Intra-articular Bleeding Research Articles

Novel injectable adhesive hydrogel loaded with exosomes for holistic repair of hemophilic articular cartilage defect

Hemophilic articular cartilage damage presents a significant challenge for surgeons, characterized by recurrent intraarticular bleeding, a severe inflammatory microenvironment, and limited self-repair capability of cartilage tissue. Currently, there is a lack of tissue engineering-based integrated therapies that address both early hemostasis, anti-inflammation, and long-lasting chondrogenesis for hemophilic articular cartilage defects. Herein, we developed an adhesive hydrogel using oxidized chondroitin sulfate and gelatin, loaded with exosomes derived from bone marrow stem cells (BMSCs) (Hydrogel-Exos). This hydrogel demonstrated favorable injectability, self-healing, biocompatibility, biodegradability, swelling, frictional and mechanical properties, providing a comprehensive approach to treating hemophilic articular cartilage defects. The adhesive hydrogel, featuring dynamic Schiff base bonds and hydrogen bonds, exhibited excellent wet tissue adhesiveness and hemostatic properties. In a pig model, the hydrogel could be smoothly injected into the knee joint cartilage defect site and gelled in situ under fluid-irrigated arthroscopic conditions. Our in vitro and in vivo experiments confirmed that the sustained release of exosomes yielded anti-inflammatory effects by modulating macrophage M2 polarization through the NF-κB pathway. This immunoregulatory effect, coupled with the extracellular matrix components provided by the adhesive hydrogel, enhanced chondrogenesis, promoted the cartilage repair and joint function restoration after hemophilic articular cartilage defects. In conclusion, our results highlight the significant application potential of Hydrogel-Exos for early hemostasis, immunoregulation, and long-term chondrogenesis in hemophilic patients with cartilage injuries. This innovative approach is well-suited for application during arthroscopic procedures, offering a promising solution for addressing the complex challenges associated with hemophilic articular cartilage damage.

Preliminary study of extracorporeal shock wave alleviating joint capsule fibrosis caused by internal bleeding of knee joint in rats

ABSTRACT Purpose Joint contracture is a common disease in clinical practice, joint bleeding is an important factor affecting the progression of joint contracture. This study aimed to explore the effect of extracorporeal shock wave on alleviating joint capsule fibrosis caused by intra-articular hemorrhage in rats. Methods Forty two SD rats were randomly divided into seven groups. Perform simple fixation and fixation after blood injection separately. Measure the range of motion of each group’s knee joints and calculate the corresponding degree of contraction. Use HE staining and Masson staining to detect the number of anterior joint capsule cells and collagen deposition. Detection of changes in Wnt1, β-catenin protein expression in joint capsule using Western blotting. Results Compared to group C, the degree of knee joint contracture in M1 and M2 groups of rats increased, and collagen deposition, cell number and Wnt1, β-catenin protein expression also increased accordingly. Compared to M1 and M2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased, and the degree of joint contracture in NR1 and NR2 groups showed no significant improvement. Compared to NR1 and NR2 groups, the degree of knee contraction in E1 and E2 groups were reduced, while collagen deposition, cell number and Wnt1, β-catenin protein expression were decreased. Conclusions Both rat models of knee joint contracture were successful, and joint bleeding can exacerbate joint contracture. Extracorporeal shock waves alleviate joint capsule fibrosis caused by intra-articular bleeding in rats.

Poster 180: TXA Administration After Hip Arthroscopy: Preliminary Data of a Randomized Controlled Trial

