Publications by authors named "Shuntaro Sato"

89 Publications

Comparison of Central Venous Port Procedures Between Puncture . Cut-down and Residents . Senior Surgeons.

In Vivo 2021 Mar-Apr;35(2):1197-1204

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background/aim: To compare operative results between venous puncture (P) with real-time ultrasonography vs. cut-down (CD) with preoperative ultrasonography for totally implantable central vein access device (TICVAD) implantation performed by residents (R) vs. senior surgeons (S).

Patients And Methods: Adult oncologic patients (n=268) undergoing TICVAD implantations were retrospectively compared between 172 Ps and 96 CDs. Then, we compared Ps performed by R (P-R, n=131) and S (P-S, n=41) and CDs performed by R (CD-R, n=59) and S (CD-S, n=37).

Results: Median operation times were 40 min in the P group and 53.5 min in the CD group, and times were significantly shorter for P-S and CD-S. Completion rates were comparable for each method and each surgeon. Intraoperative complication rates were 3.8% (P-R), 2.4% (P-S), and 0% (CD-R and CD-S).

Conclusion: P with real-time ultrasonography did not avoid complications compared to CD with preoperative ultrasonography. The latter performed safely even by residents.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/invivo.12369DOI Listing
December 2020

Single-arm, open-label pilot intervention study to investigate an effect of oral 5-aminolevulinic acid plus sodium ferrous citrate on glucocorticoid reduction in patients with adult-onset Still disease: Study protocol for clinical trial (SPIRIT compliant).

Medicine (Baltimore) 2020 Dec;99(50):e22708

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences.

Background: Glucocorticoids are an important class of medication for patients with adult-onset Still disease (AOSD), however, relapse following glucocorticoid reduction and adverse events due to long-term effects of glucocorticoid are still problematic. It is of course essential to minimize the risk of treatment. Immunosuppressive therapies such as methotrexate and biologics including tocilizumab are used in glucocorticoid-dependent patients with AOSD, but no second-line treatments for patients with glucocorticoid dependence have been established yet. Given that these drugs also have the potential to cause adverse events, alternative treatments are sought. Recently, elevated heme oxygenase-1 (HO-1) has been reported in the serum of patients with AOSD, suggesting that HO-1 activity contributes to AOSD pathogenesis and may represent a new therapeutic target for the treatment of AOSD. The amino acid 5-aminolevulinic acid (5-ALA) is a non-proteinogenic δ amino acid in human body. An addition of ferrous iron to 5-ALA enhances heme biosynthesis. The increase in heme in vivo induces HO-1 production, a heme-degrading enzyme. Elevated HO-1 has been suggested to contribute to the pathogenesis of AOSD, and administration of 5-ALA and ferrous iron may be a potential treatment for AOSD.

Methods/design: This study is a single-arm, open-label pilot intervention study using clinical endpoints to investigate the effects of oral 5-ALA with sodium ferrous citrate on glucocorticoid reduction in patients with AOSD receiving glucocorticoid therapy.

Discussion: This pilot intervention study will provide evidence regarding the effectiveness and safety of 5-ALA/sodium ferrous citrate as a potential new therapeutic agent for glucocorticoid-dependent patients with AOSD.

Trial Registration: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on January 14, 2020 as jRCTs071190042.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000022708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738081PMC
December 2020

Effects of monthly intravenous ibandronate on bone mineral density and microstructure in patients with primary osteoporosis after teriparatide treatment: The MONUMENT study.

Bone 2021 Mar 27;144:115770. Epub 2020 Nov 27.

Department of Orthopedic Surgery, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Purpose: To investigate the effects of sequential therapy with monthly intravenous ibandronate on bone mineral density (BMD) and microstructure in patients with primary osteoporosis who received teriparatide treatment.

Methods: Sixty-six patients with primary osteoporosis who had undergone teriparatide treatment for more than 12 months (mean 18.6 months) received sequential therapy with 1 mg/month intravenous ibandronate for 12 months. The patients were evaluated using dual-energy X-ray absorptiometry (DXA), quantitative ultrasound, bone turnover markers, and high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 6 and 12 months after beginning administration.

Results: At 12 months after beginning sequential therapy, the bone resorption marker, tartrate-resistant acid phosphatase-5b, decreased by 39.5%, with 82.3% of the patients exhibiting levels within the normal limit. DXA revealed that the BMD of the lumbar spine increased by 3.2%, with 79.0% of the patients exhibiting a response, and 40.3% experiencing an increase in BMD over 5%. HR-pQCT revealed that the cortical thickness of the distal tibia was increased by 2.6%. The cortical area increased by 2.5%, and the buckling ratio (an index of cortical instability) decreased by 2.5%. Most parameters of the trabecular bone showed no significant changes. These changes in the cortical bone were observed in both the distal radius and tibia and appeared beginning 6 months after treatment initiation.

Conclusions: Sequential therapy with monthly intravenous ibandronate increased the BMD and improved the cortical bone microstructure of osteoporotic patients who had undergone teriparatide treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bone.2020.115770DOI Listing
March 2021

Characteristics of aneurysmal subarachnoid hemorrhage associated with rheumatic disease.

Neurosurg Rev 2020 Nov 11. Epub 2020 Nov 11.

Department of Neurosurgery, Nagasaki University School of Medicine, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan.

Spontaneous subarachnoid hemorrhage (SAH) occurs due to intracranial aneurysm rupture in most cases. Rheumatic disease may cause vessel wall inflammation, which can increase the risk of rupture. However, the characteristics of SAH with rheumatic disease are unknown. This study aimed to evaluate SAH features in patients with rheumatic disease. We retrospectively analyzed clinical data of 5066 patients from the Nagasaki SAH Registry Study who had been diagnosed with aneurysmal SAH between 2001 and 2018. We evaluated the SAH characteristics in patients with rheumatic disease using multivariable logistic regression analysis. In total, 102 patients (2.0%, 11 men and 91 women, median age 69.0 [57.0-75.5]) had rheumatic disease. In these patients, univariate logistic regression analysis showed that sex, hypertension, family history of SAH, smoking history, World Federation of Neurosurgical Societies grade on admission, aneurysm size, multiple aneurysms, treatment, and symptomatic spasms were associated with SAH. Multivariable logistic regression analysis showed that characteristics independently associated with SAH in rheumatic disease were female sex (odds ratio [OR] 3.38; 95% confidence interval [CI] 1.81-6.93, P < 0.001), hypertension (OR 0.60; 95% CI 0.40-0.90, P = 0.012), family history of SAH (OR 0.18; 95% CI 0.01-0.80, P = 0.020), small ruptured aneurysms (OR 1.50; 95% CI 1.02-2.24, P = 0.048), and multiple aneurysms (OR 1.69; 95% CI 1.09-2.58, P = 0.021) in comparison with SAH without rheumatic disease. In conclusion, SAH in patients with rheumatic disease was characterized by small multiple aneurysms, regardless of the low incidence of hypertension and family history of SAH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10143-020-01435-8DOI Listing
November 2020

Life prognosis and renal relapse after induction therapy in Japanese patients with proliferative and pure membranous lupus nephritis.

