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STUDY DESIGN: Prospective multicenter study. OBJECTIVES: Palliative surgery is crucial for maintaining the quality of life (QOL) in patients with spinal metastases. This study aimed to compare the short-term outcomes of QOL after palliative surgery between patients with metastatic spinal tumors at different segments. METHODS: We prospectively compared the data of 203 patients with spinal metastases at 2-3 consecutive segments who were divided into the following three groups: cervical, patients with cervical spine lesions; thoracic, patients with upper-middle thoracic spine lesions; and TL/L/S, patients with lesions at the thoracolumbar junction and lumbar and sacral regions. Preoperative and postoperative EuroQol 5-dimension (EQ5D) 5-level were compared. RESULTS: All groups exhibited improvement in the Frankel grade, performance status, pain, Barthel index, EQ5D health state utility value (HSUV), and EQ5D visual analog scale (VAS) postoperatively. Although preoperative EQ5D HSUVs did not significantly differ between the groups (cervical, 0.461 ± 0.291; thoracic, 0.321 ± 0.292; and TL/L/S, 0.376 ± 0.272), the thoracic group exhibited significantly lower postoperative EQ5D HSUVs than the other two groups (cervical, 0.653 ± 0.233; thoracic, 0.513 ± 0.252; and TL/L/S, 0.624 ± 0.232). However, postoperative EQ5D VAS was not significantly different between the groups (cervical, 63.4 ± 25.8; thoracic, 54.7 ± 24.5; and TL/L/S, 61.7 ± 21.9). CONCLUSIONS: Palliative surgery for metastatic spinal tumors provided comparable QOL improvement, irrespective of the spinal segment involved. Patients with upper and middle thoracic spinal metastases had poorer QOL outcomes than those with metastases in other segments; however, sufficient QOL improvement was achieved.
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STUDY DESIGN: Retrospective study. OBJECTIVES: To investigate the impact of diabetes mellitus on neurological recovery and determine the relationship between moderate-severe diabetes and neurological recovery in patients with cervical spinal cord injury (CSCI) without bone injury. METHODS: A retrospective study was conducted on 389 consecutive patients aged ≥65 years with CSCI without bone injury across 33 medical institutes. The patients were divided into a nondiabetic group (n = 270) and a diabetic group (n = 119). Neurological outcomes were compared between the two groups through propensity score matching. The impact of moderate-severe diabetes (defined as hemoglobin A1c ≥ 7.0% or requiring insulin treatment) on neurological recovery was evaluated through multiple linear regression analysis. RESULTS: Propensity score matching revealed no significant differences between the diabetic and nondiabetic groups in terms of American Spinal Injury Association (ASIA) impairment scale grade and mean total ASIA motor scores (AMS) at 6 months post-injury. Multiple linear regression analysis indicated that age on admission (B = -0.34; 95% confidence interval [CI], -0.59 to -0.08; P = 0.01), dementia (B = -16.50; 95% CI, -24.99 to -8.01; P < 0.01), and baseline total AMS (B = -0.62; 95% CI, -0.72 to -0.51; P < 0.01) were negative predictors of neurological recovery at 6 months post-injury. The presence of moderate-severe diabetes did not influence neurological recovery at 6 months post-injury. CONCLUSIONS: Diabetic patients with CSCI without bone injury achieved improvements in neurological function comparable to those of nondiabetic patients. Moderate-severe diabetes did not affect neurological recovery in patients with CSCI without bone injury.
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Objectives: Respiration plays an important function in sustaining life. The diaphragm is the primary muscle involved in respiration, and plays an important role in trunk stabilization. Although it has been reported that respiratory function is important for trunk muscle stability, the correlation between respiratory function and abdominal trunk muscle strength remains undetermined. This study aimed to clarify this correlation among middle-aged and older patients. Methods: This observational study included 398 patients scheduled for surgery for degenerative conditions of the lower extremities. Respiratory function was evaluated using forced vital capacity and forced expiratory volume in 1 s measured using spirometry. Each patient underwent a physical function test before surgery, which included the assessment of the abdominal trunk muscle strength, grip power, knee extensor strength, one-leg standing time, and gait speed. Correlations between abdominal trunk muscle strength, respiratory function, and physical function were evaluated. Results: Abdominal trunk muscle strength was significantly correlated with forced vital capacity, forced expiratory volume in 1 s, grip power, knee extensor strength, one-leg standing time, and gait speed. Multiple linear regression analyses revealed that sex, forced vital capacity, forced expiratory volume in 1 s, and knee extensor strength were significant factors associated with abdominal trunk muscle strength. Conclusions: In middle-aged and older patients, abdominal trunk muscle strength including that of the diaphragm, is associated with forced vital capacity and forced expiratory volume in 1 s.
