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Neural Regeneration Research May 2024Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic...
Traumatic spinal cord injury is potentially catastrophic and can lead to permanent disability or even death. China has the largest population of patients with traumatic spinal cord injury. Previous studies of traumatic spinal cord injury in China have mostly been regional in scope; national-level studies have been rare. To the best of our knowledge, no national-level study of treatment status and economic burden has been performed. This retrospective study aimed to examine the epidemiological and clinical features, treatment status, and economic burden of traumatic spinal cord injury in China at the national level. We included 13,465 traumatic spinal cord injury patients who were injured between January 2013 and December 2018 and treated in 30 hospitals in 11 provinces/municipalities representing all geographical divisions of China. Patient epidemiological and clinical features, treatment status, and total and daily costs were recorded. Trends in the percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department and cost of care were assessed by annual percentage change using the Joinpoint Regression Program. The percentage of traumatic spinal cord injuries among all hospitalized patients and among patients hospitalized in the orthopedic department did not significantly change overall (annual percentage change, -0.5% and 2.1%, respectively). A total of 10,053 (74.7%) patients underwent surgery. Only 2.8% of patients who underwent surgery did so within 24 hours of injury. A total of 2005 (14.9%) patients were treated with high-dose (≥ 500 mg) methylprednisolone sodium succinate/methylprednisolone (MPSS/MP); 615 (4.6%) received it within 8 hours. The total cost for acute traumatic spinal cord injury decreased over the study period (-4.7%), while daily cost did not significantly change (1.0% increase). Our findings indicate that public health initiatives should aim at improving hospitals' ability to complete early surgery within 24 hours, which is associated with improved sensorimotor recovery, increasing the awareness rate of clinical guidelines related to high-dose MPSS/MP to reduce the use of the treatment with insufficient evidence.
PubMed: 37862218
DOI: 10.4103/1673-5374.382257 -
Frontiers in Immunology 2023To report the case of a patient with refractory neuromyelitis optica spectrum disorder (NMOSD), who, despite showing poor response or intolerance to multiple...
OBJECTIVE
To report the case of a patient with refractory neuromyelitis optica spectrum disorder (NMOSD), who, despite showing poor response or intolerance to multiple immunosuppressants, was successfully treated with Ofatumumab.
CASE PRESENTATION
A 42-year-old female was diagnosed with NMOSD in the first episode of the disease. Despite treatment with intravenous methylprednisolone, immunoglobulin, rituximab and immunoadsorption, together with oral steroids, azathioprine, mycophenolate mofetil and tacrolimus, she underwent various adverse events, such as abnormal liver function, repeated infections, fever, rashes, hemorrhagic shock, etc., and experienced five relapses over the ensuing four years. Finally, clinicians decided to initiate Ofatumumab to control the disease. The patient received 9 doses of Ofatumumab over the next 10 months at customized intervals. Her symptoms were stable and there was no recurrence or any adverse events.
CONCLUSION
Ofatumumab might serve as an effective and safe alternative for NMOSD patients who are resistant to other current immunotherapies.
Topics: Humans; Female; Adult; Neuromyelitis Optica; Treatment Outcome; Immunosuppressive Agents; Azathioprine
PubMed: 37449206
DOI: 10.3389/fimmu.2023.1208017 -
Medicina (Kaunas, Lithuania) Feb 2024IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage...
IgA nephropathy (IgAN) represents the most prevalent form of primary glomerulonephritis, and, on a global scale, it ranks among the leading culprits behind end-stage kidney disease (ESKD). Presently, the primary strategy for managing IgAN revolves around optimizing blood pressure and mitigating proteinuria. This is achieved through the utilization of renin-angiotensin system (RAS) inhibitors, namely, angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs). As outlined by the KDIGO guidelines, individuals who continue to show a persistent high risk of progressive ESKD, even with comprehensive supportive care, are candidates for glucocorticoid therapy. Despite these therapies, some patients have a disease refractory to treatment, defined as individuals that present a 24 h urinary protein persistently >1 g after at least two rounds of regular steroids (methylprednisolone or prednisone) and/or immunosuppressant therapy (e.g., mycophenolate mofetil), or who do not tolerate regular steroids and/or immunosuppressant therapy. The aim of this Systematic Review is to revise the current literature, using the biomedical database PubMed, to investigate possible therapeutic strategies, including SGLT2 inhibitors, endothelin receptor blockers, targeted-release budesonide, B cell proliferation and differentiation inhibitors, fecal microbiota transplantation, as well as blockade of complement components.
