Publications by authors named "Kenji Takahashi"

333 Publications

Direct Conversion of Human Fibroblasts into Adipocytes Using a Novel Small Molecular Compound: Implications for Regenerative Therapy for Adipose Tissue Defects.

Cells 2021 Mar 9;10(3). Epub 2021 Mar 9.

Immunology, Graduate School of Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan.

There is a need in plastic surgery to prepare autologous adipocytes that can be transplanted in patients to reconstruct soft tissue defects caused by tumor resection, including breast cancer, and by trauma and other diseases. Direct conversion of somatic cells into adipocytes may allow sufficient functional adipocytes to be obtained for use in regeneration therapy. Chemical libraries of 10,800 molecules were screened for the ability to induce lipid accumulation in human dermal fibroblasts (HDFs) in culture. Chemical compound-mediated directly converted adipocytes (CCCAs) were characterized by lipid staining, immunostaining, and qRT-PCR, and were also tested for adipokine secretion and glucose uptake. CCCAs were also implanted into mice to examine their distribution in vivo. STK287794 was identified as a small molecule that induced the accumulation of lipid droplets in HDFs. CCCAs expressed adipocyte-related genes, secreted adiponectin and leptin, and abundantly incorporated glucose. After implantation in mice, CCCAs resided in granulation tissue and remained adipose-like. HDFs were successfully converted into adipocytes by adding a single chemical compound, STK287794. C/EBPα and PPARγ were upregulated in STK287794-treated cells, which strongly suggests involvement of these adipocyte-related transcription factors in the chemical direct conversion. Our method may be useful for the preparation of autogenous adipocytes for transplantation therapy for soft tissue defects and fat tissue atrophy.
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http://dx.doi.org/10.3390/cells10030605DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000077PMC
March 2021

Synthesis and Evaluation of a Novel Series of 2,7-Substituted-6-tetrazolyl-1,2,3,4-tetrahydroisoquinoline Derivatives as Selective Peroxisome Proliferator-Activated Receptor γ Partial Agonists.

Chem Pharm Bull (Tokyo) 2021 ;69(4):333-351

Drug Discovery Research Department, Kyoto Pharmaceutical Industries, Ltd.

A novel series of 7-substituted-2-[3-(2-furyl)acryloyl]-6-tetrazolyl-1,2,3,4-tetrahydroisoquinoline derivatives were synthesized to clarify structure-activity relationships for peroxisome proliferator-activated receptor γ (PPARγ) partial agonist activity and identify more efficacious PPARγ partial agonists with minor adverse effects. Among the derivatives synthesized, compound 26v with a 2-(2,5-dihydropyrrol-1-yl)-5-methyloxazol-4-ylmethoxy group at the 7-position of the tetrahydroisoquinoline structure exhibited stronger PPARγ agonist and antagonist activities (EC = 6 nM and IC = 101 nM) than previously reported values for compound 1 (EC = 13 nM and IC = 512 nM). Compound 26v had very weak protein tyrosine phosphatase 1B (PTP1B) inhibitory activity and showed higher oral absorption (C = 11.4 µg/mL and area under the curve (AUC) = 134.7 µg·h/mL) than compound 1 (C = 7.0 µg/mL and AUC = 63.9 µg·h/mL) in male Sprague-Dawley (SD) rats. A computational docking calculation revealed that 26v bound to PPARγ in a similar manner to that of compound 1. In male Zucker fatty rats, 26v and pioglitazone at 10 and 30 mg/kg for 4 weeks similarly reduced plasma triglyceride levels, increased plasma adiponectin levels, and attenuated increases in plasma glucose levels in the oral glucose tolerance test, while only pioglitazone decreased hematocrit values. In conclusion, 6-tetrazolyl-1,2,3,4-tetrahydroisoquinoline derivatives provide a novel scaffold for selective PPARγ partial agonists and 26v attenuates insulin resistance possibly by adiponectin enhancements with minor adverse effects.
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http://dx.doi.org/10.1248/cpb.c20-00841DOI Listing
January 2021

Cryptococcal Osteomyelitis of the Entire Humerus: A Case Report.

JBJS Case Connect 2020 Oct-Dec;10(4):e2000279

1Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan 2Department of Surgical Pathology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Case: We describe a case of cryptococcal osteomyelitis in a 70-year-old man who presented with left elbow and shoulder pain. Subsequent imaging indicated osteomyelitis of the entire humerus, and he underwent debridement of the elbow and shoulder. Pathological findings revealed Cryptococcus neoformans infection. Surgical management was followed by a prolonged course of antibiotics.

Conclusion: Although C. neoformans is rare as the etiology of infection of the entire humerus, orthopaedic surgeons should consider cryptococcosis as a potential cause of infection.
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http://dx.doi.org/10.2106/JBJS.CC.20.00279DOI Listing
March 2021

Adjustable-Loop Devices Promote Graft Revascularization in the Femoral Tunnel After ACL Reconstruction: Comparison With Fixed-Loop Devices Using Magnetic Resonance Angiography.

Orthop J Sports Med 2021 Feb 26;9(2):2325967121992134. Epub 2021 Feb 26.

Department of Orthopedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

Background: Hamstring tendon grafts are usually fixed in anterior cruciate ligament (ACL) reconstruction using either an adjustable-loop device (ALD) or a fixed-loop device (FLD). The contact area between the graft and the tunnel wall is different between the 2 devices.

Purpose: To determine using magnetic resonance angiography (MRA) whether ALD and FLD result in different blood flow of the graft in the femoral tunnel during the early postoperative period.

Study Design: Cohort study; Level of evidence, 3.

Methods: Between 2008 and 2018, a total of 42 patients (17 men and 25 women) underwent MRA at 3 months after ACL reconstruction. All surgical procedures were performed using semitendinosus tendon autografts folded into 4 strands. Overall, 23 patients underwent the FLD procedure and 19 patients underwent the ALD procedure. The signal intensity of the superior portion of the graft in the femoral tunnel was evaluated using transverse MRA images perpendicular to the femoral tunnel axis.

Results: MRA images showed high signal intensity in the superior portion of the graft in the femoral tunnel in 94.7% and 60.9% of the ALD patients and FLD patients, respectively, a statistically significant difference ( = .03).

