ABSTRACT
Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We discovered DS44470011 in our previous study, which showed potent in vitro activity and in vivo efficacy based on HIF-PHD inhibition. However, DS44470011 was also found to exert genotoxic effects. By converting the biphenyl structure, which is suspected to be the cause of this genotoxicity, to a 1-phenylpiperidine structure, we were able to avoid genotoxicity and further improve the in vitro activity and in vivo efficacy. Furthermore, through the optimization of pyrimidine derivatives, we discovered DS-1093a, which has a wide safety margin with potent in vitro activity and an optimal pharmacokinetic profile. DS-1093a achieved an increase in hemoglobin levels in an adenine-induced rat model of chronic kidney disease after its continuous administration for 4 days.
ABSTRACT
For small-molecule drugs, lipidation via a cleavable linkage can extend half-life in circulation through interaction with albumin. Here we modified the cysteinylprolyl ester (CPE) system used in peptide thioester synthesis, which normally requires basic conditions, for use as an self-immolative linker and release device for a lipid-gemcitabine conjugate. To improve release under physiological conditions for medical application, a methyl group at the α-position of cysteine on the CPE unit was incorporated in anticipation of the Thorpe-Ingold effect. As a result, Ac-Gly-(α-Me)Cys(SH)-Pro-gemcitabine 11 drastically promoted the release of gemcitabine in comparison with Ac-Gly-Cys(SH)-Pro-gemcitabine 10. Furthermore, in the presence of bovine serum albumin and/or 2-mercaptoethanesulfonic acid, the gentle and continuous release of gemcitabine from the lipid-gemcitabine conjugate 16 was achieved. In addition to gemcitabine, this method could allow high clearance drugs, including nucleic acid and prostacyclin derivatives, to maintain their biological activity long enough to become effective.
Subject(s)
Deoxycytidine , Esters , Gemcitabine , Lipids , Deoxycytidine/chemistry , Deoxycytidine/analogs & derivatives , Deoxycytidine/pharmacology , Lipids/chemistry , Esters/chemistry , Esters/pharmacology , Esters/chemical synthesis , Drug Liberation , Cysteine/chemistry , Humans , Molecular Structure , Serum Albumin, Bovine/chemistry , AnimalsABSTRACT
Globally, the rapid aging of the population is predicted to become even more severe in the second half of the 21st century. Thus, it is expected to establish a growing expectation for innovative, non-invasive health indicators and diagnostic methods to support disease prevention, care, and health promotion efforts. In this study, we aimed to establish a new health index and disease diagnosis method by analyzing the minerals and free amino acid components contained in hair shaft. We first evaluated the range of these components in healthy humans and then conducted a comparative analysis of these components in subjects with diabetes, hypertension, androgenetic alopecia, major depressive disorder, Alzheimer's disease, and stroke. In the statistical analysis, we first used a student's t test to compare the hair components of healthy people and those of patients with various diseases. However, many minerals and free amino acids showed significant differences in all diseases, because the sample size of the healthy group was very large compared to the sample size of the disease group. Therefore, we attempted a comparative analysis based on effect size, which is not affected by differences in sample size. As a result, we were able to narrow down the minerals and free amino acids for all diseases compared to t test analysis. For diabetes, the t test narrowed down the minerals to 15, whereas the effect size measurement narrowed it down to 3 (Cr, Mn, and Hg). For free amino acids, the t test narrowed it down to 15 minerals. By measuring the effect size, we were able to narrow it down to 7 (Gly, His, Lys, Pro, Ser, Thr, and Val). It is also possible to narrow down the minerals and free amino acids in other diseases, and to identify potential health indicators and disease-related components by using effect size.
