1.Pharmacoepidemiological Examination for the Safety of the Oral laxatives in the Elderly Patients
Yoshihiro Noguchi ; Yuta Hayashi ; Aki Yoshida ; Ikuto Sugita ; Hiroki Esaki ; Kousuke Saito ; Kazumasa Usui ; Misa Kato ; Tomoya Tachi ; Hitomi Teramachi
Japanese Journal of Drug Informatics 2016;18(3):179-185
Objective: Many of the elderly patients are suffering from constipation, are using the oral laxative. However the risk assessment of the oral laxative is not performed. Therefore, we used Japanese Adverse Drug Event Report database (JADER) and examined for the safety of the oral laxative in the elderly patients.
Methods: Since the analysis target medicines; 12 oral laxatives and target ADEs; “digestive disorders” and “electrolyte abnormality,” the JADER database for April 2004 to January 2015 were analyzed in adults of age exceeds 60. We used the reporting odds ratio for a safety index of drugs, using reporting odds ratio, when the Lower bound of the 95% two-sided confidence interval exceeds 1, it is the signal detection of ADE.
Results: The oral laxatives detected the signal of “digestive disorders” were three medicines, and “electrolyte abnormality” were five medicines. Especially, for electrolyte abnormalities not only increases the blood magnesium values as magnesium oxide, that there is also affect other electrolyte revealed.
Conclusion: Some oral laxatives were also intended to signal detections of the adverse events that are not listed in the attached document, it is necessary to pay attention to the use of them for the elderly patients.
2.Search for Oral Medicine That Might Exacerbate the Prognosis of Adverse Drug Events in Elderly Patients
Yoshihiro Noguchi ; Yuta Hayashi ; Aki Yoshida ; Ikuto Sugita ; Hiroki Esaki ; Kousuke Saito ; Kazumasa Usui ; Misa Kato ; Tomoya Tachi ; Hitomi Teramachi
Japanese Journal of Drug Informatics 2017;18(4):277-283
Objective: Elderly patients commonly experience adverse drug events (ADEs) owing to their poor drug metabolizing and excretion ability, and these often cause multiple organ dysfunction syndrome. Therefore, it is important that we identify the adverse drug events early on during prognosis. We searched for oral medicines that might exacerbate the prognosis of ADEs in elderly patients.
Methods: The objects under analysis were oral medicines that were registered in the Japanese Adverse Drug Event Report database (JADER). The associations between the elderly/non-elderly patients and exacerbation risk/non-exacerbation risk were analyzed by risk ratios (RR). The signal detection of exacerbation risk was defined as 95% confidence interval of lower limit of risk ratio>1 and χ2≥4.
Results: The oral medicines that might markedly exacerbate the prognosis of ADEs in the elderly patients in comparison with the ADEs of young patients included 84 items, of which 63 have not been described as potentially inappropriate medicines in all guidelines for medical treatment of the elderly patients.
Conclusion: In this study, while we could not search for oral medicines having a high risk of ADEs, we were able to search for oral medicines that might exacerbate the prognosis of ADEs in elderly patients. This result could contribute to the proper use of medicines in the elderly patients.
3.Advanced Erosive Gout as a Cause of Fever of Unknown Origin.
Mikiro KATO ; Yuta OISHI ; Makoto INADA ; Yasuharu TOKUDA
Korean Journal of Family Medicine 2015;36(3):146-149
A 61-year-old man was referred to our hospital due to a 3-month history of fever of unknown origin, and with right knee and ankle joint pains. At another hospital, extensive investigations had produced negative results, including multiple sterile cultures of blood and joint fluids, and negative autoantibodies. His serum uric acid level was not elevated. However, after admission to our hospital, we performed right knee arthrocentesis, which revealed uric acid crystals. These findings, combined with the results of imaging tests, which showed joint degeneration, led to a diagnosis of advanced erosive gout. After receiving a therapeutic non-steroidal anti-inflammatory drug and a maintenance dose of colchicine for prophylaxis against recurrence, the patient's symptoms subsided and did not return. Advanced erosive gout should be considered a possible cause of fever of unknown origin and diagnostic arthrocentesis should be performed in patients with unexplained arthritis.
Ankle Joint
;
Arthritis
;
Autoantibodies
;
Colchicine
;
Diagnosis
;
Fever of Unknown Origin*
;
Gout*
;
Humans
;
Joints
;
Knee
;
Middle Aged
;
Recurrence
;
Uric Acid
4.Segmental Arteries and Veins at Higher Lumbar Levels Can Intersect the Adjacent Caudal Intervertebral Disc in the Anterior Part of the Spinal Column: A Cadaveric Analysis
Kiyoshi YAGI ; Nobuyuki SUZUKI ; Jun MIZUTANI ; Kenji KATO ; Akira KONDO ; Yuya WASEDA ; Yuta GOTO ; Hideki MURAKAMI
Asian Spine Journal 2022;16(1):1-8
Methods:
Five formalin-embalmed human cadavers were used. We assessed the proportion of segmental arteries and veins that intersected the IVD in the L2–L5 range and their course on the anterior part of the spinal column.
