Background Coronavirus disease 2019 (COVID-19), a highly infectious disease, has been rapidly spreading all over the world and remains a great threat to global public health. Patients diagnosed with severe or critical cases have a poor prognosis. Hence, it is crucial for us to identify potentially severe or critical cases early and give timely treatments for targeted patients. In the clinical practice of treating patients with COVID-19, we have observed that the neutrophil-to-lymphocyte ratio (NLR) of severe patients is higher than that in mild patients. We performed this systematic review and meta-analysis to evaluate the predictive values of NLR on disease severity and mortality in patients with COVID-19. Methods We searched PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases to identify eligible studies (up to August 11, 2020). Two authors independently screened studies and extracted data. The methodological quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Results Thirteen studies involving 1579 patients reported the predictive value of NLR on disease severity. The pooled sensitivity (SEN), specificity (SPE) and area under curve (AUC) were 0.78 (95% CI 0.70–0.84), 0.78 (95% CI 0.73–0.83) and 0.85 (95% CI 0.81–0.88), respectively. Ten studies involving 2967 patients reported the predictive value of NLR on mortality. The pooled SEN, SPE and AUC were 0.83 (95% CI 0.75–0.89), 0.83 (95% CI 0.74–0.89) and 0.90 (95% CI 0.87–0.92), respectively. Conclusions NLR has good predictive values on disease severity and mortality in patients with COVID-19 infection. Evaluating NLR can help clinicians identify potentially severe cases early, conduct early triage and initiate effective management in time, which may reduce the overall mortality of COVID-19. Trial registry This meta-analysis was prospectively registered on PROSPERO database (Registration number: CRD42020203612).

BackgroundRegional citrate or heparin is often prescribed as an anticoagulant for continuous renal replacement therapy (CRRT). However, their efficacy and safety remain controversial. Therefore, we performed this meta-analysis to compare these two agents and to determine whether the currently available evidence is sufficient and conclusive by using trial sequential analysis (TSA).MethodsWe searched for relevant studies in PubMed, Embase, the Cochrane Library databases and the China National Knowledge Infrastructure (CNKI) Database from database inception until September 2015. We selected randomized controlled trials comparing regional citrate with heparin in adult patients with acute kidney injury (AKI) who were prescribed CRRT.ResultsFourteen trials (n = 1134) met the inclusion criteria. Pooled analyses showed that there was no difference in mortality between the regional citrate and heparin groups (relative risk (RR) 0.97, 95 % confidence interval (CI) 0.84, 1.13, P > 0.05), which was confirmed by TSA. Compared with heparin, regional citrate significantly prolonged the circuit life span in the continuous venovenous haemofiltration (CVVH) subgroup (mean difference (MD) 8.18, 95 % CI 3.86, 12.51, P < 0.01) and pre-dilution subgroup (MD 17.51, 95 % CI 9.85, 25.17, P < 0.01) but not in the continuous venovenous haemodiafiltration (CVVHDF) subgroup (MD 28.60, 95 % CI −3.52, 60.73, P > 0.05) or post-dilution subgroup (MD 13.06, 95 % CI −2.36, 28.48, P > 0.05). However, the results were not confirmed by TSA. A reduced risk of bleeding was found in the regional citrate compared with the systemic heparin group (RR 0.31, 95 % CI 0.19, 0.51, P < 0.01) and TSA provided conclusive evidence. Fewer episodes of heparin-induced thrombocytopoenia (HIT) (RR 0.41, 95 % CI 0.19, 0.87, P = 0.02) and a greater number of episodes of hypocalcaemia (RR 3.96, 95 % CI 1.50, 10.43, P < 0.01) were found in the regional citrate group. However, TSA did not provide conclusive evidence.ConclusionIn adult patients with AKI, there is no difference in mortality between the regional citrate and heparin treated groups. However, regional citrate is more efficacious in prolonging circuit life span and reducing the risk of bleeding and should be recommended as the priority anticoagulant for critically ill patients who require CRRT.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1299-0) contains supplementary material, which is available to authorized users.

