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1.
J Orthop Sci ; 2024 May 16.
Article in English | MEDLINE | ID: mdl-38760247

ABSTRACT

BACKGROUND: The purpose of this study was to determine the effects of high tibial osteotomy (HTO) on varus thrust during gait in patients with medial compartment knee osteoarthritis (KOA), and to identify factors that influence thrust before and one year after surgery. METHODS: HTO was performed in 60 KOA patients (70 knees, including 56 knees by open wedge and 14 by closed wedge). The control group comprised 28 normal, control subjects. Several parameters were evaluated before surgery and one year thereafter. Varus thrust was defined as acceleration of the thigh relative to the lower leg in the coronal plane. Knee-injury-and-osteoarthritis-outcome scores (KOOSs), knee joint angles, radiography, and mediolateral knee acceleration during free speed gait were measured and analyzed. RESULTS: One-year after HTO, KOOSs, knee extension angles, and range of knee motion were improved (p < 0.001). The hip-knee-ankle angle and joint-line-convergent angle (JLCA) had decreased (p < 0.001), and walking speed had increased (p < 0.001). Preoperatively, patient acceleration was significantly (p < 0.05) higher than that of controls, and it did not change after HTO. However, it was reduced significantly (p < 0.05) after adjusting for walking speed. Walking speed correlated significantly with acceleration preoperatively, postoperatively, and among controls. Surgical methods (open-wedge/closed-wedge HTO) and correction angle did not affect postoperative acceleration. There was a low correlation between acceleration and KOOSs (KOOSa, KOOSp), knee joint angles, or JLCA postoperatively, but no relationship was found between acceleration and these parameters in the preoperative or the control group. CONCLUSIONS: Walking speed correlated significantly with acceleration preoperatively, postoperatively, and with those of controls. Mediolateral acceleration of the thigh relative to the lower leg in patients with KOA was significantly higher than that of normal controls before surgery, and it did not change after HTO. However, after surgery it was reduced significantly after adjusting for walking speed.

2.
Sci Rep ; 14(1): 9145, 2024 04 21.
Article in English | MEDLINE | ID: mdl-38644389

ABSTRACT

Adjacent segment degeneration (ASD) is a major postoperative complication associated with posterior lumbar interbody fusion (PLIF). Early-onset ASD may differ pathologically from late-onset ASD. The aim of this study was to identify risk factors for early-onset ASD at the cranial segment occurring within 2 years after surgery. A retrospective study was performed for 170 patients with L4 degenerative spondylolisthesis who underwent one-segment PLIF. Of these patients, 20.6% had early-onset ASD at L3-4. In multivariate logistic regression analysis, preoperative larger % slip, vertebral bone marrow edema at the cranial segment on preoperative MRI (odds ratio 16.8), and surgical disc space distraction (cut-off 4.0 mm) were significant independent risk factors for early-onset ASD. Patients with preoperative imaging findings of bone marrow edema at the cranial segment had a 57.1% rate of early-onset ASD. A vacuum phenomenon and/or concomitant decompression at the cranial segment, the degree of surgical reduction of slippage, and lumbosacral spinal alignment were not risk factors for early-onset ASD. The need for fusion surgery requires careful consideration if vertebral bone marrow edema at the cranial segment adjacent to the fusion segment is detected on preoperative MRI, due to the negative impact of this edema on the incidence of early-onset ASD.


Subject(s)
Lumbar Vertebrae , Magnetic Resonance Imaging , Postoperative Complications , Spinal Fusion , Spondylolisthesis , Humans , Spinal Fusion/adverse effects , Spinal Fusion/methods , Male , Female , Risk Factors , Lumbar Vertebrae/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/pathology , Middle Aged , Aged , Retrospective Studies , Postoperative Complications/etiology , Spondylolisthesis/surgery , Spondylolisthesis/diagnostic imaging , Intervertebral Disc Degeneration/surgery , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/etiology , Adult
3.
J Clin Med ; 12(21)2023 Oct 27.
Article in English | MEDLINE | ID: mdl-37959260

ABSTRACT

The incidence of cervical spinal cord injury (CSCI) without major bone injury is increasing, possibly because older people typically have pre-existing cervical spinal canal stenosis. The demographics, neurological injury, treatment, and prognosis of this type of CSCI differ from those of CSCI with bone or central cord injury. Spine surgeons worldwide are debating on the optimal management of CSCI without major bone injury. Therefore, this narrative review aimed to address unresolved clinical questions related to CSCI without major bone injury and discuss treatment strategies based on current findings. The greatest divide among spine surgeons worldwide hinges on whether surgery is necessary for patients with CSCI without major bone injury. Certain studies have recommended early surgery within 24 h after injury; however, evidence regarding its superiority over conservative treatment remains limited. Delayed MRI may be beneficial; nevertheless, reliable factors and imaging findings that predict functional prognosis during the acute phase and ascertain the necessity of surgery should be identified to determine whether surgery/early surgery is better than conservative therapy/delayed surgery. Quality-of-life assessments, including neuropathic pain, spasticity, manual dexterity, and motor function, should be performed to examine the superiority of surgery/early surgery to conservative therapy/delayed surgery.

