Publications by authors named "Takashi Nakayama"

248 Publications

Efficacy and safety of onabotulinumtoxinA in patients with overactive bladder: subgroup analyses by sex and by serum prostate-specific antigen levels in men from a randomized controlled trial.

Int Urol Nephrol 2021 Jul 22. Epub 2021 Jul 22.

Specialty Medical and Development, GlaxoSmithKline, Tokyo, Japan.

Purpose: We aimed to assess onabotulinumtoxinA treatment outcomes by sex in patients with overactive bladder (OAB) and then explore the impact of serum prostate-specific antigen (PSA) levels in men.

Methods: Patients inadequately managed with OAB medications were randomized to receive single-dose onabotulinumtoxinA (100 U) or placebo intravesical injection in a phase III trial in Japan. We performed subgroup analyses by sex and post-hoc subgroup analyses using male PSA categories.

Results: In women (n = 186), onabotulinumtoxinA demonstrated statistically significant and clinically relevant improvements in all urinary symptoms at Week 12. In men with lower PSA (< 1.5 ng/mL, n = 40), onabotulinumtoxinA also showed numerically greater reductions in urinary symptom frequency than placebo; the between-group differences (onabotulinumtoxinA minus placebo) in change from baseline in the average daily number at Week 12 for urinary incontinence (UI), urgency UI, micturition, urgency, and nocturia were - 1.43, - 1.79, - 2.81, - 2.45, and - 0.32 episodes, respectively. In men with higher PSA (≥ 1.5 ng/mL, n = 22), onabotulinumtoxinA did not reduce urinary symptom frequency. Some patients treated with onabotulinumtoxinA showed elevated post-void residual urine volume at Week 2 (≥ 200 mL): 4 of 91 women, none of the men with lower PSA and 3 of 11 men with higher PSA.

Conclusions: OnabotulinumtoxinA was efficacious and well tolerated in women and in men with lower PSA levels. Given our post-hoc subgroup analyses which suggested that onabotulinumtoxinA treatment is a good treatment option for OAB males with lower PSA levels, future studies having prostate volume data with larger sample size are warranted to verify our findings. CLINICALTRIALS.

Gov Identifier: NCT02820844 (first posted July 1, 2016). https://clinicaltrials.gov/ct2/show/NCT02820844 .
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http://dx.doi.org/10.1007/s11255-021-02962-zDOI Listing
July 2021

Evaluation of identification accuracy using AIQS for GC-MS for measuring heavily contaminated samples.

Chemosphere 2021 Jul 3;285:131401. Epub 2021 Jul 3.

Health and Environmental Risk Division, National Institute for Environmental Studies, Japan; Graduate School of Pharmaceutical Sciences, Chiba University, Japan.

Automated identification and quantification systems with gas chromatography-mass spectrometry (GC-MS) (i.e., AIQS-GC) are used as a simple and comprehensive method for screening chemicals existing in the environment and are expected to be useful for emergency surveys in the event of a disaster. However, reports on the potential of AIQS-GC in heavily contaminated samples (HCSs) are limited. In this study, the identification performance of AIQS-GC was confirmed by comparing the exact mass of the targets identified by AIQS-GC with the measured accurate mass using GC-quadrupole-time-of-flight MS (GC-QTofMS) and by employing firefighting wastewater as HCS. In HCS, the mass spectrum interference was determined to cause false positives. The GC-QTofMS method revealed the presence of false positives and the false rate of AIQS-GC in HCS. Herein, AIQS-GC showed high identification accuracy in a normal sample such as river water. Conversely, in HCS, AIQS-GC may lead to incorrect evaluations. The combination of AIQS-GC and support method using GC-QTofMS, which can avoid the false positive is extremely useful for the rapid and easy analysis of HCS.
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http://dx.doi.org/10.1016/j.chemosphere.2021.131401DOI Listing
July 2021

Safety of Once-Daily Single-Inhaler Triple Therapy with Fluticasone Furoate/Umeclidinium/Vilanterol in Japanese Patients with Asthma: A Long-Term (52-Week) Phase III Open-Label Study.

J Asthma Allergy 2021 6;14:809-819. Epub 2021 Jul 6.

GSK, Tokyo, Japan.

Purpose: The pivotal CAPTAIN study reported a favorable safety profile with once-daily inhaled corticosteroid/long-acting muscarinic antagonist/long-acting β-agonist (ICS/LAMA/LABA) triple combination of fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) in patients with inadequately controlled asthma, some of whom were Japanese. Here, we evaluate the long-term (52 weeks) safety of FF/UMEC/VI in Japanese patients with asthma.

Patients And Methods: This was a Phase III, 52-week, multicenter, non-comparator, non-randomized, open-label study (NCT03184987) in Japanese adults receiving maintenance therapy with ICS/LABA, with or without LAMA. At enrollment, patients were allocated to either FF/UMEC/VI 100/62.5/25mcg (Group 1) or 200/62.5/25mcg (Group 2). Patients in Group 1 could have their treatment stepped up to 200/62.5/25mcg at Week 24 if their Asthma Control Questionnaire (ACQ)-7 score was >0.75. The primary endpoint was the incidence of adverse events (AEs) and serious AEs (SAEs). Secondary endpoints included vital signs, electrocardiogram measurements, and clinical laboratory tests (biochemistry, hematology, urinalysis). Efficacy was assessed as "other" endpoints.

Results: A total of 111 Japanese patients were included in the intention-to-treat (ITT) population. Overall, 77 (69%) patients reported ≥1 AE (Group 1: n=30 [64%]; step-up group: n=7 [78%]; Group 2: n=40 [73%]). SAEs were reported for 1 (2.1%) and 2 (3.6%) patients in Groups 1 and 2, respectively. All SAEs were considered unrelated to study treatment. One AE and one SAE led to study withdrawal: oropharyngeal discomfort (Group 1); eosinophilic granulomatosis with polyangiitis (Group 2). No new safety concerns were identified throughout the 52-week treatment period.

Conclusion: In this uncontrolled open-label study, no new safety concerns were observed with long-term (52 weeks) treatment with once-daily FF/UMEC/VI among 111 Japanese patients with asthma.
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http://dx.doi.org/10.2147/JAA.S305918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275015PMC
July 2021

Factors that predict ventricular arrhythmias in the late phase after acute myocardial infarction.

ESC Heart Fail 2021 Jun 25. Epub 2021 Jun 25.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chiba, Chuo-ku, 260-8677, Japan.

Aims: Little is known regarding factors that predict the occurrence of lethal ventricular arrhythmias (VAs) occurring after acute myocardial infarction (AMI). This observational cohort study aimed to identify factors that predicted lethal VAs during the late phase after AMI in patients with reduced left ventricular ejection fraction (LVEF).

