A systematic review and meta-analysis of glucocorticoids treatment in severe COVID-19: methylprednisolone versus dexamethasone.

OBJECTIVE: The preferred agent of glucocorticoids in the treatment of patients with severe COVID-19 is still controversial. This study aimed to compare the efficacy and safety of methylprednisolone and dexamethasone in the treatment of patients with severe COVID-19. METHODS: By searching the electronic literature database including PubMed, Cochrane Central Register of Controlled Trials, and Web of Science, the clinical studies comparing methylprednisolone and dexamethasone in the treatment of severe COVID-19 were selected according to the inclusion criteria and exclusion criteria. Relevant data were extracted and literature quality was assessed. The primary outcome was short-term mortality. The secondary outcomes were the rates of ICU admission and mechanical ventilation, PaO2/FiO2 ratio, plasma levels of C-reactive protein (CRP), ferritin, and neutrophil/lymphocyte ratio, hospital stay, and the incidence of severe adverse events. Statistical pooling applied the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95% confidence interval (CI). Meta-analysis was performed using Review Manager 5.1.0. RESULTS: Twelve clinical studies were eligible, including three randomized controlled trials (RCTs) and nine non-RCTs. A total of 2506 patients with COVID-19 were analyzed, of which 1242 (49.6%) received methylprednisolone and 1264 (50.4%) received dexamethasone treatment. In general, the heterogeneity across studies was significant, and the equivalent doses of methylprednisolone were higher than that of dexamethasone. Our meta-analysis showed that methylprednisolone treatment in severe COVID-19 patients was related to significantly reduced plasma ferritin and neutrophil/lymphocyte ratio compared with dexamethasone, and that no significant difference in other clinical outcomes between the two groups was found. However, subgroup analyses of RCTs demonstrated that methylprednisolone treatment was associated with reduced short-term mortality, and decreased CRP level compared with dexamethasone. Moreover, subgroup analyses observed that severe COVID-19 patients treated with a moderate dose (2 mg/kg/day) of methylprednisolone were related to a better prognosis than those treated with dexamethasone. CONCLUSIONS: This study showed that compared with dexamethasone, methylprednisolone could reduce the systemic inflammatory response in severe COVID-19, and its effect was equivalent to that of dexamethasone on other clinical outcomes. It should be noted that the equivalent dose of methylprednisolone used was higher. Based on the evidence of subgroup analyses of RCTs, methylprednisolone, preferably at a moderate dose, has an advantage over dexamethasone in the treatment of patients with severe COVID-19.

Effects of different doses of methylprednisolone therapy on acute respiratory distress syndrome: results from animal and clinical studies.

BACKGROUND: The optimal dose of glucocorticoids for acute respiratory distress syndrome (ARDS) is uncertain. This study aimed to evaluate the effects of different doses of methylprednisolone on sepsis-induced acute lung injury (ALI) rats and a cohort of moderate and severe ARDS patients. METHODS: ALI rats, challenged with lipopolysaccharide, were randomly received intraperitoneal injection of normal saline (model group) and different doses of methylprednisolone (0.5, 2, 8 mg/kg, named as low-, moderate- and high-dose group, respectively) for 5 days. The body weight changes of rats, inflammatory factors in bronchoalveolar lavage fluid (BALF), lung wet/dry ratio, histopathological score, and the mRNA expressions of glucocorticoid receptor α (GRα), GRß and nuclear factor-κB (NF-κB) were measured. Forty moderate and severe ARDS patients were treated with standard of care or plus different doses of methylprednisolone (40, 80, 120 mg/day, named as low-, moderate- and high-dose group, respectively) for 5 days. Clinical outcomes were PaO2/FiO2 ratio and C-reactive protein (CRP) level at day 5, intubation rate, hospital stay, 28-day mortality, and adverse events rate. RESULTS: In animal experiment, different doses of methylprednisolone could increase the body weight of rats, and reduce inflammatory factors in BALF and the degree of lung injury compared with model group. The efficacy of methylprednisolone at moderate-dose was better than that at low-dose, but was equivalent to that at high-dose, which was consistent with the differential changes in the mRNA expression of GRα, GRß and NF-κB. In clinical study, the moderate-dose group was associated with higher PaO2/FiO2 ratio and lower CRP level. No significant difference in other clinical outcomes among groups was detected. CONCLUSIONS: This study showed that the efficacy of methylprednisolone in ARDS treatment was not always dose-dependent due to the differential regulation of related receptors. The moderate-dose of methylprednisolone may be the potential optimal dose for ARDS treatment, which needs to be further verified by larger clinical trials.

