The February 2023 Foot & Ankle Roundup360 looks at: Joint inflammatory response in ankle and pilon fractures; Tibiotalocalcaneal fusion with a custom cage; Topical application of tranexamic acid can reduce blood loss in calcaneal fractures; Risk factors for failure of total ankle arthroplasty; Pain catastrophizing: the same as pain forecasting?.
To test the hypothesis that reseeded anterior cruciate ligament (ACL)-derived cells have a better ability to survive and integrate into tendon extracellular matrix (ECM) and accelerate the ligamentization process, compared to adipose-derived mesenchymal stem cells (ADMSCs). Acellularized tibialis allograft tendons were used. Tendons were randomly reseeded with ACL-derived cells or ADMSCs. ACL-derived cells were harvested and isolated from remnants of ruptured ACLs during reconstruction surgery and cultured at passage three. Cell suspensions (200 µl) containing 2 × 106 ACL-derived cells or ADMSCs were prepared for the purpose of reseeding. At days 1, 3, and 7 post-reseeding, graft composites were assessed for repopulation with histological and immunohistochemical analysis. Matrix protein contents and gene expression levels were analyzed.Aims
Methods
To assess the safety of tranexamic acid (TXA) in a large cohort of patients aged over 65 years who have sustained a hip fracture, with a focus on transfusion rates, mortality, and thromboembolic events. This is a consecutive cohort study with prospectively collected registry data. Patients with a hip fracture in the Region of Southern Denmark were included over a two-year time period (2015 to 2017) with the first year constituting a control group. In the second year, perioperative TXA was introduced as an intervention. Outcome was transfusion frequency, 30-day and 90-day mortality, and thromboembolic events. The latter was defined as any diagnosis or death due to arterial or venous thrombosis. The results are presented as relative risk (RR) and hazard ratio (HR) with 95% confidence intervals (CIs).Aims
Methods
The aim of this study was to investigate the hypothesis that a single dose of tranexamic acid (TXA) would reduce blood loss and transfusion rates in elderly patients undergoing surgery for a subcapital or intertrochanteric (IT) fracture of the hip. In this single-centre, randomized controlled trial, elderly patients undergoing surgery for a hip fracture, either hemiarthroplasty for a subcapital fracture or intramedullary nailing for an IT fracture, were screened for inclusion. Patients were randomly allocated to a study group using a sealed envelope. The TXA group consisted of 77 patients, (35 with a subcapital fracture and 42 with an IT fracture), and the control group consisted of 88 patients (29 with a subcapital fracture and 59 with an IT fracture). One dose of 15 mg/kg of intravenous (IV) TXA diluted in 100 ml normal saline (NS,) or one dose of IV placebo 100 ml NS were administered before the incision was made. The haemoglobin (Hb) concentration was measured before surgery and daily until the fourth postoperative day. The primary outcomes were the total blood loss and the rate of transfusion from the time of surgery to the fourth postoperative day.Aims
Methods
Staphylococcus aureus is the main cause of osteomyelitis and forms biofilm and staphylococcal abscess communities (SACs) in humans. While S. aureus has several toxins with specificity for human targets and working with human host cells would be preferred, for SACs no in vitro models, two-dimensional (2D) or three-dimensional (3D), have been described in literature to date. Advanced 3D in vitro cell culture models enable the incorporation of human cells and resemble in vivo tissue more closely than conventional 2D cell culture. Therefore, the aim of this study was to develop an in vitro model of SACs by using a 3D system. The model should allow for studies into antibiotic tolerance and S. aureus - human host cells interactions. With a clinical isolate (S. aureus JAR) or a lab strain (S. aureus ATCC 49230-GFP), SACs were grown in a collagen gel (1.78 mg/ml, Gibco) supplemented with 200 µl human plasma at 37 °C. Transmission and scanning electron microscopy was used to obtain a detailed overview of SACs, whereas immunofluorescent stainings were done to determine whether the pseudocapsule around SACs consist of fibrin. Antibiotic tolerance of SACs was assessed with 100× the minimal inhibitory concentration (MIC) of gentamicin (Roth). Bacterial clearance of non-establised SACs and established SACs with or without pseudocapsule was determined by exposure to differentiated PLB neutrophil-like cells (differentiation with 1.25% DMSO and 5% FBS for 5 days; dPLB) or primary neutrophils isolated with lymphoprep from fresh heparin blood. Degradation of the pseudocapsule was done with 7.5 µl/ml
