Mechanism Of Injury Research Articles

Increased index of microcirculatory resistance, capillary rarefaction, elevated troponin levels, and their association with transthyretin amyloidosis cardiomyopathy

Abstract Background The pathophysiology of coronary microvascular disease (CMD) in patients with transthyretin amyloidosis cardiomyopathy (ATTR-CM) remains unclear. Objective This study aims to functionally and pathologically assess coronary microvasculature to elucidate the underlying mechanisms of myocardial injury in patients with ATTR-CM. Methods Fifty patients (median age, 74 years; men, n=46, 92%) with echocardiographic evidence of left ventricular hypertrophy (≥12 mm) who underwent endomyocardial biopsy (EMB) and invasive coronary physiological assessments following coronary angiography were enrolled between October 2021 and September 2023 and divided into ATTR-CM (n=30) and non-cardiac amyloidosis (CA) (n=20) groups according to EMB results. All patients with ATTR-CM exhibited positive heart-to-contralateral (H/CL) ratios (>1.5) on technetium 99m pyrophosphate scintigraphy. Fractional flow reserve (FFR), coronary flow reserve (CFR), and index of microcirculatory resistance (IMR) were measured using the PressureWire X guidewire in the left anterior descending artery. Capillary density (/mm2) was determined with EMB tissues by counting the number of CD31 immunopositive luminal structures, whereas the amyloid deposition burden was assessed by measuring the transthyretin immunopositive areas. Circulating cardiac troponin T (hs-cTnT) and brain natriuretic peptide (BNP) were measured. Results Compared to the non-CA group, the ATTR-CM group exhibited lower CFR (2.4±0.3 vs. 3.6±0.4, p=0.01), higher IMR (35.4±3.0 vs. 18.7±3.7, p=0.0009), lower capillary density (255.3±24.9 /mm2 vs. 408.6±29.5 /mm2 , p=0.0002), and elevated hs-cTnT levels (0.056±0.006 ng/mL vs. 0.036±0.004 ng/mL, p=0.01), with similar FFR (0.87±0.015 vs. 0.84±0.013, p=0.1) and BNP levels (229.6±38.1 pg/mL vs. 210.2±46.7 pg/mL, p=0.75). In the overall and ATTR-CM groups, capillary density had no significant correlation with IMR (r=0.16, p=0.41 and r=0.04, p=0.84, respectively) and a significant inverse correlation with hs-cTnT (r=-0.47, p=0.001, and r=-0.48, p=0.009, respectively). In the ATTR-CM group, capillary density was not significantly correlated with the H/CL ratio (r=-0.23, p=0.09); nevertheless, transthyretin immunopositive areas were positively correlated with the H/CL ratio (r=0.47, p=0.01). Conclusion Capillary rarefaction correlates with elevated hs-cTnT levels but not with elevated IMR, and H/CL ratios, suggesting that CMD is involved at the capillary level in ATTR-CM-related myocardial injury independent of the amyloid deposition burden.

Preliminary findings of the TB-HEART Study: prevalence of cardiac pathology among newly diagnosed patients with tuberculosis with and without HIV in Zambia

Abstract Background Cardiovascular diseases (CVD) burden is rapidly increasing in sub-Saharan Africa (SSA) where tuberculosis and HIV prevalence remain high.(1-3) Recent data suggest pulmonary tuberculosis (PTB) is associated with increased CVD morbidity.(4) However, the mechanisms of cardiac injury remain poorly understood. Purpose The TB-HEART study is a cross-sectional and natural history study consecutively recruiting participants with newly-diagnosed PTB, living with and without HIV in Zambia. The primary outcome is the burden of cardiac pathology in PTB patients with and without HIV. Methods Participants with bacteriologically-proven PTB, consecutively recruited from an outpatient settings in Zambia, undergo detailed clinical and functional assessments including point-of-care and standard two-dimensional (2D) echocardiography. Participants are reviewed at completion of TB treatment when all assessments are repeated. The target sample size is 250 participants with PTB, with and without HIV, matched 2: 1 to participants without PTB, stratified by HIV. Results Since 1 November 2023, we have recruited 73 participants with a mean age of 35.3±10.9 years of whom 51/73 (69.9%) are male and 19/73 (23.5%) are living with HIV. Baseline characteristics including cardiovascular risk factors, TB symptoms, anthropometry and clinical and functional observations at presentation, stratified by HIV status, are summarised in Table 1. We detected significant cardiac pathology (defined as left ventricular ejection fraction (LVEF) <51% and/or pericardial effusion >2cm in depth) in 8/65 (12.3%) participants for whom 2D-echocardiography had been completed. Median LVEF was 61.2% (IQR 57.7-67.8). LVEF was normal in 59/65 (91%); mildly abnormal in 5/65 (7.7%); and moderately abnormal in 1/65 (1.5%) participants, respectively. Pericardial effusion >0.5cm was detected in 16/65 (24.6% ) participants and maximum effusion depth was >2cm in 2/16 (3.1%), 1-2cm in 12/16 (75%) and <1cm in 2/16 (12.5%). 2D-echocardiography findings, stratified by HIV-status, are described in Table 2 alongside two echocardiography stills of typical pericardial effusion findings in one participant. Conclusions Our preliminary results demonstrate a higher than expected prevalence of cardiac pathology among participants with PTB with and without HIV, which ranges from 1-7% in autopsy studies and case series.(5-7) The most common cardiac pathology was pericardial effusion. Further analyses will include cardiac biomarkers; repeat clinical and echocardiographic assessments at TB treatment completion; and comparator data, to determine associations between prevalent cardiac pathology and PTB controlling for HIV and TB status, respectively. This may have important implications for clinical practice to prevent complications such as constrictive pericarditis; and policy design to better integrate TB and HIV patient services with preventative care to reduce future CVD risk.Table 1 - Baseline characteristicsFigure 1 and Table 2