Rheumatology (Oxford) 2020 Nov 7. Epub 2020 Nov 7.

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki.

Objective: We aimed to compare life prognosis and renal relapse after induction therapy in proliferative (PLN) and pure membranous LN (MLN).

Methods: We retrospectively analysed the cases of 140 of 172 patients with LN who underwent a renal biopsy at our hospital or community hospitals from 1993 to 2016. We determined the complete response (CR) rate at 12 months after the patients had started induction therapy, and we evaluated the predictive factors for CR, life prognosis and renal relapse in PLN and pure MLN. We defined PLN as International Society of Neurology and the Renal Pathology Society (ISN/RPS) Class III or IV and MLN as ISN/RPS Class V.

Results: The renal pathology of 99 (70.7%) patients was classified as PLN, and that of the other 41 (29.3%) patients as MLN. Fifty patients (50.5%) with PLN and 22 patients (53.7%) with MLN achieved a CR at 12 months. A multivariate analysis showed that a lower index of chronicity in PLN and a higher total haemolytic complement (CH50) level in MLN were predictive factors for achieving a CR at 12 months. A Kaplan-Meier analysis showed that the life prognosis (P = 0.93) and renal relapse (P = 0.52) were not significantly different between PLN and MLN.

Conclusions: The predictive factors for a CR at 12 months post-induction therapy were index of chronicity in PLN and CH50 level in MLN. There were no significant differences in life prognosis or renal relapse between PLN and MLN in the achievement of a CR at 12 months post-induction therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/rheumatology/keaa599DOI Listing
November 2020

Clinical significance of a positive Clostridioides difficile glutamate dehydrogenase test on the outcomes of hospitalized older patients.

Geriatr Gerontol Int 2020 Dec 24;20(12):1138-1144. Epub 2020 Oct 24.

Department of Respiratory Medicine, Nagasaki University Hospital, Nagasaki, Japan.

Aim: Clostridioides difficile infection worsens the outcome of older hospitalized patients; thus, its diagnosis is necessary for the nosocomial infection control. The standard diagnostic test's limited sensitivity for Clostridioides difficile infection, an enzyme immunoassay for Clostridioides difficile toxins, is of clinical concern. Glutamate dehydrogenase detection is usually tested combined with Clostridioides difficile toxins. However, the clinical significance of a positive glutamate dehydrogenase result is unclear. We evaluated the association between positive glutamate dehydrogenase results, in-hospital mortality and hospital stay length among older patients with suspected Clostridioides difficile infection.

Methods: In this retrospective cohort study, we examined the data of patients who received antibiotics (except for Clostridioides difficile infection treatment) after admission and tested for Clostridioides difficile infection using an enzyme immunoassay for Clostridioides difficile toxins and glutamate dehydrogenase in a secondary care hospital located in a rural region with high aging rate, between 2015 and 2018.

Results: In total, 188 patients were included (83.5% of them aged >75 years). Glutamate dehydrogenase positivity was independently associated with in-hospital mortality (adjusted odds ratio 2.19, 95% confidence interval 1.14-4.21) and hospital stay length (regression coefficient 16.0, 95% confidence interval 5.15-26.9). Clostridioides difficile toxin positivity was independently associated with hospital stay duration (regression coefficient 14.5, 95% confidence interval 0.04-29.1), unlike in-hospital mortality.

Conclusions: Glutamate dehydrogenase was closely related to in-hospital mortality and prolonged hospitalization compared with Clostridioides difficile toxin. Clinicians should not neglect glutamate dehydrogenase-positive patients, even when they are Clostridioides difficile toxin-negative, and consider them as having poor prognostic potential. Geriatr Gerontol Int 2020; 20: 1138-1144.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ggi.14054DOI Listing
December 2020

Corticosteroids are associated with reduced skeletal muscle function in interstitial lung disease patients with mild dyspnea.

Respir Med 2020 Nov - Dec;174:106184. Epub 2020 Oct 6.

Cardiorespiratory Division, Department of Rehabilitation Medicine, Nagasaki University Hospital, Nagasaki, Japan; Department of Cardiopulmonary Rehabilitation Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Interstitial lung diseases (ILDs) patients receiving steroid treatment tend to be immobilized by dyspnea and muscle weakness as the disease progresses. We therefore expected that steroid treatment for ILDs would have a greater effect on muscle function under severe dyspnea. To test this hypothesis, we evaluated whether the effect of corticosteroid treatment on peripheral muscle force and exercise capacity varied according to patients' dyspnea severity.

Methods: In this retrospective cross-sectional study of 87 ILD patients enrolled between 2008 and 2017, quadriceps force (QF), handgrip force (HF), and 6-min walk distance (6 MWD) were compared between a low (grades 0-2) and a high (grades 3-4) modified-Medical Research Council (mMRC) dyspnea scale score group.

Results: In patients with lower levels of dyspnea, corticosteroid treatments were associated with lower QF and HF (20.0 vs. 30.0 kgf, p = 0.01; 22.5 vs. 28.4 kgf, p = 0.03, respectively) values; however, no significant differences were observed between the corticosteroid and control subgroups in the high mMRC group (QF: 18.5 vs. 17.3 kgf, p = 0.64; HF: 21.0 vs. 17.1 kgf, p = 0.24, respectively). Analysis of covariance indicated that both corticosteroid treatment and mMRC dyspnea scale interacted with QF, HF, and 6 MWD. The effects of the corticosteroid treatment varied according to the level of dyspnea (interaction β = 7.52, p = 0.034; interaction β = 8.78, p = 0.048; interaction β = 131.08, p < 0.001).

Conclusions: Muscle weakness and exercise capacity in ILD patients in the low mMRC group were associated with corticosteroid treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.rmed.2020.106184DOI Listing
October 2020

Next-generation sequencing of the whole MEFV gene in Japanese patients with familial Mediterranean fever: a case-control association study.

Clin Exp Rheumatol 2020 Sep-Oct;38 Suppl 127(5):35-41. Epub 2020 Sep 23.

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Japan.

Objectives: We aimed to identify the whole nucleotide sequence of the Mediterranean fever (MEFV) gene in familial Mediterranean fever (FMF) and reveal novel single nucleotide variants (SNVs) associated with the susceptibility of FMF.

