Home The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
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The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture

  • Ivan B. Stojadinovic , Branko M. Ristic , Dragan R. Knezevic , Zoran S. Milenkovic , Nikola S. Prodanovic EMAIL logo , Nenad R. Zornic and Jelena B. Milosevic
Published/Copyright: April 29, 2022

Abstract

The aim of this study is to determine whether the use of tranexamic acid (TXA) in patients with hip fracture reduces intraoperative and postoperative blood loss, and on the other hand, whether it increases thromboembolic risk. The study was performed on patients with hip fracture for a period of one year. Patients were divided into two groups (1:1): the first group receiving TXA and the second group receiving placebo. The amount of blood aspiration during the surgery was measured as well as drainage in the postoperative period of 24 h. The occurrence of deep vein thrombosis (DVT) was monitored before and after the surgery by ultrasound of the lower extremities. The amount of total blood loss was two times lower in patients who received TXA (291.8 ± 65.5 mL of blood vs 634.7 ± 150.5 mL of blood). Among the patients who developed DVT, one patient was from the group that did not receive TXA, and two patients were from the group that received TXA. The use of TXA in patients with hip fracture significantly reduces intraoperative and postoperative blood loss, without a significant thromboembolic risk.

1 Introduction

Fractures of the proximal part of the femur represent a major clinical problem due to numerous complications and high mortality. According to some authors, mortality in these patients in the first year is 25% [1,2,3]. One of the main problems in people with hip fracture is blood loss [1,2]. It occurs immediately after the injury, although it can also occur as a complication of surgical treatment. This often leads to postoperative anemia [4] and the need for blood transfusion. Transfusions of blood and blood derivatives carry with them the risk of transmitting various diseases, the occurrence of immune reactions, and the risk of developing postoperative infections [5]. In recent years, tranexamic acid (TXA) has been increasingly used as one way to reduce blood loss. Together with ε-aminocaproic acid and aprotinin, TXA belongs to antifibrinolytics [6]. On the other hand, there is a suspicion that the use of such preparations increases thromboembolic risk.

The aim of our study is to determine whether the use of TXA in patients with hip fracture affects the reduction of intraoperative and postoperative blood loss, hemoglobin and hematocrit values in patients after surgery, reduction of the need for blood transfusion, and whether it increases thromboembolic risk.

2 Materials and method

A prospective randomized clinical study lasting one year was conducted. The study included patients with hip fractures who were surgically treated at the Clinic for Orthopedics and Traumatology of the University Clinical Center Kragujevac. The study was approved by the ethics committee of our hospital. Written informed consent was obtained from each patient.

We divided the patients into two groups: the first group receiving TXA and the second group receiving placebo. TXA was administered in two equal doses. The first dose of 15 mg/kg body weight was given immediately before the surgery, and the second, in the same dose 3 h afterward. Randomization was carried out by the method of closed envelopes with the group number, which were opened immediately before the surgery.

2.1 Inclusion and exclusion criteria

The study included patients of both genders, over 18 years of age, with a confirmed diagnosis of hip fracture acquired in the last 24 h (fractures of the proximal part of the femur). Excluding factors are patients with polytrauma, impaired coagulation status, suspected hypersensitivity to TXA, patients with open fractures, long-term uninterrupted anticoagulant therapy, patients with a history of arterial or venous thrombosis or thromboembolic risk, patients with pathological fractures, patients who have suffered from deep vein thrombosis (DVT), pulmonary embolism (PE), cerebrovascular stroke or myocardial infarction in the last year, patients with disseminated intravascular coagulation, patients who have experienced subarachnoid hemorrhage, renal failure, severe liver diseases, pregnant, breastfeeding, or women taking oral contraceptives.

2.2 Outcome measurements

The following variables were recorded and analyzed for each patient: gender, age, type of fracture (the femur neck, trochanteric region), preoperative values of hemoglobin, hematocrit, D-dimer, blood pressure, the amount of blood aspiration during surgery, postoperative values of hemoglobin and hematocrit, number of blood units required for transfusion in the postoperative period of 14 days, total blood loss (measured by Gross equation [7]), presence of DVT diagnosed by ultrasound of the lower extremities, and diagnosed lung embolization (if in doubt, we performed lung scintigraphy and multi-slice computed tomography diagnostics).