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Brown adipose tissue (BAT) plays an important role in energy metabolism because it uses fatty acids for thermogenesis during cold exposure. Preclinical studies found that boysenberry anthocyanins (BoyACs) activate BAT. Therefore, the aim of this preliminary study was to evaluate how BoyAC intake affects BAT in humans. We performed an open-label single-arm nonrandomized study in healthy volunteers. Before and after 4 weeks of daily consumption of 100 ml boysenberry juice (BoyJ) containing 61 mg of BoyACs, participants were assessed at 24 °C and then after 1 h of mild cold exposure (18 °C). An infrared thermography camera was used to measure skin surface temperatures in the supraclavicular BAT region (Tscv) and the non-BAT region of the upper chest (Tch). Energy metabolism was measured by indirect calorimetry. For each endpoint, we calculated Δ as the difference between values before and after cold exposure and compared the values before and after BoyJ intake. 10 volunteers participated (age: 36.1 ± 4.1, body mass index (BMI): 20.9 ± 0.6). After BoyJ intake, ΔTscv-ch was significantly higher (p = 0.029), but Δ energy expenditure, Δ fat oxidation, and Δ carbohydrate oxidation were not significantly different. We found a significant positive correlation between BMI and Δfat oxidation with BoyJ intake. The results indicate that 4 weeks of BoyJ intake activates cold-induced thermogenesis in the scv-BAT but does not have a significant effect on energy metabolism. BoyJ intake may increase fat oxidation during cold exposure in individuals with higher BMI.Trial registry number: UMIN000043476, 05/03/2021.
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Tecido Adiposo Marrom , Metabolismo Energético , Sucos de Frutas e Vegetais , Voluntários Saudáveis , Termogênese , Humanos , Tecido Adiposo Marrom/metabolismo , Masculino , Adulto , Feminino , Antocianinas/metabolismo , Temperatura BaixaRESUMO
Introduction: In high-grade spinal osteotomy involving large anterior column resection, restoration of the structural integrity of the posterior column at the osteotomy site can reduce postoperative instrumentation failure (IF). This study aimed to describe our technique of posterior strut bone grafting using an en bloc resected vertebral arch, which is useful for posterior column reconstruction after high-grade osteotomies during surgeries for spinal tumor and deformity in the lower lumbar spine. Technical Note: Using a posterior approach, en bloc resection of the targeted vertebral arch was performed in accordance with the surgical technique for total en bloc spondylectomy (TES). The posterior elements in the upper and lower adjacent vertebrae were separated by a significant space after vertebral body resection followed by cage insertion in TES or anterior column osteotomy followed by correction in deformity surgery. To create a new posterior column, the en bloc resected vertebral arch was placed at 90° rotation to bridge the upper and lower vertebral arches. Using this technique, an abundant amount of bone chips made from the resected vertebral elements were placed over the en bloc resected posterior arch as an additional bone graft. The technique was used in three patients who underwent TES for spinal tumors and in one patient who underwent grade 4 osteotomy for adult spinal deformity in the lower lumbar spine. One year after surgery, computed tomography showed that the structural integrity of bony fusion was successfully achieved between the en bloc resected arch and the posterior elements of the adjacent vertebrae in all patients and showed no postoperative IFs. Conclusions: This bone graft technique created new continuity of the posterior column after high-grade osteotomies in the lower lumbar spine. Bone fusion was achieved in the posterior elements to prevent IF after surgery.
