To assess the clinical efficacy and safety of neutralizing monoclonal antibodies (mABs) for outpatients with coronavirus disease 2019 (COVID‐19). PubMed, Embase, Web of Science, Cochrane Library, ...ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform (ICTRP) databases were searched from inception to July 19, 2021. Only randomized controlled trials (RCTs) that assessed the clinical efficacy and safety of neutralizing mABs in the treatment of COVID‐19 outpatients were included. The Cochrane risk‐of‐bias tool was used to assess the quality of the included RCTs. The primary outcome was the risk of COVID‐19‐related hospitalization or emergency department (ED) visits. The secondary outcomes were the risk of death and adverse events (AEs). Five articles were included, in which 3309 patients received neutralizing mAB and 2397 patients received a placebo. A significantly lower rate of hospitalization or ED visits was observed among patients who received neutralizing mABs than those who received a placebo (1.7% vs. 6.5%, odds ratios (OR): 0.26; 95% confidence interval (CI): 0.19–0.36; I2 = 0%). In addition, the rate of hospitalization was significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.24; 95% CI: 0.17−0.34; I2 = 0%). The mortality rate was also significantly lower in the patients who received neutralizing mABs than in the control group (OR: 0.16; 95% CI: 0.05−0.58; I2 = 3%). Neutralizing mABs were associated with a similar risk of any AE (OR: 0.81; 95% CI: 0.64–1.01; I2 = 52%) and a lower risk of serious AEs (OR: 0.37; 97% CI: 0.19–0.72; I2 = 45%) compared with a placebo. Neutralizing mABs can help reduce the risk of hospitalization or ED visits in COVID‐19 outpatients. For these patients, neutralizing mABs are safe and not associated with a higher risk of AEs than a placebo.
Highlights
Neutralizing monoclonal antibodies (mABs) decreased risk of hospitalization or emergence department visits in coronavirus disease 2019 (COVID‐19) outpatients.
Neutralizing mABs reduced mortality in COVID‐19 outpatients.
Neutralizing mABs had no increased risk of any adverse events (AEs) and lower risk of serious AEs.
This meta-analysis aimed to assess the usefulness of colchicine in patients with COVID-19.
PubMed, Web of Science, Ovid MEDLINE, the Cochrane Library, Embase, and Clinicaltrials.gov were searched for ...relevant randomised controlled trials (RCTs) published between database inception and November 12, 2021. Only RCTs that compared the clinical efficacy and safety of colchicine with other alternative treatments or placebos in patients with COVID-19 were included.
Overall, 7 RCTs involving 16,024 patients were included; 7,794 patients were in the study group receiving colchicine and 8,230 were in the control group receiving placebo or standard treatment. The study and control groups had similar risk of mortality (odds ratio OR, 1.00; 95% CI, 0.91-1.09; I
2
= 0%). No significant difference was observed between the study and control groups in terms of the need for non-invasive ventilation (OR, 0.92; 95% CI, 0.83-1.03; I
2
= 0%), the need for mechanical ventilation (OR, 0.64; 95% CI, 0.32-1.32; I
2
= 58%), and length of hospital stay (mean difference, −0.42 days; 95% CI, −1.95 to 1.11; I
2
= 62%). In addition, colchicine was associated with significantly higher risks of gastrointestinal adverse events (OR, 1.81; 95% CI, 1.56-2.11; I
2
= 0%) and diarrhoea (OR, 2.12; 95% CI, 1.75-2.56; I
2
= 9%).
Colchicine does not improve clinical outcomes in patients with COVID-19, so it did not support the additional use of colchicine in the treatment of patients with COVID-19.
Key message
Colchicine could not reduce the mortality of patients with COVID-19.
No significant difference was observed between the colchicine and comparators in terms of the need for non-invasive ventilation, need for mechanical ventilation, and length of hospital stay.
Colchicine was associated with a higher risk of gastrointestinal adverse events.
