VOLUME 84 NUMBER 2 May 2022

Current Issue

ISSN 2186-3326
(Online ISSN)
ISSN 0027-7622
(Print ISSN--v.72no.3/4)

Impact Factor(2020)


Adipose-derived regenerative cells as a promising therapy for cardiovascular diseases: an overview

Shukuro Yamaguchi, Yuki Shimizu, Toyoaki Murohara and Rei Shibata
pg(s) 208 - 215

<Abstract> - < PDF >

The number of patients with ischemic cardiovascular diseases is significantly increasing as populations age. Therapeutic angiogenesis has been developed as a new treatment strategy for such patients. In recent years, the presence of mesenchymal stem cells in adipose tissues was reported, and regenerative medicine using these cells has attracted attention worldwide. In this review, we describe how the transplantation of adipose-derived regenerative cells enhances angiogenesis and tissue regeneration because of their multilineage potential and cytokine secretion. Then, the current status of therapeutic angiogenesis using adipose-derived regenerative cells in the field of cardiovascular medicine was also described. These cells present great advantages over bone marrow mononuclear cells, as these need easier, shorter, and less invasive preparations as well as less ethical concerns and immunological problems. The efficacy of adipose-derived regenerative cell transplantation in the treatment of various diseases was examined in several clinical trials with favorable results. Currently, a multicenter study of therapeutic angiogenesis using these cells is being conducted in patients with critical limb ischemia. In conclusion, we expect that this method will soon be established as a treatment for cardiovascular diseases that have been refractory to conventional treatments.
The molecular understanding of super-enhancer dysregulation in cancer

Seiko Yoshino and Hiroshi I. Suzuki
pg(s) 216 - 229

<Abstract> - < PDF >

Abnormalities in the regulation of gene expression are associated with various pathological conditions. Among the distal regulatory elements in the genome, the activation of target genes by enhancers plays a central role in the formation of cell type–specific gene expression patterns. Super-enhancers are a subclass of enhancers that frequently contain multiple enhancer-like elements and are characterized by dense binding of master transcription factors and Mediator complexes and high signals of active histone marks. Super-enhancers have been studied in detail as important regulatory regions that control cell identity and contribute to the pathogenesis of diverse diseases. In cancer, super-enhancers have multifaceted roles by activating various oncogenes and other cancer-related genes and shaping characteristic gene expression patterns in cancer cells. Alterations in super-enhancer activities in cancer involve multiple mechanisms, including the dysregulation of transcription factors and the super-enhancer–associated genomic abnormalities. The study of super-enhancers could contribute to the identification of effective biomarkers and the development of cancer therapeutics targeting transcriptional addiction. In this review, we summarize the roles of super-enhancers in cancer biology, with a particular focus on hematopoietic malignancies, in which multiple super-enhancer alteration mechanisms have been reported.


Clinico-bacterial and prognostic factors in patients with suspected blood stream infection and elevated serum procalcitonin levels

Yoko Osamura, Hideki Nishiyama, Takuya Hattori, Masaharu Gunji and Norihiro Yuasa
pg(s) 230 - 246

<Abstract> - < PDF >

This study determined prognostic factors by comparing clinico-bacterial factors based on significant elevated serum procalcitonin levels in patients with suspected bloodstream infection (BSI). We retrospectively analyzed the medical records of 1,052 patients (age ≥16 years) with fever (temperature ≥38°C) and serum procalcitonin levels of ≥2.0 ng/mL, and blood culture results. The optimal cutoff value of the significant elevation of procalcitonin was determined using the minimum P-value approach. Clinico-bacterial factors were analyzed per the procalcitonin levels, and significant independent factors for short-term survival were investigated in 445 patients with BSI. Patients with suspected BSI were aged, on average, 72.3 ±15.1 years, and the incidence of positive blood culture was 42.3%; and the 14-day survival was 83.4%. Procalcitonin ≥100 ng/mL was the most significant predictor for survival. Multivariate analysis in patients with suspected BSI showed that estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors. Microorganisms were similar between patients with procalcitonin level 2–99 ng/mL (n=359) and those with ≥100 ng/mL (n=86). Multivariate analysis in patients with BSI showed that eGFR <30 mL/min/1.73 m2, procalcitonin ≥100 ng/mL, and primary infectious foci were significant independent prognostic factors. Patients with foci in the gastrointestinal tract and respiratory system had unfavorable 14-day survival. In conclusions, eGFR <30 mL/min/1.73 m2 and procalcitonin ≥100 ng/mL were significant independent unfavorable prognostic factors for suspected BSI. Primary infectious foci (gastrointestinal tract and respiratory system) were associated with unfavorable short-term survival in patients with positive blood culture.
Clinical characteristics and risk factors for mortality in patients with community-acquired staphylococcal pneumonia

