Long-term survival following molecular-targeted therapy for intramedullary non-small-cell lung cancer metastasis.

Background: Intramedullary spinal cord metastases (ICSMs) are very rarely curable; these patients typically have very short-term survival rates. Here, a 22-year-old male with non-small-cell lung cancer (NSCLC) later developed ICSM twice; the first C4-C7 tumor responded well to surgery, radiation, and alectinib molecular-targeted therapy. The secondary ICSM C1 lesion seen years later (i.e., likely due to alectinib having been stopped) resolved once alectinib was again administered. Case Description: A 22-year-old male with a limited smoking history presented with advanced non-small-cell lung cancer (NSCLC) treated with pulmonary surgery followed by radiotherapy and chemotherapy. Four years later, he developed cervical myelopathy attributed to a C4-C7 stage IV NSCLC ICSM (i.e., notably associated with an anaplastic lymphoma kinase [ALK] rearrangement). After cervical surgery and irradiation (40 Gy/20 fr) of the resection cavity, he was also given alectinib; the patient remained disease-free for the next 7 years, remaining on alectinib. However, 1 year after alectinib was discontinued, he experienced a newly occurrent C1 ICSM lesion; the alectinib was restarted, and his tumor regressed over the next 3 years. At present, 14 years after the original ICSM surgery, the patient remains disease free but continued alectinib (Karnofsky Performance Scale: 90%). Conclusion: Although the prognosis for ICSM is generally poor, molecular-targeted therapies, such as alectinib, as administered in this case, may provide long-term survival for patients with ALK-positive NSCLC tumors.

Humanized-Aquaporin-4-Expressing Rat Created by Gene-Editing Technology and Its Use to Clarify the Pathology of Neuromyelitis Optica Spectrum Disorder.

Conventional rodent neuromyelitis optica spectrum disorder (NMOSD) models using patient-derived immunoglobulin G (IgG) are potentially affected by the differences between the human and rodent aquaporin-4 (AQP4) extracellular domains (ECDs). We hypothesized that the humanization of AQP4 ECDs would make the rodent model lesions closer to human NMOSD pathology. Humanized-AQP4-expressing (hAQP4) rats were generated using genome-editing technology, and the human AQP4-specific monoclonal antibody (mAb) or six patient-derived IgGs were introduced intraperitoneally into hAQP4 rats and wild-type Lewis (WT) rats after immunization with myelin basic protein and complete Freund's adjuvant. Human AQP4-specific mAb induced astrocyte loss lesions specifically in hAQP4 rats. The patient-derived IgGs also induced NMOSD-like tissue-destructive lesions with AQP4 loss, demyelination, axonal swelling, complement deposition, and marked neutrophil and macrophage/microglia infiltration in hAQP4 rats; however, the difference in AQP4 loss lesion size and infiltrating cells was not significant between hAQP4 and WT rats. The patient-derived IgGs bound to both human and rat AQP4 M23, suggesting their binding to the shared region of human and rat AQP4 ECDs. Anti-AQP4 titers positively correlated with AQP4 loss lesion size and neutrophil and macrophage/microglia infiltration. Considering that patient-derived IgGs vary in binding sites and affinities and some of them may not bind to rodent AQP4, our hAQP4 rat is expected to reproduce NMOSD-like pathology more accurately than WT rats.

Prevertebral Soft-tissue Swelling Following One-level Anterior Cervical Discectomy and Fusion: An Analysis Based on Surgical Level.

BACKGROUND: The purposes of this study were to identify the primary level at which PSTS occurs following one level anterior cervical discectomy and fusion (ACDF) based on surgical level, and to quantify the degree to which it occurs. Although prevertebral tissue swelling (PSTS) peaks at day 2 or 3 after ACDF, with swelling noted to be prominent at levels C2-4, the way in which the features of PSTS vary according to surgical level has not been examined. METHODS: 37 patients who underwent one-level ACDF were reviewed and classified into retropharyngeal and retrotracheal group based on surgical level. PSTS occurring at C2-C6 and the width of airway (WA) at C2-C4 was assessed using plain radiographs before surgery and at 1, 3, 5, and 7 days postoperatively. RESULTS: The retropharyngeal group comprised 10 patients while the retrotracheal group comprised 27 patients. Retropharyngeal group had the most severe PSTS on day 3 after surgery. C4 showed PSTS peaked on day 3, with a value of 3.26 times the preoperative prevertebral tissue thickness. WA at C4 was narrowest on day 1, with a value of 0.74 times and remained narrow until day 3. The retrotracheal group showed the most severe PSTS on day 1 at level C3:2.81 times. WA at C4 was narrowest on day 1 with a value of 0.78 times and increased thereafter. CONCLUSIONS: PSTS following one-level ACDF for both retropharyngeal and retrotracheal lesions was greatest at the C3 and C4 levels, with peaks on the third day after operation for the former, and the first day for the latter. WA at C4 was narrowest from day 1 in both groups. In the retrophyaryngeal group, narrowing remained until day 3.

