Volume 27 · Issue 03 · 2024

Adenosine exerts its dual functions of homeostasis and neuromodulation in the brain by acting at mainly 2 G-protein coupled receptors, called A₁ and A_2A receptors. The adenosine A_2A receptor (A_2AR) antagonists have been clinically pursued for the last 2 decades, leading to final approval of the istradefylline, an A_2AR antagonist, for the treatment of OFF-Parkinson's disease (PD) patients. The approval paves the way to develop novel therapeutic methods for A_2AR antagonists to address 2 major unmet medical needs in PD and traumatic brain injury (TBI), namely neuroprotection or improving cognition. In this review, we first consider the evidence for aberrantly increased adenosine signaling in PD and TBI and the sufficiency of the increased A_2AR signaling to trigger neurotoxicity and cognitive impairment. We further discuss the increasing preclinical data on the reversal of cognitive deficits in PD and TBI by A_2AR antagonists through control of degenerative proteins and synaptotoxicity, and on protection against TBI and PD pathologies by A_2AR antagonists through control of neuroinflammation. Moreover, we provide the supporting evidence from multiple human prospective epidemiological studies which revealed an inverse relation between the consumption of caffeine and the risk of developing PD and cognitive decline in aging population and Alzheimer's disease patients. Collectively, the convergence of clinical, epidemiological and experimental evidence supports the validity of A_2AR as a new therapeutic target and facilitates the design of A_2AR antagonists in clinical trials for disease-modifying and cognitive benefit in PD and TBI patients.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

Tibial stress fracture associated with knee osteoarthritis is an unusual and difficult clinical scenario. There is no clear existing treatment guideline for this uncommon clinical disease. The aim of this study is to review the impact of various treatment options for patients with advanced knee osteoarthritis associated with proximal tibial stress fracture.

The study was performed using the databases of PubMed and Scopus. Methodological index for non-randomized studies score was used to evaluate the included studies’ bias. The concluded data included the treatment approach, reported outcome measure, and time to fracture union. The literature search was started in December 2021 and accomplished in January 2022. A narrative description of the different methods and comparison of their results were done.

Out of total assessed 69 studies, 9 studies were included in our review. The commonest treatment approach used was total knee arthroplasty by long tibial stem extension. The mean preoperative knee society score and knee functional score were 30.62 and 23.17, respectively. The mean postoperative knee society knee score was 86.87, while the functional score was 83.52. The average reported time to achieve fracture union was 4 months (a range of 2.07 - 5.50 months).

The optimal clinical outcome for treating either acute or mobile tibial stress fracture in patients with advanced knee osteoarthritis can be achieved with long stem total knee arthroplasty. However, due to heterogeneity of data, comparison of different treatment options for chronic proximal tibial stress fracture mal-union/non-union coexisting with knee osteoarthritic and such inferences need to be judged cautiously.

Cerebral edema (CE) is the main secondary injury following traumatic brain injury (TBI) caused by road traffic accidents (RTAs). It is challenging to be predicted timely. In this study, we aimed to develop a prediction model for CE by identifying its risk factors and comparing the timing of edema occurrence in TBI patients with varying levels of injuries.

This case-control study included 218 patients with TBI caused by RTAs. The cohort was divided into CE and non-CE groups, according to CT results within 7 days. Demographic data, imaging data, and clinical data were collected and analyzed. Quantitative variables that follow normal distribution were presented as mean ± standard deviation, those that do not follow normal distribution were presented as median (Q₁, Q₃). Categorical variables were expressed as percentages. The Chi-square test and logistic regression analysis were used to identify risk factors for CE. Logistic curve fitting was performed to predict the time to secondary CE in TBI patients with different levels of injuries. The efficacy of the model was evaluated using the receiver operator characteristic curve.