The indication for postoperative transfusion was a hemoglobin value below 80 g/L. In the preoperative and postoperative period, an ultrasound examination of blood vessels of the lower extremities was performed in all patients to possibly detect asymptomatic DVT. Surgical treatment involved performing surgeries by the same surgical team that represents standard procedures for a certain type of fracture (total hip endoprosthesis, partial hip endoprosthesis, proximal femoral nail, and dynamic hip screw [DHS]). Patients follow-up was three months after the surgery.

2.3 Statistical analysis

Statistical data processing was performed using SPSS 20 statistical software. In the data analysis, the chi-square test (χ²) or the Fisher test with a low frequency of certain categories was used. The significance of the difference in the values of the continuous variables between cases and controls was tested by the student’s T test for the independent samples (in the case of normal distribution) or the Mann–Whitney U test (in the case of the absence of normal distribution).

3 Results

The study included 80 patients, 34 (42.5%) male and 46 (57.5%) female, and the average age of 75.4 ± 82 years. A fracture of the femur neck was detected in 41 patients (51.3%), while the extracapsular fracture of the upper part of the femur was found in 39 patients (48.7%). The most commonly used surgical technique for hip fracture treatment was osteosynthesis of the proximal part of the femur with the proximal femoral nail antirotation (PFNA) technique, in every third patient, and then partial hip arthroplasty with the implantation of a biarticular endoprosthesis, in every fourth patient. Hip arthroplasty with the implantation of a unipolar endoprosthesis (Austin Moore) was the least commonly used, in every tenth patient.

Forty patients, 23 (57.5%) male and 17 (42.5%) female, the average age of 74.2 ± 86 years, received TXA. The use of TXA is similar in both types of the femur fractures (χ² = 1.25, df = 1, p > 0.05). Among the operated patients who received TXA, 55% (n = 22) had a trochanteric femur fracture, and 45% had a femoral neck fracture (n = 18). In patients not receiving TXA, 57.5% (n = 23) had a femoral neck fracture, and 42.5% (n = 17) had a fracture of the proximal part of the femur.

The values of the basic laboratory parameters before surgery are mostly within the reference limits in both groups of patients that were examined. The exception is the value of hemoglobin and systolic blood pressure. The mean value of preoperative hemoglobin in patients who received TXA was 114.5 ± 15.2 g/L, and in patients who did not 121.9 ± 11.3 g/L. The mean value of preoperative systolic blood pressure in patients given TXA was lower by 4 mmHg (121.25 ± 9.4 mmHg vs 125.4 ± 7 mmHg) (Table 1).

Table 1

Preoperative and postoperative values of the basic laboratory parameters in relation to the use of TXA

Preoperative values Postoperative values
Parameters TXA TXA TXA TXA
Yes No Yes No
n x sd x sd p x sd x sd p
Erythrocytes 40 3.83 0.52 3.79 0.56 >0.05 3.48 0.56 2.76 0.53 <0.01
Platelets 40 288.33 80.78 256.38 63.14 >0.05 287.3 79.75 227.78 64.1 <0.01
Hemoglobin 40 114.5 15.24 121.85 11.26 >0.05 108.45 15.32 87.45 11.21 <0.01
Hematocrit 40 0.33 0.04 0.33 0.047 >0.05 0.327 0.04 0.233 0.07 <0.01
Prothrombin time 40 1.08 0.08 1.09 0.15 >0.05 1.09 0.08 1.07 0.08 <0.05
aPTT 40 26.13 3.52 26.67 3.46 >0.05 26.64 4.79 27.19 4.39 <0.05
Fibrinogen 40 6.63 1.96 6.57 1.82 >0.05 6.89 2.15 7.82 2.37 <0.05
Systolic blood pressure 40 121.25 9.39 125.4 7.02 >0.05 116.8 8.1 107.5 8.2 <0.01
Diastolic blood pressure 40 75.75 7.47 77.88 6.19 >0.05 72 6.3 65.1 5.1 <0.01

The mean amount of blood aspiration in patients receiving TXA was 133 ± 32.1 mL vs 305.8 ± 60.3 mL in patients receiving placebo (Figure 1) (Table 2).

Figure 1 
               Blood aspiration in the analyzed groups.
Figure 1

Blood aspiration in the analyzed groups.

