Repair Of Injury Research Articles

National analysis of outcomes in timing of cholecystectomy for acute cholangitis

BackgroundThe present study aimed to compare outcomes between cholecystectomy on index versus delayed admission for acute cholangitis. MethodsThe 2011–2020 Nationwide Readmissions Database was used to identify adult patients admitted for acute cholangitis who underwent cholecystectomy. Study cohorts were defined based on timing of surgery. Multivariable regressions and Royston-Parmar time-adjusted analysis were used to evaluate the association of cholecystectomy timing and outcomes. ResultsOf 65,753 patients, 82.0 ​% received surgery on Index and 18.0 ​% on Delayed admissions. Following adjustment, Delayed operation was associated with significantly increased odds of mortality (AOR 1.67 [95 ​% CI 1.10–2.54]), complications (1.25 [1.13–1.40]), repair of bile duct injury (1.66 [1.15–2.41]), conversion to open (1.69 [1.48–1.93]), and 30-day readmission (3.52 [3.21–3.86]). The Delayed cohort experienced a +$14,200 increment in hospitalization costs relative to Index. ConclusionsDelayed cholecystectomy for acute cholangitis is significantly associated with adverse postoperative outcomes, suggesting that index cholecystectomy may be safe to perform.

Arthroscopic assisted foveal repair of triangular fibrocartilage complex injuries associated with distal radioulnar joint instability

Introduction Foveal tears of tfcc are common causes of ulnar sided wrist pain. They are usually associted with druj instability. Reattachment using either arthroscopic or open techniques is considered the best treatment in acute settings. This is a retrospective study to evaluate clinical and functional results of arthroscopic assisted technique. Patients and methods 20 patients were enrolled in the study. 13 males and 7 females. Mean age was 26 years. Technique involved arthroscopic reattachment of the tfcc to its foveal foot print using direct foveal portal as described by Atzei et al. Results The mean follow-up period was 14 months ranging from 8 to 20 months No pain was recorded in 13 patients, mild pain in 4 patients, and moderate pain in 3 patients. The mean VAS score was 3.2. The mean Mayo score was 70%. Conclusion Arthroscopic assisted technique using direct foveal portal is a valuable technique with good reproducible results.

BDNF-loaded chitosan-based mimetic mussel polymer conduits for repair of peripheral nerve injury.

Care for patients with peripheral nerve injury is multifaceted, as traditional methods are not devoid of limitations. Although the utilization of neural conduits shows promise as a therapeutic modality for peripheral nerve injury, its efficacy as a standalone intervention is limited. Hence, there is a pressing need to investigate a composite multifunctional neural conduit as an alternative treatment for peripheral nerve injury. In this study, a BDNF-loaded chitosan-based mimetic mussel polymer conduit was prepared. Its unique adhesion characteristics allow it to be suture-free, improve the microenvironment of the injury site, and have good antibacterial properties. Researchers utilized a rat sciatic nerve injury model to evaluate the progression of nerve regeneration at the 12-week postoperative stage. The findings of this study indicate that the chitosan-based mimetic mussel polymer conduit loaded with BDNF had a substantial positive effect on myelination and axon outgrowth. The observed impact demonstrated a favorable outcome in terms of sciatic nerve regeneration and subsequent functional restoration in rats with a 15-mm gap. Hence, this approach is promising for nerve tissue regeneration during peripheral nerve injury.

A Retrospective Hospital-Based Study to Evaluate the Results of Extensor Tendon Injuries of the Hand, Wrist, and Forearm Treated Surgically in a Tertiary Care Hospital.