Results:
The segmental arteries and veins commonly intersect the anterior part of the IVD (artery, 28.1%; vein, 42.1%). Seven of 10 (70%) segmental arteries at L2 intersected the IVD, but only one artery intersected the IVD at L3 and L4. The proportions of segmental veins that intersected the IVD were 60%, 50%, and 16.7% at L2, L3, and L4, respectively.
Conclusions
The segmental arteries and veins frequently intersect the IVD in the anterior part of the spinal column. Therefore, it is necessary to consider these individual anatomical features to prevent vascular damage during lateral lumbar interbody fusion surgery.
5.Surgical Outcomes of Multilevel Posterior Lumbar Interbody Fusion versus Lateral Lumbar Interbody Fusion for the Correction of Adult Spinal Deformity: A Comparative Clinical Study
Masayoshi IWAMAE ; Akira MATSUMURA ; Takashi NAMIKAWA ; Minori KATO ; Yusuke HORI ; Akito YABU ; Yuta SAWADA ; Noriaki HIDAKA ; Hiroaki NAKAMURA
Asian Spine Journal 2020;14(4):421-429
Methods:
We retrospectively reviewed 31 ASD patients who underwent multilevel LIF combined with PCO (LIF group, n=14) or multilevel PLIF (PLIF group, n=17) and with a minimum 2-year follow-up. In the comparison between LIF and PLIF groups, their mean age at surgery was 69.4 vs. 61.8 years while the mean follow-up period was 29.2 vs. 59.3 months. We evaluated the transition of pelvic incidence–lumbar lordosis (PI–LL) and disc angle (DA) in the LIF group, in fulcrum backward bending (FBB), after LIF and after posterior spinal fusion (PSF) with PCO. The spinopelvic radiographic parameters were compared between LIF and PLIF groups.
Results:
Compared with the PLIF group, the LIF group had less blood loss and comparable surgical outcomes with respect to radiographic data, health-related quality of life scores and surgical time. In the LIF group, the mean DA and PI–LL were unchanged after LIF (DA, 5.8°; PI–LL, 15°) compared with the values using FBB (DA, 4.3°; PI–LL, 15°) and improved significantly after PSF with PCO (DA, 8.1°; PI–LL, 0°).
Conclusions
In the surgical treatment of ASD, multilevel LIF is less invasive than multilevel PLIF and combination of LIF and PCO would be necessary for optimal sagittal correction in patients with rigid deformity.
6.p38 Mitogen-Activated Protein Kinase Is Involved in Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells Stimulated by Tumor Necrosis Factor-α
Kiyoshi YAGI ; Yuta GOTO ; Kenji KATO ; Nobuyuki SUZUKI ; Akira KONDO ; Yuya WASEDA ; Jun MIZUTANI ; Yohei KAWAGUCHI ; Yuji JOYO ; Yuko WAGURI-NAGAYA ; Hideki MURAKAMI
Asian Spine Journal 2021;15(6):713-720
Methods:
HFCs were obtained from patients with LSS who underwent surgery. HFCs were stimulated by tumor necrosis factor-α (TNF-α) and a p38 MAP kinase inhibitor, SB203580. Phosphorylation of the p38 MAP kinase was analyzed by western blotting. The concentration of interleukin-6 (IL-6) in the conditioned medium was measured by enzyme-linked immunoassay and IL-6 messenger RNA expression levels were determined by real-time polymerase chain reaction.
Results:
TNF-α induced the phosphorylation of p38 MAP kinase in a time-dependent manner, which was suppressed by the p38 MAP kinase inhibitor, SB203580. TNF-α also stimulated IL-6 release in both a time- and dose-dependent manner. On its own, SB203580 did not stimulate IL-6 secretion from HFCs; however, it dramatically suppressed the degree of IL-6 release stimulated by TNF-α from HFCs.
Conclusions
This is the first report suggesting that TNF-α stimulates the gene expression and protein secretion of IL-6 via p38 MAP kinase in HFCs. A noted association between tissue hypertrophy and inflammation suggests that the p38 MAP kinase inflammatory pathway may be a therapeutic molecular target for LSS.
