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Iron supplementation and the risk of bronchopulmonary dysplasia in extremely low gestational age newborns
Garcia MR, Comstock BA, Patel RM, Tolia VN, Josephson CD, Georgieff MK, Rao R, Monsell SE, Juul SE, Ahmad KA
Pediatric research. 2022
Abstract
BACKGROUND The aim of this study was to determine the relationship between iron exposure and the development of bronchopulmonary dysplasia (BPD). METHODS A secondary analysis of the PENUT Trial dataset was conducted. The primary outcome was BPD at 36 weeks gestational age and primary exposures of interest were cumulative iron exposures in the first 28 days and through 36 weeks' gestation. Descriptive statistics were calculated for study cohort characteristics with analysis adjusted for the factors used to stratify randomization. RESULTS Of the 941 patients, 821 (87.2%) survived to BPD evaluation at 36 weeks, with 332 (40.4%) diagnosed with BPD. The median cohort gestational age was 26 weeks and birth weight 810 g. In the first 28 days, 76% of infants received enteral iron and 55% parenteral iron. The median supplemental cumulative enteral and parenteral iron intakes at 28 days were 58.5 and 3.1 mg/kg, respectively, and through 36 weeks' 235.8 and 3.56 mg/kg, respectively. We found lower volume of red blood cell transfusions in the first 28 days after birth and higher enteral iron exposure in the first 28 days after birth to be associated with lower rates of BPD. CONCLUSIONS We find no support for an increased risk of BPD with iron supplementation. TRIAL REGISTRATION NUMBER NCT01378273. https://clinicaltrials.gov/ct2/show/NCT01378273 IMPACT Prior studies and biologic plausibility raise the possibility that iron administration could contribute to the pathophysiology of oxidant-induced lung injury and thus bronchopulmonary dysplasia in preterm infants. For 24-27-week premature infants, this study finds no association between total cumulative enteral iron supplementation at either 28-day or 36-week postmenstrual age and the risk for developing bronchopulmonary dysplasia.
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Cryoprecipitate transfusion in trauma patients attenuates hyperfibrinolysis and restores normal clot structure and stability: Results from a laboratory sub-study of the FEISTY trial
Morrow, G. B., Feller, T., McQuilten, Z., Wake, E., Ariëns, R. A. S., Winearls, J., Mutch, N. J., Laffan, M. A., Curry, N.
Critical Care (London, England). 2022;26(1):290
Abstract
BACKGROUND Fibrinogen is the first coagulation protein to reach critical levels during traumatic haemorrhage. This laboratory study compares paired plasma samples pre- and post-fibrinogen replacement from the Fibrinogen Early In Severe Trauma studY (FEISTY; NCT02745041). FEISTY is the first randomised controlled trial to compare the time to administration of cryoprecipitate (cryo) and fibrinogen concentrate (Fg-C; Riastap) in trauma patients. This study will determine differences in clot strength and fibrinolytic stability within individuals and between treatment arms. METHODS Clot lysis, plasmin generation, atomic force microscopy and confocal microscopy were utilised to investigate clot strength and structure in FEISTY patient plasma. RESULTS Fibrinogen concentration was significantly increased post-transfusion in both groups. The rate of plasmin generation was reduced 1.5-fold post-transfusion of cryo but remained unchanged with Fg-C transfusion. Plasminogen activator inhibitor 1 activity and antigen levels and Factor XIII antigen were increased post-treatment with cryo, but not Fg-C. Confocal microscopy analysis of fibrin clots revealed that cryo transfusion restored fibrin structure similar to those observed in control clots. In contrast, clots remained porous with stunted fibres after infusion with Fg-C. Cryo but not Fg-C treatment increased individual fibre toughness and stiffness. CONCLUSIONS In summary, our data indicate that cryo transfusion restores key fibrinolytic regulators and limits plasmin generation to form stronger clots in an ex vivo laboratory study. This is the first study to investigate differences in clot stability and structure between cryo and Fg-C and demonstrates that the additional factors in cryo allow formation of a stronger and more stable clot.
