Subacute Injury Research Articles

Lipid nanoparticle delivery of siRNA targeting Cyp2e1 gene attenuates subacute alcoholic liver injury in mice.

To investigate the effect and mechanism of lipid nanoparticle (LNP) delivery of small interfering RNA (siRNA) targeting Cyp2e1 gene on subacute alcoholic liver injury in mice. siRNA targeting Cyp2e1 gene was encapsulated in LNP (si-Cyp2e1 LNP) by microfluidic technique and the resulting LNPs were characterized. The optimal dose of si-Cyp2e1 LNP administration was screened. Forty female C57BL/6N mice were randomly divided into blank control group, model control group, si-Cyp2e1 LNP group, LNP control group and metadoxine group. The subacute alcoholic liver injury mouse model was induced by ethanol feeding for 10 d plus ethanol gavage for the last 3 d. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities, and the superoxide dismutase (SOD) activity as well as malondialdehyde, reactive oxygen species, glutathione, triacylglycerol, total cholesterol contents in liver tissue were measured in each group, and liver index was calculated. The expression of genes related to oxidative stress, lipid synthesis and inflammation in each group of mice were measured by realtime RT-PCR. Compared with the model control group, the levels of liver index, serum ALT, AST activities, malondialdehyde, reactive oxygen species, triacylglycerol, total cholesterol contents in liver tissue decreased, but the SOD activity as well as glutathione increased in the si-Cyp2e1 LNP group (all P<0.01). Hematoxylin-eosin staining result showed disorganized hepatocytes with sparse cytoplasm and a large number of fat vacuoles and necrosis in the model control group, while the si-Cyp2e1 LNP group had uniformly sized and arranged hepatocytes with normal liver tissue morphology and structure. Oil red O staining result showed si-Cyp2e1 LNP group had lower fat content of the liver compared to the model control group (P<0.01), and no fat droplets accumulated. Anti-F4/80 monoclonal antibody fluorescence immunohistochemistry showed that the si-Cyp2e1 LNP group had lower cumulative optical density values compared to the model control group (P<0.01) and no significant inflammatory reaction. Compared with the model control group, the expression of catalytic genes P47phox, P67phox and Gp91phox were reduced (all P<0.01), while the expression of the antioxidant enzyme genes Sod1, Gsh-rd and Gsh-px were increased (all P<0.01). The mRNA expression of the lipid metabolism genes Pgc-1α and Cpt1 were increased (all P<0.01) and the lipid synthesis-related genes Srebp1c, Acc and Fasn were decreased (all P<0.01); the expression of liver inflammation-related genes Tgf-β, Tnf-α and Il-6 were decreased (all P<0.01). The si-Cyp2e1 LNP may attenuate subacute alcoholic liver injury in mice mainly by reducing reactive oxygen levels, increasing antioxidant activity, blocking oxidative stress pathways and reducing ethanol-induced steatosis and inflammation.

Anatomical and functional predictors of disorientation after first-ever brain damage

Background and objectivesDisorientation is a frequent consequence of acute brain injury or diffuse disorders, such as confusional states or dementia. Its anatomical correlates are debated. Impaired memory as its commonly assumed mechanism predicts that disorientation is associated with medial temporal damage. The alternative is that disorientation reflects defective orbitofrontal reality filtering (ORFi) – a specific failure to identify whether thoughts or memories refer to present reality or not. The latter is a function of the posterior orbitofrontal cortex and connected structures. This study examined the mechanisms and anatomical basis of disorientation in an unselected group of patients with first-ever subacute brain injury. MethodsParticipants hospitalized for neurorehabilitation were asked to participate in this observational cohort study if they had first-ever organic hemispheric brain dysfunction as evident in a localizable brain lesion or verbal amnesia (often without localizable brain damage). Orientation to time, place, situation and person was tested with a 20-items questionnaire. To identify the mechanisms of disorientation, we determined its correlations with executive tasks, verbal episodic memory, and ORFi in all patients. ORFi was examined with a continuous recognition task, which measures learning and item recognition in the first run, and ORFi as reflected in the increase of false positive responses in the second run (temporal context confusion). Lesions of patients having localizable brain damage were manually delineated and normalized before entering multivariate lesion-symptom-mapping (LSM) to determine anatomical predictors of orientation. ResultsEighty-four patients (61.1 ± 14.4 years, 29 women) were included. Among measures of memory and executive functioning, a step-wise regression retained temporal context confusion (R = −0.71, p < 0.0001), item recognition (R = 0.67, p < 0.0001) and delayed free recall (R = 0.63, p < 0.0001) as significant predictors of orientation. LSM was possible in 67 participants; it revealed an association of disorientation with damage of the right OFC and the bilateral head of the caudate nucleus. ConclusionDisorientation in non-confused, non-demented patients with first-ever brain damage is associated with impaired orbitofrontal reality filtering and memory dysfunction, but not with executive dysfunction. Its main anatomical determinant is damage to the orbitofrontal cortex and its subcortical relay, the head of the caudate.

