Publications by authors named "Akiyoshi Kuroda"

18 Publications

  • Page 1 of 1

Prevalence and location of endplate fracture and subsidence after oblique lumbar interbody fusion for adult spinal deformity.

BMC Musculoskelet Disord 2021 Oct 14;22(1):880. Epub 2021 Oct 14.

Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1, Kitazato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.

Background: Recently, Oblique lumbar interbody fusion (OLIF) is commonly indicated to correct the sagittal and coronal alignment in adult spinal deformity (ASD). Endplate fracture during surgery is a major complication of OLIF, but the detailed location of fracture in vertebral endplate in ASD has not yet been determined. We sought to determine the incidence and location of endplate fracture and subsidence of the OLIF cage in ASD surgery, and its association with fusion status and alignment.

Methods: We analyzed 75 levels in 27 patients were analyzed using multiplanar CT to detect the endplate fracture immediately after surgery and subsidence at 1 year postoperatively. The prevalence was compared between anterior and posterior, approach and non-approach sides, and concave and convex side. Their association with fusion status, local and global alignment, and complication was also investigated.

Results: Endplate fracture was observed in 64 levels (85.3%) in all 27 patients, and the incidence was significantly higher in the posterior area compared with the anterior area (85.3 vs. 68.0%, p=0.02) of affected vertebra in the sagittal plane. In the coronal plane, there was no significant difference in incidence between left (approach) and right (non-approach) sides (77.3 and 81.3%, respectively), or concave and convex sides (69.4 and 79.6%) of wedged vertebra. By contrast, cage subsidence at 1 year postoperatively was noted in 14/75 levels (18.7%), but was not associated with endplate fracture. Fusion status, local and global alignment, and complications were not associated with endplate fracture or subsidence.

Conclusion: Endplate fracture during OLIF procedure in ASD cases is barely avoidable, possibly induced by the corrective maneuver with ideal rod counter and cantilever force, but is less associated with subsequent cage subsidence, fusion status, and sustainment of corrected alignment in long fusion surgery performed even for elderly patients.
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http://dx.doi.org/10.1186/s12891-021-04769-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8518321PMC
October 2021

Investigations into the Potential of Using Open Source CFD to Analyze the Differences in Hemodynamic Parameters for Aortic Dissections (Healthy versus Stanford Type A and B).

Ann Vasc Surg 2021 Oct 12. Epub 2021 Oct 12.

Department of Cardiac Surgery, Asahikawa Medical University, Asahikawa, Japan.

Background: The objective of this study was to develop a method to evaluate the effects of an aortic dissection on hemodynamic parameters by conducting a comparison with that of a healthy (nondissected) aorta. Open-source software will be implemented, no proprietary software/application will be used to ensure accessorily and repeatability, in all the data analysis and processing. Computed tomography (CT) images of aortic dissection are used for the model geometry segmentation. Boundary conditions from literature are implemented to computational fluid dynamics (CFD) to analyze the hemodynamic parameters.

Methods: A numerical simulation model was created by obtaining accurate 3-dimensional geometries of aortae from CT images. In this study, CT images of 8 cases of aortic dissection (Stanford type-A and type-B) and 3 cases of healthy aortae are used for the actual aorta model geometry segmentation. These models were exported into an open-source CFD software, OpenFOAM, where a simplified pulsating flow was simulated by controlling the flow pressure. Ten cycles of the pulsatile flow (0.50 sec/cycle) conditions, totaling 5 sec, were calculated.

Results: The pressure distribution, wall shear stress (WSS) and flow velocity streamlines within the aorta and the false lumen were calculated and visualized. It was found that the flow velocity and WSS had a high correlation in high WSS areas of the intermittent layer between the true and false lumen. Most of the Stanford type-A dissections in the study showed high WSS, over 38 Pa, at the systole phase. This indicates that the arterial walls in type-A dissections are more likely to be damaged with pulsatile flow.

Conclusions: Using CFD to estimate localized high WSS areas may help in deciding to treat a type-A or B dissection with a stent graft to prevent a potential rupture.
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http://dx.doi.org/10.1016/j.avsg.2021.08.007DOI Listing
October 2021

Effect of parenteral energy or amino acid doses on in-hospital mortality, among patients with aspiration pneumonia: a cohort medical claims database study.

