Long-term Functional Recovery Research Articles

Transplantation of human neural stem cells repairs neural circuits and restores neurological function in the stroke-injured brain

Exogenous neural stem cell (NSC) transplantation has become one of the most promising treatment methods for chronic stroke. Recent studies have shown that most ischemia-reperfusion model rats recover spontaneously after injury, which limits the ability to observe long-term behavioral recovery. Here, we used a severe stroke rat model with 150 minutes of ischemia, which produced severe behavioral deficiencies that persisted at 12 weeks, to study the therapeutic effect of neural stem cells on neural restoration in chronic stroke. Our study showed that stroke model rats treated with human neural stem cells had long-term sustained recovery of motor function, reduced infarction volume, long-term human neural stem cell survival, and improved local inflammatory environment and angiogenesis. We also demonstrated that transplanted human neural stem cells differentiated into mature neurons in vivo, formed stable functional synaptic connections with host neurons, and exhibited the electrophysiological properties of functional mature neurons, indicating that they replaced the damaged host neurons. The findings showed that human fetal-derived neural stem cells had long-term effects for neurological recovery in a model of severe stroke, which suggests that human neural stem cells-based therapy may be effective for repairing damaged neural circuits in stroke patients.

Enhanced Recovery After Surgery Protocols in One- or Two-Level Posterior Lumbar Fusion: Improving Postoperative Outcomes.

Background/Objectives: Enhanced recovery after surgery (ERAS) protocols optimize perioperative care and improve recovery. This study evaluated the effectiveness of ERAS in one- or two-level posterior lumbar fusion surgeries, focusing on perioperative medication use, pain management, and functional outcomes. Methods: Eighty-eight patients undergoing lumbar fusion surgery between March 2021 and February 2022 were allocated into pre-ERAS (n = 41) and post-ERAS (n = 47) groups. Outcomes included opioid and antiemetic consumption, pain scores (numerical rating scale (NRS)), functional recovery (Oswestry Disability Index (ODI) and EuroQol 5 Dimension (EQ-5D)), and complication rates. Pain was assessed daily for the first four postoperative days and at 6 months. Linear Mixed Effects Model analysis evaluated pain trajectories. Results: The post-ERAS group showed significantly lower opioid (p = 0.005) and antiemetic (p < 0.001) use. No significant differences were observed in NRS pain scores in the first 4 postoperative days. At 6 months, the post-ERAS group reported significantly lower leg pain (p = 0.002). The time:group interaction was not significant for back (p = 0.848) or leg (p = 0.503) pain. Functional outcomes at 6 months, particularly ODI and EQ-5D scores, showed significant improvement in the post-ERAS group. Complication rates were lower in the post-ERAS group (4.3% vs. 19.5%, p = 0.024), while hospital stay and fusion rates remained similar. Conclusions: The ERAS protocol significantly reduced opioid and antiemetic use, improved long-term pain management and functional recovery, and lowered complication rates in lumbar fusion patients. These findings support the implementation of ERAS protocols in spinal surgery, emphasizing their role in enhancing postoperative care.

Surgical intervention for distal radial fractures with concurrent ulnar styloid fractures may be beneficial for the elderly patients: a retrospective study

