Abstract

BACKGROUND Non-transfusion-dependent β-thalassaemia (NTDβT) is a subset of inherited haemoglobin disorders characterised by reduced production of the β-globin chain of haemoglobin leading to anaemia of varying severity. Although blood transfusion is not a necessity for survival, it may be required to prevent complications of chronic anaemia, such as impaired growth and hypercoagulability. People with NTDβT also experience iron overload due to increased iron absorption from food sources which becomes more pronounced in those requiring blood transfusion. People with a higher foetal haemoglobin (HbF) level have been found to require fewer blood transfusions, thus leading to the emergence of treatments that could increase its level. HbF inducers stimulate HbF production without altering any gene structures. Evidence for the possible benefits and harms of these inducers is important for making an informed decision on their use. OBJECTIVES To compare the effectiveness and safety of the following for reducing blood transfusion for people with NTDβT: 1. HbF inducers versus usual care or placebo; 2. single HbF inducer with another HbF inducer, and single dose with another dose; and 3. combination of HbF inducers versus usual care or placebo, or single HbF inducer. SEARCH METHODS We used standard, extensive Cochrane search methods. The latest search date was 21 August 2022. SELECTION CRITERIA We included randomised controlled trials (RCTs) or quasi-RCTs comparing single HbF inducer with placebo or usual care, with another single HbF inducer or with a combination of HbF inducers; or comparing different doses of the same HbF inducer. DATA COLLECTION AND ANALYSIS We used standard Cochrane methods. Our primary outcomes were blood transfusion and haemoglobin levels. Our secondary outcomes were HbF levels, the long-term sequelae of NTDβT, quality of life and adverse events. MAIN RESULTS We included seven RCTs involving 291 people with NTDβT, aged two to 49 years, from five countries. We reported 10 comparisons using eight different HbF inducers (four pharmacological and four natural): three RCTs compared a single HbF inducer to placebo and seven to another HbF inducer. The duration of the intervention lasted from 56 days to six months. Most studies did not adequately report the randomisation procedures or whether and how blinding was achieved. HbF inducer against placebo or usual care Three HbF inducers, HQK-1001, Radix Astragali or a 3-in-1 combined natural preparation (CNP), were compared with a placebo. None of the comparisons reported the frequency of blood transfusion. We are uncertain whether Radix Astragali and CNP increase haemoglobin at three months (mean difference (MD) 1.33 g/dL, 95% confidence interval (CI) 0.54 to 2.11; 1 study, 2 interventions, 35 participants; very low-certainty evidence). We are uncertain whether Radix Astragali and CNP have any effect on HbF (MD 12%, 95% CI -0.74% to 24.75%; 1 study, 2 interventions, 35 participants; very low-certainty evidence). Only medians on haemoglobin and HbF levels were reported for HQK-1001. Adverse effects reported for HQK-1001 were nausea, vomiting, dizziness and suprapubic pain. There were no prespecified adverse effects for Radix Astragali and CNP. HbF inducer versus another HbF inducer Four studies compared a single inducer with another over three to six months. Comparisons included hydroxyurea versus resveratrol, hydroxyurea versus thalidomide, hydroxyurea versus decitabine and Radix Astragali versus CNP. No study reported our prespecified outcomes on blood transfusion. Haemoglobin and HbF were reported for the comparison Radix Astragali versus CNP, but we are uncertain whether there were any differences (1 study, 24 participants; low-certainty evidence). Different doses of the same HbF inducer Two studies compared two different types of HbF inducers at different doses over two to six months. Comparisons included hydroxyurea 20 mg/kg/day versus 10 mg/kg/day and HQK-1001 10 mg/kg/day, 20 mg/kg/day, 30 mg/kg/day and 40 mg/kg/day. Blood transfusion, as prespecified, was not reported. In one study (61 participants) we are uncertain whether the lower levels of both haemoglobin and HbF at 24 weeks were due to the higher dose of hydroxyurea (haemoglobin: MD -2.39 g/dL, 95% CI -2.80 to -1.98; very low-certainty evidence; HbF: MD -10.20%, 95% CI -16.28% to -4.12%; very low-certainty evidence). The study of the four different doses of HQK-1001 did not report results for either haemoglobin or HbF. We are not certain if major adverse effects may be more common with higher hydroxyurea doses (neutropenia: risk ratio (RR) 9.93, 95% CI 1.34 to 73.97; thrombocytopenia: RR 3.68, 95% CI 1.12 to 12.07; very low-certainty evidence). Taking HQK-1001 20 mg/kg/day may result in the fewest adverse effects. A combination of HbF inducers versus a single HbF inducer Two studies compared three combinations of two inducers with a single inducer over six months: hydroxyurea plus resveratrol versus resveratrol or hydroxyurea alone, and hydroxyurea plus l-carnitine versus hydroxyurea alone. Blood transfusion was not reported. Hydroxyurea plus resveratrol may reduce haemoglobin compared with either resveratrol or hydroxyurea alone (MD -0.74 g/dL, 95% CI -1.45 to -0.03; 1 study, 54 participants; low-certainty evidence). We are not certain whether the gastrointestinal disturbances, headache and malaise more commonly reported with hydroxyurea plus resveratrol than resveratrol alone were due to the interventions. We are uncertain whether hydroxyurea plus l-carnitine compared with hydroxyurea alone may increase mean haemoglobin, and reduce pulmonary hypertension (1 study, 60 participants; very low-certainty evidence). Adverse events were reported but not in the intervention group. None of the comparisons reported the outcome of HbF. AUTHORS' CONCLUSIONS We are uncertain whether any of the eight HbF inducers in this review have a beneficial effect on people with NTDβT. For each of these HbF inducers, we found only one or at the most two small studies. There is no information on whether any of these HbF inducers have an effect on our primary outcome, blood transfusion. For the second primary outcome, haemoglobin, there may be small differences between intervention groups, but these may not be clinically meaningful and are of low- to very low-certainty evidence. Data on adverse effects and optimal doses are limited. Five studies are awaiting classification, but none are ongoing.

