Diagnostic and prognostic values of miR181b-5p and miR21-5p for neonatal sepsis risk and their link to SNAP II score and disease mortality.

Background: Neonatal sepsis is a lethal syndrome that necessitates prompt treatment to avoid disease complications. As a result, biomarkers that may either differentiate sepsis early or predict the outcome of sepsis are essential. Aim: The goal of this research was to find out the clinical weight of using miR181b-5p and miR21-5p expression levels as diagnostic and prognostic new genetic markers for neonatal sepsis. Method: A total of 60 neonates with sepsis and 60 healthy neonates were involved in this study. Laboratory tests include complete blood count (CBC), random blood sugar (RBS), arterial blood gases (ABG), and serum C-reactive protein (CRP). Neonates with sepsis were assessed by the Score for Neonatal Acute Physiology II (SNAP II). The serum fold changes of the target miRNAs were determined using qRT-PCR and the 2-ΔΔCt equation. Results: The relative serum level of miR181b-5p was [ median (IQR) = 0.2509 (0.0009-4.11)] and for miR21-5p was [median (IQR) = 0.07 (0.007-7.16)] which were significantly downregulated in patients with neonatal sepsis compared to controls (p < 0.001 each). There was a strong significant positive correlation between miR181b-5p and miR21-5p with r = 0.718 and p < 0.001. MiR181b-5p and miR21-5p were significantly negatively correlated with total leucocytic count (TLC), lymphocytic count, and CRP. While they were both positively correlated to the SNAP II score. Obvious association between higher expressions of target genes and higher SNAP II score groups. After a following-up period, twenty-two (36.7%) neonates died, while 38 (63.3%) of the babies became better and were released from the hospital. We reported that miR-181-5p, miR21-5p, SNAP II score and CRP were significantly higher in non-survivors than survivors. Only miR181b-5p, miR21-5p, and SNAP II were predictive factors of septic mortality. Conclusion: MiR181b-5p and miR21-5p are diagnostic and prognostic biomarkers of neonatal sepsis.

Effects of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with significant haemorrhage (CRASH-2): a randomised, placebo-controlled trial.

BACKGROUND: Tranexamic acid can reduce bleeding in patients undergoing elective surgery. We assessed the effects of early administration of a short course of tranexamic acid on death, vascular occlusive events, and the receipt of blood transfusion in trauma patients. METHODS: This randomised controlled trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, significant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min then infusion of 1 g over 8 h) or matching placebo. Randomisation was balanced by centre, with an allocation sequence based on a block size of eight, generated with a computer random number generator. Both participants and study staff (site investigators and trial coordinating centre staff) were masked to treatment allocation. The primary outcome was death in hospital within 4 weeks of injury, and was described with the following categories: bleeding, vascular occlusion (myocardial infarction, stroke and pulmonary embolism), multiorgan failure, head injury, and other. All analyses were by intention to treat. This study is registered as ISRCTN86750102, Clinicaltrials.govNCT00375258, and South African Clinical Trial RegisterDOH-27-0607-1919. FINDINGS: 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. All-cause mortality was significantly reduced with tranexamic acid (1463 [14.5%] tranexamic acid group vs 1613 [16.0%] placebo group; relative risk 0.91, 95% CI 0.85-0.97; p=0.0035). The risk of death due to bleeding was significantly reduced (489 [4.9%] vs 574 [5.7%]; relative risk 0.85, 95% CI 0.76-0.96; p=0.0077). INTERPRETATION: Tranexamic acid safely reduced the risk of death in bleeding trauma patients in this study. On the basis of these results, tranexamic acid should be considered for use in bleeding trauma patients. FUNDING: UK NIHR Health Technology Assessment programme, Pfizer, BUPA Foundation, and J P Moulton Charitable Foundation.

Final results of MRC CRASH, a randomised placebo-controlled trial of intravenous corticosteroid in adults with head injury-outcomes at 6 months.