Table 2

Intraoperative blood loss by type of fracture and application of tranexamic acid (TXA)

Type of fracture Tranexamic acid n sd p
Fractura colli femoris Yes 18 138.3 29.8 <0.01
No 23 318.9 51.6
Fractura trohanterica femoris Yes 22 128.6 33.8 <0.01
No 17 287.9 67.8

On average, 248.2 ± 127.9 mL of blood was drained after the surgery. Patients who had received TXA statistically lost less blood in the postoperative period compared with patients who had not received TXA (t = −11.2, df = 58.6, p < 0.01). The mean amount of drainage in patients who received TXA was 147.2 ± 51.5 mL compared with 346.8 ± 100.1 mL in patients who did not receive TXA (Figure 2).

Figure 2 
               Drainage in the analyzed groups.
Figure 2

Drainage in the analyzed groups.

The average total blood loss, measured using the Gross equation, was 463.2 ± 207.5 mL of blood. The amount of total blood loss was two times lower in patients who received TXA (291.8 ± 65.5 mL of blood vs 634.7 ± 150.5 mL of blood), which is a statistically significant difference (t = −13.21, df = 53.2, p < 0.01) (Figure 3).

Figure 3 
               Total blood loss in the analyzed groups.
Figure 3

Total blood loss in the analyzed groups.

Comparison of the values of the basic laboratory parameters after surgery of the examined groups of patients indicates that the patients not receiving TXA experienced a statistically significant decrease in values of the following: erythrocyte from 3.48 ± 0.56 to 2.76 ± 0.53 (t = 5.84, df = 78, p < 0.01), platelets from 287.3 ± 79.75 to 227.78 ± 64.1 (t = 3.68, df = 78, p < 0.01), hemoglobin from 108.45 ± 15.32 to 87.48 ± 11.21 (t = 6.99, df = 71.4, p < 0.01), hematocrit from 0.327 ± 0.04 to 0.233 ± 0.07 (t = 12.26, df = 79, p < 0.01) and consequently systolic blood pressure from 116.8 ± 8.1 to 107.5 ± 8.2 (t = 5.1, df = 78, p < 0.01), and diastolic blood pressure from 72 ± 6.3 to 65.1 ± 5.1 (t = 5.36, df = 78, p < 0.01) (Table 1).

The need for blood transfusion was in 13.8% of patients (n = 11), two male and nine female, and the average age was 78.1 ± 7.9 years. Two patients from the first group (18.2%), who received TXA, needed a blood transfusion, while nine patients from the second group (81.8%), who did not received TXA, needed a blood transfusion.

Deep vein thrombosis (DVT) occurred in three patients (two men/one woman). One patient developed DVT after femoral neck surgery and two patients after trochanteric femoral region surgery. Of these three patients with DVT, two were treated with TXA and one was not.

4 Discussion

Many studies describe the use of TXA in orthopedic surgery, primarily in arthroplasty and spinal surgery. Some authors (Engel et al. [8]) have failed to demonstrate a significant reduction in postoperative blood loss and the need for blood transfusion in the study and control groups. In contrast, other authors have succeeded in demonstrating a significant difference [9]. Despite proven efficacy in elective orthopedic surgery, the optimal dosage and timing of TXA administration is still being debated. Moreover, the efficacy and side effect profile of TXA in patients with fractures remain unclear [10]. By examining the effect of TXA in patients with hip fractures, we obtained the significant results on the safety and efficacy of this drug in a population that, compared to that in elective surgery, is always with higher comorbidity and of greater age.

It is important to note that hip fractures are not all the same in terms of the pattern of injury or surgical treatment. Extracapsular hip fractures are associated with higher total blood loss than intracapsular hip fractures [11]. Therefore, the effect of TXA can vary with different hip fractures as well as with different surgical procedures. Extracapsular hip fractures are usually treated with an intramedullary nail or dynamic compression screw. In a randomized controlled trial of 72 patients, Tengberg et al. examined the effect of TXA in patients with extracapsular hip fractures who underwent operative fixation with a short intramedullary nail. Their protocol consisted of a preoperative dose of 1 g TXA followed by a 24 h postoperative infusion of 3 g TXA. TXA reduced total blood loss by 600 mL and it also reduced the risk of blood transfusion, without a significant increase in venous thromboembolic events, to 90 days, postoperatively. Similarly, some authors found that one preoperative dose of TXA reduced the total blood loss in the study of 60 patients with extracapsular hip fractures treated with dynamic compression screw [11].