According to the study, almost half (47.3%) of the patients were found to have CE. The risk factors associated with CE were bilateral frontal lobe contusion, unilateral frontal lobe contusion, cerebral contusion, subarachnoid hemorrhage, and abbreviated injury scale (AIS). The odds ratio values for these factors were 7.27 (95% confidence interval (CI): 2.08 -25.42, p = 0.002), 2.85 (95% CI: 1.11 -7.31, p = 0.030), 2.62 (95% CI: 1.12 -6.13, p = 0.027), 2.44 (95% CI: 1.25 -4.76, p = 0.009), and 1.5 (95% CI: 1.10 -2.04, p = 0.009), respectively. We also observed that patients with mild/moderate TBI (AIS ≤ 3) had a 50% probability of developing CE 19.7 h after injury (χ²= 13.82, adjusted R² = 0.51), while patients with severe TBI (AIS > 3) developed CE after 12.5 h (χ²= 18.48, adjusted R² = 0.54). Finally, we conducted a receiver operator characteristic curve analysis of CE time, which showed an area under the curve of 0.744 and 0.672 for severe and mild/moderate TBI, respectively.

Our study found that the onset of CE in individuals with TBI resulting from RTAs was correlated with the severity of the injury. Specifically, those with more severe injuries experienced an earlier onset of CE. These findings suggest that there is a critical time window for clinical intervention in cases of CE secondary to TBI.

To study the clinical effectiveness of the topical application of tranexamic acid in hand tendon release.

This was a randomized controlled trial conducted after receiving approval from the local ethics committee according to guidelines from the Helsinki Declaration. Eighty patients who underwent hand tendon release operation in our hospital from January 2021 to December 2022 were included and randomly divided into 2 groups. Patients in the tranexamic acid group (40 cases) received intraoperative topical application of 2 g of tranexamic acid after tendon release, while patients in the conventional group (40 cases) did not receive topical application of tranexamic acid during operation. The operation time, perioperative hemoglobin changes, total blood loss, incidence of early postoperative complications, and total active movement (TAM) before surgery and 6 months after surgery were compared between the 2 groups. The continuous variable which follows normal distribution expressed by mean ± SD and used t-test to compare between groups. Meanwhile, categorical variables were used by Chi-square test, and a p< 0.05 indicated that the differences were statistically significant.

Both groups were followed up for 7 - 18 months, with a mean of 10.3 months. Postoperative decrease in hemoglobin was significantly less in the tranexamic acid group than in the conventional group (t= 7.611, p< 0.001). The total blood loss in the tranexamic acid group (74.33 ± 20.50) mL was less than that in the conventional group (83.05 ± 17.73) mL, and the difference was statistically significant (p< 0.05). Both groups showed improvement in thumb/finger flexion and extension range of motion after surgery, and the TAM improved compared with those before surgery, and the difference was statistically significant (p< 0.001). The TAM improved more significantly in the tranexamic acid group (87.68^° ± 10.44^°) than in the conventional group (80.47^° ± 10.93^°) at 6 months after surgery, with a statistically significant difference (t= 3.013, p< 0.001). There was no significant difference in operation time and incidence of early postoperative complications between the 2 groups (p= 0.798, 0.499, respectively).

The topical application of tranexamic acid during hand tendon release can significantly reduce postoperative bleeding and improve surgical efficacy, which is worth promoting.

To identify the risk factors for training-related lower extremity muscle injuries in young males by a non-invasive method of body composition analysis.

A total of 282 healthy young male volunteers aged 18 -20 years participated in this cohort study. Injury location, degree, and injury rate were adjusted by a questionnaire based on the overuse injury assessment methods used in epidemiological studies of sports injuries. The occurrence of training injuries is monitored and diagnosed by physicians and treated accordingly. The body composition was measured using the BodyStat QuadScan 4000 multifrequency Bio-impedance system at 5, 50, 100 and 200 kHz to obtain 4 impedance values. The Shapiro-Wilk test was used to check whether the data conformed to a normal distribution. Data of normal distribution were shown as mean ± SD and analyzed by t-test, while those of non-normal distribution were shown as median (Q₁, Q₃) and analyzed by Wilcoxon rank sum test. The receiver operator characteristic curve and logistic regression analysis were performed to investigate risk factors for developing training-related lower extremity injuries and accuracy.