Spatial amine metabolomics and histopathology reveal localized brain alterations in subacute traumatic brain injury and the underlying mechanism of herbal treatment.

Spatial changes of amine metabolites and histopathology of the whole brain help to reveal the mechanism of traumatic brain injury (TBI) and treatment. A newly developed liquid microjunction surface sampling-tandem mass tag-ultra performance liquid chromatography-mass spectrometry technique is applied to profile brain amine metabolites in five brain regions after impact-induced TBI at the subacute stage. H&E, Nissl, and immunofluorescence staining are performed to spatially correlate microscopical changes to metabolic alterations. Then, bioinformatics, molecular docking, ELISA, western blot, and immunofluorescence are integrated to uncover the mechanism of Xuefu Zhuyu decoction (XFZYD) against TBI. Besides the hippocampus and cortex, the thalamus, caudate-putamen, and fiber tracts also show differentiated metabolic changes between the Sham and TBI groups. Fourteen amine metabolites (including isomers such as L-leucine and L-isoleucine) are significantly altered in specific regions. The metabolic changes are well matched with the degree of neuronal damage, glia activation, and neurorestoration. XFZYD reverses the dysregulation of several amine metabolites, such as hippocampal Lys-Phe/Phe-Lys and dopamine. Also, XFZYD enhances post-TBI angiogenesis in the hippocampus and the thalamus. This study reveals the local amine-metabolite and histological changes in the subacute stage of TBI. XFZYD may promote TBI recovery by normalizing amine metabolites and spatially promoting dopamine production and angiogenesis.

Pulmonary Histopathologic Findings in Pediatric Patients After Hematopoietic Stem Cell Transplantation: An Autopsy Study.

Pathologic characterization of pulmonary complications following hematopoietic stem cell transplantation (HSCT) is limited. We describe lung findings in pediatric patients who died following HSCT and attempt to identify potential clinical associations. Pathology databases at Texas Children's Hospital and the Children's Hospital of Philadelphia were queried (2013-2018 CHOP and 2017-2018 TCH). Electronic medical records and slides were reviewed. Among 29 patients, 19 received HSCT for hematologic malignancy, 8 for non-malignant hematologic disorders, and 2 for metastatic solid tumors. Twenty-five patients (86%) showed 1 or more patterns of acute and organizing lung injury. Sixty-two percent had microvascular sclerosis, with venous involvement noted in most cases and not correlating with clinical history of pulmonary hypertension, clinical transplant-associated thrombotic microangiopathy, irradiation, or graft-versus-host disease. Features suggestive of graft-versus-host-disease were uncommon: 6 patients had lymphocytic bronchiolitis, and only 2 patients had evidence of bronchiolitis obliterans (both clinically unexpected), both with a mismatched unrelated donor transplant. Acute and subacute alveolar injury (diffuse alveolar damage or organizing pneumonia) is common in pediatric patients who died following HSCT and is difficult to assign to a specific etiology. Microvascular sclerosis was frequent and did not correlate with a single distinct clinical feature.

The neuro-protective role of telomerase via TERT/TERF-2 in the acute phase of spinal cord injury.

