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PurposeThe purpose of this study was to assess whether the anesthetic type is associated with the prognosis of pathological stage I non-small cell lung cancer (NSCLC).MethodsClinicopathological data from 431 consecutive patients who underwent lobectomy for NSCLC between 2010 and 2016 were collected. Patients were classified into groups according to the type of anesthesia: propofol-based total intravenous anesthesia (TIVA) or inhalation anesthesia (INHA). We investigated the prognostic differences between these two groups.ResultsA total of 72 patients in the TIVA group and 158 patients in the INHA group were eligible for the analysis. Recurrence was observed in 4 (5.6%) patients in the TIVA group and 19 (12.0%) patients in the INHA group (P = 0.159), and all-cause death occurred in 4 (5.6%) patients in the TIVA group and 24 (15.2%) patients in the INHA group (P = 0.049). The 5-year recurrence-free survival (RFS) and overall survival rates of the TIVA/INHA groups were 91.7%/77.4% and 94.4%/83.5%, respectively. TIVA was associated with a significantly better prognosis. A multivariable analysis of factors associated with RFS revealed that the type of anesthesia as a significant prognostic factor (P = 0.047).ConclusionPropofol-based TIVA was associated with a better prognosis in comparison to INHA in patients with surgically resected pathological stage I NSCLC.

Background Endoscopic resection (ER) has been accepted as minimally invasive treatment in patients with early gastric cancer (EGC) who have a negligible risk of lymph node metastasis. It has already been determined which lesions in differentiated-type EGC present a negligible risk of lymph node metastasis, and ER is being performed for these lesions. In contrast, no consensus has been reached on which lesions in undifferentiated-type (UD-type) EGC present a negligible risk for lymph node metastasis, nor have indications for ER for UD-type EGC been established. Methods We investigated 3843 patients who had undergone gastrectomy with lymph node dissection for solitary UD-type EGC at the Cancer Institute Hospital, Tokyo, and the National Cancer Center Hospital, Tokyo. Seven clinicopathological factors were assessed for their possible association with lymph node metastasis. Results Of the 3843 patients, 2163 (56.3%) had intramucosal cancers and 1680 (43.7%) had submucosal invasive cancers. Only 105 (4.9%) intramucosal cancers compared with 399 (23.8%) submucosal invasive cancers were associated with lymph node metastases. By multivariate analysis, tumor size 21 mm or more, lymphatic-vascular capillary involvement, and submucosal penetration were independent risk factors for lymph node metastasis (P < 0.001, respectively). None of the 310 intramucosal cancers 20 mm or less in size without lymphatic- vascular capillary involvement and ulcerative findings was associated with lymph node metastases (95% confidence interval, 0-0.96%). Conclusion UD-type intramucosal EGC 20 mm or less in size without lymphatic-vascular capillary involvement and ulcerative findings presents a negligible risk of lymph node metastasis. We propose that in this circumstance ER could be considered.

Asthma exacerbation impairs the quality of life of pediatric patients and negatively impacts future respiratory function and health economics. Several risk factors associated with exacerbations have been identified; however, most studies report the risk of each factor. Therefore, this study aimed to evaluate the risk of each factor and a combination of factors. We performed a retrospective cohort study using Japanese claims data and extracted factors associated with exacerbations using multivariate Cox proportional hazards regression and stepwise method. Risk scores were then calculated from the extracted factors and validated by tenfold cross validation. Of the 1,748,111 asthma patients in the database, the data of 14,980 were extracted, and 1988 (13.3%) had exacerbation. Factors associated with asthma exacerbation were age of 3–5 years, exacerbation history before cohort entry date, allergic rhinitis, chronic sinusitis, otitis externa, blepharitis, upper respiratory infections, urticaria, LTRA prescription, were determined. A four-level risk score was calculated from 9-factors and the AUC derived from cross validation was 0.700. Most factors extracted in our study are consistent with those of previous studies. We showed that combining each factor is more helpful in assessing the increased risk of asthma exacerbation than assessing each factor alone.