4.
Biosci Biotechnol Biochem ; 87(9): 981-990, 2023 Aug 23.
Article in English | MEDLINE | ID: mdl-37280168

ABSTRACT

The trisaccharide 1-kestose, a major constituent of fructooligosaccharide, has strong prebiotic effects. We used high-performance liquid chromatography and 1H nuclear magnetic resonance spectroscopy to show that BiBftA, a ß-fructosyltransferase belonging to glycoside hydrolase family 68, from Beijerinckia indica subsp. indica catalyzes transfructosylation of sucrose to produce mostly 1-kestose and levan polysaccharides. We substituted His395 and Phe473 in BiBftA with Arg and Tyr, respectively, and analyzed the reactions of the mutant enzymes with 180 g/L sucrose. The ratio of the molar concentrations of glucose and 1-kestose in the reaction mixture with wild-type BiBftA was 100:8.1, whereas that in the reaction mixture with the variant H395R/F473Y was 100:45.5, indicating that H395R/F473Y predominantly accumulated 1-kestose from sucrose. The X-ray crystal structure of H395R/F473Y suggests that its catalytic pocket is unfavorable for binding of sucrose while favorable for transfructosylation.


Subject(s)
Bacterial Proteins , Hexosyltransferases , Hexosyltransferases/genetics , Hexosyltransferases/metabolism , Sucrose/metabolism
5.
Cells ; 12(11)2023 05 25.
Article in English | MEDLINE | ID: mdl-37296591

ABSTRACT

Mesenchymal stromal cell transplantation alone is insufficient when motor dysfunction is severe; combination therapy with rehabilitation could improve motor function. Here, we aimed to analyze the characteristics of adipose-derived MSCs (AD-MSCs) and determine their effectiveness in severe spinal cord injury (SCI) treatment. A severe SCI model was created and motor function were compared. The rats were divided into AD-MSC-transplanted treadmill exercise-combined (AD-Ex), AD-MSC-transplanted non-exercise (AD-noEx), PBS-injected exercise (PBS-Ex), and no PBS-injected exercise (PBS-noEx) groups. In cultured cell experiments, AD-MSCs were subjected to oxidative stress, and the effects on the extracellular secretion of AD-MSCs were investigated using multiplex flow cytometry. We assessed angiogenesis and macrophage accumulation in the acute phase. Spinal cavity or scar size and axonal preservation were assessed histologically in the subacute phase. Significant motor function improvement was observed in the AD-Ex group. Vascular endothelial growth factor and C-C motif chemokine 2 expression in AD-MSC culture supernatants increased under oxidative stress. Enhanced angiogenesis and decreased macrophage accumulation were observed at 2 weeks post-transplantation, whereas spinal cord cavity or scar size and axonal preservation were observed at 4 weeks. Overall, AD-MSC transplantation combined with treadmill exercise training improved motor function in severe SCI. AD-MSC transplantation promoted angiogenesis and neuroprotection.


Subject(s)
Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Spinal Cord Injuries , Rats , Animals , Neuroprotection , Cicatrix/pathology , Vascular Endothelial Growth Factor A , Spinal Cord Injuries/pathology , Mesenchymal Stem Cells/metabolism
6.
Spine Surg Relat Res ; 6(6): 610-616, 2022 Nov 27.
Article in English | MEDLINE | ID: mdl-36561169

ABSTRACT

Introduction: The number of patients with degenerative cervical myelopathy (DCM) requiring surgical treatment has markedly increased in today's aging society. Such patients often exhibit impaired activities of daily living because of motor dysfunction as well as neuropathic pain (NeP). Although many studies have demonstrated the safety and efficacy of surgical treatment for DCM, residual postoperative NeP has not been well described. Therefore, this study aimed to identify the predictors of postoperative NeP improvement in patients with DCM. Methods: This retrospective study included 92 outpatients with postoperative chronic NeP (≥3 months) related to DCM. Data were obtained from clinical information, magnetic resonance imaging (MRI) findings, and patient-based questionnaires using the Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients. Univariate and multivariate analyses were performed for patients with NPSI improvement rates <30% and ≥30% to identify prognostic factors. Results: Among 92 patients, 61 (66.3%) had residual NeP, with a low improvement rate even after surgery. The independent negative prognostic factors for NeP improvement after surgery were older age at operation (odds ratio (OR): 0.932), longer symptom duration before surgery (OR: 0.589), and higher preoperative NPSI score (OR: 0.932). The cut-off value of symptom duration before surgery for postoperative NeP improvement was 1 year. By contrast, the preoperative Japanese Orthopaedic Association score and MRI findings, including signal intensity change and the degree of spinal cord compression, were not associated with postoperative NeP improvement. Moreover, even in patients with an NPSI improvement rate ≥30%, the NPSI subscores for deep pain and paresthesia/dysesthesia remained high. Conclusions: Discrepancies between physician- and image-based assessments and patient-based assessments were identified as factors associated with improvement in postoperative NeP. Our findings are important for both spine surgeons and patients to manage patient expectations with respect to recovery during the postoperative course.