To investigate the interaction of telomerase activity and telomere length on neuro-protection or neuro-degeneration effects after spinal cord injury (SCI). A contusive SCI model was developed using 56 Sprague-Dawley rats. Seven rats were allocated into acute injury phase groups (1, 3, 8, 24, and 48h), and sub-acute and chronic injury phase groups (1, 2, and 4weeks). Telomerase activity was assessed by telomerase reverse transcriptase (TERT) and telomeric repeat binding factor-2 (TERF-2). Differentiation of activated neural stem cells was investigated by co-expression of neuronal/glial cell markers. Apoptosis expression was also investigated by caspase-3, 8, and 9 using terminal deoxynucleotidyl transferase dUTP nick end labelling staining. Immunofluorescence staining and western blotting were performed for quantitative analyses. Expression of TERT increased gradually until 24h post-injury, and was decreased following SCI (P < 0.05). TERF-2 also was increased following SCI until 24h post-injury and then decreased with time (P < 0.05). Co-localization of TERT and TERF-2 was higher at 24h post-injury. High expression of TERT was seen in neurons (Neu N Ab), however, expression of TERT was relatively lower in astrocytes and oligodendrocytes. Apoptosis analysis showed persistent high expression of caspases-3, -9, and -8 during the observation period. Increased TERT and TERF-2 activity were noted 24h post-injury in the acute phase of SCI with TERF-2 maintaining telomeric-repeat length. Our results suggest that increased activity of telomere maintenance may be related to neuro-protective mechanisms against subsequent apoptosis resulting from DNA damage after acute SCI.

Untreated Moderate-to-Severe Sleep-Related Breathing Disorders Are Associated with Increased Frequency of Episodes of Autonomic Dysreflexia during Sleep in Individuals with Subacute or Chronic Spinal Cord Injury: A Prospective Cross-Sectional Study. (P1-13.002)

<h3>Objective:</h3> This ongoing cross-sectional study is focused on the potential association between moderate-to-severe sleep-related breathing disorders (SRBDs) and more severe cardiovascular dysfunction following spinal cord injury (SCI). <h3>Background:</h3> Sleep-related breathing disorders (SRBDs) are common and under-recognized among individuals living with spinal cord injury (SCI). SRBDs can affect the sympathetic response, but the impact of untreated SRBDs on cardiovascular autonomic function after SCI remains incompletely understood. <h3>Design/Methods:</h3> This cross-sectional study included adults with subacute/chronic (≥1 month after SCI onset), cervical or high-thoracic (T6 or above) SCI. The diagnosis of SRBD was established using a home-based/hospital unattended sleep screening test that quantifies the apnea-hypopnea index (AHI). Moderate-to-severe SRBD was defined as an AHI ≥ 15 events per hour. Episodes of autonomic dysreflexia (AD) were defined as a sudden increase in systolic blood pressure (BP) ≥ 20 mmHg. <h3>Results:</h3> This study included 45 individuals (14 females, 31 males with ages from 20 to 84 years; mean age: 57.0 years) with motor complete (n=22) or incomplete (n=24) SCI at cervical (n=38), or high thoracic levels. Time from SCI onset varied from 1.5 months to 52 years (mean time: 49.4 months). Mean AHI was 16.0 events per hour (AHI range: 0.8–51.7). The AHI was not associated with systolic BP (mean+/−SEM: 122.0+/−2.2 mmHg; p=0.903), diastolic BP (72.6+/−3.0 mmHg; p=0.639), mean arterial pressure (90.1+/−2.4 mmHg; p=0.714), and heart rate (70.6+/−1.4 bpm; p=0.669) during sleep. However, the AHI was significantly, positively correlated with the number of silent episodes of AD (mean +/− SEM: 3.6+/−0.4; Rsqr=0.220, p=0.001) during sleep, after excluding other causes of AD. <h3>Conclusions:</h3> The results of this cross-sectional study suggest that more severe SBRBs are associated with frequent silent episodes of AD during sleep among individuals with SCI. Future research is needed to assess the effects of continuous positive airway pressure (CPAP) therapy on cardiovascular dysfunction following SCI. <b>Disclosure:</b> The institution of Dr. Furlan has received research support from Wings for Life Spinal Cord Research Foundation. The institution of Dr. Furlan has received research support from Craig H Neilsen Foundation. The institution of Dr. Furlan has received research support from Ontario Neurotrauma Foundation. The institution of Dr. Furlan has received research support from Cervical Spine Research Society. The institution of Dr. Furlan has received research support from J P Bickell Foundation. The institution of Dr. Furlan has received research support from Praxis Spinal Cord Institute. The institution of Dr. Furlan has received research support from Cervical Spine Research Society. Dr. Loh has stock in Dara3D. Dr. Boulos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Jazz Pharmaceuticals. Dr. Boulos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Paladin Labs. Dr. Boulos has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Eisai. Dr. Boulos has received research support from Interaxon. The institution of Dr. Boulos has received research support from The Mahaffy Family Research Fund. The institution of Dr. Boulos has received research support from Canadian Institutes of Health Research. The institution of Dr. Boulos has received research support from Slamen-Fast New Initiatives in Neurology Award. The institution of Dr. Boulos has received research support from Green Mountain . Dr. Boulos has received personal compensation in the range of $5,000-$9,999 for serving as a speaker with Jazz Pharmaceuticals.