Introduction The important factors determining the treatment of extensor tendon injuries include the anatomical zone, type of injury, mode of injury, chronicity, and pathology of the adjacent tissues (principally the skin, bone, and joints). Very few studies have collectively studied the outcomes of all the wrist, forearm, and hand extensors.Hence, the major aim of this study was to evaluate the resultsof extensor tendon injuries of the hand, wrist, and forearm that were treated surgically. Methodology This was a hospital-based retrospective study done in a tertiary teaching hospital in South India. A total of 30 patients (23 males, seven females) were included in the study.All the cases of extended tendon injuries of the wrist, hand, and forearm were treated surgically, and those willing to participate were included in the study afterobtaining institutional ethics committee approval. Results The study included 30 patients, predominantly males (76.66%). The majority were aged 31-40 years (33.33%). Occupational injuries were the most common cause (36.66%), followed by road traffic accidents (RTAs) and glass cuts (26.66%). Right-sided injuries were more frequent (56.66%), with zone VI being the most affected (43.33%). Extensor digitorum communis was the most injured tendon (40%). Various suture techniques were used, including horizontal mattress and modified Kessler's. Complications occurred in four patients, including hematoma and surgical site infections. Functional outcomes, assessed by Miller's Criteria, indicated extension lag and flexion loss as key recovery measures. Conclusion Hand function is essential for daily life activities, and optimal repair and reconstruction of extensor tendon injuries are crucial to avoid functional disability. While the present study demonstrated positive outcomes, further research with larger sample sizes and more rigorous designs is needed to validate these findings and improve treatment strategies for hand injuries.

Poster 303: Outcomes Following Repair of Radial Meniscus Tears Compared to Bucket Handle Meniscus Tears

Objectives: Preserving the meniscus has become a priority in managing meniscal tears with advancement of meniscus repair techniques. Meniscal repair, as opposed to partial meniscectomy, reduces risk of development and progression of knee osteoarthritis. Radial meniscus tears have traditionally been associated with a poor prognosis because they occur perpendicular to circumferential meniscal fibers, compromising hoop tension. Advances in surgical technique and biologic augmentation have facilitated repair of these complex injuries. The purpose of this study was to compare post-operative complication and surgical revision rates in patients who underwent repair of a radial meniscus tear versus bucket-handle meniscus tear. We hypothesized the outcomes of repair of radial meniscus tear would be similar to a matched group of patients who underwent repair of a bucket handle meniscus tear. Methods: A retrospective study was performed to identify patients who underwent repair of radial meniscus tear. Chart review was performed for 1506 patients who underwent meniscus repair from 2012 to 2019, and demographic information, type of meniscus tear, concomitant ACL reconstruction, post-operative complications, repeat surgeries, and failure at the repair site were detailed in a database. Patients who underwent repair of a radial tear were matched with patients who underwent repair of a bucket-handle tear based on sex, age (within 5 years), BMI (within 5 kg/m2), meniscus laterality, and concomitant ACL reconstruction. Isolated meniscus repairs were augmented with platelet rich plasma (PRP). Results: Fifty patients (age, 31.8 ± 15.2 years; BMI, 30.2 ± 6.4 kg/m2) were identified who underwent a radial meniscus tear repair. Of these patients, 16 (32.0%) were female and 23 (46.0%) underwent concomitant ACL reconstruction. Complications including recurrent swelling, stiffness, persistent pain, and repeat injury were reported in 15 patients (30.0%). Six patients underwent repeat surgery (12.0%). Four repeat surgical patients, who had previously undergone meniscus repair and concomitant ACL reconstruction, were found to have an intact radial repair at the time of second surgery, and underwent repeat surgery for a reason unrelated to the radial tear repair (e.g. cyclops lesion, synovectomy, new meniscus tear). Two patients had a radial tear repair failure that required surgical revision (4.0%). Radial tear repair patients who underwent concomitant ACL reconstruction differed significantly from those who did not only in age (ACL group, 26.0 ± 10.9 y; non-ACL group, 36.6 ± 16.7 y; p = 0.03). There were no significant differences in post-operative complications, repeat surgeries, or failures between the radial and bucket-handle tear repair patients. Conclusions: Repair of radial meniscus tears with contemporary techniques and biological enhancement with either ACL reconstruction or PRP can be expected to have similar outcomes to repairs of bucket handle meniscus tears.

