Impact of the COVID-19 Pandemic on Adherence to Denosumab Therapy: A Single Center Study

Kobayashi Kazuyoshi,Sato Koji,Ando Toshihiro,Ando Kei,Imura Saori 대한척추외과학회 2023 Asian Spine Journal Vol.17 No.5

Study Design: A retrospective comparative study of denosumab therapy adherence before and during the coronavirus disease 2019 (COVID-19) pandemic.Purpose: To evaluate the effect of the COVID-19 pandemic on denosumab therapy adherence in Japan.Overview of Literature: Denosumab is a monoclonal antibody for osteoporosis treatment. Delayed denosumab injections are associated with reduced treatment responses, which was a concern during the COVID-19 pandemic.Methods: Participants included 376 patients who received denosumab (60 mg every 6 months) from January 2013 to June 2021. The time from therapy initiation to discontinuation was used to measure persistence, and that between initial and subsequent injections was used to determine adherence. The pandemic period was from March 2020 to December 2021.Results: Patients were divided into those treated after March 2020 (pandemic group, n=244) and those who discontinued treatment before March 2020 (non-pandemic group, n=132). Non-persistent cases accounted for 154, including 24 (20%), 64 (19%), and 66 (53%) aged ≤59 years, 60–79 years, and ≥80 years, respectively. The overall persistence rate at 78 months was 59.2%. Postponed cases were significantly lower in the non-pandemic group than in the pandemic group (8% vs. 15%, <i>p</i> =0.042). Postponement with a delay of 1–2 months did not significantly differ between the two groups, but with a significant difference for a delay of ≥3 months (0% vs. 36%, <i>p</i> =0.024).Conclusions: Denosumab adherence remained constant but postponed cases significantly increased during the COVID-19 pandemic. Better communication by health providers on denosumab adherence and alternative administration may reduce dosing interruptions in similar pandemic situations.

Persistence of Denosumab Therapy among Patients with Osteoporosis

Kobayashi Kazuyoshi,Ando Kei,Machino Masaaki,Morozumi Masayoshi,Kanbara Shunsuke,Ito Sadayuki,Inoue Taro,Yamaguchi Hidetoshi,Ishiguro Naoki,Imagama Shiro 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.4

Study Design: Retrospective study in a single center.Purpose: To examine denosumab persistence in patients of different ages with severe osteoporosis in Japan.Overview of Literature: Denosumab is an antibody drug used for the treatment of osteoporosis. It is mainly used in patients with severe osteoporosis who might have high motivation for treatment, and the need for only semi-annual subcutaneous injection might improve the continuation rate. However, no English-language articles have reported on denosumab persistence in the Japanese population, including young people, despite the importance of this issue in a super-aging society. Methods: The subjects started treatment with subcutaneous denosumab in our department from July 2013 until December 2017. Persistence rates were calculated using Kaplan-Meier curves. Patients were defined as “persistent” or “non-persistent” according to the use of therapy after 60 months.Results: The study included 101 patients (84 females) with a median follow-up period of 23.6±14.2 months. The persistence rate declined to 85.3%, 78.3%, 74.1%, 71.3%, and 69.3% at 12, 24, 36, 48, and 60 months, respectively. Age at the initiation of denosumab therapy differed significantly between non-persistent (n=31) and persistent (n=70) patients (81.3 vs. 72.8 years, <i>p</i> <0.01). Persistence was significantly lower in patients aged ≥80 years than in those aged <60 and 60–79 years (both <i>p</i> <0.01). The reasons for non-persistence of denosumab therapy were transfer to another hospital (n=13), interruption of outpatient visits (n=11), dental treatment (n=4), adverse events (n=2), and patient request (n=1).Conclusions: Persistence was significantly lower in patients aged ≥80 years than in patients of other ages, and strategies promoting persistence are needed for these elderly patients.