Studies in patients who suffered a hip fracture exist, but the results obtained are much less convincing than in studies with patients who underwent total arthroplasty of the hip or knee, especially in relation to the occurrence of thromboembolic risk [12,13]. Patients with hip fractures are quite different from patients who had elective hip arthroplasty. They are generally older and at higher postoperative risk [13]. Recently, several papers showing a sufficient level of safety in the use of TXA in patients with hip fractures [10,14,15,16,17] have been published.

In our study, in addition to the effect of TXA on hip fractures in total, the effect of intracapsular and extracapsular fractures was examined separately. Intraoperative blood loss in intracapsular fractures was slightly higher (138.3 mL on average in patients who received and 318.9 mL on average in patients who did not receive TXA) than in extracapsular fractures (128.6 and 287.9 mL). It can be explained by various surgical techniques, because hip arthroplasty, which is mainly performed in intracapsular fractures, is certainly more invasive than the PFNA and DHS techniques. There are concerns about a hypothetical increase in the thromboembolic risk, DVT, and PE following the systemic administration of TXA in major orthopedic surgeries. There is a statistically significant difference in intraoperative blood loss depending on whether the patient has been treated with TXA, regardless of the type of fracture (Table 2). Massimo Francini et al. evaluated intravenous use of TXA in major orthopedic surgeries. They observed that the overall incidence of venous thromboembolism is 86 in 4,174 (2.1%) patients with intravenous infusion of TXA infusion and 55 in 2,779 (2.0%) patients in the control group [18].

Jinwei Xie and co-workers performed ultrasonography only if DVT was suspected, while computed tomography was performed for clinically suspected cases of PE. The overall erythrocyte transfusion rate was 16.75% (102 patients), with transfusion of at least 1 erythrocyte unit given to 25 patients in the TXA group (8.65%) and 77 in the control group (24.06%, p < 0,001). This corresponds to a significant relative risk reduction of 70% (odds ratio (OR) 0.299, 95% confidence interval (CI) 0.184–0.485). TXA was associated with a 17.15% reduction in total blood loss and a 64.05% reduction in erythrocyte transfusion rate in this study [19] Studies have shown trends toward a higher incidence of postoperative vascular events with TXA in patients with hip fracture (16% vs 6%, p = 0.10) [20] and higher 90-day mortality with TXA in patients with extracapsular fracture (27.2% vs 10.2%, p = 0.07) [21]. In our study, ultrasonography was performed in all patients, due to possible asymptomatic DVT. The results showed that there was no statistically significant difference in the occurrence of the thromboembolic risk in patients who received TXA and those who did not. Farrow and co-workers conducted a systematic review of the use of TXA in hip fracture surgery in 2016. The authors believed that there was the evidence of moderate quality showing that TXA could reduce blood loss in hip fracture surgery and there was the evidence of lower quality indicating that TXA did not increase the thromboembolic risk [22]. The results of our study certainly support the efficacy of TXA in hip fracture (extra and intracapsular), with good drug safety in relation to potential thromboembolic complications.

5 Conclusion

The use of TXA in patients with hip fracture (extracapsular and intracapsular) significantly reduces the amount of blood aspiration during surgery and after surgery. The total blood loss was 2.5 times lower in patients who received TXA compared with the control group. A decrease in the value of erythrocytes, hemoglobin, and hematocrit after hip fracture surgery, in both groups and with all surgical methods, was also detected. Patients who received TXA had a reduced need for blood transfusions. These patients also had a smaller postoperative decrease in the values of basic laboratory parameters compared with patients who did not receive TXA. Finally, the use of TXA is not associated with an increased risk of thromboembolism (thromboembolic events) in this type of patients.