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BACKGROUND/AIM: The aim of the study was to develop a novel predictive scoring system based on the dynamics of serum inflammatory indicators in immune checkpoint inhibitor (ICI) treatment on non-small-cell lung cancer (NSCLC) with bone metastases. PATIENTS AND METHODS: Sixty patients with NSCLC and bone metastases treated with ICIs between January 2016 and March 2021 were included in the development cohort. Serum neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein (CRP) levels were assessed before (pre-value) and 6 weeks after (post-value) ICI treatment, and a novel predictive score was developed: pre-value ≥ post-value, 0 points; pre-value < post-value, 1 point; total score: 0-2 points. The associations of these dynamics and the score with clinical outcomes, including overall survival (OS), progression-free survival (PFS), response rate (RR) of bone metastases, and disease control rate (DCR), were evaluated. Furthermore, cross-validation was performed with 23 patients after April 2021 using the same inclusion criteria. RESULTS: The patients with decreased serum inflammation levels had significantly better OS, PFS, and RR than those with increased levels. Applying the developed score to the development cohort, the patients with 0 points had significantly better OS, PFS, and RR than others. In multivariable analysis, the score independently predicted treatment response to ICI for bone metastasis and prognosis. Cross-validation showed that OS, PFS, and RR were significantly better in the patients in the 0-point group. CONCLUSION: The early NLR and CRP dynamics were associated with therapeutic responses to ICIs in NSCLC with bone metastases. Our novel scoring system based on these dynamics is simple and has a high predictive accuracy.
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Biomarcadores Tumorais , Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Neutrófilos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/sangue , Feminino , Masculino , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/patologia , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/sangue , Proteína C-Reativa/metabolismo , Idoso de 80 Anos ou mais , Inflamação/sangue , Adulto , Prognóstico , Estudos RetrospectivosRESUMO
Previously, we successfully introduced laeA gene into a fungal strain in order to significantly increase the production of a bioactive compound, allowing use to discover novel biological activity. To demonstrate the universal applicability of the laeA gene introduction strategy for taping the potential of fungal secondary metabolism, in this present study, we created a library of microorganisms which we had the laeA gene inserted, and from that library we aimed to isolate compounds which are produced at significantly greater quantities compared to the respective wild type strains. From this investigation, we were able to isolate sclerotinin A (1) from Pochonia sp. KTF-0504 strain. We revealed that 1 showed anti-malarial activity against Plasmodium falciparum parasite strains. On the other hands, 1 showed no anti-fungal activity against multidrug-sensitive budding yeast. Our study implies that the utilization of the laeA gene in fungi is a versatile method for the discovery of drug candidates.
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Antimaláricos , Plasmodium falciparum , Antimaláricos/farmacologia , Antimaláricos/química , Antimaláricos/isolamento & purificação , Plasmodium falciparum/efeitos dos fármacos , Metabolismo Secundário , Estrutura Molecular , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Testes de Sensibilidade Parasitária , Hypocreales/metabolismo , Hypocreales/química , Relação Dose-Resposta a Droga , Relação Estrutura-AtividadeRESUMO
BACKGROUND CONTEXT: Growing evidence suggests that obesity is implicated in the progression of heterotopic ossification of the posterior longitudinal ligament of the spine (OPLL), a major cause of myelopathy in Asians. However, it remains unclear whether dysregulation of adipokine production due to fat accumulation contributes to OPLL progression. PURPOSE: To determine whether adipose-derived biochemical signals are associated with OPLL development or severity. STUDY DESIGN/SETTING: A nationwide, multicenter, case-control study. PATIENT SAMPLE: Patients with symptomatic thoracic OPLL (T-OPLL) who received treatment between June 2017 and March 2021 and 111 controls without OPLL. OUTCOME MEASURES: OPLL severity index based on whole-spine computed tomography. METHODS: Serum concentrations of adipokines, including leptin (Lep), tumor necrosis factor α (TNFα), and adiponectin (Adpn), as well as the Adpn/Lep ratio-an indicator of adipokine production dysregulation-were compared between the multiple-region OPLL and the single-region OPLL groups. Regression analysis was performed to examine the correlation between adipokine concentrations and OPLL severity index, which was calculated using whole-spine computed tomography images of 77 patients with T-OPLL within 3 years of onset. Using propensity score matching, the adipokine profiles of 59 patients with T-OPLL were compared with those of 59 non-OPLL controls. RESULTS: Patients with multiple-region OPLL exhibited a higher body mass index (BMI), lower serum Adpn/Lep ratio, and higher serum concentration of osteocalcin (OCN) than those with single-region OPLL. The OPLL severity index exhibited a weak positive correlation with BMI and serum Lep levels and a weak negative correlation with the Adpn/Lep ratio. Serum TNFα and OCN concentrations were significantly higher in patients with T-OPLL than in controls with similar age, sex, and BMI. CONCLUSIONS: Patients with diffuse OPLL over the entire spine are often metabolically obese with low Adpn/Lep ratios. In patients with OPLL, TNFα and OCN serum concentrations were essentially elevated regardless of obesity, suggesting a potential association with OPLL development. Considering the absence of therapeutic drugs for OPLL, the findings presented herein offer valuable insights that can aid in identifying therapeutic targets and formulating strategies to impede its progression.