Subject(s)
Amino Acids , Hair , Humans , Hair/chemistry , Male , Amino Acids/analysis , Amino Acids/metabolism , Female , Middle Aged , Adult , Alopecia/diagnosis , Aged , Minerals/analysis , Minerals/metabolism , Alzheimer Disease/diagnosis , Alzheimer Disease/metabolism , Stroke , Hypertension , Depressive Disorder, Major/diagnosis , Diabetes Mellitus/diagnosis , Case-Control StudiesABSTRACT
Inhibition of the hypoxia-inducible factor prolyl hydroxylase (HIF-PHD) represents a promising strategy for discovering next-generation treatments for renal anemia. We identified a pyrimidine core with HIF-PHD inhibitory activity based on scaffold hopping of FG-2216 using crystal structures of HIF-PHD2 in complex with compound. By optimizing the substituents at the 2- and 6- positions of the pyrimidine core, we discovered DS44470011, which improves the effectiveness of erythropoietin (EPO) release in cells. Oral administration of DS44470011 to cynomolgus monkeys increased plasma EPO levels.
Subject(s)
Anemia , Hypoxia-Inducible Factor-Proline Dioxygenases , Macaca fascicularis , Prolyl-Hydroxylase Inhibitors , Animals , Anemia/drug therapy , Hypoxia-Inducible Factor-Proline Dioxygenases/antagonists & inhibitors , Hypoxia-Inducible Factor-Proline Dioxygenases/metabolism , Administration, Oral , Humans , Prolyl-Hydroxylase Inhibitors/pharmacology , Prolyl-Hydroxylase Inhibitors/chemistry , Prolyl-Hydroxylase Inhibitors/chemical synthesis , Pyrimidines/chemistry , Pyrimidines/pharmacology , Pyrimidines/chemical synthesis , Structure-Activity Relationship , Molecular Structure , Erythropoietin , Drug Discovery , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesisABSTRACT
Collection and cooking of wild vegetables have provided seasonal enjoyments for Japanese local people as provisioning and cultural ecosystem services. However, the Fukushima Daiichi Nuclear Power Plant accident in March 2011 caused extensive radiocesium contamination of wild vegetables. Restrictions on commercial shipments of wild vegetables have been in place for the last 10 years. Some species, including buds of Aralia elata, are currently showing radiocesium concentrations both above and below the Japanese reference level for food (100 Bq/kg), implying that there are factors decreasing and increasing the 137Cs concentration. Here, we evaluated easy-to-measure environmental variables (dose rate at the soil surface, organic soil layer thickness, slope steepness, and presence/absence of decontamination practices) and the 137Cs concentrations of 40 A. elata buds at 38 locations in Fukushima Prefecture to provide helpful information on avoiding collecting highly contaminated buds. The 137Cs concentrations in A. elata buds ranged from 1 to 6,280 Bq/kg fresh weight and increased significantly with increases in the dose rate at the soil surface (0.10-6.50 µSv/h). Meanwhile, the 137Cs concentration in A. elata buds were not reduced by decontamination practices. These findings suggest that measuring the latest dose rate at the soil surface at the base of A. elata plants is a helpful way to avoid collecting buds with higher 137Cs concentrations and aid in the management of species in polluted regions.
Subject(s)
Aralia , Fukushima Nuclear Accident , Isoflavones , Radiation Monitoring , Soil Pollutants, Radioactive , Humans , Vegetables , Cesium Radioisotopes/analysis , Ecosystem , Soil Pollutants, Radioactive/analysis , Soil , Soybean Proteins , JapanABSTRACT
Synthetic trade-offs exist in the synthesis of single-walled carbon nanotube (SWCNT) forests, as growing certain desired properties can often come at the expense of other desirable characteristics such as the case of crystallinity and growth efficiency. Simultaneously achieving mutually exclusive properties in the growth of SWCNT forests is a significant accomplishment, as it requires overcoming these trade-offs and balancing competing mechanisms. To address this, we trained a machine-learning regression model with a set of 585 "real" experimental synthesis data, which were taken using an automatic synthesis reactor. Subsequently, 16000 exploratory "virtual" experiments were performed by our trained model to examine potential routes toward addressing the current crystallinity-height trade-off limitation, and suggestions on growth conditions were predicted. Importantly, additional validation using "real" experimental syntheses showed good agreement with the predictions as well as a 48% increase in growth efficiency while maintaining the high crystallinity (G/D-ratio). This highlighted the effectiveness and accuracy of the predictive capability of our machine-learning model, which achieved improved results in less than 50 validation tests. Furthermore, the trained model revealed the surprising importance of the nature of the carbon feedstock, particularly the reactivity and concentration, as a route for overcoming the trade-off between the SWCNT crystallinity and growth efficiency. These results of the high-efficiency synthesis of highly crystalline SWCNT forests represent a significant advance in overcoming synthetic trade-off barriers for complex multivariable systems.