Nancy Thabet, Yuichiro Shindo, Junya Okumura, Masahiro Sano, Toshihiro Sakakibara, Yasushi Murakami, Hironori Kobayashi, Hideo Saka, Masashi Kondo and Yoshinori Hasegawa, on behalf of the Central Japan Lung Study Group
pg(s) 247 - 259

<Abstract> - < PDF >

Staphylococcus aureus (S. aureus) is increasing in prevalence as a causative pathogen of community-acquired pneumonia (CAP). However, reports on the clinical features and mortality risk factors for S. aureus CAP are limited. We therefore aimed to identify the clinical characteristics and risk factors for mortality in these patients. We performed a post hoc and multivariate analysis of a multicenter prospective observational study that included adult hospitalized patients with S. aureus CAP. To elucidate the features of S. aureus CAP, we comparatively analyzed pneumococcal CAP (PCAP). We analyzed 196 patients with S. aureus CAP and 198 patients with PCAP. S. aureus CAP had a 30-day mortality of 16% (31/196) and a higher frequency of factors such as advanced age, comorbidities, poor functional ability, altered mental status, hypoalbuminemia, hyponatremia/hypernatremia, acidemia, and hypoxemia. In the multivariate analysis, the significant risk factors for mortality in S. aureus CAP were PaO2/FiO2 ≤250 [adjusted odds ratio (AOR), 3.29; 95% confidence interval (CI), 1.20–9.04] and albumin <3.0 g/dL (AOR, 2.41; 95% CI, 1.01–5.83). Non-ambulatory status tended to increase the risk (AOR, 2.40; 95% CI, 0.93–6.17). Methicillin resistance was not associated with mortality. In PCAP, hypoalbuminemia and non-ambulatory status affected mortality but hypoxemia did not. In conclusion, patients with S. aureus CAP have distinct clinical features, and their mortality risk factors can include hypoxemia and hypoalbuminemia. Physicians should recognize that the factors influencing mortality might differ somewhat among causative pathogens, and appropriate management should be performed after obtaining information on the causative pathogen.
Investigation of OLIG2 as a candidate gene for schizophrenia and autism spectrum disorder

Sho Furuta, Branko Aleksic, Yoshihiro Nawa, Hiroki Kimura, Itaru Kushima, Kanako Ishizuka, Hidekazu Kato, Miho Toyama, Yuko Arioka, Daisuke Mori, Mako Morikawa, Toshiya Inada and Norio Ozaki
pg(s) 260 - 268

<Abstract> - < PDF >

A number of genomic mutations that are thought to be strongly involved in the development of schizophrenia (SCZ) and autism spectrum disorder (ASD) have been identified. Abnormalities involving oligodendrocytes have been reported in SCZ, and as a related gene, oligodendrocyte lineage transcription factor 2 (OLIG2) has been reported to be strongly associated with SCZ. In this study, based on the common disease–rare variant hypothesis, target sequencing of candidate genes was performed to identify rare mutations with a high effect size and the possibility that the identified mutations may increase the risks of SCZ and ASD in the Japanese population. In this study, the exon region of OLIG2 was targeted; 370 patients with SCZ and 192 with ASD were subjected to next-generation sequencing. As a result, one rare missense mutation (A33T) was detected. We used the Sanger method to validate this missense mutation with a low frequency (<1%), and then carried out a genetic association analysis involving 3299 unrelated individuals (1447 with SCZ, 380 with ASD, and 1472 healthy controls) to clarify whether A33T was associated with SCZ or ASD. A33T was not found in either case group, and in only one control. We did not find evidence that p.A33T is involved in the onset of ASD or SCZ; however, associations with this variant need to be evaluated in larger samples to confirm our results.
Radiomics analysis for differentiating of cervical lymphadenopathy between cancer of unknown primary and malignant lymphoma on unenhanced computed tomography

Hayato Tomita, Tsuneo Yamashiro, Gyo Iida, Maho Tsubakimoto, Hidefumi Mimura and Sadayuki Murayama
pg(s) 269 - 285

