A phase 2 single center open label randomised control trial for convalescent plasma therapy in patients with severe COVID-19
Nature communications. 2022;13(1):383
A single center open label phase 2 randomised control trial (Clinical Trial Registry of India No. CTRI/2020/05/025209) was done to assess clinical and immunological benefits of passive immunization using convalescent plasma therapy. At the Infectious Diseases and Beleghata General Hospital in Kolkata, India, 80 patients hospitalized with severe COVID-19 disease and fulfilling the inclusion criteria (aged more than 18 years, with either mild ARDS having PaO2/FiO2 200-300 or moderate ARDS having PaO2/FiO2 100-200, not on mechanical ventilation) were recruited and randomized into either standard of care (SOC) arm (N = 40) or the convalescent plasma therapy (CPT) arm (N = 40). Primary outcomes were all-cause mortality by day 30 of enrolment and immunological correlates of response to therapy if any, for which plasma abundance of a large panel of cytokines was quantitated before and after intervention to assess the effect of CPT on the systemic hyper-inflammation encountered in these patients. The secondary outcomes were recovery from ARDS and time taken to negative viral RNA PCR as well as to report any adverse reaction to plasma therapy. Transfused convalescent plasma was characterized in terms of its neutralizing antibody content as well as proteome. The trial was completed and it was found that primary outcome of all-cause mortality was not significantly different among severe COVID-19 patients with ARDS randomized to two treatment arms (Mantel-Haenszel Hazard Ratio 0.6731, 95% confidence interval 0.3010-1.505, with a P value of 0.3424 on Mantel-Cox Log-rank test). No adverse effect was reported with CPT. In severe COVID-19 patients with mild or moderate ARDS no significant clinical benefit was registered in this clinical trial with convalescent plasma therapy in terms of prespecified outcomes.
Stability of biomaterials used in adjunct to coronally advanced flap: A systematic review and network meta-analysis
Clinical and experimental dental research. 2021
AIM: The objective of this network meta-analysis was to rank different biomaterials used in adjunct to coronally advanced flap (CAF), based on their performance in root-coverage for Miller's Class I and II gingival recessions. MATERIALS AND METHODS An electronic database search was carried out in PUBMED, CENTRAL, SCOPUS, and EMBASE to identify the eligible articles and compiled into the citation manager to remove the duplicates. The primary outcome was keratinized gingival tissue width (KGW) and percentage of root coverage (%RC). The treatment effect of different biomaterials was estimated using predictive interval plots and ranked based on biomaterials performance, using multidimensional scale ranking. RESULTS CAF + connective tissue graft (CTG), CAF + platelet concentrate matrix (PCM) and acellular dermal matrix (ADM) ranked at the top positions in performance in improving KGW. The highest ranked materials in improving percentage of root coverage in gingival recession were CAF + collagen matrix (CM) + gingival fibroblasts (GF), CAF + ADM + platelet rich plasma (PRP) and CAF + ADM, as compared to CAF alone. CONCLUSION CTG, ADM, platelet concentrates, and CM + GFs, when used in adjunct to CAF, showed improved stability over ≥12 months of follow-up, better percentage of root coverage, and improved keratinized gingival width.
Effect of Albumin Addition to Cardiopulmonary Bypass Prime on Outcomes in Children Undergoing Open-Heart Surgery (EACPO Study)-A Randomized Controlled Trial
World journal for pediatric & congenital heart surgery. 2020;:2150135120959088
BACKGROUND There is a paucity of literature regarding the association of high oncotic priming solutions for pediatric cardiopulmonary bypass (CPB) and outcomes, and no consensus exists regarding the composition of optimal CPB priming solution. This study aimed to examine the impact of high oncotic pressure priming by the addition of 20% human albumin on outcomes. METHODS Double-blinded, randomized controlled study was done in the pediatric cardiac intensive care unit of a tertiary care hospital. Consecutive children with congenital heart diseases admitted for open-heart surgery were randomized into two groups, where the study group received an additional 20% albumin to conventional blood prime before CPB initiation. RESULTS We enrolled 39 children in the high oncotic prime (added albumin) group and 37 children in the conventional prime group. In the first 24-hour postoperative period, children in the albumin group had significantly lower occurrence of hypotension (28.2% vs 54%, P = .02), requirement of fluid boluses (25.6% vs 54%, P = .006), and lactate clearance time (6 vs 9 hours, P < .001). Albumin group also had significantly higher platelet count (×10(3)/µL) at 24 hours (112 vs 91, P = .02). There was no significant difference in intra-CPB hemodynamic parameters and incidence of acute kidney injury. In subgroup analysis based on risk category, significantly decreased intensive care unit stay (4 vs 5 days, P = .04) and hospital stay (5 vs 7 days, P = .002) were found in the albumin group in low-risk category. CONCLUSION High oncotic pressure CPB prime using albumin addition might be beneficial over conventional blood prime, and our study does provide a rationale for further studies.
