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The aim of this study was to investigate the effectiveness of compost and vermicompost as soil conditioners in alleviating salt-affected soils and increasing maize productivity. A greenhouse trial, consisting of seven soil amendment treatments in a completely randomized design with three replications, was carried out at Khon Kaen University, Thailand, during the rainy season of 2011. Plant height and total dry matter of maize increased in treatments with compost and vermicompost application when compared with the control (no fertilizer) in two types of soils (saline and nonsaline) during the growing season. Soil pH and electrical conductivity in saturation paste extracts were decreased by compost and vermicompost amendments with or without earthworms when compared with unamended treatments in the saline soil. Compost and vermicompost amendments improved cation exchange capacity, soil organic carbon, total nitrogen and extractable phosphorus in both soils. These amendments also increased exchangeable K+, Ca2+ and Mg2+ while decreasing exchangeable Na+ in the saline soil, which suggested that Ca2+ was exchanged for Na+, exchangeable Na+, then leached out, and soil salinity reduced as a result. Soil microbial activities including microbial C and N and basal soil respiration were improved by the application of compost and vermicompost amendments with or without earthworms when compared with the control in both soils. This experiment showed that the compost and vermicompost were effective in alleviating salinity and improving crop growth. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study. Objective: To analyze the clinical outcomes of anterior and posterior spinal fusion (APSF) using a fibular strut autograft (FSAG) and to investigate the morphological changes in the reconstructed spinal column of dystrophic deformities in neurofibromatosis (NF)-1. Summary Of Background Data: APSF is desirable for dystrophic deformities in NF-1 with more than 50° of dystrophic kyphosis. There are few reports regarding the clinical outcomes of APSF in which the morphological changes over time of the anterior strut graft have been investigated. Methods: The clinical and radiographic outcomes of APSF with FSAG were investigated in 10 consecutive patients with dystrophic deformity in NF-1. For qualitative and quantitative analyses, the chronological changes in the FSAG configuration, length, and diameter were evaluated. Results: The mean follow-up period was 9 years, 9 months (range, 1-30 years). Graft bone erosion and postoperative curve progression were not observed in any patient. In quantitative analyses of the anterior strut, the mean ratio of the latest and immediately postoperative FSAG lengths was 0.98 (0.93-1.09). The mean central/peripheral ratios of the FSAG diameter (central portion/[upper end + lower end]/2) were 1.02 (0.92-1.10) immediately after surgery, and 1.01 (0.92-1.07) at the latest follow-up, with no significant change between these 2 time points (P = 0.937). The mean preoperative cross-sectional area of the apical vertebral body and its mean virtual cross-sectional area at the final follow-up were 3.80 (1.83-5.43) and 4.87 (2.46-7.00) cm(2), respectively, with a significant difference between these 2 parameters (P = 0.0078). The mean final/preoperative ratio was 1.31 (1.10-1.43). Conclusion: APSF with FSAG for dystrophic deformity in NF-1 successfully reconstructed a reliable spinal column with a rich bone stock. The FSAG and surrounding vertebral bodies were free from postoperative erosion due to dystrophic changes and maintained their stability for a long time. [ABSTRACT FROM AUTHOR]

Aims Dilated cardiomyopathy is partly caused by a mutation of some cytoskeletal or nuclear envelope proteins. It has been confirmed recently that a missense mutation of the gene encoding desmin, a cytoskeletal protein, can cause dilated cardiomyopathy. This study was aimed at elucidating the frequency and clinical characteristics of dilated cardiomyopathy caused by desmin mutation.Methods and Results We examined 265 Japanese patients with dilated cardiomyopathy (217 sporadic cases and 48 probands of familial dilated cardiomyopathy). The exon 8 of the desmin gene, the critical region for the pathogenesis of dilated cardiomyopathy, was analysed by polymerase chain reaction, single-strand conformation polymorphism and sequencing. The same missense mutation (Ile451Met) as reported previously was detected in three patients (1·1%). All these patients were male and sporadic, and more likely to be accompanied by characteristics such as younger age at diagnosis, lower fractional shortening and ejection fraction than each mean value of sporadic cases. The chronological changes in cardiac function were inconsistent in the three patients.Conclusion The missense mutation (Ile451Met) of the desmin gene can be the genetic cause of dilated cardiomyopathy, although with very low frequency. The ages at diagnosis were younger and the cardiac function had deteriorated further than general cases of sporadic dilated cardiomyopathy. [ABSTRACT FROM PUBLISHER]