Platelet lysate does not have an anti-inflammatory effect on monoiodoacetic acid-induced equine persistent synovitis.

OBJECTIVE: To clarify the anti-inflammatory effect of platelet lysate (PL) on equine persistent synovitis by using a model of synovitis induced by monoiodoacetic acid (MIA). METHODS: Nonseptic synovitis was induced by administering MIA into both antebrachiocarpal joints of 6 clinically healthy horses on day 0. On days 23, 30, and 37, carpal circumference measurement and synovial fluid collection for assays (leucocytes, LDH, tumor necrosis factor-α, and TGF-ß1) were performed, after which PL was injected into 1 antebrachiocarpal joint and saline into the contralateral joint. Synovium and synovial fluid were obtained on day 44 for histological analysis and quantification of inflammation-related genes (matrix metalloproteinase-13, a disintegrin and metalloproteinase with thrombospondin motifs 4, receptor activator of nuclear factor κ-Β ligand, and collagen type I α2 chain) and the abovementioned proteins. RESULTS: The LDH level on day 44 was significantly lower in the PL-injected joint than in the saline-treated one. However, no significant differences were found in the other indices quantified, including osteoclast counts on the synovium. CONCLUSIONS: Multiple IA administration of PL does not exert anti-inflammatory effects on the equine persistent synovitis induced by MIA. CLINICAL RELEVANCE: Intra-articular PL administration did not alter many inflammatory biomarkers, suggesting that PL does not have a direct anti-inflammatory effect. However, the reduction in synovial LDH levels suggests that PL promoted joint tissue repair and may consequently alleviate inflammation at the site of administration.

Different Complement Activation Patterns Following C5 Cleavage in MOGAD and AQP4-IgG+NMOSD.

OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.

State-of-the-Art and New Treatment Approaches for Spinal Cord Tumors.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

[Basic MRI Study in the Imaging Direction of a Diffusion-weighted Whole Body Imaging with Background Body Signal Suppression].

A diffusion-weighted whole body imaging with background body signal suppression (DWIBS) is usually imaged as a whole body with Transverse (Tra). However, Tra has a large number of stations and a larger number than Coronal (Cor), so the scan time is longer. There are also drawbacks, such as signal unevenness between series. It is known that the effect of distortion is large in Cor. There is no report on it in Sagittal (Sag). Therefore, in this study, we focused on Sag and examined the imaging time, image distortion, fat suppression effect, and continuity between stations. In the examination by the phantom, the scan time was the shortest for Cor and the longest for Sag. In the strain evaluation, the effect of strain could be suppressed compared to Cor by using a rectangle field of view (FOV) in the anterior to posterior (AP) direction in Tra and Sag. There was no difference in the fat suppression effect depending on the imaging direction. Similar results were obtained in a study of 10 healthy volunteers, with Sag having the best continuity between stations.

Changes in muscle activation with graded surfaces during canter in Thoroughbred horses on a treadmill.