Abstract

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

Abstract

OBJECTIVES The aim of this review is to evaluate complications in patients undergoing surgical control of bleeding after thyroid surgery. Secondly, we have analyzed the rate of the main complications. METHODS The databases PubMed and EMBASE were searched for articles regarding complications after revision thyroid surgery for bleeding. A Systematic review methodology based on Preferred Reporting Items for Systematic Reviews and Meta-analysis was performed. RESULTS Nine studies met the inclusion criteria, six are retrospectives and three retrospectives controlled. The overall rate of bleeding after thyroid surgery was 1.38%. In these patients, the most common complication after revision surgery for bleeding is hypoparathyroidism 24.9% (95% CI: 20.7-29.5) followed by recurrent laryngeal nerve injury 8.1% (95% CI: 6.4-10.1) and wound infection 4.5% (95% CI: 2.5-7.6). Tracheostomy and other lethal complications are rarely described. CONCLUSION Although rare, complications after surgical control of bleeding in patients undergoing thyroid surgery can be serious. Therefore, in order to optimize the surgical outcomes, standardized protocol providing early detection and precise hemostasis procedure, is needed. Specific patient-informed consent for this condition should be created.

Abstract

OBJECTIVE To evaluate the efficacy and safety of tranexamic acid (TXA) in hemostasis in patients undergoing posterior lumbar interbody fusion (PLIF) by meta-analysis. METHODS This study was registered on the International Prospective Register of Systematic Reviews (PROSPERO) (ID: CRD42022354812). The databases PubMed, Cochrane Library, Web of Science, and Embase were searched for randomized controlled trial (RCT) papers on the use of TXA in patients with PLIF from database establishment to August 2022. Two researchers screened the literature, extracted data, evaluated the risk of bias of the included studies, recorded the authors, sample size, type of study design, and TXA dose of each study, and extracted the intraoperative blood loss, number of blood transfusions, total blood loss, drainage volume, operation time, and incidence of deep venous thrombosis in each study. Meta-analysis was performed using RevMan 5.4 software provided by Cochrane Library. RESULTS A total of 14 RCTs with a total of 1681 patients were included in this study, including 836 patients in the TXA group and 845 patients in the control group. The intraoperative blood loss [mean difference (MD) = - 125.97, 95% confidence interval (CI) (- 138.56, - 113.37), P < 0.0001] and less total blood loss [MD = - 204.28, 95% CI (- 227.38, - 181.18), P < 0.00001] in TXA group were lower than the control group. Statistical significance was also observed in postoperative drainage volume [MD = - 115.03, 95% CI (- 123.89, - 106.17), P < 0.00001], operation time [MD = - 8.10, 95% CI (- 14.49, - 1.71), P = 0.01], and blood transfusion rate [odds ratio (OR) = 0.30, 95% CI (0.23, 0.39), P < 0.00001]. However, there was no statistical difference observed in the incidence of deep venous thrombosis [OR = 0.83, 95% CI (0.56, 1.21), P = 0.33]. CONCLUSION The application of TXA in PLIF can reduce intraoperative blood loss, total blood loss, drainage volume, the incidence of transfusion events, and operation time without increasing the risk of deep venous thrombosis.