Effects of different doses of methylprednisolone on clinical outcomes in patients with severe community-acquired pneumonia: a study protocol for a randomized controlled trial.

BACKGROUND: The specific use of methylprednisolone in severe community-acquired pneumonia (SCAP) has not yet formed a consensus. It is not clear whether the clinical efficacy of methylprednisolone in SCAP is dose-dependent, and how to balance the best efficacy with the least complications. The aim of this study is to evaluate the efficacy and safety of different doses of methylprednisolone in the adjuvant treatment for patients with SCAP. METHODS/DESIGN: This is a prospective, randomized, double-blind, parallel group, placebo-controlled trial to evaluate the efficacy and safety of different doses of methylprednisolone in the adjuvant treatment for patients with SCAP. Patients with diagnosed SCAP are randomized to the following four groups at a 1:1:1:1 ratio: group 1 (control group)-standard ICU patient care+100ml of normal saline once a day for 5 days; group 2-standard ICU patient care+40mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days; group 3-standard ICU patient care+80mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days; and group 4-standard ICU patient care+120mg of methylprednisolone (dissolved in normal saline with a final volume of 100ml) once a day for 5 days. The primary outcome is PaO2/FiO2 ratio at day 5 following randomization. The secondary outcomes are 28-day mortality, ventilator-free days at 28 days, mechanical ventilation duration at 28 days, endotracheal intubation rate, time for temperature recovery, duration of vasopressors use, serum CRP and interleukin-6 level at day 5 following randomization, hospital stay, frequency of nosocomial infections, gastrointestinal hemorrhage, and hyperglycemia. DISCUSSION: The results of our study may find the optimal dose of glucocorticoid in the adjuvant treatment of SCAP and provide evidence-based proof for clinicians to treat patients with SCAP. Since coronavirus disease 2019 (COVID-19) also belongs to community-acquired pneumonia, perhaps the results of our study will help to determine the appropriate dose of methylprednisolone in COVID-19 treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100045056 . Registered on 4 April 2021.

The roles of methylprednisolone treatment in patients with COVID-19: A systematic review and meta-analysis.

The roles of methylprednisolone in treatment of patients with COVID-19 remain unclear. The aim of this study was to evaluate the efficacy and safety of methylprednisolone in treatment of COVID-19 patients. PubMed, Cochrane and Web of Science were searched for studies comparing methylprednisolone and no glucocorticoids treatment in patients with COVID-19. Statistical pooling was reported as risk ratio (RR) or mean difference (MD) with corresponding 95 % confidence interval (CI). Thirty-three studies were eligible, including 5 randomized trials and 28 observational studies. Meta-analysis showed that compared with no glucocorticoids, methylprednisolone in treatment of COVID-19 patients was associated with reduced short-term mortality (RR 0.73; 95% CI 0.60-0.89), less need for ICU admission (RR 0.77; 95% CI 0.66-0.91) and mechanical ventilation (RR 0.69; 95% CI 0.57-0.84), increased 28-day ventilator-free days (MD 2.81; 95% CI 2.64-2.97), without increasing risk of secondary infections (RR 1.04; 95% CI 0.82-1.32), but could prolong duration of viral shedding (MD 1.03; 95% CI 0.25-1.82). Subgroup analyses revealed that low-dose (≤2mg/kg/day) methylprednisolone treatment for ≤ 7 days in severe COVID-19 patients was associated with relatively better clinical outcomes, without increasing duration of viral shedding. Compared with no glucocorticoids, methylprednisolone treatment in COVID-19 patients is associated with reduced short-term mortality and better clinical outcomes, without increasing secondary infections, but could slightly prolong duration of viral shedding. Patients with severe COVID-19 are more likely to benefit from short-term low-dose methylprednisolone treatment (1-2 mg/kg/day for ≤ 7 days).

MicroRNA-381-3p signatures as a diagnostic marker in patients with sepsis and modulates sepsis-steered cardiac damage and inflammation by binding HMGB1.