The effect of offline anosognosia for hemispatial neglect on neglect rehabilitation in patients with subacute and chronic right hemispheric brain injury. A retrospective cohort study

ABSTRACT We investigated the effects of offline anosognosia for hemispatial neglect on neglect severity, functional ability, mobility, and motor recovery in left hemispatial neglect (HN) patients with right hemisphere injury. Eighty-five patients were included in this retrospective study. All patients had undergone a routine neglect rehabilitation programme. Neglect and anosognosia severities were determined by the Catherine Bergego Scale. Functional Independence Measure (FIM) scores, Functional Ambulation Classification (FAC) levels, and Brunnstrom motor recovery stages were noted. The prevalence of anosognosia for HN was 81.2% (69 of 85 patients). Neglect and neglect anosognosia severities were strongly correlated (r = 0.85, p < 0.001). Patients with anosognosia had more severe hemispatial neglect. There was no difference in median FIM score between those with and without anosognosia. The severity of anosognosia negatively correlated with FIM and FAC scores. Linear mixed model analysis revealed a significant decrease in neglect scores in patients with anosognosia than in those without. Anosognosia severity also decreased through rehabilitation and the decrease in anosognosia significantly predicted neglect improvement. Our study emphasizes that neglect anosognosia is related to severe hemispatial neglect, poor functional ability, and limited mobility. Addressing neglect anosognosia may be a valuable component of neglect rehabilitation. Clinical Trials Registration Number NCT05145855.

Protective effect of Lactiplantibacillus pentosus CQZC01 in Kunming mice of subacute alcoholic liver injury.

To decrease the climbing rate of alcoholic liver disease, the protective effect in subacute alcoholic liver injury of newly isolated Lactiplantibacillus pentosus CQZC01 has been investigated. Lactiplantibacillus pentosus CQZC01 (1 × 109 CFU/kgbw) administered orally could keep weight of mice at 30.54±1.15g; alleviate alcoholic damage on hepatic morphology; decrease the activities of hyaluronidase (147±19U/L), procollagen III (4.82±0.54ng/mL), alanine transaminase (10.66±2.32U/L), and aspartate aminotransferase (15.18±1.98U/L); enhance the activities of alcohol dehydrogenase (65.15±3.2 U/mgprot), aldehyde dehydrogenase (16.50±0.96 U/mgprot), superoxide dismutase (623±39 U/mgprot), and glutathione (19.54±2.46µmol/gprot); and decrease liver total cholesterol (3.59±0.50mmol/gprot) and triglyceride (0.88±0.24mmol/gprot) (p<0.05). Moreover, L. pentosus CQZC01 elevated the level of interleukin-10 (IL-10; 807±44 pg/mL) but significantly decreased the levels of IL-1β (29.75±5.27pg/mL), IL-6 (58±8 pg/mL), and tumor necrosis factor-α (TNF-α, 564±13 pg/mL). Liver malondialdehyde was also significantly decreased by treatment with L. pentosus CQZC01 from 3.61±0.14 to 2.03±0.49nmol/mgprot. The relative expression of C-Jun N-terminal kinase, extracellular regulated protein kinases, and cyclooxygenase-1 was downregulated, and the SOD1, SOD2, peroxisome proliferator-activated receptor-α, glutathione peroxidase, catalase, nuclear factor erythroid-2-related factor 2, heme oxygenase-1 and nicotinamide adenine dinucleotide phosphate were upregulated by L. pentosus CQZC01. The overall protective effect of L. pentosus CQZC01 was comparable to commercial Lactobacillus delbrueckii subsp. Bulgaricus. Lactobacillus pentosus CQZC01 might be a suitable hepatoprotective measure for people who frequently ingest alcoholic drinks. PRACTICAL APPLICATION: L. pentosus CQZC01 can alleviate subacute alcoholic liver injury by raising the antioxidant status and upregulating the antioxidant-related genes.

