Abstract

PURPOSE A seroma is a collection of exudates after surgical trauma in wound healing. Fibrin glue is used to prevent seroma by reducing the generation of exudate. However, the impact of fibrin glue on the prevention of seroma remains debatable. Therefore, we conducted a randomized controlled pilot trial to investigate the effect of the amount of fibrin glue used on the generation of exudate after thyroidectomy and the sample size of future definitive trials. METHODS Between February and December 2020, 41 patients were enrolled; 21 patients in the low fibrin group and 20 in the high fibrin group. Stratified randomization was performed based on sex, body mass index, and thyroiditis. All patients underwent total thyroidectomy and bilateral central compartment dissection. In the low and high fibrin groups, 2 mL and 6 mL of fibrin glue were applied to patients, respectively. RESULTS Both the total drain volume and flow rate during the first 12 hours were lower in the high fibrin group than in the low fibrin group (65.0 mL vs. 47.6 mL, P = 0.008 and 2.7 mL/hr vs. 1.8 mL/hr, P = 0.002, respectively). The calculated sample size for future randomized controlled trial was 32 patients (α = 0.05, power = 0.8), and the power of this trial was 0.91 with µ(1) = 2.7, µ(2) = 1.8, σ = 0.9, and α = 0.05 (µ = mean, σ = standard deviation). CONCLUSION Six milliliters of fibrin glue could reduce total drain volume and flow rate of exudate after thyroidectomy. Therefore, applying an appropriate amount of fibrin glue after thyroidectomy may reduce postoperative seroma.

Abstract

OBJECTIVE In this article, the authors systematically evaluated the efficacy and safety of tranexamic acid (TXA) in surgeries for spinal trauma. METHODS Potentially relevant academic articles were identified from the Cochrane Library, MEDLINE, PubMed, and Google Scholar. Secondary sources were identified from the references of the included literature. RevMan software was used to analyze the pooled data. RESULTS A total of 7 randomized controlled trials (RCTs) and 2 non-RCTs were included in the review. There were significant differences in total blood loss (standard mean difference [SMD] = -2.54 [95% CI, -3.72, -1.37], P = 0.0001), intraoperative blood loss (SMD = -0.96 [95% CI, -1.28, -0.64], P < 0.00001), postoperative blood loss (SMD = -1.42 [95% CI, -1.72, -1.11], P < 0.00001), and length of hospital stay (SMD = -3.73 [95% CI, -4.41, -3.06], P = 0.00001). No significant differences were found regarding transfusion requirement, operative duration, deep vein thrombosis, and pulmonary embolism between the 2 groups. CONCLUSIONS The present meta-analysis indicates that the use of TXA in spinal surgery decreases blood loss and duration of hospital stay while not increasing the risk of side effects such as deep vein thrombosis and pulmonary embolism. CLINICAL RELEVANCE The study aims to provide clinicians who operate on spine trauma with information on the use of tranexamic acid to decrease blood loss and related complications.

Abstract

BACKGROUND AND AIM The choice of resuscitation fluid in cirrhosis patients with sepsis-induced hypotension (SIH) is unclear. 5% albumin has been superior to normal saline in the FRISC study. We compared the efficacy and safety of 20% albumin, which has greater oncotic properties with plasmalyte in reversing SIH. METHODS Critically-ill cirrhosis(CIC) patients underwent open-label randomization to receive either 20% albumin [0.5-1.0gm/kg over 3 hours; n=50] or plasmalyte (30ml/kg over 3 hours, n=50). The primary end-point of the study was the attainment of mean arterial pressure (MAP) above 65 mmHg at three hours. RESULTS Baseline characteristics were comparable in albumin and plasmalyte groups; arterial lactate(mmol/L) [6.16±3.18 vs. 6.38±4.77; p=0.78), MAP (mmHg) [51.4±6.52 vs. 49.9±4.45; p=0.17] and SOFA score [10.8±2.96 vs. 11.1±4.2; p=0.68] respectively. Most patients were alcoholics (39%) and had pneumonia (40%). In the intention-to-treat (ITT) analysis, albumin was superior to plasmalyte in achieving the primary end-point (62% vs. 22%; p<0.001). A rapid decline in arterial lactate (P=0.03), a lesser proportion of dialysis [48% vs. 62%; p=0.16], and a higher time to initiation of dialysis (in hours) [68.13±47.79 vs. 99.7± 63.4; p=0.06] was seen with albumin. However, the 28-day mortality was not different (58% vs. 62%, p=0.57). Patients in the albumin group required discontinuation of therapy in 11 (22%) patients due to adverse effects compared to none in plasmalyte group. CONCLUSION In patients with cirrhosis and SIH, 20% albumin transiently improves the hemodynamics with early lactate clearance than plasmalyte but needs monitoring as it is more often attended with pulmonary complications. Both fluids provide comparable 28 days survival. NCT02721238 LAY SUMMARY The current randomized controlled trial performed in critically ill patients with cirrhosis and sepsis-induced hypotension highlights that 20% albumin restores hemodynamics but causes more pulmonary complications than plasmalyte. The impact on renal functions was also modest. These effects did not result in improvement in deaths at 28-days. Plasmalyte is safer and well-tolerated and can be considered for volume resuscitation in patients with cirrhosis and sepsis-induced hypotension.