Methods And Results: Data were collected from our AMI database regarding consecutive patients with an LVEF of ≤40% after AMI (January 2012 to July 2018). The 'late phase' was defined as ≥7 days after AMI onset, and the primary endpoint was defined as lethal VAs in the late phase. The study included 136 patients (82% men; mean age: 66 ± 13 years). The average LVEF at admission was 32.7 ± 8.2%. During a mean follow-up period of 20.7 months, 14 patients (10%) experienced lethal VAs, including ventricular fibrillation (n = 8) and sustained ventricular tachycardia (n = 10). Univariate analyses revealed that lethal VAs were predicted by age and LVEF at admission. Receiver operating characteristic curve analysis indicated that the optimal cut-off value was 23% for using the LVEF at admission to predict the primary endpoint (area under the curve: 0.77, P < 0.0001). Multivariable analysis also demonstrated that LVEF at admission was an independent predictor of the primary endpoint (risk ratio = 7.12, P = 0.001).

Conclusions: Lethal VAs in the late phase are common in patients with AMI, and reduced LVEF and cardiac function at admission play a significant role in the risk stratification for future lethal VAs in this population.
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http://dx.doi.org/10.1002/ehf2.13499DOI Listing
June 2021

Prognostic Impact of Branch Vessel Involvement on Computed Tomography versus Clinical Presentation of Malperfusion in Patients With Type a Acute Aortic Dissection.

Am J Cardiol 2021 Aug 11;152:158-163. Epub 2021 Jun 11.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Type A acute aortic dissection (AAD) is a life-threatening disease. The use of contrast-enhanced computed tomography (CT) for diagnosing AAD has increased, and CT can provide pathophysiologic information on dissection such as intramural hematoma (IMH), longitudinal extent of dissection, and branch vessel involvement. However, the prognostic impact of these CT findings is poorly investigated. This multicenter registry included 703 patients with type A AAD. The longitudinal extent of dissection and IMH was determined on CT. Branch vessel involvement was defined as dissection extended into coronary, cerebral, and visceral arteries on CT. The evidence of malperfusion was defined based on clinical presentations. The primary endpoint was in-hospital death. Of 703 patients, 126 (18%) died during hospitalization. Based on contrast-enhanced CT findings, longitudinal extent of dissection was not associated with in-hospital death, while patients with IMH had lower in-hospital mortality than those without (13% vs 22%, p = 0.004). Coronary, cerebral, and visceral artery involvement on CT was found in 6%, 55%, and 32%. In patients with coronary artery involvement, 90% had clinical coronary malperfusion, while only 25% and 21% of patients with cerebral and visceral artery involvement had clinical evidence of corresponding organ malperfusion. Multivariable analysis showed evidence of malperfusion as a significant factor associated with in-hospital mortality. In conclusions, branch vessel involvement on CT was not always associated with end-organ malperfusion in patients with type A AAD, especially in cerebral and visceral arteries. Clinical evidence of malperfusion was significantly associated with in-hospital mortality beyond branch vessel involvement on CT.
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http://dx.doi.org/10.1016/j.amjcard.2021.05.005DOI Listing
August 2021

Botulinum toxin injections for Japanese patients with urinary incontinence caused by neurogenic detrusor overactivity: Clinical evaluation of onabotulinumtoxinA in a randomized, placebo-controlled, double-blind trial with an open-label extension.

Int J Urol 2021 Jun 1. Epub 2021 Jun 1.

Clinical Development (Specialty), Japan Medical and Development, GlaxoSmithKline K.K., Tokyo, Japan.

Objective: To assess the efficacy and safety of botulinum toxin treatment (onabotulinumtoxinA 200 units) for Japanese patients with neurogenic detrusor overactivity caused by spinal cord injury or multiple sclerosis.

Methods: Patients with urinary incontinence refractory to pharmacological treatment were enrolled and randomized in a phase III trial. A single dose of onabotulinumtoxinA (n = 11) or placebo (n = 10) was given in the double-blind phase, and repeat injections of onabotulinumtoxinA were given in the subsequent open-label phase. Outcomes included urinary incontinence episodes, urodynamics, patient-reported outcomes and adverse events.

Results: The onabotulinumtoxinA group showed a numerically greater reduction in the number of urinary incontinence episodes per day than the placebo group, with the difference between the groups at week 6 of -3.02 (95% confidence interval -5.85 to -0.19). The onabotulinumtoxinA group also showed greater improvements in urodynamic assessments. Adverse events related to onabotulinumtoxinA injections were hematuria, urinary retention, urinary bladder hemorrhage, autonomic dysreflexia and epididymitis. Most events were deemed mild or moderate.

Conclusions: Intradetrusor injections of onabotulinumtoxinA are efficacious and tolerable for Japanese patients with neurogenic detrusor overactivity-related symptoms that are difficult to manage with anticholinergics and/or β -adrenergic receptor agonists.
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http://dx.doi.org/10.1111/iju.14602DOI Listing
June 2021

Recent Progress in Dendritic Cell-Based Cancer Immunotherapy.

Cancers (Basel) 2021 May 20;13(10). Epub 2021 May 20.

Division of Chemotherapy, Kindai University Faculty of Pharmacy, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan.

Cancer immunotherapy aims to treat cancer by enhancing cancer-specific host immune responses. Recently, cancer immunotherapy has been attracting much attention because of the successful clinical application of immune checkpoint inhibitors targeting the CTLA-4 and PD-1/PD-L1 pathways. However, although highly effective in some patients, immune checkpoint inhibitors are beneficial only in a limited fraction of patients, possibly because of the lack of enough cancer-specific immune cells, especially CD8 cytotoxic T-lymphocytes (CTLs), in the host. On the other hand, studies on cancer vaccines, especially DC-based ones, have made significant progress in recent years. In particular, the identification and characterization of cross-presenting DCs have greatly advanced the strategy for the development of effective DC-based vaccines. In this review, we first summarize the surface markers and functional properties of the five major DC subsets. We then describe new approaches to induce antigen-specific CTLs by targeted delivery of antigens to cross-presenting DCs. In this context, the chemokine receptor XCR1 and its ligand XCL1, being selectively expressed by cross-presenting DCs and mainly produced by activated CD8 T cells, respectively, provide highly promising molecular tools for this purpose. In the near future, CTL-inducing DC-based cancer vaccines may provide a new breakthrough in cancer immunotherapy alone or in combination with immune checkpoint inhibitors.
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http://dx.doi.org/10.3390/cancers13102495DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8161242PMC
May 2021

Prognostic value of preoperative psoas muscle index as a measure of nutritional status in patients with esophageal cancer receiving neoadjuvant therapy.

Nutrition 2021 Mar 6;90:111232. Epub 2021 Mar 6.