Blueberry and cranberry extracts mitigate CCL4-induced liver damage, suppressing liver fibrosis, inflammation and oxidative stress

The current study aims to evaluate potential hepatoprotective effect of lingonberry, cranberry and blueberry polyphenols on carbon tetrachloride (CCL-4)-induced acute and subacute liver injury in rats. A total of 55 male Wistar rats, divided into six experimental and control groups. With the exception of the negative control group, all groups received an intraperitoneal injection of CCl-4, twice a week for 14 days. An extract of lingonberry, cranberry, blueberry polyphenols and the positive control, silymarin were administered daily via intragastric route, for 14 consecutive days. The untreated control group showed characteristic of classical oxidative stress-mediated liver damage with vacuolization of the hepatocyte cytoplasm, infiltration by immune cells and proliferation of collagen fibers, decrease in body weight and increase in liver weight; increased levels of AST and ALT in serum, an increased lipid peroxidation in the liver. However, the use of cranberry and blueberry polyphenols significantly suppressed liver damage, exerting an effect comparable to the hepatoprotective effect of the positive control. The extracts prevented and reduced inflammatory liver damage by reducing IL-6, TNF-α and IFN-γ levels. In conclusion, blueberry and cranberry extracts have a protective effect against acute and subacute CCl4-induced hepatotoxicity in rats.

Interleukin-4 mitigates anxiety-like behavior and loss of neurons and fiber tracts in limbic structures in a microglial PPARγ-dependent manner after traumatic brain injury

Traumatic brain injury (TBI) is commonly followed by intractable psychiatric disorders and long-term changes in affect, such as anxiety. The present study sought to investigate the effect of repetitive intranasal delivery of interleukin-4 (IL-4) nanoparticles on affective symptoms after TBI in mice. Adult male C57BL/6 J mice (10–12 weeks of age) were subjected to controlled cortical impact (CCI) and assessed by a battery of neurobehavioral tests up to 35 days after CCI. Neuron numbers were counted in multiple limbic structures, and the integrity of limbic white matter tracts was evaluated using ex vivo diffusion tensor imaging (DTI). As STAT6 is a critical mediator of IL-4-specific transcriptional activation, STAT6 knockout mice were used to explore the role of endogenous IL-4/STAT6 signaling axis in TBI-induced affective disorders. We also employed microglia/macrophage (Mi/Mϕ)-specific PPARγ conditional knockout (mKO) mice to test if Mi/Mϕ PPARγ critically contributes to IL-4-afforded beneficial effects. We observed anxiety-like behaviors up to 35 days after CCI, and these measures were exacerbated in STAT6 KO mice but mitigated by repetitive IL-4 delivery. We discovered that IL-4 protected against neuronal loss in limbic structures, such as the hippocampus and the amygdala, and improved the structural integrity of fiber tracts connecting the hippocampus and amygdala. We also observed that IL-4 boosted a beneficial Mi/Mϕ phenotype (CD206+/Arginase 1+/PPARγ+ triple-positive) in the subacute injury phase, and that the numbers of Mi/Mϕ appositions with neurons were robustly correlated with long-term behavioral performances. Remarkably, PPARγ-mKO completely abolished IL-4-afforded protection. Thus, CCI induces long-term anxiety-like behaviors in mice, but these changes in affect can be attenuated by transnasal IL-4 delivery. IL-4 prevents the long-term loss of neuronal somata and fiber tracts in key limbic structures, perhaps due to a shift in Mi/Mϕ phenotype. Exogenous IL-4 therefore holds promise for future clinical management of mood disturbances following TBI.