Monitoring land use/land cover change at various scales is of foremost importance for the management of natural resources and pivotal to achieve effective environmental governance. The purpose of this study was to classify land use/land cover and to quantify changes in land use/land cover in Luangnamtha district, northern Laos over the past two decades, using remote sensing and Geographic Information System technologies. We used Landsat 5 Thematic Mapper (TM) images from 2000, 2005, 2010 and Landsat 8 Operational Land Imager (OLI) images from 2017. A supervised classification was achieved by applying the maximum likelihood algorithm in the ENVI software. Five land cover classes, namely agriculture, forest, rubber tree, settlement and water were thus identified. The nature and extent of change detected was analyzed on the basis of the land use maps generated for years 2000, 2005, 2010 and 2017. We applied spatial point process theory to analyze spatial relationships between land use classes and with terrain covariables. The overall accuracy of our classifications were 86.8%, 89.3%, 90.4%, and 91.7% for the years 2000, 2005, 2010, and 2017, respectively and the Kappa coefficients were 0.76, 0.85, 0.85, and 0.89, respectively. The results of these classifications indicated that over the 2000 to 2017 period, settled areas increased by 2.35% (5,038 ha), water bodies increased very marginally (0.01% or 20 ha), but that rubber tree cover increased by as much as 7.60% (16,314 ha). During the same period, agricultural land decreased by 0.11% (224 ha) and the forested area shrunk by 9.84% (21,129 ha). Spatial analysis indicates that rubber tree plantations expanded from the lowest part of the landscape, in close spatial association with agricultural land, to increasingly higher locations where it most likely replaced forest. This study confirms that drivers such as government policies for permanent allocation of agricultural land poverty eradication, as well as foreign investments, had a major impact on the expansion of rubber tree plantation in Luangnamtha district from 2000 to 2017. [ABSTRACT FROM AUTHOR]

The fundamental electronic structure of the widely used battery material LixCoO2 still remains a mystery. Soft x-ray absorption spectroscopy of LixCoO2 reveals that holes with strong O 2p character play an essential role in the electronic conductivity of the Co3+/Co4+ mixed valence CoO2 layer. The oxygen holes are bound to the Co4+ sites and the Li-ion vacancy, suggesting that the Li-ion flow can be stabilized by oxygen hole back flow. Such an oxygen hole state of LixCoO2 is unique among the various oxide-based battery materials and is one of the key ingredients to improving their electronic and Li-ion conductivities. [ABSTRACT FROM AUTHOR]

To test the hypothesis that coronary spasm could be a coronary manifestation of systemic endothelial dysfunction and that the activity of coronary spasm could influence systemic endothelial function, we examined brachial flow-mediated, endothelium-dependent vasodilation and nitroglycerin-induced endothelium-independent vasodilation with high-resolution ultrasound in 11 men with variant angina pectoris (6 active and 5 inactive) without established coronary atherosclerosis. Endothelium-dependent vasodilation in peripheral circulation was preserved in men with active and inactive variant angina pectoris, suggesting that systemic endothelial dysfunction is not involved in either the pathogenesis or the activity of coronary spasm. [ABSTRACT FROM AUTHOR]

We report an angle-resolved photoemission spectroscopy (ARPES) study of LixCoO2 single crystals which have a hole-doped CoO2 triangular lattice. Similar to NaxCoO2, the Co 3da1g band crosses the Fermi level with strongly renormalized band dispersion while the Co 3de'g bands are fully occupied in LixCoO2 (x=0.46 and 0.71). At x=0.46, the Fermi surface area is consistent with the bulk hole concentration indicating that the ARPES result represents the bulk electronic structure. On the other hand, at x=0.71, the Fermi surface area is larger than the expectation which can be associated with the inhomogeneous distribution of Li reported in the previous scanning tunneling microscopy study by Iwaya et al. [Phys. Rev. Lett. 111, 126104 (2013)]. However, the Co 3d peak is systematically shifted towards the Fermi level with hole doping excluding phase separation between hole rich and hole poor regions in the bulk. Therefore, the deviation of the Fermi surface area at x=0.71 can be attributed to hole redistribution at the surface avoiding polar catastrophe. The bulk Fermi surface of Co 3da1g is very robust around x=0.5 even in the topmost CoO2 layer due to the absence of the polar catastrophe. [ABSTRACT FROM AUTHOR]

