Publications by authors named "Kenichi Watanabe"

312 Publications

Pleurography (thoracography) for pleural fistulas: A case series.

JTCVS Tech 2021 Jun 23;7:285-291. Epub 2021 Mar 23.

Department of Thoracic Surgery, Pneumothorax Research Center, Nissan Tamagawa Hospital, Tokyo, Japan.

Background: Pleurography (PG) has been described previously but has not gained popularity. PG can determine the exact air leak points in the lung, which is important for treating pneumothorax and pleural fistulas. We believe that the usefulness of PG should be reassessed, and here we describe the method, air leak detection rate, and common complications.

Methods: From the 1210 cases of pleural fistulas that were treated at our institution between March 2015 and October 2018, 275 patients with recurrent primary pneumothorax or secondary spontaneous pneumothorax were selected for this study. PG was performed in 127 patients with persistent air leakage during exhalation. In addition, 35 patients with postoperative complications of air leakage persisting for 7 days or longer were included.

Results: Air leak points were detected in 119 patients (73%), in the apex of the lung in 65 cases, in the basal segment in 13 cases, and in the middle lobe or lingular segment in 9 cases. There were 8 cases of hilar lesions, 12 cases of S6 lesions, 8 cases of upper lobe lesions other than apex, and 4 cases of upper mediastinal lesions. Complications within 30 days were observed in 10 cases (6.2%), with 8 grade 2 cases involving fever, 1 grade 3 case involving infection, and one grade 1 case with abdominal distension.

Conclusions: The incidence of grade ≥3 adverse events after PG was 0.6%, which is considered acceptable. Our findings suggest that PG is a safe examination method to identify air leaks before surgery for pleural fistulas.
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http://dx.doi.org/10.1016/j.xjtc.2021.03.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312103PMC
June 2021

Impact of focal apex angle on postoperative decompression status of the spinal cord and neurological recovery after cervical laminoplasty.

J Neurosurg Spine 2021 Jul 23:1-9. Epub 2021 Jul 23.

3Department of Orthopedics, Yokohama City University School of Medicine, Yokohama City, Japan.

Objective: Although anterior compression factors and cervical alignment affect neural decompression, cervical laminoplasty may be used to achieve indirect posterior decompression. The focal apex (FA) angle of the anterior compression factor of the spine represents the degree of anterior prominence toward the spinal cord. The authors investigated the mechanism underlying the influence of FA angle and cervical alignment on spinal cord alignment (SCA) after laminoplasty, including how high-intensity signal cord change (HISCC) on preoperative T2-weighted MRI (T2-MRI) may affect neurological improvement.

Methods: We performed a retrospective study of patients who underwent laminoplasty for CSM or OPLL at two hospitals (Kanto Rosai Hospital, Kawasaki City, and Yokohama Minami Kyousai Hospital, Yokohama City, Japan) between April 2004 and March 2015. In total, 109 patients (mean age 67.3 years) with cervical compression myelopathy were included. FA angle was defined as the preoperative angle between the lines from the top of the prominence to the upper and lower adjacent vertebrae. Preoperative cervical alignment was measured between the C2 and C7 vertebrae (C2-7 angle). MRI was used to classify SCA as lordosis (type-L SCA), straight (type-S), local kyphosis (type-LK), or kyphosis (type-K). Preoperative HISCC was investigated by using T2-MRI. Neurological status was evaluated by using the Japanese Orthopaedic Association score.

Results: The mean preoperative FA and C2-7 angles were 32.1° and 12.4°, respectively. Preoperative SCA was type-L or type-S in 53 patients. The neurological recovery rate (NRR) was significantly higher for patients with preoperative type-L and type-S SCA (51.4% for those with type-L and 45.0% for those with type-S) than for patients with other types (35.3% for those with type-LK and 31.7% for those with type-K). Among patients with preoperative type-L or type-S SCA, 87.3% maintained SCA; however, 5/12 (41.7%) patients with a preoperative average C2-7 angle < 12.4° and an average FA angle > 32.1° had postoperative type-LK or type-K SCA. SCA changed to type-L or type-S in 13.0% of patients with preoperative type-LK or type-K SCA. Moreover, in these patients, FA angle was significantly smaller and NRR was significantly higher than in other patients in whom postoperative SCA remained type-LK or type-K. Preoperative T2-MRI showed 73 patients with HISCC (43 with type-L and type-S, and 30 with type-LK and type-K SCA) and 36 without HISCC (20 with type-L and type-S, and 16 with type-LK and type-K SCA); the NRRs of these patients were 42.6% and 41.2%, respectively. No significant differences in SCA or NRR were observed between patients with and without HISCC.

Conclusions: NRR depends on preoperative SCA type; however, it is possible to change the type of SCA after laminoplasty. Preoperative FA and C2-7 angles influence change in SCA; therefore, they are important parameters for successful decompression with cervical laminoplasty.
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http://dx.doi.org/10.3171/2020.12.SPINE201831DOI Listing
July 2021

[Chemo-Resistant Breast Carcinoma with Cartilaginous Differentiation Manifestation after Neoadjuvant Chemotherapy-A Case Report].

Gan To Kagaku Ryoho 2021 Jul;48(7):951-953

Dept. of Surgery, Sapporo Century Hospital.