Objectives: Previous studies in shoulder and knee arthroscopy have reported that tranexamic acid (TXA) may improve early functional recovery, prevent postoperative intra-articular bleeding, reduce subjective pain, and improve intra-operative visual field clarity. However, there is a paucity of literature describing the use of TXA in hip arthroscopy. Previous studies have reported statistically significant improvements in VAS pain and Modified Hip Harris scores. However, they used a limited subset of Patient Reported Outcome Measures (PROMs) and did not characterize the effects of TXA on visibility during arthroscopy. The primary objective of this study is to determine the role of TXA in hip arthroscopy based on assessment of postoperative pain and function. A second objective of this study is to determine whether TXA influences intra-operative visual clarity and pump pressures. Methods: This double blinded randomized controlled trial is enrolling 70 patients undergoing primary hip arthroscopy. Subjects are randomized to receive TXA (n=35) or not receive TXA (n=35). The TXA group receives 1g of TXA intravenously at the time of incision and another 1g of TXA during closure. For the duration of the surgery, arthroscopic visual field clarity is rated by the surgeon every 15 minutes as poor, fair, or good and assigned a score of 1, 2, and 3, respectively. Each time the visual clarity is rated, pump pressure is also recorded. Range of motion, VAS Pain, iHOT-12, HOS Sport and activities of daily living, PROMIS Physical Function (PF), and PROMIS Pain Interference (PI) scores are collected preoperatively and postoperatively at days 14 and 42. Additionally, VAS pain is assessed at postoperative day 1. At the completion of all study activities, patient charts are reviewed to determine whether they have requested any additional analgesic medication during the study. Results: The preliminary data for this study includes completed data from 16 (9 female, 7male) patients with a mean age of 44 years. The TXA and control groups had 9 and 7 patients, respectively. No significant difference in VAS pain scores were observed preoperatively, at 1 day postoperatively, or at 42 days postoperatively. There was a significant difference (p=0.01) in VAS pain scores between the two groups at 14 days postoperatively, with the TXA and control groups having mean scores of 2.22 ± 1.48 and 4.33 ± 1.21, respectively. Both groups have shown improvements in PROMs between preoperative scores and postoperative day 42, with larger improvements being seen in the TXA group (although failing to meet statistical significance). Complete preliminary data for PROMs can be seen in Table 1. The average visual score in the TXA group (2.85 ± 0.25) was better than that of the control group (2.67 ± 0.2) but failed to meet statistical significance (p=0.132). The frequency that each rating was assigned was calculated for each group and can be seen in Table 2. A chi-squared test of independence was conducted to examine the relationship between the distribution of grades (Good, Fair, Poor) and the treatment groups (TXA and Control). The test indicated no association between the two variables (Pearson’s χ² = 5.6, df = 2, p = 0.06). Although the p-value did not reach significance level (α<0.05), the preliminary data favored the TXA group in terms of visibility. Pump pressures did not show any significant difference between the TXA group and the control group at any of the time points. No patients have requested additional pain medications during their involvement in this study at this time. Conclusions: The use of TXA in hip arthroscopy descriptively demonstrated improvements in post-operative pain and function, but not intraoperative visual clarity. The trends in the preliminary data, particularly for visual clarity and the measures of pain such as VAS Pain (Figure 1) and PROMIS-PI (Figure 2), suggest a clinical benefit to intraoperative TXA use. Larger sample sizes are needed to establish the significance of these findings and further explore the relationship between TXA and postoperative outcomes, visual clarity, and pump pressures in hip arthroscopy.

Treatment of hemophilic arthropathy by immunomodulatory extracellular vesicle delivered by liposome hybrid nanoparticles

In individuals afflicted with hemophilia, characterized by a deficiency of coagulation factor VIII (FVIII), the occurrence of spontaneous recurrent intra-articular hemorrhage precipitates the emergence of hemophilic arthropathy (HA). Although clotting factor replacement therapy reduces joint bleeding clinically, clotting factors need to be injected frequently due to the rapid diffusion of the drug. Hence, a novel drug delivery approach may be developed to improve the drug therapy. Platelet-derived extracellular vesicles (PEVs) are known to possess anti-inflammatory and hemostatic properties and could be used as a potential HA therapy. In this study, we constructed a PEV-LS@FVIII nanotherapeutic system by combining thioketal (TK), liposomes (LS), and FVIII to form the LS@FVIII complexes, and then hybridizing PEV with LS@FVIII. Our results demonstrated that PEV-LS@FVIII could efficiently facilitate FVIII delivery and specifically target the injured knee joint. Both in vitro and in vivo studies showed a reduction in the M1 phenotype of macrophages and an enhancement of the M2 phenotype, compared to FVIII free control. Furthermore, PEV-LS@FVIII appeared to alleviate HA-induced cartilage damage. In conclusion, our findings demonstrate that PEV-LS@FVIII could delay the progression of HA by targeting bleeding joints, modulating macrophage polarization to suppress inflammation, and mitigating cartilage damage.

Monitoring of Hemophilia A in Morocco

Hemophilia A is a hemorrhagic disorder caused by a deficiency in factor VIII coagulation. Its incidence is 1 to 2 per 10,000 male births. Hemophilia A is characterized by intra-articular, mucosal, or cutaneous bleeding, and its management relies on the substitution of factor VIII with plasma derived or recombinant products. However, the major complication of treatment is the development of anti-factor VIII inhibitors, rendering substitution therapy ineffective. The aim of this study is to investigate the prevalence of anti-factor VIII inhibitors, the severity of hemophilia, and the follow-up of hemophilia patients developing anti-FVIII inhibitors in a hemophiliac population by presenting their epidemiological and biological characteristics. We conducted a retrospective descriptive cross-sectional study at the Central Hematology Laboratory of the Ibn Sina Hospital Center in Rabat (Morocco) over a period of 37 months, from December 1, 2020, to December 31, 2023. The study included 172 hemophilia A patient, with a mean age of 25 years. 55 patients developed anti-FVIII inhibitors (32%). The majority of positive inhibitor hemophiliacs were severe hemophiliacs (87%), including 23 cases of low responders (42%) and 32 cases of high responders (58%). The results obtained partly agree with most national studies (H. Mamad 2021, Y. El Aissaoui 2016, and F. Zizi in 2011), and international ones. However, the development of inhibitors varies from one individual to another according to several criteria (genetic and non-genetic).