Study Design: Multicenter, prospective registry study., Objective: To clarify minimal clinically important differences (MCIDs) for surgical interventions for spinal metastases, thereby enhancing patient care by integrating quality of life assessments with clinical outcomes., Background: Despite its proven usefulness in degenerative spinal diseases and deformities, the MCID remains unexplored regarding surgery for spinal metastases., Patients and Methods: This study included 171 (out of 413) patients from the multicenter "Prospective Registration Study on Surgery for Metastatic Spinal Tumors" by the Japan Association of Spine Surgeons. These were evaluated preoperatively and at 6 months postoperatively using the Face Scale, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), including the Visual Analog Scale, and performance status. The MCIDs were calculated using an anchor-based method, classifying participants into the improved, unchanged, and deteriorated groups based on the Face Scale scores. Focusing on the improved and unchanged groups, the change in the EQ-5D-5L values from before to after treatment was analyzed, and the cutoff value with the highest sensitivity and specificity was determined as the MCID through receiver operating characteristic curve analysis. The validity of the MCIDs was evaluated using a distribution-based calculation method for patient-reported outcomes., Results: The improved, unchanged, and deteriorated groups comprised 121, 28, and 22 participants, respectively. The anchor-based MCIDs for the EQ-5D-5L index, EQ-Visual Analog Scale, and domains of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 0.21, 15.50, 1.50, 0.50, 0.50, 0.50, and 0.50, respectively; the corresponding distribution-based MCIDs were 0.17, 15,99, 0.77, 0.80, 0.78, 0.60, and 0.70, respectively., Conclusion: We identified MCIDs for surgical treatment of spinal metastases, providing benchmarks for future clinical research. By retrospectively examining whether the MCIDs are achieved, factors favoring their achievement and risks affecting them can be explored. This could aid in decisions on surgical candidacy and patient counseling., Level of Evidence: II., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Study Design: Clinical and basic study., Objectives: This study aimed to investigate whether transforaminal lumbar interbody fusion (TLIF) using 2 banana-shaped cages leads to good clinical outcomes., Methods: First, we conducted a clinical study to compare outcomes among patients who underwent TLIF using different types or numbers of cages. Propensity matched patients in each group were reviewed. Thirty-four patients who underwent surgery with 2 bullet-shaped cages (group A), 34 with a banana-shaped cage (group B), and 34 with 2 banana-shaped cages (group C) were compared. Twelve months after the surgery, bony fusion and cage subsidence were evaluated., Results: The mean amount of cage subsidence was 14.9% in group A, 19.9% in group B, and 11.8% in group C. Subsidence in group B was significantly greater than that in group C ( P < .01). Radiological bony fusion was not achieved in 2 cases in group B. Second, we performed a finite element model (FEM) analysis to determine the biomechanical stress of the vertebral endplate by comparing the single-banana cage construct with a double banana-shaped cage construct. FEM analysis showed that the maximum stress of the endplate in the single-cage model was 1.72-times greater than the maximum stress in the double-cage model. Furthermore, the maximal stress in the single-cage model was significantly higher than in the double-cage model during lumbar extension and side bending., Conclusion: This study showed that TLIF with double banana-shaped cages led to good clinical outcomes with less cage subsidence, probably because of decreased mechanical stress on the vertebral endplate., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: It is unclear whether the sequential administration of programmed death (PD)-1/programmed death-ligand 1 (PD-L1) inhibitors and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) is associated with the development of severe interstitial pneumonitis (IP)., Patients and Methods: We identified 69,107 eligible patients with non-small cell lung cancer (NSCLC) from a Japanese national inpatient database, who initiated EGFR-TKI therapy. The study population was divided into the PD-1/PD-L1 inhibitor and non-prior PD-1/PD-L1 groups based on PD-1/PD-L1 administration before EGFR-TKI therapy. We conducted 1:4 matched-pair cohort analyses (n = 9,725) to compare the incidence of IP and in-hospital mortality within 90 days of administration of EGFR-TKI between the two groups after adjusting for the clinical background. Furthermore, we performed subgroup analyses categorized according to the duration of prior PD-1/PD-L1 inhibitor use., Results: IP occurred in 4.4% of patients in the matched-pair cohort. PD-1/PD-L1 inhibitor-use before EGFR-TKI therapy was significantly associated with IP (odds ratio [OR], 1.79; 95% confidence interval [CI], 1.34-2.38) and in-hospital mortality (OR, 2.10; 95% CI, 1.72-2.55). Prior PD-1/PD-L1 inhibitor use in an interval of <6 months before EGFR-TKI administration was associated with a higher risk of IP than EGFR-TKI administration without prior PD-1/PD-L1 inhibitor. In-hospital mortality was higher in patients with prior PD-1/PD-L1 inhibitor use than that in those without prior PD-1/PD-L1 inhibitor use, irrespective of the treatment duration., Conclusion: Sequential use of PD-1/PD-L1 inhibitors and EGFR-TKIs in patients with non-small cell lung cancer was significantly associated with IP compared to EGFR-TKIs without prior PD-1/PD-L1 inhibitor administration., Competing Interests: Disclosure The authors have declared no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments., Methods: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation., Results: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months., Conclusion: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer., Competing Interests: Declaration of competing interest The Authors declare that there is no conflict of interest., (Copyright © 2024 The Japanese Orthopaedic Association. Published by Elsevier B.V. All rights reserved.)