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BACKGROUND: The concomitant use of denosumab and immune checkpoint inhibitor (ICI) treatment may have synergistic effects and enhance antitumor activity; however, this has not been fully evaluated. This study aimed to evaluate the clinical outcomes of non-small cell lung cancer (NSCLC) patients with bone metastases receiving combination therapy and to identify the best combination regimen. METHODS: Eighty-six NSCLC patients with bone metastases who received ICI treatment were enrolled in this study. The patients were divided into two groups; a denosumab combination group (D + ICI group; n = 47) and a non-combination group (non-D + ICI group; n = 39). The response rate (RR) for bone metastases, disease control rate (DCR), overall survival (OS), real world progression-free survival (rwPFS), and the incidence of immune-related adverse events (irAEs) were evaluated. Additionally, the time when denosumab treatment should commence and concomitant treatment duration were evaluated. RESULTS: The D + ICI group showed significantly better RR (40.4 % vs. 20.5 %, p = 0.01), DCR (67.3 % vs. 38.7 %, p = 0.02), OS (14.2 vs. 8.6 months, p = 0.02), and rwPFS (7.4 vs. 3.6 months, p < 0.01) than the non-D + ICI group; however, incidence of irAEs showed no difference (29.7 % vs. 12.8 %, p = 0.07). Although clinical outcomes did not differ regardless of whether denosumab was initiated before or after ICI treatment, the group that received concomitant denosumab for more than four months had significantly better RR (46.2 % vs. 17.4 %, p = 0.03), OS (20.3 vs. 3.8 months, p < 0.01), and rwPFS (10.9 vs. 2.8 months, p < 0.01) than the group that received concomitant denosumab for less than four months. However, the landmark analysis showed no significant differences in OS (20.4 vs. 12.7 months, p = 0.11) and rwPFS (22.8 vs. 11.2 months, p = 0.21), and the results of denosumab duration were influenced by long-term survivors. CONCLUSION: Denosumab showed favorable synergistic effects with ICI treatment and may significantly improve the response to bone metastasis and prognosis without increasing the incidence of irAEs.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ósseas , Carcinoma Pulmonar de Células não Pequenas , Denosumab , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Humanos , Denosumab/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Ósseas/secundário , Neoplasias Ósseas/tratamento farmacológico , Masculino , Feminino , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/mortalidade , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Idoso de 80 Anos ou mais , Adulto , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVES: We aimed to investigate the association of the dynamics of serum inflammatory and nutritional indicators with immune checkpoint inhibitor (ICI) response in non-small-cell lung cancer (NSCLC) with bone metastases, and to develop a novel predictive scoring system based on these indicators. METHODS: Patients with NSCLC having bone metastases treated with ICIs were categorized as: the development cohort (January 2016 to March 2021, n = 60) and the validation cohort (April 2021 to June 2023, n = 40). Serum indicators of inflammation and nutrition such as C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), albumin, prognostic nutritional index (PNI) were investigated before and six weeks after ICI initiation. The correlations of these dynamics with bone metastasis response rate (BoMRR) and overall survival (OS) were analyzed. A scoring system consisting of independent predictors was developed (IMMUNO-SCORE) and correlations with clinical outcomes were validated using the validation cohort. RESULTS: In the development cohort, multivariable analysis showed that NLR and PNI dynamics and CRP, NLR, and PNI dynamics were independent predictors of BoMRR and OS, respectively. The IMMUNO-SCORE consisting of NLR and PNI dynamics, which were the common predictors of the clinical outcomes, was significantly correlated with BoMRR (p < 0.01) and OS (p < 0.001) in cross-validation. The area under the curve of the score (0.786) was higher than individual NLR and PNI dynamics (0.72 and 0.684). CONCLUSION: Dynamics in NLR and PNI were demonstrated as biomarkers of treatment response and prognosis in ICI treatment of NSCLC with bone metastases, and the score combining these biomarkers was significantly correlated with clinical outcomes.