BackgroundDistal radius fractures are highly prevalent among older adults. Ulnar styloid fractures frequently accompany distal radius fractures, raising concerns about treatment outcomes due to the risk of distal radioulnar joint (DRUJ) instability. This study investigated the necessity of surgical intervention (open reduction internal fixation; ORIF) for distal radius fractures in very old patients with coexisting ulnar styloid fractures.Materials and methodsA retrospective analysis of 96 patients aged ≥ 80 years with AO classification 23-A2 to 23-B3 distal radius fractures with concomitant ulnar styloid fracture between 2019 and 2022 was performed. Patients were excluded if they were aged < 80 years, had a preinjury Barthel index of < 90, or had high-energy multiple trauma. The primary outcome was the Disabilities of the Arm, Shoulder, and Hand (DASH) score assessed at 3, 6, and 12 months. We compared the DASH score and their trajectories between the ORIF and conservative treatment groups.ResultsORIF group demonstrated significantly better DASH functional scores (25.31 ± 4.71) at the 12-month follow-up compared with the conservative group (34.42 ± 8.03; p < 0.001). Treatment choice was identified as a significant predictor of DASH scores at 12 months, with ORIF significantly improved patient’s wrist function and demonstrated a β coefficient of − 9.11 (95% confidence interval: −11.95 to − 6.27, p < 0.001). The other factors investigated, namely age, lowest T-score, and medical history of diabetes mellitus, hypertension, coronary artery disease, cerebrovascular accidents, cancer, and dementia, did not exhibit a significant association with the 12-month DASH scores in the adjusted model (p > 0.05).ConclusionsOur findings suggest that very old patients with distal radius fracture accompanied by ulnar styloid fractures may benefit from ORIF to achieve optimal long-term functional recovery.

A Comparative Study of the Efficacy of Platelet-Rich Plasma (PRP) vs. Other Conservative Treatments for Lateral Epicondylitis.

Background Lateral epicondylitis, also known as tennis elbow, is a degenerative condition that affects a significant portion of the adult population, particularly those between the ages of 35 and 55. Conventional treatments, including analgesics, physiotherapy, and bracing, often lead to a high recurrence rate. Platelet-rich plasma (PRP) therapy has emerged as a promising alternative, offering regenerative benefits that may enhance tissue healing. This study evaluates the effectiveness of PRP injections compared to traditional conservative therapies in alleviating pain and improving function in individuals with chronic lateral epicondylitis. Methods This prospective observational study was conducted at Father Muller Medical College Hospital from April 2018 to August 2019. A total of 44 patients aged 18-60 years with chronic lateral epicondylitis were randomly assigned to two groups: PRP (n = 22) and conservative treatment (n = 22). The conservative group received a combination of physiotherapy, analgesics, and a counterforce brace. The primary outcome was measured using the Patient-Rated Tennis Elbow Evaluation (PRTEE) score, assessed at baseline, four weeks, eight weeks, three months, and six months. The PRTEE score includes pain and function subscales. Data was analyzed using appropriate statistical methods, and significance was considered at p < 0.05. Results Both groups significantly improved pain and function during the first eight weeks. However, the PRP group demonstrated superior long-term outcomes. At three and six months, the PRP group had significantly lower pain scores (26.00 ± 3.55 and 19.55 ± 3.33, respectively, p < 0.001) compared to the conservative group (32.23 ± 3.75 and 33.64 ± 3.63). Similarly, the PRP group showed better functional improvement at six months (PRTEE function subscale: 20.00 ± 3.19 in PRP vs. 30.73 ± 4.11 in conservative, p < 0.001). No complications were reported in either group. Conclusions PRP injections provide superior long-term pain relief and functional recovery compared to conservative management in patients with chronic lateral epicondylitis. While conservative treatments are effective in the short term, PRP offers a more durable solution with no reported complications. These findings support the use of PRP as a viable alternative for the long-term management of lateral epicondylitis.

Downregulation of Circular RNA Gla Reduced Astrocyte Inflammatory Status by Regulating miR-488/MEKK1 Levels and Promoted Functional Recovery After Spinal Cord Injury.