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Phase 3 Study of Subcutaneous Versus Intravenous Ravulizumab in Eculizumab-Experienced Adult Patients with PNH: Primary Analysis and 1-Year Follow-Up
Yenerel MN, Sicre de Fontbrune F, Piatek C, Sahin F, Füreder W, Ortiz S, Ogawa M, Ozol-Godfrey A, Sierra JR, Szer J
Advances in therapy. 2022
Abstract
INTRODUCTION This study compared the pharmacokinetics (PK) of the ravulizumab on-body delivery system for subcutaneous (SUBQ) administration with intravenous (IV) ravulizumab in eculizumab-experienced patients with paroxysmal nocturnal hemoglobinuria (PNH). METHODS Patients with PNH received SUBQ ravulizumab (n = 90) or IV ravulizumab (n = 46) during the 10-week randomized treatment period; all patients then received SUBQ ravulizumab during an extension period (< 172 weeks; data cutoff 1 year). Primary endpoint was day 71 serum ravulizumab trough concentration (C(trough)). Secondary endpoints were ravulizumab C(trough) and free C5 over time. Efficacy endpoints included change in lactate dehydrogenase (LDH), breakthrough hemolysis (BTH), transfusion avoidance, stabilized hemoglobin, and Treatment Administration Satisfaction Questionnaire (TASQ) score. Safety, including adverse events (AEs) and adverse device effects (ADEs), was assessed until data cutoff. RESULTS SUBQ ravulizumab demonstrated PK non-inferiority with IV ravulizumab (day 71 SUBQ/IV geometric least-squares means ratio 1.257 [90% confidence interval 1.160-1.361; p < 0.0001]). Through 1 year of SUBQ administration, ravulizumab C(trough) values were > 175 μg/mL (PK threshold) and free C5 < 0.5 μg/mL (PD threshold). Efficacy endpoints remained stable: mean (standard deviation, SD) LDH percentage change was 0.9% (20.5%); BTH events, 5/128 patients (3.9%); 83.6% achieved transfusion avoidance; 79.7% achieved stabilized hemoglobin. Total TASQ score showed improved satisfaction with SUBQ ravulizumab compared with IV eculizumab (mean [SD] change at SUBQ day 351, - 69.3 [80.1]). The most common AEs during SUBQ treatment (excluding ADEs) were headache (14.1%), COVID-19 (14.1%), and pyrexia (10.9%); the most common ADE unrelated to a device product issue was injection site reaction (4.7%). Although many patients had ≥ 1 device issue-related ADE, full SUBQ dose administration was achieved in 99.9% of attempts. CONCLUSIONS SUBQ ravulizumab provides an additional treatment choice for patients with PNH. Patients may switch to SUBQ ravulizumab from IV eculizumab or ravulizumab without loss of efficacy. TRIAL REGISTRATION NCT03748823. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder characterized by the destruction of red blood cells (hemolysis) within blood vessels. In addition to hemolysis, patients with PNH are susceptible to life-threatening blood clots (thromboses). Eculizumab and ravulizumab are types of treatments for PNH, called C5 inhibitors. In the blood, these treatments bind to C5 protein and prevent the destruction of red blood cells, reducing the symptoms and complications of PNH. Both treatments are approved for use via intravenous (through the vein) administration. Ravulizumab is also approved in the USA for use via subcutaneous (under the skin) administration. This study compared subcutaneous ravulizumab with intravenous ravulizumab in patients with PNH who had previously been treated with eculizumab. During the initial treatment period of 71 days, 90 patients received subcutaneous ravulizumab and 46 received intravenous ravulizumab. Following this period, all patients received subcutaneous ravulizumab. At day 71, the amount of ravulizumab in the blood of patients taking subcutaneous ravulizumab was no less than in patients taking intravenous ravulizumab and was maintained over 1 year of treatment. Efficacy measures (how well it works) remained stable in patients taking subcutaneous ravulizumab for 1 year and side effects were comparable with those of intravenous ravulizumab. Patients reported more satisfaction with subcutaneous ravulizumab than intravenous eculizumab, as assessed by the Treatment Administration Satisfaction Questionnaire. This study showed that patients with PNH can switch from intravenous eculizumab or ravulizumab to subcutaneous ravulizumab without loss of efficacy. Subcutaneous ravulizumab provides an additional treatment choice for patients with PNH. eng
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Is intravenous tranexamic acid effective in reduction of blood loss during pelvic and acetabular surgery?