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Biomarcadores Tumorais , Neoplasias Ósseas , Proteína C-Reativa , Carcinoma Pulmonar de Células não Pequenas , Inibidores de Checkpoint Imunológico , Neoplasias Pulmonares , Neutrófilos , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/sangue , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/sangue , Inibidores de Checkpoint Imunológico/uso terapêutico , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Neoplasias Ósseas/secundário , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/sangue , Biomarcadores Tumorais/sangue , Proteína C-Reativa/análise , Neutrófilos/imunologia , Prognóstico , Inflamação/sangue , Avaliação Nutricional , Idoso de 80 Anos ou mais , Adulto , Estudos RetrospectivosRESUMO
We found that the culture broth of fungi showed anti-fungal activity against multidrug-sensitive budding yeast. However, we could not identify the anti-fungal compound due to the small quantity. Therefore, we attempted to increase the productivity of the target compound by the introduction of a global secondary metabolism regulator, laeA to the strain, which led to the successful isolation of 10-folds greater amount of MS-347a (1) than Aspergillus sp. FKI-5362. Compound 1 was not effective against Candida albicans and the detailed anti-fungal activity of 1 remains unverified. After our anti-fungal activity screening, 1 was found to inhibit the growth of broad plant pathogenic fungal species belonging to the Ascomycota. It is noteworthy that 1 showed little insecticidal activity against silkworms, suggesting its selective biological activity against plant pathogenic fungi. Our study implies that the combination strategy of multidrug-sensitive yeast and the introduction of laeA is useful for new anti-fungal drug discovery.
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Descoberta de Drogas , Saccharomyces cerevisiae , Saccharomyces cerevisiae/efeitos dos fármacos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Descoberta de Drogas/métodos , Candida albicans/efeitos dos fármacos , Metabolismo Secundário , Fungicidas Industriais/farmacologia , Antifúngicos/farmacologia , Antifúngicos/química , Testes de Sensibilidade Microbiana , Ascomicetos/efeitos dos fármacos , Ascomicetos/genética , Aspergillus/efeitos dos fármacos , Aspergillus/genética , Aspergillus/metabolismo , Avaliação Pré-Clínica de Medicamentos/métodos , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismoRESUMO
BACKGROUND AND PURPOSE: Although the application of cryoablation to metastatic spinal tumors has been attempted, spinal cryoablation has the unique complication of cryogenic spinal cord injury. This study aimed to elucidate the conditions for the development of cryogenic spinal cord injury. MATERIALS AND METHODS: Fifteen canines were used in this study. A metal probe was inserted into the 13th thoracic vertebral body. Cryoablation was performed for 10 minutes by freezing the probe in liquid nitrogen. The control canine underwent probe insertion only. Spinal cord monitoring, epidural temperature measurement, motor function assessment, and pathologic examination of the spinal cord were performed. RESULTS: During the 10 minutes of cryoablation, the epidural temperature decreased and reached the lowest epidural temperature (LET) at the end of cryoablation. The LETs (degrees celsius [°C]) of each canine were -37, -30, -27, -8, -3, -2, 0, 1, 4, 8, 16, 18, 20, and 25, respectively. As the epidural temperature decreased, waveform amplitudes also decreased. At the end of cryoablation (10 minutes after the start of cryoablation), abnormal waves were observed in 92.9% (13/14) of canines. With epidural rewarming, the amplitude of the waveforms tended to recover. After epidural rewarming (2 hours after the start of cryoablation), abnormal waves were observed in 28.6% (4/14) of canines. The LETs (°C) of the canines with abnormal waves after epidural rewarming were -37, -30, -27, and -8. None of the canines with normal waves after epidural rewarming had any motor impairment. In contrast, all canines with remaining abnormal waves after epidural rewarming had motor impairment. In the pathologic assessment, cryogenic changes were found in canines with LETs (°C) of -37 -30, -27, -8, 0, and 1. CONCLUSIONS: This study showed that 10-minute spinal cryoablation with LETs (°C) of -37, -30, -27, -8, 0, and 1 caused cryogenic spinal cord injury. There was no evidence of cryogenic spinal cord injury in canines with LET of ≥4°C. The epidural temperature threshold for cryogenic spinal cord injury is between 1 and 4°C, suggesting that the epidural temperature should be maintained above at least 4°C to prevent cryogenic spinal cord injury.