J Gerontol A Biol Sci Med Sci 2021 Oct 9. Epub 2021 Oct 9.

Research and Development Center, Otsuka Pharmaceutical Factory, Inc., Kanda-Tsukasamachi, Chiyoda-ku, Tokyo, Japan.

Background: This study examined the association between parenteral energy/amino acid doses and in-hospital mortality among inpatients on long-term nil per os (NPO) status, using a medical claims database in Japan.

Methods: Hospitalized patients with aspiration pneumonia, aged ≥65 years and on >7-days NPO status, were identified in a medical claims database between January 2013 and December 2018. Using multivariate logistic regression and regression analyses, we examined the association between mean parenteral energy/amino acid doses and in-hospital mortality, and secondarily the association between prognosis (in-hospital mortality, inability to receive full oral intake, re-admission, hospital stay length) among four groups classified by mean amino acid dose (No dose: 0 g/kg/day; Very low dose: >0, ≤0.3 g/kg/day; Low dose: >0.3, ≤0.6 g/kg/day; Moderate dose: >0.6 g/kg/day).

Results: The analysis population included 20,457 inpatients (≥80 years: 78.3%). In total, 5,920 mortalities were recorded. Increased amino acid doses were significantly associated with reduced in-hospital mortality (p <0.001). With a No dose reference level, the odds ratios (95% confidence interval) of in-hospital mortality adjusted for potential confounders, were 0.78 (0.72-0.85), 0.74 (0.67-0.82), and 0.69 (0.59-0.81) for Very low, Low, and Moderate amino acid doses, respectively. Additionally, patients prescribed amino acid dose levels >0.6 g/kg/day had shorter hospitalization periods than those prescribed none.

Conclusions: Increased amino acid doses were associated with reduced in-hospital mortality. Sufficient amino acid administration is recommended for patients with aspiration pneumonia requiring NPO status.
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http://dx.doi.org/10.1093/gerona/glab306DOI Listing
October 2021

Expression of nerve growth factor in the callus during fracture healing in a fracture model in aged mice.

Biomed Mater Eng 2021 Sep 2. Epub 2021 Sep 2.

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

Background: Impaired fracture healing results in extensive and prolonged disability and long-term pain. Previous studies reported that nerve growth factor (NGF) was expressed during fracture healing and that anti-NGF antibody improves physical activity associate with facture pain. However, NGF expression levels in delayed or non-union are not fully understood.

Objective: We compared chronological changes in NGF in the callus of young mice after femur fracture with those in aged mice after femur fracture as a model of bone fracture in the elderly.

Methods: We used young (age 8 weeks) and aged (age 10 months) male C57BL/6J mice. A fracture was generated in the femur. At 5, 7, 10, 14, 17, and 21 days after creation of a fracture, mRNA expression levels of Col2a1, Col10a1, NGF were evaluated using quantitative PCR. We examined NGF protein expression levels and localization in the callus at day 14 using ELISA and immunohistochemistry, respectively.

Results: Expression of NGF in the callus after femur fracture in aged mice was significantly greater than that in young mice at days 5, 7, 10, 17, and 21 days. NGF protein levels in the callus of aged mice were also significantly higher than that in young mice. Immunohistochemical staining showed that NGF was heavily expressed in hypertrophic chondrocytes in the callus in aged mice.

Conclusions: It is suggested that delayed Col2a1 and Col10a1 expression reflects delayed chondrocyte formation and delayed chondrocyte maturation in aged mice and that higher NGF expression in aged mice at day 14 may be associated with the presence of remaining hypertrophic chondrocytes in callus with delaying endochondral ossification.
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http://dx.doi.org/10.3233/BME-211284DOI Listing
September 2021

Reduced TGF- Expression and CD206-Positive Resident Macrophages in the Intervertebral Discs of Aged Mice.

Biomed Res Int 2021 12;2021:7988320. Epub 2021 Jul 12.

Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa 252-0374, Japan.