<Abstract> - < PDF >

To investigate the usefulness of texture analysis to discriminate between cervical lymph node (LN) metastasis from cancer of unknown primary (CUP) and cervical LN involvement of malignant lymphoma (ML) on unenhanced computed tomography (CT). Cervical LN metastases in 17 patients with CUP and cervical LN involvement in 17 patients with ML were assessed by 18F-FDG PET/CT. The texture features were obtained in the total cross-sectional area (CSA) of the targeted LN, following the contour of the largest cervical LN on unenhanced CT. Values for the max standardized uptake value (SUVmax) and the mean SUV value (SUVmean), and 34 texture features were compared using a Mann-Whitney U test. The diagnostic accuracy and area under the curve (AUC) of the combination of the texture features were evaluated by support vector machine (SVM) with nested cross-validation. The SUVmax and SUVmean did not differ significantly between cervical LN metastases from CUP and cervical LN involvement from ML. However, significant differences of 9 texture features of the total CSA were observed (p = 0.001 – 0.05). The best AUC value of 0.851 for the texture feature of the total CSA were obtained from the correlation in the gray-level co-occurrence matrix features. SVM had the best AUC and diagnostic accuracy of 0.930 and 84.8%. Radiomics analysis appears to be useful for differentiating cervical LN metastasis from CUP and cervical LN involvement of ML on unenhanced CT.
Changes in perioperative C-reactive protein levels in patients with rheumatoid arthritis undergoing total knee arthroplasty in the biologic era

Kenji Kishimoto, Shuji Asai, Nobunori Takahashi, Kenya Terabe, Yasumori Sobue, Tsuyoshi Nishiume, Mochihito Suzuki, Naoki Ishiguro and Toshihisa Kojima
pg(s) 286 - 300

<Abstract> - < PDF >

This study aimed to investigate changes in and factors associated with perioperative serum C-reactive protein (CRP) levels in rheumatoid arthritis (RA) patients undergoing total knee arthroplasty (TKA) in the biologic era. A total of 173 patients (228 knees) with RA underwent elective primary TKA at our institute between January 1, 2006 and December 31, 2018. Of these, 214 cases among 161 patients were examined in this retrospective study after excluding 3cases among 3 patients who developed postoperative complications and 11 cases among 9 patients who were treated with tocilizumab. Factors associated with changes in CRP levels between baseline (preoperative) and day 7 after TKA [ΔCRP (0–7days)] were assessed by multiple regression analysis. Median (interquartile range) CRP levels were 0.69 (0.21, 1.82) mg/dl preoperatively, 5.66 (4.21, 7.61) mg/dl on postoperative day 1, 12.75 (9.79, 16.74) mg/dl on postoperative days 3–4, 3.26 (2.21, 4.85) mg/dl on postoperative day 7, and 0.87 (0.45, 1.81) mg/dl on postoperative day 14. Multivariate regression analysis revealed that body mass index ≥25 [partial regression coefficient (B)=1.03, P=0.012] and use of glucocorticoids (B=–0.86, P=0.017) were independently associated with ΔCRP (0–7days), whereas use of methotrexate and targeted drug modifying antirheumatic drugs and preoperative CRP levels (an objective biomarker of RA activity) were not. In conclusion, serum CRP levels increased rapidly after TKA and peaked on postoperative days 3–4, followed by a return to preoperative levels by postoperative day 14 in patients with RA. Obesity and the use of glucocorticoids were independently associated with changes in CRP levels.
Recurrence of Overdose Suicide Attempt index: a novel scoring system for predicting the recurrence of intentional overdose

Masayuki Hirose, Daisuke Kasugai, Kousuke Tajima, Hiroshi Takahashi, Shigeki Yamada and Akihiko Hirakawa
pg(s) 301 - 310

<Abstract> - < PDF >

Repeated suicide attempts through intentional overdose are not infrequent, but little is known about the risk factors associated with intentional overdose. We investigated these risk factors within 1 year of discharge from hospital and developed an index predicting recurrence. This retrospective observational study included 419 patients admitted to our hospital between 2011 and 2018 due to intentional overdose. Of these, 43 (10.0%) repeated an overdose within 1 year of discharge. The risk factors with the highest odds ratios from multivariate logistic regression analyses were used to develop an index assessing Recurrence of Overdose Suicide Attempt. The following variables were significantly associated with recurrence and were included in the index: anxiety and/or insomnia at discharge; use of five or more psychotropic medications; diagnosis of an ICD-F4 anxiety disorders; and female sex (odds ratios: 4.24; 5.52; 2.41; and 3.41, respectively). The area under the receiver operating characteristic curve of the index was 0.797. Sensitivity, specificity, and positive and negative predictive values for Recurrence of Overdose Suicide Attempt >4 points (out of 6) were 72.1%, 75.8%, 25.4%, and 96.0%, respectively. Our novel index predicted the recurrence of intentional overdose with a good negative predictive value and may therefore be a useful screening tool for this high-risk population.
Validity of a fall risk assessment score sheet for patients hospitalized in general wards

Tetsuo Hagino, Satoshi Ochiai, Shinya Senga, Takashi Yamashita, Masanori Saito, Masanori Wako, Naofumi Taniguchi, Takashi Ando and Hirotaka Haro
pg(s) 311 - 318