ABSTRACT
Hypoxia in cancer is important in the development of cancer-selective medicines. Here, a novel hypoxia-responsible dual-prodrug is described. We designed and synthesized 2-nitroimidazole derivatives which spontaneously release both a PYG inhibitor and gemcitabine under hypoxic conditions. One such derivative, a prodrug 9 was found to be stable against chemical and enzymatic hydrolysis, and upon chemical reduction of the nitro group on imidazole, successfully releases both drugs. In an in vitro proliferation assay using human pancreatic cells, compound 9 exhibited significant anti-proliferative effects in hypoxia but fewer effects in normoxia. Consequently, prodrug 9 should be useful for cancer treatment due to its improved cancer selectivity and potential to overcome drug resistance.
ABSTRACT
Biological rhythms are involved in almost all types of biological processes, not only physiological processes but also morphogenesis. Currently, how periodic morphological patterns of tissues/organs in multicellular organisms form is not fully understood. Here, using mouse zigzag hair, which has 3 bends, we found that a change in the combination of hair progenitors and their micro-niche and subsequent bend formation occur every three days. Chimeric loss-of-function and gain-of-function of Ptn and Aff3, which are upregulated immediately before bend formation, resulted in defects in the downward movement of the micro-niche and the rhythm of bend formation in an in vivo hair reconstitution assay. Our study demonstrates the periodic change in the combination between progenitors and micro-niche, which is vital for the unique infradian rhythm.
Subject(s)
Infradian Rhythm , Mice , Animals , Hair , Periodicity , Hair FollicleABSTRACT
Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development.
Subject(s)
Diabetes Mellitus, Type 2 , Ossification of Posterior Longitudinal Ligament , Animals , Mice , Osteogenesis , Genome-Wide Association Study , Diabetes Mellitus, Type 2/pathology , Spine/pathology , Ossification of Posterior Longitudinal Ligament/genetics , Ossification of Posterior Longitudinal Ligament/pathologyABSTRACT
While the functionalization of carbon nanotubes (CNTs) has attracted extensive interest for a wide range of applications, a facial and versatile strategy remains in demand. Here, we report a microwave-assisted, solvent-free approach to directly functionalize CNTs both in raw form and in arbitrary macroscopic assemblies. Rapid microwave irradiation was applied to generate active sites on the CNTs while not inducing excessive damage to the graphitic network, and a gas-phase deposition afforded controllable grafting for thorough or regioselective functionalization. Using methyl methacrylate (MMA) as a model functional group and a CNT sponge as a model assembly, homogeneous grafting was exhibited by the increased robust hydrophobicity (contact angle increase from 30 to 140°) and improved structural stability (compressive modulus increased by 135%). Therefore, when our MMA-functionalized CNTs served as a solar absorber for saline distillation, high operating stability with a superior water evaporation rate of â¼2.6 kg m-2 h-1 was observed. Finally, to highlight the efficacy and versatility of this functionalization approach, we fabricated asymmetrically hydrophobic CNT sponges by regioselective functionalization to serve as a moisture-driven generator, which demonstrated a stable open-circuit voltage of 0.6 mV. This versatile, solvent-free approach can complement conventional solution-based techniques in the design and fabrication of multifunctional nanocarbon-based materials.