Unraveling Neurotoxicity Discrepancies: Comparative In vitro and In vivo Analysis of Colistin and Polymyxin B and the Underlying Mechanisms.

Polymyxins, including colistin and polymyxin B, are the final resort against Gram-negative bacterial infections. However, its clinical application is restricted due to concerns related to neurotoxicity. Despite the similar antibacterial spectrum and mode of action shared between colistin and polymyxin B, there is still a lack of definitive evidence to support the idea that their neurotoxicity profiles are identical. To comprehensively compare the neurotoxicity between colistin and polymyxin B both in vivo and in vitro and establish a theoretical foundation to guide the rational use of polymyxins within clinical settings. in vitro experiments simulated nerve damage by exposing N2a and RSC96 cells to colistin and polymyxin B. The evaluation of nerve injury included assessments of cell viability and apoptosis. To discern the variance in the mechanisms of nerve injury between colistin and polymyxin B, oxidative stress levels were examined, such as SOD, CAT, GSH, and malondialdehyde (MDA). In in vivo experiments, a rat nerve injury model was created by intraventricular injections of colistin and polymyxin B, respectively. The impact of these drugs on brain injury in rats, particularly within the hippocampus and medulla oblongata, was measured using HE and Nissl staining. The potential influence of polymyxins on the ferroptosis pathway was evaluated by assessing LPO and Fe2+ levels and the degree of mitochondrial impairment. At equivalent doses, colistin demonstrated a reduced level of neurotoxicity compared to polymyxin B, both in vitro and in vivo. in vitro experiments revealed greater cell viability and a lower apoptosis rate after colistin treatment than after polymyxin B treatment. This variance in outcomes could be attributed to the comparatively lower levels of oxidative stress associated with colistin administration.In a rat model, nerve injury resulted in observable damage to both the hippocampus and the medulla oblongata. A comprehensive assessment of the extent of damage in the CA1 to CA4 regions of the hippocampus, and the solitary tract nucleus of the medulla oblongata underscored that the neurotoxic effects of colistin remained milder compared to those elicited by polymyxin B. Even when evaluated at equivalent multiples of clinically recommended doses, colistin exhibited lower neurotoxicity in vivo than polymyxin B. For the first time, this study demonstrated the role of ferroptosis in polymyxin B-induced nerve damage. The activation levels observed within the ferroptosis pathway due to polymyxin B exceeded those triggered by colistin. Colistin exhibited a marked reduction in neurotoxicity compared to polymyxin B, evident in both the equivalent and clinically recommended doses. These findings suggest that, from the perspective of neurotoxicity, colistin presents a more favorable option for clinical use.

Role of sumoylation modification of sirtuin 3 in hypertension-associated

Abstract Objective The present study was designed to investigate whether mitochondrial dysfunction and oxidative stress in HTN-injured cardiomyocytes are associated with SIRT3 SUMOylation and whether SIRT3 deSUMOylation can ameliorate the related cardiomyocyte injury. Design and method The human cardiomyocyte AC16 cell line was used for the study. The SIRT3-K288R cell line was constructed by lentiviral transfection;The expression of SOD2, acetyl-SOD2 (MnSOD), protein acetylation level, inflammatory vesicle NLRP3, etc. in different subgroups were detected by Western Blot, and the roles of SUMOylation modification and SIRT3 deacetylation in HTN-associated cell injury were investigated by flow cytometry. Results (1) Western Blot results showed that compared to the HTN cell injury model, the cardiomyocytes in the SIRT3-K288R intervention group had increased Acetyl- SOD2/SOD2 levels were increased (p < 0.05) and protein acetylation levels were decreased in the SIRT3-K288R intervention group compared with the HTN cell injury model, indicating that SIRT3 increased the deacetylation effect on mitochondria and increased cellular antioxidant stress enzyme activity; (2) Western Blot results showed that compared with the HTN cell injury model, cardiomyocytes in the SIRT3-K288R intervention group NLRP3 and NOX4 levels were significantly reduced, indicating that SIRT3 deSUMOylation could improve the inflammatory response to Ang-II-related cell injury. (3) Flow cytometry results showed that K288R transfection ameliorated the reduction of cellular membrane potential, suggesting that deSUMOylation modification of SIRT3 reduces Ang-II damage to mitochondrial membrane potential. Conclusions In the HTN-associated cell injury model, the removal of SUMOylation modification by viral transfection could improve oxidative stress, protein acetylation levels and associated inflammatory responses in HTN-injured cardiomyocytes, indicating that SIRT3 SUMOylation may play an important mechanism in HTN-associated cell injury, and reducing SIRT3 SUMOylation modification may be a possible direction for future research.