Perioperative Management of Patients with Hemophilia during Spinal Surgery

Kazuyoshi Kobayashi,Shiro Imagama,Kei Ando,Kenyu Ito,Mikito Tsushima,Masayoshi Morozumi,Satoshi Tanaka,Masaaki Machino,Kyotaro Ota,Yoshihiro Nishida,Naoki Ishiguro 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.3

Study Design: Single-center retrospective study. Purpose: To optimize the perioperative management of patients with hemophilia who are undergoing spinal surgery. Overview of Literature: Hemophilia is a rare disease in which there is a tendency of bleeding because of a congenital deficiency in blood coagulation factor activity. There has been no previous report on spinal surgery in patients with hemophilia. Methods: The subjects were five patients (all males) with hemophilia who underwent spinal surgery at Nagoya University Hospital. Two patients had hemophilia A (deficiency of factor VIII) and three had hemophilia B (deficiency of factor IX). The mean age at the time of surgery was 63 years (range, 46–73 years). The following surgeries were performed: posterior lumbar interbody fusion (PLIF) in two patients, and lumbar fenestration, cervical laminoplasty and lumbar fenestration, and cervical laminoplasty and PLIF in one patient each. Results: Coagulation factor at a mean dose of 4.8 ×103 U (range, 3–6 ×103 U) was intravenously injected before surgery, and a mean dose of 5.2 ×103 U (rang, 4–6 ×103 U) was continuously administered for 24 hours after surgery. Factor activity was maintained at ≥80% until postoperative day 14 and at ≥50% thereafter. The average duration of surgery was 178 minutes (range, 133–233 minutes), the estimated blood loss was 661 mL (range, 272–1,344 mL), and a drain tube was left subfascially in place for 2 days in all patients. Reoperation due to postoperative surgical site infection was required in one patient, but there were no complications due to hemorrhagic diathesis. The total dose of coagulation factor administered during hospitalization was 102 ×103 U (range, 46–198 ×103 U). Conclusions: Coordination with a hematologist and dose adjustment of the coagulation factor preparation to maintain a target level of coagulation factor activity facilitated a smooth postoperative course with perioperative control of bleeding during spinal surgery for patients with hemophilia.

Spinal Metastasis from Struma Ovarii: Case Report and Review of the Literature

Kazuyoshi Kobayashi,Shiro Imagama,Shin Tsunekawa,Kaori Hosokawa,Minemori Watanabe,Zenya Ito,Kei Ando,Naoki Ishiguro 대한척추외과학회 2015 Asian Spine Journal Vol.9 No.2

Struma ovarii is a rare tumor that is defined as an ovarian teratoma with a thyroid tissue component exceeding 50%. Most of these tumors are benign, with malignant struma ovarii occurring in <1% of patients. Here, we describe the case of a 49-year-old female patient with malignant struma ovarii who developed thoracic spine metastasis. She had undergone an oophorectomy and was diagnosed with struma ovarii 10 years previously. She had remained recurrence-free thereafter. At 49 years of age, she developed low back pain and was admitted to our hospital for evaluation of a spinal tumor at the Th7 level. An emergency bone biopsy led to a diagnosis of metastasis from malignant struma ovarii. External beam radiotherapy inhibited further tumor growth and there was no resulting muscle weakness. This is the first report of spinal metastasis occurring 10 years after resection of struma ovarii, indicating the need for long-term follow-up.

Efficacy of Anal Needle Electrodes for Intraoperative Spinal Cord Monitoring with Transcranial Muscle Action Potentials

Kazuyoshi Kobayashi,Kei Ando,Hideki Yagi,Kenyu Ito,Mikito Tsushima,Masayoshi Morozumi,Satoshi Tanaka,Masaaki Machino,Kyotaro Ota,Yukihiro Matsuyama,Naoki Ishiguro,Shiro Imagama 대한척추외과학회 2018 Asian Spine Journal Vol.12 No.4