Post-spinal cord injury (SCI) inflammation correlates with neurologic recovery. Through sequencing, we explored the roles of a differentially expressed circRNA in mice after SCI, circGla, on inflammation and recovery of SCI. The T8-T10 SCI model was established in C57BL6 mice. HE staining and RT-qPCR verified circGla upregulation results after injury obtained through sequencing. RNase R digestion and primer amplification experiments confirmed the circular properties of circGla. Nucleus and cytoplasm isolation experiments and FISH confirmed circGla expression in the astrocyte cytoplasm. AAV was used to establish a circGla knockdown mouse model. Behavioral tests were conducted to assess the recovery of the neurological function. The key inflammatory molecules after SCI were evaluated through MRI, RT-qPCR, and ELISA. For in vitro experiments, circGla was upregulated or knocked down in mouse astrocytes to detect its effect. The binding between miR-488 and circGla was confirmed through RIP and the dual luciferase experiment. RT-qPCR and ELISA confirmed the content correlation of the two molecules and the in vitro inflammatory function of miR-488. The binding experiment in astrocytes confirmed the binding between miR-488 and MEKK1 mRNA. Western blotting of MAPK pathway-related proteins confirmed that MEKK1 is a downstream effector for circGla and miR-488 in astrocytes. Following SCI, the circular RNA circGla levels increased and it existed in the astrocyte cytoplasm. circGla knockdown reduced inflammation and improved neurological recovery in vivo. The correlation between circGla and proinflammatory factors was confirmed in vitro. circGla bound to miR-488, and the high miR-488 level was associated with the low astrocyte inflammatory state. miR-488 bound to MEKK1 mRNA, and upregulation or knockdown of circGla or miR-488 affected MAPK pathway-related protein expression. Following SCI, downregulation of circGla expression in astrocytes can reduce inflammatory manifestations and stimulate long-term functional recovery in mice through miR-488 and MEKK1.

J147 treatment protects against traumatic brain injury by inhibiting neuronal endoplasmic reticulum stress potentially via the AMPK/SREBP-1 pathway

Endoplasmic reticulum (ER) stress is recognized as a crucial contributor to the progression of traumatic brain injury (TBI) and represents a potential target for therapeutic intervention. This study aimed to assess the potential of J147, a novel neurotrophic compound, in alleviating ER stress by modulating related signaling pathways, thereby promoting functional recovery in TBI. To this end, adult mice underwent controlled cortical impact (CCI) injury to induce TBI, followed by oral administration of J147 one-hour post-injury, with daily dosing for 3 to 7 days. Multiple behavioral assessments were conducted over 35 days, revealing a significant, dose-dependent improvement in neurofunctional recovery with J147 treatment. The neuropathological analysis demonstrated reduced acute neurodegeneration (observed at three days through FJC staining), enhanced long-term neuron survival (H&E and Nissl staining), and improved neuroplasticity (Golgi staining) at 35 days post-TBI. At the molecular level, TBIinduced AMP-activated protein kinase (AMPK) dephosphorylation, sterol regulatory element binding protein-1 (SREBP-1) activation, and upregulation of ER stress marker proteins, including phosphorylated eukaryotic initiation factor-2α (p-eIF2a), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP) in perilesional cortex neurons at three days post-injury. Notably, the J147 treatment significantly attenuated AMPK dephosphorylation, SERBP-1 activation, and expression of the ER stress markers. In summary, this study reveals the therapeutic promise of J147 in mitigating secondary brain damage associated with TBI and improving long-term functional recovery by modulating ER stress pathways.

Covert Consciousness in the ICU.

For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries. We reviewed salient medical literature regarding covert consciousness. We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness. We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries. Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited.

Functional rehabilitation and long‑term efficacy of rotationplasty in pediatrics: A retrospective study.