Fibrinolysis plays a key transition step from haematoma formation to angiogenesis and fracture healing. Low-magnitude high-frequency vibration (LMHFV) is a non-invasive biophysical modality proven to enhance fibrinolytic factors. This study investigates the effect of LMHFV on fibrinolysis in a clinically relevant animal model to accelerate osteoporotic fracture healing. A total of 144 rats were randomized to four groups: sham control; sham and LMHFV; ovariectomized (OVX); and ovariectomized and LMHFV (OVX-VT). Fibrinolytic potential was evaluated by quantifying fibrin, tissue plasminogen activator (tPA), and plasminogen activator inhibitor-1 (PAI-1) along with healing outcomes at three days, one week, two weeks, and six weeks post-fracture.Aims
Methods
Dystrophic calcification (DC) is the abnormal appearance of calcified deposits in degenerating tissue, often associated with injury. Extensive DC can lead to heterotopic ossification (HO), a pathological condition of ectopic bone formation. The highest rate of HO was found in combat-related blast injuries, a polytrauma condition with severe muscle injury. It has been noted that the incidence of HO significantly increased in the residual limbs of combat-injured patients if the final amputation was performed within the zone of injury compared to that which was proximal to the zone of injury. While aggressive limb salvage strategies may maximize the function of the residual limb, they may increase the possibility of retaining non-viable muscle tissue inside the body. In this study, we hypothesized that residual dead muscle tissue at the zone of injury could promote HO formation. We tested the hypothesis by investigating the cellular and molecular consequences of implanting devitalized muscle tissue into mouse muscle pouch in the presence of muscle injury induced by cardiotoxin.Aims
Methods
Aims. The anterior cruciate ligament (ACL) is known to have a poor wound healing capacity, whereas other ligaments outside of the knee joint capsule such as the medial collateral ligament (MCL) apparently heal more easily.
Antifibrinolytic agents, including tranexamic acid (TXA) and epsilon-aminocaproic acid (EACA), have been shown to be safe and effective for decreasing perioperative blood loss and transfusion following total hip arthroplasty (THA) and total knee arthroplasty (TKA). However, there are few prospective studies that directly compare these agents. The purpose of this study was to compare the benefits of intraoperative intravenous TXA with EACA. A total of 235 patients (90 THA and 145 TKA) were enrolled in this prospective, randomized controlled trial at a single tertiary-care referral centre. In the THA cohort, 53.3% of the patients were female with a median age of 59.8 years (interquartile range (IQR) 53.3 to 68.1). In the TKA cohort, 63.4% of the patients were female with a median age of 65.1 years (IQR 59.4 to 69.5). Patients received either TXA (n = 119) or EACA (n = 116) in two doses intraoperatively. The primary outcome measures included change in haemoglobin level and blood volume, postoperative drainage, and rate of transfusion. Secondary outcome measures included postoperative complications, cost, and length of stay (LOS).Aims
Patients and Methods
Tranexamic acid (TXA) is an anti-fibrinolytic medication commonly used to reduce perioperative bleeding. Increasingly, topical administration as an intra-articular injection or perioperative wash is being administered during surgery. Adult soft tissues have a poor regenerative capacity and therefore damage to these tissues can be harmful to the patient. This study investigated the effects of TXA on human periarticular tissues and primary cell cultures using clinically relevant concentrations. Tendon, synovium, and cartilage obtained from routine orthopaedic surgeries were used for Objectives
Methods