Objective To compare the acute effects of 0.9% saline versus a balanced electrolyte solution on acute kidney injury in a rat model of sepsis. Design Controlled laboratory experiment. Setting University laboratory. Subjects Sixty adult, male Sprague-Dawley rats. Interventions We induced sepsis by cecal ligation and puncture and randomized animals to receive fluid resuscitation with either 0.9% saline or Plasma-Lyte solution for 4 hours after 18 hours of cecal ligation and puncture (10 mL/kg in the first hour and 5 mL/kg in the next 3 hr). Blood and urine specimens were obtained from baseline, 18 hours after cecal ligation and puncture, immediately after 4 hours fluid resuscitation, and 24 hours later. We measured blood gas, plasma electrolytes, creatinine, interleukin-6, cystatin C, and neutrophil gelatinase-associated lipocalin concentrations. We also analyzed urine for cystatin C and neutrophil gelatinase-associated lipocalin. We used Risk, Injury, Failure, Loss and End-stage criteria for creatinine to assess severity of acute kidney injury. We observed all animals for survival up to 1 day after resuscitation. Surviving animals were killed for kidney histology. Finally, we carried out an identical study in 12 healthy animals. Measurements and Main Results Compared with Plasma-Lyte, 0.9% saline resuscitation resulted in significantly greater blood chloride concentrations (p < 0.05) and significantly decreased pH and base excess. Acute kidney injury severity measured by RIFLE criteria was increased with 0.9% saline compared with Plasma-Lyte resuscitation (p < 0.05), and these results were consistent with kidney histology and biomarkers of acute kidney injury. Twenty-four-hour survival favored Plasma-Lyte resuscitation (76.6% vs 53.3%; p = 0.03). Finally, in healthy animals, we found no differences between fluids and no evidence of acute kidney injury. Conclusion Volume resuscitation with Plasma-Lyte resulted in less acidosis and less kidney injury and improved short-term survival when compared with 0.9% saline in this experimental animal model of sepsis.

Objectives Although blood purification improves outcomes in animal studies of sepsis, results of clinical trials have been mixed. We conducted a systematic review and meta-analysis of randomized trials to determine the association between various blood purification techniques and all-cause mortality in humans with sepsis. Data Sources We searched for relevant studies in MEDLINE, EMBASE, and the Cochrane Library database from January 1966 until May 2012. Study Selection Inclusion required a diagnosis of sepsis and comparison of blood purification techniques including hemofiltration, hemoperfusion, plasma exchange, or hemodialysis with no blood purification (control group). Data Extraction Two authors independently selected studies and extracted data. Summary statistics, risk ratios (RRs), and CIs were calculated using random-effects modeling. Study quality was assessed using Jadad score, and publication bias using funnel plots and Egger’s statistic. Data Synthesis Overall, blood purification decreased mortality compared to no blood purification (35.7% versus 50.1%; RR, 0.69; 95% CI, 0.56–0.84; p < 0.001; 16 trials, n=827). However, these results were driven mainly by hemoperfusion (RR, 0.63; 95% CI, 0.50–0.80; p < 0.001; 10 trials, n=557), and plasma exchange (RR, 0.63; 95% CI, 0.42–0.96; p = 0.03; 2 trials, n=128). Pooling of all trials of blood purification for treatment of sepsis was no longer associated with lower mortality (RR, 0.89; 95% CI, 0.71–1.13; p = 0.36; 8 trials, n=457) after excluding trials using polymyxin B hemoperfusion. Conclusions Blood purification techniques including hemoperfusion, plasma exchange, and hemofiltration with hemoperfusion were associated with lower mortality in patients with sepsis. These results were mainly influenced by studies using polymyxin B hemoperfusion from Japan.

BackgroundPotential benefits of subglottic secretion suction for preventing ventilator-associated pneumonia (VAP) are not fully understood.MethodsWe searched Cochrane Central, PubMed, and EMBASE up to March 2016 to identify randomized controlled trials (RCTs) that compared subglottic secretion suction versus non-subglottic secretion suction in adults with mechanical ventilation. Meta-analysis was conducted using Revman 5.3, trial sequential analysis (TSA) 0.9 and STATA 12.0. The primary outcome was incidence of VAP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) was used to evaluate the level of evidence.ResultsTwenty RCTs (N = 3544) were identified. Subglottic secretion suction was associated with reduction of VAP incidence in four high quality trials (relative risk (RR) 0.54, 95 % confidence interval (CI) 0.40–0.74; p < 0.00001) and in all trials (RR = 0.55, 95 % CI 0.48– 0.63; p < 0.00001). Sensitivity analyses did not show differences in the pooled results. Additionally, the results of the above-mentioned analyses were confirmed in TSA. GRADE level was high. Subglottic secretion suction significantly reduced incidence of early onset VAP, gram-positive or gram-negative bacteria causing VAP, and duration of mechanical ventilation. It delayed the time-to-onset of VAP. However, no significant differences in late onset VAP, intensive care unit (ICU) mortality, hospital mortality, or ICU length of stay were found.ConclusionsSubglottic secretion suction decreased VAP incidence and duration of mechanical ventilation and delayed VAP onset. However, subglottic secretion suction did not reduce mortality and length of ICU stay. Subglottic secretion suction is recommended for preventing VAP and for reducing ventilation length, especially in the population at high risk of early onset VAP.Trial registrationA protocol of this meta-analysis has been registered on PROSPERO (registration number: CRD42015015715); registered on 5 January 2015.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-016-1527-7) contains supplementary material, which is available to authorized users.