Study Design: Retrospective study. Purpose: To examine the relationship between postoperative bowel bladder disorder (BBD) and the efficacy of needle electrodes for the external anal sphincter (EAS) in intraoperative spinal cord monitoring with transcranial muscle action potentials (Tc-MsEP). Overview of Literature: Spinal surgery for spina bifida, spinal cord tumor, and spinal tethered cord syndrome has a high rate of postoperative BBD. Monitoring of the EAS with Tc-MsEP is frequently performed during spinal surgery. We initially used plug-surface electrodes for this purpose, but have more recently switched to needle electrodes for the monitoring of the EAS. To date, there has been no comparison between the utility of these electrodes. Methods: Waveform derivation, exacerbation of postoperative BBD, and sensitivity and specificity for prediction of BBD by 70% amplitude reduction of EAS activity using needle and plug-surface electrodes were investigated in 239 spine surgeries. The cut-off for the % drop in amplitude for BBD prediction was determined for EAS monitoring using a needle electrode. Results: The overall rate of postoperative BBD aggravation was 7.1% (17/239 cases), with the individual rates using needle and plug-surface electrodes being 6.9% (8/116) and 7.3% (9/123), respectively. The waveform derivation rate was significantly higher using needle electrodes (91.3% [106/116] vs. 76.4% [94/123], p <0.01). In patients with baseline waveform detection, the sensitivity and specificity for postoperative BBD were similar in the two groups. With needle electrodes, a cutoff amplitude of Tc-MsEP for the EAS at the end of surgery of 25% of the baseline amplitude had a sensitivity of 89% and specificity of 82% for the prediction of postoperative BBD aggravation. Conclusions: The significantly higher waveform derivation rate using needle electrodes suggests that these electrodes are effective for monitoring the EAS in spinal surgery in cases with preoperative BBD.

Utility of a Computed Tomography-Based Navigation System (O-Arm) for En Bloc Partial Vertebrectomy for Lung Cancer Adjacent to the Thoracic Spine: Technical Case Report

Kazuyoshi Kobayashi,Shiro Imagama,Zenya Ito,Kei Ando,Kohei Yokoi,Naoki Ishiguro 대한척추외과학회 2016 Asian Spine Journal Vol.10 No.2

We describe successful vertebrectomy from a posterior approach using a computed tomography (CT)-based navigation system (O-arm) in a 53-year-old man with adenocarcinoma of the posterior apex of the right lung with invasion of the adjacent rib, thoracic wall, and T2 and T3 vertebral bodies. En bloc partial vertebrectomy for lung cancer adjacent to the thoracic spine was planned using O-arm. First, laminectomy was performed from right T2 to T3, and pedicles and transverse processes of T2 to T3 were resected. O-arm was used to confirm the location of the cutting edge in the T2 to 3 right vertebral internal body, and osteotomy to the anterior cortex was performed with a chisel. Next, the patient was placed in a left decubitus position. The surgical specimen was extracted en bloc . This case shows that O-arm can be used reliably and easily in vertebrectomy from a posterior approach and can facilitate en bloc resection.

Scoliosis Caused by Limb-Length Discrepancy in Children

Kobayashi Kazuyoshi,Ando Kei,Nakashima Hiroaki,Machino Masaaki,Morozumi Masayoshi,Kanbara Shunsuke,Ito Sadayuki,Inoue Taro,Yamaguchi Hidetoshi,Mishima Kenichi,Ishiguro Naoki,Imagama Shiro 대한척추외과학회 2020 Asian Spine Journal Vol.14 No.6

Study Design: Single-center retrospective study in pediatric patients.Purpose: The purpose of the study was to investigate the effects of the presence and severity of leg-length discrepancy (LLD) on scoliosis in children.Overview of Literature: LLD is a common orthopedic problem that can result in standing imbalance, low back pain, and stress fractures. It may cause structural changes in the spine over time, but the exact effect of LLD on scoliosis is unknown.Methods: The subjects were 23 children with LLD ≥20 mm (range, 27–65 mm) treated at Nagoya University Hospital between 2007 and 2017. Whole spine posteroanterior standing radiographs and whole lower limb radiographs in a supine position were recorded. Data were collected for demographics, LLD, Cobb angle, pelvic obliquity, and Nash/Moe index. Scoliosis was defined as a Cobb angle ≥10°. Leg length was measured from the top of the femoral head to the middle of the tibial plafond, and LLD was defined as the difference between the left and right leg lengths.Results: The patients (nine males and 14 females) had a mean age of 14.0 years (range, 5–18 years). The average LLD was 44.3±17.2 mm, with LLDs of 20 to 39 mm, 40 to 59 mm, and ≥60 mm in 13, five, and five subjects, respectively. The average Cobb angle was 13.0°±7.0°, and 15 subjects (65%) had scoliosis. Convexity of the scoliosis was to the short leg side in all cases. The Cobb angle was significantly related to the severity of the LLD (<i>R</i>=0.736, <i>p</i><0.01), pelvic obliquity (<i>R</i>=0.966, <i>p</i><0.01), and Nash/Moe index (<i>p</i><0.05).Conclusions: LLD is a common pediatric condition that can cause scoliosis of the spine. Severe scoliosis may develop if the LLD is ≥30 mm. Long-term studies are needed to examine the effect of LLD resolution on the elimination of scoliosis.