Rehabilitation plays a critical role in the functional recovery of pediatric patients following rotationplasty for lower extremity malignant bone tumors. However, due to the limited number of cases and the unique characteristics of the surgery, there is a paucity of studies that have longitudinally evaluated the effect of rehabilitation strategies on long-term functional recovery after rotationplasty. Therefore, the present study aimed to identify an effective rehabilitation approach for pediatric patients undergoing rotationplasty for malignant bone tumors of the lower limb. Additionally, the study aimed to assess the effect of rehabilitation on long-term functional recovery and quality of life. A total of 12 patients were included in the current study, with a mean age at surgery of 6.58±1.73 years (range, 4-10 years). These patients underwent rotationplasty for malignant bone tumors of the lower extremity at the Fourth Medical Center of the Chinese People's Liberation Army General Hospital (Beijing, China) between March 2014 and March 2019. After surgery, patients underwent a 6-month postoperative rehabilitation programme, either on an outpatient or inpatient basis, with exercise therapy as the key training modality. The follow-up outcomes at 3, 6 and 12 months and at 3 and 5 years were recorded and analyzed, ensuring a comprehensive evaluation of long-term progress. The results demonstrated a gradual enhancement in functional performance and quality of life. Within a year of surgery, the patients displayed significant improvements in both functional recovery and quality of life, and all indicators remained stable 1 year later compared with those at 1 year post-surgery. More specifically, patients showed restored muscle strength and walking ability to normal levels, with a significant increase in muscle strength to 5/5. In addition, the study revealed that the mean distance covered in the 6-min walk test was 403.08±12.52 meters, while a duration of 8.83±0.72 sec was recorded in the timed up and go test. All patients have been continuously monitored up to date. The follow-up period for all patients ranged from 60 to 120 months, with a mean of 89.83±17.55 months. Overall, the findings indicated that the early postoperative period was a critical period for functional recovery, and that early postoperative rehabilitation interventions resulted in significant improvements to the rate and quality of functional recovery over time, thus further improving quality of life.

Minimally invasive techniques utilizing the “Joy Stick” method for managing irreducible flexion-type supracondylar fractures of the humerus in older children

ObjectiveIn this study, we investigated the efficacy of percutaneous poking reduction and Kirschner wire fixation in older children with irreducible supracondylar flexion-type fractures of the humerus.MethodsThis retrospective investigation included 27 children, comprising 15 males and 12 females, aged between 10 years and 3 months to 14 years and 11 months, all diagnosed with a flexion-type supracondylar fracture of the humerus within one week of trauma. All patients underwent surgery under general anesthesia. Following unsuccessful manual reduction, percutaneous poking reduction with Kirschner wires was performed under C-arm fluoroscopy to achieve fracture reduction. Following successful reduction, three 2.0 mm Kirschner wires were inserted in a cross pattern to secure the fracture ends. Postoperatively, the elbow joint was immobilized in a functional position with a plaster cast for four weeks.ResultsFollow-up in the outpatient department ranged from 9 to 36 months. Clinical functional assessment using Flynn’s criteria rated 24 cases as excellent, 2 as good, and 1 as fair, yielding an overall efficacy of 96.3%. No cases of fracture re-displacement, fracture fragment necrosis, or other complications such as nonunion, iatrogenic nerve injury, myositis ossificans, or long-term elbow joint dysfunction were observed during the postoperative follow-up.ConclusionThe percutaneous poking reduction and Kirschner wire fixation technique is a simple and reliable procedure for treating irreducible flexion-type supracondylar fractures of the humerus in older children, with minimal trauma. This technique offers substantial stability for the fracture and results in excellent long-term recovery of joint function.

Selective deletion of interleukin-1 alpha in microglia does not modify acute outcome but regulates neurorepair processes after experimental ischemic stroke.

Inflammation is a key contributor to stroke pathogenesis and exacerbates brain damage leading to poor outcome. Interleukin-1 (IL-1) is an important regulator of post-stroke inflammation, and blocking its actions is beneficial in pre-clinical stroke models and safe in the clinical setting. However, the distinct roles of the two major IL-1 receptor type 1 agonists, IL-1α and IL-1β, and the specific role of IL-1α in ischemic stroke remain largely unknown. Here we show that IL-1α and IL-1β have different spatio-temporal expression profiles in the brain after experimental stroke, with early microglial IL-1α expression (4 h) and delayed IL-1β expression in infiltrated neutrophils and a small microglial subset (24-72 h). We examined for the first time the specific role of microglial-derived IL-1α in experimental permanent and transient ischemic stroke through microglial-specific tamoxifen-inducible Cre-loxP-mediated recombination. Microglial IL-1α deletion did not influence acute brain damage, cerebral blood flow, IL-1β expression, neutrophil infiltration, microglial nor endothelial activation after ischemic stroke. However, microglial IL-1α knock out (KO) mice showed reduced peri-infarct vessel density and reactive astrogliosis at 14 days post-stroke, alongside long-term impaired functional recovery. Our study identifies for the first time a critical role for microglial IL-1α on neurorepair and functional recovery after stroke, highlighting the importance of targeting specific IL-1 mechanisms in brain injury to develop more effective therapies.

Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol

IntroductionTherapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and...

Impact of previous COVID-19 infection on postoperative complications and functional recovery: a one-year follow-up ambispective cohort study.

It's necessary to reassess the patients' short-term and long-term postoperative outcome in the post-COVID-19 era. This study aims to provide more comprehensive evidence regarding the timing of surgery after COVID-19 infection among the vaccinated population upon Omicron variant, considering the duration after acute COVID-19 infection, severity of COVID-19, patients' comorbidities, and the full course quality of postoperative recovery. This is a single-center cohort study. Patients diagnosed with preoperative COVID-19 infection were consecutively included before surgery. Patients' demographics, surgical characteristics, and COVID-19 related factors were documented. Exposure was the time interval from COVID-19 infection to surgery. The primary outcome was postoperative complications within 30 days. The secondary outcomes included postoperative mortality within 30 days, functional disability at 6 and 12 months after surgery. A total of 4953 patients were included, and postoperative complications occurred in 353 patients (7.1%) within 30 days after surgery. Time interval from COVID-19 infection to surgery was associated with postoperative complications within 30 days after surgery (adjusted odds ratio [aOR] per day: 0.99; 95% CI, 0.99-1.00; P<0.01), as well as postoperative 6- and 12-month functional disability ([aOR]: 1.00; 95% CI, 0.99-1.00; P<0.01; and [aOR] 0.99; 95% CI, 0.98-1.00; P=0.01, respectively). Delaying surgery beyond a time interval of 2 weeks was associated with reduced postoperative 30-day complications ([aOR]: 0.63; 95% CI, 0.43-0.91; P=0.01) and mortality ([aOR]: 0.07; 95% CI, 0.01-0.38; P<0.01). Meanwhile, delaying surgery beyond a time interval of 7 weeks was associated with reduced functional disability at both 6-month ([aOR]: 0.67; 95% CI, 0.58-0.79; P<0.01) and 12-month postoperatively ([aOR]: 0.71; 95% CI, 0.53-0.95; P=0.02). A 2 weeks delay after COVID-19 infection is necessary for decreasing short-term postoperative risks, and a longer waiting period could be beneficial for long-term functional recovery.

Loss of microRNA-15a/16-1 function promotes neuropathological and functional recovery in experimental traumatic brain injury.

The diffuse axonal damage in white matter and neuronal loss, along with excessive neuroinflammation, hinder long-term functional recovery after traumatic brain injury (TBI). MicroRNAs (miRs) are small noncoding RNAs that negatively regulate protein-coding target genes in a posttranscriptional manner. Recent studies have shown that loss of function of the miR-15a/16-1 cluster reduced neurovascular damage and improved functional recovery in ischemic stroke and vascular dementia. However, the role of the miR-15a/16-1 cluster in neurotrauma is poorly explored. Here, we report that genetic deletion of the miR-15a/16-1 cluster facilitated the recovery of sensorimotor and cognitive functions, alleviated white matter/gray matter lesions, reduced cerebral glial cell activation, and inhibited infiltration of peripheral blood immune cells to brain parenchyma in a murine model of TBI when compared with WT controls. Moreover, intranasal delivery of the miR-15a/16-1 antagomir provided similar brain-protective effects conferred by genetic deletion of the miR-15a/16-1 cluster after experimental TBI, as evidenced by showing improved sensorimotor and cognitive outcomes, better white/gray matter integrity, and less inflammatory responses than the control antagomir-treated mice after brain trauma. miR-15a/16-1 genetic deficiency and miR-15a/16-1 antagomir also significantly suppressed inflammatory mediators in posttrauma brains. These results suggest miR-15a/16-1 as a potential therapeutic target for TBI.