Comparative evaluation of bone regeneration with platelet-rich fibrin in mandibular third molar extraction socket: A randomized split-mouth study
National journal of maxillofacial surgery. 2020;11(2):241-247
PURPOSE Platelet-rich fibrin (PRF) is a new platelet concentrate concept consisting of an autologous fibrin gel having accumulation of platelets and the released cytokines in a fibrin clot. The study aims to evaluate the efficacy of autologous PRF in accelerating bone regeneration and repair in fresh third molar extraction sockets. The investigators hypothesized the cicatricial properties and accumulation of growth factors in a single clot which will improve bone density and quality. MATERIALS AND METHODS PRF results from a natural and progressive polymerization occurring during centrifugation. Two groups were made with bilaterally impacted third molar patients. PRF was obtained and surgical extraction was carried out under aseptic conditions. Quantitative data are presented as mean. Statistical significance was inferred at P < 0.05. RESULTS Results obtained were evaluated statistically and found a significant difference between the groups in improvement in alveolar bone density of regenerate measured radiographically. The study demonstrates a faster bone formation in the extracted sockets with PRF as compared to control. CONCLUSION PRF proved to be an autologous biomaterial with useful features that allowed efficient postextraction bone defect filling and faster bone regeneration.
Additive Effect of Platelet Rich Fibrin with Coronally Advanced Flap Procedure in Root Coverage of Miller's Class I and II Recession Defects-A PRISMA Compliant Systematic Review and Meta-Analysis
Materials (Basel, Switzerland). 2020;13(19)
AIM: This systematic review and meta-analysis aims to assess the additive effect of leukocyte and platelet-rich fibrin (L-PRF) on coronally advanced flap (CAF) procedures in root coverage of Miller's class I and II gingival recession defects. Review methodology: A comprehensive search in MEDLINE (PubMed), Scopus and CENTRAL (the Cochrane Central Register of Controlled Trials), along with an additional hand search, provided eight randomized clinical trials to be included in this review. A total of 167 patients with 470 gingival recession defects were analyzed. A meta-analysis was carried out to assess the change in gingival thickness (GT), width of keratinized gingiva (WKG), root coverage percentage (%RC), clinical attachment level (CAL) and recession depth (RD) at all follow-ups between CAF alone and CAF + L-PRF groups for all included studies. A subgroup analysis was carried out based on recession type (single/multiple). RESULTS Overall, a significant improvement in GT, CAL and RD was found when treated with CAF + L-PRF. There was a trend for a positive effect in terms of an increase in WKG when using L-PRF, especially in the treatment of single recession, though significance was not achieved (p = 0.08 overall). The results of heterogeneity among the subgroups were varied and were found to be greater than 91.3% for GT and 32.8% for WKG. CONCLUSION L-PRF when used in addition to CAF showed favorable results for the treatment of class I and II gingival recession defects.
Plasma rich in growth factors (PRGF) in non-surgical periodontal therapy: a randomized clinical trial
Braz Oral Res. 2020;34:e034
The aim of this split mouth, double blinded, randomized clinical trial was to evaluate the clinical efficacy of use of Plasma rich in growth factors (PRGF) as an adjunct to scaling and root planing (SRP) in the treatment of periodontal pockets. Twenty six patients (15 males, 11 females) diagnosed with generalized periodontitis with Pocket Depth > 5mm and plaque index score < 1.5, were randomly allocated by using computer generated random sequence, into two groups, one treated with intra-pocket application of PRGF adjunct to SRP and other with SRP alone. The clinical outcomes like pocket depth (PD), relative attachment level (RAL) and sulcus bleeding index (SBI) were assessed at baseline, 3 months and 6 months. Twenty two patients (44 sites) were analyzed at the end of 6 month follow-up, using SPSS 20.0v software. There was a significant statistical difference observed between both the groups favouring SRP +PRGF group in terms of PD (p = 0.007) and RAL (p = 0.021) at the end of 6 month follow-up. Also there was a statistical significant difference (< 0.001) at all time points compared to baseline, for all parameters in intra-group comparison. Moreover, the sites with PD>4mm necessitating further treatment after 6-month follow-up were significantly lesser for SRP+PRGF group. The use of PRGF technology in non-surgical periodontal therapy, by single intra-pocket application in to periodontal pockets as an adjunct to SRP, in chronic periodontitis patients, was found to be effective in reduction of pocket depth and gain in clinical attachment level.
