INVITED REVIEW ARTICLES
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.
ORIGINAL PAPERS
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.
NOTE
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.
CASE REPORTS
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.