Topics: Humans; Angiotensin-Converting Enzyme Inhibitors; Glomerulonephritis, IGA; Angiotensin Receptor Antagonists; Nephrologists; Antihypertensive Agents; Kidney Failure, Chronic; Steroids; Immunosuppressive Agents
PubMed: 38399561
DOI: 10.3390/medicina60020274 -
Scientific Reports Oct 2023Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted,...
Whilst the presence of 2 subphenotypes among the heterogenous Acute Respiratory Distress Syndrome (ARDS) population is becoming clinically accepted, subphenotype-specific treatment efficacy has yet to be prospectively tested. We investigated anti-inflammatory treatment in different ARDS models in sheep, previously shown similarities to human ARDS subphenotypes, in a preclinical, randomized, blinded study. Thirty anesthetized sheep were studied up to 48 h and randomized into: (a) OA: oleic acid (n = 15) and (b) OA-LPS: oleic acid and subsequent lipopolysaccharide (n = 15) to achieve a PaO/FiO ratio of < 150 mmHg. Then, animals were randomly allocated to receive treatment with methylprednisolone or erythromycin or none. Assessed outcomes were oxygenation, pulmonary mechanics, hemodynamics and survival. All animals reached ARDS. Treatment with methylprednisolone, but not erythromycin, provided the highest therapeutic benefit in Ph2 animals, leading to a significant increase in PaO/FiO ratio by reducing pulmonary edema, dead space ventilation and shunt fraction. Animals treated with methylprednisolone displayed a higher survival up to 48 h than all others. In animals treated with erythromycin, there was no treatment benefit regarding assessed physiological parameters and survival in both phenotypes. Treatment with methylprednisolone improves oxygenation and survival, more so in ovine phenotype 2 which resembles the human hyperinflammatory subphenotype.
Topics: Animals; Anti-Inflammatory Agents; Erythromycin; Methylprednisolone; Oleic Acid; Respiration; Respiratory Distress Syndrome; Sheep; Random Allocation; Disease Models, Animal
PubMed: 37863994
DOI: 10.1038/s41598-023-45081-8 -
Annals of the Rheumatic Diseases Jan 2024Secukinumab is monoclonal antibody that targets interleukin 17 (IL-17) for treatment of psoriatic arthritis, psoriasis, and ankylosing spondylitis. We herein present a...
Secukinumab is monoclonal antibody that targets interleukin 17 (IL-17) for treatment of psoriatic arthritis, psoriasis, and ankylosing spondylitis. We herein present a psoriatic arthritis patient who developed leukocytoclastic vasculitis (LCV) following treatment with secukinumab. Genetic studies identified amino acid changes in two different IL-17 receptors, IL-17RA and IL-17-RC, and interacting DOCK8, Rab27A, and STX1 proteins. LCV completely resolved after withdrawal of the drug, transient treatment with dapsone and methylprednisolone, and switching to long-term therapy to IL-23 inhibitor tildrakizumab. This case reveals potential molecular bases of disease pathogenesis, intolerance of IL-17 blockade, and responsiveness to IL-23 inhibition in psoriatic arthritis.