Visual Outcomes and Risk of Endophthalmitis in Open Globe Injuries without Intraocular Foreign Bodies with Delayed Repair

To assess and compare the rate of endophthalmitis and visual outcomes in cases of OGI's without intraocular foreign bodies repaired within and greater than 24 hours from the time of injury. A retrospective review of 2,002 cases of OGI's presenting to a single institution. Patients with OGI's were admitted and managed according to a standardized protocol. The impact of timing of repair was assessed between those undergoing OGI repair within (i) 24 hours, (ii) 25-36 hours, and (iii) greater than 36 hours from the time of injury. Rates of endophthalmitis and postoperative visual acuity of logMAR 1.3, logMAR 1.0, and logMAR 0.3 at 180 days and 1 year following open globe repair. 1,382 patients with OGI's were included, of which 75% were male with an average age of 41 years. Maximal zone of injury was zone 1 for 468 patients, zone 2 for 529 patients and zone 3 for 508 patients. 84% of all OGI's underwent repair within 24 hours from the time of injury, 9% from 25-36 hours, and 7% greater than 36 hours. Average preoperative visual acuity was hand motion. Risk factors associated with repair performed greater than 36 hours from the time of injury included female sex (p=0.042). Endophthalmitis was associated with time to repair greater than 36 hours (p=0.049) but not with 25-36 hours or zone of injury (p=0.111). Time to repair had no significant impact on visual acuity outcomes. Although repair of OGI's within 24 hours is the current standard of care, this study found no statistically significant difference in rates of endophthalmitis or visual outcomes in eyes undergoing repair within 24 hours of injury compared to repair extending to 25 to 36 hours . Endophthalmitis rates did increase after 36 hours. We recommend urgent repair of open globe injuries, but in certain circumstances, it may be reasonable to delay repair beyond 24 hours to optimize operating conditions.

Characterization of sciatic nerve myelin sheath during development in C57BL/6 mice.

Myelin sheath plays important roles in information conduction and nerve injury repair in the peripheral nerve system (PNS). Enhancing comprehension of the structure and components of the myelin sheath in the PNS during development would contribute to a more comprehensive understanding of the developmental and regenerative processes. In this research, the structure of sciatic nerve myelin sheath in C57BL/6 mice from embryonic day 14 (E14) to postnatal 12 months (12M) was observed with transmission electron microscopy. Myelin structure appeared in the sciatic nerve as early as E14, and the number and thickness of myelin lamellar gradually increased with the development until 12M. Transcriptome analysis was performed to show the expressions of myelin-associated genes and transcriptional factors involved in myelin formation. The genes encoding myelin proteins (Mag, Pmp22, Mpz, Mbp, Cnp and Prx) showed the same expression pattern, peaking at postnatal day 7 (P7) and P28 after birth, whereas the negative regulators of myelination (c-Jun, Tgfb1, Tnc, Cyr61, Ngf, Egr1, Hgf and Bcl11a) showed an opposite expression pattern. In addition, the expression of myelin-associated proteins and transcriptional factors was measured by Western blot and immunofluorescence staining. The protein expressions of MAG, PMP22, MPZ, CNPase and PRX increased from E20 to P14. The key transcriptional factor c-Jun co-localized with the Schwann cells Marker S100β and decreased after birth, whereas Krox20/Egr2 increased during development. Our data characterized the structure and components of myelin sheath during the early developmental stages, providing insights for further understanding of PNS development.

Open Globe Injury Repairs Among Medicare Beneficiaries from 2011 to 2020

ABSTRACT Purpose To explore patient and surgeon characteristics for open globe injury repairs (OGRs) and rates of subsequent operations. Methods Using a retrospective cohort design, eyes of patients ≥18 years who underwent OGR among 100% Medicare Fee-For-Service dataset from 2011 to 2020 were included. Current Procedural Terminology (CPT®) codes were used to identify OGR. Patient characteristics were reported, and surgeon characteristics were stratified by sex and compared using Chi-square and Student’s t-test. Overall rate of subsequent operations was reported, and trends of subsequent operations over time were assessed using Cochrane-Armitage trend test. Results A total of 16,576 patients with a mean age of 73.89 years (±12.89) underwent OGR. Most patients were White (79.68%, n = 13,207) and 49.44% (n = 8196) were female. More patients resided in a rural area (18.71%; n = 3102) relative to surgeon location (4.51%, n = 748; p < 0.001). A total of 5,898 surgeons performed these OGRs with 77.33% (n = 4,561) male and 22.67% (n = 1,337) female surgeons. Male surgeons performed most of the OGRs (76.35%, n = 12,655; p < 0.001). On average, a surgeon performed a single OGR annually (Mean: 1.08 ± 1.04; Range: 0.11–40). Among all OGRs, 51% (8,452/16,576) had ≥1 subsequent operations in median 29 days (IQR: 10–86), which increased during the last decade from 47% to 51% (p = 0.008). Conclusion Geographic and workforce disparities in ocular trauma warrant future investigation. Further studies can also assess the reasons for increase in the incidence of subsequent procedures after OGR over time.