Conclusion: MRA images at 3 months after surgery revealed that blood flow reached the superior end of the tendon graft in the femoral tunnel in more patients who underwent ACL reconstruction with an ALD compared with an FLD.
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http://dx.doi.org/10.1177/2325967121992134DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934042PMC
February 2021

Comprehensive assessment of alterations in hand deformities over 11 years in patients with rheumatoid arthritis using cluster analysis and analysis of covariance.

Arthritis Res Ther 2021 02 27;23(1):66. Epub 2021 Feb 27.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: Although drug therapy for rheumatoid arthritis (RA) has recently improved, treating patients with established disease, whose hands have three major deformities (thumb deformity, finger deformities, and ulnar drift), remains a challenge. The underlying complex pathophysiology makes understanding these deformities difficult, and comprehensive assessment methods require accumulated skill with long learning curves. We aimed to establish a simpler composite method to understand the pathophysiology of and alterations in the hand deformities of patients with RA.

Methods: We established a rheumatoid hand cohort in 2004 and clinically evaluated 134 hands (67 patients). We repeated the evaluations in 2009 (100 hands of 52 patients) and 2015 (63 hands of 37 patients) after case exclusion. Thumb deformities, finger deformities (swan-neck and boutonnière deformity), and ulnar drift were semi-quantitated and entered as parameters into a two-step cross-sectional cluster analysis for the data in 2004. The parameters in each cluster were plotted at each evaluation point. Two-way analysis of covariance was used to examine whether differences existed between evaluation points and clusters of deformity parameters.

Results: Five clusters most appropriately described hand deformity: (i) cluster 1, minimal deformity; (ii) cluster 2, type 1 thumb deformity; (iii) cluster 3, thumb deformity and severe boutonnière deformity; (iv) cluster 4, type 2 or 3 thumb deformity and severe ulnar drift; and (v) cluster 5, thumb deformity and severe swan-neck deformity. Clusters 1 and 2 had higher function than cluster 5, and cluster 3 had moderate function. Clusters 1-4 had similar disease duration but showed different paths of deformity progression from disease onset. Clusters 1 and 2 represented conservative deformity parameters and clusters 3, 4, and 5 represented progressive deformity parameters. Over time, thumb deformity evolved into other types of deformities and swan-neck deformity worsened significantly.

Conclusions: Our comprehensive analysis identified five deformity patterns and a progressive course in the rheumatoid hand. Knowledge of the characteristics of progressive deformity parameters may allow rheumatologists to more easily implement practical interventions and determine functional prognosis.
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http://dx.doi.org/10.1186/s13075-021-02448-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913439PMC
February 2021

Femoral nerve versus adductor canal block for early postoperative pain control and knee function after anterior cruciate ligament reconstruction with hamstring autografts: a prospective single-blind randomised controlled trial.

Arch Orthop Trauma Surg 2021 Feb 20. Epub 2021 Feb 20.

Sports Medicine and Joint Center, Funabashi Orthopaedic Hospital, 1-833 Hasama, Funabashi, Chiba, 274-0822, Japan.

Introduction: The optimal pain management strategy for postoperative pain after anterior cruciate ligament reconstruction (ACLR) remains unclear. This study compared femoral nerve block (FNB) and adductor canal block (ACB) for pain management of early postoperative pain, knee function, and recovery of activity of daily living (ADL) after ACLR using hamstring autografts.

Material And Methods: In this prospective, single-blind, randomised controlled trial, 64 patients aged 12-56 years who underwent anatomical double-bundle ACLR with a hamstring autograft between August 2019 and May 2020 were randomised to undergo preoperative FNB (n = 32) or ACB (n = 32). The peripheral nerve block was performed by a single experienced anaesthesiologist under ultrasound guidance. The primary outcomes were postoperative pain as evaluated using the visual analogue scale (VAS) at 3, 6, 12, 24, and 48 h postoperatively and the need for pain relief. The secondary outcome was knee function, including the recovery of range of motion, contraction of the vastus medialis, and stable walking with a double-crutch (ADL), as evaluated by blinded physical therapists.

Results: There were no significant differences in patient demographics between the two groups. The VAS scores, need for pain relief, knee function, and ADL did not significantly differ between the groups.

Conclusion: FNB and ACB provided comparable outcomes related to early postoperative pain, knee function, and ADL after double-bundle ACLR using hamstring autografts. Further research is necessary to evaluate the mid- to long-term effect of each block on recovery of knee function and ADL.

Level Of Evidence: I.
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http://dx.doi.org/10.1007/s00402-021-03823-1DOI Listing
February 2021

Hip fractures among the elderly in Kyoto, Japan: a 10-year study.

Arch Osteoporos 2021 02 12;16(1):30. Epub 2021 Feb 12.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

In Kyoto Prefecture, Japan, the number of hip fractures increased during 2013-2017 compared to 2008-2012. However, the estimated overall incidence rate increased only in femoral neck fractures in men aged ≥75 and women aged ≥85.

Purpose: The incidence rate of hip fractures in Japan has plateaued or decreased. We investigated the annual hip fracture occurrences in Kyoto Prefecture, Japan, from 2008 to 2017.

Methods: Patients aged 65 years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The total number of beds in these institutions was 3701, accounting for 21.5% of the 17,242 acute-care beds in Kyoto Prefecture. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015.

Results: The total number of hip fractures was 10,060, with 47.5% femoral neck fractures and 52.5% trochanteric fractures. A decrease in number was seen only in trochanteric fractures in the group of 75- to 84-year-old women. The population-adjusted numbers of femoral neck fractures showed a significant increase in all age groups in men, whereas in women, there was an increase in femoral neck fractures in the ≥85 group and trochanteric fractures in the age group 65-74, and a decrease in trochanteric fractures in the age group 75-84. The estimated change in incidence rate showed an increase in femoral neck fractures in men aged ≥75 and women aged ≥85.

Conclusion: In Kyoto Prefecture, the number of hip fractures increased in the second half of the study period (2013-2017) compared to the first half (2008-2012). However, the incidence rate had not increased, except in femoral neck fractures in men aged ≥75 and women aged ≥85.
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http://dx.doi.org/10.1007/s11657-021-00888-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880939PMC
February 2021

Low waste process of rapid cellulose transesterification using ionic liquid/DMSO mixed solvent: Towards more sustainable reaction systems.