Background：Coronavirus disease 2019 (COVID-19), a highly infectious disease, has been rapidly spreading all over the world and posted a great threat to global public health. Patients diagnosed with severe or critical cases have a poor prognosis. Hence, it is crucial for us to identify potential severe or critical cases early, and give timely treatments for the targeted patients. In the clinical practice of treating COVID-19 patients, we have observed that the neutrophil-to-lymphocyte ratio (NLR) of severe patients is higher than that in mild patients. We performed this systematic review and meta-analysis to evaluate the predictive values of NLR on disease severity and mortality in COVID-19 patients. Methods: We searched PubMed, EMBASE, China National Knowledge Infrastructure (CNKI) and Wanfang databases to identify eligible studies (up to August 11, 2020). Two authors independently screened studies and extracted data. The methodological quality of the included studies was assessed by Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2).Results: Thirteen studies involving 1579 patients reported the predictive value of NLR on disease severity. The pooled sensitivity (SEN), specificity (SPE) and area under curve (AUC) were 0.78 (95% CI 0.70-0.84), 0.78 (95% CI 0.73-0.83) and 0.85 (95% CI 0.81-0.88), respectively. Ten studies involving 2967 patients reported the predictive value of NLR on mortality. The pooled SEN, SPE and AUC were 0.83 (95% CI 0.75-0.89), 0.83 (95% CI 0.74-0.89) and 0.90 (95% CI 0.87-0.92), respectively. Conclusions: NLR has good predictive values on disease severity and mortality in COVID-19 patients. Evaluating NLR can help clinicians identify potentially severe cases early, conduct early triage and initiate effective management in time, which may reduce the overall mortality of COVID-19. Moreover, we can better allocate scarce medical resources in this unprecedented time. Trial registration: This meta-analysis was prospectively registered on PROSPERO database (Registration number: CRD42020203612).

IntroductionPrior work suggests that leukocyte trafficking is determined by local chemokine gradients between the nidus of infection and the plasma. We recently demonstrated that therapeutic apheresis can alter immune mediator concentrations in the plasma, protect against organ injury, and improve survival. Here we aimed to determine whether the removal of chemokines from the plasma by apheresis in experimental peritonitis changes chemokine gradients and subsequently enhances leukocyte localization into the infected compartment, and away from healthy tissues.MethodsIn total, 76 male adult Sprague–Dawley rats weighing 400 g to 600 g were included in this study. Eighteen hours after inducing sepsis by cecal ligation and puncture, we randomized these rats to apheresis or sham treatment for 4 hours. Cytokines, chemokines, and leukocyte counts from blood, peritoneal cavity, and lung were measured. In a separate experiment, we labeled neutrophils from septic donor animals and injected them into either apheresis or sham-treated animals. All numeric data with normal distributions were compared with one-way analysis of variance, and numeric data not normally distributed were compared with the Mann–Whitney U test.ResultsApheresis significantly removed plasma cytokines and chemokines, increased peritoneal fluid-to-blood chemokine (C-X-C motif ligand 1, ligand 2, and C-C motif ligand 2) ratios, and decreased bronchoalveolar lavage fluid-to-blood chemokine ratios, resulting in enhanced leukocyte recruitment into the peritoneal cavity and improved bacterial clearance, but decreased recruitment into the lung. Apheresis also reduced myeloperoxidase activity and histologic injury in the lung, liver, and kidney. These Labeled donor neutrophils exhibited decreased localization in the lung when infused into apheresis-treated animals.ConclusionsOur results support the concept of chemokine gradient control of leukocyte trafficking and demonstrate the efficacy of apheresis to target this mechanism and reduce leukocyte infiltration into the lung.

The aim of this study was to determine the effectiveness of corneal collagen cross-linking (CXL) for the treatment of progressive keratoconus (KC). Some of the published literature, including a few small, randomized controlled trials (RCTs), demonstrated good results after CXL, but large RCTs with long-term follow-up to establish a cause-effect relationship are lacking. Using PubMed, EMBASE, and the Cochrane Library database, we searched for relevant studies published between October 2007 and March 2014. A comprehensive literature search was performed using the Cochrane Collaboration methodology to identify the effectiveness of CXL for treating KC. The primary outcome parameters included uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refraction, corneal topography, and corneal thickness at baseline and at 1, 3, 6, 12, and 18 months after CXL. A total of 1171 participants (1557 eyes) were enrolled in this meta-analysis. CXL may be effective in halting the progress of KC for at least 12 months under certain conditions. However, further research from randomized trials is needed to confirm our findings.