First Department of Surgery, Faculty of Medicine University of Yamanashi, Yamanashi, Japan.

Objectives: It has been reported that preoperative nutritional status in some gastrointestinal cancers has a significant effect on postoperative prognosis. However, there are few reports on esophageal cancer, especially for esophageal cancer patients who have undergone neoadjuvant therapy and surgery. Psoas muscle index (PMI) is widely known as an index for assessing preoperative nutritional status, and has recently been reported for its prognostic value in many malignancies. The aim of this study was to investigate and evaluate the clinical results in our hospital using the PMI method.

Methods: We retrospectively investigated esophageal cancer in patients (clinical stage II or III) who underwent neoadjuvant therapy and surgical treatment (R0 cases) from January 2008 to December 2015. Applicable 63 cases were entered accordingly. In our hospital, nutritional supplements are used for nutritional management during preoperative adjuvant therapy, and these are administered to patients who have difficulty ingesting nutrition by feeding tube or total parenteral nutrition. The target value for nutritional supplement administration was 36 kcal/kg. Taking into account that chemotherapy for esophageal cancer was being performed using Harris-Benedict's basal energy expenditure (25 kcal/kg), we multiplied by 1.44 (active factor; 1.2, stress factor; 1.2) and set 36 kcal/kg as a guide. PMI was evaluated before neoadjuvant therapy and before surgery. We defined sarcopenia by PMI of the third lumbar vertebra (L3) by a computed tomography (CT) examination using 3-dimensional image analysis software, <6.36 for men and <3.92 for women, and investigated the effect of each on prognosis.

Results: The prevalence of sarcopenia decreased from 74.6% (47 of 63) to 69.84% (44 of 63) during the pretherapeutic to preoperative period (P = 0.691), suggesting improved nutritional status. Regarding PMI divided by cutoff value for each sex (the cutoff value was the PMI mean value -2 SD [6.36 cm m for men and 3.92 cm/m for women] of healthy individuals <50 y of age, which was reported as a standard for low skeletal muscle mass in Japanese individuals), there was an improvement observed in the preoperative compared to pretherapeutic period, but it was not obtained as a significant difference (pretherapeutic PMI; 0.87 ± 0.06 [mean ± SD], preoperative PMI; 0.89 ± 0.06 [mean ± SD], P = 0.18). In overall survival (OS) and disease-free survival (DFS), there was no significant difference in the short-term results with and without sarcopenia in the pretherapeutic group (both OS and DFS, P = 0.17). There was a significant difference with and without sarcopenia in the preoperative group in terms of OS and DFS (OS, P = 0.045; DFS, P = 0.043), which was short term due to nutritional intervention during preoperative adjuvant therapy. It was suggested that the results would be improved.

Conclusions: Improving nutritional status before surgery was shown to improve short-term prognosis in patients with esophageal cancer. It is hence suggested that it is important to maintain or improve nutritional status by intervention from the time of neoadjuvant therapy.
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http://dx.doi.org/10.1016/j.nut.2021.111232DOI Listing
March 2021

Partial anomalous pulmonary venous connection and a tracheal bronchus associated with lung cancer in the same lobe: classification of partial anomalous pulmonary venous connection in lung resection.

Gen Thorac Cardiovasc Surg 2021 Aug 29;69(8):1261-1266. Epub 2021 Apr 29.

Department of General Thoracic Surgery, National Hospital Organization, Kanagawa National Hospital, 666-1 Ochiai Hadano, Kanagawa, 257-8585, Japan.

A 73-year-old man with primary lung adenocarcinoma (StageIA3), which was solid nodule in the posterior segment, was simultaneously diagnosed as having partial anomalous pulmonary venous connection (PAPVC) and a tracheal bronchus in the same lobe on preoperative chest computed tomography. Right upper lobectomy was performed as the definitive treatment for both the lung cancer and the PAPVC. The superior pulmonary vein connected to the proximal superior vena cava and the pulmonary artery to the apical segment diverged at the proximal portion of the right pulmonary artery trunk along with the tracheal bronchus. The patient's pulmonary arterial pressure improved after lobectomy. The patient is living well without recurrence of lung cancer 6 months after surgery. In conclusion, it is important to confirm the presence of anomalous pulmonary vein drainage to prevent the lethal change of pulmonary-systemic blood flow. Based on the classification of PAPVC proposed, surgical plan should be considered carefully.
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http://dx.doi.org/10.1007/s11748-021-01638-wDOI Listing
August 2021

A novel role for bone marrow-derived cells to recover damaged keratinocytes from radiation-induced injury.

Sci Rep 2021 Mar 11;11(1):5653. Epub 2021 Mar 11.

Department of Stem Cell Biology and Regenerative Medicine, Shiga University of Medical Science, Shiga, Japan.

Exposure to moderate doses of ionizing radiation (IR), which is sufficient for causing skin injury, can occur during radiation therapy as well as in radiation accidents. Radiation-induced skin injury occasionally recovers, although its underlying mechanism remains unclear. Moderate-dose IR is frequently utilized for bone marrow transplantation in mice; therefore, this mouse model can help understand the mechanism. We had previously reported that bone marrow-derived cells (BMDCs) migrate to the epidermis-dermis junction in response to IR, although their role remains unknown. Here, we investigated the role of BMDCs in radiation-induced skin injury in BMT mice and observed that BMDCs contributed to skin recovery after IR-induced barrier dysfunction. One of the important mechanisms involved the action of CCL17 secreted by BMDCs on irradiated basal cells, leading to accelerated proliferation and recovery of apoptosis caused by IR. Our findings suggest that BMDCs are key players in IR-induced skin injury recovery.
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http://dx.doi.org/10.1038/s41598-021-84818-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952382PMC
March 2021

CCR4 Involvement in the Expansion of T Helper Type 17 Cells in a Mouse Model of Psoriasis.

J Invest Dermatol 2021 Aug 2;141(8):1985-1994. Epub 2021 Mar 2.