Predicting brain edema and outcomes after thrombectomy in stroke: Frontal delta/alpha ratio as an optimal quantitative EEG index

ObjectiveWe aimed to determine whether quantitative electroencephalography (QEEG) measures have predictive value for cerebral edema (CED) and clinical outcomes in acute ischemic stroke (AIS) patients with anterior circulation large vessel occlusion who underwent mechanical thrombectomy (MT). MethodsA total of 105 patients with AIS in the anterior circulation were enrolled in this prospective study. The occurrence and severity of CED were assessed through computed tomography conducted 24 h after MT. Clinical outcomes were evaluated based on early neurological deterioration (END) and 3-month functional status, as measured by the modified Rankin scale (mRS). Electroencephalography (EEG) recordings were performed 24 h after MT, and QEEG indices were calculated from the standard 16 electrodes and 2 frontal channels (F3-C3, F4-C4). The delta/alpha ratio (DAR), the (delta + theta) / (alpha + beta) ratio (DTABR), and relative delta power were averaged over all electrodes (global) and the F3-C3 and F4-C4 channels (frontal). The predictive effect and value of QEEG indices for CED and clinical outcomes were assessed using ordinal and logistic regression models, as well as receiver operating characteristic (ROC) curves. ResultsSignificantly, both global and frontal DAR were found to be associated with the severity of CED, END, and poor functional outcomes at 90 days, while global and frontal DTABR and relative delta power were not associated with outcomes. In ROC analysis, the best predictive effect was observed in frontal DAR, with an area under the curve of approximately 0.80. It exhibited approximately 75% sensitivity and 71% specificity for radiological and clinical outcomes when a threshold of 3.3 was used. ConclusionsQEEG techniques may be considered an efficient bedside monitoring method for assessing treatment efficacy, identifying patients at higher risk of severe CED and END, and predicting long-term functional outcomes. SignificanceQEEG can help identify patients at risk of severe neurological complications that can impact long-term functional recovery in AIS patients who underwent MT.

Myostatin gene invalidation does not prevent skeletal muscle mass loss during experimental sepsis in mice.

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long-term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13-week-old C57BL/6J wild-type and myostatin knock-out male mice. Survival rates were similar in wild-type and myostatin knock-out mice seven days after CLP. Loss in muscle mass was also similar in wild-type and myostatin knock-out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3-ubiquitin ligases and autophagy-lysosome markers. This transcriptional response was blunted in myostatin knock-out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway. Muscle strength was similarly decreased in wild-type and myostatin knock-out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation-contraction coupling, suggesting that a long-term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation-contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis. KEY POINTS: Survival rates are similar in wild-type and myostatin knock-out mice seven days after the induction of sepsis. Loss in muscle mass and muscle strength are similar in wild-type and myostatin knock-out mice 4 and 7 days after the induction of an experimental sepsis. Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway remained unchanged. RT-qPCR analysis of autophagy-lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild-type and myostatin knock-out mice. Experimental sepsis induces greater variations in the mRNA levels of wild-type mice than those of myostatin knock-out mice, without providing any significant catabolic resistance or functional benefits.

Higher Discharge GCS Score is Associated with Both Survival and Long-term Functional Recovery in Patients with Clinically Defined Diffuse Axonal Injury