Carbohydr Polym 2021 Mar 24;256:117560. Epub 2020 Dec 24.

Faculty of Natural System, Institute of Science and Engineering, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan. Electronic address:

The recent progress in the manufacturing of new functional cellulose-derived materials shows that the renewable side of these materials does not ensure sustainable development. In contrast, reaction/process design and waste minimization play a key role here. Herein, reactive extrusion was used as a fast method for cellulose transesterification with vinyl laurate in 1-ethyl-3-methylimidazolium acetate (EmimOAc)/DMSO system. It was demonstrated that cellulose laurate can be synthesized with high reaction efficiency (91 %). The low amount of solvent during the process provides high cellulose concentration (20 wt%) mild chemical modification within minutes and without any depolymerization. Temperature has a significant influence on the reaction kinetics. To examine the sustainability of the process E-factor was employed. Processing properties of obtained cellulose laurates were investigated. Samples with DS of 2.5 and higher can be easily extruded showing low melt viscosity. EmimOAc was recovered and reused for subsequent cellulose transesterification exhibiting high catalytic activity.
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http://dx.doi.org/10.1016/j.carbpol.2020.117560DOI Listing
March 2021

Joint effusion at 6 months is a significant predictor of joint effusion 1 year after anterior cruciate ligament reconstruction.

Knee Surg Sports Traumatol Arthrosc 2021 Jan 21. Epub 2021 Jan 21.

Musculoskeletal Pain and Disease, Center for Preventive Medical Sciences, School of Medicine, Chiba University, 1-8-1, Inohana, Chiba, 260-8677, Japan.

Purpose: This study aimed to assess the risk factors for prolonged joint effusion in patients undergoing double-bundle anterior cruciate ligament reconstruction (ACLR).

Methods: In total, 160 patients who underwent primary ACLR using autograft hamstring between 2015 and 2018 were retrospectively reviewed. Joint effusion was defined as any grade ≥ 2 (range, 0-3) according to the MRI Osteoarthritis Knee Score (MOAKS). Univariate and multivariate logistic regression analyses were performed.

Results: The median age of the patients was 25 years (range 14-68 years) at the time of the surgery; there were 89 women and 71 men. At 1 year, 46 (28.8%) patients experienced knee joint effusion, as defined by the MOAKS. Univariate analysis revealed that age, preoperative Kellgren-Lawrence (K-L) grade, and joint effusion at 6 months were significantly associated with joint effusion at 1 year. In the multivariate analysis, joint effusion at 6 months was significantly associated with joint effusion at 1 year (odds ratio, 68.0; 95% confidence interval, 22.1-209.4). No significant difference in the Lysholm scores was observed between patients with and without joint effusion at 1 year (n.s.).

Conclusions: Joint effusion at 6 months was significantly associated with joint effusion 1 year after ACLR.

Level Of Evidence: III.
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http://dx.doi.org/10.1007/s00167-021-06433-xDOI Listing
January 2021

Clinical and Radiographic Outcomes After Fixation of Chondral Fragments of the Knee in 6 Adolescents Using Autologous Bone Pegs.

Orthop J Sports Med 2020 Nov 17;8(11):2325967120963050. Epub 2020 Nov 17.

Sports Medicine and Joint Center, Funabashi Orthopaedic Hospital, Funabashi, Chiba, Japan.

Background: Little is known regarding the optimal treatment for displaced, purely chondral fragments in the knee.

Purpose: To report the clinical and radiographic outcomes of chondral fragment fixation in adolescents through use of autologous bone pegs.

Study Design: Case series; Level of evidence, 4.

Methods: This retrospective, single-center study evaluated 6 patients (mean age, 12.9 years) who underwent fixation of chondral fragments (no visualized bone attached) using autologous bone pegs (mean postoperative follow-up, 5.2 years; range, 1.4-10.9 years). The causes were trauma (n = 5) and osteochondritis dissecans (n = 1). Lesions were located in the trochlear groove (lateral, n = 3; medial, n = 2) or posterior part of the lateral femoral condyle (n = 1). The mean lesion size was 3.8 cm (range, 0.8-9.0 cm). Patients were evaluated via physical examination and magnetic resonance imaging (MRI) using magnetic resonance observation of cartilage repair tissue scores.

Results: In total, 5 patients successfully returned to sports without restrictions at a mean of 7 months (range, 6-8 months) postoperatively. At the latest follow-up, these 5 patients had full range of motion and no joint effusion. The mean magnetic resonance observation of cartilage repair tissue score was 85 (range, 70-95) at a mean duration of 3 years (range, 1-5 years). One patient experienced failure at 1.3 years postoperatively after a traumatic injury and subsequently underwent removal of the fixed fragment and a drilling procedure.

Conclusion: In most adolescents, fixation of chondral fragments with no visualized bony portion using autologous bone pegs provided a satisfactory success rate and good healing of cartilage tissue confirmed on MRI scans.
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http://dx.doi.org/10.1177/2325967120963050DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787012PMC
November 2020

Deep heat therapy system with resonant cavity applicator for articular cartilage in knee osteoarthritis.

J Phys Ther Sci 2020 Dec 11;32(12):823-827. Epub 2020 Dec 11.

Department of Mechanical Engineering Informatics, Meiji University, Japan.

[Purpose] Heat can prevent cartilage degeneration when applied to articular cartilage, but the size of the human knee joint makes it difficult to target cartilage during heat treatment. In this study, we aimed to establish a heat therapy method capable of safely applying heat to deep intra-articular tissues utilizing a resonant cavity applicator and to confirm the extent of cartilage heating in the human knee when using this system. [Participants and Methods] Heating experiments were carried out on the knees of healthy three volunteers using a resonant cavity applicator and a microwave diathermy system. After heat application, temperature distributions inside the knee were measured noninvasively using our measurement method based on ultrasound imaging techniques. [Results] We observed an increase in the temperature around the cartilage tissue in the knees of the volunteers using an ultrasonic thermometer; there was no increase in temperature in the overlying layers. During heating with up to 20 W of power, none of the volunteers experienced adverse reactions. [Conclusion] This study indicates the potential safety and effectiveness of the resonant cavity heat therapy system for knee osteoarthritis in a clinical setting.
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http://dx.doi.org/10.1589/jpts.32.823DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758613PMC
December 2020

Radiologic results of additional single screw fixation with lateral locking plate after hybrid closed-wedge high tibial osteotomy.