Sharaby MMF, El-Deeb YM
International orthopaedics. 2022
Abstract
PURPOSE Pelvic and acetabular surgery is associated with one of the highest amounts of blood loss. Tranexamic acid is a good choice to reduce blood loss during this type of surgery. However, being antifibrinolytic drug, the chance to have coagulation complications including DVT is a risk that should be considered particularly in such major trauma patients with the body's response to trauma and with possible prolonged bed stay. The aim of this study is to evaluate the effectiveness of intravenous tranexamic acid injection during pelvic and acetabular surgery for reduction of blood loss during surgery and after surgery and to evaluate any possible complications for its use. METHODS This prospective randomized clinical trial includes 97 patients divided between two groups; group 1 (G1) which received TXA, while the second group (G2) is the control group. The primary outcome measures were total blood loss (TBL), allogenic blood units transfused, and the blood lost intra-operatively (IBL). The TBL was calculated by the haemoglobin balance method while the intra-operative blood loss was measured by the gravimetric method. Any complications related to the drug were evaluated particularly DVT. RESULTS The study showed significantly less TBL (G1 = 829.7 ± 219.2, G2 = 1036.9 ± 314.9) and blood transfusion (G1 = 52.4 ± 40 g, G2 = 89.4 ± 60.6 g) in G1 compared to the G2. CONCLUSION This study proved the possible reduction of TBL and the need of blood transfusion by the use of TXA in pelvic and acetabular injuries.
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Prothrombin Complex Concentrate vs Plasma for Post-Cardiopulmonary Bypass Coagulopathy and Bleeding: A Randomized Clinical Trial
Smith MM, Schroeder DR, Nelson JA, Mauermann WJ, Welsby IJ, Pochettino A, Montonye BL, Assawakawintip C, Nuttall GA
JAMA surgery. 2022
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Abstract
IMPORTANCE Post-cardiopulmonary bypass (CPB) coagulopathy and bleeding are among the most common reasons for blood product transfusion in surgical practices. Current retrospective data suggest lower transfusion rates and blood loss in patients receiving prothrombin complex concentrate (PCC) compared with plasma after cardiac surgery. OBJECTIVE To analyze perioperative bleeding and transfusion outcomes in patients undergoing cardiac surgery who develop microvascular bleeding and receive treatment with either PCC or plasma. DESIGN, SETTING, AND PARTICIPANTS A single-institution, prospective, randomized clinical trial performed at a high-volume cardiac surgical center. Patients were aged 18 years or older and undergoing cardiac surgery with CPB. Patients undergoing complex cardiac surgical procedures (eg, aortic replacement surgery, multiple procedures, or repeated sternotomy) were preferentially targeted for enrollment. During the study period, 756 patients were approached for enrollment, and 553 patients were randomized. Of the 553 randomized patients, 100 patients met criteria for study intervention. INTERVENTIONS Patients with excessive microvascular bleeding, a prothombin time (PT) greater than 16.6 seconds, and an international normalized ratio (INR) greater than 1.6 were randomized to receive treatment with either PCC or plasma. The PCC dose was 15 IU/kg or closest standardized dose; the plasma dose was a suggested volume of 10 to 15 mL/kg rounded to the nearest unit. MAIN OUTCOMES AND MEASURES The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. Secondary outcomes were PT/INR, rates of intraoperative red blood cell (RBC) transfusion after treatment, avoidance of allogeneic transfusion from the intraoperative period to the end of postoperative day 1, postoperative bleeding, and adverse events. RESULTS One hundred patients (mean [SD] age, 66.8 [13.7] years; 61 [61.0%] male; and 1 [1.0%] Black, 1 [1.0%] Hispanic, and 98 [98.0%] White) received the study intervention (49 plasma and 51 PCC). There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799-1575] mL vs 937 [708-1443] mL). After treatment, patients in the PCC arm had a greater improvement in PT (effect estimate, -1.37 seconds [95% CI, -1.91 to -0.84]; P < .001) and INR (effect estimate, -0.12 [95% CI, -0.16 to -0.07]; P < .001). Fewer patients in the PCC group required intraoperative RBC transfusion after treatment (7 of 51 patients [13.7%] vs 15 of 49 patients [30.6%]; P = .04); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events. CONCLUSIONS AND RELEVANCE The results of this study suggest a similar overall safety and efficacy profile for PCCs compared with plasma in this clinical context, with fewer posttreatment intraoperative RBC transfusions, improved PT/INR correction, and higher likelihood of allogeneic transfusion avoidance in patients receiving PCCs. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT02557672.
