centromere protein I (CENP-I), in gastric cancer (GC) and identified its clinical significance and cellular functions. CENP-I expression in GC was studied by cDNA microarray, quantitative real-time PCR (qRT-PCR), and immunohistochemistry (IHC), and using datasets from The Cancer Genome Atlas (TCGA), UALCAN, and Gene Expression Omnibus (GEO) databases. Microarray and bioinformatic analyses identified upregulated CENP-A/E/F/H/I/K/P/W and HJURP in stomach adenocarcinoma (STAD), but not in signet ring cell carcinoma (SRCC). Significantly higher CENP-I mRNA expression was also confirmed in 40 pairs of GC tissues than in paired normal gastric tissues by qRT-PCR ( P<.001). IHC showed that elevated CENP-I expression was associated with higher tumor stage, lymph node invasion, increased HER2-positive rate (36.7% vs 10.0%), and intestinal Lauren classification in 69 GC samples compared to paired paracancerous normal tissues. The survival of the high-CENP-I group members was poor compared with that of the low-CENP-I group ( P = .0011). Cox univariate regression analysis identified tumor size ( P = .008), HER2 status ( P = .027), and CENP-I expression ( P = .049) were independent prognostic factors of GC. The cellular function of CENP-I was studied in MKN45 and MKN28 GC cell lines in vitro. Cell proliferation, migration, and apoptosis were determined using CCK-8, transwell assay, TUNEL assay, and flow cytometry. Our results showed that CENP-I promoted GC cell proliferation, inhibited apoptosis, facilitated cell migration, and induced epithelial–mesenchymal transition (EMT), possibly by activating the AKT pathway. CENP-I expression was correlated with genetic signatures of the proliferative subtype of GC, characterized by intestinal Lauren classification, HER2 amplification, and TP53 mutation. In conclusion, this study revealed an elevated CENP-I expression in GC, which was associated with malignant features and poor prognosis of GC patients, and identified its function in modulating cell proliferation, apoptosis, and migration.

scholarly journals Prevalence and characteristics of fever in adult and paediatric patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of 17515 patients

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249788
Author(s):  
Md Asiful Islam ◽  
Shoumik Kundu ◽  
Sayeda Sadia Alam ◽  
Tareq Hossan ◽  
Mohammad Amjad Kamal ◽  
...  
Keyword(s):  
Systematic Review ◽  
Meta Analysis ◽  
Clinical Manifestations ◽  
Sensitivity Analyses ◽  
Clinical Feature ◽  
High Grade ◽  
High Grade Fever ◽  
Paediatric Patients ◽  
Pooled Prevalence ◽  
Significant Difference

Background Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 started to spread globally since December 2019 from Wuhan, China. Fever has been observed as one of the most common clinical manifestations, although the prevalence and characteristics of fever in adult and paediatric COVID-19 patients is inconclusive. We aimed to conduct a systematic review and meta-analysis to estimate the overall pooled prevalence of fever and chills in addition to fever characteristics (low, medium, and high temperature) in both adult and paediatric COVID-19 patients. Methods The protocol of this systematic review and meta-analysis was registered with PROSPERO (CRD42020176327). PubMed, Scopus, ScienceDirect and Google Scholar databases were searched between 1st December 2019 and 3rd April 2020 without language restrictions. Both adult (≥18 years) and paediatric (<18 years) COVID-19 patients were considered eligible. We used random-effects model for the meta-analysis to obtain the pooled prevalence and risk ratio (RR) with 95% confidence intervals (CIs). Quality assessment of included studies was performed using the Joanna Briggs Institute critical appraisal tools. Heterogeneity was assessed using the I² statistic and Cochran’s Q test. Robustness of the pooled estimates was checked by different subgroups and sensitivity analyses. Results We identified 2055 studies, of which 197 studies (n = 24266) were included in the systematic review and 167 studies with 17142 adults and 373 paediatrics were included in the meta-analysis. Overall, the pooled prevalence of fever in adult and paediatric COVID-19 patients were 79.43% [95% CI: 77.05–81.80, I2 = 95%] and 45.86% [95% CI: 35.24–56.48, I2 = 78%], respectively. Besides, 14.45% [95% CI: 10.59–18.32, I2 = 88%] of the adult COVID-19 patients were accompanied with chills. In adult COVID-19 patients, the prevalence of medium-grade fever (44.33%) was higher compared to low- (38.16%) and high-grade fever (14.71%). In addition, the risk of both low (RR: 2.34, 95% CI: 1.69–3.22, p<0.00001, I2 = 84%) and medium grade fever (RR: 2.79, 95% CI: 2.21–3.51, p<0.00001, I2 = 75%) were significantly higher compared to high-grade fever, however, there was no significant difference between low- and medium-grade fever (RR: 1.17, 95% CI: 0.94–1.44, p = 0.16, I2 = 87%). 88.8% of the included studies were of high-quality. The sensitivity analyses indicated that our findings of fever prevalence for both adult and paediatric patients are reliable and robust. Conclusions The prevalence of fever in adult COVID-19 patients was high, however, 54.14% of paediatric COVID-19 patients did not exhibit fever as an initial clinical feature. Prevalence and risk of low and medium-grade fevers were higher compared to high-grade fever.