The contribution of SLC7A11-mediated ferroptosis to cardiac injury in iron overload cardiomyopathy: an in vitro study

Abstract Background Recent studies have indicated that iron overload can induce myocardial ferroptosis in iron overload cardiomyopathy (IOC), but the specific mechanisms, including the role of SLC7A11, remain unclear. Purpose By delving into the role of SLC7A11-mediated ferroptosis in IOC, this research endeavors to provide novel insights and therapeutic strategies for understanding and treating IOC. Methods To induce an in vitro model of IOC, wild-type rat cardiomyocytes (H9C2) were cultured in a ferric citrate (FAC) medium. Cardiomyocytes were exposed to various concentrations of iron overload (ranging from 0 mM to 2 mM) for durations of 4, 8, 12, and 24 hours. Cell viability at different FAC concentrations was assessed by the cell counting kit-8 (CCK8) assay and the level of the ferroptosis indicator malondialdehyde (MDA) was measured to determine the optimal concentration and duration of FAC treatment which was required to establish the IOC cell model. Next, ferroptosis indicators, including MDA, prostaglandin peroxide synthase 2 (PTGS2), and glutathione peroxidase 4 (GPX4), and the pivotal factor, SLC7A11 of IOC cardiomyocytes were evaluated. The protein and mRNA levels of SLC7A11 were assessed by molecular biology techniques. Additionally, the mitochondrial morphology of the IOC cardiomyocytes was meticulously examined by transmission electron microscopy (TEM). Flow cytometry was employed for detecting reactive oxygen species (ROS) levels. Furthermore, we elucidated the underlying mechanism of myocardial injury in IOC by overexpressing SLC7A11 and subsequently detecting changes in ferroptosis markers. Results CCK-8 results showed that the viability of cardiomyocytes exhibited dose-dependently with increasing FAC concentration (R2=0.5483, p<0.0001). Furthermore, the viability of cardiomyocytes remained relatively stable, with survival rates of approximately 50% and not decreasing below 50%. Additionally, the MDA content in IOC cardiomyocytes increased dose-dependently with the elevation of FAC concentration (R2=0.75, p<0.05), with a significant increase observed at 0.75mM. Expression levels of ferroptosis marker genes, GPX4 and PTGS2, both at the mRNA and protein levels, are indicative of diminished antioxidant capacity. Meanwhile, the level of myocardial MDA and ROS were markedly elevated, indicating underscoring increased oxidative stress within the IOC cardiomyocytes. Moreover, there was a downregulation in the expression of SLC7A11 mRNA and protein in IOC cardiomyocytes, suggesting a potential compensatory mechanism to counteract oxidative damage. TEM further elucidated cardiac mitochondrial injuries in IOC rats, including focal vacuolization, swelling, crest disruption, and even disappearance. Overexpression of SLC7A11 resulted in a significant augmentation of GPX4 and a reduction of PTGS2mRNA and protein expression levels. Conclusions Ferroptosis, mediated by SLC7A11, may represent a pivotal mechanism underlying myocardial injury in IOC.

Risk factors affecting cervical spondylotic myelopathy complicated with traumatic central cord syndrome and the efficacy of different treatment options