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BACKGROUND CONTEXT: Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have closely investigated the factors contributing to the quality of life (QOL) in the chronic phase after thoracolumbar OVFs using detailed radiographic evaluation. PURPOSE: This study aimed to identify factors associated with the QOL in the chronic phase after thoracolumbar OVF. DESIGN: Post hoc analysis of a prospective randomized study. PATIENT SAMPLE: Participants included 195 patients with fresh thoracolumbar OVF managed conservatively with a brace who were available for radiographic analysis 48 weeks after injury. OUTCOME MEASURES: The degree of QOL impairment at 48 weeks after thoracolumbar OVF was assessed using the Japanese three-level version of the EuroQol five-dimensional questionnaire (EQ-5D) score. METHODS: Univariate and multivariate regression analyses were used to evaluate the relationships between the QOL and radiographic factors. RESULTS: The univariate analysis showed that age, analgesic use, T10/L5 Cobb angle on magnetic resonance imaging (MRI), subsequent vertebral fracture, and nonunion were significantly associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. The multiple regression analysis showed that nonunion, analgesic use, subsequent vertebral fracture, and sacral slope on MRI were independently associated with the EQ-5D score at 48 weeks after thoracolumbar OVF. Receiver operating characteristic analysis for the deterioration of QOL showed that the cutoff value for sacral slope on MRI was 35 degrees. CONCLUSIONS: This study demonstrated that nonunion, subsequent vertebral fracture, and lower sacral slope were independently associated with poorer QOL in the chronic phase of thoracolumbar OVF managed conservatively with a brace. Therefore, improving or preventing these factors in patients with thoracolumbar OVF in the chronic phase may improve the QOL of the affected patients.
Subject(s)
Osteoporotic Fractures , Spinal Fractures , Humans , Osteoporotic Fractures/diagnostic imaging , Osteoporotic Fractures/therapy , Osteoporotic Fractures/complications , Spinal Fractures/diagnostic imaging , Spinal Fractures/therapy , Spinal Fractures/complications , Quality of Life , Prospective Studies , AnalgesicsABSTRACT
BACKGROUND: The Japanese Orthopaedic Association (JOA) guideline for the management of lumbar spinal stenosis (LSS) was first published in 2011. Since then, the medical care system for LSS has changed and many new articles regarding the epidemiology and diagnostics of LSS, conservative treatments such as new pharmacotherapy and physical therapy, and surgical treatments including minimally invasive surgery have been published. In addition, various issues need to be examined, such as verification of patient-reported outcome measures, and the economic effect of revised medical management of patients with lumbar spinal disorders. Accordingly, in 2019 the JOA clinical guidelines committee decided to update the guideline and consequently established a formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline, incorporating the recent advances of evidence-based medicine. METHODS: The JOA LSS guideline formulation committee revised the previous guideline based on the method for preparing clinical guidelines in Japan proposed by the Medical Information Network Distribution Service in 2017. Background and clinical questions were determined followed by a literature search related to each question. Appropriate articles based on keywords were selected from all the searched literature. Using prepared structured abstracts, systematic reviews and meta-analyses were performed. The strength of evidence and recommendations for each clinical question was decided by the committee members. RESULTS: Eight background and 15 clinical questions were determined. Answers and explanations were described for the background questions. For each clinical question, the strength of evidence and the recommendation were both decided, and an explanation was provided. CONCLUSIONS: The 2021 clinical practice guideline for the management of LSS was completed according to the latest evidence-based medicine. We expect that this guideline will be useful for all medical providers as an index in daily medical care, as well as for patients with LSS.
Subject(s)
Practice Guidelines as Topic , Spinal Stenosis , Humans , Lumbar Vertebrae/surgery , Orthopedics , Spinal Stenosis/surgery , Japan , Societies, MedicalABSTRACT
Salivary glands act as virus reservoirs in various infectious diseases and have been reported to be targeted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). However, the mechanisms underlying infection and replication in salivary glands are still enigmatic due to the lack of proper in vitro models. Here, we show that human induced salivary glands (hiSGs) generated from human induced pluripotent stem cells can be infected with SARS-CoV-2. The hiSGs exhibit properties similar to those of embryonic salivary glands and are a valuable tool for the functional analysis of genes during development. Orthotopically transplanted hiSGs can be engrafted at a recipient site in mice and show a mature phenotype. In addition, we confirm SARS-CoV-2 infection and replication in hiSGs. SARS-CoV-2 derived from saliva in asymptomatic individuals may participate in the spread of the virus. hiSGs may be a promising model for investigating the role of salivary glands as a virus reservoir.