Knee Surg Relat Res 2020 Dec 14;32(1):65. Epub 2020 Dec 14.

Department of Sports and Para-Sports Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajiicho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan.

Background: Hybrid closed-wedge high tibial osteotomy (hybrid CWHTO) is an effective surgical treatment for medial compartment osteoarthritis of the knee. Our study investigated whether the combination of a lateral locking plate and a single medial screw promoted bone union after hybrid CWHTO.

Methods: The study cohort consisted of 30 patients (15 men and 15 women) who underwent hybrid CWHTO for medial compartment osteoarthritis or spontaneous osteonecrosis of the knee. Sixteen knees were fixed with a lateral locking plate (LP group), and 17 were fixed with both a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia (LPS group). The times to bone union, radiolucency, and callus formation at the osteotomy site were evaluated radiographically.

Results: The mean postoperative time to radiographic confirmation of bone union was 5.5 ± 2.6 months in the LP group and 3.4 ± 1.5 months in the LPS group. Radiolucency at the osteotomy site and excess callus formation on the posterior side of the tibia were lower in the LPS group than in the LP group.

Conclusions: This modified hybrid CWHTO combining a lateral locking plate and a cannulated cancellous screw on the medial side of the tibia improves the stability of the osteotomy site and shortens the period of bone union.
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http://dx.doi.org/10.1186/s43019-020-00085-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7734755PMC
December 2020

Arthroscopic Fixation Technique for Avulsion Fracture of the Posterior Cruciate Ligament From the Tibia.

Arthrosc Tech 2020 Nov 23;9(11):e1819-e1824. Epub 2020 Oct 23.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.

This study describes an arthroscopic pullout fixation technique for small and comminuted avulsion fractures of the posterior cruciate ligament from the tibia. Intra-articular surgery required 3 arthroscopic portals, the anterolateral, anteromedial, and posteromedial portals. To simplify surgery, the posterolateral portal was omitted. A 2.4-mm K-wire was inserted through the anterior incision to the center of the bone fragment. This central guidewire was subsequently overdrilled with a 4.0-mm cannulated drill. The fixation material consisted of Pass Telos artificial ligaments inserted through the fiber loop of a fixed suspensory device such as RIGIDLOOP. The leading end of the thread of the RIGIDLOOP was pulled out through the anteromedial portal. The button of RIGIDLOOP was gradually advanced through the bone tunnel. The button was pulled out and flipped over the bony fragment. The artificial ligament was pulled distally to reduce the bony fragment, and fixed onto the tibia using a ligament button while applying anterior drawer force to the proximal tibia with the knee flexed at 90°. This minimally invasive procedure was successful in treating small and comminuted avulsion fracture of the tibial attachment of the posterior cruciate ligament.
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http://dx.doi.org/10.1016/j.eats.2020.08.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695752PMC
November 2020

The Potential Role of Hepatocyte Growth Factor in Degenerative Disorders of the Synovial Joint and Spine.

Int J Mol Sci 2020 Nov 18;21(22). Epub 2020 Nov 18.

Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.

This paper aims to provide a comprehensive review of the changing role of hepatocyte growth factor (HGF) signaling in the healthy and diseased synovial joint and spine. HGF is a multifunctional growth factor that, like its specific receptor c-Met, is widely expressed in several bone and joint tissues. HGF has profound effects on cell survival and proliferation, matrix metabolism, inflammatory response, and neurotrophic action. HGF plays an important role in normal bone and cartilage turnover. Changes in HGF/c-Met have also been linked to pathophysiological changes in degenerative joint diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IDD). A therapeutic role of HGF has been proposed in the regeneration of osteoarticular tissues. HGF also influences bone remodeling and peripheral nerve activity. Studies aimed at elucidating the changing role of HGF/c-Met signaling in OA and IDD at different pathophysiological stages, and their specific molecular mechanisms are needed. Such studies will contribute to safe and effective HGF/c-Met signaling-based treatments for OA and IDD.
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http://dx.doi.org/10.3390/ijms21228717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698933PMC
November 2020

Heterogeneous Structures of Ionic Liquids as Probed by CO Rotation with Nuclear Magnetic Resonance Relaxation Analysis and Molecular Dynamics Simulations.

J Phys Chem B 2020 11 6;124(46):10465-10476. Epub 2020 Nov 6.

Department of Molecular Chemistry and Biochemistry, Faculty of Science and Engineering, Doshisha University, 1-3 Tatara Miyakodani, Kyotanabe, Kyoto 610-0394, Japan.

The rotational dynamics of carbon monoxide (CO) in ionic liquids (ILs) was investigated by nuclear magnetic resonance (NMR) relaxation measurements and molecular dynamics (MD) simulations. NMR spin-lattice relaxation time measurements were performed for O-enriched CO in 10 ILs (four imidazolium-cation-based, four phosphonium-cation-based, and two ammonium-cation-based ILs, all paired with the bis(trifluorosulfonylmethane)imide anion). In combination with previously reported data for five ILs and viscosity data, our results indicated that the obtained rotational relaxation times (τ) were much smaller than those predicted using the Stokes-Einstein-Debye (SED) theory. For the same viscosity/temperature values, the τ value increased linearly with increasing carbon number of the alkyl group in the cation. The deviation from the SED equation was due to the insensitivity of τ to the carbon number, even though a higher carbon number generally leads to higher viscosity values for ILs. To investigate the unique rotational properties of CO in the ILs, MD simulations were performed on five representative ILs (two imidazolium, two phosphonium, and one ammonium) containing CO solutes. From rotational correlation function analyses, the CO rotation mainly occurred in a free rotation-like manner within 1 ps, which explained the relative insensitivity of CO rotation to viscosity. In the subsequent time scale (>1 ps), the minor component of the CO rotation was discriminated among different ILs. It was strongly suggested that, because CO preferably locates in the outer part of the alkyl groups in the cation, the slow CO rotation is correlated with the outer alkyl dynamics, which are decoupled from the whole cation rotation.
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http://dx.doi.org/10.1021/acs.jpcb.0c08030DOI Listing
November 2020

Mussel-Inspired Design of a Carbon Fiber-Cellulosic Polymer Interface toward Engineered Biobased Carbon Fiber-Reinforced Composites.