ObjectiveTo analyze the influencing factors and treatment options of cervical spondylotic myelopathy (CSM) complicated with traumatic central cord syndrome (TCCS).MethodsA total of 243 patients with CSM admitted to our hospital from January 2021 to September 2022 were retrospectively analyzed, and then divided into the control group (n = 152) and the observation group (n = 91) according to the presence or absence of concurrent TCCS. The clinical data and imaging data of the two groups were compared, and multivariate logistic regression was used to analyze the influencing factors of CSM complicated with TCCS. Patients in the observation group were further divided into the zero notch anterior cervical interbody fusion device (Zero-P) group (n = 45) and the cervical spine locking plate (CSLP) group (n = 46) according to the treatment mode, and the perioperative indexes of the two groups were compared. The treatment effects were evaluated by the American Spinal Injury Association (ASIA) and the Japanese Orthopedic Association (JOA) before surgery, 1 week after surgery and 6 months after surgery. The height of intervertebral space and the cervical lordosis angle were measured.ResultsMultivariate logistic regression analysis showed that the injury mechanism (hyperextension injury), hand muscle weakness, cervical instability, age, degree of cervical spinal stenosis, degree of cervical spinal cord compression, and changes in intramedullary high signal were the risk factors, while the type of compression (soft), ASIA score and JOA score were the protective factor for CSM complicated with TCCS (P < 0.05). Patients in Zero-P group had much shorter operation time and hospitalization time than these in CSLP group (P < 0.05). The cervical lordosis angle and intervertebral space height at 1 week and 6 months after operation in the two groups were both largely higher than these before operation, and the cervical lordosis angle and intervertebral space height in the Zero-P group were significantly higher than these in the CSLP group one week after surgery (P < 0.05). The ASIA score and JOA score were obviously increased in the two groups 1 week and 6 months after surgery, and the ASIA score and JOA score in the Zero-P group were significantly higher than these in the CSLP group at 1 week after surgery (P < 0.05).ConclusionThe mechanism of TCCS in CSM is still controversial, which it is generally believed to be caused by cervical hyperextension injury. The clinical symptoms are diverse, and the treatment methods are also different. This study shows that the mechanism of injury, type of compression, hand muscle weakness, cervical instability, age, cervical stenosis compression, and intramedullary high signal changes are all risk factors for CSM complicated with TCCS. Early identification of risk factors and targeted interventions can effectively reduce the complicated rate of TCCS. Zero-P and CSLP surgical fixation have good efficacy in the treatment of TCCS, and there is little difference in efficacy between the two. However, Zero-P fixation surgery has the advantages of short operation time and fast postoperative recovery.

Study of clinical and functional outcome of malleoli fracture

Background: Ankle fractures are a common orthopedic injury, accounting for 9% of all fractures, with an increasing incidence among both young and elderly populations. These fractures often result from road traffic accidents, falls, and sports injuries. Malleolar fractures, involving the bony prominences of the ankle, are particularly prevalent and necessitate accurate reduction and stable internal fixation to prevent complications such as post-traumatic arthritis and restricted motion. This study aims to assess the functional outcomes and results of surgical treatment of malleolar fractures. Methods: The study utilized Lauge-Hansen’s classification to analyze the mechanism of injury in 32 patients with ankle fractures. Surgical techniques included the fixation of syndesmotic injuries with anatomical fibular plates, (AFP) posterior malleolus fractures with percutaneous screws or Ellis plates, and medial malleolus fractures with tension band wiring (TBW). The outcomes were measured in terms of union time, range of motion, and stability. Results: The most common injury mechanism was supination external rotation (SER) in 14 patients, followed by pronation external rotation (PER) in 7 patients, pronation abduction (PAB) in 6 patients, and supination adduction (SAD) in 5 patients. Syndesmotic injuries were found in 7 patients, all treated surgically except one. Posterior malleolus fractures were present in 3 patients and treated with screws or plates. Fixation of medial malleolus fractures with TBW showed better union rates and improved range of motion compared to screw fixation. Lateral malleolar fractures treated with AFP provided additional stability. The average union time was 6 to 8 weeks. Conclusions: Anatomical reduction and stable internal fixation are crucial for the successful treatment of malleolar fractures. TBW for medial malleolus fractures and AFP for lateral malleolar fractures provide favorable outcomes. However, a larger sample size and longer follow-up duration are required to further evaluate the outcomes of ankle injuries, particularly in older patients with osteoporosis and comorbidities.

Rare case of medial Hoffa fracture with ipsilateral femur shaft fracture with unusual mechanism of injury

Hoffa’s fracture is a rare fracture which involves coronal fracture of the distal femur involving one or both the condyles. We report a rare combination of Hoffa fracture with ipsilateral femur shaft fracture with an unusual mechanism of injury. This case report will help increase awareness about such combined fracture pattern and eventually avoid missing these important intra-articular injuries- Hoffa’s fracture. In a patient with ipsilateral femur shaft fracture and in polytrauma patients, diagnosis of Hoffa’s fracture is very challenging because of presence of other long bone fracture and injuries. Missed Hoffa’s fracture in a patient with ipsilateral femur shaft fracture may restrict post-operative knee range of motion, knee pain, increased risk of early arthritis and joint deformity and stiffness.