Adolescents with hemophilic knee arthropathy can improve their gait characteristics, functional ability, and physical activity level through kinect-based virtual reality: A randomized clinical trial

BackgroundHemophilic arthropathy is caused by recurrent intra-articular bleeding, most commonly in the knee joints. In terms of physical impact, this arthropathy causes significant disability and hampers the physical activity and functionality of he affected individuals. ObjectiveThis study intended to examine the effect of a physical rehabilitation program incorporating Kinect-based virtual reality (KBVR) on gait characteristics, functional ability, and physical activity level in adolescents diagnosed with hemophilic knee arthropathy (HKA) Materials and methodsIn a randomized clinical trial, 56 boys, aged 10–14 years, with moderate HKA, were randomly allocated into two groups. The control group (n = 28) received conventional physical therapy (CPT), while the KBVR group (n = 52) received a 30-min KBVR exercise program in addition to the CPT. Training was conducted three times/week for 12 successive weeks. Gait characteristics (step length, cadence, velocity, peak knee extension moment during stance, and knee flexion amplitude during swing) were assessed using a gait analysis system, the functional ability was assessed through the 6-min walk test, and physical activity level assessed by the Adolescents' Physical Activity Questionnaire on the pre- and post-treatment occasions. ResultsThe KBVR group achieved more favorable changes in the gait characteristics [step length (P = 0.015), cadence (P = 0.004), velocity (P = 0.024), peak knee extension moment during stance (P = 0.018), and Knee flexion amplitude during swing (P = 0.032)], functional capacity (P = 0.002), and physical activity levels (P = 0.007) compared to the control group. ConclusionThe use of KBVR exercises within a rehabilitation program is a potentially effective therapeutic option for the total care of adolescents with HKA.

Comparison between dual-energy computed tomography and ultrasound in the diagnosis of gout

Objectives: Gout is one of the most common inflammatory arthritic conditions that arise due to the super saturation of urate levels in body tissues, resulting in the formation of monosodium urate (MSU) crystals that get deposited in and around the joints. Clinical diagnosis of gout is generally made based on signs and symptoms. The biochemical diagnosis is based on the levels of serum uric acid. However, hyperuricemia is a weak marker for gout diagnosis. The gold standard for diagnosing gout is the identification of MSU crystals in the synovial fluid by Polaroid microscopy. However, it is an invasive procedure that could lead to complications such as joint effusion and intra-articular hemorrhage. Imaging offers a non-invasive method for the diagnosis of gout. Ultrasound (USG) has emerged as a useful measure for detecting joint effusion and synovitis, studying cartilage, describing early bone erosions, and evaluating tendons and crystal deposition. Dual-energy computed tomography (DECT) is a useful non-invasive technique that helps visualize MSU crystals, along with other soft tissue changes and erosive pathologies, at high resolution, much earlier than conventional radiography could do. Material and Methods: Clinically suspected or diagnosed gout patients in the age group of 20–75 years of both genders attending outpatient services were selected for the study. All the patients fulfilling the inclusion criteria of clinical suspicion of gout or already proven cases of gout were clinically examined, and body mass index, presenting complaints, symptomatic joints, past medical history, family history, and personal habits were noted. The diagnosis of gout was confirmed using the 2015 American college of rheumatology/European league against rheumatism (ACR/EULAR) classification criteria: A cut-off score >8 was considered diagnostic. Thereafter, all the patients underwent ultrasonographic and computed tomography evaluations. All the patient’s assessments were made at nine locations bilaterally – shoulder, neck, wrist, metacarpal, metatarsophalangeal, ankle, hip, knee, and elbow to check for multiple joint involvements. All the DECT images were post-processed, allowing analysis of images using the three material decomposition methods. On reconstructed DECT images, green color-coded MSU crystals were considered suggestive of gout. Results: The present study reported a higher detection of gout on DECT (97.1%) as compared to the USG (88.2%). Similarly, several studies reported a higher detection rate of MSU crystal deposition by DECT as compared to the detection of the double-contour sign by USG. This study reported sensitivity, specificity, positive predictive, and negative predictive value (PPV and NPV) of USG as 91%, 92%, 95%, and 85%, respectively. In contrast, DECT’s sensitivity, specificity, PPV, and NPVs were 96%, 100%, 100%, and 92%, respectively. DECT showed to have a high sensitivity as well as specificity. Conclusion: The study showed that DECT is more sensitive and had a better PPV and accuracy than USG in the diagnosis of gout. Keeping in view the high efficacy of DECT in diagnosing gouty joints, it is a strong candidate to emerge as a non-invasive imaging modality of choice for diagnosing gout.