Immune response imbalance and cardiac dysfunction caused by sepsis are the main reasons for death in sepsis. This study aimed to confirm the expression and diagnostic possibility of microRNA-381-3p (miR-381-3p) and its mechanism in sepsis. Quantitative real-time PCR (qRT-PCR) and receiver operating characteristic (ROC) were used to reveal the levels and clinical significance of miR-381-3p. Pearson correlation was conducted to provide the correlations between miR-381-3p and several indexes of sepsis. The H9c2 cell models were constructed by lipopolysaccharide (LPS), and cecal ligation and puncture (CLP) was applied to establish the Sprague-Dawley (SD) rat models. Cell Counting Kit-8 (CCK-8) and flow cytometry were the methods to detect the cell viability and death rate of H9c2. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the concentration of inflammatory cytokines. The target gene of miR-381-3p was validated via the luciferase report system. The low expression of miR-381-3p was found in the serum of patients with sepsis. The lessened miR-381-3p could be a marker in the discrimination of sepsis patients. Overexpression of miR-381-3p could repress the mRNA expression of HMGB1, inhibit the cell apoptosis and inflammatory response, and motivate the viability of sepsis cells. At the same time, enhanced miR-381-3p promoted the inhibition of inflammation and cardiac dysfunction in the rat model of sepsis. Collectively, reduced levels of serum miR-381-3p can be used as an index to detect sepsis patients. MiR-381-3p restored the inflammatory response and myocardial dysfunction caused by sepsis via HMGB1.

The roles of noninvasive mechanical ventilation with helmet in patients with acute respiratory failure: A systematic review and meta-analysis.

OBJECTIVE: To compare the safety and effectiveness between helmet and face mask noninvasive mechanical ventilation (NIMV) in patients with acute respiratory failure (ARF). METHODS: English databases included PubMed, EMBASE, Cochrane Central Register of Controlled Trials and Web of Science. Chinese databases involved Wanfang Data, China Knowledge Resource Integrated Database and Chinese Biological Medicine Database. Randomized controlled trials (RCTs) comparing helmet and face mask NIMV for patients with ARF were searched. Meta-analysis was performed using Review manager 5.1.0. RESULTS: Twelve trials with a total of 569 patients were eligible. Our meta-analysis showed that, comparing with face mask, helmet could significantly decrease the incidences of intolerance [risk ratio (RR) 0.19; 95% confidence interval (CI) 0.09-0.39], facial skin ulcer (RR 0.19; 95% CI 0.08-0.43) and aerophagia (RR 0.15; 95% CI 0.06-0.37), reduce respiratory rate [mean difference (MD) -3.10; 95% CI -4.85 to -1.34], intubation rate (RR 0.39; 95% CI 0.26-0.59) and hospital mortality (RR 0.62; 95% CI 0.39-0.99) in patients with ARF, and improve oxygenation index in patients with hypoxemic ARF (MD 55.23; 95% CI 31.37-79.09). However, subgroupanalysis for hypercapnic ARF revealed that PaCO2 was significantly reduced in face mask group compared with helmet group (MD 5.34; 95% CI 3.41-7.27). CONCLUSION: NIMV with helmet can improve the patient's tolerance, reduce adverse events, increase oxygenation effect, and decrease intubation rate and hospital mortality comparing to face mask. However, the low number of patients from included studies may preclude strong conclusions. Large RCTs are still needed to provide more robust evidence.

[Meta-analysis of clinical efficacy of Helmet non-invasive ventilation and oxygen therapy on patients with hypoxemic respiratory failure].