OA pathophysiology has a vascular component consisting of venous stasis resulting in intraosseous hypertension and hypoxia. In response, osteoblasts change their cytokine expression, accelerating bone remodelling and cartilage breakdown consistent with OA. We have characterized circulatory kinetics in OA bone in animal models with dynamic contrast enhanced MRI (DCE-MRI) and . 18. F PET and have demonstrated venous stasis and reduced perfusion that temporally precede and spatially coincide with OA lesions. Osteoblast uptake of . 18. F is consistent with abnormal perfusion, bone remodelling, and severity of OA. Circulatory kinetics with DCE-MRI in humans with OA of the knee exhibit similar venous outflow obstruction. Venous stasis is associated with hypoxia in subchondral bone. As an example of the effects of hypoxia on OA osteoblasts, we have described upregulation of fibrinolytic peptides, but a deficiency in the upregulation of PAI-1, leading to the generation of
The aim of this study was to identify the most effective regimen
of multiple doses of oral tranexamic acid (TXA) in achieving maximum
reduction of blood loss in total knee arthroplasty (TKA). In this randomized controlled trial, 200 patients were randomized
to receive a single dose of 2.0 g of TXA orally two hours preoperatively
(group A), a single dose of TXA followed by 1.0 g orally three hours
postoperatively (group B), a single dose of TXA followed by 1.0 g
three and nine hours postoperatively (group C), or a single dose
of TXA followed by 1.0 g orally three, nine, and 15 hours postoperatively
(group D). All patients followed a routine enhanced-recovery protocol.
The primary outcome measure was the total blood loss. Secondary
outcome measures were hidden blood loss (HBL), reduction in the
level of haemoglobin, the rate of transfusion and adverse events.Aims
Patients and Methods
The intra-articular administration of tranexamic acid (TXA) has
been shown to be effective in reducing blood loss in unicompartmental
knee arthroplasty and anterior cruciate reconstruction. The effects
on human articular cartilage, however, remains unknown. Our aim,
in this study, was to investigate any detrimental effect of TXA
on chondrocytes, and to establish if there was a safe dose for its
use in clinical practice. The hypothesis was that TXA would cause
a dose-dependent damage to human articular cartilage. The cellular morphology, adhesion, metabolic activity, and viability
of human chondrocytes when increasing the concentration (0 mg/ml
to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were
analyzed in a 2D model. This was then repeated, excluding cellular
adhesion, in a 3D model and confirmed in viable samples of articular cartilage.Aims
Materials and Methods
The aim of this study was to examine the efficacy and safety
of multiple boluses of intravenous (IV) tranexamic acid (TXA) on
the hidden blood loss (HBL) and inflammatory response following
primary total hip arthroplasty (THA). A total of 150 patients were allocated randomly to receive a
single bolus of 20 mg/kg IV TXA before the incision (group A), a
single bolus followed by a second bolus of 1 g IV-TXA three hours
later (group B) or a single bolus followed by two boluses of 1 g
IV-TXA three and six hours later (group C). All patients were treated
using a standard peri-operative enhanced recovery protocol. Primary
outcomes were HBL and the level of haemoglobin (Hb) as well as the
levels of C-reactive protein (CRP) and interleukin-6 (IL-6) as markers
of inflammation. Secondary outcomes included the length of stay
in hospital and the incidence of venous thromboembolism (VTE).Aims
Patients and Methods
The purpose of the present study was to evaluate the impact of
intravenous tranexamic acid on the reduction of blood loss, transfusion
rate, and early post-operative clinical outcome in total shoulder
arthroplasty. A randomised, placebo-controlled trial which included 54 patients
undergoing unilateral primary stemless anatomical or stemmed reverse
total shoulder arthroplasty was undertaken. Patients received either
100 ml saline (placebo, n = 27), or 100 ml saline together with
1000 mg of tranexamic acid (TXA, n = 27) intravenously prior to
skin incision and during wound closure. Peri-operative blood loss
via an intra-articular drain was recorded and total blood loss was
calculated. The post-operative transfusion rate was documented.