Topics: Humans; Arthritis, Psoriatic; Interleukin-17; Antibodies, Monoclonal, Humanized; Vasculitis, Leukocytoclastic, Cutaneous; Interleukin-23; Psoriasis
PubMed: 37679036
DOI: 10.1136/ard-2023-224604 -
Life (Basel, Switzerland) Dec 2023Sarcoidosis is a chronic granulomatous disease of unknown cause characterized by the presence of non-caseating granulomas. The disease can affect any organ including the... (Review)
Review
Sarcoidosis is a chronic granulomatous disease of unknown cause characterized by the presence of non-caseating granulomas. The disease can affect any organ including the nervous system. Neurosarcoidosis occurs in about 5% patients with sarcoidosis. The clinical presentation of neurosarcoidosis is varied, and it can involve the brain, spinal cord and peripheral nervous system, separately or in different combinations. The diagnosis of neurosarcoidosis is challenging, as biopsies from the nervous system are not readily available. Anti-TNFα agents are becoming one of the cornerstone treatments for neurosarcoidosis. In this case-based review, we discuss two cases of neurosarcoidosis with different clinical presentations. The first patient presented with confusion, while the second presented with walking difficulty and neurogenic bladder. Both patients were treated with methylprednisolone pulse therapy with rapid, but non-complete, improvement. Therefore, infliximab was initiated in both cases with subsequent improvement in the clinical manifestations and imaging findings, emphasizing the effectiveness and safety of infliximab in cases of severe neurosarcoidosis. In conclusion, the goal of neurosarcoidosis management is to prevent organ system damage and minimize the toxic cumulative adverse effects of glucocorticoid use. In this case-based review we discuss the various presentations, the diagnosis and the treatment of neurosarcoidosis.
PubMed: 38255684
DOI: 10.3390/life14010069 -
Journal of Orthopaedic Surgery and... Dec 2023Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and...
Exosomes from bone marrow mesenchymal stem cells ameliorate glucocorticoid-induced osteonecrosis of femoral head by transferring microRNA-210 into bone microvascular endothelial cells.
OBJECTIVES
Bone microvascular endothelial cells (BMECs) played an important role in the pathogenesis of glucocorticoid-induced osteonecrosis of femoral head (GCS-ONFH), and exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) may provide an effective treatment. This study aimed to evaluate the effects of BMSC-Exos and internal microRNA-210-3p (miRNA-210) on GCS-ONFH in an in vitro hydrocortisone-induced BMECs injury model and an in vivo rat GCS-ONFH model.
METHODS
BMECs, BMSCs and BMSC-Exos were isolated and validated. BMECs after the treatment of hydrocortisone were cocultured with different concentrations of BMSC-Exos, then proliferation, migration, apoptosis and angiogenesis of BMECs were evaluated by CCK-8, Annexin V-FITC/PI, cell scratch and tube formation assays. BMSCs were transfected with miRNA-210 mimics and miRNA-210 inhibitors, then BMSC-Exos and BMSC-Exos secreted from such cells were collected. The differences between BMSC-Exos, BMSC-Exos and BMSC-Exos in protecting BMECs against GCS treatment were analyzed by methods mentioned above. Intramuscular injections of methylprednisolone were performed on Sprague-Dawley rats to establish an animal model of GCS-ONFH, then tail intravenous injections of BMSC-Exos, BMSC-Exos or BMSC-Exos were conducted after methylprednisolone injection. Histological and immunofluorescence staining and micro-CT were performed to evaluate the effects of BMSC-Exos and internal miRNA-210 on the in vivo GCS-ONFH model.
RESULTS
Different concentrations of BMSC-Exos, especially high concentration of BMSC-Exos, could enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs treated with GCS. Compared with BMSC-Exos, BMSC-Exos could further enhance the proliferation, migration and angiogenesis ability and reduce the apoptosis rates of BMECs, while BMECs in the GCS + BMSC-Exos group showed reduced proliferation, migration and angiogenesis ability and higher apoptosis rates. In the rat GCS-ONFH model, BMSC-Exos, especially BMSC-Exos, could increase microvascular density and enhance bone remodeling of femoral heads.
CONCLUSIONS
BMSC-Exos containing miRNA-210 could serve as potential therapeutics for protecting BMECs and ameliorating the progression of GCS-ONFH.
Topics: Rats; Animals; Glucocorticoids; Endothelial Cells; Femur Head; Exosomes; Hydrocortisone; Rats, Sprague-Dawley; Osteonecrosis; Mesenchymal Stem Cells; Methylprednisolone; MicroRNAs
PubMed: 38062514
DOI: 10.1186/s13018-023-04440-x -
Frontiers in Pediatrics 2023This study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki... (Review)
Review
BACKGROUND
This study aimed to gather evidence from clinical trials on the efficacy and safety of the available treatments for intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) in children.