A 49-year-old woman was admitted to our hospital because of a tumor in her right breast. The tumor was localized to the C area and was approximately 3 cm in size. A right axillary lymphadenopathy was also found. Histopathological examination and needle biopsy of the breast tumor revealed invasive lobular carcinoma, and she was diagnosed with Stage ⅡB triple-negative breast cancer(cT2N1M0). Paclitaxel plus bevacizumab chemotherapy followed by ddAC chemotherapy was administered as neoadjuvant chemotherapy, but the tumor remained stable. Thus, she underwent mastectomy and lymph node dissection. Pathological findings of the resected specimen showed invasive carcinoma with cartilaginous differentiation. She was then treated with capecitabine 15 days after the surgery; however, multiple lung metastases were found on CT after 6 courses. Therefore, she was transferred to another hospital and received other chemotherapies, but died after 5 months.
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July 2021

Case report: The case of a 17 kg ovarian granulosa cell tumor in a Breton draft mare.

J Equine Sci 2021 Jun 18;32(2):67-72. Epub 2021 Jun 18.

United Graduate School of Veterinary Sciences, Gifu University, Gifu 501-1193, Japan.

Granulosa cell tumor (GCT) is a benign tumor which affects the mare's ovaries. In this report, a case of unilateral GCT in an ovary, which weighed 17.04 kg, of a 9-year-old Breton draft mare is described. A transrectal ultrasonography exam revealed a unilateral multi-cystic enlarged ovary. Laparoscopic ovariectomy was difficult due to enlargement of blood vessels in the ovarian broad ligament. The mare was necropsied, and the pathological changes in the GCT-affected ovary and unaffected ovary were evaluated. The ovarian mass in the GCT-affected ovary had a cribriform pattern and was positive for anti-Müllerian hormone (AMH) and its receptor (AMHR2). The contralateral ovary showed no follicular development and was negative for AMH. AMHR2 was positively expressed in stromal cells. The AMH concentration in plasma was 4,210 ng/ml. This is the first report showing the presence of AMH (2,210 ng/ml) in ascites fluid, and it also shows that laparoscopic ovariectomy might not be suitable for larger ovaries affected by a GCT. Ultrasonographic, endocrine, and histopathological analyses were helpful for making a definitive diagnosis of GCT in this mare.
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http://dx.doi.org/10.1294/jes.32.67DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8240524PMC
June 2021

The Impact of Cefazolin Shortage on Surgical Site Infection Following Spine Surgery in Japan.

Spine (Phila Pa 1976) 2021 Jul;46(14):923-930

Department of Orthopaedic Surgery, Faculty of Medicine, The University of Tokyo Hospital, Tokyo, Japan.

Study Design: Retrospective study using prospectively collected data.

Objective: This study aimed to investigate the effect of alternative antimicrobial prophylaxis agents on surgical site infections (SSIs) after spine surgery.

Summary Of Background Data: Although the use of alternative antimicrobial prophylaxis agents might have a negative effect on SSI prevention, their association with SSI risk in spine surgery remains unclear.

Methods: We used the registry data of consecutive patients undergoing spine surgery from April 2017 to January 2020 in four institutions participating in the University of Tokyo Spine Group. Before March 2019, all institutions used cefazolin for antimicrobial prophylaxis. After March 2019, the institutions used broad-spectrum beta-lactam agents as an alternative due to a cefazolin shortage in Japan.

Results: Among the 3841 enrolled patients (2289 males), 2024 received cefazolin and 1117 received alternative agents. The risk of reoperation for deep SSI within 30 days of spine surgery was significantly higher in the alternative antimicrobial prophylaxis agent group (adjusted odds ratio [aOR] 1.96; 95% confidence interval [CI], 1.15-3.35; P = 0.014). In subgroup analyses, the SSI risk was significantly higher in the thoracolumbar surgery group (aOR 1.98; 95% CI, 1.06-3.73; P = 0.03). A nonsignificant consistent trend was found in all other subgroups: posterior decompression (aOR 1.91; 95% CI, 0.86-4.21; P = 0.11); posterior fixation (aOR 2.05; 95% CI, 0.99-4.24; P = 0.05); and cervical spine surgery (aOR 2.30; 95% CI, 0.82-6.46; P = 0.11).

Conclusion: Alternative antimicrobial prophylaxis agents increased the risk of reoperation for SSI after spine surgery compared with cefazolin. Our study supports the current practice of using first-generation cephalosporins as first-line antimicrobial prophylaxis agents in spine surgery as recommended in multiple guidelines.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003946DOI Listing
July 2021

Pathology of female mice experimentally infected with an in vitro cultured strain of Trypanosoma equiperdum.

J Vet Med Sci 2021 Jun 16. Epub 2021 Jun 16.

Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine.

Dourine, caused by infection with Trypanosoma equiperdum, is one of the trypanosomiasis in equids. The clinical course of dourine is long-term, ranging from 1-2 months to several years. Since the pathogenesis of dourine has not yet been elucidated, experimental studies using mouse infection models are needed. Although mice are not susceptible to most T. equiperdum strains, some strains can infect mice. Even in such strains, infected mice develop rapidly transient parasitemia and die within 2-8 days. Therefore, mice experimentally infected with these T. equiperdum strains are not suitable for mouse infection models to analysis the pathogenesis of dourine. A sequential method of isolating parasites from dourine-affected horses and adapting them to in vitro cultures using soft agarose media was recently developed. Various T. equiperdum strains adapted to in vitro conditions have been established using this technique. We used one of these strains, the T. equiperdum IVM-t2 strain. In the present study, T. equiperdum IVM-t2 strain inoculated mice developed periodic parasitemia during the experimental period of 60 days. Histopathologically, vaginitis and dermatitis were observed. These findings were comparable to those of dourine-affected horses. Therefore, mice infected with T. equiperdum IVM-t2 strain may be a valuable tool for pathological, immunological, and parasitological in vivo research, and will contribute to investigations on the mechanisms underlying the disease process and the host-parasite relationship.
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http://dx.doi.org/10.1292/jvms.21-0056DOI Listing
June 2021

Efficacy of hydrated phospholipid polymer interfaces between all-polymer bearings for total hip arthroplasty.