Abbreviations

TXA

tranexamic acid

MSCT

multi-slice computed tomography

PFNA

(proximal femoral nail antirotation) antirotation intramedullary nail for the proximal part of the femur

DHS

dynamic hip screw

BHP

(biarticular hip prosthesis) partial biarticular hip prosthesis

AM

(Austin Moore) Austin Moore partial hip prosthesis

VTE

venous thromboembolism

DVT

deep vein thrombosis

CVI

cerebrovascular insult

  1. Funding information: The study was conducted without financial support and sponsorship.

  2. Conflict of interest: There is no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2021-12-15
Revised: 2022-03-24
Accepted: 2022-04-10
Published Online: 2022-04-29

© 2022 Ivan B. Stojadinovic et al., published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  61. Notoginsenoside R1 alleviates spinal cord injury through the miR-301a/KLF7 axis to activate Wnt/β-catenin pathway
  62. Moscatilin suppresses the inflammation from macrophages and T cells
  63. Zoledronate promotes ECM degradation and apoptosis via Wnt/β-catenin
  64. Epithelial-mesenchymal transition-related genes in coronary artery disease
  65. The effect evaluation of traditional vaginal surgery and transvaginal mesh surgery for severe pelvic organ prolapse: 5 years follow-up
  66. Repeated partial splenic artery embolization for hypersplenism improves platelet count
  67. Low expression of miR-27b in serum exosomes of non-small cell lung cancer facilitates its progression by affecting EGFR
  68. Exosomal hsa_circ_0000519 modulates the NSCLC cell growth and metastasis via miR-1258/RHOV axis
  69. miR-455-5p enhances 5-fluorouracil sensitivity in colorectal cancer cells by targeting PIK3R1 and DEPDC1
  70. The effect of tranexamic acid on the reduction of intraoperative and postoperative blood loss and thromboembolic risk in patients with hip fracture
  71. Isocitrate dehydrogenase 1 mutation in cholangiocarcinoma impairs tumor progression by sensitizing cells to ferroptosis
  72. Artemisinin protects against cerebral ischemia and reperfusion injury via inhibiting the NF-κB pathway
  73. A 16-gene signature associated with homologous recombination deficiency for prognosis prediction in patients with triple-negative breast cancer
  74. Lidocaine ameliorates chronic constriction injury-induced neuropathic pain through regulating M1/M2 microglia polarization
  75. MicroRNA 322-5p reduced neuronal inflammation via the TLR4/TRAF6/NF-κB axis in a rat epilepsy model
  76. miR-1273h-5p suppresses CXCL12 expression and inhibits gastric cancer cell invasion and metastasis
  77. Clinical characteristics of pneumonia patients of long course of illness infected with SARS-CoV-2
  78. circRNF20 aggravates the malignancy of retinoblastoma depending on the regulation of miR-132-3p/PAX6 axis
  79. Linezolid for resistant Gram-positive bacterial infections in children under 12 years: A meta-analysis
  80. Rack1 regulates pro-inflammatory cytokines by NF-κB in diabetic nephropathy
  81. Comprehensive analysis of molecular mechanism and a novel prognostic signature based on small nuclear RNA biomarkers in gastric cancer patients
  82. Smog and risk of maternal and fetal birth outcomes: A retrospective study in Baoding, China
  83. Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1
  84. β2-Adrenergic receptor expression in subchondral bone of patients with varus knee osteoarthritis
  85. Possible impact of COVID-19 pandemic and lockdown on suicide behavior among patients in Southeast Serbia
  86. In vitro antimicrobial activity of ozonated oil in liposome eyedrop against multidrug-resistant bacteria
  87. Potential biomarkers for inflammatory response in acute lung injury
  88. A low serum uric acid concentration predicts a poor prognosis in adult patients with candidemia
  89. Antitumor activity of recombinant oncolytic vaccinia virus with human IL2
  90. ALKBH5 inhibits TNF-α-induced apoptosis of HUVECs through Bcl-2 pathway
  91. Risk prediction of cardiovascular disease using machine learning classifiers
  92. Value of ultrasonography parameters in diagnosing polycystic ovary syndrome
  93. Bioinformatics analysis reveals three key genes and four survival genes associated with youth-onset NSCLC
  94. Identification of autophagy-related biomarkers in patients with pulmonary arterial hypertension based on bioinformatics analysis
  95. Protective effects of glaucocalyxin A on the airway of asthmatic mice