Abstract Background: Diffuse axonal injury (DAI) refers to widespread axonal damage due to traumatic brain injury. There are very few studies that have specifically looked at outcomes in patients with DAI, where the injury is not associated with accompanying focal lesions (such as haematomas and other mass lesions) or ischaemic brain injury. In this study, we assessed factors that predict mortality and long-term functional outcome of patients with DAI who underwent treatment and rehabilitation in a tertiary care hospital in South India. Methodology: Long-term outcome and neuropsychiatric sequelae were assessed in 160 patients with DAI, who underwent rehabilitation and were on regular follow-up for a median duration of 5 years (interquartile range = 3–6). Cox proportional hazards and logistic regression models were used to determine factors associated with mortality and functional outcome (Glasgow Outcome Scale-Extended [GOSE], Mayo-Portland Adaptability Inventory [MPAI] and Neuropsychiatric Inventory [NPI]). Results: Majority of the 160 patients included in this study were young males (92%) who presented with severe head injury (Glasgow Coma Scale [GCS] score of 5.6 ± 2.1). At the time of follow-up, 94 (58.75%) patients were alive, while 66 (41.25%) were dead. Patients who were alive at the time of follow-up were significantly younger, had higher GCS score and lower Rotterdam computed tomography (CT) grade at presentation compared to those who died. Compromised airway requiring tracheostomy (χ 2 = 21.3; P &lt; 0.001) and abnormal pupil reactivity (χ2 = 30.2, P &lt; 0.001) were significantly associated with mortality. GCS score at discharge was the single most important determinant of mortality (hazard ratio = 0.802, P &lt; 0.001). Among those who were alive, majority (73.4%) had good functional recovery (GOSE score 8). GCS scores (at admission and that at discharge) and Rotterdam CT score independently and significantly predicted MPAI, NPI and caregiver distress scores. Among them, GCS score at discharge was the strongest predictor. In-hospital improvement in GCS correlated with GOSE but not with MPAI and NPI. Conclusion: Higher GCS scores at discharge were strongly associated with both survival and functional recovery in patients with DAI.

Blocking cGAS-STING pathway promotes post-stroke functional recovery in an extended treatment window via facilitating remyelination

Ischemic stroke is a major cause of worldwide death and disability, with recombinant tissue plasminogen activator being the sole effective treatment, albeit with a limited treatment window. The cyclic GMP-AMP synthase (cGAS) and stimulator of interferon genes (STING) pathway is emerging as the major DNA-sensing pathway to invoke immune responses in neuroinflammatory disorders. By performing a series of neurobehavioral assessments, electrophysiological analysis, high-throughput sequencing, and cell-based assays based on the transient middle cerebral artery occlusion (tMCAO) mouse stroke model, we examined the effects and underlying mechanisms of genetic and pharmacological inhibition of the cGAS-STING pathway on long-term post-stroke neurological functional outcomes. Blocking the cGAS-STING pathway, even 3days after tMCAO, significantly promoted functional recovery in terms of white matter structural and functional integrity as well as sensorimotor and cognitive functions. Mechanistically, the neuroprotective effects via inhibiting the cGAS-STING pathway were contributed not only by inflammation repression at the early stage of tMCAO but also by modifying the cell state of phagocytes to facilitate remyelination at the sub-acute phase. The activation of the cGAS-STING pathway significantly impeded post-stroke remyelination through restraining myelin debris uptake and degradation and hindering oligodendrocyte differentiation and maturation. Manipulating the cGAS-STING pathway has an extended treatment window in promoting long-term post-stroke functional recovery via facilitating remyelination in a mouse stroke model. Our results highlight the roles of the cGAS-STING pathway in aggregating stroke pathology and propose a new way for improving functional recovery after ischemic stroke. This work was primarily funded by the National Key R&D Program of China.

Influence of preoperative anatomy and functional status on outcomes after total temporomandibular joint replacement with patient-specific endoprostheses: A retrospective cohort study.

