Abstract

OBJECTIVES To evaluate the effect of recombinant erythropoietin on hospitalised COVID-19 patients. TRIAL DESIGN Concealed, randomized, single-blinded, phase 2 controlled clinical trial with two arm parallel-group design of 20 patients allocated with 1:1 ratio and using the placebo in the control group. PARTICIPANTS This study will be performed at Shahid Mohammadi Hospital in Bandar Abbas, Hormozgan in Iran. All positive (PCR confirmed) COVID-19 patients ≤65 years old who have Hb≤9 and at least one of the severe COVID-19 symptoms (tachypnea (breathing rate> 30 beats per minute), hypoxemia (O2 ≤93 saturation, the partial pressure ratio of arterial oxygen <300), Lung infiltration (> 50% of lung field within 24 to 48 hours), progressive lymphopenia, LDH>245 U/I, CRP>100) and are willing to cooperate in this project will be included in the study. Patients with a history of coronary heart disease, thrombosis, deep vein thrombosis, chronic lung disease, diabetes mellitus, weakened immune system, end-stage renal disease, liver disease, and patients with a history of taking oral contraceptive pills, systolic blood pressure more than 160 mm Hg, diastolic blood pressure more than 90 mm Hg and age over 65 and erythropoietin above 500 are excluded. INTERVENTION AND COMPARATOR Patients will receive the standard of care (SOC) based on the treatment protocols of the Iranian National Committee of COVID-19 and recombinant erythropoietin (EPREX Manufactured by Johnson and Johnson Pharmaceutical Company) 300 units / Kg or 4000IU as subcutaneous (SQ) injection three times a day for 5 days and simultaneously Enoxaparin 1 mg/kg SQ daily is also taken to prevent thrombosis in the intervention group. Patients' blood pressure, along with other vital signs, are checked regularly and at regular intervals. In the control group, patients received SOC and the placebo (distilled water) is given as a subcutaneous injection three times a day for 5 days. We use sterile water for injection (EXIRpharmaceutical company) as the placebo. To the same appearance of the placebo and the recombinant erythropoietin, they are taken in a separate room in the same size syringes and cover with labels before injection. MAIN OUTCOMES The main outcome for this study is a composite endpoint for Patient clinical symptoms (Respiratory rate, Oxygen saturation state and arterial oxygen partial pressure ratio, Lung infiltration status, blood pressure), Laboratory tests (LDH, CRP, Lymphocyte count, Endogenous erythropoietin, and Haemoglobin level). All of these will be assessed at the beginning of the study (before the intervention) and day 5 after the intervention. The study will also evaluate side effects and how to manage them. RANDOMISATION Eligible participants (20) will be randomized in two arms in the ratio of 1: 1 (10 per arm) by permuted block randomization method using online web-based tools. BLINDING (MASKING): Patients participating in the study will not be aware of the assignment to the intervention or control group. The principal investigator, health care personnel, data collectors, and those evaluating the outcome are aware of patient grouping. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): A total of 20 patients will participate in this study, who are randomly allocated to the 2 arms with a 1:1 ratio; 10 patients in the intervention group will receive SOC and recombinant erythropoietin, and 10 patients in the control group will receive SOC and placebo. TRIAL STATUS The protocol version is 3.0, approved by the Deputy of Research and Technology and the ethics committee of Hormozgan University of Medical Sciences on 6(th) June 2020, with the local grant number of 990108. The expected recruitment end date was on 21(th) December 2020 but since we had a wide and careful exclusion criteria because of the adverse reactions of the medication, the recruitment (for both cases and controls) was not so easy and did not finish on the expected date and we are still recruiting now. Recruitment began on 17(th) August 2020 and the updated expected recruitment end date is 1(st) August 2021. TRIAL REGISTRATION The protocol was registered before starting subject recruitment under the title: Evaluation of the effect of recombinant erythropoietin on the improvement of COVID-19 patients, IRCT20200509047364N1, at Iranian Registry of clinical trials ( https://en.irct.ir/trial/49282 ) on 2020/08/09. FULL PROTOCOL The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol. The study protocol has been reported in accordance with the Standard Protocol Items: Recommendations for Clinical Interventional Trials (SPIRIT) guidelines (Additional file 2).