Age is a key factor in intervertebral disc (IVD) degeneration; however, the changes that occur in IVDs with age are not fully understood. Tissue-resident macrophages are critical for tissue homeostasis and are regulated by transforming growth factor- (TGF-) . We examined changes in the proportion of resident macrophages in young versus aged mice and the role of TGF- in regulating resident macrophages in IVDs. IVDs were harvested from 4-month (young) and 18-month-old (aged) C57BL/6J mice. The proportion of macrophages in IVDs was determined using flow cytometry ( = 5 for each time point) and the expression of , , and genes, which encode CD11b, CD206, and TGF- protein, respectively, using real-time PCR. To study the role of TGF- in the polarization of resident macrophages, resident macrophages isolated from IVDs from young and aged mice were treated with recombinant TGF- with and without a TGF- inhibitor (SB431542). Additionally, SB431542 was intraperitoneally injected into young and aged mice, and expression was examined using real-time PCR ( = 10 for each time point). The proportion of CD11b+ and CD11b+ CD206+ cells was significantly reduced in aged versus young mice, as was , , and expression. TGF-/IL10 stimulation significantly increased the expression of , an M2 macrophage marker, in disc macrophages from both young and aged mice. Meanwhile, administration of a TGF- inhibitor significantly reduced expression compared to vehicle control in both groups. . Resident macrophages decrease with age in IVDs, which may be associated with the concomitant decrease in TGF-. Our findings provide new insight into the mechanisms of age-related IVD pathology.
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http://dx.doi.org/10.1155/2021/7988320DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289593PMC
September 2021

Prevalence and Characteristics of Spinal Sagittal Malalignment in Patients with Osteoporosis.

J Clin Med 2021 Jun 26;10(13). Epub 2021 Jun 26.

Department of Orthopaedic Surgery, School of Medicine, Kitasato University, Kanagawa 252-0374, Japan.

Spinal sagittal malalignment due to vertebral fractures (VFs) induces low back pain (LBP) in patients with osteoporosis. This study aimed to elucidate spinal sagittal malalignment prevalence based on VF number and patient characteristics in individuals with osteoporosis and spinal sagittal malalignment. Spinal sagittal alignment, and VF number were measured in 259 patients with osteoporosis. Spinal sagittal malalignment was defined according to the SRS-Schwab classification of adult spinal deformity. Spinal sagittal malalignment prevalence was evaluated based on VF number. In patients without VFs, bone mineral density, bone turnover markers, LBP scores and health-related quality of life (HRQoL) scores of normal and sagittal malalignment groups were compared. In 205 of the 259 (79.2%) patients, spinal sagittal malalignment was detected. Sagittal malalignment prevalence in patients with 0, 1, or ≥2 VFs was 72.1%, 86.0%, and 86.3%, respectively. All LBP scores and some subscale of HRQoL scores in patients without VFs were significantly worse for the sagittal malalignment group than the normal alignment group ( < 0.05). The majority of patients with osteoporosis had spinal sagittal malalignment, including ≥70% of patients without VFs. Patients with spinal sagittal malalignment reported worse LBP and HRQoL. These findings suggest that spinal sagittal malalignment is a risk factor for LBP and poor HRQoL in patients with osteoporosis.
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http://dx.doi.org/10.3390/jcm10132827DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8268752PMC
June 2021

Incidence of Unintentional Intraoperative Hypothermia in Pediatric Scoliosis Surgery and Associated Preoperative Risk Factors.

Spine Surg Relat Res 2021 20;5(3):154-159. Epub 2020 Nov 20.

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

Introduction: Intraoperative hypothermia is associated with perioperative complications such as blood loss and wound infection. Thus, perioperative heat retention methods to prevent perioperative hypothermia such as providing a warmed blanket and active patients' warming are important. Although major surgery and pediatric patient age are noted as risk factors, only a few studies focus on hypothermia as an intraoperative complication in pediatric scoliosis surgery. The aim of this study is to investigate the incidence of intraoperative hypothermia in pediatric scoliosis surgery and the associated preoperative risk factors.

Methods: We retrospectively reviewed the records of pediatric patients who underwent posterior spinal fusion at a single institution between 2015 and 2019. We recorded the background data, perioperative data, lowest recorded core temperature, and perioperative complications. Patients were divided into those whose temperature decreased below 36°C (Group H) and those who maintained a temperature of 36°C or greater (Group N) during surgery. We compared the two groups and performed multivariate analysis to identify preoperative risk factors for intraoperative hypothermia.