Purpose: To describe the surgical treatment in a patient with a partial omega deformity in the thoracic spine with neurofibromatosis type 1., Methods: The patient was a 55-year-old man with an omega deformity, which is defined as a curvature in which the end vertebra is positioned at the level of, above, or below the apical vertebra (i.e., a horizontal line bisecting it). We performed halo gravity traction (HGT) for 7 weeks, followed by posterior spinal instrumented nearly equal in situ fusion from T2-L5 with three femoral head allografts and a local bone autograft. We avoided reconstruction of the thoracic anterior spine because of his severe pulmonary dysfunction., Results: HGT improved the % vital capacity from 32.5 to 43.5%, and improved the Cobb angle of the kyphosis from > 180° before traction to 144° after traction. The Cobb angle of kyphosis and scoliosis changed from > 180° preoperatively to 155° and 146°, respectively, postoperatively, and 167° and 156°, respectively, at final follow-up. His postoperative respiratory function deteriorated transiently due to bilateral pleural effusions and compressive atelectasis, which was successfully treated with a frequent change of position and nasal high flow for 1 week. At final follow-up, his pulmonary function improved from 0.86 to 1.04 L in VC, and from 32.5 to 37.9% in %VC. However, there was no overall improvement in preoperative distress following surgery, although his modified Borg scale improved from 3 preoperatively to 0.5 postoperatively. One month after discharge, he felt worsening respiratory distress (SpO2:75%) and was readmitted for pulmonary hypertension for 2 months. He was improved by non-invasive positive pressure ventilation (biphasic positive airway pressure) for 1 week, medication and daily lung physiotherapy. Thereafter, he has been receiving permanent daytime (0.5 L/min) and nighttime (2 L/min) oxygen therapy at home. A solid arthrodesis through the fusion area was confirmed on computed tomography. However, the kyphosis correction loss was 12° (i.e., 155°-167°), while the scoliosis correction loss was 10° (i.e., 146°-156°) at 2 years of recovery., Conclusions: We suggest that nearly equal in situ fusion is a valid option for preventing further deformity deterioration and avoiding fatal complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Case: A 30-year-old man had cervical radiculomyelopathy and neck pain caused by a massive intraosseous neurofibroma (IONF) originating from the C6 vertebrae. We performed posterior tumor resection with spinal instrumentation and fusion from C3 to T2 and a follow-up resection procedure of the remaining C6 anterior tumor, sacrificing the affected vertebral artery (VA), which accordingly required bypass surgery at 2 months recovery. Reconstruction using a titanium mesh cage was successfully performed. There were no local recurrences at 2 years postoperatively., Conclusions: Total tumor resection split into 2 stages with sacrifice of the affected VA is a feasible option for treatment of IONF., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C293)., (Copyright © 2024 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Meningioma is the second most common intradural extramedullary tumor, following schwannoma. Meningioma is primarily categorized as benign World Health Organization grade 1, but clear cell meningioma is grade 2 of the intermediate malignant category. Clear cell meningiomas are rare, accounting for less than 1% of all meningioma tumors. There is no previous report of multiple intraspinal clear cell meningiomas without dural attachment., Case Presentation: A 27-year-old Asian male patient presented with lower right extremity pain, and had undergone tumor resection for intracranial clear cell meningioma 7 years previously, with re-resection and radiotherapy for local tumor recurrence at our hospital's department of neurosurgery being carried out 4 years previously. No recurrence was observed since then. Preoperative lumbar magnetic resonance imaging showed two tumors at the L1 and L4 levels, both mimicking schwannoma with well-defined margins, no dural tail sign and homogeneous internal contrast. Intraoperative findings on tumor resection showed two tumors contiguous with the right L2 and L5 roots, which were not attached to the dura mater, similar to a schwannoma. After gross total resection, the postoperative pathology revealed no nuclear SMARCE1 antibody staining. The patient was diagnosed with clear cell meningioma. The patient's postoperative course went well, with no symptoms of nerve dropout and no recurrence 2 years after surgery. In this case, both lumbar lesions were well demarcated and spherical in shape, occurring with single roots. Tumor characteristics suggested a primary rather than a metastatic lesion. Clear cell meningioma is characterized by a SMARCE1 mutation and is different from other types of meningiomas., Conclusion: To the best of our knowledge, this is the first report of multiple intraspinal clear cell meningiomas without dural attachment at the lumbar spine after resection of intracranial clear cell meningioma. We speculate that the two tumors were de novo lesions on the basis of the features of the tumors, although they were detected 7 years after the resection of intracranial clear cell meningioma., (© 2024. The Author(s).)