Division of Chemotherapy, Faculty of Pharmacy, Kindai University, Higashiosaka, Japan. Electronic address:

Psoriasis is a chronic skin disease associated with T helper (Th)17-mediated inflammation. Because CCR4 is a major chemokine receptor expressed on Th17 cells, we investigated the role of CCR4 in a modified imiquimod-induced psoriasis model that showed enhanced skin infiltration of Th17 cells. CCR4-deficient mice had less severe skin disease than wild-type mice. Th17 cells were decreased in the skin lesions and regional lymph nodes of CCR4-deficient mice. In the regional lymph nodes of wild-type mice, CD44 memory Th17 cells expressing CCR4 were found to be clustered with dendritic cells expressing CCL22, a ligand for CCR4. Such dendritic cell‒Th17 cell clusters were significantly decreased in CCR4-deficient mice. Similar results were obtained using the IL-23‒induced psoriasis model. In vitro, compound 22, a CCR4 antagonist, significantly reduced the expansion of Th17 cells in the coculture of CD11c dendritic cells and CD4 T cells separately prepared from the regional lymph nodes of wild-type mice with psoriasis. In vivo, compound 22 ameliorated the psoriasis-like skin disease in wild-type mice with significant decreases of Th17 cells in the regional lymph nodes and skin lesions. Collectively, CCR4 is likely to play a role in the pathogenesis of psoriasis through the expansion of Th17 cells.
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http://dx.doi.org/10.1016/j.jid.2020.12.034DOI Listing
August 2021

[Nab-Paclitaxel plus Gemcitabine for Patients with Recurrence after Resection for Adenocarcinoma of the Pancreas].

Gan To Kagaku Ryoho 2021 Jan;48(1):107-109

First Dept. of Surgery, Faculty of Medicine, University of Yamanashi.

Purpose: The purpose of this study was to clarify the predictors of efficacy of nab-paclitaxel plus gemcitabine(GnP)for patients with recurrence after resection for adenocarcinoma of the pancreas.

Method: Patients who had received GnP at our hospital were divided into 2 groups; effective group and non-effective group and we compared them. In addition, we compared the therapeutic effect of patients between well-differentiated adenocarcinoma and moderately differentiated adenocarcinoma. Furthermore, we compared the efficacy depending on the time of recurrence.

Results: In patients with well-differentiated adenocarcinoma, the disease control rate was 93.6% and progression free survival was 8.6 months, whereas those in patients with moderately differentiated adenocarcinoma were 57.1% and 4.4 months, respectively. Patients who recurred at 7 months or later, had a better therapeutic response than the patients who recurred within 6 months after surgery.

Conclusions: GnP may be effective in patients with well-differentiated adenocarcinoma and in patients who recurred at 7 months or later.
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January 2021

Stroke Volume Variation Monitoring to Minimize Blood Loss in Hepatocellular Carcinoma Resection.

Anticancer Res 2021 Jan;41(1):409-415

First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan

Background/aim: We aimed to evaluate the correlation between stroke volume variation (SVV) and intraoperative blood loss (IBL) in hepatocellular carcinoma (HCC) resection and examine the perioperative utility of SVV-based management.

Patients And Methods: Ninety-five patients who underwent partial or sub-segmental hepatectomy for HCC between 2013 and 2019 at the University of Yamanashi Hospital were retrospectively analyzed. A correlation analysis between IBL and SVV was performed, and then all cases were divided into three groups: high, middle, and low-SVV groups. Perioperative short-term outcomes based on SVV groups were analyzed.

Results: There was a weak but significant negative correlation between SVV and IBL (ρ=-0.372, p<0.001). Comparative analysis revealed that low-SVV was associated with a high incidence of postoperative complications and blood transfusion (p=0.018 and 0.037, respectively), and high-SVV was not related with postoperative complications.

Conclusion: SVV-based management is a significant and feasible strategy to achieve safe and exact surgical resection of HCC.
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http://dx.doi.org/10.21873/anticanres.14790DOI Listing
January 2021

Early Drain Removal Regardless of Drain Fluid Amylase Level Might Reduce Risk of Postoperative Pancreatic Fistula.

Anticancer Res 2021 Jan;41(1):403-408

First Department of Surgery, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.

Background/aim: Drains are frequently placed at the time of distal pancreatectomy (DP) to evacuate pancreatic juice and intra-abdominal exudate and obtain information on abdominal cavity status. However, the timing of drain removal remains debatable. Meanwhile, prolonged drain placement might increase the risk of postoperative pancreatic fistula (POPF), with a prevalence of 5-40%. Therefore, we examined the effect of removing the drain within postoperative day (POD) 3 on the risk of POPF development.

Patients And Methods: A total of 108 consecutive patients who underwent DP between April 2015 and March 2020 were examined and divided into two groups according to the day of drain removal; hence, for some patients, the drain was removed on POD 1 (POD 1 group) and for others on POD 3 (POD 3 group). Furthermore, risk factors, including drain fluid amylase (DFA) levels, for developing POPF were investigated.

Results: The overall rate of clinically relevant POPF was 4.6% and did not significantly differ between the POD 1 and POD 3 groups [4.5% and 4.9%, respectively (p=0.924)]. DFA levels on POD 1 did not significantly differ between patients with and without POPF. On POD 3 and POD 5, C-reactive protein (CRP) levels were significantly higher in patients with POPF than in those without (p=0.03 and p<0.001, respectively).

Conclusion: Early drain removal regardless of DFA level may reduce the risk of developing POPF. CRP measured on POD 3 and POD 5 appeared to be a useful predictor of clinically relevant POPF.
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http://dx.doi.org/10.21873/anticanres.14789DOI Listing
January 2021

Postpneumonectomy syndrome related to the thickness of the fat tissue in the anterior mediastinum: a retrospective observational study.

J Thorac Dis 2020 Nov;12(11):6761-6768

Department of General Thoracic Surgery, National Hospital Organization, Kanagawa National Hospital, Kanagawa Japan.

Background: Postpneumonectomy syndrome (PPS) is a life-threatening condition characterized by the extrinsic compression of the mainstem bronchus after pneumonectomy, causing rapidly progressive dyspnea. Information regarding the predictive factors of this condition is limited. Thus, the current study aimed to identify the predictive findings that can help prepare the treatment of PPS in advance.

Methods: The present study is a retrospective observational study. We reviewed the medical records of 12 consecutive patients who underwent pneumonectomy for lung cancer or tuberculosis between 2009 and 2020. The anatomical findings evaluated via computed tomography scan, nutritional status assessed using laboratory data, respiratory function, intraoperative variables between PPS and non-postpneumonectomy-syndrome patients were compared.

Results: There were two female patients who presented with left PPS (PPS 1 and PPS 2 aged 73 and 55 years, respectively). The median age of 10 non-postpneumonectomy-syndrome patients (n=6, men and n=4 women) was 66 (range, 54-76 years). Four and six patients underwent right and left pneumonectomy, respectively. The fat tissue thickness in the anterior mediastinum was significantly thinner in PPS than in non-postpneumonectomy-syndrome patients. However, the body mass index (BMI) and other nutritional parameters did not differ between PPS and non-postpneumonectomy-syndrome patients. The median vital capacity was higher in PPS than in non-postpneumonectomy-syndrome patients. The decrement of respiratory function and body weight after pneumonectomy did not differ between two groups. The intraoperative variables did not also differ between two groups.