Abstract

IMPORTANCE Direct oral anticoagulant (DOAC)-associated intracranial hemorrhage (ICH) has high morbidity and mortality. The safety and outcome data of DOAC reversal agents in ICH are limited. OBJECTIVE To evaluate the safety and outcomes of DOAC reversal agents among patients with ICH. DATA SOURCES PubMed, MEDLINE, The Cochrane Library, Embase, EBSCO, Web of Science, and CINAHL databases were searched from inception through April 29, 2022. STUDY SELECTION The eligibility criteria were (1) adult patients (age ≥18 years) with ICH receiving treatment with a DOAC, (2) reversal of DOAC, and (3) reported safety and anticoagulation reversal outcomes. All nonhuman studies and case reports, studies evaluating patients with ischemic stroke requiring anticoagulation reversal or different dosing regimens of DOAC reversal agents, and mixed study groups with DOAC and warfarin were excluded. DATA EXTRACTION AND SYNTHESIS Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used for abstracting data and assessing data quality and validity. Two reviewers independently selected the studies and abstracted data. Data were pooled using the random-effects model. MAIN OUTCOMES AND MEASURES The primary outcome was proportion with anticoagulation reversed. The primary safety end points were all-cause mortality and thromboembolic events after the reversal agent. RESULTS A total of 36 studies met criteria for inclusion, with a total of 1832 patients (967 receiving 4-factor prothrombin complex concentrate [4F-PCC]; 525, andexanet alfa [AA]; 340, idarucizumab). The mean age was 76 (range, 68-83) years, and 57% were men. For 4F-PCC, anticoagulation reversal was 77% (95% CI, 72%-82%; I2 = 55%); all-cause mortality, 26% (95% CI, 20%-32%; I2 = 68%), and thromboembolic events, 8% (95% CI, 5%-12%; I2 = 41%). For AA, anticoagulation reversal was 75% (95% CI, 67%-81%; I2 = 48%); all-cause mortality, 24% (95% CI, 16%-34%; I2 = 73%), and thromboembolic events, 14% (95% CI, 10%-19%; I2 = 16%). Idarucizumab for reversal of dabigatran had an anticoagulation reversal rate of 82% (95% CI, 55%-95%; I2 = 41%), all-cause mortality, 11% (95% CI, 8%-15%, I2 = 0%), and thromboembolic events, 5% (95% CI, 3%-8%; I2 = 0%). A direct retrospective comparison of 4F-PCC and AA showed no differences in anticoagulation reversal, proportional mortality, or thromboembolic events. CONCLUSIONS AND RELEVANCE In the absence of randomized clinical comparison trials, the overall anticoagulation reversal, mortality, and thromboembolic event rates in this systematic review and meta-analysis appeared similar among available DOAC reversal agents for managing ICH. Cost, institutional formulary status, and availability may restrict reversal agent choice, particularly in small community hospitals.

Abstract

INTRODUCTION Low dose factor VIII prophylactic therapy in hemophilia has not been well established till date. This randomized controlled trial compared the efficacy of twice vs. thrice weekly schedule of low dose prophylactic factor VIII in children with hemophilia A as evaluated by the bleeding rate and clinico-radiological evaluation. METHODS Thirty-three children with severe hemophilia A (≤18 years) were randomized into two groups. Baseline evaluation included detailed history, clinical (HJHS 2.1 score and FISH score) and radiological examination (Pettersson score and ultrasound score). Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose being 10 U/kg in both groups. All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at the end of follow up were recorded. RESULTS We analyzed 14 children in twice weekly prophylaxis group and 16 children in thrice weekly prophylaxis group. Statistically insignificant difference was found between the bleeding rates in both the groups after prophylaxis with the median values of monthly bleeding rate being 0.17 and p-value of 0.79. The differences between the initial and final clinical and radiological scores within each group were found to be statistically significant. There was no significant difference in the clinical and radiological scores in between the groups. CONCLUSION Twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A. Lay summaryHemophilia A is one of the most common congenital coagulation factor deficiencies. Low dose factor VIII prophylaxis is recommended for hemophilia in resource-poor settings to reduce the bleeding episodes and improve the quality of life, although the optimal schedule for the same has not been well established. A randomized controlled trial on 33 children with hemophilia A (≤18 years) was done to compare the efficacy of twice versus thrice weekly schedule of prophylactic factor VIII. Group 1 received twice weekly factor VIII prophylaxis while group 2 received thrice weekly factor VIII prophylaxis, the dose in both groups being 10 U/kg. They were evaluated by the bleeding rate and clinical (HJHS 2.1 score and FISH score) and radiological scores (Pettersson score and ultrasound score). All participants were followed up over next 6 months to one year. Data regarding acute bleeding episodes and repeat clinico-radiological assessment at end of follow up were recorded. When analyzed, statistically insignificant difference was found between the bleeding rates after the two prophylaxis regimes. There was a significant improvement between initial and final clinical and radiological scores in both the groups and no difference was recorded in between the groups. To conclude, twice weekly FVIII therapy is effective, easily administered prophylactic schedule to prevent long-term complications of hemophilia A.