OBJECTIVE: To systematically evaluate the clinical efficacies of Helmet non-invasive ventilation and oxygen therapy on patients with hypoxemic respiratory failure. METHODS: The randomized controlled trials (RCTs) for comparison of efficacy between Helmet non-invasive ventilation and oxygen therapy for treatment of patients with hypoxemic respiratory failure published by Wanfang database, China National Knowledge Infrastructure (CNKI), China Biology Medicine (CBM), PubMed, Embase, Cochrane Library and Web of Science were retrieved. The retrieval time was from the establishment of database to February 1st, 2019. The indexes of the study outcomes included oxygenation index, arterial partial pressure of carbon dioxide (PaCO2), endotracheal intubation rate, hospital mortality and intolerance rate. Literature search and data extraction was performed separately by two researchers. Quality assessment of literature was conducted according to the risk of bias criterion provided by Cochrane collaboration net. The extractive data were Meta-analyzed by RevMan 5.1.0. Funnel plot and Egger regression analysis was employed to detect publication bias. RESULTS: Six RCTs including 5 English studies and 1 Chinese study were selected. Finally, 547 patients were enrolled, with 270 patients in Helmet non-invasive ventilation group and 277 in oxygen therapy group. The study quality assessment revealed that the overall risk of bias was low, and no publication bias was detected by the funnel plot and Egger regression analysis. Meta-analysis showed that the oxygenation index in Helmet non-invasive ventilation group was significantly higher than that in oxygen therapy group [mean difference (MD) = 73.47, 95% confidence interval (95%CI) was 52.01 to 94.92, P = 0.000 01], and PaCO2 (MD = -2.46, 95%CI was -4.54 to -0.39, P = 0.02), endotracheal intubation rate [relative risk ratio (RR) = 0.38, 95%CI was 0.20 to 0.73, P = 0.004] and hospital mortality (RR = 0.35, 95%CI was 0.19 to 0.65, P = 0.000 8) in Helmet non-invasive ventilation group were significantly lower than those in oxygen therapy group. There was no significant difference in patient's intolerance between the two groups (RR = 2.38, 95%CI was 0.74 to 7.67, P = 0.15). CONCLUSIONS: Compared with oxygen therapy, the Helmet non-invasive ventilation used for treatment of patients with hypoxemic respiratory failure can effectively improve the oxygenation index, decrease the PaCO2, reduce the endotracheal intubation rate and hospital mortality, and the patients are well tolerated to the Helmet method.

High inspired oxygen versus low inspired oxygen for reducing surgical site infection: a meta-analysis.

To perform a meta-analysis of published literature to assess the role of high-concentration inspired oxygen in reducing the incidence of surgical site infections (SSIs) following all types of surgery, a comprehensive search for published randomized controlled trials (RCTs) comparing high- with low-concentration inspired oxygen for SSIs was performed. The related data were extracted by two independent authors. The fixed and random effects methods were used to combine data. Twelve RCTs involving 6750 patients were included. Our pooled result found that no significant difference in the incidence of SSIs was observed between the two groups, but there was high statistic heterogeneity across the studies [risk ratio (RR): 0·91; 95% confidence interval (CI): 0·72-1·14; P = 0·40; I2 = 54%]. The sensitivity analysis revealed the superiority of high-concentration oxygen in decreasing the SSI rate (RR: 0·86; 95% CI: 0·75-0·98; P = 0·02). Moreover, a subgroup analysis of studies with intestinal tract surgery showed that patients experienced less SSI when high-concentration inspired oxygen was administrated (RR: 0·53; 95% CI: 0·37-0·74; P = 0·0003). Our study provided no direct support for high-concentration inspired oxygen in reducing the incidence of SSIs in patients undergoing all types of surgery.

Subcuticular sutures versus staples for skin closure after cesarean delivery: a meta-analysis.

OBJECTIVE: To compare the clinical efficacy between subcuticular sutures and staples for skin closure after cesarean delivery. METHODS: PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and Web of Science were searched. Only RCTs comparing subcuticular sutures to staples following cesarean delivery were included. The primary outcome was the incidence of wound complications, consisting of wound infection, wound separation, hematoma and seroma. Risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI) was calculated. RESULTS: Ten RCTs were included in this analysis. Subcuticular sutures were associated with significantly decreased incidence of wound complications compared to staples (RR 1.88, 95% CI 1.45-2.45). The operation time was significantly shortened when closure with staples was performed (MD -8.66 min, 95% CI -10.90 to -6.42). The two groups were comparable regarding cosmetic outcome at 6-8 weeks postoperatively, whereas subcuticular sutures were associated with a better cosmesis at 6-12 months postoperatively. There were no significant differences between groups in terms of hospital stay, postoperative pain and patient satisfaction. CONCLUSIONS: Compared with staples following cesarean delivery, subcuticular sutures are associated with decreased risk of wound complications and better long-term cosmetic outcome, but slightly prolong duration of surgery.

Controlled-release dinoprostone insert versus Foley catheter for labor induction: a meta-analysis.