This meta-analysis assessed the association between vitamin D supplementation and the outcomes of critically ill adult patients. A literature search was conducted using the PubMed, Web of Science, ...EBSCO, Cochrane Library, Ovid MEDLINE, and Embase databases until March 21, 2020. We only included randomized controlled trials (RCTs) comparing the efficacy of vitamin D supplementation with placebo in critically ill adult patients. The primary outcome was their 28-day mortality. Overall, 9 RCTs with 1867 patients were included. In the pooled analysis of the 9 RCTs, no significant difference was observed in 28-day mortality between the vitamin D supplementation and placebo groups (20.4% vs 21.7%, OR, 0.73; 95% CI, 0.46-1.15; I
= 51%). This result did not change as per the method of vitamin D supplementation (enteral route only: 19.9% vs 18.2%, OR, 1.19; 95% CI, 0.88-1.57; I
= 10%; intramuscular or intravenous injection route: 25.6% vs 40.8%, OR, 0.48; 95% CI, 0.21-1.06; I
= 19%) or daily dose (high dose: 20.9% vs 19.8%, OR, 0.83; 95% CI, 0.51-1.36; I
= 53%; low dose: 15.6% vs 21.3%, OR, 0.74; 95% CI, 0.32-1.68; I
= 0%). No significant difference was observed between the vitamin D supplementation and placebo groups regarding the length of ICU stay (standard mean difference SMD, - 0.30; 95% CI, - 0.61 to 0.01; I
= 60%), length of hospital stay (SMD, - 0.17; 95% CI, - 041 to 0.08; I
= 65%), and duration of mechanical ventilation (SMD, - 0.41; 95% CI, - 081 to 0.00; I
= 72%). In conclusion, this meta-analysis suggested that the administration of vitamin D did not provide additional advantages over placebo for critically ill patients. However, additional studies are needed to confirm our findings.
We previously showed that microRNA-429 (miR-429) played an important role in epithelial–mesenchymal transition (EMT) of urothelial cell carcinoma of the bladder. We herein evaluated the expression of ...miR-429 in bladder cancer and its potential relevance to clinicopathological characteristics and patient survival. Relative expression levels of miR-429 in surgical bladder cancer tissue specimens obtained from 76 patients with bladder cancer were measured by chromogenic in situ hybridization. miR-429 expression was significantly higher in specimens from alive patients than expired patients in both of 5-year overall survival (OS) (0.59 ± 0.09 vs. 0.27 ± 0.12; p < 0.05) and 5-year recurrence-free survival (RFS) (0.63 ± 0.10 vs. 0.33 ± 0.10; p < 0.05). The univariate Cox proportional hazards analysis revealed that tumor grade, stage, and miR-429 expression were significantly associated with patient survival. In multivariate analysis, tumor stage and miR-429 expression were significantly associated with 5-year OS (hazard ratio HR 4.70, p < 0.001) and 5-year-RFS (HR 2.20, p < 0.05). The Kaplan–Meier analysis showed that patients with miR-429 expression had significantly better 5-year OS and 5-year RFS rates than those without miR-429 expression (84.4% vs. 61.4%, p < 0.05 and 71.9% vs. 45.5%, p < 0.05, respectively). miR-429 may be considered as an adjunctive prognostic marker in addition to tumor grade and stage in bladder cancer.
This study was conducted to compare the number of cases of non-airborne/droplet-transmitted notifiable infectious disease (NID) before and after COVID-19 pandemic.
This study used an open database - ...National Notifiable Diseases Surveillance System to collect the epidemiological data of NIDs. Ten fecal-oral-, six vector-borne-, four direct-contact, and four sexually-transmitted NIDs between pandemic period (defined as from January 2020 to December 2021) and the pre-pandemic period (defined as the period from January 2018 to December 2019) were included for the analysis.
Overall, the annual case number of these 24 non-airborne/droplet-transmitted NIDs was 19,186, 19,101, 19,567, and 19,863 in 2018, 2019, 2020 and 2021, respectively. The overall case number in the pandemic period was higher than those in pre-pandemic period (39,430 vs 38,287) and the monthly case number was significantly higher in pandemic period than pre-pandemic period (1643 vs 1595, p < 0.05). However, the lower case number in the pandemic period than those in pre-pandemic period was observed in overall ten fecal-oral-transmitted NIDs (1278 vs 1775), six vector-borne-NIDs (922 vs 2210), and four direct-contact transmitted NIDs (196 vs 344). In contrast, the case number of sexually-transmitted NIDs in the pandemic period was higher than those in pre-pandemic period (37,034 vs 33,958), particularly for gonorrhea (14,463 vs 8732).
Most of the fecal-oral-, vector-borne, and direct-contact transmitted NIDs had declined during pandemic in Taiwan. In contrast, gonorrhea had large increase, and other NPIs were needed.