scholarly journals Is the Urokinase-type Plasminogen Activator System a Reliable Prognostic Factor in Gastric Cancer?

2006 ◽  
Vol 21 (3) ◽  
pp. 162-169 ◽  
Author(s):  
T. Luebke ◽  
S.E. Baldus ◽  
D. Spieker ◽  
G. Grass ◽  
E. Bollschweiler ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Prospective Study ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Lauren Classification ◽  
Plasminogen Activator System ◽  
Number Of Patients ◽  
Laurén Classification ◽  
Gastric Cancer Patients ◽  
Pai 1

Aim The aim of this prospective study was to evaluate the clinical and prognostic impact of immunohisto-chemically assessed uPA and PAI-1 in patients with gastric cancer. Methods This prospective study analyzed specimens obtained from 105 gastric cancer patients who underwent gastrectomy with extended lymphadenectomy. The immunohistochemical expression of uPA and PAI-1 was studied semiquantitatively in the tumor epithelium and was correlated with the clinicopathological features of each patient. Results Univariate analysis revealed no statistically significant association of uPA levels with pT and pN category (p=0.655 and 0.053, respectively), grading (p=0.374), depth of tumor invasion (p=0.665), UICC classification (p=0.21) and the Laurén classification (p=0.578). PAI-1 expression showed no statistically significant correlation with pT, pN and M category (p=0.589, 0.414, and 0.167, respectively), grading (p=0.273), and the Laurén classification (p=0.368). Only the UICC classification was significantly correlated with PAI-1 (p=0.016). Kaplan-Meier analysis revealed no significant association of uPA and PAI-1 with overall survival (p=0.0929 and 0.0870, respectively). Conclusions Our results could not verify any prognostic value of uPA and PAI-1 levels in patients with gastric carcinoma. Therefore, the uPA-system as a biologically defined prognostic marker to identify high-risk gastric cancers should be applied with caution. However, considering the number of patients involved and the borderline level of significance observed in this study, a larger number of events may have resulted in significant differences.

scholarly journals Superiority of Tumor Location-Modified Lauren Classification System for Gastric Cancer: A Multi-Institutional Validation Analysis

2018 ◽  
Vol 25 (11) ◽  
pp. 3257-3263 ◽  
Author(s):  
Lin-Yong Zhao ◽  
Jun-Jiang Wang ◽  
Yong-Liang Zhao ◽  
Xin-Zu Chen ◽  
Kun Yang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Classification System ◽  
Tumor Location ◽  
Lauren Classification ◽  
Laurén Classification

Serotonin–norepinephrine reuptake inhibitors for the prevention of migraine and vestibular migraine: a systematic review and meta-analysis