Assessment of early clinical parameters included the visual analogue
scale for pain (VAS), documentation of haematoma formation and adverse events.Aims
Patients and Methods
This study investigated whether the use of tranexamic acid (TXA)
decreased blood loss and transfusion related cost following surface
replacement arthroplasty (SRA). A retrospective review of patients treated with TXA during a
SRA, who did not receive autologous blood (TXA group) was performed.
Two comparison groups were established; the first group comprised
of patients who donated their own blood pre-operatively (auto group)
and the second of patients who did not donate blood pre-operatively
(control). Outcomes included transfusions, post-operative haemoglobin
(Hgb), complications, and length of post-operative stay. Aims
Methods
Tranexamic acid (TXA), an inhibitor of fibrinolysis,
reduces blood loss after total knee arthroplasty. However, its effect
on minimally invasive total hip arthroplasty (THA) is not clear.
We performed a prospective, randomised double-blind study to evaluate
the effect of two intravenous injections of TXA on blood loss in
patients undergoing minimally invasive THA. In total, 60 patients (35 women and 25 men with a mean age of
58.1 years; 17 to 84) who underwent unilateral minimally invasive
uncemented THA were randomly divided into the study group (30 patients,
20 women and ten men with a mean age of 56.5 years; 17 to 79) that
received two intravenous injections 1 g of TXA pre- and post-operatively
(TXA group), and a placebo group (30 patients, 15 women and 15 men
with a mean age of 59.5 years; 23 to 84). We compared the peri-operative
blood loss of the two groups. Actual blood loss was calculated from
the maximum reduction in the level of haemoglobin. All patients
were followed clinically for the presence of venous thromboembolism. The TXA group had a lower mean intra-operative blood loss of
441 ml (150 to 800) This prospective, randomised controlled study showed that a regimen
of two intravenous injections of 1 g TXA is effective for blood
conservation after minimally invasive THA. Cite this article:
Exsanguination is the second most common cause
of death in patients who suffer severe trauma. The management of
haemodynamically unstable high-energy pelvic injuries remains controversial,
as there are no universally accepted guidelines to direct surgeons
on the ideal use of pelvic packing or early angio-embolisation.
Additionally, the optimal resuscitation strategy, which prevents
or halts the progression of the trauma-induced coagulopathy, remains
unknown. Although early and aggressive use of blood products in
these patients appears to improve survival, over-enthusiastic resuscitative
measures may not be the safest strategy. This paper provides an overview of the classification of pelvic
injuries and the current evidence on best-practice management of
high-energy pelvic fractures, including resuscitation, transfusion
of blood components, monitoring of coagulopathy, and procedural
interventions including pre-peritoneal pelvic packing, external
fixation and angiographic embolisation. Cite this article:
Despite improvements in surgical technique, blood loss continues to be an issue following TJR in 2013. Peri-operative blood loss averages between 1000 and 1500 cc during THR and TKR. Multiple methods have been employed in attempts to minimise this loss. Concepts such as hypotensive anesthesia, tourniquet use, intraoperative blood salvage and autologous pre-donation and postoperative re-infusion drains as well as the use of bipolar sealants, fibrin sprays and thrombin agents have been tried with varying degrees of success. Recently there has been a surge of interest in the use of antifibrinolytics such as Tranexamic Acid (TXA), Aprotinin and Aminocaproic Acid. These medications have a long history of use in other fields such as cardiac and oral surgery but are just recently being utilised following TJR. Of these medications, TXA has been by far the best studied. TXA is a synthetic amino acid that inhibits fibrinolysis by competitively and reversibly blocking the Lysine binding sites on plasminogen. This inhibits its activation and slows the conversion from plasminogen to