Iron overload causes macrophages to produce a pro-inflammatory phenotype in the synovium of hemophiliac arthritis via the acetyl-p53 pathway.

Haemophiliac arthritis (HA) is caused by spontaneous intra-articular hemorrhage and repeated intra-articular hematomas, leading to iron overload, which, in turn, induces M1 macrophage polarisation and inflammatory cytokine secretion, resulting in synovitis. Here, we explored the mechanism by which iron overload in HA induces the polarisation of M1 macrophages, providing a new approach for the treatment of HA synovitis. The synovium from the knee joints of normal amputees and patients with HA was collected. Pathological changes in the synovial tissues were analysed using hematoxylin and eosin staining. Iron tissue deposition was evaluated using the iron assay kit and Prussia Blue staining, while macrophage phenotype was determined using immunofluorescence. The levels of pro-inflammatory cytokines and p53 acetylation were determine using western blotting. An in vitro iron overload model was established by inducing THP-1 macrophages with ferric ammonium citrate, and the involvement of acetylated p53 in M1 macrophage polarisation was investigated. Compared to control samples, the iron content in the synovium of patients with HA was significantly increased. The protein levels of M1 macrophage markers, pro-inflammatory cytokines, and acetylated p53, were also significantly elevated in the synovial tissues of patients with HA. Similar results were observed in the in vitro iron overload model. Furthermore, the inhibition of p53 acetylation in vitro reversed these iron overload-induced effects. In patients with HA, iron overload induced synovial p53 acetylation, leading to macrophage polarisation toward the M1 phenotype and increased inflammatory cytokine secretion, resulting in synovitis. Synovial iron overload is associated with changes in P53 acetylation in hemophiliac arthritis (HA). Acetylated p53, a known regulator of macrophage polarization, is highly expressed in HA synovium, suggesting a potential role in M1 polarization. HA synovial macrophages predominantly polarize into the pro-inflammatory M1 phenotype, secreting elevated levels of pro-inflammatory cytokines.

Economic and Clinical Impact Evaluation of AI-Aided Point-of-Care Ultrasound (POCUS) in the Management of Early-Stage Joint Damage in Hemophilia

Background: In previous studies, we reported that regular semi-annual POCUS over three years led to modifications in prophylaxis, contributing to the disappearance of synovitis, improvement in the annual bleeding rate, and joint function in hemophilia patients. Most modifications involved increasing doses, shortening intervals, and changing to new drugs. With ongoing AI technology development to offer accurate POCUS delivery, often dubbed as provider-dependent, we foresee active modifications of prophylaxis in clinical settings as AI-enabled ultrasound becomes prevalent. Such interventions could improve patient joint prognosis through early synovitis treatment but may also lead to increased consumption of therapeutic drugs. Objective: To compare the ‘improvement in prognosis’ with ‘increased costs’ from a health economic perspective, primarily from an insurer's viewpoint. Method: Patient states were defined to create a state transition model as follows: No bleeding: Normal state with no bleeding or synovitis.Bleeding present: State of having 1-2 bleeding episodes in six months.Synovitis: Chronic bleeding-prone state due to synovitis. This state worsens at a certain rate, necessitating modification of regular replacement therapy.Joint destruction: An irreversible state of terminal arthritis where the cartilage and bone are destroyed.Death: Regardless of the association with hemophilia. Transition probabilities were set based on prior studies, and the state transition model is depicted in Figure 1. We assumed all patients were receiving regular replacement therapy. We obtained the distribution of age, compliance rate, and the number of intra-articular bleedings from the transition model and optimized the transition probabilities to minimize the difference between the obtained distribution and the distribution from prior studies. The treatment cost for each state was referenced from the standard cost ascertainable in Japan. The model assumes the perfect sensitivity of the AI technology in identifying patients who require modifications in their therapy. We also assume that there would be no false negatives when a physician's judgement is involved, and the model does not consider the AI's specificity. In the scenario where a physician disagrees with the AI's judgement, we assume that the physician would maintain their decision. Results: The comparison of Incremental cost-effectiveness ratio (ICER) with or without POCUS, when the post-therapeutic modification drug cost increases by 1.25 times, is shown in Figure 2. With the cost increase at 1.25 times, the ICER is below 5 million yen, a threshold value suggested by guidelines that indicates superior cost-effectiveness. However, if the cost increase is twofold, the ICER becomes 6.04 million yen, indicating poorer cost-effectiveness with POCUS. The result implies that diagnostic AI-POCUS proves superior in terms of cost-effectiveness when the ‘cost increase ratio’ is below or equal to 1.85. In evaluating the cost-effectiveness of POCUS, the ‘drug cost increase ratio’ was a significant factor influencing ICER, while the costs, sensitivity, and specificity of POCUS had a smaller impact. Limitation: Our model assumes the ‘additional cost is uniformly fixed for all patients’, which may not reflect the reality of clinical practice. Additionally, we have not considered the possible clinical benefits and quality of life improvements that can occur regardless of the cost implications. Conclusion: This preliminary study suggests that AI-aided POCUS is cost-effective compared to regular POCUS management in treating early-stage joint damage in hemophilia patients when the increase in medication costs remains below a 1.85 multiplier, from an insurer's perspective. The study focuses on the improvement of underdiagnoses by evaluators through AI technology. Further studies are required to refine these estimates, validate our model in a real-world clinical setting, and to fully understand the sensitivity and specificity of the AI system. Figure1: The transition model of patients states Figure2: Incremental Cost-Effectiveness Ratio with and without AI-POCUS in Response to a 1.25 Fold Increase in Post-Therapeutic Modification Drug Cost