ACS Omega 2020 Oct 13;5(42):27072-27082. Epub 2020 Oct 13.

Institute of Science and Engineering, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan.

Tuning interactions at the interfaces in carbon fiber (CF)-reinforced polymer composites necessitates the implementation of CF surface modification strategies that often require destructive environmentally unfriendly chemistries. In this study, interfacial interactions in cellulose-based composites are tailored by means of a mussel-inspired adhesive polydopamine (PDA) coating, being inherently benign for the environment and for the structure of CFs. The step-by-step growth of PDA was followed by increasing treatment time leading to a hydrophilic PDA-coated surface, presumably via surface-based polymerization mechanisms attributed to strong π-π stacking interactions. Although PDA deposition led to an initial increase in the interfacial shear strength (IFSS) (5 h), it decreased at a longer reaction time (24 h), the formation of weakly attached PDA particles on the coated surface can possibly lie behind the latter phenomenon. Nevertheless, the mechanical properties of the prepared short CF-reinforced composite were improved (tensile strength increased ∼12% compared to the unmodified surface) with decreasing IFSS owing to the particular morphological design, resulting in longer fiber segments. Our study underlines the importance of the morphological design at the interface and considers PDA as a promising bioinspired material to tailor interfacial interactions.
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http://dx.doi.org/10.1021/acsomega.0c02356DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7594004PMC
October 2020

Efficacy of a deep thermal therapy system for osteoarthritis of the knee.

J Nippon Med Sch 2020 Sep 30. Epub 2020 Sep 30.

Department of Orthopaedic Surgery, Nippon Medical School.

Background: This study sought to assess the efficacy of a deep-tissue thermal therapy system with a resonant cavity applicator (DTT-RCA), which safely heats deep joint tissue for treating osteoarthritis (OA) of the knee.

Methods: Two groups of participants were recruited. The DTT-RCA group comprised 20 knees. Kellgren-Lawrence (K-L) grade was I and II in 8 knees (DTT-RCA I/II group) [mean age 73.3 years (standard deviation 11.4) ], III and VI in 12 knees (DTT-RCA III/IV group) [75.4 (8.6) years]. The control group comprised 13 knees [68.2 (10.8) years]. K-L grade was I in 7 knees and II in 6 knees. This group received exercise therapy. The DTT-RCA I/II group and the control group were imaged by MRI T2 mapping at baseline and 6 months to determine the area of cartilage degeneration.

Results: Visual Analogue Scale improved only in the DTT-RCA I/II post-intervention (p < 0.01). Japanese Orthopedic Association knee rating scores (DTT-RCA I/II: p < 0.01, control group: p < 0.01), the Japanese Knee Osteoarthritis Measure (DTT-RCA I/II: p < 0.05, control: p < 0.01), and the Knee injury and Osteoarthritis Outcome Score (DTT-RCA I/II: p < 0.01, DTT-RCA III/IV: p < 0.05, control: p < 0.01) post-intervention. The magnitude of change did not differ significantly between the three groups. The area of cartilage degeneration did not change significantly post-intervention in the DTT-RCA I/II group, not even relative to the control group.

Conclusions: This was the first study to test a DTT-RCA system in patients with knee OA. The system reduced the clinical symptoms of knee OA and could potentially be effective for conservative therapy.
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http://dx.doi.org/10.1272/jnms.JNMS.2021_88-505DOI Listing
September 2020

Effects of repeated intra-articular hyaluronic acid on cartilage degeneration evaluated by T1ρ mapping in knee osteoarthritis.

Mod Rheumatol 2020 Oct 16:1-7. Epub 2020 Oct 16.

Minami-Shinjuku Orthopaedic Rehabilitation Clinic, Tokyo, Japan.

Objectives: Intra-articular injection of hyaluronic acid (IAHA) has been used for the treatment of knee osteoarthritis (OA), but its effectiveness remains controversial. This study analyzed knee OA over time by magnetic resonance imaging (MRI) T1ρ mapping to objectively evaluate whether long-term repeated administration of IAHA influences cartilage degeneration.

Methods: Sixty knees of 60 patients [58.3 ± 12.5 years (mean ± standard deviation)] who had multiple T1ρ mapping images were retrospectively analyzed. We calculated the T1ρ values of the medial femorotibial cartilage and classified changes in degenerative areas over time into 3 groups: Improvement, No Change, and Deterioration.

Results: Average time between 2 MRI scans was 7.6 ± 1.2 months. The number of IAHA administrations was 15.5 ± 21.3, 8.39 ± 7.19, and 5.80 ± 7.49 in the Improvement, No Change, and Deterioration groups, respectively. Body mass index and number of IAHA administrations were significant factors causing change in the area of degeneration ( < .05) independent of age, sex, Kellgren-Lawrence grade, and posterior horn meniscus tears.

Conclusion: Cartilage degeneration may be improved with a higher number of administrations of IAHA, based on T1ρ mapping results. This highlights the possibility of increased treatment effectiveness of IAHA for knee OA with repeated administrations.
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http://dx.doi.org/10.1080/14397595.2020.1830483DOI Listing
October 2020

Influence of different energy patterns on efficacy of radial shock wave therapy.

J Orthop Sci 2020 Aug 28. Epub 2020 Aug 28.

Department of Orthopedic Surgery, Kitasato University School of Medicine, Sagamihara, Japan.

Background: One of the mechanisms of the efficacy of extracorporeal shock wave therapy (ESWT) for impaired muscle coordination of limbs is the destruction of Acetylcholine receptors (AChRs) at neuromuscular junction. The highly increased density of AChRs can change the acoustic impedance, and this change of the acoustic impedance can be the reason that radial shock wave (rESW) destroy AChRs selectively. However, the relationship between applied energy of rESWs and the therapeutic efficacy remains unclear, although some studies compared the clinical efficacy of rESWT between high- and low-energy applications. This study aimed to compare the CMAP change among different energy and pulses of rESW application.

Methods: Male Sprauger-Dawley rats were used. A device that generates radial shock waves pneumatically, was used to apply the following six patterns of radial extracorporeal shockwaves in different energy flux densities and pulses to the right calf of each rat: 1, 8000 pulses at 0.045 mJ/mm; 2, 4000 pulses at 0.09 mJ/mm; 3, 2000 pulses at 0.18 mJ/mm; 4, 4000 pulses at 0.045 mJ/mm; 5, 2000 pulses at 0.09 mJ/mm; 6, 1000 pulses at 0.18 mJ/mm. Left calf muscles were considered controls.