Tectona grandis Callus Produces Antibacterial Triterpene Acids Not Detected in the Intact Plant

Marwani, Erly,Kobayashi, Akio,Kajiyama, Shin-ichiro,Fukusaki, Eiichiro,Nitoda, Teruhiko,Kanzaki, Hiroshi,Kawazu, Kazuyoshi The Korean Society of Pharmacognosy 1997 Natural Product Sciences Vol.3 No.1

Preliminary antibacterial assay data that the Tectona grandis callus extract showed more antibacterial activity against E. coli and B. subtilis than the leaf extract led the authors to isolate the following antibacterial compounds from the callus. A mixture (3) of $2{\alpha},3{\beta}-dihydroxy-olean-12-en-28-oic$ acid (3a) and $2{\alpha},3{\beta}-dihydroxy-urs-12-en-28-oic$ acid (3b) exhibited the most potent antibacterial activity against both bacteria. The other 3 compounds, in the decreasing order of the activity, were identified as $2{\alpha},3{\beta}-dihydroxy-urs-12-en-28-oic$ acid (2), betulinic acid (1), and $2{\alpha},3{\alpha}$,23-trihydroxy-urs-12-en-28-oic acid (4). The antibacterial compounds (2, 3a, 3b and 4) were not detected or occurring in small quantities in the intact tissue, while they were observed in the callus. Only the less active compound 1 was present more abundantly in intact tissues than the callus.

Rapid Changes in Serum Lipid Profiles during Combination Therapy with Daclatasvir and Asunaprevir in Patients Infected with Hepatitis C Virus Genotype 1b

Takeshi Chida,Kazuhito Kawata,Kazuyoshi Ohta,Erika Matsunaga,Jun Ito,Shin Shimoyama,Satoru Yamazaki,Hidenao Noritake,Tetsuro Suzuki,Takafumi Suda,Yoshimasa Kobayashi 거트앤리버 소화기연관학회협의회 2018 Gut and Liver Vol.12 No.2

Background/Aims: Changes in lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antiviral therapy have been reported in recent years. However, the clinical aspects of disturbed lipid metabolism in chronic HCV infection have not been fully elucidated. Methods: Dynamic changes in serum total, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) cholesterol and apolipoprotein levels in patients infected with HCV genotype 1b were examined during combination therapy with daclatasvir (DCV) and asunaprevir (ASV). Results: Total, LDL-, and HDL-cholesterol levels increased rapidly and persistently after week 4. Apolipoprotein (apo) A-I, apo B, apo C-II, and apo C-III levels were significantly higher at week 4 than at week 0. In contrast, apo A-II and apo E levels were significantly lower. The differences in LDL- and HDL-cholesterol levels were positively correlated with those of apo B and apo A-I, respectively. Interestingly, in patients with non-sustained virological response, these cholesterol levels decreased rapidly after viral breakthrough or viral relapse. Furthermore, similar changes were observed for apo A-I, apo B and apo C-III levels. Conclusions: Clearance of HCV using combination therapy with DCV and ASV results in rapid changes in serum lipid profiles, suggesting an influence of HCV infection on disturbed lipid metabolism.

Progressive Relapse of Ligamentum Flavum Ossification Following Decompressive Surgery

Kei Ando,Shiro Imagama,Zenya Ito,Kazuyoshi Kobayashi,Junichi Ukai,Akio Muramoto,Ryuichi Shinjo,Tomohiro Matsumoto,Hiroaki Nakashima,Naoki Ishiguro 대한척추외과학회 2014 Asian Spine Journal Vol.8 No.6

Thoracic ossification of the ligamentum flavum (T-OLF) is a relatively rare spinal disorder that generally requires surgical intervention, due to its progressive nature and the poor response to conservative therapy. The prevalence of OLF has been reported at 3.8%–26%, which is similar to that of cervical ossification of the posterior longitudinal ligament (OPLL). The progression of OPLL after cervical laminoplasty for the treatment of OPLL is often shown in long-term follow-up. However, there have been no reports on the progression of OLF following surgery. We report a case of thoracic myelopathy secondary to the progressive relapse of OLF following laminectomy.