Subject(s)
COVID-19 , Induced Pluripotent Stem Cells , Humans , Animals , Mice , SARS-CoV-2 , Organoids , Salivary GlandsABSTRACT
Age-related changes in the posterior extensor muscles of the cervical and lumbar spine have been reported in some studies; however, longitudinal changes in the thoracic spine of healthy subjects are rarely reported. Therefore, this study aimed to evaluate changes in the cross-sectional areas (CSAs) of posterior extensor muscles in the thoracic spine over 10 years and identify related factors. The subjects of this study were 85 volunteers (mean age: 44.7 ± 11.5) and the average follow-up period was about 10 years. The CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles from T1/2 to T11/12 were measured on magnetic resonance imaging. The extent of muscle fat infiltration was assessed by the signal intensity (luminance) of the extensor muscles' total cross-section compared to a section of pure muscle. We applied a Poisson regression model, which is included in the generalized linear model, and first examined the univariate (crude) association between each relevant factor (age, sex, body mass index, lifestyle, back pain, neck pain, neck stiffness, and intervertebral disc degeneration) and CSA changes. Then, we constructed a multivariate model, which included age, sex, and related factors in the univariate analysis. The mean CSAs of the transversospinalis muscles, erector spinae muscles, and total CSAs of the extensor muscles significantly increased over 10 years. Exercise habit was associated with increased CSAs of the erector spinae muscles and the total area of the extensor muscles. The cross-section mean luminance significantly increased from baseline, indicating a significant increase of fat infiltration in the posterior extensor muscles. Progression of disc degeneration was inversely associated with increased fat infiltration in the total extensor muscles.
Subject(s)
Intervertebral Disc Degeneration , Neck Pain , Adult , Humans , Intervertebral Disc Degeneration/pathology , Lumbar Vertebrae , Magnetic Resonance Imaging/methods , Middle Aged , Neck Pain/pathology , Paraspinal Muscles/diagnostic imaging , Paraspinal Muscles/pathologyABSTRACT
BACKGROUND: Gastrointestinal stromal tumors (GISTs), which are the most common soft tissue tumors of the gastrointestinal tract, originate from Cajal interneurons. The main metastatic sites of GISTs are the liver and intra-abdominal cavity, and metastasis to the heart is rare. CASE PRESENTATION: The patient was a 78-year-old man who was diagnosed with a rectal GIST 20 years previously. Since then, he had undergone repeated operations for metastasis. A follow-up thoracoabdominal computed tomography scan 4 months prior to the operation revealed GIST metastasis to the left ventricular myocardium. The patient wanted the tumor removed and consequently underwent an operation. The surgical findings showed a 3-cm × 3-cm mass in the lateral wall of the left ventricle. The mass was resected from the left ventricular wall in the shape of a tear drop. The left ventricular cavity was closed with a 4-0 polypropylene mattress suture and continuous suture. Postoperative histopathological findings showed nodular tumor growth consisting of bundles of spindle-shaped cells in the myocardium. The margins were negative. Immunostaining showed c-KIT (CD17) positivity and CD34 positivity, consistent with GIST metastasis. CONCLUSIONS: This case involved GIST metastasis to the heart muscle, which has rarely been reported worldwide.
ABSTRACT
Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have investigated the factors contributing to residual low back pain in the chronic phase after OVFs by using radiographic evaluation. We examined the contribution of nonunion, vertebral deformity, and thoracolumbar alignment to the severity of residual low back pain post-OVF. This post hoc analysis of a prospective randomized study included 195 patients with a 48-week follow-up period. We investigated the associations between radiographic variables with the visual analog scale (VAS) scores for low back pain at 48 weeks post-OVF using a multiple linear regression model. Univariate analysis revealed that analgesic use, the local angle on magnetic resonance imaging, anterior vertebral body compression percentage on X-ray, and nonunion showed a significant association with VAS scores for low back pain. Multiple regression analysis produced the following equation: VAS for low back pain at 48 weeks = 15.49 + 0.29 × VAS for low back pain at 0 weeks + (with analgesics: +8.84, without analgesics: -8.84) + (union: -5.72, nonunion: -5.72). Among local alignment, thoracolumbar alignment, and nonunion, nonunion independently contributed to residual low back pain at 48 weeks post-OVF. A treatment strategy that reduces the occurrence of nonunion is desirable.