Results: There was a significant reduction in CMAP amplitude between control and rESW-exposed muscles in the group applied 4000 pulses with EFD at 0.09 mJ/mm and the group applied 2000 pulses with EFD at 0.18 mJ/mm. However, the group applied 8000 pulses with EFD at 0.045 mJ/mm and all groups which was exposed to total 180 mJ rESW application did not show a significantly decreased CMAP amplitude compared with the untreated side.

Conclusions: Total energy and energy flux density correlate with a decrease in CMAP amplitude by rESW application. These findings could be availed by clinicians in actual clinical setting for the proper application of rESW.
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http://dx.doi.org/10.1016/j.jos.2020.07.009DOI Listing
August 2020

The Influence of Posterior Cruciate Ligament Resection on Tibiofemoral Joint Gap in Varus Osteoarthritic Knees.

J Knee Surg 2020 Jul 13. Epub 2020 Jul 13.

Department of Orthopaedic Surgery, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.

Posterior cruciate ligament (PCL) resection during posterior-stabilized total knee arthroplasty (PS-TKA) has been reported to preferentially increase the tibiofemoral joint gap in flexion compared with extension. However, previous assessments of the joint gaps have been performed after bone resection and medial soft tissue release. Thus, these procedural steps may have the potential to influence soft tissue balance. In native knees, soft tissue laxity is generally greater in the lateral compartment than in the medial compartment both with the knee in extension and in flexion. Some surgeons may retain this natural soft tissue balance with less aggressive medial release during TKA. We performed this study to evaluate the impact of the PCL resection on the extension and flexion gaps in the absence of bone resection or medial soft tissue release. Tibiofemoral joint gaps for 41 patients (10 males and 31 females) in full extension and at 90 degrees of flexion both before and after the resections of both the anterior cruciate ligament (ACL) and PCL were assessed using a ligament tensioner device. The statistical analyze was performed using the Mann-Whitney U test. The results showed that medial gap in extension and flexion were 6.7 ± 1.0 and 7.3 ± 0.9 mm, and lateral gap in extension and flexion were 7.6 ± 1.1 and 8.4 ± 1.6 mm, respectively. Thus, physiological tibiofemoral gaps just after knee arthrotomy were trapezoidal and asymmetric shape with the significantly wider gaps in lateral and flexion, compared with the medial and extension, respectively ( < 0.05). However, the increases of the gaps with the ACL and PCL resections were less than 1 mm under the existence of medial soft tissues. As the medial collateral ligament is the primary restraint for the valgus instability, it was also considered to prevent the increase of the flexion gap although the PCL-which is the secondary restraint for the valgus instability-was resected. This finding is critically important for orthopedic surgeons applying PS-TKA implants, particularly for preserving soft tissues to achieve natural knee kinematics postoperatively.
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http://dx.doi.org/10.1055/s-0040-1713810DOI Listing
July 2020

The Interaction Between Long Non-coding RNA HULC and MicroRNA-622 via Transfer by Extracellular Vesicles Regulates Cell Invasion and Migration in Human Pancreatic Cancer.

Front Oncol 2020 23;10:1013. Epub 2020 Jun 23.

Division of Metabolism and Biosystemic Science, Department of Medicine, Asahikawa Medical University, Asahikawa, Japan.

Although non-coding RNAs (ncRNAs) are involved in disease pathogenesis, their contributions to pancreatic ductal adenocarcinoma (PDAC) remain unclear. Recently, the interrelationship between two classes of ncRNA, long non-coding RNAs (lncRNAs), and microRNAs (miRNAs), has been reported to contribute to the epigenetic regulation of gene expression in several diseases including cancers. Moreover, some ncRNAs can be transferred by extracellular vesicles (EVs) from their donor cells to recipient cells. We previously verified that lncRNA HULC is up-regulated in PDAC cells and the intercellular transfer of HULC by EVs can promote PDAC cell invasion and migration through the induction of epithelial-mesenchymal transition (EMT). Therefore, we identified the miRNA that could target HULC and investigated the functional contributions of the miRNA-HULC interaction and EV transfer of miRNA to the EMT pathway in PDAC. Microarray analysis revealed 187 miRNAs that were decreased to <0.87-fold in Panc-1 cells treated with TGF-β compared with the control. Of these, miR-622 was predicted to target HULC directly by bioinformatics analysis. Expression of miR-622 was significantly down-regulated by TGF-β in a panel of PDAC cells. miR-622 overexpression by a miRNA mimic significantly decreased HULC expression, increased E-cadherin expression, and decreased expression of Snail, N-cadherin, and vimentin. Moreover, overexpression of miR-622 significantly reduced cell invasion and migration whereas inhibition of miR-622 increased HULC expression and promoted EMT signaling, invasion, and migration of PDAC cells. Furthermore, incubation with miR-622-overexpressing EVs could transfer miR-622, which significantly elevated miR-622 expression and decreased cell invasion and migration via inhibition of the EMT pathway in recipient PDAC cells. These results provide mechanistic insights into the development of PDAC by demonstrating that miR-622, as a miRNA downregulated by TGF-β, could target HULC and suppress invasion and migration by inhibiting EMT signaling via EV transfer. These observations may identify EV-encapsulated miRNA as a novel therapeutic target for human PDAC.
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http://dx.doi.org/10.3389/fonc.2020.01013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324724PMC
June 2020

Primary central nervous system lymphomas associated with chronic inflammation: diagnostic pitfalls of central nervous system lymphomas.

Brain Tumor Pathol 2020 Oct 5;37(4):127-135. Epub 2020 Jul 5.

Department of Pathology, Kurume University School of Medicine, 67 Asahimachi, Kurume, Fukuoka, 830-0011, Japan.