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Neoplasias do Sistema Nervoso Central , Criocirurgia , Hipotermia Induzida , Traumatismos da Medula Espinal , Neoplasias da Medula Espinal , Neoplasias da Coluna Vertebral , Animais , Cães , Neoplasias da Coluna Vertebral/patologia , Criocirurgia/efeitos adversos , Traumatismos da Medula Espinal/etiologia , Traumatismos da Medula Espinal/cirurgia , Temperatura Corporal , Medula Espinal/patologia , Neoplasias da Medula Espinal/patologia , Neoplasias do Sistema Nervoso Central/patologiaRESUMO
STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes. METHODS: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared. RESULTS: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory. CONCLUSIONS: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups.
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STUDY DESIGN: A mouse study of the Slc7a5 gene using conditional knockout to assess the effects of its inactivation on spinal deformity. OBJECTIVES: This study aimed to investigate whether the mice with scoliosis [induced by chondrocyte-specific inactivation of L-type amino acid transporter 1 (LAT1)] show a developmental process similar to that of pediatric scoliosis and to examine the relationship between reduced bone mineral density (BMD) and scoliosis. Furthermore, we aimed to obtain insights into elucidating the etiology and pathophysiology of scoliosis. SUMMARY OF BACKGROUND DATA: The etiology and pathogenesis of scoliosis are not fully understood despite substantial investigative efforts. LAT1 is an amino acid transporter that mediates the cellular uptake of large neutral amino acids. A recent study revealed that chondrocyte-specific inactivation of LAT1 in mice results in scoliosis (Col2a1-Cre;Slc7a5fl/fl mice: "Sko mice"). MATERIALS AND METHODS: Body length, body weight, Cobb angle, vertebral body rotation angle, and BMD at 1, 2, 4, 6, and 8 weeks of age were examined and statistically compared with those of normal control mice. Pathologic and morphologic evaluation was performed on specimens from 10-week-old euthanized mice. RESULTS: The Sko mice developed thoracic scoliosis in infancy without congenital malformations. This spinal deformity progressed rapidly during growth, with diverse curve patterns and hypoplastic vertebral bodies. Pathologic examination revealed thickening of the growth plates and decreased osteoblasts, suggesting that impaired endochondral ossification was the cause of the scoliosis. Sko mice were also observed to have decreased BMD and degraded bone microstructure. Reduced BMD and bone quality may not be the causes of the onset and progression of scoliosis in the Sko mice. CONCLUSIONS: In Sko mice, the characteristics of scoliosis and vertebral pathology showed many similarities with syndromic scoliosis in humans. Endochondral ossification defects may impair growth, leading to scoliosis and decreased BMD.
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Escoliose , Humanos , Criança , Animais , Camundongos , Condrócitos/patologia , Coluna Vertebral/patologia , Osteogênese , Osso e OssosRESUMO
BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.