Conclusions: The fat tissue in the anterior mediastinum between the bilateral lungs is an anchor that can help maintain the normal position of the mediastinum after pneumonectomy. Thus, the fat tissue thickness between the bilateral lungs can be a predictive factor for the occurrence of PPS before surgery.
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http://dx.doi.org/10.21037/jtd-20-2370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711408PMC
November 2020

Impact of clinical presentations on lipid core plaque assessed by near-infrared spectroscopy intravascular ultrasound.

Int J Cardiovasc Imaging 2021 Apr 17;37(4):1151-1158. Epub 2020 Nov 17.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, 260-8677, Japan.

Near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS) studies have demonstrated that lipid core plaque (LCP) is frequently observed in the culprit segment of myocardial infarction (MI). However, little is known about the impact of clinical presentations such as chronic coronary syndrome (CCS) and acute coronary syndrome (ACS) including unstable angina (UA), non ST-segment elevation MI (NSTEMI), and ST-segment elevation MI (STEMI) on LCP. The present prospective single-center registry included a total of 178 patients who underwent percutaneous coronary intervention under NIRS-IVUS guidance. Patients were divided into CCS and ACS groups, and ACS patients were further sub-divided into the 3 groups according to the clinical presentation. The primary endpoint was coronary LCP in the target lesion assessed by NIRS-IVUS with maximal lipid core burden index over any 4 mm segment (maxLCBI). The study population included 124 and 54 patients with CCS and ACS. MaxLCBI in the target lesion was significantly higher in the ACS group than in the CCS group (503 [284-672] vs. 406 [250-557], p = 0.046). Among ACS patients, MaxLCBI in the target lesion was also significantly different in those with UA (n = 18), NSTEMI (n = 21), and STEMI (n = 15) (288 [162-524] vs. 518 [358-745] vs. 646 [394-848], p = 0.021). In conclusion, LCP assessed by NIRS-IVUS, a surrogate of coronary plaque vulnerability, was significantly different according to the clinical presentations such as CCS, UA, NSTEMI, and STEMI.
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http://dx.doi.org/10.1007/s10554-020-02107-wDOI Listing
April 2021

Stagnant forearc mantle wedge inferred from mapping of shear-wave anisotropy using S-net seafloor seismometers.

Nat Commun 2020 Nov 10;11(1):5676. Epub 2020 Nov 10.

National Research Institute for Earth Science and Disaster Resilience, 3-1 Tennodai, Tsukuba, Ibaraki, 305-0006, Japan.

Shear-wave anisotropy in Earth's mantle helps constrain the lattice-preferred orientation of anisotropic minerals due to viscous flow. Previous studies at the Japan Trench subduction zone using land-based seismic networks identified strong anisotropy in the mantle wedge, reflecting viscous flow induced by the subducting slab. Here we map anisotropy in the previously uninvestigated offshore region by analyzing shear waves from interplate earthquakes that are recorded by a new seafloor network (the S-net). The newly detected anisotropy is not in the mantle wedge but only in the overlying crust (∼0.1 s time delay and trench-parallel fast direction). The distinct lack of anisotropy indicates that the forearc mantle wedge offshore is decoupled from the slab and does not participate in the viscous flow, in sharp contrast with the rest of the mantle wedge. A stagnant forearc mantle wedge provides a stable and cold tectonic environment that is important for the petrological evolution and earthquake processes of subduction zones.
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http://dx.doi.org/10.1038/s41467-020-19541-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655809PMC
November 2020

In-Hospital Blood Pressure Variability: A Novel Prognostic Marker of Renal Function Decline and Cardiovascular Events in Patients with Coronary Artery Disease.

Kidney Blood Press Res 2020 7;45(5):748-757. Epub 2020 Oct 7.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Introduction: Several measures of blood pressure (BP) variability have been associated with kidney disease and cardiovascular events. Although BP is routinely measured during hospitalization in daily practice, the prognostic impact of in-hospital BP and its variability are uncertain.

Methods: A total of 226 participants who underwent elective percutaneous coronary intervention (PCI) for stable coronary artery disease (CAD) were included. BP was measured by trained nurses during the 4-day hospitalization for PCI. BP variability was assessed by standard deviation (SD) and coefficient variation of systolic BP. Estimated glomerular filtration rate (eGFR) was calculated at baseline and follow-up (≥6 months). The cardiovascular end point was defined as a composite of cardiovascular death, acute coronary syndrome, stroke, heart failure hospitalization, and any coronary revascularization.

Results: In-hospital BP was measured 9.5 ± 0.8 times. During a median follow-up period of 1.7 years, mean eGFR change was -1.7 mL/min/1.73 m2 per year, and 35 (15.5%) participants met the cardiovascular end point. Mean systolic BP and SD were negatively correlated with eGFR change. In the receiver operating characteristic curve analysis, SD of systolic BP predicted the cardiovascular end point (AUC 0.63, best cutoff value 14.2 mm Hg, p = 0.003). Kaplan-Meier analysis demonstrated a significantly higher incidence of the cardiovascular end point in patients with SD of systolic BP ≥14.2 mm Hg compared to their counterpart (p = 0.003). A multivariable analysis showed SD of systolic BP as an independent predictor for the cardiovascular end point. When assessed with coefficient variation, BP variability was similarly related to eGFR change and clinical outcomes.

Conclusion: Greater in-hospital BP variability was associated with renal function decline and cardiovascular events in patients with stable CAD.
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http://dx.doi.org/10.1159/000509291DOI Listing
May 2021

P2X receptor agonist enhances tumor-specific CTL responses through CD70+ DC-mediated Th17 induction.

Int Immunol 2021 Jan;33(1):49-55

Division of Chemotherapy, Kindai University Faculty of Pharmacy, Higashi-osaka, Osaka, Japan.

Extracellular ATP is known to promote Th17 cell differentiation in the intestinal lamina propria by stimulating CD70+CD11clow dendritic cells (DCs) via P2X receptors (P2XRs). Recent studies have also shown that Th17 cells enhance antitumor immunity by directly promoting proliferation of cytotoxic T lymphocytes (CTLs). These finding led us to test a P2XR agonist, αβ-methylene ATP (αβ-ATP), as a mucosal vaccine adjuvant to promote CTL responses through Th17 induction. We demonstrated that (i) CD70+CD11clow DCs were present in the nasal lamina propria and expressed P2X1R, P2X2R and P2X4R; (ii) CD70+CD11clow DCs isolated from the nasal lamina propria enhanced Th17 cell differentiation of cocultured splenic CD4+ T cells upon stimulation with αβ-ATP; (iii) mice intranasally immunized with ovalbumin (OVA) and αβ-ATP had increased OVA-specific Th17 cells and CTLs in the nasal lamina propria and regional lymph nodes; (iv) mice intranasally immunized with OVA and αβ-ATP also had elevated resistance to E.G7-OVA tumor growth compared with those intranasally immunized with OVA alone; (v) suramin, a broad-range inhibitor of P2 receptors, suppressed the increases of OVA-specific Th17 cells and CTLs in mice intranasally immunized with OVA and αβ-ATP; and (vi) suramin also abrogated the enhanced antitumor immunity of mice intranasally immunized with OVA and αβ-ATP against E.G7-OVA. Collectively, αβ-ATP may be a promising mucosal adjuvant that promotes antigen-specific CTL responses via CD70+CD11clow DC-mediated Th17 induction.
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http://dx.doi.org/10.1093/intimm/dxaa068DOI Listing
January 2021

Vasospastic angina and overlapping cardiac disorders in patients resuscitated from cardiac arrest.