7.
Sci Rep ; 12(1): 19439, 2022 11 14.
Article in English | MEDLINE | ID: mdl-36376360

ABSTRACT

Extensive surgical spinopelvic fusion for patients with adult spinal deformity (ASD) to achieve optimal radiological parameters should be avoided. The aim of this study was to review clinical and imaging findings in patients with ASD with postural and radiological abnormalities who underwent a novel three-level limited lumbar fusion as two-stage surgery in an attempt to propose a better tolerated alternative to spinopelvic long fusion to the pelvis. The subjects were 26 patients with a minimum follow-up period of 2 years. Cobb angle, C7 sagittal vertical axis, and pelvic incidence (PI) minus lumbar lordosis (LL) were significantly improved after surgery and maintained at follow-up. Most radiological parameters were corrected with lateral interbody fusion (LIF) as the initial surgery, and few with posterior fusion. PI-LL remained high after limited lumbar fusion, but scores on patient-based questionnaires and sagittal and coronal tilt in gait analysis improved. In cases with postoperative progression of proximal junctional kyphosis (11.5%), residual L1-L2 local kyphosis after LIF was the most significant radiological feature. In some cases of ASD with postural abnormalities, short limited lumbar fusion gives sufficient postoperative clinical improvement with preservation of spinal mobility and activities of daily living. The range of fixation should be determined based on radiological parameters after LIF to avoid postoperative complications.


Subject(s)
Kyphosis , Lordosis , Spinal Fusion , Humans , Adult , Animals , Spinal Fusion/methods , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Activities of Daily Living , Retrospective Studies , Treatment Outcome , Lordosis/diagnostic imaging , Lordosis/surgery , Lordosis/etiology , Kyphosis/diagnostic imaging , Kyphosis/surgery , Kyphosis/complications
8.
Sci Rep ; 12(1): 7192, 2022 05 03.
Article in English | MEDLINE | ID: mdl-35504949

ABSTRACT

Existing guidelines advocate an updated therapeutic algorithm for chronic neuropathic pain (NeP), but pharmacotherapeutic management should be individualized to pain phenotypes to achieve higher efficacy. This study was aimed to evaluate the efficacy of medications, based on NeP phenotypes, and to propose symptom-based pharmacotherapy. This retrospective study was enrolled 265 outpatients with chronic NeP related to spinal disorders. The patients were classified into three groups: spinal cord-related pain, radicular pain, and cauda equina syndrome. Data were obtained from patient-based questionnaires using Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients, and from clinical information. The proportions of patients with ≥ 30% and ≥ 50% reduction in NPSI score for each pain subtype (spontaneous pain, paroxysmal pain, evoked pain, and paresthesia/dysesthesia) and drugs were evaluated. The pain reduction rate was significantly lower in patients with spinal cord-related pain, especially for paresthesia/dysesthesia. For spinal cord-related pain, duloxetine and neurotropin had insufficient analgesic effects, whereas mirogabalin was the most effective. Pregabalin or mirogabalin for radicular pain and duloxetine for cauda equina syndrome are recommended in cases of insufficient analgesic effects with neurotropin. The findings could contribute to better strategies for symptom-based pharmacotherapeutic management.


Subject(s)
Cauda Equina Syndrome , Musculoskeletal Pain , Neuralgia , Spinal Diseases , Analgesics/therapeutic use , Duloxetine Hydrochloride , Humans , Musculoskeletal Pain/drug therapy , Neuralgia/diagnosis , Neuralgia/drug therapy , Neuralgia/etiology , Pain Measurement , Paresthesia , Retrospective Studies
9.
Appl Microbiol Biotechnol ; 106(7): 2455-2470, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35267055