Abstract

BACKGROUND Kawasaki disease (KD) is often complicated by coronary artery lesion (CAL), including dilatation or aneurysms. Intravenous immunoglobulin (IVIG) is used with aspirin to prevent CAL in KD. OBJECTIVE Given that the primary treatment for other vasculitis is the use of corticosteroids, this study has been performed to evaluate the effect of intravenous methylprednisolone pulse (IVMP) therapy in preventing CAL in KD. METHOD A randomized, single-blind clinical trial was conducted on 40 KD patients aged six months to five years. Patients were randomized into two groups according to the main treatment plan in addition to aspirin: case group (IVMP for three consecutive days and then oral prednisolone for three days) and control group (intravenous immunoglobulin 2 g/kg). Echocardiography was performed for all children at least three times, during the acute phase, two weeks, and two months later. RESULTS Data analysis at the end of the study was done on 40 patients (20 patients in each group). There were no significant differences in age and sex distribution, mean fever, and acute phase duration, as well as baseline echocardiography in the two groups. The frequency of CAL was 20% in the case group and 45% in the control group, after two weeks (p<0.05), but there was no significant difference between two groups in types of coronary artery lesion after two weeks and the frequency and severity of CAL after two months. CONCLUSION IVMP as initial line therapy effectively control systemic and vascular inflammation and decrease coronary artery damage in KD.

Abstract

PURPOSE The purpose of the study was to evaluate, as a pilot trial, safety and tolerability of CAM-101 10% and 30% topical ophthalmic fibrinogen-depleted human platelet lysate (FD hPL) solution in patients with dry eye disease (DED) secondary to graft-versus-host disease (GvHD) after 6 weeks of treatment. DESIGN A phase I/II, pilot, prospective, multicenter, randomized, double-masked clinical trial. PARTICIPANTS Patients with DED secondary to GvHD. METHODS Sixty-four adult patients were stratified by "symptom severity" (Ocular Surface Disease Index [OSDI], ocular discomfort Visual Analog Scale (VAS), ocular symptom frequency, and use of artificial tears) and then randomized 1:1:1 to CAM-101 (FD hPL) at 10% or 30% concentration or an electrolyte (Plasma-Lyte A) vehicle control, 1 drop in both eyes, 4 times daily, for 42 days. After 42 days, control patients were offered 42 days of open-label treatment with 30% FD hPL. MAIN OUTCOME MEASURES Primary outcome safety measures were ocular and systemic adverse events and the number of patients in each group with clinically significant change from normal to abnormal in any ocular findings. Secondary outcomes were changes from baseline to day 42 in ocular discomfort, OSDI, fluorescein corneal staining, and lissamine green conjunctival staining relative to the vehicle control. The ocular symptom frequency was assessed on a 100-point VAS. RESULTS FD hPL 10% and 30% were safe and well tolerated. Relative to the vehicle control, significant decreases from baseline to day 42 were seen in the FD hPL 30% group with regard to ocular discomfort (mean decrease = -18.04; P = 0.018), frequency of burning/stinging (-20.23; P = 0.022), eye discomfort (-32.97; P < 0.001), eye dryness (-21.61; P = 0.020), pain (-15.12; P = 0.044), photophobia (-24.33; P = 0.0125), and grittiness (-20.08; P = 0.0185). Decreases were also seen for itching and foreign body sensation, though not statistically significant. Improvements were seen in tear breakup time (mean increase = 1.30 seconds; P = 0.082) and the investigator's global evaluation 4-point scale (mean decrease = -0.86; P = 0.026). Corneal fluorescein staining was not improved. The OSDI had a mean decrease of -8.88 compared to the vehicle, although not statistically significant. CONCLUSIONS Fibrinogen-depleted human platelet lysate appears to be well tolerated, with no significant toxicity at concentrations of 10% and 30%. These initial data suggest some efficacy, especially for subjective outcome measures relative to baseline assessments and treatment with the vehicle, but larger studies are needed to confirm these effects.