Research progress of neurotrophic factor 4 in nerve injury repair

Neurotrophin-4 (NT-4), the fourth member of the nerve growth factor family (NGFs), was found in vipers and African toad in 1991, and it was named for its similar gene sequence structure and biological activity with the first three growth factors of NGFs. Up to now, much evidence has addressed the role of NT-4 in nerve injury and repair. With the study of NT-4 gradually deepening, a certain understanding of its biochemical characteristics and distribution in tissues needs to be clarified. This paper gives a brief review of the biological role of NT-4 and its relationship with nerve injury repair. It gives a preliminary discussion on the role of NT-4 in nerve injury repair.

P7C3 ameliorates barium chloride-induced skeletal muscle injury activating transcriptomic and epigenetic modulation of myogenic regulatory factors.

Skeletal muscle injury affects the quality of life in many pathologies, including volumetric muscle loss, contusion injury, and aging. We hypothesized that the nicotinamide phosphoribosyltransferase (Nampt) activator P7C3 improves muscle repair following injury. In the present study, we tested the effect of P7C3 (1-anilino-3-(3,6-dibromocarbazol-9-yl) propan-2-ol) on chemically induced muscle injury. Muscle injury was induced by injecting 50 µL 1.2% barium chloride (BaCl2) into the tibialis anterior (TA) muscle in C57Bl/6J wild-type male mice. Mice were then treated with either 10 mg/kg body weight of P7C3 or Vehicle intraperitoneally for 7 days and assessed for histological, biochemical, and molecular changes. In the present study, we show that the acute BaCl2-induced TA muscle injury was robust and the P7C3-treated mice displayed a significant increase in the total number of myonuclei and blood vessels, and decreased serum CK activity compared with vehicle-treated mice. The specificity of P7C3 was evaluated using Nampt+/- mice, which did not display any significant difference in muscle repair capacity among treated groups. RNA-sequencing analysis of the injured TA muscles displayed 368 and 212 genes to be exclusively expressed in P7C3 and Veh-treated mice, respectively. There was an increase in the expression of genes involved in cellular processes, inflammatory response, angiogenesis, and muscle development in P7C3 versus Veh-treated mice. Conversely, there is a decrease in muscle structure and function, myeloid cell differentiation, glutathione, and oxidation-reduction, drug metabolism, and circadian rhythm signaling pathways. Chromatin immunoprecipitation-quantitative polymerase chain reaction (qPCR) and reverse transcription-qPCR analyses identified increased Pax7, Myf5, MyoD, and Myogenin expression in P7C3-treated mice. Increased histone lysine (H3K) methylation and acetylation were observed in P7C3-treated mice, with significant upregulation in inflammatory markers. Moreover, P7C3 treatment significantly increased the myotube fusion index in the BaCl2-injured human skeletal muscle in vitro. P7C3 also inhibited the lipopolysaccharide-induced inflammatory response and mitochondrial membrane potential of RAW 264.7 macrophage cells. Overall, we demonstrate that P7C3 activates muscle stem cells and enhances muscle injury repair with increased angiogenesis.

Mesenchymal Stromal Cells for the Enhancement of Surgical Flexor Tendon Repair in Animal Models: A Systematic Review and Meta-Analysis.

Flexor tendon lacerations are primarily treated by surgical repair. Limited intrinsic healing ability means the repair site can remain weak. Furthermore, adhesion formation may reduce range of motion post-operatively. Mesenchymal stromal cells (MSCs) have been trialled for repair and regeneration of multiple musculoskeletal structures. Our goal was to determine the efficacy of MSCs in enhancing the biomechanical properties of surgically repaired flexor tendons. A PRISMA systematic review was conducted using four databases (PubMed, Ovid, Web of Science, and CINAHL) to identify studies using MSCs to augment surgical repair of flexor tendon injuries in animals compared to surgical repair alone. Nine studies were included, which investigated either bone marrow- or adipose-derived MSCs. Results of biomechanical testing were extracted and meta-analyses were performed regarding the maximum load, friction and properties relating to viscoelastic behaviour. There was no significant difference in maximum load at final follow-up. However, friction, a surrogate measure of adhesions, was significantly reduced following the application of MSCs (p = 0.04). Other properties showed variable results and dissipation of the therapeutic benefits of MSCs over time. In conclusion, MSCs reduce adhesion formation following tendon injury. This may result from their immunomodulatory function, dampening the inflammatory response. However, this may come at the cost of favourable healing which will restore the tendon's viscoelastic properties. The short duration of some improvements may reflect MSCs' limited survival or poor retention. Further investigation is needed to clarify the effect of MSC therapy and optimise its duration of action.