Allogenic bone marrow-derived mesenchymal stem cells and its conditioned media for repairing acute and sub-acute peripheral nerve injuries in a rabbit model

The present study evaluated healing potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) and BM-MSCs-conditioned medium (BM-MSCs-CM) for acute and subacute injuries in the rabbit peripheral nerve injury model. The regenerative capacity of MSCs was evaluated in 40 rabbits divided into eight groups, four groups each for acute and subacute injury models. BM-MSCs and BM-MSCS-CM were prepared by isolating allogenic bone marrow from the iliac crest. After inducing sciatic nerve crush injury, different treatments consisting of PBS, Laminin, BM-MSCs + laminin, and BM-MSCS-CM + laminin were used on the day of injury in the acute injury model and after ten days of crush injury in the subacute groups. The parameters studied included: pain, total neurological score, gastrocnemius muscle weight and volume ratio, histopathology of the sciatic nerve and gastrocnemius muscle, and scanning electron microscopy (SEM). Findings indicate that BM-MSCs and BM-MSCS-CM have augmented the regenerative capacity in acute and subacute injury groups with a slightly better improvement in the subacute groups than the animals in acute injury groups. Histopathology data revealed different levels of regenerative process undergoing in the nerve. Neurological observations, gastrocnemius muscle evaluation, muscle histopathology, and the SEM results depicted better healing in animals treated with BM-MSCs and BM-MSCS-CM. With this data, it could be concluded that BM-MSCs support the healing of injured peripheral nerves, and the BM-MSCS-CM does accelerate the healing of acute and subacute peripheral nerve injuries in rabbits. However, stem cell therapy may be indicated during the subacute phase for better results.

Potential Antifibrotic Effect of Blueberry and Grape Polyphenol Extracts in Acute and Subacute Bleomycin-Induced Lung Tissue Injury Models in Mice

An experimental morphological and morphometric study of the antifibrotic function of blueberry and grape extracts was carried out on a model of lung injury in mice induced by intraperitoneal administration of bleomycin. During intraperitoneal administration of bleomycin to mice, acute and subacute damage to the pulmonary system was noted. Both patterns had the same prevalence and severity. The administration of polyphenolic extracts of blueberry and grape to mice showed a significant reduction in the severity of the acute and subacute pattern of lung injury. Blueberry and grape extracts reduce the acute phase of damage to the microvasculature, enhance phagocytic function, have an anti-inflammatory effect, reducing the degree of lymphohistiocytic infiltration and locoregional foci of residual inflammatory effects.

Subacute and Chronic Spinal Cord Injury: A Scoping Review of Epigenetics and Secondary Health Conditions.

Epigenetics studies the impact of environmental and behavioral factors on stable phenotypic changes; however, the state of the science examining epigenomic mechanisms of regulation related to secondary health conditions (SHCs) and neuroepigenetics in chronic spinal cord injury (SCI) remain markedly underdeveloped. This scoping review seeks to understand the state of the science in epigenetics and secondary complications following SCI. A literature search was conducted, yielding 277 articles. The inclusion criteria were articles (1) investigating SCI and (2) examining epigenetic regulation as part of the study methodology. A total of 23 articles were selected for final inclusion. Of the 23 articles 52% focused on histone modification, while 26% focused on DNA methylation. One study had a human sample, while the majority sampled rats and mice. Primarily, studies examined regeneration, with only one study looking at clinically relevant SHC, such as neuropathic pain. The findings of this scoping review offer exciting insights into epigenetic and neuroepigenetic application in SCI research. Several key genes, proteins, and pathways emerged across studies, suggesting the critical role of epigenetic regulation in biological processes. This review reinforced the dearth of studies that leverage epigenetic methods to identify prognostic biomarkers in SHCs. Preclinical models of SCI were genotypically and phenotypically similar, which is not reflective of the heterogeneity found in the clinical population of persons with SCI. There is a need to develop better preclinical models and more studies that examine the role of genomics and epigenomics in understanding the diverse health outcomes associated with traumatic SCI.

