Contribution of methylglyoxal to delayed healing of bone injury in diabetes

13301甲第4592号博士（医学）金沢大学博士論文要旨Abstract 以下に掲載：Molecular Medicine Reports 16(1) pp.403-409 2017. SPANDIDOS publications. 共著者：相川 敬男，松原 秀憲，宇賀治 修平，永井 竜児, 白河 潤一, 棟居 聖一，原島 愛, 山本 靖彦, 土屋 弘

Intra-articular osteoid osteoma of the calcaneus: a case report and review

AbstractOsteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis

Intra-articular osteoid osteoma of the calcaneus: A case report and review

Osteoid osteoma of the calcaneus is rare and frequently misdiagnosed as arthritis because of similar symptoms. In addition, radiographic findings may be nonspecific, and magnetic resonance imaging (MRI) may show a bone marrow edema and changes in adjacent soft tissue. A 19-year-old man presented with a 6-month history of persistent pain and swelling in the left hind foot; diagnostic computed tomography and MRI analyses revealed lesions suggesting an intra-articular osteoid osteoma of the calcaneus. Initial MRI did not show specific findings. On operation, the tumor was removed by curettage; pathologic findings demonstrated woven bone trabeculae surrounded by connective tissue, confirming the diagnosis. To the best of our knowledge, MRI scans in all cases of calcaneal osteoid osteoma reported till 3 months after the injury exhibited a nidus. We believe that calcaneal osteoid osteoma should be considered as a differential diagnosis in patients undergoing MRI 3 months after symptom presentation; early computed tomography is critical in diagnosis. © 2016 The Authors.Embargo Period 12 month

Significant Impact of Age on Mortality and Non-significant Impact of Age on Thrombosis and Major Bleeding in Patients with COVID-19: From the CLOT-COVID Study.

AIM: There is scarce data on the impact of age on clinical outcomes in patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study was a retrospective, multicenter cohort study enrolling 2894 consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021. We divided the entire cohort into five groups according to age strata; -19, 20-39, 40-59, 60-79, and 80- years. RESULTS: Most patients under 19 had mild COVID-19 on admission (99%), while older patients had more severe COVID-19. The incidence rates of clinical outcomes during hospitalization in patients aged ≤ 19, 20-39, 40-59, 60-79, and 80 ≥ years were 0.0%, 0.5%, 2.2%, 2.7%, and 1.5% for thrombosis; 0.0%, 1.2%, 1.5%, 3.4%, and 2.0% for major bleeding; and 0.0%, 0.4%, 2.0%, 12.1%, and 16.8% for all-cause death, respectively. In the stratified analysis according to COVID-19 severity on admission, the incidences of thrombosis were generally higher among patients with more severe status, although those were not significantly different among age strata in all sub-types of COVID-19 severity. However, the incidences of all-cause death were significantly higher with increasing age in all sub-types of COVID-19 severity. CONCLUSIONS: In the current large observational study of patients with COVID-19, the risk of mortality became markedly higher with increased age. However, the risks of thrombosis and major bleeding did not necessarily increase as age increases, which seemed to be consistent irrespective of COVID-19 severity on admission

The current status of thrombosis and anticoagulation therapy in patients with COVID-19 in Japan: From the CLOT-COVID study

BACKGROUND: Data on thrombosis and current real-world management strategies for anticoagulation therapy are scarce but important for understanding current issues and unmet needs of an optimal management of patients with coronavirus disease 2019 (COVID-19). METHOD: The CLOT-COVID Study (thrombosis and antiCoaguLatiOn Therapy in patients with COVID-19 in Japan Study: UMIN000045800) was a retrospective, multicenter cohort study enrolling consecutive hospitalized patients with COVID-19 among 16 centers in Japan from April 2021 to September 2021, and we tried to capture the status of the patients in the fourth and fifth waves of the COVID-19 infections in Japan. We enrolled consecutive hospitalized patients who were diagnosed with COVID-19 and had a positive polymerase chain reaction test obtained from the hospital databases. RESULTS: Among 2894 patients with COVID-19, 1245 (43%) received pharmacological thromboprophylaxis. The proportion of pharmacological thromboprophylaxis increased according to the severity of the COVID-19 in 9.8% with mild COVID-19, 61% with moderate COVID-19, and 97% with severe COVID-19. The types and doses of anticoagulants varied widely across the participating centers. During the hospitalization, 38 patients (1.3%) and 126 (4.4%) underwent ultrasound examinations for the lower extremities and contrast-enhanced computed tomography examinations, respectively, and 55 (1.9%) developed thrombosis, mostly venous thromboembolism (71%). The incidence of thrombosis increased according to the severity of the COVID-19 in 0.2% with mild COVID-19, 1.4% with moderate COVID-19, and 9.5% with severe COVID-19. Major bleeding occurred in 57 patients (2.0%) and 158 (5.5%) died, and 81% of them were due to respiratory failure from COVID-19 pneumonia. CONCLUSIONS: In the present large-scale observational study, pharmacological thromboprophylaxis for hospitalized patients with COVID-19 was common especially in patients with severe COVID-19, and management strategies varied widely across the participating centers. The overall incidence of thrombosis was substantially low with an increased incidence according to the severity of the COVID-19