<Abstract> - < PDF >

Falls (including fall on same level and fall to a lower level) are frequent medical accidents among hospitalized patients. We investigated the status of falls in our hospital, aiming to verify the usefulness of a fall risk assessment sheet and identify the risk factors of falls. 5219 patients who were admitted to the general wards of our hospital between April 2016 and March 2019 were studied. Patient background data and the result of risk assessment based on a fall risk assessment score sheet at admission were registered. The frequency and location of falls during hospitalization, and the impact on patients were investigated. Risk factors for falls were analyzed based on the assessment results at admission. 218 falls occurred during hospitalization in 152 of 5219 patients (2.9%). The most common location of falls was bedside (68%). Falls occurred at night in 28%. The impact of falls was level 1 in 18 patients, level 2 in 117, level 3a in 11, and level 3b in 6 (all had head injuries, and one had concurrent fracture). Fall rate was 1.1% (41/3791 patients) at risk level I, 6.8% (91/1335 patients) at level II, and 21.5% (20/93 patients) at level III. Multiple logistic regression analysis identified age, history of fall, tendency to act without pressing nurse call button, unstable gait, unstable when standing, and use of narcotic as risk factors of falls. The incidence of falls at our hospital was lower compared to previous reports, and fall risk assessment was useful overall.
Risk factors for postoperative sore throat associated with i-gel™, a supraglottic airway device

Tomoya Taniguchi, Tasuku Fujii, Nanako Taniguchi and Kimitoshi Nishiwaki
pg(s) 319 - 326

<Abstract> - < PDF >

i-gel™ is a supraglottic airway device widely used for airway management during general anesthesia as an alternative to tracheal intubation. It sometimes results in a sore throat postoperatively; however, the risk factors for a postoperative sore throat caused by i-gel remain unclear. Here, we clarify the risk factors for a postoperative sore throat associated with i-gel insertion. We retrospectively reviewed the data of 426 adult patients who received general anesthesia with i-gel at our institution from January 2018 to December 2019. The incidence of postoperative sore throat and intraoperative data (size of i-gel, number of insertion attempts, total insertion time, and dose of the neuromuscular blocker and opioid) were evaluated. Logistic regression analysis was performed to identify the risk factors. Postoperative sore throat following i-gel insertion occurred in 24/426 patients (5.6%). The insertion time was significantly associated with the incidence of postoperative sore throat in the univariate analysis, but not in the multivariate analysis (P=0.519). Increased doses of neuromuscular blockers before i-gel insertion (odds ratio [OR], 5.46; 95% confidence interval [CI], 1.50–19.80; P=0.001) and reduced doses of intraoperative fentanyl (OR, 0.51; 95% CI, 0.28–0.93; P=0.028) were risk factors in the univariate and multivariate analyses. In the subgroup that used neuromuscular blockers before i-gel insertion, only an increased dose of neuromuscular blocker (OR, 17.2; 95%, CI 1.06–280; P=0.046) was an associated risk factor in the univariate and multivariate analyses. Overall, increased doses of neuromuscular blockers before i-gel insertion could contribute to the development of postoperative sore throat.
Editors' Choice
Elective nodal irradiation versus involved field radiotherapy for limited disease small cell lung cancer: a single-institution experience

Gen Suzuki, Hideya Yamazaki, Norihiro Aibe, Koji Masui, Daisuke Shimizu, Takuya Kimoto, Shinsuke Nagasawa, Tadashi Takenaka, Norihisa Masai, Sho Watanabe, Sho Seri, Nagara Tamaki, Koichi Takayama and Kei Yamada
pg(s) 327 - 338

<Abstract> - < PDF >

Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with limited-disease small cell lung cancer (LD-SCLC). However, no solid consensus exists on their optimal target volume. The current study aimed to assess the clinical outcomes of patients with LD-SCLC who received definitive ENI or IFRT. A retrospective single-institution study of patients who received definitive radiotherapy between 2008 and 2020 was performed. All patients underwent whole-body positron emission tomography/computed tomography before three-dimensional conformal radiotherapy. Among the 37 patients analyzed, 22 and 15 received ENI and IFRT, respectively. The thoracic radiotherapy dose was mostly either 60 Gy in 30 fractions delivered in 2-Gy fractions once daily or 45 Gy in 30 fractions delivered in 1.5-Gy fractions twice daily. The median follow-up period was 21.4 months. A total of 12 patients (32%) experienced locoregional relapse: 10 within and 2 outside the irradiation fields. One patient in the IFRT group experienced isolated nodal failure. Differences in locoregional relapse-free, progression-free, and overall survival rates between ENI and IFRT were not significant. Overall, IFRT did not promote a significant increase in locoregional recurrence compared to ENI. Our findings suggested the utility of IFRT in standard clinical practice and support its use for patients with LD-SCLC.
Patient delay and health system delay of patients with newly diagnosed pulmonary tuberculosis in Mongolia, 2016–2017