Objectives: To determine the associated thromboembolism risk with adding immune checkpoint inhibitors (ICI) to platinum combination chemotherapy compared with platinum combination chemotherapy alone in patients with advanced non-small cell lung cancer., Materials and Methods: This study identified 75,807 patients with advanced non-small cell lung cancer from the Japanese Diagnosis Procedure Combination database who started platinum combination chemotherapy between July 2010 and March 2021. The incidence of venous thromboembolism (VTE), arterial thromboembolism (ATE), and all-cause mortality within 6 months after commencing platinum combination chemotherapy was compared between patients receiving chemotherapy with ICI (ICI group, n = 7,177) and without ICI (non-ICI group, n = 37,903). Survival time analysis was performed using the overlap weighting method with propensity scores to adjust for background factors. The subdistribution hazard ratio for developing thromboembolism was calculated using the Fine-Gray model with death as a competing risk. The hazard ratio for all-cause mortality was also calculated using the Cox proportional hazards model., Results: Overall, VTE and ATE occurred in 761 (1.0%) and 389 (0.51%) patients, respectively; mortality was 11.7%. Propensity score overlap weighting demonstrated that the subdistribution hazard ratio (95% confidence interval) for VTE and ATE in the ICI group was 1.27 (1.01-1.60) and 0.96 (0.67-1.36), respectively, compared with the non-ICI group. The mortality hazard ratio in the ICI group was 0.68 (0.62-0.74)., Conclusion: The addition of ICI to platinum combination therapy was associated with a higher risk of VTE compared with platinum combination therapy alone, while the risk of ATE might be comparable., (© 2023. The Author(s).)

Purpose: Osteoid osteoma occasionally occur in the spine, but their malignant transformation is not common. We present an extremely rare case of the malignant transformation of an osteoid osteoma to high-grade osteosarcoma that formed in the pedicle and spread to the lateral mass of the cervical spine., Case Presentation: We report the case of an 18-year-old man who suffered from neck pain as an initial symptom. The size of the radiolucent lesion was 12 mm in diameter at the time of diagnosis. Intralesional tumour resection and autologous bone grafting were performed. The remaining tumour grew gradually for 40 months after the surgery; therefore, the tumour had grown rapidly till 51 months after the initial diagnosis. At this stage, the tumour size was approximately 6-fold larger than the initial size, and resulted in progressive paraplegia. A biopsy revealed that the tumour had transformed into a high-grade osteosarcoma. Heavy charged particle irradiation was performed to control tumour growth., Conclusions: There is a possibility of malignant transformation of osteoid osteoma. Patients with osteoid osteoma or osteoblastoma should be carefully observed, especially for recurrent tumours after an intralesional resection.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are clinically available to control blood glucose levels in diabetic patients via an insulin-independent mechanism. It was found that some carbasugar analogs of known SGLT2 inhibitors exert a high inhibiting ability toward SGLT2 and have a prolonged blood glucose lowering effect. In this study, we designed new candidates of carbasugar SGLT2 inhibitor that can be synthesized using copper-catalyzed azide-alkyne cycloaddition (CuAAC) into an aromatic ring, which is a part of the pharmacophore at the final stage in the synthetic protocol for the easier discovery of superior SGLT2 inhibitors. Based on the results of molecular docking studies, some selected compounds have been synthesized. Evaluation of these compounds using a cell-based assay revealed that the majority of these compounds had SGLT2 inhibitory activity in a dose-dependent manner. The SGLT2 inhibitory activity of 7b and 7c was almost equal to that of SGLT2 inhibitors in current use. Furthermore, molecular dynamics simulations also revealed that 7c is a promising novel SGLT2 inhibitor.