J Biomed Mater Res B Appl Biomater 2021 Jun 15. Epub 2021 Jun 15.

Department of Materials Engineering, School of Engineering, The University of Tokyo, Tokyo, Japan.

Measurements of wear resistance and metal ion release are important for designing bearing couples or interfaces in total hip arthroplasty (THA). In this study, we investigated wear resistance and metal ion release of surface-modified metal-free all-polymer hip bearings, such as poly(ether-ether-ketone), (PEEK) on cross-linked polyethylene (PEEK-on-CLPE), with a hydrated gel-like surface layer, to propose an improved alternative to the conventional materials used to design THA bearings. The PEEK surface resulted in less metal ion release than the cobalt-chromium-molybdenum (Co-Cr-Mo) alloy surface owing to the lack of metal. The PEEK-on-CLPE bearing (6.33 mg/10  cycles) had lower wear (rate) than the bearing with Co-Cr-Mo alloy-on-CLPE (10.47 mg/10  cycles) under controlled laboratory conditions; the wear performance of the all-polymer hip bearings was further improved with hemi- or both-surface modified with a hydrated poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC) layer (3.74 and 3.06 mg/10  cycles, respectively). The PMPC-grafted interface of PEEK-on-CLPE will be especially suitable for THA candidates. This study is of key importance for the design of lifelong THA and a better understanding of the limitations resulting from using PEEK. Further studies are necessary to evaluate the possibility of using this material in artificial hips.
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http://dx.doi.org/10.1002/jbm.b.34892DOI Listing
June 2021

Myocardial Fibrosis with Cartilaginous Tissue Formation in Right Atrial Auricle of a Dog.

J Comp Pathol 2021 May 18;185:45-48. Epub 2021 May 18.

Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Hokkaido, Japan. Electronic address:

A 13-year-old castrated male Miniature Dachshund exhibited oedema of the face and cervical region. Clinical examination, including computed tomography, revealed a mass on the right atrial wall. Histopathological examination of the mass revealed proliferation of spindle cells, which formed intersecting bundles and abundant proteoglycan material. Multiple islands of hyaline cartilage were also observed within foci of proliferated spindle cells. Although the proliferated spindle cells replaced the myocardial parenchyma, there was no evidence of malignancy. The spindle cells were immunopositive for vimentin and α-smooth muscle actin, while chondrocytes were immunopositive for vimentin and S100. Neither the spindle cells nor the chondrocytes were immunolabelled for cytokeratin AE1/AE3, desmin, factor VIII, melan A, p63 or Ki-67. These findings indicate that the lesion represented myocardial fibrosis with cartilaginous tissue formation.
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http://dx.doi.org/10.1016/j.jcpa.2021.04.001DOI Listing
May 2021

Morphological and Histological Features of the Vomeronasal Organ in African Pygmy Hedgehog ().

Animals (Basel) 2021 May 19;11(5). Epub 2021 May 19.

Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-11 Inada-cho, Obihiro 080-8555, Japan.

The vomeronasal organ (VNO) detects specific chemicals such as pheromones and kairomones. Hedgehogs (Eulipotyphla: Erinaceidae) have a well-developed accessory olfactory bulb that receives projections from the VNO, but little is known about the hedgehog VNO. Here, we studied the histological features of the VNO in five individual African pygmy hedgehogs by hematoxylin-eosin, periodic acid-Schiff, and Alcian blue stains. The hedgehog VNO comprises a hyaline cartilage capsule, soft tissue and epithelial lumen, and it branches from the site just before the incisive duct opening into the nasal cavity. The soft tissues contain several small mucous (or mucoserous) glands and a large serous gland, and many venous sinuses all around the lumen. The VNO lumen is round to oval throughout the hedgehog VNO, and the sensory epithelium lines almost the entire rostral part and medial wall of the middle part. These findings indicate that the VNO is functional and plays an important role in the hedgehog. Notably, the VNO apparently has a characteristic flushing mechanism with serous secretions like those of gustatory glands, which the hedgehog might frequently use to recognize the external environment.
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http://dx.doi.org/10.3390/ani11051462DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160653PMC
May 2021

Clinical usefulness of eribulin as first- or second-line chemotherapy for recurrent HER2-negative breast cancer: a randomized phase II study (JBCRG-19).

Int J Clin Oncol 2021 Jul 23;26(7):1229-1236. Epub 2021 Apr 23.

Breast Oncology Center, The Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan.

Background: Anthracycline (A) or taxane T-based regimens are the standard early-line chemotherapy for metastatic breast cancer (BC). A previous study has shown a survival benefit of eribulin in heavily pretreated advanced/recurrent BC patients. The present study aimed to compare the benefit of eribulin with treatment of physician's choice (TPC) as first- or second-line chemotherapy for recurrent HER2-negative BC.