Batmunkh Batbayar, Tetsuyoshi Kariya, Tsolmon Boldoo, Enkhtamir Purevdorj, Naranzul Dambaa, Yu Mon Saw, Eiko Yamamoto and Nobuyuki Hamajima
pg(s) 339 - 351

<Abstract> - < PDF >

Although diagnosis and treatment of tuberculosis (TB) have been improved in many countries, delays in the diagnosis and treatment remain problematic in resource-limited countries. This study aimed to identify factors affecting delays in TB care in Mongolia. Data on TB cases registered from January 2016 to December 2017 were obtained from the national registry of TB at the Department of TB Surveillance and Research in National Center for Communicable Disease. The total number of TB cases registered in these two years was 8,166, including 3,267 cases of newly diagnosed pulmonary TB. Pulmonary TB cases (1,836 males and 1,431 females) were analyzed to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Patient delays longer than the median (28 days) were significantly associated with patient age >32 years (aOR=1.31, 95%CI: 1.14–1.51), residence in areas other than Ulaanbaatar (aimags) (aOR=1.38, 95%CI: 1.20–1.59), and smear-negative (aOR=0.57, 95%CI: 0.47–0.69). Health system delays longer than the median (7 days) were significantly associated with patient age >32 years (aOR=1.16, 95%CI: 1.00–1.33), residence in aimags (aOR=0.82, 95%CI: 0.71–0.95), special facilities including a prison hospital (aOR=4.40, 95%CI: 2.42–7.83), registration in 2017 relative to 2016 (aOR=0.83, 95%CI: 0.71–0.95), and smear-negative (aOR=1.72, 95%CI: 1.42–2.07). Total delays longer than the median (45 days) were significantly associated with patient age >32 years (aOR=1.39, 95%CI: 1.21–1.60), residence in aimags (aOR=1.27, 95%CI: 1.11–1.47), and smear-negative (aOR=0.74, 95%CI: 0.62–0.90). To shorten the total delay, improvement of the access to medical facilities in aimags is necessary.
Editors' Choice
Very long-term clinical outcomes after percutaneous coronary intervention for complex vs non-complex lesions: 10-year outcomes following sirolimus-eluting stent implantation

Shuro Riku, Susumu Suzuki, Tsuyoshi Yokoi, Teruhiro Sakaguchi, Toshihiko Yamamoto, Yasushi Jinno, Akihito Tanaka, Hideki Ishii, Yasuya Inden and Toyoaki Murohara
pg(s) 352 - 365

<Abstract> - < PDF >

Few studies have reported the long-term outcomes (>10 years) following first-generation drug-eluting stent implantation. In this single-center retrospective study, we investigated the very long-term clinical outcomes after first-generation sirolimus-eluting stent (SES) implantation in patients with complex lesions. The study included 383 consecutive patients who underwent initial SES implantation between July 2004 and January 2006; 84 and 299 of these patients reported a history of percutaneous coronary intervention (PCI) for complex and noncomplex lesions, respectively. Complex PCI was defined as having at least one of the following features: left main trunk PCI, implantation of ≥3 stents, bifurcation lesions with implantation of 2 stents, total stent length >60 mm, or chronic total occlusion. The target lesion revascularization (TLR) rate was significantly higher in the complex PCI than in the noncomplex PCI group (29.4% vs 13.0%, P=0.001), and we observed a significant intergroup difference in the late TLR (>1 year) rates (21.6% vs 9.5%, P=0.008). Late TLR continued over 10 years at a rate of 2.4%/year in the complex PCI and 1.1%/year in the noncomplex PCI group. Cox regression analysis revealed that complex PCI was related to TLR both over 10 years (hazard ratio 2.29, P=0.003) and beyond 1 year (hazard ratio 2.32, P=0.01). Cardiac death was more common in the complex PCI than in the noncomplex PCI group, particularly 4 years after PCI (15.8% vs 7.5%, P=0.031). Sudden death was the major cause of cardiac death beyond 4 years in the complex PCI group. These data indicate that long-term careful follow-up is essential for patients implanted with SES, especially those treated for complex lesions.
Efficacy of semi-solidification of enteral nutrients for postoperative nutritional management with a nasogastric tube

Kazuto Okabe, Ryuji Kaneko, Takamasa Kawai, Yuya Ohta, Go Ohara and Hideharu Hibi
pg(s) 366 - 373