Comparison of Blood-Conserving and Allogenic Transfusion-Sparing Effects of Antifibrinolytics in Scoliosis Correction Surgery
Anesthesia, essays and researches. 2020;14(2):259-265
BACKGROUND Intraoperative antifibrinolytic drug administration is a safe and effective method of reducing blood loss and allogenic transfusions in patients undergoing spine deformity correction. AIM: This study aimed to compare the effectiveness of two antifibrinolytic drugs tranexamic acid (TXA) and epsilon amino caproic acid (EACA) in reducing peri-operative blood loss and transfusion requirements against a placebo control in patients with idiopathic scoliosis undergoing correction surgery. SETTING AND DESIGN This is a prospective, randomized, double-blinded, controlled comparative study. METHODOLOGY Patients in TXA group received 50 mg.kg(-1) bolus and 10 mg.kg(-1).h(-1) infusion as against 100 mg.kg(-1) and 10 mg.kg(-1).h(-1) infusion in EACA group. The placebo group had saline bolus and infusion. Parameters observed included baseline demographic and deformity data, duration of surgery, total peri-operative blood loss, and allogenic packed red cell transfusion requirements. STATISTICAL ANALYSIS Mean and standard deviation were used to represent the quantitative continuous data, and percentage was used to represent categorical data. The Student's t-test and ANOVA were used to compare means between groups. Bonferroni's multiple comparison test was used to find out the association between categorical variables. RESULTS A total of 36 patients were enrolled with 12 patients in each group. Peri-operative blood loss was 50.1% lower in patients receiving TXA and 17.7% lower in patients receiving EACA compared with the placebo group. The volume of total packed red cell transfusion was 66.7% lower in patients receiving TXA and 45.6% lower in patients receiving EACA compared with placebo. CONCLUSION TXA was more effective in reducing total peri-operative blood loss and allogenic transfusion requirement in idiopathic scoliosis correction surgery compared to EACA.
Patients with idiopathic scoliosis undergoing correction surgery (n= 36).
Tranexamic acid (TXA, n= 12).
Epsilon amino caproic acid (EACA, n= 12). Placebo (saline, n= 12).
Peri-operative blood loss was 50.1% lower in patients receiving TXA and 17.7% lower in patients receiving EACA compared with the placebo group. The volume of total packed red cell transfusion was 66.7% lower in patients receiving TXA and 45.6% lower in patients receiving EACA compared with placebo.
Thromboelastography-Guided Blood Component Use in Patients With Cirrhosis With Nonvariceal Bleeding: A Randomized Controlled Trial
Hepatology (Baltimore, Md.). 2019
Thromboelastography (TEG) provides a more comprehensive global coagulation assessment than routine tests (international normalized ratio [INR] and platelet [PLT] count), and its use may avoid unnecessary blood component transfusion in patients with advanced cirrhosis and significant coagulopathy who have nonvariceal upper gastrointestinal (GI) bleeding. A total of 96 patients with significant coagulopathy (defined in this study as INR >1.8 and/or PLT count <50 x 10(9) /L) and nonvariceal upper GI bleed (diagnosed after doing upper gastrointestinal endoscopy [UGIE], which showed ongoing bleed from a nonvariceal source) were randomly allocated to TEG-guided transfusion strategy (TEG group; n = 49) or standard-of-care (SOC) group (n = 47). In the TEG group, only 26.5% patients were transfused with all three blood components (fresh frozen plasma [FFP], PLTs, and cryoprecipitate) versus 87.2% in the SOC group (P < 0.001). Whereas 7 (14.3%) patients in the TEG group received no blood component transfusion, there were no such patients in the SOC group (P = 0.012). Also, there was a significantly lower use of blood components (FFP, PLTs, and cryoprecipitate) in the TEG group compared to the SOC group. Failure to control bleed, failure to prevent rebleeds, and mortality between the two groups were similar. CONCLUSION In patients with advanced cirrhosis with coagulopathy and nonvariceal upper GI bleeding, TEG-guided transfusion strategy leads to a significantly lower use of blood components compared to SOC (transfusion guided by INR and PLT count), without an increase in failure to control bleed, failure to prevent rebleed, and mortality.