Methods: SeqCap capturing technique followed by Illumina next-generation sequencing have been used to assess two hundred SNVs in the whole region of MEFV in 266 Japanese patients with FMF and 288 ethnically matched controls. We performed an association analysis using these SNVs to identify genetic variants that predispose to FMF.

Results: We identified the two most significant SNVs [rs28940578; M694I in exon 10, odds ratio (OR) = 153, p=2.47×10-21 and rs3743930; E148Q in exon 2, OR = 1.65, p<0.0005]. Stratified analysis identified rs28940578 as a risk allele in typical FMF. Haplotype AG, defined by rs401298 and rs28940578, was the most significant and prevalent among patients with typical FMF compared with controls (22.4% vs. 0%, respectively; OR = 137, p=1.44×10-31). Haplotype GTC, defined by rs11466018, rs224231, and rs401877, was the most significant among patients with typical FMF without the rs28940578 mutation compared with controls (15.9% vs. 6%, respectively; OR = 12.4, p=0.004).

Conclusions: rs28940578 is associated with the highest risk in typical FMF cases. This is consistent with results from previous studies in Japan. We found a novel MEFV gene haplotype that confers susceptibility of FMF among typical FMF without the rs28940578 mutation. There were no relevant SNVs identified in MEFV among the atypical FMF group.
View Article and Find Full Text PDF

Download full-text PDF

Source
December 2020

Short-Physical Performance Battery (SPPB) score is associated with postoperative pulmonary complications in elderly patients undergoing lung resection surgery: A prospective multicenter cohort study.

Chron Respir Dis 2020 Jan-Dec;17:1479973120961846

Department of Rehabilitation Medicine, 88380Nagasaki University Hospital, Nagasaki, Japan.

Elderly patients awaiting lung resection surgery often have poor physical function, which puts them at a high risk of postoperative pulmonary complications. The aim of this study was to investigate the impact of preoperative physical performance on postoperative pulmonary complications in patients awaiting lung resection surgery. In this prospective multicenter cohort study, the characteristics of patients and postoperative pulmonary complications were compared between subjects with low (<10) and high (≥10) Short Physical Performance Battery (SPPB) scores. Postoperative pulmonary complications were defined as over grade II in Clavien-Dindo classification system. We estimated the effects of physical performance on postoperative pulmonary complications using multivariable hierarchical logistic regression. The postoperative pulmonary complications were compared between 331 patients in the high and 33 patients in the low SPPB group. Patients in the low SPPB score group had a significantly higher rate of postoperative pulmonary complications (p < 0.001). Low SPPB score was associated with a higher risk of postoperative pulmonary complications (odds ratio, 8.80; p < 0.001). The SPPB is a clinically useful evaluation tool to assess surgical patients' physical performance. The low physical performance indicated by the SPPB may be predictive of postoperative pulmonary complications after lung resection surgery. Clinical Trials. University hospital Medical Information Network Center (UMIN-CTR) UMIN000021875.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1479973120961846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545757PMC
September 2020

How to Safely Prevent Venous Thromboembolism in Severe Trauma Patients.

Int Heart J 2020 Sep 12;61(5):993-998. Epub 2020 Sep 12.

Acute and Critical Care Center, Nagasaki University Hospital.

Venous thromboembolism (VTE) is a life-threatening complication after trauma. Several studies have reported VTE prophylaxis using low-molecular-weight heparin; however, there is no consensus for prophylaxis after trauma. This study aimed to assess the efficacy and safety of our new anticoagulation therapy protocol using unfractionated heparin (UFH) plus intermittent pneumatic compression (IPC) to prevent post-traumatic VTE in high-risk trauma patients.This study enrolled 70 trauma patients who were admitted to the emergency medical center of Nagasaki University Hospital and had Risk Assessment Profile (RAP) scores ≥ 5. After stopping bleeding at the trauma site, all patients received intravenous UFH (10,000 U/day) plus IPC, which was continued for 14 days or until the patients could walk. On days 7 and 14, all patients underwent lower extremity sonography for deep-vein thrombosis screening. VTE incidences between patients with the above intervention and historical controls with IPC alone were compared.No significant differences in age, sex, and the RAP score were observed between the 105 controls and intervention patients. VTE occurrence was fewer in patients with the intervention (14.3%) than in the controls (28.6%; P = 0.029). No hemorrhagic complications occurred after UFH administration. Multivariable logistic analysis revealed a significant association between the intervention and low incidence of VTE (odds ratio: 0.390; 95% confidence interval: 0.163-0.913; P = 0.030).Routine UFH administration with IPC may prevent post-traumatic VTE without adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1536/ihj.20-153DOI Listing
September 2020

Switching from originator infliximab to biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving clinical remission (the IFX-SIRIUS study I): Study protocol for an interventional, multicenter, open-label, single-arm and noninferiority clinical trial with clinical, ultrasound, and biomarker assessments.

Medicine (Baltimore) 2020 Jul;99(30):e21151

Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences.

Background: The introduction of biological disease-modifying anti-rheumatic drugs (bDMARDs) into clinical practice has dramatically improve the clinical outcomes of individuals with rheumatoid arthritis (RA). However, bDMARDs are associated with high costs, which has resulted in restricted treatment access and a burden on medical insurance finances. Although biosimilars offer cost-saving, their effectiveness and safety must be established in Post-Marketing Surveillance (PMS). Infliximab (IFX), a chimeric monoclonal antibody to TNF-alpha, is the first bDMARD; its biosimilar, CT-P13, is the first biosimilar DMARD approved for RA treatment in Japan. We will evaluate whether switching from originator IFX to CT-P13 is not inferior for maintaining non-clinical relapse to continued treatment with originator IFX in RA patients achieving clinical remission.

Methods/design: This study is an interventional, multicenter, open-label, single-arm against historical control and noninferiority clinical trial with a 24-week follow-up. Eighty RA patients who are treated by originator IFX for ≥24 weeks and are achieving clinical remission will be included. Patients will be switched to CT-P13 with the unchanged dosing regimen. We will evaluate disease activity by measuring clinical disease activity indices and by using musculoskeletal ultrasound (MSUS). The primary endpoint is the ratio of patients who experience a nonclinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of many biomarkers such as cytokines and chemokines.

Discussion: The study results are expected to show the noninferiority of switching to CT-P13 over the continuation of originator IFX. The strength of this study is its prospective evaluation of therapeutic efficacy using not only clinical disease activity indices but also MSUS to accurately and objectively evaluate disease activity at the joint level among patients drawn from multiple centers with a standardized evaluation by MSUS. We will explore whether parameters at baseline can predict a nonclinical relapse after switching from originator IFX to CT-P13 by integrating multilateral assessments, i.e., clinical disease activity indices, MSUS findings, and serum biomarkers.