Abstract

PURPOSE During intracranial meningioma surgery, surgeons experience considerable blood loss. Tranexamic acid (TXA) is used to minimize blood loss in several neurosurgical settings. However, evidence and trials are lacking. Our objective is to establish the most recent evidence on TXA safety and efficacy in intracranial meningioma surgery. METHODOLOGY Based upon Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), the authors collected fully published English literature on the administration of tranexamic acid for patients undergoing intracranial meningioma surgery using the keywords ["tranexamic acid" and "meningioma"] and its synonyms from Cochrane Central Database, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov, and PubMed. The primary outcome of the current study was total blood loss. The secondary outcomes include individuals requiring blood transfusion, anesthesia duration, surgical duration, and complication rate. Each included studies' quality was assessed using the JADAD scale. RESULTS For qualitative and quantitative data synthesis, we included five RCTs (n = 321) with the mean age was 47.5 ± 11.9 years for the intervention group and 47.2 ± 11.9 years for the control group. Our meta-analysis showed that the administration of TXA is associated with decreased total blood loss of standardized mean difference (SMD) of -1.40 (95% CI [-2.49, -0.31]), anesthetic time SMD -0.36 (95% CI [-0.63, -0.09]), and blood transfusion requirements RR 0.58 (95% CI [0.34, 0.99]). CONCLUSIONS The current study showed that TXA was associated with reduced intraoperative blood loss and intra- and postoperative blood transfusion. However, the studies are small. More RCT studies with a greater sample size are favorable.

Abstract

Tranexamic Acid (TXA) has been used in medical and surgical practice to reduce haemorrhage. The aim of this review was to evaluate the effect of TXA use on intraoperative and postoperative outcomes of meningioma surgery. A systematic review and meta-analysis was conducted in accordance with the PRISMA statement and registered in PROSPERO (CRD42021292157). Six databases were searched up to November 2021 for phase 2-4 control trials or cohort studies, in the English language, examining TXA use during meningioma surgery. Studies ran outside of dedicated neurosurgical departments or centres were excluded. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Random effects meta-analysis were performed to delineate differences in operative and postoperative outcomes. Four studies (281 patients) were included. TXA use significantly reduced intraoperative blood loss (mean difference 315.7 mls [95% confidence interval [CI] -532.8, -98.5]). Factors not affected by TXA use were transfusion requirement (odds ratio = 0.52; 95% CI 0.27, 0.98), operation time (mean difference = -0.2 h; 95% CI -0.8, 0.4), postoperative seizures (Odds Ratio [OR] = 0.88; 95% CI 0.31, 2.53), hospital stay (mean difference = -1.2; 95% CI -3.4, 0.9) and disability after surgery (OR = 0.50; 95% CI 0.23, 1.06). The key limitations of this review were the small sample size, limited data for secondary outcomes and a lack of standardised method for measuring blood loss. TXA use reduces blood loss in meningioma surgery, but not transfusion requirement or postoperative complications. Larger trials are required to investigate the impact of TXA on patient-reported postoperative outcomes.

Abstract

Chitosan and gelatin were the most widely used natural materials in pharmaceutical and medical fields, especially as local hemostatic agents, independently or as a composite material with the addition of other active substances. Chitosan and gelatin have excellent properties in biocompatibility, biodegradability, non-toxicity and water absorption capacity. The objective of this review was to analyze the characteristics of chitosan-gelatin (CG) composite-based biomaterial and its effectivity as a local hemostatic agent. We used PRISMA guidelines and the PICO framework to compile this review. The findings demonstrated that the CG composite-based biomaterial had excellent physical, chemical, mechanical properties and local hemostatic agent activity by adding other active substances such as oxidized fibers (OF), silica nanoparticles (SiNPs), calcium (Ca) and biphasic calcium phosphate (BCP) or by setting the CG composite proportion ratio.