Autologous Platelet Concentrates in Treatment of Furcation Defects-A Systematic Review and Meta-Analysis
International journal of molecular sciences. 2019;20(6)
BACKGROUND The aim of this review was to evaluate the adjunctive effect of autologous platelet concentrates (APCs) for the treatment of furcation defects, in terms of scientific quality of the clinical trials and regeneration parameters assessment. METHODS A systematic search was carried out in the electronic databases MEDLINE, SCOPUS, CENTRAL (Cochrane Central Register of Controlled Trials), and EMBASE, together with hand searching of relevant journals. Two independent reviewers screened the articles yielded in the initial search and retrieved the full-text version of potentially eligible studies. Relevant data and outcomes were extracted from the included studies. Risk of bias assessment was also carried out. The outcome variables, relative to baseline and post-operative defect characteristics (probing pocket depth (PPD), horizontal and vertical clinical attachment loss (HCAL, VCAL), horizontal and vertical furcation depth (HFD, VFD) were considered for meta-analysis. RESULTS Ten randomized trials were included in this review. Only one study was judged at high risk of bias, while seven had a low risk, testifying to the good level of the evidence of this review. The meta-analysis showed a favorable effect regarding all outcome variables, for APCs used in adjunct to open flap debridement (p < 0.001). Regarding APCs in adjunct to bone grafting, a significant advantage was found only for HCAL (p < 0.001, mean difference 0.74, 95% CI 0.54, 0.94). The sub-group analysis showed that both platelet-rich fibrin and platelet-rich plasma in adjunct with open flap debridement, yielded significantly favorable results. No meta-analysis was performed for APCs in combination with guided tissue regeneration (GTR) as only one study was found. CONCLUSION For the treatment of furcation defects APCs may be beneficial as an adjunct to open flap debridement alone and bone grafting, while limited evidence of an effect of APCs when used in combination with GTR was found.
Screening for undiagnosed bleeding disorders in post-tonsillectomy bleed patients: Retrospective review and systematic review of the literature
International journal of pediatric otorhinolaryngology. 2019;124:210-214
OBJECTIVES There is currently no standard for screening children with post-tonsillectomy bleeds (PTB) for coagulopathy disorders. This study aims to identify children with occult coagulopathy diagnosed at PTB and to identify factors associated with diagnosis. A systematic review of the literature further identified trends in this topic. METHODS A retrospective chart review of patients returning to the operating room for PTB at a tertiary children's hospital was undertaken from 2012 to 2016. A systematic review using Medline OVID was subsequently performed. RESULTS Of 12,503 tonsillectomies, 311 children (52% male, mean age 8 years) required surgery for PTB (2.5% rate). Twenty-one patients (7%) had multiple episodes. Only two patients (0.6%) (both with known coagulopathy) underwent pre-tonsillectomy labs and 260 (84%) had labs at PTB. Six patients (2%) were diagnosed with a new coagulopathy, most commonly von Willebrand's Disease (vWD) in five (2%). Three patients (1%) were diagnosed at first PTB and three (1%) at second PTB. Of the three diagnosed at second PTB, two had normal partial thromboplastin time (PTT). In systematic review, 1243 manuscripts were reviewed and 8 papers discussing this topic are presented. CONCLUSION Occult coagulopathy was rarely diagnosed at PTB, but this may be limited by inconsistent screening. PT and PTT are not sensitive tests for vWD, and normal coagulation labs may lead to delayed diagnosis. The literature reveals occult coagulopathy is rare but often diagnosed after severe or recurrent hemorrhage. In order to provide efficient care and medical management, a standardized algorithm and sensitive labs for screening PTB patients are needed.