Abstract

OBJECTIVES/HYPOTHESIS Post-tonsillectomy hemorrhage (PTH) is a potentially life-threatening complication. A recent meta-analysis suggests that ibuprofen may increase the risk of PTH. The aims of this study were to 1) re-evaluate the effect of ibuprofen on PTH given additional recent evidence and 2) to evaluate a potential dose effect of ibuprofen. STUDY DESIGN Meta-analysis and meta-regression; single-institution retrospective review. METHODS We conducted a systematic review of the literature and a meta-analysis of 12 studies comparing postoperative ibuprofen analgesia to non-nonsteroidal anti-inflammatory drug (NSAID) controls. Next, we performed a meta-regression analysis to assess for an effect of dose, if any, on rates of PTH. Five studies specifying a dose of 5 mg/kg (828 patients, 1,411 controls) and 7 studies using 10 mg/kg (5,633 patients, 7,656 controls) were included. We then conducted a novel single-institution, retrospective review of data for 1,046 patients prescribed intermediate-dose 7.5 mg/kg ibuprofen. RESULTS Ibuprofen was not associated with an increased rate of PTH (log odds ratio [OR], 0.21; 95% confidence interval [CI] -0.15, 0.57). Meta-regression showed that ibuprofen dose (5 and 10 mg/kg) did not have a statistically significant effect on PTH (OR, 1.32; 95% CI 0.30, 5.84). Uncontrolled, aggregate rates of PTH across all studies were 2.29% (N = 828) for 5 mg/kg and 4.65% (N = 5,633) for 10 mg/kg dosing. The rate of secondary hemorrhage in patients prescribed 7.5 mg/kg ibuprofen was 3.10% (N = 1,046). CONCLUSION We found no statistically significant increased risk of PTH when ibuprofen is prescribed at the low or high range of commonly used clinical dosages, compared to a non-ibuprofen regimen. Further studies with less heterogeneity are needed to determine if there is a clinically relevant dose-dependent difference in PTH with ibuprofen. LEVEL OF EVIDENCE 3 Laryngoscope, 2021.

Abstract

PURPOSE Iron supplementation has been evaluated in several randomized controlled trials (RCTs) for its potential to increase baseline hemoglobin and decrease red blood cell transfusion during cardiac surgery. This study's main objective was to evaluate the current evidence for iron administration in cardiac surgery patients. METHODS We searched MEDLINE, EMBASE, CENTRAL, Web of Science databases, and Google Scholar from inception to 19 November 2020 for RCTs evaluating perioperative iron administration in adult patients undergoing cardiac surgery. The RCTs were assessed using a risk of bias assessment and the quality of evidence was assessed using the grading of recommendations, assessments, development, and evaluations. RESULTS We reviewed 1,767 citations, and five studies (n = 554) met the inclusion criteria. The use of iron showed no statistical difference in incidence of transfusion (risk ratio, 0.86; 95% confidence interval, 0.65 to 1.13). Trial sequential analysis suggested an optimal information size of 1,132 participants, which the accrued information size did not reach. CONCLUSION The current literature does not support or refute the routine use of iron therapy in cardiac surgery patients. TRIAL REGISTRATION PROSPERO (CRD42020161927); registered 19 December 2019.

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

Aim and objectives The aim of the study was to assess the amount of blood loss in minimally invasive hepatectomy and open liver resection for both benign and neoplastic conditions. Introduction Minimally invasive surgery has progressively developed to a stage where once-novel and highly specialized surgical techniques are now common practice. Colorectal surgery is the key example that has shown minimally invasive surgery as highly beneficial. Successes in the colorectal laparoscopic approach have now been integrated into the speciality of hepatopancreaticobiiary (HPB) surgery. In this review, we will compare the amount of blood loss in minimally invasive liver resection with the more traditional approach of open liver resection. Methods A literature review was conducted which included the length of patient mobilization as a postoperative complication following laparoscopic and open liver resections. Medline, PubMed, and Cochrane were accessed to review previously published studies. Twelve studies were selected, and all of them were in English, ranged from the year 2000 to 2020. Results Eleven out of the 12 included studies indicated that minimally invasive liver resection is associated with reduced blood loss. Conclusion In comparing both minimally invasive liver resection and classic open surgery, minimally invasive liver resection was shown to have reduced blood loss; this was seen in both malignant and benign tumours. Therefore, laparoscopic liver resection could be favoured over the classical open approach to avoid excessive blood loss intra-operatively.