ABSTRACT
BACKGROUND: The latest clinical guidelines are mandatory for physicians to follow when practicing evidence-based medicine in the treatment of low back pain. Those guidelines should target not only Japanese board-certified orthopaedic surgeons, but also primary physicians, and they should be prepared based entirely on evidence-based medicine. The Japanese Orthopaedic Association Low Back Pain guideline committee decided to update the guideline and launched the formulation committee. The purpose of this study was to describe the formulation we implemented for the revision of the guideline with the latest data of evidence-based medicine. METHODS: The Japanese Orthopaedic Association Low Back Pain guideline formulation committee revised the previous guideline based on a method for preparing clinical guidelines in Japan proposed by Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Two key phrases, "body of evidence" and "benefit and harm balance" were focused on in the revised version. Background and clinical questions were determined, followed by literature search related to each question. Appropriate articles were selected from all the searched literature. Structured abstracts were prepared, and then meta-analyses were performed. The strength of both the body of evidence and the recommendation was decided by the committee members. RESULTS: Nine background and nine clinical qvuestions were determined. For each clinical question, outcomes from the literature were collected and meta-analysis was performed. Answers and explanations were described for each clinical question, and the strength of the recommendation was decided. For background questions, the recommendations were described based on previous literature. CONCLUSIONS: The 2019 clinical practice guideline for the management of low back pain was completed according to the latest evidence-based medicine. We strongly hope that this guideline serves as a benchmark for all physicians, as well as patients, in the management of low back pain.
Subject(s)
Low Back Pain , Orthopedics , Evidence-Based Medicine , Humans , Japan , Low Back Pain/diagnosis , Low Back Pain/therapy , Practice Guidelines as Topic , Societies, MedicalABSTRACT
BACKGROUND: Patients with diffuse idiopathic skeletal hyperostosis (DISH) are susceptible to spinal column injuries with neurological deterioration. Previous studies indicated that the prevalence of diabetes mellitus (DM) in patients with DISH was higher than that in patients without DISH. This study investigates the impact of DM on surgical outcomes for spinal fractures in patients with DISH. METHODS: We retrospectively evaluated 177 spinal fractures in patients with DISH (132 men and 45 women; mean age, 75 ± 10 years) who underwent surgery from a multicenter database. The subjects were classified into two groups according to the presence of DM. Perioperative complications, neurological status by Frankel grade, mortality rate, and status of surgical site infection (SSI) were compared between the two groups. RESULTS: DM was present in 28.2% (50/177) of the patients. The proportion of men was significantly higher in the DM group (DM group: 86.0% vs. non-DM group: 70.1%) (p = 0.03). The overall complication rate was 22.0% in the DM group and 19.7% in the non-DM group (p = 0.60). Poisson regression model revealed that SSI was significantly associated with DM (DM group: 10.0% vs. non-DM group: 2.4%, Relative risk: 4.5) (p = 0.048). Change in neurological status, mortality rate, instrumentation failure, and nonunion were similar between both groups. HbA1c and fasting blood glucose level (SSI group: 7.2% ± 1.2%, 201 ± 67 mg/dL vs. non-SSI group: 6.6% ± 1.1%, 167 ± 47 mg/dL) tended to be higher in patients with SSI; however, there was no significant difference. CONCLUSIONS: In spinal fracture in patients with DISH, although DM was an associated factor for SSI with a relative risk of 4.5, DM did not negatively impact neurological recovery. Perioperative glycemic control may be useful for preventing SSI because fasting blood glucose level was high in patients with SSI.