Among the 282 subjects, 78 (27.7%) developed training injuries. Lower extremity training injuries revealed the highest incidence, accounting for 23.4% (66 cases). These patients showed higher percentages of lean body mass (p = 0.001), total body water (TBW, p=0.006), extracellular water (p=0.020) and intracellular water (p=0.010) as well as a larger ratio of basal metabolic rate/total weight (p=0.006), compared with those without lower extremity muscle injuries. On the contrary, the percentage of body fat (p=0.001) and body fat mass index (p=0.002) were lower. Logistic regression analysis showed that TBW percentage > 65.35% (p=0.050, odds ratio =3.114) and 3rd space water > 0.95% (p=0.045, odds ratio =2.342) were independent risk factors for lower extremity muscle injuries.

TBW percentage and 3rd space water measured with bio-impedance method are potential risk factors for predicting the incidence of lower extremity muscle injuries in young males following training.

The purpose of the National Spinal Cord Injury Registry of Iran (NSCIR-IR) is to create an infrastructure to assess the quality of care for spine trauma and in this study, we aim to investigate whether the NSCIR-IR successfully provides necessary post-discharge follow-up data for these patients.

An observational prospective study was conducted from April 11, 2021 to April 22, 2022 in 8 centers enrolled in NSCIR-IR, respectively Arak, Rasht, Urmia, Shahroud, Yazd, Kashan, Tabriz, and Tehran. Patients were classified into 3 groups based on their need for care resources, respectively: (1) non-spinal cord injury (SCI) patients without surgery (group 1), (2) non-SCI patients with surgery (group 2), and (3) SCI patients (group 3). The assessment tool was a self-designed questionnaire to evaluate the care quality in 3 phases: pre-hospital, in-hospital, and post-hospital. The data from the first 2 phases were collected through the registry. The post-hospital data were collected by conducting follow-up assessments. Telephone follow-ups were conducted for groups 1 and 2 (non-SCI patients), while group 3 (SCI patients) had a face-to-face visit. This study took place during the COVID-19 pandemic. Data on age and time interval from injury to follow-up were expressed as mean ± standard deviation (SD) and response rate and follow-up loss as a percentage.

Altogether 1538 telephone follow-up records related to 1292 patients were registered in the NSCIR-IR. Of the total calls, 918 (71.05%) were related to successful follow-ups, but 38 cases died and thus were excluded from data analysis. In the end, post-hospital data from 880 patients alive were gathered. The success rate of follow-ups by telephone for groups 1 and 2 was 73.38% and 67.05% respectively, compared to 66.67% by face-to-face visits for group 3, which was very hard during the COVID-19 pandemic. The data completion rate after discharge ranged from 48% - 100%, 22% - 100% and 29% - 100% for groups 1 - 3.

To improve patient accessibility, NSCIR-IR should take measures during data gathering to increase the accuracy of registered contact information. Regarding the loss to follow-ups of SCI patients, NSCIR-IR should find strategies for remote assessment or motivate them to participate in follow-ups through, for example, providing transportation facilities or financial support.

Irreducible anteromedial radial head dislocation (IARHD) caused by transposed biceps tendon is rare. Delayed diagnosis and surgical failure often occur. A 46-year-old fisherman presented with 10 days history of painful swelling and restricted movement of his right elbow due to strangulation injury by a fishing boat cable. On examination, the images of the right elbow reveals in a "semi-extended and pronated" elastic fixation position. Radiography and 3-dimensional reconstruction CT reveals an isolated anteromedial radial head dislocation with extreme protonation of the radius and the bicipital tuberosity towards the posterior aspect of the elbow joint, and MRI shows biceps tendon wrapping around the radial neck, similar to umbilical cord wrapping seen in newborns. The Henry approach was applied for the first time to reduce the biceps tendon. The patient achieved a good functional recovery at 26 months, which represents the first reported case of IARHD without fracture caused by biceps tendon in an adult. In treatment of IARHD, attention should be paid to the phenomenon of biceps tendon transposition. Careful clinical examination, comprehensive imaging modalities, and appropriate surgical approach are the keys to successful management.