Determinants of symptom presentation and resolution following concussions in high school sports

ABSTRACT Sport-related concussions (SRCs) are prevalent in high school (HS) sports, though the determinants of, and relationships between concussion symptoms in this population remain relatively unknown. We analysed SRC data captured within the HS RIO injury surveillance system during 2014/15-2018/19. We used Generalized Estimating Equations to simultaneously assess covariate predictors of symptom presentations and identify pairwise symptom associations and employed multivariable ordinal logistic regressions to determine symptom resolution time (SRT) predictors. Among the 8,969 concussions assessed, headaches (94.3%) and dizziness (73.3%) were the most prevalently reported symptoms. In 5,953 boys’ concussion assessed, class year, event type and injury mechanism emerged as determinants of various concussion symptoms, while in 3,016 girls’ concussions assessed, class year, event type, injury mechanism, and sport type emerged as significant symptom determinants. In both groups, difficulty concentrating, sensitivity to light, sensitivity to noise, and disorientation were symptoms with the strongest associations with other symptoms. Odds of longer SRT were higher with greater endorsement (i.e. counts) of the subset of symptoms with strongest cross-domain associations (ORadj. = 1.35; 95% CI = [1.30, 1.40]). Our findings provide valuable information for informing sideline and follow-up clinical concussion assessment algorithms in high school athletes.

Soft Tissue Glenohumeral Internal Rotation Deficit Revealed Detailed Musculoskeletal Factors of Baseball Players.

Weng, Y-H, Huang, T-S, Chang, C-Y, Yang, J-L, Chen, W-S, and Lin, J-J. Soft tissue glenohumeral internal rotation deficit revealed detailed musculoskeletal factors of baseball players. J Strength Cond Res XX(X): 000-000, 2024-Glenohumeral internal rotation deficit (GIRD) remains contentious regarding its role in shoulder injuries. Soft tissue GIRD (ST-GIRD), reflecting soft tissue changes, may offer a more precise understanding of the injury mechanism. This study investigates correlations between ST-GIRD, self-perceived function/performance, and musculoskeletal factors in baseball players, comparing them with traditional GIRD measurements. Subjects completed the Kerlan-Jobe Orthopedic Clinic self-report questionnaire for function and performance. Soft tissue GIRD, adjusted for humeral retrotorsion, was calculated. Eighty baseball players from various levels were recruited. Kerlan-Jobe Orthopedic Clinic scores significantly correlated with ST-GIRD (r = 0.307, p = 0.046) but not with GIRD (r = 0.164, p = 0.161). Soft tissue GIRD significantly correlated with scapula root of spine alignment (r = -0.303, p = 0.023) but not with GIRD (r = -0.069, p = 0.614). Higher correlation coefficients were found between acromiohumeral distance and posterior capsule thickness with ST-GIRD (r = -0.241 and 0.236, respectively) than with GIRD (r = 0.183 and 0.122, respectively). Soft tissue GIRD offers more detailed musculoskeletal insights than GIRD, showing improved correlations with function/performance, scapular alignment, acromiohumeral distance, and posterior capsule thickness. This supports the notion that internal rotation deficiency is associated with increased posterior capsule thickness and decreased acromiohumeral distance. These results provide coaches and health care practitioners a more detailed way to monitor function and performance of baseball players.

Deoxynivalenol-mediated kidney injury via endoplasmic reticulum stress in mice

ObjectiveDeoxynivalenol (DON) is a common fungal toxin that poses significant health risks to humans and animals. The present study aimed to investigate the adverse effects and molecular mechanisms of DON-induced kidney injury. MethodsMale C57BL/6 mice aged 5–6 weeks were used to establish a DON-induced acute kidney injury model. Histological analysis, biochemical assays, molecular techniques, Western blot, RNA sequencing, and transmission electron microscopy were employed to analyze kidney damage, inflammation, oxidative stress, apoptosis, and endoplasmic reticulum (ER) stress. ResultsDON disrupted kidney morphology, induced inflammatory cell infiltration, and triggered inflammatory responses. DON increased MDA content while decreasing antioxidant enzyme activity (SOD and CAT). It also triggered apoptosis, evidenced by elevated levels of caspase-12, cleaved caspase-3, and BAX, and reduced levels of Bcl-2. Transcriptomic analysis identified distinct expression patterns in 1756 genes in DON-exposed mouse kidneys, notably upregulating ER stress-related genes. Further investigation revealed ultrastructural changes in the ER and mitochondrial damage induced by DON, along with increased levels of p-IRE1, p-PERK, and their downstream targets, indicating unfolded protein response (UPR) activation in the kidney. The ER stress inhibitor 4-Phenylbutyric acid (4-PBA) significantly mitigated DON-induced ER stress, oxidative damage, apoptosis, tissue injury, ER expansion, and mitochondrial damage. ConclusionOur findings highlight the role of ER stress in DON-induced kidney injury and the protective effect of 4-PBA against these adverse effects.

Paediatric e-scooter riders at high risk of life-threatening traffic accidents.