Trial Registration: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on October 11, 2019 as jRCTs071190030.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000021151DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387067PMC
July 2020

Discontinuation of biosimilar infliximab in Japanese patients with rheumatoid arthritis achieving sustained clinical remission or low disease activity during the IFX-SIRIUS STUDY I (the IFX-SIRIUS STUDY II): Study protocol for an interventional, multicenter, open-label, single-arm clinical trial with clinical, ultrasound and biomarker assessments.

Medicine (Baltimore) 2020 Aug;99(32):e21480

Departments of Immunology and Rheumatology.

Background: The introduction of biological disease-modifying anti-rheumatic drugs into clinical practice has dramatically improved the clinical outcomes of individuals with rheumatoid arthritis (RA). We are conducting the IFX-SIRIUS STUDY I that evaluates whether switching from originator infliximab (IFX) to its biosimilar, CT-P13, is not inferior in maintaining nonclinical relapse to continue treatment with originator IFX in patients with RA achieving clinical remission. It is the next great issue whether disease activity can be maintained in good condition after discontinuation of CT-P13 because no evidence is available regarding the clinical value of discontinuing biosimilars in patients with RA. Thus, we will evaluate whether a condition without clinical relapse will be maintained after discontinuation of CT-P13 in patients with RA, achieving clinical remission or low disease activity during the IFX-SIRIUS STUDY I.

Methods/design: This study is an interventional, multicenter, open-label, single-arm clinical trial with a 48-week follow-up. Patients with RA who are treated with CT-P13 and sustained nonclinical relapse during the IFX-SIRIUS STUDY I will be included. Patients will discontinue CT-P13 after the study period of the IFX-SIRIUS STUDY I. We will evaluate disease activity by clinical disease activity indices and musculoskeletal ultrasound (MSUS). The primary endpoint is the proportion of patients who do not have clinical relapse during the study period. Important secondary endpoints are the changes from the baseline of the MSUS scores. We will also comprehensively analyze the serum levels of multiple biomarkers, such as cytokines and chemokines. In addition, if a clinical relapse occurs in patients after the discontinuation of CT-P13, we will evaluate the effectiveness and safety of restarting CT-P13.

Discussion: The study results are expected to show the clinical benefit of the discontinuation of CT-P13 and effectiveness and safety of restarting CT-P13 after clinical relapse. The strength of this study is to prospectively evaluate the therapeutic effectiveness by not only clinical disease activity indices but also standardized MSUS findings in multiple centers. We will explore whether parameters at baseline can predict a nonclinical relapse after the discontinuation of CT-P13 by integrating multilateral assessments, that is, patient's characteristics, clinical disease activity indices, MSUS findings, and serum biomarkers.

Trial Registration: This study was registered in the Japan Registry of Clinical Trials (https://jrct.niph.go.jp) on April 20, 2020 as jRCTs071200007.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000021480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7593062PMC
August 2020

A study on respiratory management in acute postoperative period by nasal high flow for patients undergoing surgery under general anesthesia.

Medicine (Baltimore) 2020 Jul;99(31):e21537

Department of Dental Anesthesiology.

In head and neck surgery where the oropharyngeal area is the operative field, postoperative respiratory depression and upper airway obstruction are common. Therefore, supplemental oxygen is administered to prevent severe postoperative early hypoxemia. However, a high concentration of oxygen increases the likelihood of secondary complications, such as carbon dioxide (CO2) narcosis. Nasal high-flow (NHF) therapy generates high flows (≤60 L/min) of heated and humidified gas delivered via nasal cannula and provides respiratory support by generating positive airway pressure, clearance of dead space and reduction of work of breathing. This study aims to determine whether the postoperative hypoxemia and hypercapnia can be prevented by NHF without the requirement of supplemental oxygen. The study will recruit adult patients undergoing planned oral surgery under general anesthesia at Nagasaki University Hospital. It is a randomized parallel group comparative study with 3 groups: NHF with room air only and no supplemental oxygen, no respiratory support, and face mask oxygen administration. The study protocol will begin at the time that the patient is returned to the general ward and will finish 3 hours later. The primary endpoint is the time-weighted average of transcutaneous O2 over the 180 minutes and secondary endpoints are the time-weighted average of transcutaneous CO2 (tcpCO2), SpO2, and respiratory rate, incidence rate of marked hypercapnia (tcpCO2 ≥60 mm Hg for 5 minutes or longer), incidence rate of moderate hypercapnia (tcpCO2 ≥50 mm Hg for 5 minutes or longer) and the percentage of time that SpO2 is <90%. Included also is a group in which the postoperative management is performed only by spontaneous breathing without performing respiratory support such as oxygen administration, to investigate the efficacy and necessity of conventional oxygen administration. This exploratory study will investigate the use of NHF without supplemental oxygen as an effective respiratory support during the acute postoperative period. TRIAL REGISTRATION:: The study was registered the jRCTs072200018. URL https://jrct.niph.go.jp/latest-detail/jRCTs072200018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000021537DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402890PMC
July 2020

Comparison of complete renal response and mortality in early- and late-onset lupus nephritis: a multicenter retrospective study of a Japanese cohort.

Arthritis Res Ther 2020 07 22;22(1):175. Epub 2020 Jul 22.

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Most patients with systemic lupus erythematosus (SLE) progress to lupus nephritis (LN) within 5 years of their SLE diagnosis, although it is not uncommon for LN to develop at later time points. Here we evaluated the clinical features of early- and late-onset LN.

Patients And Methods: We retrospectively analyzed the cases of 184 of the 201 patients who underwent a renal biopsy at Nagasaki University Hospital and associated community hospitals between 1990 and 2016 and were diagnosed as having LN. Early onset was defined as the development of LN within the first 5 years after the patient's SLE diagnosis, and late onset was defined as LN development > 5 years post-diagnosis. We analyzed the complete renal response (CR) at 6 and 12 months after induction therapy, the classification of renal pathology, and the mortality of the early- and late-onset LN groups.

Results: The mean follow-up duration after the renal biopsy was 123 ± 85 months. There were 113 (61.4%) early-onset patients and 71 (38.6%) late-onset patients. A multivariate analysis revealed that the following factors were predictive of CR: at 6 months: female sex (odds ratio [OR] 3.93, 95% confidence interval [CI] 1.31-11.77, p = 0.010), proteinuria (OR 0.83, 95% CI 0.71-0.97, p = 0.009), index of activity (0-24) (OR 0.83, 95% CI 0.70-0.99, p = 0.030), and early-onset LN (OR 2.39, 95% CI 1.15-4.98, p = 0.018); at 12 months: female sex (OR 3.60, 95% CI 1.32-9.83, p = 0.013), mixed LN (OR 0.18, 95% CI 0.04-0.80, p = 0.024), index of activity (0-24) (OR 0.80, 95% CI 0.68-0.94, p = 0.007), and early-onset LN (OR 2.10, 95% CI 1.05-4.23, p = 0.035). In a Cox proportional hazards and Fine-Gray regression model, the early-onset LN group had a significantly better mortality rate than the late-onset LN group (p = 0.038 and p = 0.043, respectively).