Results: A total of 103 patients underwent posterior spinal fusion; 56 for adolescent idiopathic scoliosis and 47 for neuromuscular scoliosis. Hypothermia was observed in 40 patients (38.8%). Group H had more non-adolescent idiopathic scoliosis (AIS) patients, lower mean body mass index, greater mean blood loss, greater number of fused vertebrae, larger preoperative Cobb angle, and lower initial core body temperature (immediately after induction of anesthesia). On multivariate analysis, a diagnosis of neuromuscular scoliosis, a lower body mass index, and a lower initial core body temperature were identified as independent risk factors for intraoperative hypothermia.

Conclusions: The incidence of hypothermia in pediatric posterior scoliosis surgery is 38.8%. Diagnosis of non-AIS, lower body mass index, and lower core body temperature at the time of anesthesia induction are preoperative risk factors for intraoperative hypothermia.
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http://dx.doi.org/10.22603/ssrr.2020-0170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208945PMC
November 2020

Posterior Spinal Correction and Fusion Surgery in Patients with Spinal Muscular Atrophy-Associated Scoliosis for Whom Treatment with Nusinersen Was Planned.

Spine Surg Relat Res 2021 31;5(2):109-113. Epub 2020 Aug 31.

Department of Orthopaedic Surgery, School of Medicine, Kitasato University, Sagamihara, Kanagawa, Japan.

Introduction: Spinal muscular atrophy (SMA) is defined as a neuromuscular disorder induced by progressive weakness of the skeletal muscle and is usually accompanied by progressive spinal deformity including scoliosis. The newly developed Nusinersen, which is the first approved drug worldwide for SMA, requires accurate intrathecal injection, which is sometimes difficult in patients with severe spinal deformity.

Technical Note: For an accurate intrathecal approach in patients who have spinal fusion surgery to treat neuromuscular scoliosis, we have combined an L3 laminectomy with spinal correction and fusion surgery. Here, we review four cases of SMA in patients who underwent the additional L3 laminectomy during surgery to treat spinal scoliosis. A successful intrathecal approach was made using fluoroscopic guidance in all four patients, who were then administered with Nusinersen.

Conclusions: Our findings show that additional lumbar laminectomy during surgery for spinal scoliosis has effectively allowed for intrathecal injection of Nusinersen.
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http://dx.doi.org/10.22603/ssrr.2020-0091DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026202PMC
August 2020

Nutritional management in inpatients with aspiration pneumonia: a cohort medical claims database study.

Arch Gerontol Geriatr 2021 Jul-Aug;95:104398. Epub 2021 Mar 18.

Medical Affairs Department, Otsuka Pharmaceutical Factory, Inc., 2-9 Kanda-Tsukasamachi, Chiyoda-ku, Tokyo, Japan.

Background/objectives: This study aimed to describe real-world nutrition management patterns among inpatients hospitalized for aspiration pneumonia, using a medical claims database in Japan.

Methods: Patients aged ≥65 years hospitalized for aspiration pneumonia treatment were identified in a medical claims database between January 2013 and December 2018, to evaluate nutrition management initiation and adjustment timing, factors associated with >7-days nil per os (NPO) status, prescribed nutrition doses, and types of parenteral nutrition solutions. Patients who received oral intake or enteral nutrition on the day of admission (Day 1) were excluded.

Results: The analysis population included 72,315 inpatients. The median (first quartile, third quartile) initiation date of oral nutrition intake was Day 4 (3, 7) and 65.1% of patients received oral nutrition intake by Day 7. Factors associated with >7-day NPO included sex, BMI, treatment years, Barthel Index score, Japan Coma Scale score, and oxygen inhalation on the day of hospital admission. Amongst NPO patients on Day 7, only 5.3% were prescribed the recommended doses of ≥20 kcal/kg; 6.4% were prescribed ≥1.0 g/kg amino acids, and 5.7% were prescribed fat energy ratio at ≥15% of non-protein calories. Commonly prescribed parenteral nutrition solutions on Day 7 were carbohydrate/electrolyte solutions (52.8%) and peripheral parenteral nutrition solutions (49.0%).