This study presents the epidemiology and the development of e-scooter and non-electric scooter injuries in children and adolescents to highlight the nature and the severity of such injuries. All children and adolescents with electric or non-electric scooter related injuries between January 2019 until December 2022 were included in this single-centre study and retrospectively evaluated. An epidemiological overview including age, sex, type of scooter, injury mechanism, diagnosed injuries and surgical interventions were presented. Further, statistical comparisons of the means and proportions of injuries and the number of surgical interventions between electric and non-electric scooter riders were made. The study consists of 633 children and adolescents (9.1 ± 5.0 years; 231 female, 36.5%, 402 male, 63.5%). 80.1% (8.0 ± 4.1 years) used non-electric scooters, while 19.9% (14.2 ± 4.1 years) used e-scooters. In comparison, adolescent e-scooter riders were significantly more likely to be involved in traffic accidents (non-electric scooter: 16/507; e-scooter: 21/126; p = 0.0001) and suffered severe head injuries more often (non-electric scooter: 8/134; e-scooter: 7/37; p = 0.0217) than patients riding non-electric scooters. Adolescent e-scooter riders were more likely to be involved in potentially life-threatening traffic accidents having a higher risk of severe head injuries requiring surgery compared to non-electric scooter riders. Adolescent e-scooter riders have a higher risk to be involved in potentially life-threatening traffic accidents than riders of non-electric scooters. E-scooter riders have a higher risk of sustaining serious head injuries requiring surgical intervention than non-electric scooter riders. The data highly recommends the implementation of prevention strategies especially educating youth and parents and wearing protective clothing. Legislation and law enforcement could help prevent such injuries and potentially life-threatening traffic accidents involving children and adolescents who ride e-scooters.

3D-printed model is a useful addition in orthopedic resident education for the understanding of tibial plateau fractures

This study aimed to explore the role of the three-dimension (3D) printed models in orthopedic resident training of tibial plateau fractures. A total of 41 residents from our institution were divided into two groups. The intervention group, consisting of 20 residents, had access to 3D-printed models illustrating thirteen tibial plateau fractures. In contrast, the control group, comprising 21 residents, received digital images of thirteen identical tibial plateau fractures. Evaluation of learning outcomes included the accurate identification of tibial plateau fracture patterns, deduction of traumatic mechanisms, preoperative plan, assessment time, and subjective questionnaire responses. The participants with 3D printed models scored significantly higher in both the Schatzker classification and Luo three-column classification compared to those without 3D printed models. Residents in the intervention group performed better in accuracy in deducing traumatic mechanisms compared to the control group. In addition, the sum score of preoperative plan in the intervention group was significantly higher than that in the control group. Specifically, participants with 3D printed models scored higher in surgical approach choice and implants placement than these in the control group. Residents exposed to 3D printed models also spent less time to complete the assessment than those with access only to digital imaging. Subjective assessments indicated that 3D-printed models boosted confidence in fracture identification, improved preoperative plan for fracture management and enhanced the understanding in injury mechanism of tibial plateau fractures. Furthermore, residents agreed that the use of 3D-printed models heightened their interest in learning tibial plateau fractures. Therefore, the addition of 3D printed models significantly contributed to a comprehensive understanding of tibial plateau fractures, the improvement in fracture identification, inferring injury mechanisms and preoperative plan.

Effects of WN1703 on Cardiovascular Function in Chronic Hyperuricemia Rats and Myocardial Injury Mechanism Exploration in H9C2 Cells.

Hyperuricemia, a prevalent condition, is typically preceded by disturbances in purine metabolism and is frequently associated with hyperlipidemia and other dysfunctions of metabolism. WN1703 demonstrated an inhibitory activity against xanthine oxidoreductase (XOR) that was comparable to febuxostat in our prior investigation. In this study, we assessed the cardiovascular safety of WN1703 in a chronic hyperuricemia rat model induced by potassium oxonate in combination with hypoxanthine. We investigated the changes in cardiovascular biomarkers in chronic hyperuricemia rats treated with febuxostat and WN1703, including creatine kinase (CK), CK-MB, B type natriuretic peptide (BNP), Corin protein (CRN), Neprilysin (NEP), myeloperoxidase (MPO), 8-hydroxy-2-deoxyguanosine (8-OHdG), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), and interleukin-8 (IL-8). Additionally, we validated the potential mechanism of cardiac injury induced by WN1703 in H9C2 cells, guided by cardiotoxicity predictions from the cardioToxCSM database and network pharmacology. We observed that excessively rapid urate-lowering, oxidative stress, and inflammation could disrupt myocardial functional homeostasis and increase the risk of cardiovascular injury in hyperuricemia rats, and WN1703 treatment effectively reduced the levels oxidative stress marker 8-OHdG and inflammatory factor TNF-α. Despite the absence of organic damage to the heart with prolonged treatment of febuxostat and WN1703, potential hazard of cardiovascular injury could be associated with the modulation of the TGFβ and RHO/ROCK signaling pathways by febuxostat and WN1703. This could offer new insights into the mechanisms underlying the adverse effects caused by XOR inhibitors.