ABSTRACT

Fructooligosaccharide is a mixture of mostly the trisaccharide 1-kestose (GF2), tetrasaccharide nystose (GF3), and fructosyl nystose (GF4). Enzymes that hydrolyze GF3 may be useful for preparing GF2 from the fructooligosaccharide mixture. A ß-fructofuranosidase belonging to glycoside hydrolase family 32 (GH32) from the honeybee gut bacterium Frischella perrara (FperFFase) was expressed in Escherichia coli and purified. The time course of the hydrolysis of 60 mM sucrose, GF2, and GF3 by FperFFase was analyzed, showing that the hydrolytic activity of FperFFase for trisaccharide GF2 was lower than those for disaccharide sucrose and tetrasaccharide GF3. The crystal structure of FperFFase and its structure in complex with fructose were determined. FperFFase was found to be structurally homologous to bifidobacterial ß-fructofuranosidases even though bifidobacterial enzymes preferably hydrolyze GF2 and the amino acid residues interacting with fructose at subsite - 1 are mostly conserved between them. A proline residue was inserted between Asp298 and Ser299 using site-directed mutagenesis, and the activity of the variant 298P299 was measured. The ratio of activities for 60 mM GF2/GF3 by wild-type FperFFase was 35.5%, while that of 298P299 was 23.6%, indicating that the structure of the loop comprising Trp297-Asp298-Ser299 correlated with the substrate preference of FperFFase. The crystal structure also shows that a loop consisting of residues 117-127 is likely to contribute to the substrate binding of FperFFase. The results obtained herein suggest that FperFFase is potentially useful for the manufacture of GF2. KEY POINTS: • Frischella ß-fructofuranosidase hydrolyzed nystose more efficiently than 1-kestose. • Trp297-Asp298-Ser299 was shown to be correlated with the substrate preference. • Loop consisting of residues 117-127 appears to contribute to the substrate binding.


Subject(s)
Oligosaccharides , beta-Fructofuranosidase , Animals , Bees , Fructose , Gammaproteobacteria , Oligosaccharides/metabolism , Sucrose , Trisaccharides/metabolism , beta-Fructofuranosidase/metabolism
10.
J Orthop Sci ; 27(6): 1222-1227, 2022 Nov.
Article in English | MEDLINE | ID: mdl-34702669

ABSTRACT

BACKGROUND: Symptom-based therapeutic management is required for neuropathic pain (NeP) to achieve higher treatment efficacy. In spinal disorders, which have a high prevalence of NeP, neurological symptoms are classified into myelopathy, radiculopathy, and cauda equina syndrome. The characteristics of pain and the treatment efficacy for each of these symptoms require clarification. METHODS: A retrospective patient-based outcome study was conducted in 265 outpatients with chronic NeP (≥3 months) related to spinal disorders. The patients were classified into three groups according to their neurological symptoms: spinal cord-related pain, radicular pain, and cauda equina syndrome. Data were obtained from patient-based questionnaires using the Neuropathic Pain Symptom Inventory (NPSI) and the Brief Scale for Psychiatric Problems in Orthopaedic Patients (BS-POP), and from clinical information. RESULTS: Most of the patients with NeP had a NPSI score >10 (moderate to severe pain) and 40% had psychiatric problems. The common subtype of NeP was spontaneous pain and paresthesia/dysesthesia in patients with radicular pain and cauda equina syndrome, whereas more severe paresthesia/dysesthesia was particularly prominent in patients with spinal cord-related pain. The pain reduction rate was significantly lower in these latter patients, especially in association with residual paresthesia/dysesthesia. CONCLUSIONS: The characteristics and treatment efficacy of NeP in patients with spinal disorders varied according to neurological symptoms. Effective treatment was difficult, especially for paresthesia/dysesthesia in patients with spinal cord-related pain. These findings enhance the understanding of the underlying mechanisms of pain and could help in design of symptom-based therapeutic management.


Subject(s)
Cauda Equina Syndrome , Neuralgia , Spinal Diseases , Humans , Paresthesia , Pain Measurement , Retrospective Studies , Neuralgia/diagnosis , Neuralgia/etiology , Neuralgia/therapy , Treatment Outcome
11.
J Neurosurg Spine ; 36(3): 392-398, 2022 Mar 01.
Article in English | MEDLINE | ID: mdl-34653984