Abstract

BACKGROUND Standard dose (≤ 1 g) tranexamic acid (TXA) has established mortality benefit in trauma patients. The role of high dose IV TXA (≥2 g or ≥30 mg/kg as a single bolus) has been evaluated in the surgical setting, however, it has not been studied in trauma. We reviewed the available evidence of high dose IV TXA in any setting with the goal of informing its use in the adult trauma population. METHODS We searched MEDLINE, EMBASE and unpublished sources from inception until July 27, 2022 for studies that compared standard dose with high dose IV TXA in adults (≥ 16 years of age) with hemorrhage. Screening and data abstraction was done independently and in duplicate. We pooled trial data using a random effects model and considered randomized controlled trials (RCTs) and observational cohort studies separately. We assessed the individual study risk of bias using the Cochrane Risk of Bias for RCTs and the Newcastle-Ottawa Scale for observational cohort studies. The overall certainty of evidence was assessed using the GRADE approach (Grading of Recommendations Assessment, Development and Evaluation). RESULTS We included 20 studies with a combined total of 12,523 patients. Based on pooled RCT data, and as compared to standard dose TXA, high dose IV TXA probably decreases transfusion requirements (odds ratio [OR] 0.86, 95% confidence interval [CI] 0.76 to 0.97, moderate certainty) but with possibly no effect on blood loss (mean difference [MD] 43.31 ml less, 95% CI 135.53 to 48.90 ml less, low certainty), and an uncertain effect on thromboembolic events (OR 1.33, 95% CI 0.86 to 2.04, very low certainty) and mortality (OR 0.70, 95% CI 0.37 to 1.32, very low certainty). CONCLUSION When compared to standard dose, high dose IV TXA probably reduces transfusion requirements with an uncertain effect on thromboembolic events and mortality. LEVEL OF EVIDENCE Systematic review and meta-analysis, level IV.

Abstract

BACKGROUND The last two decades have seen the reintroduction of tourniquets into guidelines for the management of acute limb trauma requiring hemorrhage control. Evidence supporting tourniquet application has demonstrated low complication rates in modern military settings involving rapid evacuation timeframes. It is unclear how these findings translate to patients who have prolonged transport times from injury in rural settings. This scoping review investigates the relationship between time and distance on metabolic complications, limb salvage and mortality following tourniquet use in civilian and military settings. METHODS A systematic search strategy was conducted using PubMed, Embase, and SafetyLit databases. Study characteristics, setting, mechanism of injury, prehospital time, tourniquet time, distance, limb salvage, metabolic response, mortality, and tourniquet removal details were extracted from eligible studies. Descriptive statistics were recorded, and studies were grouped by ischemia time (< 2 h, 2-4 h, or > 4 h). RESULTS The search identified 3103 studies, from which 86 studies were included in this scoping review. Of the 86 studies, 55 studies were primarily in civilian environments and 32 were based in military settings. One study included both settings. Blast injury was the most common mechanism of injury sustained by patients in military settings (72.8% [5968/8200]) followed by penetrating injury (23.5% [1926/8200]). In contrast, in civilian settings penetrating injury was the most common mechanism (47.7% [1633/3426]) followed by blunt injury (36.4% [1246/3426]). Tourniquet time was reported in 66/86 studies. Tourniquet time over four hours was associated with reduced limb salvage rates (57.1%) and higher mortality rates (7.1%) compared with a tourniquet time of less than two hours. The overall limb salvage and mortality rates were 69.6% and 6.7% respectively. Metabolic outcomes were reported in 28/86 studies with smaller sample sizes and inconsistencies in which parameters were reported. CONCLUSION This scoping review presents literature describing comparatively safe tourniquet application when used for less than two hours duration. However, there is limited research describing prolonged tourniquet application or when used for protracted distances, such that the impact of tourniquet release time on metabolic outcomes and complications remains unclear. Prospective studies utilizing the development of an international database to provide this dataset is required.