7.Transforming Growth Factor-β Induces Interleukin-6 Secretion from Human Ligamentum Flavum–Derived Cells through Partial Activation of p38 and p44/42 Mitogen-Activated Protein Kinases
Yuta GOTO ; Kenji KATO ; Kiyoshi YAGI ; Yohei KAWAGUCHI ; Hiroki YONEZU ; Tomoko KOSHIMAE ; Yuko WAGURI-NAGAYA ; Hideki MURAKAMI ; Nobuyuki SUZUKI
Asian Spine Journal 2023;17(6):997-1003
Methods:
HFCs were obtained from patients with LSS who had undergone decompression surgery. The cells were stimulated with TGF-β and pretreated with either the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 or the p44/42 MAP kinase inhibitor FR180204. IL-6 secretion in the cell culture medium and IL-6 messenger RNA (mRNA) expression levels were analyzed using an enzyme-linked immunoassay and real-time polymerase chain reaction, respectively.
Results:
TGF-β administration resulted in a dose- and time-dependent stimulation of IL-6 release. Treatment with SB203580 and FR180204 markedly suppressed TGF-β–induced IL-6 secretion from HFCs. Moreover, these inhibitors suppressed IL-6 mRNA expression in response to TGF-β stimulation.
Conclusions
Our findings indicate that TGF-β induces IL-6 protein secretion and gene expression in HFCs through the activation of p38 or p44/42 MAP kinases. These results suggest a potential association between IL-6–mediated inflammatory response and tissue hypertrophy in LSS, and we provide insights into molecular targets for therapeutic interventions targeting LSS-related inflammation through our analysis of the MAP kinase pathway using HFCs.
8.Short-Term Risk Factors for Distal Junctional Kyphosis after Spinal Reconstruction Surgery in Patients with Osteoporotic Vertebrae
Yuta SAWADA ; Shinji TAKAHASHI ; Hidetomi TERAI ; Minori KATO ; Hiromitsu TOYODA ; Akinobu SUZUKI ; Koji TAMAI ; Akito YABU ; Masayoshi IWAMAE ; Hiroaki NAKAMURA
Asian Spine Journal 2024;18(1):101-109
Methods:
This study included 46 patients who underwent spinal reconstruction surgery for thoracolumbar osteoporotic vertebral fractures and kyphosis and were followed up for 1 year postoperatively. DJK was defined as an advanced kyphosis angle >10° between the LIV and one lower vertebra. The patients were divided into groups with and without DJK. The risk factors of the two groups, such as patient background, surgery-related factors, radiographic parameters, and clinical outcomes, were analyzed.
Results:
The DJK and non-DJK groups included 14 and 32 patients, respectively, without significant differences in patient background. Those with instability in the distal adjacent LIV disc had a significantly higher risk of DJK occurrence (28.6% vs. 3.2%, p=0.027). DJK occurrence significantly increased in those with the sagittal stable vertebra not included in the fixation range (57.1% vs. 18.8%, p=0.020). Other preoperative radiographic parameters were not significantly different. Instability in the distal adjacent LIV disc (adjusted odds ratio, 14.50; p=0.029) and the exclusion of the sagittal stable vertebra from the fixation range (adjusted odds ratio, 5.29; p=0.020) were significant risk factors for DJK occurrence.
Conclusions
Regarding spinal reconstruction surgery in patients with osteoporotic vertebral fractures, instability in the distal adjacent LIV disc and the exclusion of the sagittal stable vertebra from the fixation range were risk factors for DJK occurrence in the short term.
9.Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy
Ryoya SAKAKIBARA ; Shinya SUGIMOTO ; Kaoru TAKABAYASHI ; Hiroki KIYOHARA ; Yusuke WAKISAKA ; Yuta KAIEDA ; Miho KAWAIDA ; Yusuke YOSHIMATSU ; Tomohisa SUJINO ; Naoki HOSOE ; Motohiko KATO ; Masayuki SHIMODA ; Yohei MIKAMI ; Yasushi IWAO ; Takanori KANAI
Intestinal Research 2024;22(4):428-438
Background/Aims:
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods:
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results:
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.
10.Ulcerative colitis-associated neoplasms often harbor poor prognostic histologic components with low detection by biopsy
Ryoya SAKAKIBARA ; Shinya SUGIMOTO ; Kaoru TAKABAYASHI ; Hiroki KIYOHARA ; Yusuke WAKISAKA ; Yuta KAIEDA ; Miho KAWAIDA ; Yusuke YOSHIMATSU ; Tomohisa SUJINO ; Naoki HOSOE ; Motohiko KATO ; Masayuki SHIMODA ; Yohei MIKAMI ; Yasushi IWAO ; Takanori KANAI
Intestinal Research 2024;22(4):428-438
Background/Aims:
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
Methods:
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
Results:
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
Conclusions
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.