Introduction: Venous thromboembolism (VTE) is a life-threatening complication occurring in cancer patients. Direct oral anticoagulants (DOACs) or warfarin are widely prescribed for treating cancer-associated VTE. However, data are sparse as to the effectiveness and bleeding complications associated with these medications in elderly patients. The purpose of this study was to compare effectiveness and safety profiles between DOACs and warfarin in elderly cancer patients undergoing chemotherapy., Methods: Using the Diagnosis Procedure Combination inpatient database, we retrospectively identified cancer patients aged ≥75 years who developed VTE during chemotherapy (n = 4,278, January 2016 to March 2020). Eligible patients were divided into those receiving warfarin (n = 557) and DOACs (n = 3,721). We conducted a 1:4 propensity score matching analysis to adjust for measured confounders. The primary outcome was VTE recurrence requiring hospitalization. Secondary outcomes were major bleeding requiring hospitalization and inhospital death from all causes within 6 months., Results: The propensity-matched cohort included 557 patients in the warfarin group and 2,278 patients in the DOACs group. The proportion of VTE recurrence requiring hospitalization was lower in the DOACs group (5.3% vs. 7.5%; odds ratio [OR], 0.69; 95% confidence interval [CI], 0.48-0.98). The proportion of recurrent deep vein thrombosis was 6.3% and 4.4%, while that of recurrent pulmonary emboli was 1.3% and 1.3% in the warfarin and DOACs groups, respectively. No statistically significant differences were found in the proportion of major bleeding events requiring hospitalization (1.6% vs. 1.1%; OR, 1.47; 95% CI, 0.62-3.50) or all-cause inhospital mortality (11.1% vs. 9.9%; OR, 1.14; 95% CI, 0.84-1.56) between the DOACs and warfarin groups., Conclusion: Our findings suggest that DOACs may be more effective than warfarin in terms of VTE recurrence requiring hospitalization and that these medications may be equivalent in terms of safety., (© 2022 The Author(s). Published by S. Karger AG, Basel.)

This study is the first attempt to examine anatomical characteristics using three-dimensional computed tomography (3DCT) bone images with some parameters, in order to achieve correct and uncomplicated accesses. In addition, the study addresses a long-standing problem in the field and evaluates whether the trigonum sacrale forms an equilateral triangle or not. A detailed anatomic study of the sacral region was carried out on 91 patient 3DCT images. The CT data, in DICOM format, was read into VINCENT software from Fuji Film, with a slice thickness of 0.5 mm. The average length of sacral hiatus was 28.6 ± 8.4 (range 13.8-45.2 mm). The average width of sacral hiatus at the level of sacral cornua was 10.9 ± 2.7 (range 3.8-16.5 mm). The ratio between the length of the oblique and base line formed by the sacral triangle was 0.81 ± 0.12 (range 0.54-1.00). Using 3DCT images translated by the volume rendering technique, we can remove soft tissue from bones virtually. A slice thickness of 0.5 mm makes it a fine image, and permits meticulous measurement, which is different from previous cadaveric studies. Interestingly, our data showed that the ratio between oblique and base line on sacral triangle was <1.0, average 0.81. Findings demonstrated that the trigonum sacrale is not an equilateral triangle. This is useful information for the identification of the sacral hiatus when the landmark-based technique is employed., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Traumatic occipitocervical dislocation (OCD) occurs due to fatal high-energy injury. Modern screw-based constructs enable successful reduction and stabilisation. In view of this, there are no previous reports on the spontaneous remodelling of the O-C1 joint after posterior fusion. We report the first case of postoperative spontaneous remodelling and stabilisation of the O-C1 joint after traumatic OCD. Case description: A 9-year-old girl suffered from traumatic OCD, accompanied by complete rupture of the O-C1-C2 ligamentous complex. Halo-vest fixation, and subsequently posterior fusion surgery from the occipital bone to C2, with autologous iliac crest bone graft and an allograft were performed. However, we could not achieve complete reduction of the O-C1 joint during surgery owing to extremely severe instability.Postoperative X-ray and computed tomography scan showed incomplete reduction of the O-C1 joint. Insufficient congruity of the O-C1 joint persisted. Afterwards, gradual spontaneous remodelling of the O-C1 joint occurred, both anteriorly and posteriorly 3 months postoperatively. Solid union was achieved 6 months postoperatively. Two years later, bilateral O-C1 joints in the patient were completely reformed and restabilised by incredible vigorous remodelling. Insufficient reduction and persisting poor joint congruence after surgery for OCD was probably restabilised by further spontaneous remodelling of articular morphology in such a young patient., Conclusions: Postoperative spontaneous remodelling of the O-C1 joint after posterior reconstruction for OCD may occur in young patients. Incomplete reduction of the O-C1 joint during surgery may be acceptable due to the possibility of postoperative bone remodelling and restabilisation.