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Medula Cervical , Lesões dos Tecidos Moles , Traumatismos da Medula Espinal , Idoso , Humanos , Resultado do Tratamento , Medula Cervical/lesões , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/cirurgia , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/lesões , Estudos Multicêntricos como AssuntoRESUMO
STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate the treatments of the geriatric population with hangman's fractures using a multicenter database under the Japan Association of Spine Surgeons with Ambition (JASA). METHODS: The multicenter database included data from 1512 patients. We employed the Levine and Edwards classification for categorizing hangman's fractures. The study incorporated epidemiological data, including the prevalence of hangman's fractures, patient age, and follow-up duration. Bony fusion rates and length of hospitalization were recorded for Type I and Type II fractures, and the degree of neurological impairment was assessed. RESULTS: Hangman's fractures represented 62 cases, accounting for 7.4% of all cervical spine injuries. The patients had an average age of 76.6 ± 6.5 years, and the mean duration of follow-up was 21.5 ± 23.6 months. The study found that the bony fusion rate for hangman's fractures in the geriatric population was 88.9%. Surgical treatment was associated with a shorter hospitalization period for Type II fractures compared to conservative treatment. Thirteen cases of hangman's fractures in the geriatric population, accounting for 21%, were complicated by spinal cord injury. CONCLUSIONS: This is the largest study to date on hangman's fractures in geriatric population ≥65 years. Type I and Type II fractures, according to the Levine and Edwards classification, had a bony fusion rate of up to 90%. In patients with Type II fractures, surgical treatment led to a shorter initial hospital stay. Geriatric patients are at risk of spinal cord injury due to hangman's fractures.
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Introduction: The number of patients on antithrombotic drugs for coronary heart disease or cerebrovascular disease has been increasing with the aging of society. We occasionally need to decide whether to continue or discontinue antithrombotic drugs before spine surgery. The purpose of this study is to understand the current perioperative management of antithrombotic drugs before elective spine surgery in Japan. Methods: In 2021, members of the Japanese Society for Spine Surgery and Related Research (JSSR) were asked to complete a web-based questionnaire survey that included items concerning the respondents' surgical experience, their policy regarding discontinuation or continuation of antithrombotic drugs, their reasons for decisions concerning the management of antithrombotic drugs, and their experience of perioperative complications related to the continuation or discontinuation of these drugs. Results: A total of 1,181 spine surgeons returned completed questionnaires, giving a response rate of 32.0%. JSSR board-certified spine surgeons comprised 75.1% of the respondents. Depending on the management policy regarding antithrombotic drugs for each comorbidity, approximately 73% of respondents discontinued these drugs before elective spine surgery, and about 80% also discontinued anticoagulants. Only 4%-5% of respondents reported continuing antiplatelet drugs, and 2.5% reported continuing anticoagulants. Among the respondents who discontinued antiplatelet drugs, 20.4% reported having encountered cerebral infarction and 3.7% reported encountering myocardial infarction; among those who discontinued anticoagulants, 13.6% reported encountering cerebral embolism and 5.4% reported encountering pulmonary embolism. However, among the respondents who continued antiplatelet drugs and those who continued anticoagulants, 26.3% and 27.2%, respectively, encountered an unexpected increase in intraoperative bleeding, and 10.3% and 8.7%, respectively, encountered postoperative spinal epidural hematoma requiring emergency surgery. Conclusions: Our findings indicate that, in principle, >70% of JSSR members discontinue antithrombotic drugs before elective spine surgery. However, those with a discontinuation policy have encountered thrombotic complications, while those with a continuation policy have encountered hemorrhagic complications.
RESUMO
Polybutylene succinate (PBS) is an eco-friendly green plastic. However, PBS was shown as being non-biodegradable in marine environments, and up until now, only a limited number of PBS-degrading marine microbes have been discovered. We first set up in vitro PBS- and PBSA (polybutylene succinate adipate)-plastispheres to characterize novel PBS-degrading marine microbes. Microbial growth and oxygen consumption were observed in both PBS- and PBSA-plastispheres enriched with natural seawater collected from Usujiri, Hokkaido, Japan, and Vibrionaceae and Pseudoalteromonadaceae were significantly enriched on these films. Further gene identification indicated that vibrios belonging to the Gazogenes clade possess genes related to a PBS degrading enzyme (PBSase). The PBS degradation assay for six Gazogenes clade vibrios identified Vibrio ruber, Vibrio rhizosphaerae, and Vibrio spartinae as being capable of degrading PBS. We further identified the gene responsible for PBSase from the type strain of V. ruber, and the purified recombinant vibrio PBSase was found to have low-temperature adaptation and was active under high NaCl concentrations. We also provided docking models between the vibrio PBSase and PBS and PBSA units to show how vibrio PBSase interacts with each substrate compared to the Acidovorax PBSase. These results could contribute to a more sustainable society through further utilization of PBS in marine environments and plastic recycling.