Methods: Patients with recurrent HER2-negative BC previously receiving anthracycline and taxane AT-based chemotherapy in the adjuvant or first-line setting were eligible for this open-label, randomized, parallel-group study. Patients were randomized 1:1 by the minimization method to receive either eribulin (1.4 mg/m on day one and eight of each 21-day cycle) or TPC (paclitaxel, docetaxel, nab-paclitaxel or vinorelbine) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). Secondary endpoints included time to treatment failure (TTF), overall response rate (ORR), duration of response, and safety (UMIN000009886).

Results: Between May 2013 and January 2017, 58 patients were randomized, 57 of whom (26 eribulin and 31 TPC) were analyzed for efficacy. The median PFS was 6.6 months with eribulin versus 4.2 months with TPC (hazard ratio: 0.72 [95% confidence interval (CI), 0.40-1.30], p = 0.276). Median TTF was 6.0 months with eribulin versus 3.6 months with TPC (hazard ratio: 0.66 [95% CI, 0.39-1.14], p = 0.136). Other endpoints were also similar between groups. The most common grade ≥ 3 adverse event was neutropenia (22.2% with eribulin versus 16.1% with TPC).

Conclusions: Eribulin seemed to improve PFS or TTF compared with TPC without statistical significance. Further validation studies are needed.
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http://dx.doi.org/10.1007/s10147-021-01920-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8213561PMC
July 2021

Evaluation of olive oil effects on human stress response by measuring cerebral blood flow.

Food Sci Nutr 2021 Apr 16;9(4):1851-1859. Epub 2021 Feb 16.

Department of Neuropsychiatry Keio University School of Medicine Tokyo Japan.

In this paper, we evaluated the effects of olive oil on human's stress level. In recent years, mental stress from harsh working environment have been causing serious problems to human health, both mentally and physically. Symptoms of stress may include feelings of worthlessness, agitation, anxiety, lethargy, insomnia, and behavioral changes. Additionally, the harsh working environments may cause the workers to adopt unhealthy dietary habits, contributing to the health issue. On the other hand, olive oil has been known to provide stress-relieving effects both by ingestion and by inhaling the scent. Here, we examined the effects of extravirgin olive oil ingestion for mitigating stress from deskwork. Three best-selling extravirgin olive oil in Japan were tested, and typing task was selected to emulate deskwork situation. Near-infrared spectroscopy (NIRS) is utilized in this study to visualize the response in brain via cerebral blood flow analysis and to measure participants' stress level. Statistical analysis showed that the stress levels were lower during the olive oil ingestion experiment compared to no-oil experiment, even when measured one hour after the ingestion.
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http://dx.doi.org/10.1002/fsn3.2099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020963PMC
April 2021

Author Correction: Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure.

Hypertens Res 2021 Jul;44(7):894

Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.1038/s41440-021-00645-xDOI Listing
July 2021

Abnormal anastomosis of peripheral pulmonary arteries, initially suspected to be an arteriovenous fistula, in an adult with Williams syndrome.

Respirol Case Rep 2021 Apr 9;9(4):e00738. Epub 2021 Mar 9.

Department of Thoracic Surgery Okazaki City Hospital Okazaki Japan.

Abnormal anastomosis of peripheral pulmonary arteries is rare and resembles a pulmonary arteriovenous fistula; thus, when the inflow or outflow route cannot be clearly identified in a suspected pulmonary arteriovenous fistula, the possibility of peripheral pulmonary artery anastomosis should be considered. However, the final diagnosis requires a catheterization study.
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http://dx.doi.org/10.1002/rcr2.738DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943904PMC
April 2021

Analysis of Dysphagia and Cough Strength in Patients with Unilateral Vocal Fold Paralysis.

Dysphagia 2021 Mar 17. Epub 2021 Mar 17.

Department of Otolaryngology, Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai, 980-8574, Japan.

The association between swallowing function and cough strength in patients with unilateral vocal fold paralysis (UVFP) is unknown. We evaluated the relationship between voluntary cough strength and dysphagia among patients with UVFP (UVFP group) by comparing their data with that of corresponding healthy participants (healthy control [HC] group) in a prospective observational study. From February 1st, 2018 to March 30th, 2019, we recruited patients with a voice disorder due to UVFP, who were referred to our university hospital. Patients with a history of laryngeal surgery, vagal nerve paralysis, or cardiac and respiratory failure were excluded. Descriptive and clinical data regarding swallowing, voice, and cough peak flow (CPF) were collected as a measure of cough strength. The UVFP group comprised six women and seven men (median age, 68.0 years), and the HC group comprised six women and eight men (median age 65.5 years). The groups differed significantly in the Eating Assessment Tool (EAT)-10 scores and CPF rates (P < 0.001). Among patients with UVFP, 84.6% had an abnormal EAT-10 score of ≥ 3. Additionally, 16.7% of the patients exhibited liquid aspiration with contrast medium on a videofluorographic swallowing study (VFSS). There was no correlation between the CPF values, EAT-10 scores, or the VFSS results. Therefore, patients with severe UVFP, whose condition had been fixed, had difficulties when swallowing (85% of cases), and some even presented with aspiration on VFSS (20% of cases), while receiving a regular diet.
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http://dx.doi.org/10.1007/s00455-021-10274-8DOI Listing
March 2021

Age-Related Arteriolar Changes With Lipid and Amyloid Deposits in the Gonads of Dogs.