Understanding how muscle activity changes with different surface grades during canter is essential for developing training protocols in Thoroughbreds because canter is their primary gait in training and races. We measured the spatiotemporal parameters and the activation of 12 surface muscles in the leading limb side of 7 Thoroughbreds. Horses were equipped with hoof strain gauges and cantered at 10 m/s on a treadmill set to grades of -4%, 0%, 4%, and 8%, randomly, for 30 seconds each without a lead change. Integrated electromyography (iEMG) values during stance and swing phases were calculated and normalized to mean iEMG values during stride duration at 0% grade in each muscle. The iEMG values at each grade were compared using a generalized mixed model. Stride duration significantly decreased due to shorter swing duration on an 8% grade (P < 0.001) compared to all other grades, where no significant changes were observed. Compared to a 0% grade, the normalized iEMG values during the stance phase on an 8% grade in five muscles significantly increased (Musculus infraspinatus; +9%, M. longissimus dorsi (LD); +4%, M. gluteus medius (GM); +29%, M. biceps femoris; +47%, M. flexor digitorum lateralis; +16%). During the swing phase, the normalized iEMG values in six muscles significantly increased on an 8% grade compared to a 0% grade (M. splenius; +21%, M. triceps brachii; +54%, LD; +37%, GM; +24%, M. semitendinosus; +51%, M. extensor digitorum longus; +10%). No significant changes were observed in iEMG values on -4% and 4% grades compared to the 0% grade. Although +/- 4% grades had little effect on neuromuscular responses, 8% uphill canter reduced stride duration due to decreased swing duration and required increase of muscle activation during either stance and swing phase. Canter on an 8% grade might strengthen equine muscles to increase propulsive force and stride frequency.

Prognostic Factors Associated with Poor Treatment Outcomes After Balloon Kyphoplasty in Elderly Patients Aged ≥81 years.

OBJECTIVE: Balloon kyphoplasty (BKP) is an effective procedure for osteoporotic vertebral compression fractures; however, there is limited data regarding its outcomes in patients aged ≥81 years. This study investigated the treatment outcomes and prognostic factors for BKP in this age group. METHODS: A retrospective analysis was conducted on 115 patients with osteoporotic vertebral compression fracture undergoing single-level BKP after failed conservative treatment, classified into the <81 years (n=70) and ≥81 years (n=45) groups. Surgical results were evaluated as good outcomes (independent indoors 1 year postoperatively) and poor outcomes, followed by univariate and multivariate analyses to determine prognostic factors correlating with these outcomes. RESULTS AND CONCLUSION: The majority of patients (<81 years: 85.7%; ≥81 years: 73.3%) had a good degree of independence at 1 year postoperatively, which was comparable in both groups. Further analysis of patients aged ≥81 years showed that longer duration from onset to surgery, more subsequent vertebral fractures, and lower preoperative body mass index were correlated with poorer outcomes postoperatively, and low body mass index, time from onset to surgery, and female sex were independent risk factors for these outcomes (area under the receiver operating characteristics curve: 0.91).

Acute cervical epidural abscess with concurrent calcium pyrophosphate deposition after cervical spinal surgery: A case report.

Background: Spinal epidural abscess (SEA) is a rare condition that may result in catastrophic outcomes. On the other hand, calcium pyrophosphate (CPP) deposition disease (CPPD) causes inflammatory arthritis. Spinal involvement of a crystal-induced inflammation caused by CPPD is also common. Surgery is a common risk factor for both SEA and CPPD; however, the postoperative acute onset of SEA complicated with CPPD is extremely rare. Case Description: A man in his 70s presented to our hospital, complaining of right upper limb weakness, loss of dexterity, and gait disturbance. The diagnosis of cervical spondylotic myelopathy was made, and he performed laminectomy at C3, C4, and C5 levels. Four days after the laminectomy, he suffered from acute neck pain, weakness, and hypoesthesia in his arms and legs. Magnetic resonance imaging revealed a mass occupying the dorsal epidural space of C6 and C7, compressing the cervical spinal cord. Considering the acute symptomatology, an acute spinal epidural hematoma after surgery was suspected; therefore, emergency C6 and C7 laminectomy was performed. Surgical findings indicated that the pressure inside the spinal canal was elevated, and the mass was purulent exudate. Pathological examination showed suppurative inflammation with concomitant deposition of CPP. SEA complicated with CPPD was considered; therefore, antibiotics and non-steroidal anti-inflammatory drugs were administered. The motor weakness and hypoesthesia were improved despite a slight residual deficit in his dexterity. Conclusion: An acute onset of SEA complicated with CPPD after cervical surgery has rarely been reported. The suppurative inflammation fostered by the crystal-induced inflammation may account for the acute symptomatology.