Conclusions: In our cohort, early-onset LN was a better predictor of CR at 6 and 12 months than late-onset LN. Our results suggest that early-onset LN patients had lower mortality than late-onset LN patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02271-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7374914PMC
July 2020

Association between Enterocyte Injury and Mortality in Patients on Hemodialysis Who Underwent Cardiac Surgery: An Exploratory Study.

J Surg Res 2020 11 30;255:420-427. Epub 2020 Jun 30.

Department of Anesthesiology and Intensive Care Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Intestinal ischemia and enterocyte injury are significant causes of death after cardiac surgery. Hemodialysis is a well-known risk factor for intestinal ischemia. However, the relationship between enterocyte injury and mortality is unclear. This exploratory study assessed the association between intestinal fatty acid-binding protein (I-FABP), a specific marker of enterocyte injury, at intensive care unit (ICU) admission and in-hospital mortality in patients on hemodialysis who underwent cardiac surgery with cardiopulmonary bypass.

Materials And Methods: Forty-seven consecutive patients on long-term hemodialysis who underwent elective cardiac surgery (median age, 70 y; men, 27 [57%]) were prospectively enrolled. The association between serum I-FABP levels at ICU admission and in-hospital mortality was compared with the associations between serum I-FABP levels and prognostic severity scores, vasoactive-inotropic scores, and lactate levels.

Results: Only I-FABP levels at ICU admission were significantly related to in-hospital mortality (odds ratio, 5.54; 95% confidence interval [CI], 1.08-28.43) in the simple logistic regression analysis. Univariate and multiple linear regression analyses indicated prolonged cardiopulmonary bypass (ρ, 0.49; 95% CI, 0.15-0.83), higher mean norepinephrine dose (ρ, 0.07; 95% CI, 0.02-0.12), lower mean dopamine dose (ρ, -0.51; 95% CI, -0.94 to -0.08), and intra-aortic balloon pump use (ρ, 3.63; 95% CI, 1.68-5.59) were significant risk factors for high I-FABP levels.

Conclusions: Enterocyte injury at ICU admission was associated with in-hospital mortality after cardiac surgery for patients on hemodialysis. Intraoperative hidden hypoperfusion of the intestine may impact prognoses. Enterocyte injury prevention, early diagnosis, and intervention for intestinal ischemia might be required to improve outcomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jss.2020.05.091DOI Listing
November 2020

Left upper lobectomy is a risk factor for cerebral infarction after pulmonary resection: a multicentre, retrospective, case-control study in Japan.

Surg Today 2020 Nov 17;50(11):1383-1392. Epub 2020 Jun 17.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Purpose: The anatomical site of resected lobes may influence postoperative cerebral infarction. The objective of the current study was to determine if left upper pulmonary lobectomy is a risk factor for postoperative cerebral infarction.

Methods: This was a retrospective case-control study in patients undergoing pulmonary lobectomy from 2004 to 2013 in Japan. We retrospectively identified 610 patients from 153 institutions who had developed postoperative cerebral infarction following pulmonary lobectomy. The control group consisted of 773 patients who underwent lobectomy without cerebral infarction during a randomly selected single month in 2009 at the same institutions.

Results: Factors associated with cerebral infarction were age [10-year intervals, odds ratio (OR): 1.46; 95% confidence interval (CI): 1.23-1.73; p < 0.001], male sex (OR 1.92; 95% CI 1.29-2.86; p = 0.001), presence of comorbidities (OR 1.82; 95% CI 1.35-2.44; p < 0.001), perioperative anti-platelet or anti-coagulant drug use (OR 1.71; 95% CI 1.20-2.45; p = 0.003), and lobectomy. Subgroup analyses revealed that cerebral infarction was strongly associated with left upper lobectomy.

Conclusions: Our findings suggest that left upper lobectomy is associated with a higher risk of cerebral infarction than other types of lobectomy, particularly in the early postoperative period.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00595-020-02032-4DOI Listing
November 2020

Surgery or stereotactic body radiotherapy for metachronous primary lung cancer? A propensity score matching analysis.

Gen Thorac Cardiovasc Surg 2020 Nov 23;68(11):1305-1311. Epub 2020 May 23.

Department of Surgical Oncology, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Objective: We compared outcomes after surgery or stereotactic body radiotherapy (SBRT) among patients with metachronous primary lung cancer (MPLC).

Methods: Patients with MPLC were treated with either surgery (2008-2018) or SBRT (2010-2018). We used propensity score matching (PSM) to reduce bias from various clinicopathological factors. MPLC was defined by the Martini and Melamed criteria.

Results: Of 77 patients, 51 underwent surgery and 26 received SBRT. Most median clinicopathological characteristics did not significantly differ between the surgery and SBRT groups (male sex: 67% vs 65%; age: 73 vs 77 years; time after first surgery: 6.2 vs 4.7 years; lobectomy as first procedure: 82% vs 85%; second tumor size: 11 vs 12 mm; clinical stage I: 96% vs 100%; CEA: 2.9 vs 3.0 ng/ml). However, the surgery group had significantly more ipsilateral second tumors (n = 71, 58%, P = 0.003), better performance status (P = 0.03), and preserved lung function (P = 0.02). Surgery, thus, tended to be selected for patients with good physical function and for the MPLC in the contralateral side. Five-year overall survival did not significantly differ between the surgery and SBRT groups, either before PSM (86.5% vs 65.8%, P = 0.24, log-rank) or after PSM (100% vs 84.4%, P = 0.73).

Conclusions: Surgery and SBRT for MPLC patients are safe and feasible treatments with similar outcomes. However, this finding should be verified by a random controlled trial with a larger study cohort.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11748-020-01394-3DOI Listing
November 2020

Upper-airway collapsibility and compensatory responses under moderate sedation with ketamine, dexmedetomidine, and propofol in healthy volunteers.

Physiol Rep 2020 05;8(10):e14439

Division of Clinical Physiology, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Background: Ketamine is a potent sedative drug that helps to maintain upper-airway patency, due to its higher upper-airway dilator muscular activity and higher level of duty cycle, as seen in rats. However, no clinical trials have tested passive upper-airway collapsibility and changes in the inspiratory duty cycle against partial upper-airway obstruction in humans. The present study evaluated both the passive mechanical upper-airway collapsibility and compensatory response against acute partial upper-airway obstruction using three different sedative drugs in a crossover trial.