METHODS
This work adopted the Newcastle-Ottawa scale to analyse the quality of the enrolled articles. A network meta-analysis was performed using clinical trials that compared drugs used to treat IVIG-resistant KD. Aggregate Data Drug Information System software v.1.16.5 was employed to analyse whether infliximab, second IVIG infusions, and intravenous pulse methylprednisolone (IVMP) were safe and effective.
RESULTS
Ten studies, involving 704 patients with IVIG-resistant KD, were identified and analysed. Overall, infliximab exhibited remarkable antipyretic activity compared with the second IVIG infusions (2.46, 1.00-6.94). According to the drug rank, infliximab was the best option against IVIG-resistant KD. Regarding adverse effects, the infliximab group was more prone to hepatomegaly. A second IVIG infusion was more likely to result in haemolytic anaemia. IVMP treatment was more susceptible to bradycardia, hyperglycaemia, hypertension, and hypothermia. In addition, infliximab, IVMP, and the second IVIG infusions showed no significant differences in the risk of developing a coronary artery aneurysm (CAA).
CONCLUSION
Infliximab was the best option against IVIG-resistant KD, and IVMP, infliximab, and second IVIG infusions have not significant differences of prevent CAA in patients with IVIG-resistant KD.
SYSTEMATIC REVIEW REGISTRATION
Identifier: https://osf.io/3894y.
PubMed: 37520059
DOI: 10.3389/fped.2023.1149519 -
Cureus Nov 2023Immune checkpoint inhibitors (ICIs) have considerably changed the management of several malignancies. Although these agents transformed the scope of management in...
Immune checkpoint inhibitors (ICIs) have considerably changed the management of several malignancies. Although these agents transformed the scope of management in oncology and proved long-term efficacy, they have been associated with numerous autoimmune-related adverse events. We presented a case of a 61-year-old male with a history of non-small cell lung cancer (NSCLC) who presented with respiratory failure requiring mechanical ventilation. He was discharged with a working diagnosis of myasthenia gravis crisis secondary to the use of pembrolizumab. On further evaluation, he was found to possibly have pembrolizumab-induced myositis. He was treated with plasmapheresis, methylprednisolone, and rituximab and achieved significant improvement. Pembrolizumab, a monoclonal antibody, is an ICI that targets programmed death protein 1 (PD-1), thereby blocking the interaction between PD-1 and PDL-1, leading to an enhancement of T-cell mediated immune response against tumor cells. Pembrolizumab has been used to treat a variety of malignancies including melanoma, NSCLC, and other solid tumors. Though ICIs have revolutionized the field of oncology, they should be used with caution. ICIs can cause immune-related adverse events (irAEs), including myasthenia gravis and myositis. Diagnosing irAEs is challenging due to their nonspecific presentations and lack of antibody markers. Therefore, patients and clinicians should be aware of irAEs in order to initiate timely intervention.
PubMed: 38111441
DOI: 10.7759/cureus.49007 -
Clinical Medicine (London, England) Jul 2023We present a case where a 63-year-old right-handed man who presented with a 6-month history of progressive asymmetrical sensorimotor symptoms in lower limbs. This was...
We present a case where a 63-year-old right-handed man who presented with a 6-month history of progressive asymmetrical sensorimotor symptoms in lower limbs. This was associated with concomitant rash on the lower limbs, and mild sicca symptoms. MRI spine showed focal T2 hyperintensity in the left hemicord at C3-4 level. Skin biopsy of the rash revealed urticarial vasculitis, and lip biopsy revealed lymphocytic sialadenitis. Initial anti-Ro antibody was negative, but subsequent Ro52 antibody testing returned positive. There was also matched serum and cerebrospinal fluid oligoclonal bands. He was subsequently diagnosed as Sjogren's myelitis and treated with intravenous methylprednisolone, then transitioned to a steroid sparing agent. This case highlights the difficulties in reaching a rheumatological diagnosis in the early stages with typical negative antibodies, and shows a rare neurological manifestation of a systemic rheumatological condition.
Topics: Male; Humans; Middle Aged; Sjogren's Syndrome; Brown-Sequard Syndrome; Myelitis; Magnetic Resonance Imaging; Exanthema
PubMed: 37524434
DOI: 10.7861/clinmed.2023-0158