Evaluation of Steroid Pulse Therapy Responsiveness in Myelin-Oligodendrocyte Glycoprotein Antibody-Positive Optic Neuritis.

PURPOSE: Myelin-oligodendrocyte glycoprotein antibody-positive optic neuritis (MOGON) is usually responsive to the steroid, but, for some patients, steroid pulse therapy alone may be inadequate. This study aimed to investigate the factors predicting the response to steroid pulse therapy in MOGON. METHODS: This study included 17 patients (24 eyes) with MOGON, who received single steroid pulse therapy as initial treatment. Best corrected visual acuity (BCVA) and mean deviation (MD) values after treatment were examined concerning findings at onset. RESULTS: No correlation was found between BCVA at onset and after treatment, but a correlation was observed between MD values at onset and after treatment (correlation coefficient 0.48, p=0.01, Spearman's rank correlation coefficient). Age, gender, duration from onset to treatment, magnetic resonance imaging findings, and optical coherence tomography findings did not affect visual function after treatment. CONCLUSIONS: Severe visual field impairment at onset may indicate that additional treatment may be necessary.

Stochastic models for the onset and disease course of multiple sclerosis.

OBJECTIVE: Exact causes and mechanisms regulating the onset and progression in many chronic diseases, including multiple sclerosis (MS), remain uncertain. Until now, the potential role of random process based on stochastic models in the temporal course of chronic diseases remains largely unevaluated. Therefore, the present study investigated the applicability of stochastic models for the onset and disease course of MS. METHODS: Stochastic models with random temporal process in disease activity, underlying clinical relapse and/or subclinical brain atrophy, were developed. The models incorporated parameters regarding the distribution of temporal changes in disease activity and the drift constant. RESULTS: By adjusting the parameters (temporal change dispersion and drift constant) and the threshold for the onset of disease, the stochastic disease progression models could reproduce various types of subsequent disease course, such as clinically isolated syndrome (monophasic), relapsing-remitting MS, primary-progressive MS, and secondary-progressive MS. Furthermore, the disease prevalence and distribution of onset age could be also reproduced with stochastic models by adjusting the parameters. The models could further explain why approximately half of the patients with relapsing-remitting MS will eventually experience a transition to secondary-progressive MS. CONCLUSION: Stochastic models with random temporal changes in disease activity could reproduce the characteristic onset age distribution and disease course forms in MS. Further studies by using real-world data to underscore the significance of random process in the occurrence and progression of MS are warranted.

Relationship between Treatment Choices according to the Modified Osteoporotic Fracture Score and Posttreatment Radiographic Outcomes.

STUDY DESIGN: Retrospective observational study. PURPOSE: To evaluate the modified osteoporotic fracture (mOF) scores in three treatment groups and compare imaging findings in patients treated and not treated according to the mOF score-based treatment recommendation. OVERVIEW OF LITERATURE: The osteoporotic fracture (OF) score was established by the AO Spine to guide therapeutic decisions. To enhance its applicability, a mOF score was recently introduced. METHODS: Consecutive patients diagnosed with OFs at Fujieda Heisei Memorial Hospital were divided into three groups: nonsurgical therapy, balloon kyphoplasty (BKP), and open surgery groups. The mOF score was calculated, and the levels of independence and posttreatment imaging data were compared between patients treated and not treated according to the mOF score-based treatment recommendation. RESULTS: In total, 118 patients were included (nonsurgical therapy, n=57; BKP, n=48; open surgery, n=13), of whom 100 (85%) received treatment consistent with the mOF score-based treatment recommendation. In the BKP and open surgery groups, the mOF scorebased treatment recommendations were consistent with the actual treatment in 93% of the patients. However, in the nonsurgical group, the mOF score-based treatment recommendation was not consistent with the actual treatment in 25% of the patients. In this group, patients not treated according to the mOF score had significantly shorter vertebral body height, greater local kyphosis, and smaller sacral slope after treatment than patients treated according to the mOF score-based treatment recommendation. CONCLUSIONS: In the BKP and open surgery groups, the mOF scores were consistent with actual clinical selection. In the nonsurgical therapy group, patients not treated according to the mOF score-based treatment recommendation exhibited severe vertebral body deformity and a less well-balanced spine shape after treatment. The mOF score may help in selecting suitable treatments for OFs.