Conclusion: Prescribed parenteral energy, amino acids, and fat during the NPO period were lower than the recommended doses in the majority of patients. Prescribing recommended doses of each of these component nutrients may be beneficial when managing parenteral nutrition of patients during NPO.
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http://dx.doi.org/10.1016/j.archger.2021.104398DOI Listing
June 2021

Acceleration of bone formation using in situ-formed hyaluronan-hydrogel containing bone morphogenetic protein-2 in a mouse critical size bone defect model.

Biomed Mater Eng 2021 ;32(4):207-215

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

Background: An enzymatic crosslinking strategy using hydrogen peroxide and horseradish peroxidase is receiving increasing attention for application with in situ-formed hydrogels (IFHGs). IFHGs may also be ideal carrier materials for bone repair, although their ability to carry bone morphogenetic protein-2 (BMP2) has yet to be examined.

Objective: We examined the effectiveness of an IFHG made of hyaluronan (IFHG-HA) containing BMP2 for promoting bone formation in a mouse critical size bone defect model.

Methods: C57/BL6J mice received a 2-mm femoral critical-sized bone defect before being randomly assigned to one of the following treatment groups (n = 6): control (no treatment), IFHG-HA only, PBS with BMP2, and IFHG-HA with BMP2. X-ray radiographs were utilized to track new bone formation, and micro-computed tomography and histological examination were performed on new bone formed at the bone defect site two weeks after surgery.

Results: Mice treated with PBS with BMP2 and IFHG-HA with BMP2 had greater bone volume (BV) and bone mineral content (BMC) than those receiving control, and successfully achieved consolidation. Mice treated with IFHG-HA with BMP2 had significantly higher BV and BMC than those treated with PBS with BMP2.

Conclusions: IFHG-HA may be an effective carrier for BMP2 to enable delivery for bone defect repair.
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http://dx.doi.org/10.3233/BME-201172DOI Listing
September 2021

Chylous retroperitoneum following 720 degree anteroposterior-combined corrective surgery for adult spinal deformity with split vertebral fracture subluxation: a case report.

Spine Deform 2021 07 2;9(4):1183-1189. Epub 2021 Mar 2.

Department of Orthopaedic Surgery, Kitasato University School of Medicine, 1-15-1, Kitazato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan.

Study Design: Clinical case report.

Purpose: To report the rare case with post-operative chylous retroperitoneum after corrective surgery for adult spinal deformity.

Methods: We present a case of a 73-year-old woman with Parkinson's disease. She sustained a severe split fracture subluxation of the L3 vertebra with AO Spine Thoracolumbar classification type CN2M2, resulting in severe kyphoscoliosis in global alignment. She underwent a two-stage 720-degree anteroposterior-combined corrective surgery with anterior vertebral column resection of L3 and posterior fusion from T4 to the pelvis. On post-operative day 1, milky fluid in the drainage tube was noted, which was diagnosed as post-operative chylous retroperitoneum.

Results: Oral intake was discontinued immediately and peripheral parenteral nutrition was started. A low-fat, high-protein diet was started on post-operative day 4, and drainage was removed on day 6. A low-fat diet was continued until 3 months post-operatively, with dietary counselling by a nutritionist. The chylous retroperitoneum resolved without recurrence at the final follow-up evaluation at 3 years.

Conclusion: Surgeons should recognize this rare complication, which might be induced by direct damage to the lymphatic flow during an operative maneuver anterior to the lumbar vertebral body and indirect damage due to shearing force during correction of a subluxated vertebra, especially in cases with a severe deformity.
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http://dx.doi.org/10.1007/s43390-021-00309-3DOI Listing
July 2021

New parallel computing algorithm of molecular dynamics for extremely huge scale biological systems.

J Comput Chem 2021 02 16;42(4):231-241. Epub 2020 Nov 16.

Computational Biophysics Research Team, RIKEN Center for Computational Science, Kobe, Hyogo, Japan.