PICO Summary
Population
Patients undergoing cardiac surgery who developed microvascular bleeding (n= 100).
Intervention
Prothrombin complex concentrate (PCC), (n= 51).
Comparison
Plasma (n= 49).
Outcome
The primary outcome was postoperative bleeding (chest tube output) from the initial postsurgical intensive care unit admission through midnight on postoperative day 1. There was no significant difference in chest tube output between the plasma and PCC groups (median [IQR], 1022 [799, 1575] mL vs. 937 [708, 1443] mL). After treatment, patients in the PCC group had a greater improvement in prothombin time, (effect estimate, -1.37 seconds, 95% CI [-1.91, -0.84]) and international normalized ratio (effect estimate, -0.12, 95% CI [-0.16, -0.07]). Fewer patients in the PCC group required intraoperative red blood cell transfusion after treatment (7 of 51 patients [13.7%] vs. 15 of 49 patients [30.6%]); total intraoperative transfusion rates were not significantly different between groups. Seven (13.7%) of 51 patients receiving PCCs avoided allogeneic transfusion from the intraoperative period to the end of postoperative day 1 vs. none of those receiving plasma. There were no significant differences in postoperative bleeding, transfusions, or adverse events.
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Efficacy of Bovine Hydroxyapatite and Collagen Along With Platelet-Rich Fibrin as a Scaffold and Human Chorion as a Membrane for Ridge Preservation: A Case-Control Study
BT, Kondareddy KM, AR, NR, ESRR, Prakash R
Cureus. 2022;14(1):e21362
Abstract
AIM: The present study aims to determine the efficacy of bovine hydroxyapatite and collagen (G-graft) mixed with platelet-rich fibrin (PRF) used as a scaffold and chorion membrane as a barrier in post-extraction sockets with extraction sites alone. METHODS AND MATERIAL Thirty individuals were randomly assigned into two groups. In the control group, after debridement of the extracted tooth socket, no additional treatment was done. In the test group, after debridement of the extracted tooth socket, the sockets were filled with bovine hydroxyapatite and collagen (G-graft) mixed with PRF. They were covered by a chorion membrane, and a non-absorbable suture material was used to secure the membrane in place. Clinical parameters assessed were plaque index, gingival index, buccolingual width, buccal bone plate height, and lingual bone plate height at baseline and at six months. RESULTS Clinically, there was a more significant reduction in the buccolingual width of the control group than the test group after six months. A statistically significant difference between the two groups for vertical ridge height at the mesial and distal socket sites was observed. No statistically significant difference in buccal and lingual bone plate height was observed between the two groups (p>0.05). CONCLUSIONS Both groups showed a significant reduction in the Buccolingual width, but it was less in the ridge preservation group. Thus, the use of G-graft with PRF and chorion membrane was highly effective in ridge preservation. Key messages: Natural bovine bone mineral, along with PRF and chorion as a membrane, can be utilized effectively for ridge preservation in extracted tooth sockets due to periodontal disease.