A case of subacute renal injury with myxoedema coma treated with hemodialysis and successfully weaned from dialysis with thyroid hormone replacement

A case of subacute renal injury with myxoedema coma treated with hemodialysis and successfully weaned from dialysis with thyroid hormone replacement

The Efficacy of Hyperbaric Oxygen Therapy in Traumatic Brain Injury Patients: Literature Review and Clinical Guidelines

Introduction: The application of hyperbaric oxygen therapy for patients with both acute and chronic traumatic brain injury has been suggested for over five decades. In the past decade, the design and quality of studies were more detailed and thorough leading to an improved unerstanding of the uses of HBOT and the profiles of the patients who can benefit the most. Objectives: Perform a comprehensive literature review of hyperbaric oxygen therapy application for the treatment of patients with both acute, subacute and chronic traumatic brain injury. Methods: Extensive literature search from 1969 to April 2023 was performed on April 1st 2023 within the following databases: Cochrane Library, PubMed, Google Scholar, and Web of Science, including humans clinical data, in articles providing information on the type of treatment and clinical outcomes. Articles were first categorized into acute-subacute traumatic brain inury and chronic traumatic brain injury and further classified into low, medium or high level quality. Results: There was high level evidence including nine randomized controlled trials, one meta-analysis and two prospective study evaluating the clinical effects of hyperbaric oxygen therapy in patients suffering from traumatic brain injuries in the acute and subacute settings. Mortality was significantly reduced in all studies that used it as an endpoint, while favorable functional outcomes in survivors showed mixed results. In chronic severe traumatic brain injury, there is low to moderate evidence including two uncontrolled prospective studies, two cohort studies and eight case reports suggesting improved outcomes. In chronic mild traumatic brain injury, there is high level evidence including seven randomized controlled trials, and six prospective studies suggesting significant improvement in cognitive function, symptoms and quality of life. Conclusions: Hyperbaric oxygen therapy may be recommended in acute moderate-severe traumatic brain injury patients (Type 2a recommendation, level A evidence). However, further studies are needed to both evaluate outcomes and to determine the optimal treatment protocols for the different types of injuries (Type 1 recommendation, level A evidence). Hyperbaric oxygen threrapy should be recommended in chronic traumatic brain injury for a selected group of patients suffering from prolonged post-concussion syndrome who have clear evidence of metabolic dysfunctional brain regions as determined by neuroimaging (Type 2a recommendation, level B-R evidence). Patients should be properly evaluated by standardized cognitive tests and functional brain imaging (Type 1 recommendation, level B-R evidence).

A Missed Pediatric Achilles Tendon Rupture with a Large Gap Managed with Surgical Reconstruction with Allograft: A Case Report.

A 15-year-old adolescent girl presented with a complete Achilles tendon rupture from playing netball, which was diagnosed 6 weeks later. Unfortunately, there was a significant deficit of 92 mm, and an allograft reconstruction was required to bridge the gap. Achilles tendon ruptures are rare in children and adolescents without a penetrating injury, but the diagnosis must not be missed. Achilles tendon ruptures should be considered in children with acute-onset ankle pain during running, jumping, or sudden dorsiflexion of the ankle. Tendon transfers and allograft may be required after rupture and retraction has occurred in subacute or chronic injuries.

Functional connectivity and amplitude of low-frequency fluctuations changes in people with complete subacute and chronic spinal cord injury

After spinal cord injury (SCI), reorganization processes and changes in brain connectivity occur. Besides the sensorimotor cortex, the subcortical areas are strongly involved in motion and executive control. This exploratory study focusses on the cerebellum and vermis. Resting-state functional magnetic resonance imaging (fMRI) was performed. Between-group differences were computed using analysis of covariance and post-hoc tests for the seed-based connectivity measure with vermis and cerebellum as regions of interest. Twenty participants with complete SCI (five subacute SCI, 15 with chronic SCI) and 14 healthy controls (HC) were included. Functional connectivity (FC) was lower in all subjects with SCI compared with HC in vermis IX, right superior frontal gyrus (pFDR = 0.008) and right lateral occipital cortex (pFDR = 0.036). In addition, functional connectivity was lower in participants with chronic SCI compared with subacute SCI in bilateral cerebellar crus I, left precentral- and middle frontal gyrus (pFDR = 0.001). Furthermore, higher amplitude of low-frequency fluctuations (ALFF) was found in the left thalamus in individuals with subacute SCI (pFDR = 0.002). Reduced FC in SCI indicates adaptation with associated deficit in sensory and motor function. The increased ALFF in subacute SCI might reflect reorganization processes in the subacute phase.