In this paper, we address high performance extreme-scale molecular dynamics (MD) algorithm in the GENESIS software to perform cellular-scale molecular dynamics (MD) simulations with more than 100,000 CPU cores. It includes (1) the new algorithm of real-space nonbonded interactions maximizing the performance on ARM CPU architecture, (2) reciprocal-space nonbonded interactions minimizing communicational cost, (3) accurate temperature/pressure evaluations that allows a large time step, and (4) effective parallel file inputs/outputs (I/O) for MD simulations of extremely huge systems. The largest system that contains 1.6 billion atoms was simulated using MD with a performance of 8.30 ns/day on Fugaku supercomputer. It extends the available size and time of MD simulations to answer unresolved questions of biomacromolecules in a living cell.
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http://dx.doi.org/10.1002/jcc.26450DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7975918PMC
February 2021

Clinical Impact of Prescribed Doses of Nutrients for Patients Exclusively Receiving Parenteral Nutrition in Japanese Hospitals: A Retrospective Cohort Study.

JPEN J Parenter Enteral Nutr 2021 09 11;45(7):1514-1522. Epub 2020 Nov 11.

Medical Affairs Department, Otsuka Pharmaceutical Factory, Inc, Kanda-Tsukasamachi, Chiyoda-ku, Tokyo, Japan.

Background: In patients receiving parenteral nutrition (PN), the association between nutrition achievement in accordance with nutrition guidelines and outcomes remains unclear. Our purpose was to assess the association between nutrition achievement and clinical outcomes, including in-hospital mortality, activity of daily living (ADL), and readmission.

Methods: In this retrospective cohort study, data were extracted from an inpatient medical-claims database at 380 acute care hospitals. This study included patients who underwent central venous catheter insertion between January 2009 and December 2018. Patients were classified into 3 groups: (1) target-not-achieved; (2) target-partially-achieved; and (3) target-achieved. The target doses of energy, amino acids, and lipid were defined as ≥20 kcal/kg/day, ≥1.0 g/kg/day, and ≥2.5 g/day, respectively. To examine the effect of nutrition achievement on outcomes, a multivariable logistic regression analysis was performed.

Results: A total of 54,687 patients were included; of these, 21,383 patients were in the target-not-achieved group, 29,610 patients were in the target-partially-achieved group, and 3694 patients were in the target-achieved group. The adjusted odds ratio (OR) (95% CI) for in-hospital mortality was 0.69 (0.66-0.72) in the target-partially-achieved group and 0.47 (0.43-0.52) in the target-achieved group with reference to the target-not-achieved group. The adjusted ORs for deteriorated ADL was 0.93 (0.85-1.01) in the target-partially-achieved group and 0.77 (0.65-0.92) in the target-achieved group with reference to the target-not-achieved group. Readmission was not associated with nutrition achievement.

Conclusion: In-hospital mortality was lower and deteriorated ADL was suppressed in patients whose PN management was in accordance with the nutrition guidelines.
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http://dx.doi.org/10.1002/jpen.2033DOI Listing
September 2021

Short-Term Impact of Staying Home on Bone Health in Patients With Osteoporosis During a State of Emergency Declaration Due to COVID-19 in Kanagawa, Japan.

Cureus 2020 Sep 6;12(9):e10278. Epub 2020 Sep 6.

Department of Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN.

Background On April 16, 2020, the Japanese government declared a state of emergency due to the spread of COVID-19 infection, leading prefectural governors to announce a stay-at-home order for 39 days until May 25, 2020. As physical inactivity is a risk factor for osteoporosis, we investigated the short-term impact of the stay-at-home order on bone health among patients with osteoporosis in our hospital in Kanagawa prefecture. Methods Thirty patients with osteoporosis with no delays in their regular medication who received care at our hospital's osteoporosis outpatient clinic within one month after the end of the state of emergency were included. Lumbar spine and femur proximal bone mineral density (BMD) were measured at the last follow-up date (May 25 to June 30, 2020; 0M) and six (6M) and 12 months (12M) before the last follow-up using dual-energy X-ray absorptiometry. Bone alkaline phosphatase (BAP), Tartrate-resistant Acid Phosphatase 5b (TRACP5b), calcium and phosphorus were assessed at the same time points. Results Serum BAP concentrations were significantly lower at 0M than 12M (p=0.040), but were comparable between 0M and 6M (p=0.527). Serum TRACP5b was significantly lower at 6M than 12M (p=0.009), but was similar between 0M and 6M (p=1.000). Serum calcium and phosphorus did not differ among the time points (p=0.516 and p=0.358, respectively). Similarly, lumbar spine and femoral neck BMD were comparable (p=0.679 and p=0.076, respectively). Conclusion Bone health in patients with osteoporosis was maintained during the short-term COVID-19 stay-at-home order among patients who experienced no delays in medication. However, larger and long-term studies are needed.
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http://dx.doi.org/10.7759/cureus.10278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7478512PMC
September 2020

Acceleration of Bone Healing by In Situ-Forming Dextran-Tyramine Conjugates Containing Basic Fibroblast Growth Factor in Mice.