<Abstract> - < PDF >

Postoperative nutritional management with a nasogastric tube is often used to prevent malnutrition after oral and maxillofacial surgery. However, enteral nutrients (EN) may cause various complications due to their liquid formulation. In this study, we retrospectively evaluated the efficacy of semi-solid EN with a xanthan gum thickener through a nasogastric tube and examined patients’ complications, nutritional status, and quality of life. We established two groups: an L group (n=20) to which we administered liquid EN, and an SS group (n=20) to which we administered semi-solidified EN. The primary outcome was the occurrence of gastrointestinal complications. The secondary outcome was a change in nutritional status based on body weight and controlling nutritional status. The other outcome was the improvement in the patients’ quality of life, assessed by the administration time. During nutritional management with a nasogastric tube, the median daily administration time in the L group was 9.0 hours, and 9 patients experienced diarrhea. In the SS group, the median daily feeding time was 2.3 hours, and only 2 patients experienced diarrhea. Both groups exhibited a decrease in body weight while controlling nutritional status scores were maintained. Semi-solidification of EN may be useful for postoperative nutritional management after oral and maxillofacial surgery by reducing complications, maintaining nutritional status, and shortening administration time.
Impact of socioeconomic status and sibling number on the prevalence of Helicobacter pylori infection: a cross-sectional study in a Japanese population

Moaz Elshair, Tomotaka Ugai, Isao Oze, Yumiko Kasugai, Yuriko N. Koyanagi, Kazuo Hara, Hidemi Ito and Keitaro Matsuo
pg(s) 374 - 387

<Abstract> - < PDF >

Helicobacter pylori infection is a significant risk factor for gastric cancer. The infection is acquired mainly in early childhood and is influenced by environmental factors, including socioeconomic status and sibling number. However, the impact of socioeconomic status and sibling number on Helicobacter pylori infection has not been well studied in Japan. We conducted a cross-sectional study to evaluate the impact of socioeconomic status, represented by education level, and sibling number on the prevalence of Helicobacter pylori infection among 3,423 non-cancer subjects who visited Aichi Cancer Center between 2005 and 2013. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a logistic regression model adjusted for potential confounding variables. Of the 3,423 subjects, 1,459 (42.6%) were Helicobacter pylori-positive. The prevalence of Helicobacter pylori infection linearly decreased with increasing socioeconomic status [ORs (95% CIs) of moderate and high socioeconomic status relative to low socioeconomic status of 0.67 (0.53–0.84) and 0.43 (0.34–0.54), respectively; P trend=9.7×10–17 ]. In contrast, the prevalence of Helicobacter pylori infection linearly increased with increasing sibling number [ORs (95% CIs) of SN 3–4 and ≥5 relative to sibling number ≤2 of 1.74 (1.47–2.06) and 2.54 (2.12–3.04), respectively; P trend=1.2×10–24 ]. This study showed that socioeconomic status and sibling number were significantly associated with the prevalence of Helicobacter pylori infection.
Tolerability of neoadjuvant chemotherapy for esophageal cancer in elderly patients over 76 years of age

Takafumi Suzuki, Yusuke Ishibashi, Hironori Tsujimoto, Hidekazu Sugasawa, Kotaro Wakamatsu, Keita Kouzu, Yujiro Itazaki, Takao Sugihara, Manabu Harada, Nozomi Ito, Yoji Kishi and Hideki Ueno
pg(s) 388 - 401

<Abstract> - < PDF >

Although the Japan Clinical Oncology Group trial demonstrated that neoadjuvant chemotherapy (NAC) with 5-fluorouracil plus cis-diamminedichloroplatinum had significant survival benefits, it excluded elderly patients aged ≥ 76 years. Therefore, our study aimed to evaluate the tolerability of NAC in elderly patients with esophageal cancer. Classified 174 patients with clinical stage II/III esophageal cancer who underwent esophagectomy from 2010 to 2020 into the E (aged ≥ 76 years; 55 patients) and Y (aged < 76; 119 patients) groups, and retrospectively investigated for clinicopathological findings, tolerability of NAC, relative dose intensity (RDI) and short- and long-term result. Patients who received NAC were fewer in the E group than in the Y group (51% vs 77%, p = 0.001). The E group had relatively lower completion rate of NAC (71% vs 85%, p = 0.116) and significantly lower mean RDI of 5-fluorouracil and cis-diamminedichloroplatinum than the Y group (73% vs 89%, p < 0.001). However, histological and radiological were comparable between both groups. Severe adverse events (grade ≥ 3) were relatively frequent (E, 42.9%; Y, 27.5%, p = 0.091), especially, neutropenia was significantly more frequent in the E group (25.0% vs 7.7%, p = 0.022). There were no differences in the incidence of postoperative complications between with and without NAC in both E and Y groups. Elderly patients with esophageal cancer might be more susceptible to toxicity of NAC. Hence, adequate case selection and careful of dose reduction are needed for elderly with esophageal cancer.
Development of a Vietnamese version of the Revised Hasegawa’s Dementia scale