Methods: Eight male volunteers entered this nonblinded, randomized crossover study. Upper-airway collapsibility (passive critical closing pressure) and inspiratory duty cycle were measured under moderate sedation with ketamine, propofol, and dexmedetomidine. Propofol, dexmedetomidine, and ketamine anesthesia were induced to obtain adequate, same-level sedation, with a BIS value of 50-70 and the OAA/S score of 2-3 and RASS score of -3.

Results: The median passive critical closing pressure of 0.08 [-5.51 to 1.20] cm H O was not significantly different compared to that of propofol sedation (-0.32 [-1.41 to -0.19] cm H O) and of dexmedetomidine sedation (-0.28 [-0.95 to -0.03] cm H O) (p = .045). The median passive R for ketamine 54.35 [32.00 to 117.50] cm H O/L/s was significantly higher than that for propofol 5.50 [2.475 to 19.60] cm H O/L/s; (mean difference, 27.50; 95% CI 9.17 to 45.83) (p = .009) and for dexmedetomidine 19.25 [4.125 to 22.05] cm H O/L/s; (mean difference, 22.88; 95% CI 4.67 to 41.09) (p = .021). The inspiratory duty cycle increased significantly as the inspiratory airflow decreased in passive conditions for each sedative drug, but behavior differed among the three sedative drugs.

Conclusion: Our findings demonstrate that ketamine sedation may have an advantage of both maintained passive upper-airway collapsibility and a compensatory respiratory response, due to both increase in neuromuscular activity and the increased duty cycle, to acute partial upper-airway obstruction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.14814/phy2.14439DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243198PMC
May 2020

Interleukin-18 and fibroblast growth factor 2 in combination is a useful diagnostic biomarker to distinguish adult-onset Still's disease from sepsis.

Arthritis Res Ther 2020 05 7;22(1):108. Epub 2020 May 7.

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.

Objective: To identify potential biomarkers to distinguish adult-onset Still's disease (AOSD) from sepsis.

Method: We recruited 70 patients diagnosed with AOSD according to the Yamaguchi criteria, 22 patients with sepsis, and 118 age-matched controls. Serum levels of 40 cytokines were analyzed using multi-suspension cytokine array. We performed a cluster analysis of each cytokine in the AOSD and sepsis groups in order to identify specific molecular networks. Further, multivariate classification (random forest analysis) and logistic regression analysis were used to rank the cytokines by their importance and determine specific biomarkers for distinguishing AOSD from sepsis.

Results: Seventeen of the 40 cytokines were found to be suitable for further analyses. The serum levels of eleven were significantly higher in patients with AOSD than healthy controls. Levels of serum fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor (VEGF), granulocyte colony-stimulating factor (G-CSF), and interleukin (IL)-18 were significantly elevated in patients with AOSD compared with those with sepsis, and cytokine clustering patterns differed between these two groups. Multivariate classification followed by logistic regression analysis revealed that measurement of both FGF-2 and IL-18 could distinguish AOSD from sepsis with high accuracy (cutoff value for FGF-2 = 36 pg/mL; IL-18 = 543 pg/mL, sensitivity 100%, specificity 72.2%, accuracy 93.8%).

Conclusion: Determination of FGF-2 and IL-18 levels in combination may represent a biomarker for the differential diagnosis of AOSD from sepsis, based on the measurement of multiple cytokines.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13075-020-02200-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7206754PMC
May 2020

The effect of luseogliflozin on bone microarchitecture in older patients with type 2 diabetes: study protocol for a randomized controlled pilot trial using second-generation, high-resolution, peripheral quantitative computed tomography (HR-pQCT).

Trials 2020 May 5;21(1):379. Epub 2020 May 5.

Department of Endocrinology and Metabolism, Division of Advanced Preventive Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Older patients with type 2 diabetes mellitus (T2DM) have an increased risk of bone fracture independent of their bone mineral density (BMD), which is explained mainly by the deteriorated bone quality in T2DM compared to that in non-diabetic adults. Sodium-glucose co-transporter (SGLT) 2 inhibitors have been studied in several trials in T2DM, and the Canagliflozin Cardiovascular Assessment Study showed an increased fracture risk related to treatment with the SGLT2 inhibitor canagliflozin, although no evidence of increased fracture risk with treatment with other SGLT2 inhibitors has been reported. The mechanism of the difference in the fracture risk between the SGLT2 inhibitors is unknown, but the differences among the SGLT2 inhibitors in the selectivity of SGLT2 against SGLT1 may affect bone metabolism, since among the SGLT2 inhibitors the selectivity of canagliflozin is lowest. We will investigate whether the SGLT2 inhibitor luseogliflozin, which has the higher SGLT2 selectivity, affects bone metabolism by using high-resolution, peripheral quantitative computed tomography (HR-pQCT) which provides direct in vivo morphometric information about the bone microarchitecture.

Methods/design: This is a single-center, randomized, open-label, active-controlled, parallel pilot trial. Eligible participants are older (age ≥ 60 years) individuals with T2DM with HbA1c levels at 7.0-8.9%. A total of 24 participants will be allocated to either the luseogliflozin group (taking luseogliflozin) or the control group (taking metformin) in a 1:1 ratio to compare the groups' changes in bone microarchitecture of the radius and tibia which are analyzed by HR-pQCT before and at 48 weeks after the administration of each medication. The laboratory data associated with glycemic control and bone metabolism will be collected every 12 weeks during the study. Recruitment began in June 2019.

Discussion: The reason that we use metformin as an active control is to avoid yielding differences in glycemic control between the luseogliflozin and control groups. Besides, metformin is considered to have a neutral effect on bone. This trial should reveal the effect of luseogliflozin on bone metabolism in older patients with T2DM.

Trial Registration: The study was registered with the University Hospital Medical Information Network (UMIN000036202) on 1 April 2019 and with the Japan Registry of Clinicla Trials (jRCTs071180061) on 14 March 2019.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13063-020-04276-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201752PMC
May 2020

The Efficacy of Software to Help Patients Understand Drug for Adjuvant Treatment for Breast Cancer: A Pilot Randomized Controlled Trial.

Acta Med Okayama 2020 Apr;74(2):95-101

Department of Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki 852-8501, Japan.