Radial Collateral Ligament Injuries of the Thumb Metacarpophalangeal Joint.

Injuries to the radial collateral ligament (RCL) of the thumb are thought to be relatively uncommon, especially when compared to the ulnar collateral ligament. However, the radial collateral ligament is increasingly recognized as critical for the overall stability of the thumb metacarpophalangeal joint. This article sets out to provide a comprehensive review of RCL injuries of the thumb MCP joint, including epidemiology, biomechanics, diagnosis, and treatment. Although traditionally thought to respond well to conservative management, especially when compared to injuries to the ulnar collateral ligament, there is mounting evidence that chronic RCL injury leads to thumb metacarpophalangeal joint instability and can accelerate post-traumatic joint degeneration. Thus, much of the recent literature details surgical treatment options for radial collateral ligament injury, including repair and reconstruction. While incomplete tears of the thumb RCL respond well to immobilization, complete tears should generally be treated with operative management, either direct repair or anatomic reconstruction, depending on tissue quality. Even subacute and chronic injuries may be amenable to direct repair, with good to excellent outcomes, including in high-demand patient populations, such as professional athletes.

Outcome of using the spinal accessory nerve for functional muscle innervation in facial paralysis reconstruction: The first two cases in Vietnam and literature review

Abstract Facial nerve injuries with various causes, such as after trauma, tumor dissection, radiotherapy, etc., resulting the patient's functional, aesthetic, and psychological sequelae. For many decades, plastic surgeons have introduced numerous different nerve sources to overcome the above sequelae, such as contralateral facial nerve, the hypoglosal nerve, the masseter nerve, and the spinal accessory nerve (CN XI). There were various advantages and disadvantages of donor nerves sources. However, the use of ipsilateral donor nerve is said to have many benefits. In this report, we would like to present preliminary results of using the CN XI source in treatment of subacute and chronic VII nerve injury. These were the first two cases of successful surgery using this nerve source in Vietnam. Keywords: Facial nerve injury, facial paralysis, nerve transfer, spinal accessory nerve.

Assessment of behavioral, neuroinflammatory, and histological responses in a model of rat repetitive mild fluid percussion injury at 2 weeks post-injury.

Repetitive mild traumatic brain injury (rmTBI) is a prominent public health concern, with linkage to debilitating chronic sequelae. Developing reliable and well-characterized preclinical models of rmTBI is imperative in the investigation of the underlying pathophysiological mechanisms, as models can have varying parameters, affecting the overall pathology of the resulting injury. The lateral fluid percussion injury (FPI) model is a reliable and frequently used method of TBI replication in rodent subjects, though it is currently relatively underutilized in rmTBI research. In this study, we have performed a novel description of a variation of the lateral repetitive mild FPI (rmFPI) model, showing the graded acute behavioral impairment and histopathology occurring in response to one, two or four mild FPI (1.25 atm) or sham surgeries, implemented 24h apart. Beam walking performance revealed significant motor impairment in injured animals, with dysfunction increasing with additional injury. Based upon behavioral responses and histological observations, we further investigated the subacute pathophysiological outcomes of the dual FPI (dFPI). Immunoreactivity assessments showed that dFPI led to regionally-specific reductions in the post-synaptic protein neurogranin and increased subcortical white matter staining of the presynaptic protein synaptophysin at 2 weeks following dFPI. Immunohistochemical assessments of the microglial marker Iba-1 showed a striking increase in in several brain regions, and assessment of the astrocytic marker GFAP showed significantly increased immunoreactivity in the subcortical white matter and thalamus. With this study, we have provided a novel account of the subacute post injury outcomes occurring in response to a rmFPI utilizing these injury and frequency parameters, and thereby also demonstrating the reliability of the lateral FPI model in rmTBI replication.