ABSTRACT

OBJECTIVE: The development of diffuse idiopathic skeletal hyperostosis (DISH) often requires further surgery after posterior decompression without fusion because of postoperative intervertebral instability. However, there is no information on whether fusion surgery is recommended for these patients as the standard surgery. The aim of this study was to review the clinical and imaging findings in lumbar spinal canal stenosis (LSS) patients with DISH affecting the lumbar segment (L-DISH) and to assess the indication for fusion surgery in patients with DISH. METHODS: A total of 237 patients with LSS underwent 1- or 2-level posterior lumbar interbody fusion (PLIF) at the authors' hospital and had a minimum follow-up period of 2 years. Patients with L-DISH were classified as such (n = 27, 11.4%), whereas those without were classified as controls (non-L-DISH; n = 210, 88.6%). The success rates of short-level PLIF were compared in patients with and those without L-DISH. The rates of adjacent segment disease (ASD), pseudarthrosis, postoperative symptoms, and revision surgery were examined in the two groups. RESULTS: L-DISH from L2 to L4 correlated significantly with early-onset ASD, pseudarthrosis, and the appearance of postsurgical symptoms, especially at a lower segment and one distance from the segment adjacent to L-DISH, which were associated with the worst clinical outcome. Significantly higher percentages of L-DISH patients developed ASD and pseudarthrosis than those in the non-L-DISH group (40.7% vs 4.8% and 29.6% vs 2.4%, respectively). Of those patients with ASD and/or pseudarthrosis, 69.2% were symptomatic and 11.1% underwent revision surgery. CONCLUSIONS: The results highlighted the negative impact of short-level PLIF surgery for patients with L-DISH. Increased mechanical stress below the fused segment was considered the reason for the poor clinical outcome.

12.
Spine (Phila Pa 1976) ; 47(2): 114-121, 2022 Jan 15.
Article in English | MEDLINE | ID: mdl-34474445

ABSTRACT

STUDY DESIGN: A retrospective study. OBJECTIVES: The aim of this study was to review clinical and imaging features in patients with lumbar spinal canal stenosis (LSS) with and without postoperative early progression of intervertebral disc degeneration (IDD) and to identify predictive factors. SUMMARY OF BACKGROUND DATA: Progression of IDD after lumbar decompression surgery can induce low back pain and leg pain, and may require revision surgery. However, risk factors for postoperative radiological changes indicating IDD linked to development of symptoms have not been described. METHODS: We included 564 patients with LSS without degenerative lumbar scoliosis who underwent lumbar decompression surgery without fusion. Clinical features and imaging findings were compared in cases with (group P) and without (group N) progression of IDD (intervertebral disc wedge or narrowing) at 1 year after surgery. RESULTS: Of the 564 patients, 49 (8.7%) were in group P. On preoperative MRI, all patients in group P had findings of vertebral bone marrow edema (diffuse high intensity on T2-weighted images and low-intensity on T1-weighted images), compared to only 5.4% in group N. The rate of revision surgery was significantly higher in group P in 5 years' follow-up (12.2% vs. 1.4%, P < 0.01). In group P, 44.9% of patients developed postoperative symptoms associated with postoperative radiological changes, and the frequency was higher in narrowing-type than in wedge-type cases. Vertebral bone marrow edema area and IDD grade were not predictors for postoperative early IDD progression. CONCLUSION: Careful consideration is required to determine whether lumbar decompression surgery should be performed if vertebral bone marrow edema is detected on MRI, since this is a predictor for a negative clinical outcome. If surgery is symptomati-cally urgent, careful clinical and radiological follow-up is required.Level of Evidence: 4.


Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc , Spinal Stenosis , Bone Marrow/diagnostic imaging , Decompression, Surgical/adverse effects , Edema/diagnostic imaging , Edema/etiology , Humans , Intervertebral Disc Degeneration/diagnostic imaging , Intervertebral Disc Degeneration/surgery , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Stenosis/diagnostic imaging , Spinal Stenosis/surgery , Treatment Outcome
13.
Clin Spine Surg ; 35(1): E274-E279, 2022 02 01.
Article in English | MEDLINE | ID: mdl-33979101

ABSTRACT

STUDY DESIGN: This was a retrospective study. OBJECTIVE: The objective of this study was to review clinical and imaging findings after anterior cervical decompression and fusion, as a basis for prevention of C5 palsy. SUMMARY OF BACKGROUND DATA: C5 palsy is a common postoperative complication in spine surgery, but the mechanistic basis for this condition is unknown. MATERIALS AND METHODS: The subjects were 239 patients with cervical myelopathy who underwent anterior cervical decompression and fusion including at C4-C5 disk level at our hospital from 2001 to 2018. Twelve of these patients (5.0%) had C5 palsy postoperatively. Clinical features and imaging findings were compared in patients with and without C5 palsy. RESULTS: In patients with C5 palsy, the sagittal alignment of the cervical spine was kyphotic, the width of the C5 intervertebral foramen was narrower, and the lateral decompressed line was wider beyond the medial part of the Luschka joint. Age, sex, disease, the number of fused segments, decompression width, and anterior shift of the spinal cord did not differ significantly between patients with and without C5 palsy. CONCLUSIONS: These results indicate that the pathomechanism of C5 palsy may be dependent on the location of the lateral decompression line, especially in patients with cervical kyphosis and a narrow C5 intervertebral foramen. Excessive lateral decompression beyond the Luchka joint might lead to C5 root kinking between the intervertebral foramen and posterior edge of vertebra. This pathomechanism may be similar in anterior and posterior approaches. To prevent C5 palsy, the medial line of the Luschka joint should be confirmed intraoperatively and decompression should be performed within the Luschka joints. Alternatively, medial foraminotomy should be used in cases needing wide decompression, such as those with massive ossification of the posterior longitudinal ligament, lateral osteophytes, and symptomatic foraminal stenosis. LEVEL OF EVIDENCE: Level III.