Abstract

OBJECTIVES Neonatal sepsis is one of the leading causes of neonatal deaths in neonatal intensive care units. Hence, it is essential to review the evidence from systematic reviews on interventions for reducing late-onset sepsis (LOS) in neonates. METHODS PubMed and the Cochrane Central were searched from inception through August 2020 without any language restriction. Cochrane reviews of randomized clinical trials (RCTs) assessing any intervention in the neonatal period and including one or more RCTs reporting LOS. Two authors independently performed screening, data extraction, assessed the quality of evidence using Cochrane Grading of Recommendations Assessment, Development and Evaluation, and assessed the quality of reviews using a measurement tool to assess of multiple systematic reviews 2 tool. RESULTS A total of 101 high-quality Cochrane reviews involving 612 RCTs and 193,713 neonates, evaluating 141 interventions were included. High-quality evidence showed a reduction in any or culture-proven LOS using antibiotic lock therapy for neonates with central venous catheters (CVC). Moderate-quality evidence showed a decrease in any LOS with antibiotic prophylaxis or vancomycin prophylaxis for neonates with CVC, chlorhexidine for skin or cord care, and kangaroo care for low birth weight babies. Similarly, moderate-quality evidence showed reduced culture-proven LOS with intravenous immunoglobulin prophylaxis for preterm infants and probiotic supplementation for very low birth weight (VLBW) infants. Lastly, moderate-quality evidence showed a reduction in fungal LOS with the use of systemic antifungal prophylaxis in VLBW infants. CONCLUSIONS The overview summarizes the evidence from the Cochrane reviews assessing interventions for reducing LOS in neonates, and can be utilized by clinicians, researchers, policymakers, and consumers for decision-making and translating evidence into clinical practice.

Abstract

BACKGROUND Clinical practice guidelines (CPGs) are statements that should be rigorously developed to guide clinicians' decision-making. However, given the scarce evidence for certain vulnerable groups like children, CPGs' recommendations formulation could be challenging. METHODS We conducted a scoping review of CPGs for COVID-19 management in children. Documents were included if they claimed to be a "clinical practice guideline", published between January and October 2021, and described the process followed to issue their recommendations. We assessed the quality using the "Appraisal of Guidelines for Research and Evaluation II" (AGREE-II) and described how the recommendations were reached. RESULTS We found five CPGs that fulfilled our inclusion criteria. The median score on the overall AGREE-II evaluation was 61% (range: 49%-72%), and the score on the third domain referred to the rigor of methodological development was 52% (range: 25%-88%). Recommendations for remdesivir, tocilizumab, and intravenous immunoglobulin were heterogeneous across CPGs (in favor, against, no recommendation), as well as the methodologies used to present the evidence, perform the benefits/harms balance, and issue the recommendation. CONCLUSIONS Heterogeneous recommendations and justifications across CPGs were found in the three assessed topics. Future CPGs should describe in detail their evidence-to-decision process to issue reliable and transparent recommendations.

Abstract

BACKGROUND The exact prevalence of Multisystem Inflammatory Syndrome in Adults (MIS-A) is largely unknown. Vague and multiple definitions and treatment options often add to the confusion on how to label the diagnosis with certainty. OBJECTIVES The objective of the study was to determine the demographic profile, clinical presentation, laboratory findings and outcomes of MIS-A in COVID-19. METHODS A systematic review was conducted after registering with PROSPERO. Multiple databases were systematically searched to encompass studies characterizing MIS-A from 1st January 2020 up to 31st August 2021. The inclusion criteria were- to incorporate all published or in press peer-reviewed articles reporting cases of MIS-A. We accepted the following types of studies: case reports, case-control, case series, cross-sectional studies and letters to the editors that incorporated clinical, laboratory, imaging, as well as the hospital course of MIS-A patients. The exclusion criteria for the review were- articles not in English, only abstracts published, no data on MIS-A and articles which have focus on COVID-19, and not MIS-A. Two independent authors screened the articles, extracted the data, and assessed the risk of bias. RESULTS A total of 53 articles were included in this review with a sample size of 79 cases. Majority of the patients were males (73.4%) with mean age of 31.67±10.02 years. Fever (100%) and skin rash (57.8%) were the two most common presenting symptoms. Echocardiographic data was available for 73 patients of whom 41 (73.2%) had reduced left ventricular ejection fraction. Cardiovascular system was most frequently involved (81%) followed by gastrointestinal (73.4%) and mucocutaneous (51.9%) involvement. Anti-inflammatory therapies used in treatment included steroids (60.2%), intravenous immunoglobulin (37.2%) and biologics (10.2%). Mean duration of the hospital stay was 11.67±8.08 days. Data regarding the outcomes was available for all 79 subjects of whom 4 (5.1%) died during course of hospital stay. CONCLUSIONS Emergence of MIS-A calls for further large-scale studies to establish standard case definitions and definite treatment guidelines.