Heart Vessels 2021 Mar 29;36(3):321-329. Epub 2020 Sep 29.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba, Chiba, 260-8677, Japan.

Background: Vasospastic angina (VSA) reportedly accounts for one form of sudden cardiac arrest (SCA). Intracoronary acetylcholine (ACh) testing is useful for diagnosing VSA although invasive provocation testing after SCA is a clinical challenge. In addition, even if the ACh test is positive, any causal relationship between VSA and SCA is often unclear because patients with VSA may have other underlying cardiac disorders.

Methods: A total of 20 patients without overt structural heart disease who had been fully resuscitated from SCA were included. All patients underwent the ACh provocation test and scrutiny such as cardiac computed tomography or magnetic resonance imaging. Patients were followed up for all-cause death or recurrent SCA including appropriate implantable cardioverter defibrillator therapy.

Results: An ACh provocation test was performed 20 ± 17 days after cardiac arrest. Fifteen out of 20 (75.0%) patients had a positive ACh test and 2 (10.0%) had adverse events such as ventricular tachycardia and transient cardiogenic shock during the test. In patients with a positive ACh test, 6 of 15 (40.0%) patients had other overlapping cardiac disorders such as long QT syndrome, Brugada syndrome, cardiac sarcoidosis, myocarditis, or cardiomyopathy. Long-term prognosis was not different regardless of a positive ACh test or the presence of other cardiac disorders overlapping with VSA.

Conclusions: Three-quarters of the patients who had been resuscitated from SCA had a positive ACh test. Further examinations revealed other overlapping cardiac disorders in addition to VSA in 40% of patients with a positive ACh test.
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http://dx.doi.org/10.1007/s00380-020-01705-xDOI Listing
March 2021

Kidney GATA3 regulatory T cells play roles in the convalescence stage after antibody-mediated renal injury.

Cell Mol Immunol 2021 May 11;18(5):1249-1261. Epub 2020 Sep 11.

Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan.

FoxP3 regulatory T cells (Tregs) play crucial roles in peripheral immune tolerance. In addition, Tregs that reside or accumulate in nonlymphoid tissues, called tissue Tregs, exhibit tissue-specific functions and contribute to the maintenance of tissue homeostasis and repair. In an experimental mouse model of crescentic glomerulonephritis induced by an anti-glomerular basement membrane antibody, Tregs started to accumulate in the kidney on day 10 of disease onset and remained at high levels (~30-35% of CD4 T cells) during the late stage (days 21-90), which correlated with stable disease control. Treg depletion on day 21 resulted in the relapse of renal dysfunction and an increase in Th1 cells, suggesting that Tregs are essential for disease control during the convalescence stage. The Tregs that accumulated in the kidney showed tissue Treg phenotypes, including high expression of GATA3, ST2 (the IL33 receptor subunit), amphiregulin (Areg), and PPARγ. Although T-bet Tregs and RORγt Tregs were observed in the kidney, GATA3 Tregs were predominant during the convalescence stage, and a PPARγ agonist enhanced the accumulation of GATA3 Tregs in the kidney. To understand the function of specific genes in kidney Tregs, we developed a novel T cell transfer system to T cell-deficient mice. This experiment demonstrates that ST2, Areg, and CCR4 in Tregs play important roles in the accumulation of GATA3 Tregs in the kidney and in the amelioration of renal injury. Our data suggest that GATA3 is important for the recruitment of Tregs into the kidney, which is necessary for convalescence after renal tissue destruction.
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http://dx.doi.org/10.1038/s41423-020-00547-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8093306PMC
May 2021

Questionnaire in patients with aborted sudden cardiac death due to coronary spasm in Japan.

Heart Vessels 2020 Dec 12;35(12):1640-1649. Epub 2020 Jun 12.

Toyama Prefectural Central Hospital, Toyama, Japan.

Objectives: We investigated the medical or mechanical therapy, and the present knowledge of Japanese cardiologists about aborted sudden cardiac death (ASCD) due to coronary spasm.

Methods: A questionnaire was developed regarding the number of cases of ASCD, implantable cardioverter-defibrillator (ICD), and medical therapy in ASCD patients due to coronary spasm. The questionnaire was sent to the Japanese general institutions at random in 204 cardiology hospitals.

Results: The completed surveys were returned from 34 hospitals, giving a response rate of 16.7%. All SCD during the 5 years was observed in 5726 patients. SCD possibly due to coronary spasm was found in 808 patients (14.0%) and ASCD due to coronary spasm was observed in 169 patients (20.9%). In 169 patients with ASCD due to coronary spasm, one or two coronary vasodilators was administered in two-thirds of patients [113 patients (66.9%)], while more than 3 coronary vasodilators were found in 56 patients (33.1%). ICD was implanted in 117 patients with ASCD due to coronary spasm among these periods including 35 cases with subcutaneous ICD. Majority of cause of ASCD was ventricular fibrillation, whereas pulseless electrical activity was observed in 18 patients and complete atrioventricular block was recognized in 7 patients. Mean coronary vasodilator number in ASCD patients with ICD was significantly lower than that in those without ICD (2.1 ± 0.9 vs. 2.6 ± 1.0, p < 0.001). Although 16 institutions thought that the spasm provocation tests under the medications had some clinical usefulness of suppressing the next fatal arrhythmias, spasm provocation tests under the medication were performed in just 4 institutions.

Conclusions: In the real world, there was no fundamental strategy for patients with ASCD due to coronary spasm. Each institution has each strategy for these patients. Cardiologists should have the same strategy and the same knowledge about ASCD patients due to coronary spasm in the future.
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http://dx.doi.org/10.1007/s00380-020-01644-7DOI Listing
December 2020

[Thoracic Spinal Chordoma Need to be Differentiated from the Bacteremia-associated Paravertebral Abscess].

Kyobu Geka 2020 May;73(5):362-365

Department of Thoracic Surgery, Tokyo Metropolitan Tama Medical Center, Fuchu, Japan.