Subject(s)
Cervical Vertebrae , Decompression, Surgical , Cervical Vertebrae/diagnostic imaging , Cervical Vertebrae/surgery , Decompression, Surgical/adverse effects , Decompression, Surgical/methods , Humans , Paralysis/etiology , Paralysis/prevention & control , Postoperative Complications/etiology , Postoperative Complications/surgery , Retrospective Studies , Risk Factors
14.
Int J Hematol ; 115(1): 129-134, 2022 Jan.
Article in English | MEDLINE | ID: mdl-34591291

ABSTRACT

Human herpesvirus-8 (HHV8)-positive, human immunodeficiency virus (HIV)-negative multicentric Castleman disease (MCD) is a rare and age-related lymphoproliferative disorder caused by cytokine storm. Rituximab treatment is currently recommended because B-cell depletion eliminates the primary reservoir for HHV8. We report the first case of effective rituximab treatment of a Japanese patient (an 87-year-old woman) with this disorder. Her inflammatory symptoms and lymphadenopathy improved after medium-dose steroid therapy, but these symptoms recurred during steroid tapering. After one course of rituximab therapy, she achieved sustained remission. HHV8-associated MCD should be considered as a possible diagnosis in HIV-negative patients with inflammatory symptoms and lymphadenopathy.


Subject(s)
Castleman Disease/drug therapy , Rituximab/administration & dosage , Rituximab/therapeutic use , Administration, Oral , Adult , Age Factors , Aged , Aged, 80 and over , Asian People , B-Lymphocyte Subsets/immunology , Castleman Disease/diagnosis , Castleman Disease/immunology , Castleman Disease/virology , Female , HIV , Humans , Male , Middle Aged , Prednisolone/administration & dosage , Recurrence , Remission Induction
15.
Cells ; 10(10)2021 10 01.
Article in English | MEDLINE | ID: mdl-34685592

ABSTRACT

(1) Background: CIC-DUX4 sarcoma is a rare mesenchymal small round cell tumor which belongs to rare cancers that occupy a significant percentage of cancer cases as a whole, despite each being rare. Importantly, each rare cancer type has different features, and thus there is a need to develop a model that mimics the features of each of these cancers. We evaluated the idea that the chicken chorioallantoic membrane assay (CAM), a convenient and versatile animal model, can be established for the CIC-DUX4 sarcoma. (2) Methods: Patient-derived cell lines of CIC-DUX4 were applied. These cells were transplanted onto the CAM membrane and tumor formation was examined by H&E staining, immunohistochemistry and Western blotting. The CAM tumor was transferred onto a fresh CAM and was also used to form organoids. Retention of the fusion gene was examined. (3) Results: H&E staining as well as molecular characterization demonstrated the formation of the CIC-DUX4 tumor on the CAM membrane. Expression of cyclin D2 and ETV4 was identified. The CAM tumor was transferred to a fresh CAM to form the second-generation CAM tumor. In addition, we were successful in forming tumor organoids using the CAM tumor. Retention of the fusion gene CIC-DUX4 in the CAM, second-generation CAM, and in the CAM-derived organoids was confirmed by RT-PCR. (4) Conclusions: The CAM assay provides a promising model for CIC-DUX4 sarcoma.


Subject(s)
Chorioallantoic Membrane , Homeodomain Proteins/metabolism , Oncogene Proteins, Fusion/metabolism , Repressor Proteins/metabolism , Sarcoma/metabolism , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Chorioallantoic Membrane/metabolism , Chorioallantoic Membrane/pathology , Humans
16.
Spine Surg Relat Res ; 5(4): 264-271, 2021.
Article in English | MEDLINE | ID: mdl-34435150