OBJECTIVE: To compare the effectiveness and safety of controlled-release dinoprostone insert with Foley catheter balloon for cervical ripening and labor induction. METHODS: PubMed, Cochrane Central Register of Controlled Trials, Web of Science, and China Knowledge Resource Integrated Database were searched. Only randomized controlled trials comparing controlled-release dinoprostone insert with Foley catheter balloon were included. Risk ratio (RR) or mean difference (MD) with 95% confidence interval (CI) was calculated. RESULTS: Six studies were included with 731 women received dinoprostone insert and 722 Foley catheter. Time from induction to delivery was significantly shortened in dinoprostone insert group compared to Foley catheter group (MD 5.73 h, 95% CI 1.26-10.20). There were no significant differences in vaginal delivery within 24 h (RR 0.75, 95% CI 0.43-1.30) or cesarean section (RR 0.94, 95% CI 0.80-1.12) between two ripening methods. Dinoprostone insert was related with increased rate of excessive uterine contraction (RR 0.07, 95% CI 0.03-0.19), but less oxytocin use (RR 1.86, 95% CI 1.25-2.77) when compared with Foley catheter. CONCLUSIONS: Induction of labor with controlled-release dinoprostone insert seems to be more effective than Foley catheter. However, the former method causes excessive uterine contraction more frequently.

RC-3095, a gastrin-releasing peptide receptor antagonist, synergizes with gemcitabine to inhibit the growth of human pancreatic cancer CFPAC-1 in vitro and in vivo.

OBJECTIVES: Pancreatic cancer remains a lethal disease. In this study, we investigated the efficacy of a combination of gastrin-releasing peptide receptor antagonist RC-3095 and gemcitabine on pancreatic cancer CFPAC-1. METHODS: The antiproliferation effects of RC-3095, gemcitabine, or the combination on pancreatic cancer were monitored in vitro. Nude mice bearing xenografts of CFPAC-1 cell received injections of the vehicle (control), RC-3095 (20 µg, subcutaneously, daily), gemcitabine (15 mg/kg, intraperitoneally, every 3 days), or the combination of RC-3095 and gemcitabine for 4 weeks. The histological changes and protein expression were tested using immunohistochemistry and Western blotting. RESULTS: Treatment with the combination in culture exhibited a powerful inhibition effect on CFPAC-1 cell proliferation. In xenograft mice model, RC-3095 or gemcitabine significantly reduced the volume and weight of tumors after 4 weeks of treatment, as compared with controls. The combination more potently inhibited the tumor growth than either agent used individually. Immunohistochemistry and Western blotting showed gastrin-releasing peptide receptor/bombesin receptor subtype-3 positive cells and protein expression in tumors decreased by treatment with RC-3095 or gemcitabine alone or greater in combination. CONCLUSIONS: Our data suggested that the combination could be considered for the possible new approaches for treatment of pancreatic cancers.

External stent versus no stent for pancreaticojejunostomy: a meta-analysis of randomized controlled trials.

BACKGROUND: The effectiveness of an external pancreatic duct stent for reduction of the pancreatic fistula after pancreaticoduodenectomy remains controversial. METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials were searched for eligible randomized controlled trials (RCTs). Reviews of each trial were conducted and data were extracted. The primary outcome was pancreatic fistula. Statistical pooling used the fixed or random effects model and reported as risk ratio (RR) or mean difference (MD) with the corresponding 95 % confidence intervals (CI). RESULTS: Four RCTs including a total of 416 patients were detected. Methodological quality assessment revealed a better quality of all analyzed trials. Placing an external stent across pancreaticojejunal anastomosis could significantly reduce the incidence of pancreatic fistula (RR = 0.57, 95 % CI = 0.41-0.80, P = 0.001, I (2) = 0 %), overall morbidity (RR = 0.79, 95 % CI = 0.64-0.98, P = 0.03), and the length of hospital stay (MD = -3.98 days, 95 % CI = -6.42 to -1.54, P = 0.001, I (2) = 13 %). No significant difference was found in terms of hospital mortality, delayed gastric emptying, operation time, operative blood loss, blood replacement, and reoperation rate. CONCLUSIONS: This meta-analysis provides compelling evidence that the application of an external pancreatic duct stent after pancreaticoduodenectomy can decrease the incidence of pancreatic leakage when compared with no stent. Moreover, the external drainage of pancreatic juice is associated with lower postoperative overall morbidity and shorter hospital stay.