A 71-year-old woman presented to our hospital with fever and dyspnea. Computed tomography showed shadows of bilateral pneumonia and anterior vertebral mass. She was admitted to our hospital for respiratory failure. Despite treatment with antibiotics, she developed right thoracic empyema. A high level of inflammation and fever persisted, despite chest tube drainage and continued treatment with antibiotics. Therefore, thoracoscopic curettage was conducted. The histopathological findings of the curetted anterior vertebral body lesion revealed the diagnosis of chordoma. After confirming that all the culture results and inflammation findings had turned negative, the patient was discharged from the hospital. Thoracic vertebral chordoma is being treated at the department of orthopedics.
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May 2020

Transcutaneous immunization with a highly active form of XCL1 as a vaccine adjuvant using a hydrophilic gel patch elicits long-term CD8 T cell responses.

J Pharmacol Sci 2020 Jul 10;143(3):182-187. Epub 2020 Apr 10.

Division of Chemotherapy, Kindai University Faculty of Pharmacy, 3-4-1 Kowakae, Higashi-osaka, Osaka 577-8502, Japan. Electronic address:

Memory CD8 cytotoxic T-lymphocytes (CTLs) play a key role in protective immunity against infection and cancer. However, the induction of memory CTLs with currently available vaccines remains difficult. The chemokine receptor XCR1 is predominantly expressed on CD103 cross-presenting dendritic cells (DCs). Recently, we have demonstrated that a high activity form of murine lymphotactin/XCL1 (mXCL1-V21C/A59C), a ligand of XCR1, can induce antigen-specific memory CTLs by increasing the accumulation of CD103 DCs in the vaccination site and the regional lymph nodes. Here, we combined a hydrophilic gel patch as a transcutaneous delivery device and mXCL1-V21C/A59C as an adjuvant to further enhance memory CTL responses. The transcutaneous delivery of ovalbumin (OVA) and mXCL1-V21C/A59C by the hydrophilic gel patch increased CD103 DCs in the vaccination site and the regional lymph nodes for a prolonged period of time compared with the intradermal injection of OVA and mXCL1-V21C/A59C. Furthermore, the hydrophilic gel patch containing OVA and mXCL1-V21C/A59C strongly induced OVA-specific memory CTLs and efficiently inhibited the growth of OVA-expressing tumors more than the intradermal injection of OVA and mXCL1-V21C/A59C. Collectively, this type of hydrophilic gel patch and a high activity form of XCL1 may provide a useful tool for the induction of memory CTL responses.
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http://dx.doi.org/10.1016/j.jphs.2020.04.004DOI Listing
July 2020

Decreased Double Product at Rest in Patients With Severe Vasospasm.

Heart Lung Circ 2020 Oct 18;29(10):1511-1516. Epub 2020 Mar 18.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Autonomic nerve system and endothelial function play important roles in vasospastic angina. Elevated heart rate (HR), blood pressure (BP), and double product (DP) can increase endothelial-dependent coronary artery dilation and blood flow. However, the impact of HR, BP, and DP on occurrence and severity of VSA in the clinical setting is unclear.

Method: A total of 170 patients undergoing intracoronary acetylcholine (ACh) provocation test during hospitalisation was included. Resting HR, BP, and DP were measured at least four times, and their variabilities were evaluated by standard deviations (SD) and coefficient of variations (CVs). Angiographic coronary artery vasospasm was defined as total or subtotal occlusion induced by ACh provocation.

Results: Mean±SD HR (65.7±9.1 vs 69.6±7.9 beats per minute; p=0.003), systolic BP (122.3±13.4 vs 127.7±14.6 mmHg; p=0.01), and DP (8,001±1,229 vs 8,903±1,495; p<0.001) were significantly lower in patients with a positive ACh test than the counterpart, whereas SD and CV of both HR and systolic BP were not significantly different between the two groups. Mean HR, BP, and DP progressively decreased with increase in the number of vessels with angiographic vasospasm. Multivariate analysis showed current smoking and lower DP as independent predictors of the greater number of vessels with provoked angiographic vasospasm.

Conclusions: Resting HR, BP, and DP were lower in patients with vasospastic angina, especially in those with severe vasospasm.
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http://dx.doi.org/10.1016/j.hlc.2020.02.007DOI Listing
October 2020

Association between Achilles tendon xanthoma and severity of coronary artery disease in patients undergoing percutaneous coronary intervention.

J Cardiol 2020 06 25;75(6):654-658. Epub 2020 Jan 25.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Tendon xanthoma, represented as Achilles tendon xanthoma (ATX), is one of the important diagnostic criteria for familial hypercholesterolemia (FH). However, there are some cases with ATX who do not meet these criteria. This study aimed to investigate the severity of coronary artery disease (CAD) in patients with ATX.

Methods: A total of 394 patients with CAD undergoing percutaneous coronary intervention (PCI) at Chiba University Hospital between June 2016 and February 2018 were enrolled. Soft X-ray radiography of Achilles tendon was performed, and a maximum thickness of 9 mm or more was regarded as ATX. Heterozygous FH was diagnosed according to the diagnostic criteria proposed by the Japan Atherosclerosis Society in 2017. CAD severity was assessed by SYNTAX score before the first PCI during the study period.

Results: There were 43 (10.9%) patients with ATX, and 16 (4.1%) were diagnosed as FH (15 with ATX and 1 without ATX). The ATX group showed greater body mass index, lower high-density lipoprotein cholesterol level, and the higher prevalence of FH, diabetes, prior myocardial infarction, acute coronary syndrome, multivessel disease, hemodialysis, and prior statin administration. SYNTAX score and the rate of SYNTAX score ≥23 were significantly higher in the ATX group compared with the non-ATX group (p < 0.001 for each). When patients were divided into quartiles according to Achilles tendon thickness, SYNTAX score and the prevalence of SYNTAX score ≥23 were progressively increased in favor of greater Achilles tendon thickness (p < 0.001 for each). Multivariate analysis determined male, diabetes, and ATX as independent predictors for higher SYNTAX score.

Conclusions: In CAD patients undergoing PCI, ATX was independently associated with severity of CAD. Detecting ATX may be useful not only for diagnosing FH, but also for identifying patients with advanced CAD.
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http://dx.doi.org/10.1016/j.jjcc.2020.01.002DOI Listing
June 2020

OnabotulinumtoxinA (botulinum toxin type A) for the treatment of Japanese patients with overactive bladder and urinary incontinence: Results of single-dose treatment from a phase III, randomized, double-blind, placebo-controlled trial (interim analysis).

Int J Urol 2020 Mar 20;27(3):227-234. Epub 2020 Jan 20.

Medicines Development, Japan Development Division, GlaxoSmithKline, Tokyo, Japan.

Objective: To evaluate the efficacy and safety of onabotulinumtoxinA (botulinum toxin type A) 100 U in patients with overactive bladder and urinary incontinence.