Clinical Features and Prognostic Factors in Anti-Myelin Oligodendrocyte Glycoprotein Antibody Positive Optic Neuritis.

In order to review the clinical features of anti-myelin oligodendrocyte glycoprotein antibody positive optic neuritis (MOGON), we investigated the clinical characteristics, visual function, optical coherence tomography findings, and magnetic resonance imaging of 31 patients (44 eyes). MOGON was more common in middle age without sex difference and was characterised by pain on eye movement and optic disc swelling. Magnetic resonance imaging lesions tended to be long with inflammation around the optic nerve sheath; longer lesions were associated with worse visual acuities at onset. Recurrence was significantly associated with retinal nerve fibre layer thinning, and thus, it is important to reduce recurrence as much as possible.

The Effectiveness of Tritanium Cages in Preventing Osteolytic Vertebral Endplate Cysts After Lumbar Interbody Fusion.

OBJECTIVE: Lumbar interbody fusion (LIF) is a common surgical procedure, but postoperative complications, such as osteolytic vertebral endplate cysts, can adversely affect patient outcomes. This study aims to investigate whether tritanium cages (Stryker, Mahwah, New Jersey, USA) are effective in preventing osteolytic vertebral endplate cysts after LIF. METHODS: Clinical data from 8 years (2013-2020) of LIF procedures at our hospital were analyzed. Computed tomography was used to assess the formation of osteolytic vertebral endplate cysts 6 months after surgery. Clinical factors potentially associated with cyst formation were compared among 3 different interbody spacer materials: tritanium, titanium, and polyetheretherketone. RESULTS: LIF was performed for 169 patients at 205 spinal levels, employing tritanium cages in 56 levels (48 patients), titanium in 103 levels (86 patients), and polyetheretherketone in 46 levels (35 patients). At 6 months after LIF, 27.3% of patients showed worsening of osteolytic vertebral endplate cysts. Multivariate logistic regression analysis showed that tritanium cages (odds ratio [OR], 3.86; 95% confidence interval [CI], 1.46-10.21) and titanium (OR, 2.55; 95% CI, 1.13-5.75), and posterior LIF (OR, 5.74; 95% CI, 2.24-14.74) were associated with a reduced risk of postoperative osteolytic vertebral endplate cysts. CONCLUSIONS: Tritanium cages have shown promise in preventing postoperative osteolytic vertebral endplate cysts, suggesting their potential as a stable and effective choice in LIF procedures. These findings have significant implications for improving patient outcomes and warrant further investigation to optimize surgical techniques and materials.

Clinical Features of 544 Patients With Ruptured Aortic Aneurysm　- A Report From the Tokyo Acute Aortic Super Network Database.

BACKGROUND: Epidemiological data on ruptured aortic aneurysms from large-scale studies are scarce. The aims of this study were to: clarify the clinical course of ruptured aortic aneurysms; identify aneurysm site-specific therapies and outcomes; and determine the clinical course of patients receiving conservative therapy. METHODS AND RESULTS: Using the Tokyo Acute Aortic Super Network database, we retrospectively analyzed 544 patients (mean [±SD] age 78±10 years; 70% male) with ruptured non-dissecting aortic aneurysms (AAs) after excluding those with impending rupture. Patient characteristics, status on admission, therapeutic strategy, and outcomes were evaluated. Shock or pulselessness on admission were observed in 45% of all patients. Conservative therapy, endovascular therapy (EVT), and open surgery (OS) accounted for 32%, 23%, and 42% of cases, respectively, with corresponding mortality rates of 93%, 30%, and 29%. The overall in-hospital mortality rate was 50%. The prevalence of pulselessness was highest (48%) in the ruptured ascending AA group, and in-hospital mortality was the highest (70%) in the ruptured thoracoabdominal AA group. Multivariable logistic regression analysis indicated in-hospital mortality was positively associated with pulselessness (odds ratio [OR] 10.12; 95% confidence interval [CI] 4.09-25.07), and negatively associated with invasive therapy (EVT and OS; OR 0.11; 95% CI 0.06-0.20). CONCLUSIONS: The outcomes of ruptured AAs remain poor; emergency invasive therapy is essential to save lives, although it remains challenging to reduce the risk of death.