Thi Phuong Tran, Duy Cuong Nguyen, Thi Van Quy Dang, Thi Khuyen Tran, Phong Tuc Vu, Minh Hoang Vu, Thu Hang Le, Thu Nandar Saw, Su Myat Cho, Tetsuyoshi Kariya, Eiko Yamamoto, Nobuyuki Hamajima and Yu Mon Saw
pg(s) 402 - 417

<Abstract> - < PDF >

As the aging population grows worldwide, the problem of age-related health is becoming an important public health concern. Dementia is a devastating disease that places a significant physical, emotional, and financial burden on patients, their caregivers, and society. It is predicted to increase in developing countries. The Revised Hasegawa’s Dementia Scale (HDS-R) has been used in many Asian countries to measure cognitive function. However, there is still no Vietnamese version of the HDS-R. Therefore, this paper describes the development of the HDS-R scale and manual in Vietnamese language. Two Vietnamese researchers translated the HDS-R from English to Vietnamese. To confirm the accuracy of the translation, two other Vietnamese researchers conducted a back-translation. Another pair of Vietnamese researchers compared the back-translated English version to the original one. All six researchers discussed the inconsistencies between English HDS-R scale and manual and derived the most suitable version for the Vietnamese context. In Questions 4 and Question 7, we changed the words from “cherry blossom” and “train” to “daisy flower” and “bicycle” for the first option, and from “plum blossom” to “rose” for the second option. We also changed the expressions in some places in the manual to fit the Vietnamese language. Future studies are needed to validate this version to be able to access cognitive function in both clinical and public healthcare settings.
Change in ground reaction force parameters according to the frailty level of older women in the Timed Up and Go test

Yuji Hirano, Yasumoto Matsui, Tetsuya Nemoto, Susumu Ota, Yoji Yamada and Hidenori Arai
pg(s) 418 - 432

<Abstract> - < PDF >

As older people become frail, they tend to fall more easily. Moreover, women have a higher rate of falls than men. However, effective strategies to avoid elderly women falling are lacking. The Timed Up and Go test is a well-known indicator of falling tendency. This study clarifies the motor elements related to the Timed Up and Go test according to the degree of weakness in older outpatients to specify exercise intervention to improve weakness and prevent falls. Participants were 145 female outpatients who visited the Locomo-Frail outpatient clinic, classified into three groups (robust, prefrail, and frail, according to the definition of the Japanese Cardiovascular Health Study. Vertical ground reaction force parameters were measured for all participants when they stood up from a chair, walking speed, and the Timed Up and Go test. Results showed that walking speed is related to the Timed Up and Go test in the robust group; balance ability is related to the Timed Up and Go test in the prefrail group; and instantaneous force is related to the Timed Up and Go test in the frail group. These results suggest that weakness can be improved by performing exercise interventions of balance and instantaneous force elements in the prefrail and frail groups, respectively.
Redox status biomarkers in the fast-twitch extensor digitorum longus resulting from the hypoxic exercise

Eda Ağaşcıoğlu, Rıdvan Çolak and Ufuk Çakatay
pg(s) 433 - 447

<Abstract> - < PDF >

The fast-twitch muscle may be affected from over-produced reactive oxygen species (ROS) during hypoxia/hypoxic exercise. The study aims to investigate redox status biomarkers in the fast-twitch extensor digitorum longus (EDL) muscle after hypoxic exercise. Male Sprague Dawley rats (eight-week-old) were randomly divided into six groups of the experimental “live high train high (LHTH), live high train low (LHTL) and live low train low (LLTL)” and their respective controls. Before the EDLs’ extraction, the animals exercised for a 4-week familiarization period, then they exercised for four-weeks at different altitudes. The LHTH group had higher ratios of lipid hydroperoxides (LHPs) than the experimental groups of LHTL (p=0.004) and LLTL (p=0.002), while having no difference than its control ‘LH’. Similarly, a higher percentage of advanced oxidation protein products (AOPP) was determined in the LHTH than the LHTL (p=0.041) and LLTL (p=0.048). Furthermore, oxidation of thiol fractions was the lowest in the LHTH and LH. However, redox biomarkers and thiol fractions illustrated no significant change in the LHTL and LLTL that might ensure redox homeostasis due to higher oxygen consumption. The study shows that not hypoxic exercise/exercise, but hypoxia might itself lead to a redox imbalance in the fast-twitch EDL muscle.