In recent years, the features of lymphomas associated with chronic inflammation, referred to as diffuse large B-cell lymphoma (DLBCL) associated with chronic inflammation (DLBCL-CI), have been elucidated. DLBCL-CI is an aggressive lymphoma occurring in the context of long-standing chronic inflammation and showing an association with Epstein-Barr virus. Fibrin-associated diffuse large B-cell lymphoma (F-DLBCL) was suggested as a new and unusual form of DLBCL-CI in the most recent version of the World Health Organization classification. From the perspective of genetics, DLBCL-CI was associated with frequent TP53 mutation, MYC amplification and complex karyotypes, but cases of F-DLBCL behaved indolently and showed a relatively lower genetic complexity. In the central nervous system (CNS), several examples of DLBCL-CI and F-DLBCL have been reported. As with DLBCL-CI outside the CNS, DLBCL-CI in the CNS is an aggressive lymphoma. However, the clinical outcome of F-DLBCL in the CNS is good. Immunohistochemistry for p53 and c-Myc in DLBCL-CI and F-DLBCL in the CNS showed similar findings of those outside the CNS. However, one aggressive case showed transitional genetics and morphology between F-DLBCL and DLBCL-CI. These findings suggest that some cases of F-DLBCL in the CNS might have the potential to progress to DLBCL-CI.
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http://dx.doi.org/10.1007/s10014-020-00373-zDOI Listing
October 2020

IgG4-related Disease Manifesting as Gastroduodenal Ulcer Diagnosed by an Endoscopic Biopsy.

Intern Med 2020 Oct 23;59(20):2491-2497. Epub 2020 Jun 23.

Department of Gastroenterology, National Hospital Organization Asahikawa Medical Center, Japan.

A 26-year-old man was admitted to our hospital due to upper abdominal pain. He had previously been diagnosed with gastroduodenal ulcer at 23 and 25 years old and had been treated with proton-pump inhibitors. Endoscopic hemostasis and a biopsy were performed on the hemorrhagic gastroduodenal ulcers. Laboratory and pathologic examinations demonstrated elevated serum IgG4 levels and the infiltration of IgG4-positive plasma cells into the gastroduodenal tissues. Based on the clinicopathologic findings and after excluding other causes, he was diagnosed with IgG4-related gastroduodenal ulcer. We herein report a rare case of IgG4-related disease manifesting as a gastroduodenal ulcer diagnosed by an endoscopic biopsy.
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http://dx.doi.org/10.2169/internalmedicine.4483-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7662039PMC
October 2020

Anaerobic glucose consumption is accelerated at non-proliferating elevated temperatures through upregulation of a glucose transporter gene in Corynebacterium glutamicum.

Appl Microbiol Biotechnol 2020 Aug 17;104(15):6719-6729. Epub 2020 Jun 17.

Faculty of Natural System, Institute of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa, Japan.

Cell proliferation is achieved through numerous enzyme reactions. Temperature governs the activity of each enzyme, ultimately determining the optimal growth temperature. The synthesis of useful chemicals and fuels utilizes a fraction of available metabolic pathways, primarily central metabolic pathways including glycolysis and the tricarboxylic acid cycle. However, it remains unclear whether the optimal temperature for these pathways is correlated with that for cell proliferation. Here, we found that wild-type Corynebacterium glutamicum displayed increased glycolytic activity under non-growing anaerobic conditions at 42.5 °C, at which cells do not proliferate under aerobic conditions. At this temperature, glucose consumption was not inhibited and increased by 28% compared with that at the optimal growth temperature of 30 °C. Transcriptional analysis revealed that a gene encoding glucose transporter (iolT2) was upregulated by 12.3-fold compared with that at 30 °C, with concomitant upregulation of NCgl2954 encoding the iolT2-regulating transcription factor. Deletion of iolT2 decreased glucose consumption rate at 42.5 °C by 28%. Complementation of iolT2 restored glucose consumption rate, highlighting the involvement of iolT2 in the accelerating glucose consumption at an elevated temperature. This study shows that the optimal temperature for glucose metabolism in C. glutamicum under anaerobic conditions differs greatly from that for cell growth under aerobic conditions, being beyond the upper limit of the growth temperature. This is beneficial for fuel and chemical production not only in terms of increasing productivity but also for saving cooling costs. KEY POINTS: • C. glutamicum accelerated anaerobic glucose consumption at elevated temperature. • The optimal temperature for glucose consumption was above the upper limit for growth. • Gene expression involved in glucose transport was upregulated at elevated temperature. Graphical abstract.
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http://dx.doi.org/10.1007/s00253-020-10739-0DOI Listing
August 2020

Native Valve Endocarditis due to Staphylococcus warneri Developing in a Patient with Type 1 Diabetes.

Intern Med 2020 Sep 15;59(18):2269-2274. Epub 2020 Jun 15.

Department of Diabetes and Metabolism, Tohoku University Hospital, Japan.

A 59-year-old man with type 1 diabetes presented with heart failure. Echocardiography showed large vegetations on the mitral and aortic valves. Blood bacterial culture was positive for Staphylococcus warneri, a coagulase-negative staphylococcus (CoNS) family member. He was diagnosed with native valve endocarditis (NVE) induced by the resident bacteria and ultimately underwent double valve replacement. Retrospectively, slight laboratory data abnormalities and weight loss beginning four months before may have been signs of NVE. He had no history of immunosuppressive therapies or medical device implantation. Thus, CoNS can cause NVE after a long asymptomatic course in patients with poorly controlled diabetes.
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http://dx.doi.org/10.2169/internalmedicine.4661-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578594PMC
September 2020

Requirement of de novo synthesis of pyruvate carboxylase in long-term succinic acid production in Corynebacterium glutamicum.

Appl Microbiol Biotechnol 2020 May 30;104(10):4313-4320. Epub 2020 Mar 30.

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa, 920-1192, Japan.