Multilevel analysis of the central-peripheral-target organ pathway: contributing to recovery after peripheral nerve injury.

Peripheral nerve injury is a common neurological condition that often leads to severe functional limitations and disabilities. Research on the pathogenesis of peripheral nerve injury has focused on pathological changes at individual injury sites, neglecting multilevel pathological analysis of the overall nervous system and target organs. This has led to restrictions on current therapeutic approaches. In this paper, we first summarize the potential mechanisms of peripheral nerve injury from a holistic perspective, covering the central nervous system, peripheral nervous system, and target organs. After peripheral nerve injury, the cortical plasticity of the brain is altered due to damage to and regeneration of peripheral nerves; changes such as neuronal apoptosis and axonal demyelination occur in the spinal cord. The nerve will undergo axonal regeneration, activation of Schwann cells, inflammatory response, and vascular system regeneration at the injury site. Corresponding damage to target organs can occur, including skeletal muscle atrophy and sensory receptor disruption. We then provide a brief review of the research advances in therapeutic approaches to peripheral nerve injury. The main current treatments are conducted passively and include physical factor rehabilitation, pharmacological treatments, cell-based therapies, and physical exercise. However, most treatments only partially address the problem and cannot complete the systematic recovery of the entire central nervous system-peripheral nervous system-target organ pathway. Therefore, we should further explore multilevel treatment options that produce effective, long-lasting results, perhaps requiring a combination of passive (traditional) and active (novel) treatment methods to stimulate rehabilitation at the central-peripheral-target organ levels to achieve better functional recovery.

Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor.

This study examined the role of endoplasmic reticulum stress in pediatric acute kidney injury and the therapeutic effect of midbrain astrocyte-derived neurotrophic factor. Two-week-old Sprague-Dawley rats were divided into: Sham, ischemia-reperfusion injury-induced acute kidney injury (AKI), mesencephalic astrocyte-derived neurotrophic factor (MANF)-treated, tauroursodeoxycholic acid (TUDCA)-treated. Analyses were conducted 24h post-treatment. Serum creatinine, cystatin C, Albumin, MANF levels were measured, cytokine concentrations in serum and renal tissues were determined using a Luminex assay. Histopathology was assessed via light and electron microscopy. Western blotting and RT-qPCR analyzed markers for oxidative stress, apoptosis, endoplasmic reticulum (ER) stress, and autophagy. HK-2 cells underwent hypoxia/reoxygenation (H/R) to simulate AKI and were treated with MANF or TUDCA. AKI rats had increased serum creatinine, cystatin C, and inflammatory cytokines, along with significant renal damage, and showed loose and swollen ER structures, reduced cell proliferation, and elevated levels of IRE1, PERK, ATF6, CHOP, LC3-II/I, KIM-1, TLR4, JNK, and NF-κB. MANF treatment reduced these biomarkers and protein levels, improved ER structure and cell proliferation, alleviated oxidative stress, apoptosis, ER stress, and inhibited JNK/TLR4/NF-κB signaling. In HK-2 cells, MANF reduced ER stress and inflammation post-H/R exposure. MANF treatment alleviates ER stress, oxidative stress, apoptosis, and inflammation in pediatric AKI, improving renal function and morphology.

Palmar Displacement in Distal Radius Fractures following Extension Injuries of the Wrist

Fractures of the distal radius have been traditionally classified based on the suspected mechanism of injury. Among clinicians, the terms "Colles" and "Smith" fractures are commonly used to refer to a distal radius fracture that is either displaced to the dorsal (Colles) or palmar (Smith) side of the radius. When analysing x-rays, it is not uncommon for a Smith fracture to be detected in cases where patients describe a fall on the wrist in an extended position. Thus, the question arises how a flexion-type fracture can occur after an extension injury. So far, only little research has been conducted into this subject. The aim of this study was to analyse the mechanisms of injury that lead to various types of distal radius fractures. Particular emphasis was placed on "Smith" fractures and on the biomechanical, physiological and anatomical characteristics that contribute to their occurrence. To assess these relationships, data of fractures were collected following a life-like fracture simulation using a "drop-bench" in non-formalin fixated human specimens. These fractures were produced between January 2016 and December 2021. Biographic data of all specimens used were available. Additionally, all biomechanical and physical characteristics of the fracture simulation were fully documented. Of the 122 specimens with a full data set, 17 (13.9%) fractures were determined to be Smith fractures based on their radiological appearance. In 10 of these flexion fractures, the wrist was set in dorsal extension. The mean angle of extension was 86.3 degrees for flexion fractures compared to 90.5 degrees for extension fractures. Six out of 10 Smith-type fractures that were set in dorsal extension were also exposed to pronation, whereas only one was exposed to supination. The mean potential energy for fracture creation was 168.0 joules for Smith fractures in dorsal extension, whereas all other fractures showed a mean of 185.2 joules. It can be concluded that a Smith fracture is not limited to being the result of a fall on the wrist in a flexed position. The same fracture may also be the result of a fall with the wrist in an extended position if certain physical factors are applicable.