Vet Pathol 2021 May 9;58(3):558-567. Epub 2021 Mar 9.

13143The University of Tokyo, Tokyo, Japan.

Arteriolar lesions with lipid and/or amyloid deposits are frequently detected in canine gonads by routine histopathologic examination; however, they have never been examined in detail. In the present study, a total of 139 testes/epididymides and 200 ovaries from 72 male (4 months to 14 years old) and 105 female (7 months to 16 years old) dogs were examined for arteriolar lesions. Arteriolar lesions were detected in 21 of 72 male dogs (29%) and 54 of 105 female dogs (51%). These lesions were histologically classified into 4 types: "fibromuscular hypertrophy," characterized by thickening of the tunica intima; "focal vasculitis," characterized by mononuclear cell infiltration; "vacuolar change," consisting of lipid accumulation and infiltration of foamy cells; and "hyalinosis," characterized by irregular thickening with amyloid deposits. In the lesions of vacuolar change and hyalinosis, lipid deposition and infiltration of α-SMA-positive cells and Iba-1-positive cells were also observed. Foamy cells and amyloid deposits were immunopositive for apolipoproteins and oxidized low-density lipoprotein-related proteins. These results indicate that vacuolar change is possibly an early stage of atherosclerosis, and that amyloid may deposit as a consequence of the microenvironment associated with atherogenesis. Logistic regression analysis revealed that arteriolar lesions with lipid deposits were associated with age and interstitial cell tumors in male dogs, and with age in female dogs. Aging is likely an important risk factor of arteriolar lesions with lipid deposits of the canine gonads.
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http://dx.doi.org/10.1177/0300985821996670DOI Listing
May 2021

Characteristics of the spinopelvic parameters of patients with sacroiliac joint pain.

Sci Rep 2021 Mar 4;11(1):5189. Epub 2021 Mar 4.

Department of Medical Research and Management for Musculoskeletal Pain, 22nd Century Medical and Research Center, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.

To evaluate the characteristics of the spinopelvic parameters on radiography in patients with sacroiliac joint pain (SIJP). Two hundred fifty patients were included and divided into the SIJP group (those diagnosed with SIJP based on physical findings and response to analgesic periarticular injections; n = 53) and the non-SIJP group (those with low back pain [LBP] because of other reasons; n = 197). We compared their demographic characteristics and spinopelvic parameters using radiography. All differences found in the patients' demographic characteristics and spinopelvic parameters were analyzed. More female participants experienced SIJP than male participants (P = 0.0179). Univariate analyses revealed significant differences in pelvic incidence (PI) (P = 0.0122), sacral slope (SS) (P = 0.0034), and lumbar lordosis (LL) (P = 0.0078) between the groups. The detection powers for PI, SS, and LL were 0.71, 0.84, and 0.66, respectively. Logistic regression analyses, after adjustment for age and sex, revealed significant differences in PI (P = 0.0308) and SS (P = 0.0153) between the groups, with odds ratios of 1.03 and 1.05, respectively. More female participants experienced SIJP than male participants. Higher PI and SS values were related to SIJP among LBP patients.
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http://dx.doi.org/10.1038/s41598-021-84737-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7970840PMC
March 2021

Meta-analytic research of the dose-response relationship between salt intake and risk of heart failure.

Hypertens Res 2021 Jul 2;44(7):885-887. Epub 2021 Mar 2.

Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

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http://dx.doi.org/10.1038/s41440-021-00632-2DOI Listing
July 2021

The effects of total pleural covering on pneumothorax recurrence and pulmonary function in lymphangioleiomyomatosis patients without history of pleurodesis or thoracic surgeries for pneumothorax.

J Thorac Dis 2021 Jan;13(1):113-124

Study Group for Pneumothorax and Cystic Lung Diseases, Tokyo, Japan.

Background: Total pleural covering (TPC) is an innovative surgical procedure in which the entire visceral pleura is wrapped with sheets of oxidized regenerated cellulose (ORC) mesh under video-assisted thoracoscopic surgery. We have previously reported that TPC could successfully prevent pneumothorax recurrence in patients with lymphangioleiomyomatosis (LAM). However, the actual efficacy and preventive effect of TPC on pneumothorax recurrence remains unclear as many LAM patients already had pleural adhesion prior to TPC that was induced by thoracic surgery and/or pleurodesis. The purpose of this study is to evaluate the effects of TPC on pneumothorax recurrence and pulmonary function in LAM patients with no history of thoracic surgeries or pleurodesis.

Methods: We retrospectively reviewed medical charts of 52 patients (60 hemithoraces) who underwent TPC at our center, from January 2003 to September 2019, as a first surgical intervention for pneumothorax.

Results: Pneumothorax recurrence occurred in 12 patients [14 of 60 hemithoraces (23.3%)] during the observation period [27 months (14.7; 56.4) = median (lower; upper quartiles)]. The probability of recurrence-free hemithorax post TPC was 81.1% at 2.5 years and 64.1% at 5 years. TPC did not produce a significant decrease in either VC %predicted (pred) or FEV/FVC. The pre- post-TPC median (lower; upper quartiles) VC %pred was 85.7% (79.7; 98.0) 87.2% (72.3; 95.6), P=0.535 and the FEV/FVC was 84.6% (75.7; 89.6) 83.0% (71.8; 87.0), P=0.667. Mechanistic/mammalian target of rapamycin (mTOR) inhibitors (mTORI) were subsequently initiated in 19 patients (36.5%) because of the progression of LAM. The postoperative FEVpred was significantly lower in patients who required mTORI than in those who did not [68.1% (57.3; 82.9) 88.7% (84.6; 89.8), P=0.020]; the decline rate in FEVpred/year from pre to post TPC was significantly greater in LAM patients who required mTORI than in those who did not [-9.37% (-4.73; 12.9) -1.94% (1.52; -4.50), P=0.029]. Postoperative complications were found in 25 of 52 hemithoraces (48.1%).