  96. Overexpression of miR-100-5p inhibits papillary thyroid cancer progression via targeting FZD8
  97. Bioinformatics-based analysis of SUMOylation-related genes in hepatocellular carcinoma reveals a role of upregulated SAE1 in promoting cell proliferation
  98. Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience
  99. Identification of osteoporosis based on gene biomarkers using support vector machine
  100. Tanshinone IIA reverses oxaliplatin resistance in colorectal cancer through microRNA-30b-5p/AVEN axis
  101. miR-212-5p inhibits nasopharyngeal carcinoma progression by targeting METTL3
  102. Association of ST-T changes with all-cause mortality among patients with peripheral T-cell lymphomas
  103. LINC00665/miRNAs axis-mediated collagen type XI alpha 1 correlates with immune infiltration and malignant phenotypes in lung adenocarcinoma
  104. The perinatal factors that influence the excretion of fecal calprotectin in premature-born children
  105. Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study
  106. Does the use of 3D-printed cones give a chance to postpone the use of megaprostheses in patients with large bone defects in the knee joint?
  107. lncRNA HAGLR modulates myocardial ischemia–reperfusion injury in mice through regulating miR-133a-3p/MAPK1 axis
  108. Protective effect of ghrelin on intestinal I/R injury in rats
  109. In vivo knee kinematics of an innovative prosthesis design
  110. Relationship between the height of fibular head and the incidence and severity of knee osteoarthritis
  111. lncRNA WT1-AS attenuates hypoxia/ischemia-induced neuronal injury during cerebral ischemic stroke via miR-186-5p/XIAP axis
  112. Correlation of cardiac troponin T and APACHE III score with all-cause in-hospital mortality in critically ill patients with acute pulmonary embolism
  113. LncRNA LINC01857 reduces metastasis and angiogenesis in breast cancer cells via regulating miR-2052/CENPQ axis
  114. Endothelial cell-specific molecule 1 (ESM1) promoted by transcription factor SPI1 acts as an oncogene to modulate the malignant phenotype of endometrial cancer
  115. SELENBP1 inhibits progression of colorectal cancer by suppressing epithelial–mesenchymal transition
  116. Visfatin is negatively associated with coronary artery lesions in subjects with impaired fasting glucose
  117. Treatment and outcomes of mechanical complications of acute myocardial infarction during the Covid-19 era: A comparison with the pre-Covid-19 period. A systematic review and meta-analysis
  118. Neonatal stroke surveillance study protocol in the United Kingdom and Republic of Ireland
  119. Oncogenic role of TWF2 in human tumors: A pan-cancer analysis
  120. Mean corpuscular hemoglobin predicts the length of hospital stay independent of severity classification in patients with acute pancreatitis
  121. Association of gallstone and polymorphisms of UGT1A1*27 and UGT1A1*28 in patients with hepatitis B virus-related liver failure
  122. TGF-β1 upregulates Sar1a expression and induces procollagen-I secretion in hypertrophic scarring fibroblasts
  123. Antisense lncRNA PCNA-AS1 promotes esophageal squamous cell carcinoma progression through the miR-2467-3p/PCNA axis
  124. NK-cell dysfunction of acute myeloid leukemia in relation to the renin–angiotensin system and neurotransmitter genes
  125. The effect of dilution with glucose and prolonged injection time on dexamethasone-induced perineal irritation – A randomized controlled trial
  126. miR-146-5p restrains calcification of vascular smooth muscle cells by suppressing TRAF6
  127. Role of lncRNA MIAT/miR-361-3p/CCAR2 in prostate cancer cells
  128. lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2
  129. Noninvasive diagnosis of AIH/PBC overlap syndrome based on prediction models
  130. lncRNA FAM230B is highly expressed in colorectal cancer and suppresses the maturation of miR-1182 to increase cell proliferation
  131. circ-LIMK1 regulates cisplatin resistance in lung adenocarcinoma by targeting miR-512-5p/HMGA1 axis
  132. LncRNA SNHG3 promoted cell proliferation, migration, and metastasis of esophageal squamous cell carcinoma via regulating miR-151a-3p/PFN2 axis
  133. Risk perception and affective state on work exhaustion in obstetrics during the COVID-19 pandemic
  134. lncRNA-AC130710/miR-129-5p/mGluR1 axis promote migration and invasion by activating PKCα-MAPK signal pathway in melanoma
  135. SNRPB promotes cell cycle progression in thyroid carcinoma via inhibiting p53