Background: Ectopic gas in the graft is occasionally encountered upon follow-up computed tomography (CT) after anterior cervical corpectomy and fusion (ACCF). However, most cases lack inflammatory responses and manifestations of infection. Although the clinical significance of ectopic gas in the graft has not yet been established, to the best of our knowledge, no previous studies have described ectopic gas in the graft after ACCF. This study evaluated ectopic gas in the fibular graft upon follow-up CT after ACCF., Methods: We reviewed 112 patients who underwent ACCF and follow-up CT, with a minimum follow-up period of 3 years. CT images were retrospectively reviewed to confirm the presence of ectopic gas in the graft and bone fusion. Bone fusion was defined as follows: mobility less than 2 mm between spinous processes on the flection-extension radiograph or a bone bridge on CT images., Results: Of the 112 patients, 30 (27%) patients had ectopic gas in the fibular grafts. Among them, ectopic gas was initially observed 3 months after surgery (early onset) in 23 (77%) patients and 6 months after surgery (late-onset) in the remaining seven (23%) patients. Upon the latest follow-up CT, ectopic gas more frequently remained in late-onset (4/7, 57%) rather than in early-onset (3/23, 13%) cases (p = 0.033). Bone fusion was not observed when CT images exhibited ectopic gas in the graft, whereas ectopic gas was not observed when CT images exhibited bone fusion., Conclusion: Ectopic gas in the fibular graft was observed at both early and late-onset after ACCF; late-onset gas remained significantly. The remaining gas was strongly associated with pseudoarthrosis; therefore, pseudoarthrosis should be considered when ectopic gas in the graft is observed on CT images., (© 2021. The Author(s).)

Purpose: Sagittal lumbar apex has been demonstrated to be a key parameter in sagittal plane morphology. Our aim was to understand its behavior with postural changes, analyzing two different concepts of lumbar apex., Materials and Methods: Prospective observational study with a cohort of patients presenting sagittal malalignment identified from a monocenter database of adult spinal deformities (ASD). Inclusion criteria were age > 30 years, SVA > 40 mm, and/or PT > 20. All patients had full-spine EOS radiographs in 2 different positions: (P1: natural position) and position 2 (P2: compensated position). Sagittal alignment, spinopelvic values, and two different methods of assessing lordosis apex location were analyzed in both P1 and P2 positions. Changes between P1 and P2 were compared using a paired t test with a significance level at p < 0.05., Results: Twenty-five patients were recruited (21 women and 4 men). The mean age was 64.8 years (range 21-79). The patient's main compensation was based on an increase in the femoral shaft angle, and pelvic retroversion, with a subsequent decrease in sacral slope, and therefore of the lower lumbar arc. When the lumbar apex was calculated as the most anterior point touching the vertical line in a lateral radiograph, postural compensation changes modified its location usually shifting it to a more caudal position. When the lumbar apex was assessed as the most distant point of the global lumbar lordosis, its position remained stable regardless of compensation., Conclusions: Postural changes can modify the location of the lumbar apex when understanding its location as the cornerstone of sagittal plane harmonic distribution. This concept can be useful as an additional sign to assess compensation. However, if the lumbar apex was calculated as the angular point of the global lordosis, its position remained stable regardless of postural changes. This concept can help to mold lumbar lordosis in ASD surgery., Level of Evidence Iv: Diagnostic: individual cross-sectional studies with consistently applied reference standard and blinding.

Attenuation of the secondary injury of spinal cord injury (SCI) can suppress the spread of spinal cord tissue damage, possibly resulting in spinal cord sparing that can improve functional prognoses. Granulocyte colony-stimulating factor (G-CSF) is a haematological cytokine commonly used to treat neutropenia. Previous reports have shown that G-CSF promotes functional recovery in rodent models of SCI. Based on preclinical results, we conducted early phase clinical trials, showing safety/feasibility and suggestive efficacy. These lines of evidence demonstrate that G-CSF might have therapeutic benefits for acute SCI in humans. To confirm this efficacy and to obtain strong evidence for pharmaceutical approval of G-CSF therapy for SCI, we conducted a phase 3 clinical trial designed as a prospective, randomized, double-blinded and placebo-controlled comparative trial. The current trial included cervical SCI [severity of American Spinal Injury Association (ASIA) Impairment Scale (AIS) B or C] within 48 h after injury. Patients are randomly assigned to G-CSF and placebo groups. The G-CSF group was administered 400 μg/m2/day × 5 days of G-CSF in normal saline via intravenous infusion for five consecutive days. The placebo group was similarly administered a placebo. Allocation was concealed between blinded evaluators of efficacy/safety and those for laboratory data, as G-CSF markedly increases white blood cell counts that can reveal patient treatment. Efficacy and safety were evaluated by blinded observer. Our primary end point was changes in ASIA motor scores from baseline to 3 months after drug administration. Each group includes 44 patients (88 total patients). Our protocol was approved by the Pharmaceuticals and Medical Device Agency in Japan and this trial is funded by the Center for Clinical Trials, Japan Medical Association. There was no significant difference in the primary end point between the G-CSF and the placebo control groups. In contrast, one of the secondary end points showed that the ASIA motor score 6 months (P = 0.062) and 1 year (P = 0.073) after drug administration tend to be higher in the G-CSF group compared with the placebo control group. Moreover, in patients aged over 65 years old, motor recovery 6 months after drug administration showed a strong trend towards a better recovery in the G-CSF treated group (P = 0.056) compared with the control group. The present trial failed to show a significant effect of G-CSF in primary end point although the subanalyses of the present trial suggested potential G-CSF benefits for specific population., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Organophosphates (OPs) inhibit cholinesterase and hyperactivate the acetylcholinergic nervous system in the brain, causing motor disorders (e.g., tremor and seizures). Here, we performed behavioral and immunohistochemical studies in mice and rats to investigate the tremorgenic mechanism of paraoxon, an active metabolite of parathion. Treating animals with paraoxon (0.15-0.6 mg/kg, i.p.) elicited kinetic tremor in a dose-dependent manner. Expressional analysis of Fos protein, a biomarker of neural excitation, revealed that a tremorgenic dose of paraoxon (0.6 mg/kg) significantly and region-specifically elevated Fos expression in the cerebral cortex (e.g., sensory cortex), hippocampal CA1, globus pallidus, medial habenula, and inferior olive (IO) among 48 brain regions examined. A moderate increase in Fos expression was also observed in the dorsolateral striatum while the change was not statistically significant. Paraoxon-induced tremor was inhibited by the nicotinic acetylcholine (nACh) receptor antagonist mecamylamine (MEC), but not affected by the muscarinic acetylcholine receptor antagonist trihexyphenidyl (THP). In addition, paraoxon-induced Fos expression in the IO was also antagonized by MEC, but not by THP, and lesioning of the IO markedly suppressed tremorgenic action of paraoxon. The present results suggest that OPs elicit kinetic tremor at least partly by activating IO neurons via nACh receptors.