ABSTRACT

INTRODUCTION: Intradiscal chondroitin sulfate ABC endolyase (condoliase) injection for lumbar disc herniation (LDH) is an intermediate between conservative treatment and surgery. This approach can only be performed once in a lifetime; therefore, understanding the factors that determine the indication for the use of condoliase and predict outcomes is important. The aim of this study was to review clinical and imaging findings in patients after intradiscal condoliase injection, and to assess the short-term outcomes and factors associated with therapeutic effects. METHODS: The subjects were 42 patients with LDH who underwent intradiscal condoliase injection. Patients with and without a ≥50% improvement from baseline of leg pain at 3 months after injection were defined as responders and non-responders, respectively. Clinical features and radiological findings were compared between these groups. RESULTS: Of the 42 patients, 32 (76.2%) were responders and 10 (23.8%) were non-responders. Of 8 patients with a history of discectomy at the same level as LDH, 6 (75.0%) were responders. Non-responders had a significantly longer time from onset to treatment, smaller herniated volume before treatment, lower percentage reduction of herniated mass, and less intervertebral disc degeneration before treatment. There were no significant differences in LDH types (subligamentous extrusion or transligamentous extrusion types), high-intensity area within the herniation, changes in disc height, and region of condoliase injection between the two groups. CONCLUSIONS: Intradiscal condoliase injection had a good short-term therapeutic effect in patients with LDH, including in transligamentous extrusion-type and revision cases as well as subligamentous extrusion-type cases. Administration of intradiscal condoliase injection may be most effective in patients with a larger herniated mass volume before treatment, and least effective in cases with a longer time and less intervertebral disc degeneration before treatment.

17.
Sci Rep ; 11(1): 14235, 2021 07 09.
Article in English | MEDLINE | ID: mdl-34244599

ABSTRACT

Osteoporosis and Parkinson's disease (PD) are age-related diseases, and surgery for osteoporotic vertebral collapse (OVC) in PD patients become more common. OVC commonly affects the thoracolumbar spine, but low lumbar OVC is frequent in patients with lower bone mineral density (BMD). The aim of this study was to identify differences in clinical and imaging features of low lumbar OVC with or without PD and to discuss the appropriate treatment. The subjects were 43 patients with low lumbar OVC below L3 who were treated surgically, including 11 patients with PD. The main clinical symptoms were radicular pain in non-PD cases and a cauda equina sign in PD cases. Rapid progression and destructive changes of OVC were seen in patients with PD. The morphological features of OVC were flat-type in non-PD cases with old compression fracture, and destruction-type in PD cases without old compression fracture. Progression of PD was associated with decreased lumbar lordosis, lower lumbar BMD, and severe sarcopenia. High postoperative complication rates were associated with vertebral fragility and longer fusion surgery. Progression of postural instability as a natural course of PD may lead to mechanical stress and instrumentation failure. Invasive long-fusion surgery should be avoided for single low lumbar OVC.


Subject(s)
Osteoporosis/diagnostic imaging , Osteoporosis/pathology , Parkinson Disease/diagnostic imaging , Parkinson Disease/pathology , Aged , Aged, 80 and over , Female , Fractures, Compression/diagnostic imaging , Fractures, Compression/pathology , Humans , Male , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/pathology , Spinal Fractures/diagnostic imaging , Spinal Fractures/pathology
18.
Spine J ; 21(6): 955-962, 2021 06.
Article in English | MEDLINE | ID: mdl-33453385

ABSTRACT

BACKGROUND CONTEXT: Diffuse idiopathic skeletal hyperostosis (DISH) is a risk factor for further surgery after posterior decompression without fusion for patients with lumbar spinal canal stenosis (LSS). However, a strategy to prevent revision surgery has not been described. PURPOSE: The aim of this study was to review clinical and imaging findings in LSS patients with DISH extending to the lumbar segment and to propose countermeasures for prevention of revision surgery. STUDY DESIGN: A retrospective study. PATIENTS SAMPLE: A total of 613 consecutive patients with LSS underwent posterior decompression without fusion at our hospital and had a minimum follow-up period of 2 years. We defined patients with DISH bridging to the lumbar segment as L-DISH cases (group D, n=111), and those without as non-L-DISH cases (group N, n=502). OUTCOME MEASURE: Demographic data including the rate of revision surgery, neurological examination using Japanese Orthopaedic Association score, radiological studies comprised plain lumbar radiography, CT, and high-resolution MRI were assessed. METHODS: Clinical features and imaging findings were compared in patients with and without L-DISH. Revision surgery and surgical procedures (conventional laminotomy or lumbar spinous process-splitting [split] laminotomy) were examined in the two groups. No funding was received for this study. RESULTS: L-DISH from L2 to L4 was a risk factor for disc degeneration such as a vacuum phenomenon and for further surgical treatment. The rate of revision surgery was higher in group D than in group N (9.0% vs. 4.0%, p=.026). There was no significant difference in this rate for patients in groups D and N who underwent conventional laminotomy; however, for those who underwent split laminotomy, the rate was significantly higher in group D (16.7% vs. 2.1%, p=.0006). Furthermore, the rate of revision surgery after split laminotomy at a lower segment adjacent to L-DISH was significantly higher than that after conventional laminotomy (37.5% vs. 7.7%, p=.037). CONCLUSIONS: A negative impact of lumbar spinous process-splitting laminotomy was found, especially with decompression at a lower segment adjacent to L-DISH. In such cases, surgery sparing the osteoligamentous structures at midline, including the spinous process and supra- and interspinous ligaments, should be selected.