Conclusions: TPC can prevent pneumothorax recurrence without causing ventilatory impairment or severe pleural symphysis in LAM patients. TPC is an effective treatment option for LAM-associated pneumothorax based on its efficacy and safety.
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http://dx.doi.org/10.21037/jtd-20-2286DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7867849PMC
January 2021

Notch signaling-modified mesenchymal stem cells improve tissue perfusion by induction of arteriogenesis in a rat hindlimb ischemia model.

Sci Rep 2021 Jan 28;11(1):2543. Epub 2021 Jan 28.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, 2-15 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Notch signaling-modified human mesenchymal stem cell, SB623 cell, is a promising cell therapy product for ischemic stroke. With the aim to expand indications for their use for critical limb-threatening ischemia (CLTI), we hypothesized that SB623 cells improved tissue perfusion by inducing angiogenesis or arteriogenesis in a hindlimb ischemia model rat. In Sprague-Dawley rats, hindlimb ischemia was generated by femoral artery removal, then seven days after ischemic induction 1 × 10 SB623 cells or PBS was injected into the ischemic adductor muscle. As compared with the PBS group, tissue perfusion was significantly increased in the SB623 group. While capillary density did not vary between the groups, αSMA- and vWF-positive arterioles with a diameter  > 15 μm were significantly increased in the SB623 group. Whole transcriptome analysis of endothelial cells co-cultured with SB623 cells showed upregulation of the Notch signaling pathway as well as several other pathways potentially leading to arteriogenesis. Furthermore, rat muscle treated with SB623 cells showed a trend for higher ephrin-B2 and significantly higher EphB4 expression, which are known as arteriogenic markers. In the hindlimb ischemia model, SB623 cells improved tissue perfusion by inducing arteriogenesis, suggesting a promising cell source for treatment of CLTI.
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http://dx.doi.org/10.1038/s41598-021-82284-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7844258PMC
January 2021

Aggregation of Mouse Serum Amyloid A Protein Was Promoted by Amyloid-Enhancing Factors with the More Genetically Homologous Serum Amyloid A.

Int J Mol Sci 2021 Jan 21;22(3). Epub 2021 Jan 21.

Muroran Institute of Technology, Graduate School of Engineering, Muroran 050-8585, Japan.

Amyloid A (AA) amyloidosis is a condition in which amyloid fibrils characterized by a linear morphology and a cross-β structure accumulate and are deposited extracellularly in organs, resulting in chronic inflammatory diseases and infections. The incidence of AA amyloidosis is high in humans and several animal species. Serum amyloid A (SAA) is one of the most important precursor amyloid proteins and plays a vital step in AA amyloidosis. Amyloid enhancing factor (AEF) serves as a seed for fibril formation and shortens the onset of AA amyloidosis sharply. In this study, we examined whether AEFs extracted and purified from five animal species (camel, cat, cattle, goat, and mouse) could promote mouse SAA (mSAA) protein aggregation in vitro using quantum-dot (QD) nanoprobes to visualize the aggregation. The results showed that AEFs shortened and promoted mSAA aggregation. In addition, mouse and cat AEFs showed higher mSAA aggregation-promoting activity than the camel, cattle, and goat AEFs. Interestingly, homology analysis of SAA in these five animal species revealed a more similar amino acid sequence homology between mouse and cat than between other animal species. Furthermore, a detailed comparison of amino acid sequences suggested that it was important to mSAA aggregation-promoting activity that the 48th amino acid was a basic residue (Lys) and the 125th amino acid was an acidic residue (Asp or Glu). These data imply that AA amyloidosis exhibits higher transmission activity among animals carrying genetically homologous SAA gene, and may provide a new understanding of the pathogenesis of amyloidosis.
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http://dx.doi.org/10.3390/ijms22031036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7864520PMC
January 2021

SARS-CoV-2 Mediated Hyperferritinemia and Cardiac Arrest: Preliminary Insights.

Drug Discov Today 2021 05 23;26(5):1265-1274. Epub 2021 Jan 23.

Houston Methodist DeBakey Heart & Vascular Center, 6550 Fannin Street, Houston, TX 77030, USA. Electronic address:

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http://dx.doi.org/10.1016/j.drudis.2021.01.014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7826001PMC
May 2021

Le Carbone prevents liver damage in non-alcoholic steatohepatitis-hepatocellular carcinoma mouse model via AMPKα-SIRT1 signaling pathway activation.

Heliyon 2021 Jan 5;7(1):e05888. Epub 2021 Jan 5.

Department of Clinical Pharmacology, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata 956-8603, Japan.