Intraarticular management of chronic haemophilic arthropathy (Review).

Hemophilia is an inherited X-linked bleeding condition with predominant joint involvement due to intra-articular bleeding, hemosiderin deposition and the synovial hypertrophy that is responsible for cartilage destruction, joint deformity and malalignment, pain and functional restriction. Management of chronic arthropathy includes conservative and surgical approaches. Conservative therapies consist of pain modulation, oral drugs, physiotherapy and intra-articular agents. For the present review, the literature was searched for intra-articular agents and 20 papers on the use of corticosteroids (CS), hyaluronic acid (HA) and platelet-rich plasma (PRP), with different regimes of administration, were included. CS had a longer record of injection, with statistically significant pain reduction and functional improvement in the short-term and moderate persistence in the long-term. HA was able to improve the clinical and functional status of joints with moderate or severe hemophilia. PRP was relatively recently introduced to joint management and the results remain controversial. Different associations between the above-mentioned agents were proposed by studies including a small number of patients, producing comparable results. It was concluded that there is a need for extensive research on intra-articular agents, with stratification according to the severity of joint involvement. The lack of a blinded or placebo-controlled arm due to ethical aspects makes the task challenging.

Ultrasound Evaluation of Tendinopathy in Hemophiliac Patients for the Purpose of Rehabilitation Indications.

Hemophilia is a inherited bleeding disorder that is characterized by intra-articular bleeding (hemarthrosis). The aim of the study was to evaluate the state of the satellite tendons of the target joints in the patient with hemophilic arthropathy and propose rehabilitation treatment with eccentric exercises. The tendons of the joints mainly affected by hemophilic arthropathy were evaluated by ultrasound. The ultrasound evaluation is associated with the use of evaluation clinical scales, such as the Hemophilia Joint Health Score (HJHS), the Functional Independence Score in Hemophilia (FISH), the Hemophilia Activity List (HAL), the DASH, the VISA-A, the VISA-P, and the VAS scale. In 20 patients with hemophilic arthropathy, the thickness of the tendons that were examined was normal. In six subjects with severe joint damage, echostructural alterations were present, and signs of hyperemia and neo-vascularization were detected on color Doppler, as well as the presence of intratendinous calcifications. The tendons of the target joints in patients with hemophilic arthropathy are compromised by the indirect biomechanical damage caused by the joint disease, and rehabilitation treatment with eccentric exercises can be considered safe and effective in improving the tenso-elastic properties of the tendons.

Towards achieving a haemophilia-free mind.

Towards achieving a haemophilia-free mind.

The effect of a single dose of intravenous tranexamic acid on visual clarity in knee arthroscopic meniscectomy without a tourniquet

Background/Aim: Tranexamic acid (TXA) is known to reduce intra-articular bleeding during arthroscopic procedures, which can improve visibility and reduce postoperative pain and knee joint swelling from hemarthrosis. However, insufficient data supports the routine use of TXA in arthroscopic meniscectomy. This study aimed to evaluate the effect of a single dose of intravenous (IV) TXA on visual clarity in arthroscopic meniscectomy without a tourniquet.
 Methods: A randomized, double-blind, controlled trial was conducted to assess the use of TXA for visibility in routine arthroscopic meniscectomy without a tourniquet. Between January 2021 and February 2022, 53 patients undergoing arthroscopic meniscectomy were randomly assigned to either the TXA group (n=27), who received 1 g IV-TXA, or the control group (n=26), who received 100 ml of normal saline. Visual clarity was evaluated using a Numeric Rating Scale (NRS). Patients were also assessed for the need for a tourniquet, tourniquet time, total operative time, volume of irrigation fluid, postoperative pain, hemarthrosis, and knee function on postoperative day 3 and weeks 1, 2, and 4, using the Lysholm knee scoring scale.
 Results: There was no significant difference in intra-operative arthroscopic visibility between the TXA and control groups (P=0.394). Tourniquet was required in three cases in the TXA group and four cases in the control group (P=0.646). There was no significant difference between the two groups regarding postoperative pain, grade of postoperative hemarthrosis, knee motion, or the Lysholm Knee Score after the operation.
 Conclusion: The administration of IV-TXA in arthroscopic meniscectomy without a tourniquet did not provide any benefits such as enhanced surgical visualization, reduction in the need to inflate the tourniquet due to obstructed visibility, or decrease in hemarthrosis, VAS pain score, or improved range of motion of the knee in the postoperative period when compared to the control group.