Methods: This was a phase III, randomized, double-blind, placebo-controlled trial in Japanese patients who were inadequately managed with overactive bladder medications (anticholinergics and/or β -adrenergic receptor agonists). Eligible patients were randomized 1:1 to receive a single dose of either onabotulinumtoxinA or placebo into the detrusor muscle (n = 124 each). The primary end-point was the change in the number of daily urinary incontinence episodes at week 12 from baseline. Secondary end-points included volume voided per micturition, other symptomatic measures (urinary urgency incontinence, micturition, urgency and nocturia) and patient-reported outcomes.

Results: In the onabotulinumtoxinA group, there was a significantly greater decrease from baseline in the mean number of daily urinary incontinence episodes compared with the placebo group (2.16; P < 0.001), and significantly greater improvement for all secondary end-points (P < 0.05). Urinary tract infection, dysuria, urinary retention and post-void residual urine volume increased represented adverse events occurring at a higher rate in the onabotulinumtoxinA group. The majority of these were mild or moderate in severity.

Conclusions: Statistically significant and clinically relevant improvements in symptoms and patient-reported outcomes, and tolerability were seen in patients with overactive bladder and urinary incontinence who had been inadequately managed with overactive bladder medications after using onabotulinumtoxinA.
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http://dx.doi.org/10.1111/iju.14176DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7154639PMC
March 2020

[A CASE REPORT: A PATIENT WITH METASTATIC ADRENOCORTICAL CARCINOMA EXCLUSIVELY TREATED WITH MITOTANE WITH LONG-TERM FOLLOW-UP].

Nihon Hinyokika Gakkai Zasshi 2019 ;110(1):12-17

Department of Pathology, Saiseikai Yokohamashi Nanbu Hospital.

A 77-year-old man with a complaint of impaired consciousness was brought to our emergency department. The patient was referred to our department because of a huge retroperitoneal tumor and multiple pulmonary nodules detected on computed tomography. Owning to an abnormally high level of dehydroepiandrosterone sulfate, right adrenal cancer was suspected. Pathological examination of the retroperitoneal tumor by echo-guided pericutaneous biopsy revealed an adrenocortical carcinoma. Under the diagnosis of stage IV adrenocortical carcinoma, mitotane therapy was started in May 2013. We adjusted the mitotane dose on the basis of the clinical evidence and the adrenocorticotropic hormone and cortisol levels.The tumors had increased in size after 2 months of the mitotane therapy. However, 2 months later, the tumor had significantly decreased in size. The treatment was continued for 53 months until he could no longer take medications orally, because of his advanced age, worse condition, and disuse syndrome.
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http://dx.doi.org/10.5980/jpnjurol.110.12DOI Listing
July 2020

The Importance of Biologically Active Vitamin D for Mineralization by Osteocytes After Parathyroidectomy for Renal Hyperparathyroidism.

JBMR Plus 2019 Nov 23;3(11):e10234. Epub 2019 Oct 23.

Department of Medicine, Kidney Center Tokyo Women's Medical University Shinjuku-ku, Tokyo Japan.

Hypomineralized matrix is a factor determining bone mineral density. Increased perilacunar hypomineralized bone area is caused by reduced mineralization by osteocytes. The importance of vitamin D in the mineralization by osteocytes was investigated in hemodialysis patients who underwent total parathyroidectomy (PTX) with immediate autotransplantation of diffuse hyperplastic parathyroid tissue. No previous reports on this subject exist. The study was conducted in 19 patients with renal hyperparathyroidism treated with PTX. In 15 patients, the serum calcium levels were maintained by subsequent administration of alfacalcidol (2.0 μg/day), i.v. calcium gluconate, and oral calcium carbonate for 4 weeks after PTX (group I). This was followed in a subset of 4 patients in group I by a reduced dose of 0.5 μg/day until 1 year following PTX; this was defined as group II. In the remaining 4 patients, who were not in group I, the serum calcium (Ca) levels were maintained without subsequent administration of alfacalcidol (group III). Transiliac bone biopsy specimens were obtained in all groups before and 3 or 4 weeks after PTX to evaluate the change of the hypomineralized bone area. In addition, patients from group II underwent a third bone biopsy 1 year following PTX. A significant decrease of perilacunar hypomineralized bone area was observed 3 or 4 weeks after PTX in all group I and II patients. The area was increased again in the group II patients 1 year following PTX. In group III patients, an increase of the hypomineralized bone area was observed 4 weeks after PTX. The maintenance of a proper dose of vitamin D is necessary for mineralization by osteocytes, which is important to increase bone mineral density after PTX for renal hyperparathyroidism. © 2019 The Authors. published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbm4.10234DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6874232PMC
November 2019

Increased platelet inhibition after switching from prasugrel to low-dose ticagrelor in Japanese patients with prior myocardial infarction.

J Cardiol 2020 05 11;75(5):473-477. Epub 2019 Nov 11.

Department of Cardiovascular Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.

Background: Ticagrelor and prasugrel are novel and potent P2Y12 inhibitors. Ticagrelor 90mg or 60mg twice daily is known to reduce ischemic events but be associated with an increased risk of bleeding in patients with prior myocardial infarction in Western countries. Although ticagrelor 90mg twice daily was tested in a randomized clinical trial in East Asia, the clinical significance of ticagrelor 60mg twice daily is unclear. This study aimed to evaluate platelet inhibition of low-dose ticagrelor compared to prasugrel in Japanese patients.

Methods: A total of 33 patients with prior myocardial infarction (>3 months) who received aspirin and prasugrel 3.75mg once daily were enrolled. Prasugrel was switched to ticagrelor 60mg twice daily. Platelet inhibition was assessed by VerifyNow assay (Accumetrics, San Diego, CA, USA) at baseline and 14 days after switching to ticagrelor. P2Y12 reaction unit (PRU) ≤95 was defined as low on-treatment platelet reactivity (LPR) and PRU≥262 as high on-treatment platelet reactivity.

Results: Ticagrelor treatment resulted in significantly lower PRU [10 (7-39) vs. 143 (102-201), p<0.001] and a higher rate of LPR (94% vs. 24%, p<0.001), compared to prasugrel treatment. Neither patients treated with ticagrelor nor prasugrel had high on-treatment platelet reactivity. During 2-week follow-up on ticagrelor therapy, no major bleeding occurred in both groups, while four minor bleeding events were observed.

Conclusion: In Japanese patients with prior myocardial infarction, significantly lower PRU and a higher rate of LPR were observed on ticagrelor 60mg twice daily compared to prasugrel 3.75mg once daily.
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http://dx.doi.org/10.1016/j.jjcc.2019.10.004DOI Listing
May 2020
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