Temporomandibular joint (TMJ) replacement may be indicated for various pathological conditions, and the type of condition can affect the surgical procedure and outcomes. The causes of limited range of motion after alloplastic TMJ replacement have not been extensively studied. The present study aimed to evaluate the impact of preoperative jaw anatomy and functional status on the immediate and long-term outcomes of total TMJ replacement using a two-component patient-specific TMJ endoprosthesis. This retrospective study included 31 patients who underwent total TMJ replacement surgery between 2016 and 2020. The main outcome variable was the maximal incisal opening (MIO) after treatment. Secondary outcome variables included MIO improvement and the presence and type of postoperative complications. The primary predictive variable was the preoperative initial MIO. Secondary predictive variables included sex, age, indications for TMJ replacement, preoperative occlusion, condition of the glenoid fossa and/or condyle, shortening of the mandibular ramus, sagittal mandible position, lateral chin deviation, shape of the coronoid process, and type of surgery. The mean preoperative MIO was 13.0 ±8.0 mm, while the mean MIO 1 month after surgery was 20.6 ±5.5 mm, which was not statistically significant. However, at a later follow-up, functional parameters showed a significant improvement (p = 0.003), with a mean MIO of 32.5 ±5.0 mm 3 years after surgery. Statistical analysis indicated that the initial mouth opening is the strongest predictor of long-term functional recovery after TMJ replacement. Postoperative complications occurred in 4 cases (12.9%) following patient-specific endoprosthesis (PSE) placement. The use of PSEs for TMJ replacement has enabled the restoration of anatomical relationships in complex clinical cases and an improvement in mouth opening. The preoperative MIO was the only factor that significantly influenced long-term functional outcomes.

Stereotactic puncture surgery combined with early hyperbaric oxygen therapy may be better for long-term functional recovery in patients with moderate amounts of thalamic-inner capsule region haemorrhage

BackgroundThe prognosis of patients with thalamic hemorrhage is poor, and their long-term neurological impairment is heavy, which seriously affects their work and life.To comparatively analyse the efficacy and prognosis of patients with moderate hemorrhage in the thalamic region who underwent conservative treatment, stereotactic puncture surgery and neuroendoscopic surgery. MethodThis study retrospectively analyzed hospitalization data from 139 adult patients with moderate-volume cerebral hemorrhage in the thalamo-endocapsular region. They were categorized into a stereotactic group (39cases), a neuroendoscopic group (36cases), and a conventional conservative group (64cases). Logistic regression analysis was used to assess risk factors for severe neurological deficits in patients. Multivariate regression modeling was used to compare the correlation of severe neurological deficits among the three groups of patients. ResultsPatients with thalamic moderate-volume cerebral hemorrhage had statistically significantly higher Assessment of Daily Living (ADL) scores in the stereotactic surgery group than in the conservative treatment group and the neuroendoscopic surgery group after 6 months of treatment (p< 0.001).The amount of residual hematoma was significantly lower in the surgery groups than in the conservative treatment group at 3 days, 7 days, and 2 weeks after the onset of the disease (P< 0.001).In multivariate logistic regression analyses, after adjusting for all covariates, the odds ratios for severe neurologic dysfunction in the stereotactic group and the neuroendoscopy group were, respectively, OR: 0.37 (0.12–0.87), P< 0.001 and 0.42 (0.23–1.13), P=0.361). ConclusionIn patients with moderate volume cerebral hemorrhage in the thalamus-inner capsule region cerebral hemorrhage, patients treated with stereotactic surgery combined with early hyperbaric oxygen therapy may have better long-term neurological recovery compared with conservative and neuroendoscopic surgical treatments.

Updates in diagnostic tools for diagnosing nerve injury and compressions.

Predicting prognosis after nerve injury and compression can be challenging, even for the experienced clinician. Although thorough clinical assessment can aid diagnosis, we cannot always be precise about long-term functional recovery of either motor or sensory nerves. To evaluate the severity of nerve injury, surgical exploration remains the gold standard, particularly after iatrogenic injury and major nerve injury from trauma, such as brachial plexus injury. Recently, advances in imaging techniques (ultrasound, magnetic resonance imaging [MRI] and MR neurography) along with multimodality assessment, including electrodiagnostic testing, have allowed us to have a better preoperative understanding of nerve continuity and prediction of nerve health and possible recovery. This article outlines the current and potential roles for clinical assessment, exploratory surgery, electrodiagnostic testing ultrasound and MRI in entrapment neuropathies, inflammatory neuritis and trauma. Emphasis is placed on those modalities that are improving in diagnostic accuracy of nerve assessment before any surgical intervention.