Acacetin (5,7-dihydroxy-4′-methoxyflavone), a flavonoid compound, has anti-peroxidative and anti-inflammatory effects. The effect of acacetin on antimetastasis in human prostate cancer DU-145 cells ...was investigated. First, the result demonstrated acacetin could exhibit an inhibitory effect on the abilities of the adhesion, invasion, and migration by cell-matrix adhesion assay, wound-healing assay, and Boyden chamber assay. Data also showed acacetin could inhibit the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) involved in the downregulation of the expressions of matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (u-PA) at both the protein and mRNA levels. Next, acacetin significantly decreased the nuclear levels of nuclear factor kappa B (NF-κB), c-Fos, and c-Jun. Also, the treatment with acacetin to DU145 cells also leads to a dose-dependent inhibition on the binding ability of NF-κB and activator protein-1 (AP-1). Furthermore, the treatment of inhibitors specific for p38 MAPK (SB203580) to DU145 cells could cause reduced expressions of MMP-2, MMP-9, and u-PA. These results showed acacetin could inhibit the invasion and migration abilities of DU145 cells by reducing MMP-2, MMP-9, and u-PA expressions through suppressing p38 MAPK signaling pathway and inhibiting NF-κB- or AP-1-binding activity. These findings proved acacetin might be offered further application as an antimetastatic agent.
•Meta-analysis of efficacy and safety of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations in adults with HAP/VAP.•No significant difference in clinical cure rate between novel BL/BLI ...combinations and comparators (OR = 1.01).•No significant difference in 28-day all-cause mortality for patients receiving novel BL/BLI versus comparators (OR = 0.90).•Novel BL/BLI combinations were associated with a similar microbiological response compared with comparators (OR = 1.06).•Clinical and microbiological response of novel BL/BLIs in nosocomial pneumonia was similar to other available antibiotics.
This study assessed the efficacy and safety of novel β-lactam/β-lactamase inhibitor (BL/BLI) combinations in adult patients with hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP).
PubMed, Web of Science, the Cochrane Library, Ovid MEDLINE, Embase and EBSCO databases were searched for randomised controlled trials (RCTs) published before 13 September 2020. Only RCTs comparing the treatment efficacy of novel BL/BLI combinations with other antibiotics for HAP/VAP in adult patients were included in this integrated analysis.
Three RCTs were included and no significant difference in clinical cure rate of test of cure was observed between the novel BL/BLI combinations and comparators odds ratio (OR) = 1.01, 95% confidence interval (CI) 0.81–1.27; I2 = 35%. The 28-day all-cause mortality was 16.2% and 17.6% for patients receiving novel BL/BLI combinations and comparators, respectively, and no significant difference was noted (OR = 0.90, 95% CI 0.69–1.16; I2 = 11%). Compared with comparators, novel BL/BLI combinations were associated with a similar microbiological response (OR = 1.06, 95% CI 0.73–1.54; I2 = 64%) and a similar risk of adverse events (AEs) treatment-emergent AEs (TEAEs): OR = 1.04, 95% CI 0.83–1.30; I2 = 0%; serious AEs: OR = 1.14, 95% CI 0.79–1.63; I2 = 68%; treatment discontinuation for TEAE: OR = 0.90, 95% CI 0.62–1.31; I2 = 11%).
Clinical and microbiological responses of novel BL/BLI combinations in the treatment of HAP/VAP were similar to those of other available antibiotics. These combinations also shared a similar safety profile to comparators.
•The optimal duration of short-course antibiotic treatment for community acquired bacterial pneumonia (CABP) and whether a 5-day antibiotic course is as effective as a long-duration course (≥7 d) ...remain uncertain•The difference in the overall clinical response rates between the 5-day and longer courses (88.3% vs 88.8%, odds ratio OR, 0.95, 95% confidence interval CI, 0.70–1.28, I2 = 19%) was nonsignificant.•The microbiological eradication rates did not differ significantly between the groups, at 94.8% and 95.8% in the 5-day and longer courses groups, respectively (OR, 0.84, 95% CI, 0.38–1.87, I2 = 0%).•The 5-day and longer course antibiotics were associated with similar risks of adverse events and all-cause mortality•Five-day treatment and longer antibiotic courses for CABP yield similar clinical and microbiological responses and exhibit similar safety profiles.
This systematic review and meta-analysis of randomized controlled trials (RCTs) investigated whether the clinical efficacy of a 5-day antibiotic course is comparable to that of a longer (≥7 d) course for treating adults with community-acquired bacterial pneumonia (CABP).
The PubMed, Web of Science, Cochrane Library, Ovid MEDLINE, and Embase. were searched before January 18, 2020. RCTs comparing the efficacy of a 5-day antibiotic course with a longer course (≥7 d) for CABP treatment were included. Primary outcomes included the clinical response, microbiological response, and risk of adverse events (AEs).