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Anemia and adverse outcomes in pregnancy: subgroup analysis of the CLIP cluster-randomized trial in India
Bone, J. N., Bellad, M., Goudar, S., Mallapur, A., Charantimath, U., Ramadurg, U., Katageri, G., Lesperance, M., Woo Kinshella, M. L., Suleman, R., et al
BMC pregnancy and childbirth. 2022;22(1):407
Abstract
BACKGROUND Iron-deficiency anemia is a known risk factor for several adverse perinatal outcomes, but data on its impact on specific maternal morbidities is less robust. Further, information on associations between anemia in early pregnancy and subsequent outcomes are understudied. METHODS The study population was derived from the Community Level Interventions for Pre-eclampsia (CLIP) trial in Karnataka State, India (NCT01911494). Included were women who were enrolled in either trial arm, delivered by trial end date, and had a baseline measure of hemoglobin (Hb). Anemia was classified by WHO standards into four groups: none (Hb ≥ 11 g/dL), mild (10.0 g/dL ≤ Hb < 11.0 g/dL), moderate (7.0 g/dL ≤ Hb < 10.0 g/dL) and severe (Hb < 7.0 g/dL). Targeted maximum likelihood estimation was used to estimate confounder-adjusted associations between anemia and a composite (and its components) of adverse maternal outcomes, including pregnancy hypertension. E-values were calculated to assess robustness to unmeasured confounding. RESULTS Of 11,370 women included, 10,066 (88.5%) had anemia, that was mild (3690, 32.5%), moderate (6023, 53.0%), or severe (68, 0.6%). Almost all women (> 99%) reported taking iron supplements during pregnancy. Blood transfusions was more often administered to those with anemia that was mild (risk ratio [RR] 2.16, 95% confidence interval [CI] 1.31-3.56), moderate (RR 2.37, 95% CI 1.56-3.59), and severe (RR 5.70, 95% CI 3.00-10.85). No significant association was evident between anemia severity and haemorrhage (antepartum or postpartum) or sepsis, but there was a U-shaped association between anemia severity and pregnancy hypertension and pre-eclampsia specifically, with the lowest risk seen among those with mild or moderate anemia. CONCLUSION In Karnataka State, India, current management strategies for mild-moderate anemia in early pregnancy are associated with similar rates of adverse maternal or perinatal outcomes, and a lower risk of pregnancy hypertension and preeclampsia, compared with no anemia in early pregnancy. Future research should focus on risk mitigation for women with severe anemia, and the potential effect of iron supplementation for women with normal Hb in early pregnancy.
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TC-325 hemostatic powder in the management of upper gastrointestinal malignant bleeding: a randomized controlled trial
Martins BC, Abnader Machado A, Scomparin RC, Paulo GA, Safatle-Ribeiro A, Naschold Geiger S, Lenz L, Lima MS, Pennacchi C, Ribeiro U, et al
Endoscopy international open. 2022;10(10):E1350-e1357
Abstract
Background and study aims Upper gastrointestinal bleeding (UGIB) from malignancy is associated with high rebleeding and mortality rates. Recently, TC-325 powder has shown promising results in the treatment of UGIB, including malignant bleeding. The aim of this study was to compare the efficacy of TC-325 versus best clinical management. Patients and methods From August 2016 to February 2020, all patients with evidence of UGIB from malignancy were randomized to receive TC-325 therapy or control group, in which endoscopic treatment was not mandatory. Exclusion criteria were hemoglobin drop without overt bleeding and UGIB from non-tumor origin. The primary outcome was 30-day mortality. Secondary outcomes were 30-day rebleeding, blood transfusion and length of hospital stay. Results Sixty-two patients were randomized, three were excluded and 59 were included in the final analysis (TC-325 group = 28; control = 31). Groups were similar at baseline. Active bleeding was observed in 22 patients in the TC-325 group and 19 in the control group ( P = 0.15). Successful initial hemostasis with TC-325 was achieved in all cases. Additional therapy (radiotherapy, surgery or arterial embolization) was equally performed in both groups (42.9 % vs 58.1 %; P = 0.243). There were no differences in 30-day mortality (28.6 % vs. 19.4 %, P = 0.406) or 30-day rebleeding rates (32.1 % vs. 19.4 %, P = 0.26). Logistic regression identified no significant predictors of rebleeding. Age, Eastern Cooperative Oncology Group (ECOG) score 3 to 4 and AIMS65 score > 1 predicted greater mortality. Conclusions TC-325 was effective in achieving immediate hemostasis in malignant gastrointestinal bleeding but did not reduce 30-day mortality, 30-day rebleeding, blood transfusion or length of hospital stay. Age, ECOG 3-4, and AIMS65 > 1 were predictive factors of mortality.