Le Carbone (LC), a fiber-enriched activated charcoal dietary supplement, claimed to be effective against inflammation associated with colitis, trimethylaminuria, and sclerosis. The study aimed to investigate the underlying mechanisms of LC to protect liver damage and its progression in non-alcoholic steatohepatitis-hepatocellular carcinoma (NASH-HCC) mice. To induce this model, C57BL/6J male baby mice were injected with a low-dose of streptozotocin and fed with a high-fat diet (HFD) 32 during 4 weeks-16 weeks of age. The LC suspension was administered orally at a dose of 5 mg/mouse/day started at the age of 6 weeks and continued until 16 weeks of age along with HFD32 feeding. At the end of the experiment, serum and liver tissues were collected for the biochemical, histological, and molecular analysis. We found that LC suspension improved the histopathological changes, serum aminotransferases in NASH mice. The hepatic expression of metabolic proteins, p-AMPKα and sirtuin 1, and proteins responsible for β-oxidation of fatty acids, peroxisome proliferator-activated receptor (PPAR) γ coactivator-α, PPARα were significantly repressed in NASH mice. LC treatment markedly restored these expressions. LC treatment significantly reduced the hepatic proteins expressions of PPARγ, tissue inhibitor of metalloproteinases 4, p47phox, p-JNK, p-ERK1/2, glypican-3, and prothrombin in NASH mice. Our findings demonstrate that LC prevents the liver damage and progression of NASH, possibly by enhancing the AMPK-SIRT1 signaling pathway.
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http://dx.doi.org/10.1016/j.heliyon.2020.e05888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7803657PMC
January 2021

A novel model of chronic limb ischemia to therapeutically evaluate the angiogenic effects of drug candidates.

Am J Physiol Heart Circ Physiol 2021 03 22;320(3):H1124-H1135. Epub 2021 Jan 22.

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Osaka, Japan.

Critical limb ischemia (CLI) is a severe state of peripheral artery disease with high unmet clinical needs. Further, there are no effective treatment options for patients with CLI. Based on preclinical study results, predicting the clinical efficacy of CLI treatments is typically difficult because conventional hindlimb ischemia (HLI) rodent models display spontaneous recovery from ischemia, which is not observed in patients with CLI. Therefore, we aimed to develop a novel chronic and severe HLI model to properly evaluate the therapeutic effects of drug candidates for CLI. Severe HLI mice (Type-N) were generated by increasing the excised area of blood vessels in a hindlimb of NOG mice. Immunohistochemistry and gene expression analysis at 9 wk after the Type-N operation revealed that the ischemic limb was in a steady state with impaired angiogenesis, like that observed in patients with CLI. We did selection of chronic Type-N mice based on the number of necrotic nails and blood flow rate at 2 wk after surgery because some Type-N mice showed mild symptoms. Therapeutic treatment with cilostazol, which is used for intermittent claudication, did not restore blood flow in chronic Type-N mice. In contrast, therapeutic transplantation of pericytes and vascular endothelial cells, which can form new blood vessels in vivo, significantly improved blood flow in a subset of Type-N mice. These findings suggest that this novel chronic and severe HLI model may be a valuable standard animal model for therapeutic evaluation of the angiogenic effects of CLI drug candidates. We developed a chronic and severe hindlimb ischemia (HLI) mouse model for preclinical research on critical limb ischemia (CLI). This model partially reflects human CLI pathology in that it does not show spontaneous restoration of blood flow or expression of angiogenic genes in the ischemic limb. This novel model may be valuable for therapeutic evaluation of the angiogenic effects of CLI drug candidates.
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http://dx.doi.org/10.1152/ajpheart.00470.2020DOI Listing
March 2021

Successful Repair of Superior Mesenteric Artery Aneurysm with Reconstruction of Branches.

Ann Vasc Dis 2020 Dec;13(4):450-453

Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.

Superior mesenteric artery aneurysms (SMAAs) are rare and potentially life-threatening. Whether surgical or endovascular repair is performed, mesenteric ischemic complication is the greatest concern. A 56-year-old gentleman with SMAA underwent surgical resection with reconstruction of the superior mesenteric artery (SMA) and its branches using the great saphenous vein with several techniques, including island reconstruction of the branches, staged segmental cross-clamping, and an external shunt, to reduce the mesenteric ischemia time. The postoperative course was uneventful with no signs of mesenteric ischemia. A computed tomography scan showed that all grafts to the SMA and its branches were patent.
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http://dx.doi.org/10.3400/avd.cr.20-00108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758580PMC
December 2020

Inferior Vena Cava Filter-Induced Thrombosis: Filter Insertion Prior to Catheter-Directed Thrombolysis and Successful Double-Filter Retrieval after Prolonged Indwelling Time.

Ann Vasc Dis 2020 Dec;13(4):437-440

Department of Cardiovascular Surgery, Suita Tokushukai Hospital, Suita, Osaka, Japan.

Extended inferior vena cava (IVC) filter implantation time increases the risk of complications in patients. Here we present the case of a 72-year-old woman with IVC filter-induced thrombosis who underwent catheter-directed thrombolysis with prophylactic IVC filter placement. Two IVC filters were successfully retrieved 70 and 1858 days post placement. The decision to insert an IVC filter should be carefully considered with appropriate indications and all filters should be removed after the risk of deep vein thrombosis has resolved.
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http://dx.doi.org/10.3400/avd.cr.20-00076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758588PMC
December 2020

First experimental verification of the neutron field of Nagoya University Accelerator-driven neutron source for boron neutron capture therapy.

Appl Radiat Isot 2021 Feb 5;168:109553. Epub 2020 Dec 5.

Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Aichi, 464-8603, Japan.

As the commissioning phase of the Nagoya University Accelerator-driven Neutron Source for boron neutron capture therapy, in-phantom thermal neutron flux measurements were conducted using a small ⁶LiF/Eu:CaF₂ scintillator detector and activation foils. The spatial distribution of the measured thermal neutron flux agreed with the Monte Carlo simulation results. Based on this comparison, the free-in-air neutron spectrum, calculated at the exit aperture, was verified and the epithermal neutron flux, at a 0.25 mA proton current, was evaluated as (1.49 ± 0.10) × 10⁷ n/(cm s).
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http://dx.doi.org/10.1016/j.apradiso.2020.109553DOI Listing
February 2021

Comparison of AA Amyloid Fibril Morphology and Serum Amyloid A Gene Sequence in 5 Animal Species.

Vet Pathol 2021 Mar 18;58(2):369-375. Epub 2020 Nov 18.

13317Muroran Institute of Technology, Muroran, Japan.

Amyloid fibrils are characterized by a linear morphology and a cross-β structure. Polymorphic and multiple fibril morphologies can be found when amyloid fibrils are extracted from amyloid-laden tissue. In this study, we report on the purification and transmission electron microscopic analysis of amyloid fibrils from 5 different animal species (mouse, cow, goat, dog, and camel) with AA amyloidosis. The results show that amyloid fibrils had a linear morphology with a cross-structure and irregular length in vivo. Although the fibrils from these different species showed highly similar conformations, there were significant differences in fibril width and crossover distance. We analyzed the sequences of homologous amyloid proteins and serum amyloid A, an evolutionarily conserved protein and a major amyloid precursor. We found 78.23% homology between the most distant amyloid proteins. The findings suggested similar fibril width and crossover distance in different animal species that displayed high homology of amyloid protein sequences. Dog and camel, as well as goat and cow, showed high genetic homology and similar fibril morphology. These data indicate that the fibrils from different animal species have similar genetic homology and morphology, which may provide a better understanding of the pathogenesis of amyloidosis.
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http://dx.doi.org/10.1177/0300985820970490DOI Listing
March 2021

Network Meta-Analysis of Drug Therapies for Lowering Uric Acid and Mortality Risk in Patients with Heart Failure.

Cardiovasc Drugs Ther 2020 Oct 23. Epub 2020 Oct 23.

Department of Hematology, Endocrinology and Metabolism, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.

Purpose: This network meta-analysis aimed to assess the current efficacy of decreasing the uric acid (UA) level with drugs to reduce mortality in patients with heart failure (HF).

Methods: Electronic literature searches using EMBASE and MEDLINE of studies published from 1 Jan 1950 to 26 Dec 2019 were conducted for randomized controlled trials or non-randomized cohort studies that included at least one group of patients who took UA-lowering drugs and with a study outcome of all-cause mortality. A random-effects network meta-analysis was performed within a frequentist framework. Hierarchy of treatments was expressed as the surface under the cumulative ranking curve (SUCRA) value, which is in proportion to mean rank (best is 100%).

Results: Nine studies, which included seven different types of groups, were eligible for analysis. The "untreated uricemia" group in which patients had hyperuricemia but without treatment had a significantly higher risk of mortality than the "no uricemia" group in which patients had no hyperuricemia (relative risk (RR)(95% confidence interval (CI), 1.43 (1.08-1.89)). The "start-allo" group wherein patients started to take allopurinol did not have a significantly lower risk of mortality than the "untreated uricemia" group (RR (95% CI), 0.68 (0.45-1.01)). However, in the "start-allo" group the SUCRA value was comparable to that in the "no uricemia" group (SUCRA: 65.4% for "start-allo"; 64.1% for "no uricemia").

Conclusions: Results suggested that allopurinol therapy was not associated with a significantly improved prognosis in terms of mortality but could potentially counteract the adverse effects associated with longstanding hyperuricemia in HF patients.
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http://dx.doi.org/10.1007/s10557-020-07097-4DOI Listing
October 2020

Effect of renal function on neutrophil decreases following eribulin administration.

Cancer Rep (Hoboken) 2020 10 17;3(5):e1258. Epub 2020 Jun 17.

Department of Breast Oncology, National Hospital Organization Hokkaido Cancer Center, Hokkaido, Japan.

Background: Eribulin therapy has recently attracted attention from various viewpoints, including quality of life, and is considered a standard therapy for inoperable or recurrent breast cancer. Although a reduction in renal function reportedly decreases total eribulin clearance, its association with dose-limiting toxicity and the reduction of neutrophils remain unclear.

Aim: This study was aimed at analyzing the association between decreased renal function prior to eribulin administration and the occurrence of neutrophil reduction and time to treatment failure in patients with breast cancer.

Methods And Results: We retrospectively assessed patients with breast cancer, who underwent eribulin therapy between July 2011 and March 2018. Multivariate analysis revealed creatinine clearance <70 mL/min and serum albumin levels <3.9 mg/dL as predictive factors for neutrophil reduction. Even on increasing the relative dose intensity by these factors, no difference in time to treatment failure was observed, suggesting that treatment efficacy is potentially unaffected.

Conclusions: For continuous eribulin therapy, eribulin may need to be administered to individual patients in accordance with renal function and albumin levels before treatment initiation.
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http://dx.doi.org/10.1002/cnr2.1258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7941480PMC
October 2020
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