Clinical efficacy of intra-articular infusion of cocktail combined with tranexamic acid in the treatment of middle-age and older patients with frozen shoulder following arthroscopic capsular release.

To investigate the clinical efficacy of arthroscopic capsular release and postoperative intra-articular infusion of cocktail combined with tranexamic acid (TXA) in the treatment of patients with frozen shoulder. A total of 85 middle-aged and older patients with frozen shoulder who underwent arthroscopic capsular release and received intra-articular infusion of TXA alone (n = 28), cocktail alone (n = 26), and cocktail plus TXA (n = 31) after surgery were retrospective analyzed. The drainage volume within 24 h after surgery, postoperative length of hospital stay, postoperative complications, visual analog scale (VAS), Neer shoulder assessment scale, ASES score, and range of motion (ROM) of the shoulder joint at 1 day, 1 week, 1 month, and 3 months after surgery in all three groups were recorded and compared. Postoperative length of hospital stay was significantly shorter in the cocktail + TXA and cocktail groups than that in the TXA group. Postoperative drainage volume was significantly higher in the cocktail group compared with TXA + cocktail group (P < 0.05). At 1 day and 1 week after surgery, pain was more pronounced in the TXA group, which was significantly relieved in the cocktail and the cocktail + TXA groups (P < 0.05). Pain was significantly relieved in all the three groups at 1 and 3 months after surgery. Significant functional improvement of the shoulder was achieved in all three groups at 1 week after surgery, the improvement was apparent in the cocktail + TXA groups (P < 0.05), followed by the cocktail group. At 1 month after surgery, patients in the cocktail + TXA groups obtained excellent functional recovery of the shoulder joint. At 3 months after surgery, patients in all the three groups both obtained good recovery of the shoulder joint function, and the recovery was apparent in the cocktail + TXA groups (P < 0.05). Arthroscopic capsular release and postoperative intra-articular infusion of cocktail combined with TXA has good safety and efficacy in the treatment of middle-age and older patients with frozen shoulder, which can reduce postoperative pain and intra-articular bleeding, promote early postoperative functional exercises and accelerate early postoperative recovery.

Посттравматический гемартроз с точки зрения теории воспаления

Introduction Post-traumatic hemarthrosis is identified as intra-articular hemorrhage accompanied by five classic signs of inflammation: hyperemia, hyperthermia, edema, pain and changes in the joint function. The objective of the study was to establish whether inflammation should be underestimated in post-traumatic hemarthrosis based on the analysis of the world scientific literature of recent years. Material and methods Internet search platform Web of Science (Clarivate Analytics, USA): databases Web of Science Core Collection (subscription access), Publons (open access), Medline (open access) were used to review scientific articles. Papers from the Scopus Elsevier database (Netherlands) were explored. The search depth was 15 years. Topics that did not receive coverage in the literature of this period were studied until the 1960s in some cases. More than 200 sources were identified on the subject. The literature published in the current year was analyzed covering 15.0 % of the materials, brought out in the last 5 years including the current year covering 56.3 %, in the last 10 years including the current year covering 73.8 %, in the last 15 years including the current year covering 81.3 %. Results and discussion The severity of injury and the accompanying inflammatory factors would characterize a rapid resolution or a more severe course of post-traumatic hemarthrosis during treatment. The combination of several variants of inflammation can lead to the development of complications including osteoarthritis in cases that show mechanisms of chronic systemic inflammation of low intensity being manifested at the time of injury; ankylosis of the joint resulting from chronic systemic inflammation of low intensity involving degenerative processes. Synovitis, as a complication of post-traumatic hemarthrosis, should be differentiated with signs of low-grade inflammation, chronic course of classical inflammation and presystemic inflammation (purulent arthritis) in view of the inflammation theory. Conclusion The analysis of modern literature has shown the complexity and versatility of aspects of inflammation in posttraumatic hemarthrosis. The lack of emphasis on the assessment of the inflammatory response in rehabilitation of patients with post‑traumatic hemarthrosis can result in complications causing preconditions for the development of osteoarthritis, ankylosis, synovitis.