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Comparison of safety and efficacy of convalescent plasma with fresh frozen plasma in severe covid-19 patients
Bajpai, M., Maheshwari, A., Kumar, S., Chhabra, K., Kale, P., Narayanan, A., Gupta, A., Gupta, E., Trehanpati, N., Agarwal, R., et al
Anais Da Academia Brasileira De Ciencias. 2022;94(4):e20210202
Abstract
BACKGROUND Role of Convalescent plasma (COPLA) to treat severe COVID-19 is under investigation. We compared efficacy and safety of COPLA with fresh frozen plasma (FFP) in severe COVID-19 patients. METHODS One group received COPLA with standard medical care (n = 14), and another group received random donor FFP, as control with standard medical care (n = 15) in severe COVID-19 disease. RESULTS The proportion of patients free of ventilation at day seven were 78.5% in COPLA group, and 93.3 % in control group were not significant (p= 0.258). However, improved respiratory rate, O2 saturation, SOFA score, and Ct value were observed in the COPLA group. No serious adverse events were noticed by plasma transfusion in both groups.
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Efficacy of convalescent plasma therapy in the patient with COVID-19: a randomised control trial (COPLA-II trial)
Bajpai, M., Maheshwari, A., Dogra, V., Kumar, S., Gupta, E., Kale, P., Saluja, V., Thomas, S. S., Trehanpati, N., Bihari, C., et al
BMJ open. 2022;12(4):e055189
Abstract
IMPORTANCE No proven treatment is available for severely ill COVID-19. Therapeutic use of COVID-19 convalescent plasma (COPLA) is under investigation. OBJECTIVE To compare the efficacy of COPLA with standard medical therapy (SMT) alone in severe COVID-19 patients. DESIGN, SETTING AND PARTICIPANTS A multicentric, open-labelled, phase-III randomised controlled trial conducted at two treatment centres with COPLA collected at the third dedicated centre in North-India, the coordinating centre during trial from June 2020 to December 2020. The study population comprised 400 participants in the ratio of 1:1 in each treatment group. INTERVENTION One group received COPLA with SMT (n=200), and another group received SMT only (n=200). MAIN OUTCOME MEASURES Primary outcome was time to clinical improvement measured by a two-point reduction in the ordinal scale. Secondary outcomes included duration of O(2) therapy, the proportion of patients on mechanical ventilation at day-7, mortality, SARS-CoV-2 antibody levels, cytokine levels and incidence of adverse events. RESULTS The median time to a two-point reduction in the ordinal scale in both groups was 9 days (IQR=7-13) (p=0.328). The median duration of O(2) therapy was 8 days (IQR=6-12) in COPLA and 10 days (IQR=6-12) in SMT group (p=0.64). The PaO(2)/FiO(2) ratio showed significant improvement at 7 days in COPLA group(p=0.036). There was no difference in mortality till 28 days in both groups (p=0.62). However, if COPLA was given within 3 days of hospital admission, a significant reduction in ordinal scale was observed (p=0.04). Neutralising antibody titres in COPLA group (80 (IQR 80-80)) were higher than SMT group (0 (IQR 0-80)) at 48 hours (p=0.001). COPLA therapy led to a significant reduction in TNF-α levels at 48 hours (p=0.048) and D-dimer at 7 days (p=0.02). Mild allergic reactions were observed in 3 (1.5%) patients in COPLA group. CONCLUSION AND RELEVANCE Convalescent plasma with adequate antibody titres should be transfused in COVID-19 patients along with SMT in the initial 3 days of hospitalisation for better clinical outcomes. TRIAL REGISTRATION NUMBER NCT04425915.