Decoding the multiple functions of ZBP1 in the mechanism of sepsis-induced acute lung injury.

Sepsis-induced acute lung injury (ALI), characterized by severe hypoxemia and pulmonary leakage, remains a leading cause of mortality in intensive care units. The exacerbation of ALI during sepsis is largely attributed to uncontrolled inflammatory responses and endothelial dysfunction. Emerging evidence suggests an important role of Z-DNA binding protein 1 (ZBP1) as a sensor in innate immune to drive inflammatory signaling and cell death during infections. However, the role of ZBP1 in sepsis-induced ALI has yet to be defined. We utilized ZBP1 knockout mice and combined single-cell RNA sequencing with experimental validation to investigate ZBP1's roles in the regulation of macrophages and lung endothelial cells during sepsis. We demonstrate that in sepsis, ZBP1 deficiency in macrophages reduces mitochondrial damage and inhibits glycolysis, thereby altering the metabolic status of macrophages. Consequently, this metabolic shift leads to a reduction in the differentiation of macrophages into pro-inflammatory states and decreases macrophage pyroptosis triggered by activation of the NLRP3 inflammasome. These changes significantly weaken the inflammatory signaling pathways between macrophages and endothelial cells and alleviate endothelial dysfunction and cellular damage. These findings reveal important roles for ZBP1 in mediating multiple pathological processes involved in sepsis-induced ALI by modulating the functional states of macrophages and endothelial cells, thereby highlighting its potential as a promising therapeutic target.

Identifying Child Abuse in Patients With Femur Fractures Through Pathway Compliance: A Pilot Study.

Background Child abuse is a significant cause of morbidity and mortality in children. A thorough history and physical exam is critical to identifying abuse. Standardized screening tools as well as clinical pathways can assist with identifying patients who may have an injury secondary to abuse. There are varied recommendations for the upper age in which to routinely evaluate pediatric patients for child abuse. Objectives The primary objective of this study was to describe the outcomes of the implementation of an evidence-based clinical pathway for suspected non-accidental trauma for all pediatric patients aged five years and under presenting with a femur fracture. This pathway includes orders for imaging, labs, and consults. In addition, the characteristics of this population and the findings were described. Methods A retrospective study of patients at a single institution who met the National Trauma Data Standard registry inclusion criteria and had a femur fracture was performed. Variables analyzed included age, demographics, mechanism and location of injury, admission status and service, injury severity, hospital characteristics, and discharge status. Patients with a metabolic bone disease were excluded. Results There were 200 patients who met the inclusion criteria. Thirty-two patients had a diagnosis of confirmed or suspected child abuse. While all 32 patients had a skeletal survey performed, only 23 (71.9%) had the complete workup per the clinical pathway, and 21 (65.6%) had a diagnosis of confirmed child abuse. Conclusion Clinical pathways are established to provide the standardization of clinical assessments and interventions; however, this process relies on a single individual to make a judgment determining whether or not to implement the pathway. Children presenting to an emergency department with confirmed or suspected child abuse are a vulnerable population. A child abuse diagnosis is a clinical judgment; however, clinical pathways aid in the diagnosis in hopes to stop any further abuse. For a pathway to be successful, each step needs to be addressed.

Exploration of the clinical characteristics and potential mechanisms of liver injury induced by proton pump inhibitors

ABSTRACT Background and aims Data related to clinical characteristics and potential mechanisms of proton pump inhibitors (PPIs)-related liver injury are sparse, thus the purpose of this study is to summarize the clinical features and molecular mechanisms of PPIs-induced liver injury. Methods We collected case report on liver injury induced by PPIs in English and Chinese for retrospective analysis. Clinical and pathological data and outcomes were obtained and analyzed. Network pharmacology and molecular docking techniques were employed to examine the mechanism. Result Twenty-three patients with PPIs-induced liver injury were enrolled. PPIs-induced liver injury is a rare adverse reaction, ranging from asymptomatic elevated transaminases to fulminant liver failure. Omeprazole was the drug with the highest number of associated reports. The most common symptom was fatigue. The most common liver injury pattern was hepatocellular injury. A total of 13 intersection targets of PPIs and liver injury were screened, and the top 10 targets were included, and the PI3K-Akt signaling pathway was significantly enriched. The results of molecular docking implied that the PPIs could combine well with key targets. Conclusion Patients receiving long-term treatment with PPIs should consider monitoring liver function. PPIs exhibit considerable capacity in liver injury via especially the PI3K-Akt signaling pathway.