Protein turnover through de novo synthesis is critical for sustainable cellular functions. We previously found that glucose consumption rate in Corynebacterium glutamicum under anaerobic conditions increased at temperature higher than the upper limit of growth temperature. Here, we showed that production of lactic and succinic acids increased at higher temperature for long-term (48 h) anaerobic reaction in metabolically engineered strains. At 42 °C, beyond the upper limit of growth temperature range, biomass-specific lactic acid production rate was 8% higher than that at 30 °C, the optimal growth temperature. In contrast, biomass-specific succinic acid production rate was highest at 36 °C, 28% higher than that at 30 °C, although the production at 42 °C was still 23% higher than that at 30 °C. As enzymes are usually unstable at high temperatures, we investigated whether protein turnover of metabolic enzymes is required for the production of lactic and succinic acids under these conditions. Interestingly, when de novo protein synthesis was inhibited by addition of chloramphenicol, after 6 h, only succinic acid production was inhibited. Because glycolytic enzymes are involved in both lactic and succinic acids synthesis, enzymes in the anaplerotic pathway and the tricarboxylic acid (TCA) cycle leading to succinic acid synthesis were likely to be responsible for its decreased production. Among the five enzymes examined, the specific activity of only pyruvate carboxylase was drastically decreased after 48 h at 42 °C. Thus, the de novo synthesis of pyruvate carboxylase is required for long-term production of succinic acid. Graphical abstract KEY POINTS: • Long-term reaction for organic acids can be improved at temperature beyond ideal growth conditions. • De novo synthesis of pyruvate carboxylase is required for long-term succinic acid production.
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http://dx.doi.org/10.1007/s00253-020-10556-5DOI Listing
May 2020

Automatic Redirection of Carbon Flux between Glycolysis and Pentose Phosphate Pathway Using an Oxygen-Responsive Metabolic Switch in .

ACS Synth Biol 2020 04 23;9(4):814-826. Epub 2020 Mar 23.

Graduate School of Natural Science and Technology, Kanazawa University, Kakuma-machi, Kanazawa, Ishikawa 920-1192, Japan.

Controlling the carbon flux into a desired pathway is important for improving product yield in metabolic engineering. After entering a cell, glucose is channeled into glycolysis and the pentose phosphate pathway (PPP), which decreases the yield of target products whose synthesis relies on NADPH as a cofactor. Here, we demonstrate redirection of carbon flux into PPP under aerobic conditions in , achieved by replacing the promoter of glucose 6-phosphate isomerase gene () with an anaerobic-specific promoter of the lactate dehydrogenase gene (). The promoter replacement increased the split ratio of carbon flux into PPP from 39 to 83% under aerobic conditions. The titer, yield, and production rate of 1,5-diaminopentane, whose synthesis requires NADPH as a cofactor, were increased by 4.6-, 4.4-, and 2.6-fold, respectively. This is the largest improvement in the production of 1,5-diaminopentane or its precursor, lysine, reported to date. After aerobic cell growth, expression was automatically induced under anaerobic conditions, altering the carbon flux from PPP to glycolysis, to produce succinate in a single metabolically engineered strain. Such an automatic redirection of metabolic pathway using an oxygen-responsive switch enables two-stage fermentation for efficient production of two different compounds by a single strain, potentially reducing the production costs and time for practical applications.
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http://dx.doi.org/10.1021/acssynbio.9b00493DOI Listing
April 2020

Successful endovascular therapy for cerebral venous sinus thrombosis accompanied by heparin-induced thrombocytopenia.

Interv Neuroradiol 2020 Jun 1;26(3):341-345. Epub 2020 Mar 1.

Department of Comprehensive Strokology, Fujita Health University School of Medicine, Toyoake, Japan.

Introduction: Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin exposure. A limited number of studies have reported cerebral venous sinus thrombosis accompanied by heparin-induced thrombocytopenia. Here, we present a case of successful endovascular therapy (EVT) without periprocedural heparinization in this situation.

Case Presentation: A 47-year-old woman taking an oral contraceptive was admitted to our hospital with severe headache to be diagnosed as cerebral venous sinus thrombosis. Initially, she got improved by medical treatment with intravenous unfractionated heparin. However, she rapidly developed disturbance of consciousness and right hemiplegia due to cerebral venous sinus thrombosis accompanied by heparin-induced thrombocytopenia on the 14th hospital day. She underwent emergent EVT by immediate conversion of anticoagulation from heparin to argatroban. Despite a large clot burden, sufficient recanalization and anterograde venous drainage were re-established by combined EVT including aspiration, balloon sinoplasty, and local thrombolysis with urokinase infusion. She got improved immediately after the intervention and discharged home without any neurological sequelae after two months.

Conclusion: This unique case of cerebral venous sinus thrombosis worsened by occurrence of heparin-induced thrombocytopenia during the treatment finally resulted in excellent outcome highlights effectiveness of emergent endovascular intervention for critical cerebral venous sinus thrombosis resistant to initial medical treatment and of immediate establishment of effective anticoagulant strategy for both of heparin-induced thrombocytopenia and cerebral venous sinus thrombosis. Neuroendovascular therapy for cerebral venous sinus thrombosis using alternative argatroban to heparin for periprocedural anticoagulation might be safe and feasible.
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http://dx.doi.org/10.1177/1591019919887821DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7254622PMC
June 2020

The Shunt Point of the Sacral Dural Arteriovenous Fistula: A Case Report and Literature Review.

World Neurosurg 2020 Nov 14;143:518-526. Epub 2020 Feb 14.

Department of Cerebrovascular Medicine, St. Mary's Hospital, Fukuoka, Japan.

Background: The occurrence of sacral dural arteriovenous fistula (dAVF) is rare. The detailed vascular architecture of sacral dAVF, including 3-dimensional (3D) angiographic images with operative findings, has not been evaluated compared with that of the thoracic and lumbar levels. We report a case of sacral dAVF with 3D angiographic examination and operative findings, with a literature review.

Case Description: A 60-year-old man presented with progressive urinary incontinence and gait disturbance. A sacral dAVF was detected at the S1-2 level. The shunt point was at the medial side of the line between the intermediate sacral crest and the most medial point of the L5 pedicle circle at the anterior posterior view of the angiography; we defined this type as the medial type. After embolization, latent inflow arteries were visualized ipsilaterally and contralaterally. During surgery, because of dAVF recurrence, a vascular tangle was found on the dura. The surgical interruption of the draining vein improved the patient's symptoms. From the literature review, 92% of cases had medial-type shunt point. It is possible for sacral dAVF to have multiple inflow arteries originating ipsilaterally or bilaterally, and a venous pouch.

Conclusions: The shunt point of sacral dAVF tended to be located medially, not in the sacral foramen. Sacral dAVF has unique angioarchitecture. The differentiation of dAVF from epidural arteriovenous fistula may not be easy in some cases of sacral lesions. Therefore, further studies with a larger number of patients focused on the detailed vascular architecture are needed.
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http://dx.doi.org/10.1016/j.wneu.2020.02.037DOI Listing
November 2020