We assessed the usefulness of ChemoCalc, a software package for calculating drug costs, in helping patients understand these costs. We randomly assigned, in a 1 : 1 ratio, 20 women who had undergone surgery for early breast cancer to a group that discussed adjuvant treatment with their physicians using the ChemoCalc software (ChemoCalc group) or a group that discussed adjuvant treatment without ChemoCalc (Usual Explanation group). The participants completed a five-grade evaluation questionnaire after these discussions. The primary endpoint was the intergroup comparison of the questionnaire scores regarding participants' understanding of their treatment-associated drug costs. Median age was not significantly different between the ChemoCalc group and Usual Explanation group (57 vs. 50, respectively; p=0.27). Patients in the ChemoCalc group had a significantly higher perceived level of understanding of the drug cost than those in the Usual Explanation group (5 [4-5] vs. 2.5 [1-5], respectively; p=0.002). Scores related to the patients' perception that understanding drug costs is an important part of breast cancer treatment were also higher in the ChemoCalc group than the Usual Explanation group (5 [2-5] vs. 3 [1-5], respectively; p=0.049). ChemoCalc was found to be useful for understanding drug costs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.18926/AMO/58266DOI Listing
April 2020

Prediction of Anti-Cancer Drug-Induced Pneumonia in Lung Cancer Patients: Novel High-Resolution Computed Tomography Fibrosis Scoring.

J Clin Med 2020 Apr 7;9(4). Epub 2020 Apr 7.

Department of Respiratory Medicine, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8523, Japan.

Background And Objective: Pre-existing interstitial lung disease (ILD) in lung cancer patients is considered a risk factor for anti-cancer drug-induced pneumonia; however, a method for evaluating ILD, including mild cases, has not yet been established. We aimed to elucidate whether the quantitative high-resolution computed tomography fibrosis score (HFS) is correlated with the risk of anti-cancer drug-induced pneumonia in lung cancer patients, even in those with mild pre-existing ILD.

Methods: The retrospective single-institute study cohort comprised 214 lung cancer patients who underwent chemotherapy between April 2013 and March 2016. The HFS quantitatively evaluated the grade of pre-existing ILD. We extracted data regarding age, sex, smoking history, and coexisting factors that could affect the incidence of anti-cancer drug-induced pneumonia. Cox proportional hazard models were used to analyze the effects of the HFS and other factors on the risk of anti-cancer drug-induced pneumonia.

Results: Pre-existing ILD was detected in 61 (29%) of 214 patients, while honeycombing and traction bronchiectasis were observed in only 15 (7.0%) and 10 (4.7%) patients, respectively. Anti-cancer drug-induced pneumonia developed in 19 (8.9%) patients. The risk of anti-cancer drug-induced pneumonia increased in proportion to the HFS (hazard ratio, 1.16 per point; 95% confidence interval, 1.09-1.22; < 0.0001).

Conclusions: The quantitative HFS was correlated with the risk of developing anti-cancer drug-induced pneumonia in lung cancer patients, even in the absence of honeycombing or traction bronchiectasis. The quantitative HFS may lead to better management of lung cancer patients with pre-existing ILD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9041045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230276PMC
April 2020

Influence of Interferon-free Direct-acting Antiviral Therapy on Primary Hepatocellular Carcinoma Recurrence: A Landmark Time Analysis and Time-dependent Extended Cox Proportional Hazards Model Analysis.

Intern Med 2020 1;59(7):901-907. Epub 2020 Apr 1.

Department of Gastroenterology and Hepatology, Nagasaki University of Graduate School of Biomedical Sciences, Japan.

Objective The influence of interferon (IFN)-free direct-acting antiviral (DAA) on hepatocellular carcinoma (HCC) recurrence remains unclear. Previous retrospective analyses revealed that the time interval between HCC curative treatment and IFN-free DAA induction is the critical factor affecting HCC recurrence. Thus, this study aimed to examine the influence of DAA therapy on HCC recurrence considering this interval. Methods Factors contributing to HCC recurrence were retrospectively analyzed using a landmark time analysis and time-dependent extended Cox proportional hazards model. Patients After screening 620 patients who were diagnosed with primary HCC from January 2001 to December 2016, 76 patients with early-stage (primary and solitary) disease who received curative treatment and were positive for serum hepatitis C virus RNA were included. Results HCC recurrence was observed in 8 of 17 (47.1%) patients who had received IFN-free DAA therapy and 45 of 59 (76.3%) who had not. No significant difference was seen between the IFN-free DAA (-) and IFN-free DAA (+) groups in the landmark time and time-dependent Cox proportional hazards model analyses. However, IFN-free DAA therapy tended to decrease the HCC recurrence rate after curative treatment for primary HCC in patients with chronic hepatitis. In addition, IFN-free DAA therapy tended to decrease the second HCC recurrence rate after treatment for the first HCC recurrence. Conclusion Our results, with a consideration of the time interval between HCC curative treatment and IFN-free DAA induction, showed that IFN-free DAA therapy was not associated with early-stage HCC recurrence after curative treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.2169/internalmedicine.3382-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7184089PMC
June 2020

Optimal Tumor Reduction Rate and Modalities for Predicting pCR in Women With Breast Cancer.

Anticancer Res 2020 Apr;40(4):2303-2309

Department of Surgery, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan.

Background/aim: To predict pCR during neoadjuvant chemotherapy is still difficult. The aim of this study was to evaluate the optimal tumor reduction rate and modalities for predicting pCR after two cycles of docetaxel.

Patients And Methods: We analyzed 52 patients with HER2-positive or triple-negative breast cancer. The tumor reduction rate was evaluated after two 3-week cycles of docetaxel (plus trastuzumab for HER2-positive cancer patients). Patients without progression completed two additional cycles of docetaxel and four cycles of an anthracycline-containing regimen.

Results: Twenty-eight patients achieved pCR. The optimal tumor reduction rates for predicting pCR were 23, 39, 32, and 40% for US, caliper, MMG, and MRI measurements, respectively. The AUC was highest for caliper measurements. The optimal modality for predicting pCR differed among subtypes.

Conclusion: Although tumor reduction rate after two cycles of chemotherapy is highly predictive of pCR, the optimal cutoff value differed among the modalities and breast cancer subtype.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.21873/anticanres.14196DOI Listing
April 2020

Study protocol for efficacy and safety of steroid-containing mouthwash to prevent chemotherapy-induced stomatitis in women with breast cancer: a multicentre, open-label, randomised phase 2 study.

BMJ Open 2020 02 13;10(2):e033446. Epub 2020 Feb 13.

Surgery, Nagasaki University School of Medicine Graduate School of Biomedical Sciences, Nagasaki, Japan.

Introduction: Stomatitis is a frequent adverse event in patients undergoing chemotherapy for breast cancer. Stomatitis can hamper oral nutrition resulting in malnutrition, reduce quality of life and introduce the need for dose reductions and interruption of chemotherapy; however, there is currently no standard approach for preventing chemotherapy-induced stomatitis. We aimed to assess the safety and efficacy of a dexamethasone-based elixir mouthwash for preventing chemotherapy-induced stomatitis in patients with early breast cancer.