Lung injury-induced activated endothelial cell states persist in aging-associated progressive fibrosis

Progressive lung fibrosis is associated with poorly understood aging-related endothelial cell dysfunction. To gain insight into endothelial cell alterations in lung fibrosis we performed single cell RNA-sequencing of bleomycin-injured lungs from young and aged mice. Analysis reveals activated cell states enriched for hypoxia, glycolysis and YAP/TAZ activity in ACKR1+ venous and TrkB+ capillary endothelial cells. Endothelial cell activation is prevalent in lungs of aged mice and can also be detected in human fibrotic lungs. Longitudinal single cell RNA-sequencing combined with lineage tracing demonstrate that endothelial activation resolves in young mouse lungs but persists in aged ones, indicating a failure of the aged vasculature to return to quiescence. Genes associated with activated lung endothelial cells states in vivo can be induced in vitro by activating YAP/TAZ. YAP/TAZ also cooperate with BDNF, a TrkB ligand that is reduced in fibrotic lungs, to promote capillary morphogenesis. These findings offer insights into aging-related lung endothelial cell dysfunction that may contribute to defective lung injury repair and persistent fibrosis.

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains.

Successful polyethylene glycol fusion (PEG-fusion) of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to: (1) rapidly restore electrophysiological continuity; (2) prevent distal Wallerian Degeneration and maintain their myelin sheaths; (3) promote primarily motor, voluntary behavioral recoveries as assessed by the Sciatic Functional Index; and, (4) rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex (e.g., toe twitch) or voluntary behaviors. The preceding companion paper describes sensory terminal field reorganization following PEG-fusion repair of sciatic nerve transections or ablations; however, sensory behavioral recovery has not been explicitly explored following PEG-fusion repair. In the current study, we confirmed the success of PEG-fusion surgeries according to criteria (1-3) above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-Dawley and inbred Lewis rats. Mechanical nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the hindpaws. Dorsal von Frey filament test was a more reliable method than plantar von Frey filament test to assess mechanical nociceptive sensitivity following sciatic nerve transections. Baseline withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not sex. Withdrawal thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated rats. Following sciatic transection, all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the injury. However, PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative Control rats. Furthermore, PEG-fused rats with significantly improved Sciatic Functional Index scores at or after 4 weeks postoperatively exhibited yet-earlier von Frey filament recovery compared with those without Sciatic Functional Index recovery, suggesting a correlation between successful pPEG-fusion and both motor-dominant and sensory-dominant behavioral recoveries. This correlation was independent of the sex or strain of the rat. Furthermore, our data showed that the acceleration of von Frey filament sensory recovery to baseline was solely due to the PEG-fused sciatic nerve and not saphenous nerve collateral outgrowths. No chronic hypersensitivity developed in any rat up to 12 weeks. All these data suggest that PEG-fusion repair of transection peripheral nerve injuries could have important clinical benefits.

Roles of cerebrospinal fluid-contacting neurons as potential neural stem cells in the repair and regeneration of spinal cord injuries.

Cerebrospinal fluid-contacting neurons (CSF-cNs) represent a distinct group of interneurons characterized by their prominent apical globular protrusions penetrating the spinal cord's central canal and their basal axons extending towards adjacent cells. Identified nearly a century back, the specific roles and attributes of CSF-cNs have just started to emerge due to the historical lack of definitive markers. Recent findings have confirmed that CSF-cNs expressing PKD2L1 possess attributes of neural stem cells, suggesting a critical function in the regeneration processes following spinal cord injuries. This review aims to elucidate the molecular markers of CSF-cNs as potential neural stem cells during spinal cord development and assess their roles post-spinal cord injury, with an emphasis on their potential therapeutic implications for spinal cord repair.