Intra-articular administration of adrenaline plus an irrigation pump system for visibility during the arthroscopic reconstruction of multiple knee ligaments without a tourniquet.

Multiple ligament knee injuries (MLKIs) are rare but severe systemic trauma. Single surgery in the acute setting is preferred, although with an extended operation time. To avoid the complications associated with a tourniquet, we herein describe a method for visibility without a tourniquet: intra-articular administration of adrenaline plus an irrigation pump system. This is a cohort study with a level of evidence of 3. From April 2020 to February 2022, 19 patients with MLKIs were reviewed retrospectively. All patients got intra-articular administration of adrenaline plus an irrigation pump system for visibility without a tourniquet. The following parameters were assessed: visibility, range of motion, knee stability, visual analog scale (VAS) score, range of motion (ROM), Lysholm score, Tegner activity level, and International Knee Documentation Committee Subjective Knee Form (IKDC). All patients were followed up for at least 6 months. At the latest follow-up, the mean VAS score, ROM, Lysholm score, and IKDC were 1.79 ± 0.86, 121.21 ± 10.96, 88.16 ± 5.21, and 88.53 ± 5.06, respectively. The average Tegner activity level decreased significantly from preinjury to postoperation (5.16 ± 0.83 vs. 3.11 ± 0.88, P < 0.001). Of the 19 patients, 17 (89.47%) had good knee function, while only two patients (10.53%) had asymptomatic knees with positive Lachman tests. A total of 17 patients (89.47%) had good or excellent visualization during arthroscopy. Of the 19 patients, three (15.79%) required an increased fluid pressure to achieve a clear operative view. Two patients converted to tourniquet inflation due to persistent intra-articular bleeding after using shavers. The intra-articular administration of adrenaline plus an irrigation pump system is recommended as an alternative to a tourniquet to achieve a good visual field. Further evidence-based work with a larger sample is needed.

Assessment of vascular endothelial growth factor a serum level in pediatric hemophilic arthropathy

BackgroundChildren with hemophilia have serious, recurrent joint bleeding that causes disabilities. Regular factor VIII concentrate replacements have not yet completely stopped intra-articular subclinical hemorrhages and permanent joint damage. The prevention of joint damage requires the early detection and management of this hemorrhage. Neoangiogenesis is crucial in the development of synovitis after recurrent hemophilic joint bleeding. This study assessed the level of serum Vascular endothelial growth factor A (VEGF-A) as a vascular biomarker in children with hemophilia A to determine its possible role as a diagnostic biomarker for hemophilic arthropathy.ResultA case–control study with 30 male children who had hemophilia A and 30 healthy controls was conducted. Patients had significantly higher serum VEGF-A levels than the control group (specificity was 70.0% and sensitivity was 83.3%). Hemophilia severity and Hemophilia Joint Health Score had a significant positive correlation with VEGF-A.ConclusionChildren with hemophilia A had significantly higher levels of VEGF-A in their serum. Additionally, VEGF-A had a significant positive correlation with Hemophilia Joint Health Score as well as the severity of the disease. In children with hemophilia A, VEGF-A can be used as a marker for early hemophilic arthropathy detection.

Predictors of bleeding events in acute decompensated heart failure patients with antithrombotic therapy: AURORA study.

Heart failure (HF) is reported to be one of the major risks of bleeding events. On the other hand, HF patients frequently receive anticoagulants or antiplatelet therapy to manage various co-morbidities. However, predictors of bleeding events in patients with HF have rarely been reported. This study aimed to evaluate the predictors of bleeding events and relationship between bleeding events and HF re-hospitalizations. We included 1660 acute decompensated heart failure (ADHF) patients from the AURORA registry between January 2015 and December 2020. A total of 1429 patients were excluded because of history of HF admission, missing echocardiographic data at discharge, lost to follow-up, haemodialysis and no antithrombotic drugs. Finally, we evaluated 231 patients from AURORA registry. The bleeding events were defined as Type 2 to 5 bleeding according to the Bleeding Academic Research Consortium definition. We divided our patients into the bleeding group and non-bleeding group. We compared the baseline characteristics, medications, laboratory data, and echocardiographic data between the two groups. Median age was 78 (IQR 71-82) years old and male accounted for 59%. Approximately half of the patients had an antiplatelet therapy and 70% had an anticoagulant therapy. During a median follow-up of 651 (IQR 357-1139) days, 32 patients (13.8%) suffered from bleeding events. The major driver of the registered events was gastrointestinal bleeding (n=21, 65.6%), and the other events were cerebral bleeding (n=4, 12.5%), intraarticular bleeding (n=2, 6.3%), urogenital bleeding (n=2, 6.3%), haemorrhagic pericardial effusions (n=1, 3.1%), subcutaneous hematomas (n=1, 3.1%), and haemothorax (n=1, 3.1%). There was a significantly lower haemoglobin level (P<0.01), higher proportion of inferior vena cava (IVC) diameter ≥21mm (P<0.01), and higher furosemide equivalent doses per kilogram (P<0.01) in the bleeding group than non-bleeding group. A multivariate analysis revealed an equivalent dose of furosemide per kilogram ≥0.66mg/kg (hazard ratios (HR) of 2.64, 95% confidence interval (CI) 1.26-5.68, P=0.01), haemoglobin ≤10.3g/dL (HR of 2.43, 95% CI 1.14-5.03, P=0.02), and IVC diameter ≥21mm (HR of 2.79, 95% CI 1.16-6.29, P=0.02) were independently associated with bleeding events. The Kaplan-Meier analysis showed that HF re-hospitalization rates were higher in the bleeding group than non-bleeding group (P=0.04). High doses of oral loop diuretics, IVC dilatation, and anaemia were predictors of bleeding events in patients hospitalized with ADHF patients. In addition, bleeding events were associated with HF re-hospitalizations.

