Abstract

OBJECTIVE We sought to characterize the timing of administration of prehospital Tranexamic Acid (TXA) and associated outcome benefits. BACKGROUND TXA has been shown to be safe in the prehospital setting post-injury. METHODS We performed a secondary analysis of a recent prehospital randomized TXA clinical trial in injured patients. Those who received prehospital TXA within 1hr (EARLY) from time of injury were compared to those who received prehospital TXA beyond 1hr (DELAYED). We included patients with a shock index of > 0.9. Primary outcome was 30-day mortality. Kaplan-Meier and Cox Hazard regression were utilized to characterize mortality relationships. RESULTS EARLY and DELAYED patients had similar demographics, injury characteristics and shock severity but DELAYED patients had greater prehospital resuscitation requirements and longer prehospital times. Stratified Kaplan-Meier analysis demonstrated significant separation for EARLY patients (N =238, log-rank chi-square test, 4.99; P = .03) with no separation for DELAYED patients (N=238, log-rank chi-square test, 0.04; P = .83). Stratified Cox Hazard regression verified, after controlling for confounders, that EARLY TXA was associated with a 65% lower independent hazard for 30-day mortality (HR 0.35, 95%CI 0.19-0.65, P = .001) with no independent survival benefit found in DELAYED patients (HR 1.00, 95%CI 0.63-1.59, P = .999). EARLY TXA patients had lower incidence of multiple organ failure and 6-hour and 24-hour transfusion requirements compared to placebo. CONCLUSIONS Administration of prehospital TXA within 1 hour from injury in patients at risk of hemorrhage is associated with 30-day survival benefit, lower incidence of multiple organ failure, and lower transfusion requirements.

Abstract

BACKGROUND Radiomics provides a framework for automated extraction of high-dimensional feature sets from medical images. We aimed to determine radiomics signature correlates of admission clinical severity and medium-term outcome from intracerebral hemorrhage (ICH) lesions on baseline head CTs. METHODS We used the ATACH-2 (Antihypertensive-Treatment-of-Acute-Cerebral-Hemorrhage-II) trial dataset. Patients included in this analysis (n=895) were randomly allocated to discovery (n=448) and independent validation (n=447) cohorts. We extracted 1130 radiomics features from hematoma lesions on baseline non-contrast head CTs and generated radiomics signatures associated with admission Glasgow Coma Scale (GCS), admission National Institutes of Health Stroke Scale (NIHSS), and 3-month modified Rankin Scale (mRS) scores. Spearman's correlation between radiomics signatures and corresponding target variables was compared with hematoma volume. RESULTS In the discovery cohort, radiomics signatures - compared to ICH volume - had significantly stronger association with admission GCS (0.47 vs 0.44, p=0.008), admission NIHSS (0.69 vs 0.57, p<0.001), and 3-month mRS scores (0.44 vs 0.32, p<0.001). Similarly, in independent validation, radiomics signatures - compared to ICH volume - had significantly stronger association with admission GCS (0.43 vs 0.41, p=0.02), NIHSS (0.64 vs 0.56, p<0.001), and 3-month mRS scores (0.43 vs 0.33, p<0.001). In multiple regression analysis adjusted for known predictors of ICH outcome, the radiomics signature was an independent predictor of 3-month mRS in both cohorts. CONCLUSIONS Limited by the enrollment criteria of the ATACH-2 trial, we showed that radiomics features quantifying hematoma texture, density and shape on baseline CT can provide imaging correlates for clinical presentation and medium-term outcome.

Abstract

BACKGROUND Pelvic fractures represent a small percent of all skeletal injuries but are associated with significant morbidity and mortality secondary to hemodynamic instability from bleeding bone surfaces and disrupted pelvic vasculature. Stabilization of the pelvis prior to arrival at a treatment facility may mitigate the hemodynamic consequences of pelvic ring injuries and improve morbidity and mortality. Whether pelvic compression devices such as pelvic binders or sheets can be safely applied in the prehospital setting has not been well-studied. This study aims to evaluate the safety of applying a pelvic binder to at-risk patients in the field after scalable training and the feasibility of conducting a randomized trial evaluating this practice in the prehospital setting. METHODS A pilot study (prospective randomized trial design) was conducted in the pre-hospital environment in an urban area surrounding a level-one trauma center. Pre-hospital emergency medical (EMS) personnel were trained to identify patients at high-risk for pelvic fracture and properly apply a commercial pelvic binder. Adult patients with a high-energy mechanism, suspected pelvic fracture, and "Priority 1" criteria were prospectively identified by paramedics and randomized to pelvic binder placement or usual care. Medical records were reviewed for safety outcomes. Secondary outcomes were parameters of efficacy including interventions needed to control hemorrhage (such as angioembolization and surgical control of bleeding) and mortality. RESULTS Forty-three patients were randomized to treatment (binder: N=20; nonbinder: N=23). No complications of binder placement were identified. Eight patients (40%) had binders placed correctly at the level of the greater trochanter. Two binders (10%) were placed too proximally and 10 (50%) binders were not visualized on x-ray. Two binder group patients and three nonbinder group patients required angioembolization. None required surgical control of pelvic bleeding. Two nonbinder group patients and one binder group patient were readmitted within 30 days and one nonbinder group patient died within 30 days. CONCLUSION Identification of pelvic fractures in the field remains a challenge. However, a scalable training model for appropriate binder placement was successful without secondary injury to patients. The model for conducting prospective, randomized trials in the prehospital setting was successful.