Intravascular Ultrasound May Not Impact Graft Sizing in Endovascular Repair of Blunt Thoracic Aortic Injury.

Thoracic endovascular aortic repair (TEVAR) is the preferred treatment for severe blunt thoracic aortic injuries (BTAI). Successful outcomes rely on accurate endograft sizing, but initial imaging may underestimate aortic diameters. This study examines the impact of intravascular ultrasound (IVUS) on endograft sizing and clinical outcomes in BTAI patients. A prospectively collected multi-institutional dataset from the Aortic Trauma Foundation was analyzed. Patients with BTAI undergoing TEVAR with IVUS were compared to patients who underwent TEVAR alone. Demographics and operative variables were compared, focusing on IVUS effects on endograft sizing by examining maximal proximal and distal aortic diameter on initial CT imaging compared to the graft diameters used during TEVAR. 293 patients underwent TEVAR for BTAI with IVUS utilized in 124 cases (42.3%). The average graft size in the IVUS and non-IVUS groups were similar proximally (26.91 ± 4.3mm IVUS vs 27.77 ± 4.7mm non-IVUS, P = 0.116) and distally (25.96 ± 4.7mm IVUS vs 26.51 ± 4.7mm non-IVUS). IVUS did not impact the difference between graft size and initial CT measurements proximally (4.32 ± 4.8mm IVUS vs 4.23 ± 3.9mm non-IVUS, P = 0.859) or distally (4.17 ± 5.9mm IVUS vs 4.50 ± 4.3mm non-IVUS, P = 0.606). Although delayed hemorrhagic and ischemic stroke occurred less frequently in IVUS patients (0.8% IVUS vs 7.1% non- IVUS, P = 0.024), in-hospital mortality was similar between groups (5.6% IVUS vs 7.7% non-IVUS, P = 0.581). IVUS is not associated with significant changes in endograft sizing compared to sizing based on CT scan alone in BTAI patients. IVUS was not associated with differences in mortality but was associated with a decrease in delayed hemorrhagic and ischemic stroke. Routine IVUS in BTAI patients may not be necessary for accurate sizing, but there may be a relationship between IVUS and stroke.

Progress on application of hydrogels in the field of peripheral nerve injury repair

As one of the common traumatic diseases in clinical practice, peripheral nerve injury (PIN) often causes nerve pain, abnormal reflexes, autonomic disorders, and even sensorimotor disorders due to the slow regeneration rate after injury, which seriously affects body function. Even as the gold standard of treatment, autologous nerve transplantation has limitations such as limited donor area and donor injury, which greatly limits its clinical application effect. Therefore, the preparation of artificial nerve grafts suitable for clinical practice has become the future development trend of peripheral nerve injury treatment, and the repair of injury defects and the promotion of nerve regeneration have also become research hotspots in tissue engineering and regenerative medicine. In recent years, extensive research has been carried out on nerve guidance conduits (NGCs) in the field of nerve regeneration and repair, in which scaffold materials and internal fillers have also become the focus of research as the core elements of neural catheters, and a series of achievements have been made in the application of new materials, embedding stem cells/precursor cells, and developing trophic factors and drug-loaded sustained-release systems. Therefore, this paper focuses on the application progress of hydrogel and its related derivative materials in the field of peripheral nerve injury repair, and provides new ideas for promoting the related research of tissue engineering and clinical medicine.

Comparison of functional outcomes following early and delayed arthroscopic repair for traumatic and non-traumatic rotator cuff injuries