A Genome-Wide Association Study Identified AFF1 as a Susceptibility Locus for Systemic Lupus Eyrthematosus in Japanese

Systemic lupus erythematosus (SLE) is an autoimmune disease that causes multiple organ damage. Although recent genome-wide association studies (GWAS) have contributed to discovery of SLE susceptibility genes, few studies has been performed in Asian populations. Here, we report a GWAS for SLE examining 891 SLE cases and 3,384 controls and multi-stage replication studies examining 1,387 SLE cases and 28,564 controls in Japanese subjects. Considering that expression quantitative trait loci (eQTLs) have been implicated in genetic risks for autoimmune diseases, we integrated an eQTL study into the results of the GWAS. We observed enrichments of cis-eQTL positive loci among the known SLE susceptibility loci (30.8%) compared to the genome-wide SNPs (6.9%). In addition, we identified a novel association of a variant in the AF4/FMR2 family, member 1 (AFF1) gene at 4q21 with SLE susceptibility (rs340630; P = 8.3×10−9, odds ratio = 1.21). The risk A allele of rs340630 demonstrated a cis-eQTL effect on the AFF1 transcript with enhanced expression levels (P<0.05). As AFF1 transcripts were prominently expressed in CD4+ and CD19+ peripheral blood lymphocytes, up-regulation of AFF1 may cause the abnormality in these lymphocytes, leading to disease onset

Critical Takotsubo Cardiomyopathy Complicated by Ventricular Septal Perforation

An 81-year-old woman was admitted with chest pain. An electrocardiogram demonstrated ST segment elevation in leads II, III and aVF, and echocardiography revealed left ventricular apical asynergy with a left-to-right ventricular shunt. Meanwhile, emergent coronary angiography showed no significant coronary artery stenosis, whereas left ventriculography indicated apical ballooning and a left-to-right ventricular shunt. We therefore diagnosed the patient with Takotsubo cardiomyopathy complicated by ventricular septal perforation and cardiogenic shock. An electrocardiogram disclosed a prolonged QT interval over time, and the patient became hemodynamically stable under treatment with inotropes; however, she suddenly developed fatal ventricular fibrillation three days after hospitalization. Takotsubo cardiomyopathy complicated by ventricular septal perforation is a critical condition that requires careful monitoring

Prolonged Fecal Shedding of Hepatitis E Virus (HEV) during Sporadic Acute Hepatitis E: Evaluation of Infectivity of HEV in Fecal Specimens in a Cell Culture System▿

To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 × 103 to 1.7 × 107 copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 × 104 copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 × 107 copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient 1 was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer of up to 107 copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein

Lengthening for functional acetabular dysplasia due to limb length discrepancy: A report of two cases

Osteoarthritis of the hip joint as a complication of limb length discrepancy (LLD) caused by lower extremity deformity is rarely reported in the literature. We report two such cases of osteoarthritic changes of the long leg hip joint due to severe LLD but no developmental dysplasia of the hip. Both underwent limb lengthening, and the symptoms were improved without further treatment. The osteoarthritic changes are secondary to functional acetabular dysplasia resulting in insufficient acetabular coverage of the femoral head and lateral inclination of the pelvis caused by LLD. Thus, lengthening treatment may be one option for such patients with osteoarthritis due to functional acetabular dysplasia