Purpose: To report a patient with bilateral vocal cord palsy following cervical laminoplasty, who survived following a tracheotomy and intensive respiratory care., Methods: Acute respiratory distress is a fatal complication of cervical spinal surgery. The incidence of bilateral vocal cord palsy after posterior cervical decompression surgery is extremely rare. The authors report a 71-year-old woman who suffered from cervical myelopathy due to ossification of the posterior longitudinal ligament. Open-door laminoplasty from C2 to C6 and laminectomy of C1 were performed. Following surgery, extubation was successfully conducted. Acute-onset dysphagia and stridor had occurred 2 h following extubation. A postoperative fiber optic laryngoscope revealed bilateral vocal cord palsy. After a tracheotomy and intensive respiratory care, she had completely recovered 2 months after surgery., Discussion: One potential cause of this pathology was an intraoperative hyper-flexed neck position, which likely induced mechanical impingement of the larynx, resulting in swelling and edema of the vocal cords and recurrent laryngeal nerve paresis. Direct trauma of the vocal cords during intubation and extubation could have also induced vocal cord paralysis., Conclusions: We reported a case of bilateral vocal cord palsy associated with posterior cervical laminoplasty. Airway complications following posterior spinal surgery are rare, but they do occur; therefore, spine surgeons should be aware of them and take necessary precautions against intraoperative neck position, intubation technique, even positioning of the intratracheal tube.

We previously showed that nicotine evoked kinetic tremor by activating the inferior olive, which is implicated in the pathogenesis of essential tremor, via α7 nicotinic acetylcholine receptors. Here, we evaluated the effects of various anti-tremor and anti-epileptic agents on nicotine-induced tremor in mice to clarify the pharmacological characteristics of nicotine tremor. Drugs effective for essential tremor, propranolol, diazepam and phenobarbital, all significantly inhibited kinetic tremor induced by an intraperitoneal (i.p.) injection of nicotine (1 mg/kg). In contrast, none of the medications for Parkinson's disease, l-DOPA, bromocriptine or trihexyphenidyl, affected the nicotine tremor. Among the anti-epileptic agents examined, valproate, carbamazepine and ethosuximide, significantly inhibited nicotine-induced tremor. In addition, a selective T-type Ca 2+ channel blocker, TTA-A2, also suppressed the nicotine tremor. However, neither gabapentin, topiramate, zonisamide nor levetiracetam significantly affected nicotine-induced tremor. The present results show that nicotine-induced tremor resembles essential tremor not only on the neural basis, but also in terms of the pharmacological responses to anti-tremor agents, implying that nicotine-induced tremor can serve as a model for essential tremor. In addition, it is suggested that anti-epileptic agents, which have stimulant actions on the GABAergic system or blocking actions on voltage-gated Na + channels and T-type Ca 2+ channels, can alleviate essential tremor., (Copyright © 2018 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)