BackgroundThe effects of the timing of surgical repair on the outcomes of traumatic and non-traumatic rotator cuff injuries (RCI) remain elusive. Thus, this study aimed to compare differences in outcomes following the repair of traumatic and non-traumatic RCI at varying time points.MethodsThe study population comprised 87 patients with traumatic and non-traumatic RCI who underwent arthroscopic rotator cuff repair and were followed up for a minimum of 6 months. Next, the trauma and the non-trauma groups were stratified into subgroups according to the time of injury (early repair: occurring within 3 months; delayed repair: occurring after 3 months). Measurements before and after surgical interventions were compared to evaluate the effect of the duration of RCI on the functional status of patients in the trauma and non-trauma groups. Primary evaluation indices included the Visual Analog Scale (VAS) pain score, American Shoulder and Elbow Surgeons (ASES) score, Constant shoulder function score, and the University of California, Los Angeles (UCLA) shoulder score. Secondary evaluation indices consisted of shoulder range of motion (ROM), postoperative rotator cuff retear rate, and incidence of joint stiffness.ResultsAmong the 40 patients in the trauma group, 22 underwent early repair, whereas the remaining 18 underwent delayed repair. In the non-trauma group consisting of 47 patients, 18 underwent early repair, whereas the remaining 29 underwent delayed repair. The minimum clinical follow-up time was 6 months, with an average follow-up time of 10.2 months. During postoperative follow-up, 1 and 6 patients who underwent early and delayed repair experienced re-tear in the trauma group, respectively. Contrastingly, 3 and 8 patients who underwent early and delayed repair presented with re-tear in the non-trauma group, respectively.ConclusionEarly repair of traumatic RCI yielded superior outcomes, including improved range of motion, lower pain symptoms, and lower risk of postoperative re-tears compared to delayed repair. Additionally, non-surgical treatment is recommended as the preferred approach for patients with non-traumatic RCI.

Macrophage GIT1 promotes oligodendrocyte precursor cell differentiation and remyelination after spinal cord injury.

Spinal cord injury (SCI) can result in severe motor and sensory deficits, for which currently no effective cure exists. The pathological process underlying this injury is extremely complex and involves many cell types in the central nervous system. In this study, we have uncovered a novel function for macrophage G protein-coupled receptor kinase-interactor 1 (GIT1) in promoting remyelination and functional repair after SCI. Using GIT1flox/flox Lyz2-Cre (GIT1 CKO) mice, we identified that GIT1 deficiency in macrophages led to an increased generation of tumor necrosis factor-alpha (TNFα), reduced proportion of mature oligodendrocytes (mOLs), impaired remyelination, and compromised functional recovery in vivo. These effects in GIT1 CKO mice were reversed with the administration of soluble TNF inhibitor. Moreover, bone marrow transplantation from GIT1 CWT mice reversed adverse outcomes in GIT1 CKO mice, further indicating the role of macrophage GIT1 in modulating spinal cord injury repair. Our in vitro experiments showed that macrophage GIT1 plays a critical role in secreting TNFα and influences the differentiation of oligodendrocyte precursor cells (OPCs) after stimulation with myelin debris. Collectively, our data uncovered a new role of macrophage GIT1 in regulating the transformation of OPCs into mOLs, essential for functional remyelination after SCI, suggesting that macrophage GIT1 could be a promising treatment target of SCI.

Il34 rescues metronidazole-induced impairment of spinal cord regeneration in zebrafish central nervous system.

Metronidazole (MTZ), a commonly used anti-infective drug in clinical practice, has also been employed as a prodrug in cell-targeted ablation systems in scientific research, exhibiting significant application value. However, it has been demonstrated that MTZ can induce neurotoxic symptoms to some extent during its use, and there is currently a lack of effective means to circumvent its toxicity in both clinical and research settings, which limits its application. Therefore, exploring the specific mechanisms underlying MTZ-induced neurotoxic symptoms and elucidating countermeasures will enhance the practical value of MTZ. In this study, using a zebrafish spinal cord injury regeneration model, we confirmed that MTZ neurotoxicity leads to impaired axon regeneration in the central nervous system. By overexpressing il34 in the central nervous system of zebrafish, we eliminated the inhibitory effect of MTZ on axonal regeneration and demonstrated that the pro-regenerative effect against MTZ neurotoxicity is not caused by excessive macrophages/microglia chemoattracted by interleukin 34(Il34). Transcriptome sequencing analysis and GO enrichment analysis of differentially expressed genes between groups revealed that Il34 may counteract MTZ neurotoxicity and promote spinal cord injury repair through biological processes that enhance cellular adhesion and cell location. In summary, our work uncovers a possible cause of MTZ neurotoxicity and provides a new perspective for eliminating MTZ toxicity.

Deficiency of SECTM1 impairs corneal wound healing in aging.

The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.