Precisión diagnóstica de la Ecografía frente a la Resonancia Magnética en la afectación articular hemofílica

Background and objectives: In hemophiliac patients, recurrent intra-articular bleeding leads to progressive arthropathy. Magnetic resonance imaging (MRI) is the gold-standard technique for joint assessment. The development of ultrasound protocols and standardized scales such as “Hemophilia Early Arthropathy Detection with Ultrasound” (HEAD-US) and “Point-of-care Ultrasonography” (POC-US) allow patient monitoring. Our main objective is to establish the diagnostic accuracy of ultrasound in the early detection of hemophilic arthropathy, with MRI as the gold standard. The interobserver variability in the ultrasound and MRI scales, the association between the POC-US and HEAD-US protocol, and the ability of ultrasound to detect haemosiderotic remnants will also be established. Patients and Methods: 45 hemophiliac patients were included. 180 joints (knees and ankles) were evaluated with MRI (Denver scale) and Ultrasound (HEAD-US and POC-US scale). Results: There is a high and statistically significant association between the ultrasound and MRI scales. Only for the ankle effusion variable the association was medium. The specificity of HEAD-US was ≥90% in both joints. Sensitivity in the knee did not exceed 82% in any assessed aspect, being high in the ankle for the cartilage and bone alterations (97%) but low for effusions (55%). In general, the predictive values ​​were high, with the exception of the negative predictive value of joint leak in knee and ankle (close to 70%). Ultrasound did not detect haemosiderotic remnants in any case. Statistically significant interobserver agreement was obtained for HEAD-US and Denver-MRI assessment. The level of association between the HEAD-US scale and the POC-US protocol was medium. Conclusions: Ultrasound is a technique with high diagnostic accuracy and reproducibility to detect and quantify the early signs of hemophilic arthropathy. Ultrasound is insensitive to detect haemosiderin in synovial hypertrophy.

Intraoperative complications in temporomandibular joint arthroscopy: A retrospective observational analysis of 899 arthroscopies

This study aims to describe intraoperative complications in temporomandibular joint arthroscopy in patients with Wilkes stage II, III y IV. An analytic observational retrospective study. Inclusion criteria were patients who had no improvement with conservative treatment diagnosed as Wilkes II stage to Wilkes stage IV, and no previous TMJ surgery. Exclusion criteria were disc perforation observed by arthroscopy. Data collected from 458 patients (899 arthroscopies). Of this population, 772 (85.8%) arthroscopies correspond to women, and 127 men (14.1%). Of the sample evaluated, 368 (40.9%) were arthroscopic without discopexy, and 531 (59%) were arthroscopic with discopexy using resorbable pins. In total, 330 complications (36.7%) were found, of which 293 (32.5%) were implicated with iatrogenic damage to the anatomy, and 36 (4%) were associated with some instrument failure. Of this total number of complications, 191 (51.9%) of 386 corresponded to the arthroscopy without discopexy group and 138 (25.9%) of 531 corresponded to the arthroscopy with discopexy group. These study data suggest that the main complications were irrigation fluid extravasation (p = 0.000), and intra-articular bleeding (p = 0.001) followed by pin problems (p = 0.001) in cases of arthroscopies with discopexy. Within the limitations of the study it seems that the learning curve has an important influence on the occurrence of complications. At the beginning of the learning curve, complications are more related to anatomy. Afterwards, the rate of complications decreases but they are more related to the instruments used in advanced techniques. Therefore, proper training and a wide learning curve can reduce the risk of complications and if any occur, more timely management could be given.