2020 ◽  
Vol 45 (5) ◽  
pp. 323-330 ◽  
Author(s):  
Fengzhi Wang ◽  
Jiaoqi Wang ◽  
Yumeng Cao ◽  
Zhongxin Xu
Keyword(s):  
Weighted Mean Difference ◽  
Meta Analysis ◽  
Mean Difference ◽  
Vestibular Migraine ◽  
Cochrane Library ◽  
Severity Scores ◽  
Significant Difference ◽  
Norepinephrine Reuptake ◽  
Better Than

Background and objectivesThe role of serotonin–norepinephrine reuptake inhibitors (SNRIs) in migraine prophylaxis has not been completely established. Current treatments for vestibular migraine (VM) are based on scarce evidence. We aimed to perform an updated review focusing on the efficacy and tolerability of SNRIs for migraine and VM prevention.MethodsWe searched the PubMed, Web of Science, and Cochrane Library databases for relevant studies. The primary outcome was migraine frequency. In the case of VM, the Dizziness Handicap Inventory (DHI) scores and Vertigo Severity Scores (VSSs) were extracted.ResultsSix randomized controlled trials involving 418 patients were analyzed. Patients receiving SNRIs had fewer migraine days than those receiving a placebo (standardized mean difference −0.38, 95% CI −0.76 to −0.01, p=0.04). The effects of SNRIs and other active drugs were comparable. In patients with VM, venlafaxine had a significant advantage over other active drugs in decreasing the VSS (weighted mean difference (MD) −1.45, 95% CI −2.11 to −0.78, p<0.0001) and the emotional domain score of the DHI (MD −2.64, 95% CI −4.97 to −0.31, p=0.03). We found no significant difference in the rate of withdrawals due to any reason or withdrawals due to side effects between SNRIs and active drugs and between SNRIs and a placebo.ConclusionsSNRIs were clinically safe and effective for migraine and VM prophylaxis, were better than a placebo, and not inferior to other active drugs. SNRIs may be a preferable choice for patients with VM with psychiatric disorders.

scholarly journals Reconstruction Methods and Complications of Esophagogastrostomy and Jejunal Interposition in Proximal Gastrectomy for Gastric Cancer: A Meta-Analysis

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Nan Du ◽  
Pei Wu ◽  
Pengliang Wang ◽  
Yuwei Du ◽  
Kai Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Lower Risk ◽  
Meta Analysis ◽  
Proximal Gastrectomy ◽  
Operating Time ◽  
Perioperative Period ◽  
Jejunal Interposition ◽  
Cochrane Library ◽  
Reconstruction Methods ◽  
Significant Difference

Background. Proximal gastrectomy is used for the treatment of primary gastric cancer by open or laparoscopic surgery in the upper third of the stomach. Esophagogastrostomy (EG) or jejunal interposition (JI) is widely used in various reconstruction methods after proximal gastrectomy. We conducted a meta-analysis of EG and JI for treatment of gastric cancer. Materials and Methods. A search of PubMed, Embase, MEDLINE, J-STAGE, and Cochrane Library identified retrospective series on EG and JI. Weight mean differences (WMDs), odds ratios (ORs), and 95% confidence intervals (CIs) were used to analyze the operation-related data and postoperative complications. Heterogeneity was evaluated by the I2 test, and potential publication bias was assessed with Egger regression tests and sensitivity analysis. Results. Eight studies were selected, and 496 patients were included. EG group benefits were 44.81 min shorter operating time (P<0.001), 56.58 mL less blood loss (P=0.03), and 7.4 days shorter hospital stay time (P<0.001) than the JI group. Between the two groups, there was no significant difference in anastomotic leakage; otherwise, the EG group had a lower risk of anastomotic stenosis (OR=0.44, 95%CI=0.20 to 0.97, P=0.04), lower risk of intestinal obstruction (OR=0.07, 95%CI=0.01 to 0.43, P=0.004), and higher risk of reflux esophagitis (OR=2.47, 95%CI=1.07 to 5.72, P=0.03). Conclusion. The results of our study indicated that EG has significant advantages during the perioperative period and in short-term outcomes compared to JI.

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