Abstract

BACKGROUND Red blood cell (RBC) transfusions have been implicated in the development of necrotizing enterocolitis (NEC) in premature infants. Some evidence exists to support that withholding feedings during transfusion reduces the risk of subsequent NEC development. PURPOSE To review the most recent literature on this topic to determine best evidence-based practice regarding withholding or not withholding feedings during RBC transfusions. METHODS/SEARCH STRATEGY Four databases were searched using keywords and MeSH terms including "necrotizing enterocolitis," "NEC," "NPO," and "transfusion," with specifications limiting the search to articles published in the last 10 years and limiting the population to neonates. FINDINGS Four studies did not demonstrate a reduction in transfusion-associated necrotizing enterocolitis (TANEC) with the implementation of feeding protocols during packed red blood cell (PRBC) transfusions. One study concluded that it could not confirm the benefit of withholding feeds during transfusion to reduce the risk of TANEC. A 2020 randomized controlled trial (RCT) found no difference in splanchnic oxygenation when enteral feeds are withheld, continued, or restricted during a PRBC transfusion. Holding feedings during PRBC transfusions did not result in adverse nutritional outcomes. IMPLICATIONS FOR PRACTICE To determine best evidence-based practice surrounding feeding protocols during RBC transfusions in very low-birth-weight and premature infants less than 37 weeks' gestation. IMPLICATIONS FOR RESEARCH It is recommended that large, multicentered, adequately powered RCTs be conducted in this area. Individual institutions should standardize their practice to improve quality, safety, and patient outcomes.

Abstract

OBJECTIVES To test whether an increased iron dose is associated with improved neurodevelopment as assessed by the Bayley Scales of Infant Development (BSID-III) among infants enrolled in the Preterm Erythropoietin (Epo) Neuroprotection Trial (PENUT). STUDY DESIGN This is a post hoc analysis of a randomized trial which enrolled infants born at 24 to 28 completed weeks of gestation. All PENUT infants who were assessed with BSID-III at 2 years were included in this study. The associations between enteral iron dose at 60 and 90 days and BSID-III component scores were evaluated using generalized estimating equations models adjusted for potential confounders. RESULTS 692 infants were analyzed (355 placebo, 337 Epo). Enteral iron supplementation ranged 0-14.7 mg/kg/day (IQR 2.1-5.8 mg/kg/day) at day 60, with a mean of 3.6 mg/kg/day in placebo-treated infants and 4.8 mg/kg/day in Epo-treated infants. A significant positive association was seen between BSID-III cognitive scores and iron dose at 60 days, with an effect size of 0.77 BSID points per 50 mg/kg increase in cumulative iron dose (P = .03). Higher iron doses were associated with higher motor and language scores, but did not reach statistical significance. Results at 90 days were not significant. The effect size in the Epo-treated infants compared with placebo was consistently higher. CONCLUSION A positive association was seen between iron dose at 60 days and cognitive outcomes. Our results suggest that increased iron supplementation in preterm infants, at the doses administered in the PENUT Trial, may have positive neurodevelopmental effects, particularly in infants treated with Epo.