In this meta-analysis, 7 RCTs were included, and the 5-day antibiotic courses group, and a longer course group comprised 1499 and 1522 patients, respectively. The difference in the overall clinical response rates between the 5-day and longer courses (88.3% vs 88.8%, odds ratio OR, 0.95, 95% confidence interval CI, 0.70–1.28, I2 = 19%) was nonsignificant. Additionally, the microbiological eradication rates did not differ significantly between the groups, at 94.8% and 95.8% in the 5-day and longer courses groups, respectively (OR, 0.84, 95% CI, 0.38–1.87, I2 = 0%). Finally, all-cause mortality did not differ between the 2 groups (OR, 0.91, 95% CI, 0.31–2.66, I2 = 0%).
Five-day treatment and longer antibiotic courses for CABP yield similar clinical and microbiological responses and exhibit similar safety profiles.
Inflammatory tumor microenvironments play pivotal roles in the development of cancer. Inflammatory cytokines such as CXCL1/GROα exert cancer-promoting activities by increasing tumor angiogenesis. ...However, whether CXCL1/GROα also plays a role in the progression of prostate cancer, particularly in highly invasive castration-resistant prostate cancer (CRPC), has not been investigated. We explored whether CXCL1/GROα enhances cell migration and invasion in PC-3 and DU145 CRPC. Induction of PC-3 and DU145 cancer progression by CXCL1/GROα is associated with increased AKT activation and IκB kinase α (IKKα) phosphorylation, resulting in nuclear factor-kappaB (NF-κB) activation. Activated NF-κB interacts with histone deacetylase 1 (HDAC1) to form a gene-silencing complex, which represses the expression of fibulin-1D by decreasing the acetylation of histone H3 and H4 on the NF-κB-binding site of the fibulin-1D promoter. Blockade of AKT2 by small hairpin RNA (shRNA) decreases IKKα phosphorylation, NF-κB nuclear translocation and cell migration, indicating that AKT is required in CXCL1/GROα-mediated NF-κB activation and cell migration. In addition, NF-κB and HDAC1 shRNA decrease the effect of CXCL1/GROα on fibulin-1D downregulation, migration and invasion, suggesting that the NF-κB/HDAC1 complex is also involved in CXCL1/GROα-mediated cancer progression. Our findings provide the first evidence that CXCL1/GROα decreases fibulin-1D expression in prostate cancer cells and also reveals novel insights into the mechanism by which CXCL1/GROα regulates NF-κB activation through the AKT pathway. Our results also clearly establish that co-operation of NF-κB and HDAC1 regulates fibulin-1D expression by epigenetic modification. Our study suggests that inhibition of CXCL1/GROα-mediated AKT/NF-κB signaling may be an attractive therapeutic target for CRPC.
•Tocilizumab does not provide a survival benefit for patients with COVID-19.•Tocilizumab reduce the risk of mechanical ventilation and ICU admission.•Tocilizumab had no more adverse events compared ...with standard of care.
This systematic review and meta-analysis of randomized controlled trials (RCTs) aimed to investigate the clinical efficacy and safety of tocilizumab for treating patients with COVID-19.
The PubMed, Embase, Cochrane Library, Clinicaltrials.gov, WHO International Clinical Trials Registry Platform and the preprint server of medRxiv.org were searched from their inception to February 20, 2021. Only RCTs that compared the treatment efficacy and safety of tocilizumab with the placebo or the standard of care for adult patients with COVID-19 were included in this meta-analysis. The primary outcome was 28-day mortality.
This meta-analysis included eight RCTs which enrolled a total of 6314 patients for randomization, in which 3267 and 3047 patients were assigned to the tocilizumab and control groups, respectively. The mortality at day 28 was 24.4% and 29.9% in patients in the tocilizumab and control groups, respectively, meaning there was no significant difference observed between these two groups (OR, 0.92; 95% CI, 0.66–1.28; I2 = 62). This finding did not change in the subgroup analysis according to the initial use of MV or steroid while enrollment. The patients receiving tocilizumab had a lower rate of mechanical ventilation (MV) and intensive care unit (ICU) admission at day 28 compared with the control group (MV use: OR, 0.75; 95% CI, 0.62–0.90; I2 = 11; ICU admission: OR, 0.51; 95% CI, 0.28–0.92; I2 = 30). There were no significant differences between these two treatment groups in terms of the risk of treatment-emergent adverse events (AEs) (OR, 1.03; 95% CI, 0.71–1.49; I2 = 43), serious AEs (OR, 0.86; 95% CI, 0.67–1.12; I2 = 0) or infection (OR, 0.87; 95% CI, 0.63–1.20; I2 = 0).
Tocilizumab does not provide a survival benefit for patients with COVID-19, but it may help reduce the risk of MV and ICU admission. In addition, tocilizumab is a safe agent to use for the treatment of COVID-19.
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