Cureus 2020 Aug 27;12(8):e10085. Epub 2020 Aug 27.

Orthopaedic Surgery, Kitasato University School of Medicine, Sagamihara, JPN.

An enzymatic crosslinking strategy using hydrogen peroxide (HO) and horseradish peroxidase (HRP) has been receiving increasing attention for use with in situ-formed hydrogels (IFHs). Several studies have reported the application of IFHs in cell delivery and tissue engineering. IFHs may also be ideal carrier materials for bone repair, although their potential as a carrier for basic fibroblast growth factor (bFGF) has yet to be evaluated. Here, we examined the effect of an IFH made of dextran (Dex)-tyramine (TA) conjugates (IFH-Dex-TA) containing bFGF in promoting bone formation in a fracture model in mice. Immediately following a fracture procedure, animals either received no treatment (control) or an injection of IFH-Dex-TA/phosphate-buffered saline (IFH-Dex-TA/PBS) or IFH-Dex-TA containing 1 μg bFGF (IFH-Dex-TA/bFGF) into the fracture site (n=10, each treatment). Fracture sites injected with IFH-Dex-TA/bFGF showed significantly greater bone volume, mineral content, and bone union than sites receiving no treatment or treated with IFH-Dex-TA/PBS alone (each n=10). This Dex-TA gel may be an effective drug delivery system for optimizing bFGF therapy.
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http://dx.doi.org/10.7759/cureus.10085DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455394PMC
August 2020

A survey on total parenteral nutrition in 55,000 hospitalized patients: Retrospective cohort study using a medical claims database.

Clin Nutr ESPEN 2020 10 21;39:198-205. Epub 2020 Jul 21.

Medical Affairs Department, Otsuka Pharmaceutical Factory, Inc., 2-9 Kanda-Tsukasamachi, Chiyoda-ku, Tokyo, 101-0048, Japan.

Background & Aims: Identifying the prevalence of underfed patients and risk factors for underfeeding in patients with total parenteral nutrition (TPN) is essential to improve the management of patients receiving TPN. The aim of this study was to examine the prevalence and risk factors for underfeeding using a medical claims database.

Methods: In this retrospective cohort study using a medical claims database, we analyzed patient characteristics, timing and duration of nutrition prescription, daily dose of nutrients, and types of parenteral nutrition products administered after central venous catheter (CVC) insertion in hospitalized Japanese patients between 2009 and 2018. The mean prescriptions of energy <20 kcal/kg/day, amino acids <1.0 g/kg/day, and fat <2.5 g/day received by patients between the 4th and 10th day after CVC insertion were regarded as underfeeding. To study the association between nutritional adequacy and body mass index (BMI) with TPN, the proportions of patients with a prescription of energy ≥20 kcal/kg/day or amino acids ≥1.0 g/kg/day were calculated and categorized according to BMI, and the Cochran-Armitage trend test was performed.

Results: Of 54,687 patients included in the study, 70.3% were aged ≥70 years, and 31.3% had a BMI <18.5. The mean prescription of energy was insufficient in 49.9% of patients, and 82.9% were insufficiently prescribed with amino acids. In addition, 44.4% of the patients were never prescribed a single dose of fat emulsion during their hospital stay. On the 10th day after CVC insertion, the majority of patients used commercial 2-in-1 compounds containing carbohydrates and amino acids. A higher BMI was associated with underfeeding of energy and amino acids (both p < 0.001).

Conclusions: It is important to adjust the nutrition dose according to the patient's body size and weight, and it is necessary to supplement inadequate nutrients by single-nutrition solutions in addition to compounded solutions.
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http://dx.doi.org/10.1016/j.clnesp.2020.06.013DOI Listing
October 2020

Sequential CCL2 Expression Profile After Disc Injury in Mice.