Abstract

PURPOSE This study aimed at evaluating the efficacy and safety of high-dose (> 0.2 L/kg of treated plasma per day) coupled plasma filtration-adsorption (CPFA) in treating patients with septic shock. METHODS Multicentre, randomised, adaptive trial, performed in 12 Italian intensive care units (ICUs). Patients aged 14 or more, admitted to the ICU with septic shock, or had developed it during the stay were eligible. The final outcome was mortality at discharge from the last hospital at which the patient received care. RESULTS Between May 2015, and October 2017, 115 patients were randomised. The first interim analysis revealed a number of early deaths, prompting an unplanned analysis. Last hospital mortality was non-significantly higher in the CPFA (55.6%) than in the control group (46.2%, p = 0.35). The 90-day survival curves diverged in favour of the controls early after randomisation and remained separated afterwards (p = 0.100). An unplanned analysis showed higher mortality in CPFA compared to controls among patients without severe renal failure (p = 0.025); a dose-response relationship was observed between treated plasma volume and mortality (p = 0.010). CONCLUSION The COMPACT-2 trial was stopped due to the possible harmful effect of CPFA in patients with septic shock. The harmful effect, if present, was particularly marked in the early phase of septic shock. Patients not requiring renal replacement therapy seemed most exposed to the possible harm, with evidence of a dose-response effect. Until the mechanisms behind these results are fully understood, the use of CPFA for the treatment of patients with septic shock is not recommended.

Abstract

Background and objective: The early detection of underlying hemorrhage of pelvic trauma has been a critical issue. The aim of this study was to systematically determine the diagnostic accuracy of computed tomography (CT) for detecting severe pelvic hemorrhage. Materials and Methods: Relevant articles were obtained by searching PubMed, EMBASE, and Cochrane databases through 28 November 2020. Diagnostic test accuracy results were reviewed to obtain the sensitivity, specificity, diagnostic odds ratio, and summary receiver operating characteristic curve of CT for the diagnosis in pelvic trauma patients. The positive finding on CT was defined as the contrast extravasation. As the reference standard, severe pelvic hemorrhage was defined as an identification of bleeding at angiography or by direct inspection using laparotomy that required hemostasis by angioembolization or surgery. A subgroup analysis was performed according to the CT modality that is divided by the number of detector rows. Result: Thirteen eligible studies (29 subsets) were included in the present meta-analysis. Pooled sensitivity of CT was 0.786 [95% confidence interval (CI), 0.574-0.909], and pooled specificity was 0.944 (95% CI, 0.900-0.970). Pooled sensitivity of the 1-4 detector row group and 16-64 detector row group was 0.487 (95% CI, 0.215-0.767) and 0.915 (95% CI, 0.848-0.953), respectively. Pooled specificity of the 1-4 and 16-64 detector row groups was 0.956 (95% CI, 0.876-0.985) and 0.906 (95% CI, 0.828-0.951), respectively. Conclusion: Multi-detector CT with 16 or more detector rows has acceptable high sensitivity and specificity. Extravasation on CT indicates severe hemorrhage in patients with pelvic trauma.

Abstract

BACKGROUND Proton pump inhibitors (PPIs) decrease the rate of rebleeding following endoscopic hemostatic therapy in patients with bleeding peptic ulcers. This study compares the efficacy of oral omeprazole vs intravenous omeprazole in decrease of rebleeding of peptic ulcer patients. METHOD The present study was authorized by the local research ethics committee of Jiangjin District Central Hospital (2020120987) and informed consent was obtained from all patients. All adult patients who were admitted to medical emergency rooms of Jiangjin District Central Hospital due to upper gastrointestinal bleeding (as evidenced by hematemesis, melena or hematochezia) were considered for inclusion in the study. Endoscopy was performed within 24 hours after admission. Patients older than 18 years with successful endoscopic therapy of high risk ulcers [defined as active bleeding (Forrest IA, IB), non-bleeding visible vessel (NBVV, Forrest IIA) or adherent clots (Forrest IIB)] were enrolled. Patients with low risk ulcers (clean base, ulcers with a simple washable clot), suspicious malignant ulcer, bleeding tendency, uremia, liver cirrhosis, Mallory Weiss tear or already on PPI as an outpatient were excluded from study. All were managed endoscopically by injecting 5-30 ml of epinephrine (diluted 1:10000) around the ulcer crater. Cavitations or flattening of bleeding vessel and disappearance of NBVV was considered as established homeostasis. A biopsy was taken from antrum for evaluating Helicobacter pylori infection. Patient with unsuccessful endoscopic therapy were not enrolled and were referred to general surgeon. Information on demography, history of previous upper gastrointestinal bleeding, NSAID or ASA ingestion, ulcer location, bleeding stigmata and blood transfusion volume at entry were recorded in all patients. In the oral omeprazole group, the patients received 40 mg omeprazole orally twice daily for 72 hours. In intravenous omeprazole group, they received omeprazole 80 mg bolus and then 8 mg/hour infusion for 48-72 hours. Then, all patients received omeprazole 20 mg orally for 30 days. On the day of discharge Helicobacter pylori infected patients received standard regimens. RESULTS Figure 1 showed the primary and secondary end points. DISCUSSION Intravenous administration of PPIs has limitations. They are expensive, require a dedicated intravenous line, need nursing supervision and hospital admission. So, it would be reasonable to prescribe oral PPIs to patients with high risk bleeding ulcers provided that it is as effective as its intravenous counterpart. Oral PPIs have a high bioavailability. Its effect initiates one hour after ingestion and the maximal plasma concentration is achieved after 2-3 hours. However, there are few studies comparing oral and intravenous PPI in decreasing risk of rebleeding in peptic ulcer patients. More high quality randomized controlled trials are still necessary. REGISTRATION NUMBER researchregistry 6588.