MRC CRASH is a randomised controlled trial (ISRCTN74459797) of the effect of corticosteroids on death and disability after head injury. We randomly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less, within 8 h of injury, to a 48-h infusion of corticosteroid (methylprednisolone) or placebo. Data at 6 months were obtained for 9673 (96.7%) patients. The risk of death was higher in the corticosteroid group than in the placebo group (1248 [25.7%] vs 1075 [22.3%] deaths; relative risk 1.15, 95% CI 1.07-1.24; p=0.0001), as was the risk of death or severe disability (1828 [38.1%] vs 1728 [36.3%] dead or severely disabled; 1.05, 0.99-1.10; p=0.079). There was no evidence that the effect of corticosteroids differed by injury severity or time since injury. These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury.

Effect of intravenous corticosteroids on death within 14 days in 10008 adults with clinically significant head injury (MRC CRASH trial): randomised placebo-controlled trial.

BACKGROUND: Corticosteroids have been used to treat head injuries for more than 30 years. In 1997, findings of a systematic review suggested that these drugs reduce risk of death by 1-2%. The CRASH trial--a multicentre international collaboration--aimed to confirm or refute such an effect by recruiting 20000 patients. In May, 2004, the data monitoring committee disclosed the unmasked results to the steering committee, which stopped recruitment. METHODS: 10008 adults with head injury and a Glasgow coma score (GCS) of 14 or less within 8 h of injury were randomly allocated 48 h infusion of corticosteroids (methylprednisolone) or placebo. Primary outcomes were death within 2 weeks of injury and death or disability at 6 months. Prespecified subgroup analyses were based on injury severity (GCS) at randomisation and on time from injury to randomisation. Analysis was by intention to treat. Effects on outcomes within 2 weeks of randomisation are presented in this report. This study is registered as an International Standard Randomised Controlled Trial, number ISRCTN74459797. FINDINGS: Compared with placebo, the risk of death from all causes within 2 weeks was higher in the group allocated corticosteroids (1052 [21.1%] vs 893 [17.9%] deaths; relative risk 1.18 [95% CI 1.09-1.27]; p=0.0001). The relative increase in deaths due to corticosteroids did not differ by injury severity (p=0.22) or time since injury (p=0.05). INTERPRETATION: Our results show there is no reduction in mortality with methylprednisolone in the 2 weeks after head injury. The cause of the rise in risk of death within 2 weeks is unclear.

Laparoscopic cholecystectomy: the outcome with minimal conversion rate: experience in a district hospital.

BACKGROUND: Since introducing laparoscopic cholecystectomy (LC) different centres have reported different conversion rate (CR) to open cholecystectomy (OC) and different reasons for conversion. OBJECTIVE: To evaluate the role of LC in the treatment of symptomatic gallstones and establish the outcomes of this treatment modality in general, looking especially into the rate of conversion to OC, at a district hospital. PATIENTS AND METHODS: From July 1992-July 1998, 751 patients who underwent LC were retrospectively reviewed. All patients with symptomatic gallstones were offered LC with no exclusion criteria apart from anaesthetic opinion. No attempts were made at selection of patients for LC. RESULTS: There were 751 patients with symptomatic gallstones (617 females, 134 males) underwent LC. Chronic cholecystitis represented the majority of cases (83%). The mean operative time was 65.52 minutes: pre-operation and main hospital stay was 2.46 days. Our total conversion rate was 0.9% and 0.4% if malignancy of the gallbladder is excluded. In comparison to the published data, there was obvious lower conversion rate, which was neither associated with increased morbidity nor mortality. CONCLUSION: Laparoscopic cholecystectomy is a reliable, safe and cost effective treatment modality for symptomatic gallstones. With growing experience in laparoscopic technique, proper settings and harmony of the operating team, it is possible to bring the conversion rate to OC to the minimum without any increment in mortality or morbidity.