J Orthop Res 2020 04 20;38(4):895-901. Epub 2019 Nov 20.

Department of Orthopedic Surgery, Kitasato University School of Medicine, 1-15-1 Minami-ku Kitasato, Sagamihara City, Kanagawa, 252-0374, Japan.

Macrophages produce proinflammatory cytokines in injured intervertebral discs (IVDs). We recently showed that macrophage-derived inflammatory cytokines contribute to the production of pain-related factors. However, the mechanism by which macrophages are recruited to injured IVDs has not been fully clarified. Here, we examined the expression dynamics of the chemokine CCL2 in a mouse IVD injury model and the mechanisms of its regulation. The percentage of macrophages increased from day 1 after injury and persisted up until day 28. At 1 and 3 days after injury, the expression of both Ccl2 messenger RNA (mRNA) and CCL2 protein was elevated in the IVD injury group, after which expression decreased to basal levels. Consistent with the increase in CCL2 expression, Ccr2 and Tnfa expression and various types of macrophages were also immediately elevated following disc injury. Further, tumor necrosis factor-α (TNF-α) stimulated Ccl2 mRNA and CCL2 protein expression in IVD cells in vitro. The expressions of M1 (Cd86 and Nos2) and M2a (Ym1) macrophage markers were all significantly elevated from  day 1 following injury in injured compared with control mice. Meanwhile, the expression of Cd206 (M2a and M2c marker) was significantly elevated on days 3, 7, 14, and 28 following injury. These results suggest that in IVD injury, TNF-α stimulates CCL2, which, in turn, mediates the recruitment of macrophages with the recruited macrophages subsequently differentiating into M1 and M2 subtypes. CCL2 signaling may, therefore, play an important role in IVD pathology via macrophage recruitment. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:895-901, 2020.
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http://dx.doi.org/10.1002/jor.24522DOI Listing
April 2020

The Relationship between Preoperative Echocardiographic Evaluation and Spinal Deformity in Patients with Neuromuscular Scoliosis.

Spine Surg Relat Res 2018 27;2(1):48-52. Epub 2018 Jan 27.

Department of Orthopaedic Surgery, Kitasato University School of Medicine, Kanagawa, Japan.

Introduction: Echocardiography is an important component of perioperative cardiac risk stratification in patients with neuromuscular scoliosis (NMS). However, there are little data regarding the relationship between preoperative echocardiographic findings and spinal deformity. We retrospectively reviewed preoperative echocardiographic data to investigate the relationship between echocardiographic evaluation and spinal deformity in NMS.

Methods: We reviewed 73 NMS patients (mean age: 13.3 years, male 66%) who underwent spinal correction surgery between 2008 and 2016. Echocardiographic data including ejection fraction (EF), valvar disease, and inferior vena cava diameter were collected from the preoperative exam. Demographic and radiographic data were also collected.

Results: Preoperative diagnoses included Duchenne muscular dystrophy, Fukuyama congenital muscular dystrophy, other dystrophy, spinal muscular atrophy, and congenital myopathies. Mean Body Mass Index (BMI) was 15.6 kg/m. Mean major Cobb angle before surgery was 86.6 ± 28.2°. Because of technical difficulty, complete echocardiographic data could only be collected and evaluated in 49.3% of patients. Neither right nor left sided cardiac evaluation could be completed in 20.5%. Patients in whom complete echocardiographic data could not be collected had significantly more extensive thoracic scoliosis with a more rigid curve and hypokyphosis, and were of lower weight and BMI than patients in whom complete data could be collected. Ten cases (13.7%) were diagnosed as having minor heart-related complications immediately after surgery, and they had higher right atrial pressures preoperatively.

Conclusions: Echocardiography can be technically difficult in NMS patients with extensive spinal deformities. We found that perioperative cardiac function could only be evaluated by echocardiogram in about half of NMS patients undergoing spinal correction surgery. The absence of an adequate preoperative cardiac evaluation could render these patients more susceptible to perioperative heart-related complications. Echocardiography may not be sufficient to evaluate cardiac conditions in children with extensive NMS.
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http://dx.doi.org/10.22603/ssrr.2017-0018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698548PMC
January 2018
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