Abstract

BACKGROUND Intraventricular hemorrhage (IVH) is a common complication in preterm infants that has poor outcomes, especially in severe cases, and there are currently no widely accepted effective treatments. Erythropoietin has been shown to be neuroprotective in neonatal brain injury. OBJECTIVE The objective of this study was to evaluate the protective effect of repeated low-dose recombinant human erythropoietin (rhEPO) in preterm infants with IVH. METHODS This was a single-blinded prospective randomized controlled trial. Preterm infants ≤ 32 weeks gestational age who were diagnosed with IVH within 72 h after birth were randomized to receive rhEPO 500 IU/kg or placebo (equivalent volume of saline) every other day for 2 weeks. The primary outcome was death or neurological disability assessed at 18 months of corrected age. RESULTS A total of 316 eligible infants were included in the study, with 157 in the rhEPO group and 159 in the placebo group. Although no significant differences in mortality (p = 0.176) or incidence of neurological disability (p = 0.055) separately at 18 months of corrected age were seen between the rhEPO and placebo groups, significantly fewer infants had poor outcomes (death and neurological disability) in the rhEPO group: 14.9 vs. 26.4%; odds ratio (OR) 0.398; 95% confidence interval (CI) 0.199-0.796; p = 0.009. In addition, the incidence of Mental Development Index scores of < 70 was lower in the rhEPO group than in the placebo group: 7.2 vs. 15.3%; OR 0.326; 95% CI 0.122-0.875; p = 0.026. CONCLUSIONS Treatment with repeated low-dose rhEPO improved outcomes in preterm infants with IVH. TRIAL REGISTRATION The study was retrospectively registered on ClinicalTrials.gov on 16 April 2019 (NCT03914690).

Abstract

BACKGROUND Aggressive fluid administration is recommended in the resuscitation of septic patients. However, the delivery of a rapid fluid bolus might cause harm by inducing degradation of the endothelial glycocalyx. This research aimed to examine the effects of the limited infusion rate of fluid on glycocalyx shedding as measured by syndecan-1 in patients with sepsis-induced hypoperfusion. METHODS A prospective, randomized, controlled, open-label trial was conducted between November 2018 and February 2020 in an urban academic emergency department. Patients with sepsis-induced hypoperfusion, defined as hypotension or hyperlactatemia, were randomized to receive either the standard rate (30 ml/kg/h) or limited rate (10 ml/kg/h) of fluid for the first 30 ml/kg fluid resuscitation. Subsequently, the fluid rate was adjusted according to the physician's discretion but not more than that of the designated fluid rate for the total of 6 h. The primary outcome was differences in change of syndecan-1 levels at 6 h compared to baseline between standard and limited rate groups. Secondary outcomes included adverse events, organ failure, and 90-day mortality. RESULTS We included 96 patients in the intention-to-treat analysis, with 48 assigned to the standard-rate strategy and 48 to the limited-rate strategy. The median fluid volume in 6 h in the limited-rate group was 39 ml/kg (interquartile range [IQR] 35-52 ml/kg) vs. 53 ml/kg (IQR 46-64 ml/kg) in the standard-rate group (p < 0.001). Patients in the limited-rate group were less likely to received vasopressors (17% vs 42%; p = 0.007) and mechanical ventilation (20% vs 41%; p = 0.049) during the first 6 h. There were no significantly different changes in syndecan-1 levels at 6 h between the two groups (geometric mean ratio [GMR] in the limited-rate group, 0.82; 95% confidence interval [CI], 0.66-1.02; p = 0.07). There were no significant differences in adverse events, organ failure outcomes, or mortality between the two groups. CONCLUSIONS In sepsis resuscitation, the limited rate of fluid resuscitation compared to the standard rate did not significantly reduce changes in syndecan-1 at 6 h. TRIAL REGISTRATION Thai Clinical Trials Registry number: TCTR20181010001. Registered 8 October 2018, http://www.clinicaltrials.in.th/index.php?tp=regtrials&menu=trialsearch&smenu=fulltext&task=search&task2=view1&id=4064.