Underlying cause of death at medical facilities in Xaiyabouli Province, Lao People’s Democratic Republic

Bounbouly Thanavanh, Singkham Hackpaserd, Souphalak Inthaphatha, Tetsuyoshi Kariya, Yunosuke Suzuki, Eiko Yamamoto and Nobuyuki Hamajima
pg(s) 448 - 461

<Abstract> - < PDF >

In Lao PDR, Ministry of Health introduced District Health Information Software 2 (DHIS2) in 2013. Although DHIS2 includes cause of death, Lao government did not request to report cause of death through DHIS2, resulting in no information on frequency of underlying cause of death even for the deaths at medical facility. This study aimed to collect the information on the underlying cause of death at all medical facilities in Xaiyabouli province, a rural area in Lao PDR. As well as the point estimate of the proportion, a 95% confidence interval (CI) based on a binomial distribution was calculated for each cause of death. According to the local government request, 226 deaths (128 males and 98 females) in 2019 were reported from all medical facilities in the province. Among them, infectious diseases were the most frequent (33.6%, 95% CI 27.5–40.2%); sepsis (16.8%, 95% CI 12.2–22.3%), pneumonia (8.8%, 95% CI 5.5–13.3%), and meningitis (4.9%, 95% CI 2.5–8.5%). Heart diseases were 15.9% (95% CI 11.4–21.4%) including heart failure and myocardial infarction. Injury was 10.2% (95% CI 6.2–14.4%) including brain injury. Neonatal death was 10.6% (95% CI 6.9–15.4%). Among those, preterm death was common (8.8%, 95% CI 5.3–13.3%). Renal failure was 8.0% (95% CI 4.8–12.3%). According to civil registration covering all deaths both at facilities and outside facilities, deaths at facilities were 16.8% of the whole deaths (1,372 deaths) in Xaiyabouli province. Although deaths outside facilities were not included, this is the first report demonstrating cause of death in one province in Lao PDR.


Successful carotid artery stenting with a double-layer micromesh stent for spontaneous extracranial internal carotid artery dissection: a case report

Taro Okumura, Kenichi Hattori, Hisashi Hatano, Shigeru Fujitani, Kentaro Wada, Yoshiki Sato and Masahiro Wakabayashi
pg(s) 462 - 469

<Abstract> - < PDF >

Extracranial internal carotid artery dissection is a relatively rare disease in Japan. We herein report a case of a 60-year-old woman with spontaneous left internal carotid artery dissection with a dilated and dissected cavity. Following the identification and measurement of the true and false lumens using intravascular ultrasound, a double-layer micromesh stent (Casper stent; Microvention, Terumo, Tustin, CA, USA) was deployed for post-dilation. No perioperative complications were observed, and the patient was discharged on postoperative day 6.
Mantle cell lymphoma with aseptic meningitis mimicking hydrocephalus on brain imaging

Satoshi Samizo , Katsuya Furukawa and Hiroyuki Umegaki
pg(s) 470 - 476

<Abstract> - < PDF >

An 83-year-old man underwent head computed tomography (CT) to investigate cognitive decline and gait disturbance and was admitted to undergo a cerebrospinal fluid (CSF) tap test for suspected idiopathic normal-pressure hydrocephalus. He had a history of chemotherapy for mantle cell lymphoma (MCL), but CT on admission showed no evidence of recurrence. After admission, his level of consciousness rapidly deteriorated and CSF examination suggested infiltration of MCL into the central nervous system (CNS). Although CNS involvement in MCL is rare, this case demonstrates that even if recurrence of MCL is not suspected based on CT findings.
Embolization using patient-specific vascular models created by a 3D printer for difficult cases: a report of two cases

Tomohiro Komada, Takeshi Kamomae, Masaya Matsushima, Ryota Hyodo and Shinji Naganawa
pg(s) 477 - 483

<Abstract> - < PDF >

With the widespread use of three-dimensional printers, organ models created by these printers are now being used in the medical field for preoperative planning of surgeries. In this article, we report two cases in which embolization was expected to be difficult, and the three-dimensional printer-based vascular modeling was helpful in planning the surgery. The first case involved an aneurysm of the splenic artery. We attempted to embolize the aneurysm but were unable to advance the catheter into the distal artery and discontinued the procedure. The second case was a perianal varicose vein, which was initially treated with percutaneous transhepatic obliteration but was recanalized and required embolization. However, we expected difficulty in selecting the inferior mesenteric vein. In both cases, the vascular models were created using a 3D printer from the patients’ computed tomography images. Preoperative planning, including treatment simulation, was based on these models. The time required to print a three-dimensional vascular model was approximately 12 hours at a cost of less than $10 each. Patient-specific vascular models using a three-dimensional printer can be a simple and inexpensive tool that can increase the success of embolization in difficult cases.