  136. Xylooligosaccharides and aerobic training regulate metabolism and behavior in rats with streptozotocin-induced type 1 diabetes
  137. Serpin family A member 1 is an oncogene in glioma and its translation is enhanced by NAD(P)H quinone dehydrogenase 1 through RNA-binding activity
  138. Silencing of CPSF7 inhibits the proliferation, migration, and invasion of lung adenocarcinoma cells by blocking the AKT/mTOR signaling pathway
  139. Ultrasound-guided lumbar plexus block versus transversus abdominis plane block for analgesia in children with hip dislocation: A double-blind, randomized trial
  140. Relationship of plasma MBP and 8-oxo-dG with brain damage in preterm
  141. Identification of a novel necroptosis-associated miRNA signature for predicting the prognosis in head and neck squamous cell carcinoma
  142. Delayed femoral vein ligation reduces operative time and blood loss during hip disarticulation in patients with extremity tumors
  143. The expression of ASAP3 and NOTCH3 and the clinicopathological characteristics of adult glioma patients
  144. Longitudinal analysis of factors related to Helicobacter pylori infection in Chinese adults
  145. HOXA10 enhances cell proliferation and suppresses apoptosis in esophageal cancer via activating p38/ERK signaling pathway
  146. Meta-analysis of early-life antibiotic use and allergic rhinitis
  147. Marital status and its correlation with age, race, and gender in prognosis of tonsil squamous cell carcinomas
  148. HPV16 E6E7 up-regulates KIF2A expression by activating JNK/c-Jun signal, is beneficial to migration and invasion of cervical cancer cells
  149. Amino acid profiles in the tissue and serum of patients with liver cancer
  150. Pain in critically ill COVID-19 patients: An Italian retrospective study
  151. Immunohistochemical distribution of Bcl-2 and p53 apoptotic markers in acetamiprid-induced nephrotoxicity
  152. Estradiol pretreatment in GnRH antagonist protocol for IVF/ICSI treatment
  153. Long non-coding RNAs LINC00689 inhibits the apoptosis of human nucleus pulposus cells via miR-3127-5p/ATG7 axis-mediated autophagy
  154. The relationship between oxygen therapy, drug therapy, and COVID-19 mortality
  155. Monitoring hypertensive disorders in pregnancy to prevent preeclampsia in pregnant women of advanced maternal age: Trial mimicking with retrospective data
  156. SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway
  157. The role of Shunaoxin pills in the treatment of chronic cerebral hypoperfusion and its main pharmacodynamic components
  158. TET3 governs malignant behaviors and unfavorable prognosis of esophageal squamous cell carcinoma by activating the PI3K/AKT/GSK3β/β-catenin pathway
  159. Associations between morphokinetic parameters of temporary-arrest embryos and the clinical prognosis in FET cycles
  160. Long noncoding RNA WT1-AS regulates trophoblast proliferation, migration, and invasion via the microRNA-186-5p/CADM2 axis
  161. The incidence of bronchiectasis in chronic obstructive pulmonary disease
  162. Integrated bioinformatics analysis shows integrin alpha 3 is a prognostic biomarker for pancreatic cancer
  163. Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway
  164. Comparison of hospitalized patients with severe pneumonia caused by COVID-19 and influenza A (H7N9 and H1N1): A retrospective study from a designated hospital
  165. lncRNA ZFAS1 promotes intervertebral disc degeneration by upregulating AAK1
  166. Pathological characteristics of liver injury induced by N,N-dimethylformamide: From humans to animal models
  167. lncRNA ELFN1-AS1 enhances the progression of colon cancer by targeting miR-4270 to upregulate AURKB
  168. DARS-AS1 modulates cell proliferation and migration of gastric cancer cells by regulating miR-330-3p/NAT10 axis
  169. Dezocine inhibits cell proliferation, migration, and invasion by targeting CRABP2 in ovarian cancer
  170. MGST1 alleviates the oxidative stress of trophoblast cells induced by hypoxia/reoxygenation and promotes cell proliferation, migration, and invasion by activating the PI3K/AKT/mTOR pathway
  171. Bifidobacterium lactis Probio-M8 ameliorated the symptoms of type 2 diabetes mellitus mice by changing ileum FXR-CYP7A1
  172. circRNA DENND1B inhibits tumorigenicity of clear cell renal cell carcinoma via miR-122-5p/TIMP2 axis
  173. EphA3 targeted by miR-3666 contributes to melanoma malignancy via activating ERK1/2 and p38 MAPK pathways