Abstract

Acute upper gastrointestinal bleeding (UGIB) is the most common indication for urgent endoscopy, but the correct timing of endoscopy in these patients is still debated. Our systematic review with meta-analysis was aimed at investigating the potential clinical benefit of very early endoscopy for UGIB patients. We performed an electronic literature search of PubMed, Scopus, Web of Science and the Cochrane Library up to 23rd May 2020 and considered only randomised controlled trials (RCTs) comparing management of UGIB patients by very early vs early endoscopy. Only five RCTs were considered eligible for quantitative analysis, with a total population of 926 cases (468 in the very early endoscopy arm and 458 in the early). The meta-analysis showed no statistically significant benefit for very early endoscopy compared to early endoscopy in terms of risk of rebleeding, mortality, ICU admission, blood transfusion, surgery and length of hospital stay. However, our results showed a significantly higher need for haemostatic treatment when very early endoscopy was performed (RR 1.23, 95% CI 1.06-1.42, p < 0.01) in comparison to early endoscopy.

Abstract

The aim of this study was to evaluate the impact of using a thromboelastometry-based protocol on transfusion requirements in patients undergoing combined coronary artery bypass grafting (CABG) and valve surgery. 80 adult patients scheduled for elective combined CABG and valve surgery were included in this clinical trial study. Patients were randomly allocated to the thromboelastometry (ROTEM) (n = 40) or control groups (n = 40). In the ROTEM group, transfusion was directed according to a thromboelastometry-based protocol. In the control group, transfusion was conducted according to the routine practices including conventional coagulation testing and clinical judgments. Finally, transfusion requirements were compared between groups. Use of thromboelastometry- based protocol resulted in 67% reduction in blood products units' consumption as well as 23% in the percentage of patients transfused. This reduction was especially evident in relation to fresh frozen plasma (FFP) and platelet consumption. No significant differences were found both in the percentage of patients receiving RBC and number of transfused RBC units. Using thromboelastometry tests incorporated a protocol results in reduction of transfusion requirements in patients undergoing elective combined CABG and valve surgery.

Abstract

BACKGROUND The use of eye tracking in the simulated setting can help improve our understanding of what sources of information clinicians are using as they deliver routine patient care. The aim of this simulation study was to observe the differences, if any, between the eye tracking patterns of leaders who performed best in a simulated postpartum hemorrhage (PPH) high-fidelity scenario, in comparison with those who performed worst. METHODS Forty anesthesia trainees from the University of Catania Medical School were divided into eight teams, to enact four times the same scenario of a patient with postpartum hemorrhage following vaginal delivery. Trainees who were assigned the leader's role wore the eye tracking glasses during the scenario, and their behavioral skills were evaluated by two observers, who reviewed the video recordings of the scenarios using a standardized checklist. The leader's eye tracking metrics, extracted from 27 selected areas of interest (AOI), were recorded by a Tobii Pro Glasses 50 Hz wearable wireless eye tracker. Team performance was evaluated using a PPH checklist. After completion of the study, the leaders were divided into two groups, based on the scores they had received (High-Performance Leader group, HPL, and Low-Performance Leader group, LPL). RESULTS In the HPL group, the duration and number of fixations were greater, and the distribution of gaze was uniformly distributed among the various members of the team as compared with the LPL group (with the exception of the participant who performed the role of the obstetrician). The HPL group also looked both at the patient's face and established eye contact with their team members more often and for longer (P < .05). The team performance (PPH checklist) score was greater in the HPL group (P < .001). The LPL group had more and/or longer fixations of technical areas of interest (P < .05). CONCLUSIONS Our findings suggest that the leaders who perform the best distribute their gaze across all members of their team and establish direct eye contact. They also look longer at the patient's face and dwell less on areas that are more relevant to technical skills. In addition, the teams led by these best performing leaders fulfilled their clinical task better. The information provided by the eye behaviors of "better-performing physicians" may lay the foundation for the future development of both the assessment process and the educational tools used in simulation. TRIAL REGISTRATION Clinical.Trial.Gov ID n. NCT04395963 .

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.