Methods And Analysis: In this multicenter, randomised, controlled phase 2 trial, we will randomly assign 120 women with early breast cancer undergoing chemotherapy to use of a dexamethasone-based elixir or standard oral care, to compare their preventive effects on chemotherapy-induced stomatitis. Patients will be assigned in a 1:1 ratio. Patients in the intervention group will receive chemotherapy, oral care and a dexamethasone-based elixir (10 mL 0.1 mg/mL; swish for 2 min and spit, four times daily for 9 weeks), and patients in the control group will receive chemotherapy and oral care. The primary endpoint is the difference in incidence of stomatitis between the two groups. The sample size allows for the detection of a minimum difference of 20% in the incidence of stomatitis between the two groups. Secondary endpoints are severity of stomatitis, duration of stomatitis, completion rate of chemotherapy and adverse events.

Ethics And Dissemination: All participants signed a written consent form, and the study protocol has been reviewed and approved by the Clinical Research Review Board of Nagasaki University (CRB7180001).

Trial Registration Number: UMIN Clinical Trials Registry (UMIN000030489).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-033446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7045258PMC
February 2020

S-1 plus cisplatin with concurrent radiotherapy for locally advanced thymic carcinoma: Study protocol of LOGIK1605/JART-1501.

Thorac Cancer 2020 03 5;11(3):693-696. Epub 2020 Feb 5.

Department of Thoracic and Breast Surgery, Oita University Faculty of Medicine, Oita, Japan.

Thymic carcinoma is a rare epithelial tumor of the thymus with a poor prognosis, and multimodal approaches are important for its treatment. Recently, a number of studies have indicated that S-1 treatment is effective against thymic carcinoma. S-1 plus cisplatin with concurrent radiotherapy is a commonly used treatment for other malignancies, including non-small cell lung cancer (NSCLC). In addition, its safety has been confirmed, and it has been reported to have a marked effect against thymic carcinoma. Therefore, we conducted a phase II study of S-1 plus cisplatin with concurrent thoracic radiotherapy for locally advanced thymic carcinoma, in which the overall response rate was employed as the primary endpoint. The secondary endpoints were overall survival, progression-free survival, and safety.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049479PMC
March 2020

Synthesis of Strophasterols C, E, and F.

Org Lett 2020 02 29;22(4):1311-1315. Epub 2020 Jan 29.

Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science , Tohoku University , 468-1 Aramaki Aza-Aoba , Aoba-ku, Sendai 980-8572 , Japan.

The synthesis of strophasterols C, E, and F has been accomplished from a 14,15-secoergostane derivative via a 1,3-dipolar cycloaddition of a nitrile oxide intermediate to simultaneously install an isolated cyclopentane ring and a C23 oxygen functionality in a diastereoselective manner and a regio- and diastereoselective selenohydroxylation of an olefinic intermediate under thermodynamic conditions. This synthesis also enabled the stereochemical confirmation of strophasterol C.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acs.orglett.9b04628DOI Listing
February 2020

Lower serum calcium and pre-onset blood pressure elevation in cerebral hemorrhage patients undergoing hemodialysis.

Clin Exp Nephrol 2020 May 14;24(5):465-473. Epub 2020 Jan 14.

Department of Nephrology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan.

Background: Asymptomatic blood pressure (BP) elevation may be associated with cerebral hemorrhage (CH); however, few studies have investigated this association. We aimed to evaluate BP elevation before CH in hemodialysis (HD) patients and elucidate its associated factors.

Methods: We reviewed HD patients treated for CH at our hospital between 2008 and 2019 (CH group). The control group comprised HD patients treated at Nagasaki Renal Center between 2011 and 2012. Data were obtained from medical records and three consecutive HD charts, made immediately before CH. HD1 was the session closest to onset, followed by HD2 and HD3. Systolic and mean BP were evaluated at the beginning of HD, and factors associated with BP elevation were investigated.

Results: The CH and control groups included 105 and 339 patients, respectively. Systolic and mean BP at HD1 were significantly higher than those at baseline (HD2 + HD3) in the CH group by 5 and 3 mmHg, respectively (P < 0.001). Multiple linear regression analysis showed that lower calcium levels were significantly associated with BP elevation in the CH group (P < 0.05). The CH group was sub-divided by June 2013; the latter group had lower calcium levels (9.2 mg/dL) and a marked systolic BP difference from baseline (+ 10 mmHg) compared with the former (9.5 mg/dL and - 4 mmHg).

Conclusion: Asymptomatic BP elevation was observed in HD patients before CH; this elevation was associated with lower serum calcium levels and observed more frequently in the recent era. The precise mechanism underlying this effect remains unknown.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10157-020-01846-3DOI Listing
May 2020

An open-label continuation trial of tocilizumab for familial Mediterranean fever with colchicine ineffective or intolerance: Study protocol for investigator-initiated, multicenter, open-label trial.

Medicine (Baltimore) 2020 Jan;99(1):e18328

Department of Immunology and Rheumatology, Division of Advanced Preventive Medical Sciences.

Background: Colchicine is the first-line treatment for familial Mediterranean fever (FMF), but secondary amyloidosis resulting from persistent inflammation is a concern in patients with colchicine-resistant or colchicine-intolerant FMF. Although tocilizumab (TCZ), which is a recombinant, humanized, anti-human interleukin 6 receptor monoclonal antibody, has been reported to prevent FMF attacks, the long-term safety and efficacy of TCZ on individuals with colchicine-resistant or colchicine-intolerant FMF have not been evaluated.

Methods/design: In this investigator-initiated, multicenter, open-label trial, the long-term safety of TCZ will be evaluated in patients participating in a placebo-controlled, randomized, double-blind, parallel-group trial on colchicine-resistant or colchicine-intolerant FMF. The study will be conducted in 9 centers in Japan. After the evaluation and examination for 24 weeks in the preceding study, this trial will be started promptly. The trial will be completed by the time the drug is approved for FMF treatment in Japan. The primary endpoint is the incidence of adverse events, and the secondary endpoints include the number of FMF attacks, number of occurrences of accompanying symptoms during attacks, serum C-reactive protein and amyloid A levels, general evaluation by a physician (100 mm visual analog scale [VAS]), general evaluation by a patient (100 mm VAS), and body temperature.

Discussion: The study is expected to obtain evidence regarding the long-term safety of TCZ as a potential new therapeutic agent for patients with colchicine-resistant or colchicine-intolerant FMF.

Trial Registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000037116) as UMIN000032557 on May 30 2018.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000018328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6946311PMC
January 2020