Subject(s)
Hyperostosis, Diffuse Idiopathic Skeletal , Spinal Stenosis , Constriction, Pathologic/surgery , Decompression, Surgical , Humans , Hyperostosis, Diffuse Idiopathic Skeletal/complications , Hyperostosis, Diffuse Idiopathic Skeletal/diagnostic imaging , Hyperostosis, Diffuse Idiopathic Skeletal/surgery , Laminectomy/adverse effects , Lumbar Vertebrae/diagnostic imaging , Lumbar Vertebrae/surgery , Retrospective Studies , Spinal Canal , Spinal Stenosis/diagnostic imaging , Spinal Stenosis/surgery , Treatment Outcome
19.
Eur Spine J ; 30(4): 829-836, 2021 04.
Article in English | MEDLINE | ID: mdl-32507919

ABSTRACT

PURPOSE: Symptomatic thoracic disc herniation (TDH) is relatively rare, but patients with progressive myelopathy require surgical treatment without delay in diagnosis. The aim of this study was to review clinical and radiological features in patients with TDH presenting with myelopathy. METHODS: A total of 28 consecutive patients with thoracic myelopathy (Frankel grade C or worse) due to TDH who underwent surgery were divided into 3 groups based on the time for development of myelopathy (acute (< 72 h), subacute (within a few weeks), and chronic [gradually over > 1 month)] and their data were analyzed. RESULTS: The patients in the acute group were significantly younger and had a higher body mass index (BMI) compared to those in the subacute and chronic groups. Most cases of acute myelopathy were affected in the upper thoracic level, whereas all patients with subacute and chronic myelopathy had lesions in the lower thoracic level below T8-9. Interestingly, the affected thoracic level in patients with acute myelopathy matched the upper line of the sternum. The rate of acquired walking ability without assistance was only 50.0% in the acute group. CONCLUSIONS: This study suggests that TDH presenting with acute myelopathy may have different clinical and radiological features compared to those of TDH with subacute and chronic myelopathy. Upper TDH should be suspected in cases of acute myelopathy that develops with sudden-onset back pain after certain triggers in younger and higher BMI people. These affected thoracic level matched with the upper line of the sternum in each case.


Subject(s)
Intervertebral Disc Displacement , Spinal Cord Diseases , Humans , Intervertebral Disc Displacement/diagnostic imaging , Radiography , Thoracic Vertebrae , Treatment Outcome
20.
Neurosci Lett ; 737: 135152, 2020 10 15.
Article in English | MEDLINE | ID: mdl-32531528

ABSTRACT

Spinal cord injury (SCI) causes loss of locomotor function and chronic neuropathic pain (NeP). Hematogenous macrophages and activated microglia are key monocytic lineage cell types in the response to SCI, and each has M1- and M2-phenotypes. To understand the roles of these cells in neuronal regeneration and chronic NeP after SCI, differences in distribution and phenotypes of activated microglia and infiltrated macrophages after SCI were examined at the injured site and the lumbar enlargement, as a remote region. Chimeric mice were used for differentiating activated microglia from hematogenous macrophages. The prevalences of activated microglia and infiltrating macrophages increased at day 14 after SCI, at the time of most severe pain hypersensitivity, with mainly M1-type hematogenous macrophages at the injured site and M2-type activated microglia at the lumbar enlargement. Peak expression of TNF-α, an M1-induced cytokine, occurred on day 4 post-SCI at the injured site, but not until day 14 at the lumbar enlargement. Expression of IL-4, a M2-induced cytokine, peaked at 4 days after SCI at both sites. These results suggest different roles of activated microglia and hematogenous macrophages, including both phenotypes of each cell, in neuronal regeneration and chronic NeP after SCI at the injured site and lumbar enlargement. The prevalence of the M1 over the M2 phenotype at the injured site until the subacute phase after SCI may be partially responsible for the lack of functional recovery and chronic NeP after SCI. Activation of M2-type microglia at the lumbar enlargement in response to inflammatory cytokines from the injured site might be important in chronic below-level pain. These findings are useful for establishment of a therapeutic target for prevention of motor deterioration and NeP in the time-dependent response to SCI.


Subject(s)
Cell Polarity/physiology , Macrophages/pathology , Microglia/pathology , Spinal Cord Injuries/pathology , Animals , Interleukin-4/metabolism , Macrophages/metabolism , Mice , Mice, Inbred C57BL , Microglia/metabolism , Motor Activity , Neuralgia/etiology , Neuralgia/metabolism , Neuralgia/pathology , Recovery of Function/physiology , Spinal Cord Injuries/complications , Spinal Cord Injuries/metabolism , Tumor Necrosis Factor-alpha/metabolism
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