  174. Pacemakers and methylprednisolone pulse therapy in immune-related myocarditis concomitant with complete heart block
  175. miRNA-130a-3p targets sphingosine-1-phosphate receptor 1 to activate the microglial and astrocytes and to promote neural injury under the high glucose condition
  176. Review Articles
  177. Current management of cancer pain in Italy: Expert opinion paper
  178. Hearing loss and brain disorders: A review of multiple pathologies
  179. The rationale for using low-molecular weight heparin in the therapy of symptomatic COVID-19 patients
  180. Amyotrophic lateral sclerosis and delayed onset muscle soreness in light of the impaired blink and stretch reflexes – watch out for Piezo2
  181. Interleukin-35 in autoimmune dermatoses: Current concepts
  182. Recent discoveries in microbiota dysbiosis, cholangiocytic factors, and models for studying the pathogenesis of primary sclerosing cholangitis
  183. Advantages of ketamine in pediatric anesthesia
  184. Congenital adrenal hyperplasia. Role of dentist in early diagnosis
  185. Migraine management: Non-pharmacological points for patients and health care professionals
  186. Atherogenic index of plasma and coronary artery disease: A systematic review
  187. Physiological and modulatory role of thioredoxins in the cellular function
  188. Case Reports
  189. Intrauterine Bakri balloon tamponade plus cervical cerclage for the prevention and treatment of postpartum haemorrhage in late pregnancy complicated with acute aortic dissection: Case series
  190. A case of successful pembrolizumab monotherapy in a patient with advanced lung adenocarcinoma: Use of multiple biomarkers in combination for clinical practice
  191. Unusual neurological manifestations of bilateral medial medullary infarction: A case report
  192. Atypical symptoms of malignant hyperthermia: A rare causative mutation in the RYR1 gene
  193. A case report of dermatomyositis with the missed diagnosis of non-small cell lung cancer and concurrence of pulmonary tuberculosis
  194. A rare case of endometrial polyp complicated with uterine inversion: A case report and clinical management
  195. Spontaneous rupturing of splenic artery aneurysm: Another reason for fatal syncope and shock (Case report and literature review)
  196. Fungal infection mimicking COVID-19 infection – A case report
  197. Concurrent aspergillosis and cystic pulmonary metastases in a patient with tongue squamous cell carcinoma
  198. Paraganglioma-induced inverted takotsubo-like cardiomyopathy leading to cardiogenic shock successfully treated with extracorporeal membrane oxygenation
  199. Lineage switch from lymphoma to myeloid neoplasms: First case series from a single institution
  200. Trismus during tracheal extubation as a complication of general anaesthesia – A case report
  201. Simultaneous treatment of a pubovesical fistula and lymph node metastasis secondary to multimodal treatment for prostate cancer: Case report and review of the literature
  202. Two case reports of skin vasculitis following the COVID-19 immunization
  203. Ureteroiliac fistula after oncological surgery: Case report and review of the literature
  204. Synchronous triple primary malignant tumours in the bladder, prostate, and lung harbouring TP53 and MEK1 mutations accompanied with severe cardiovascular diseases: A case report
  205. Huge mucinous cystic neoplasms with adhesion to the left colon: A case report and literature review
  206. Commentary
  207. Commentary on “Clinicopathological features of programmed cell death-ligand 1 expression in patients with oral squamous cell carcinoma”
  208. Rapid Communication
  209. COVID-19 fear, post-traumatic stress, growth, and the role of resilience
  210. Erratum
  211. Erratum to “Tollip promotes hepatocellular carcinoma progression via PI3K/AKT pathway”
  212. Erratum to “Effect of femoral head necrosis cystic area on femoral head collapse and stress distribution in femoral head: A clinical and finite element study”
  213. Erratum to “lncRNA NORAD promotes lung cancer progression by competitively binding to miR-28-3p with E2F2”
  214. Retraction
  215. Expression and role of ABIN1 in sepsis: In vitro and in vivo studies
  216. Retraction to “miR-519d downregulates LEP expression to inhibit preeclampsia development”
  217. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part II
  218. Usefulness of close surveillance for rectal cancer patients after neoadjuvant chemoradiotherapy
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