Background Patients with hip fractures are increasing in Japan, and lack of activities due to the fractures can significantly affect their mental health. However, the association between depressive symptoms and mortality in patients with hip fractures remains unclear because of conflicting evidence. This study aimed to evaluate whether depressive symptoms in Japanese patients after hip fracture surgery affect patient survival rates. Methods Data were obtained from a cohort study on postoperative fragility fracture at the Teikyo University Hospital that included individuals who underwent hip fracture surgery between May 2018 and November 2020. Depressive symptoms were assessed using the postoperative Patient Health Questionnaire (PHQ)-9 score. Logistic regression analysis and the Cox proportional hazards model were used to analyze the effect of depressive symptoms on survival. Results In total, 175 patients were included, of whom 130 (76.2%) were female, with a mean age of 79.8 (± 10.3) years. A high PHQ-9 score was associated with worse 6-month survival (odds ratio 1.15 [1.05–1.27], p  = 0.004; and hazard ratio 1.11 [1.00-1.23], p  = 0.057). Conclusions Postoperative depressive symptoms are associated with worse prognosis in patients with hip fractures.

Although postcapillary pulmonary hypertension (PH) is an important prognostic factor for patients with heart failure (HF), its pathogenesis remains to be fully elucidated. To elucidate the different roles of Rho-kinase isoforms, ROCK1 and ROCK2, in cardiomyocytes in response to chronic pressure overload, we performed transverse aortic constriction (TAC) in cardiac-specific ROCK1-deficient (cROCK1 −/−) and ROCK2-deficient (cROCK2 −/−) mice. Cardiomyocyte-specific ROCK1 deficiency promoted pressure-overload-induced cardiac dysfunction and postcapillary PH, whereas cardiomyocyte-specific ROCK2 deficiency showed opposite results. Histological analysis showed that pressure-overload-induced cardiac hypertrophy and fibrosis were enhanced in cROCK1 −/− mice compared with controls, whereas cardiac hypertrophy was attenuated in cROCK2 −/− mice after TAC. Consistently, the levels of oxidative stress were up-regulated in cROCK1 −/− hearts and down-regulated in cROCK2 −/− hearts compared with controls after TAC. Furthermore, cyclophilin A (CyPA) and basigin (Bsg), both of which augment oxidative stress, enhanced cardiac dysfunction and postcapillary PH in cROCK1 −/− mice, whereas their expressions were significantly lower in cROCK2 −/− mice. In clinical studies, plasma levels of CyPA were significantly increased in HF patients and were higher in patients with postcapillary PH compared with those without it. Finally, high-throughput screening demonstrated that celastrol, an antioxidant and antiinflammatory agent, reduced the expressions of CyPA and Bsg in the heart and the lung, ameliorating cardiac dysfunction and postcapillary PH induced by TAC. Thus, by differentially affecting CyPA and Bsg expressions, ROCK1 protects and ROCK2 jeopardizes the heart from pressure-overload HF with postcapillary PH, for which celastrol may be a promising agent.

We provide an overview of the physiological roles of aldehyde reductase (AKR1A) and also discuss the functions of aldose reductase (AKR1B) and other family members when necessary. Many types of aldehyde compounds are cytotoxic and some are even carcinogenic. Such toxic aldehydes are detoxified via the action of AKR in an NADPH-dependent manner and the resulting products may exert anti-diabetic and anti-tumorigenic activity. AKR1A is capable of reducing 3-deoxyglucosone and methylglyoxal, which are reactive intermediates that are involved in glycation, a non-enzymatic glycosylation reaction. Accordingly, AKR1A is thought to suppress the formation of advanced glycation end products (AGEs) and prevent diabetic complications. AKR1A and, in part, AKR1B are responsible for the conversion of d-glucuronate to l-gulonate which constitutes a process for ascorbate (vitamin C) synthesis in competent animals. AKR1A is also involved in the reduction of S-nitrosylated glutathione and coenzyme A and thereby suppresses the protein S-nitrosylation that occurs under conditions in which the production of nitric oxide is stimulated. As the physiological functions of AKR1A are currently not completely understood, the genetic modification of Akr1a could reveal the latent functions of AKR1A and differentiate it from other family members.

We analyse the relationship between population influx and the effective reproduction number in the 23 wards of Tokyo during the COVID-19 pandemic to estimate hotspots of infection. We identify some patterns of population influx via factor analysis and estimate specific areas as infection-related hotspots by focusing on influx patterns that are highly correlated with the effective reproduction number. As a result, several influx patterns are assumed to be directly related to the subsequent spread of the infection. This analytical method has the potential to detect unknown hotspots related to pandemics in the future.

Acute kidney injury (AKI) due to vitamin D therapy for osteoporosis is encountered in clinical practice, but epidemiological studies are scarce. We aimed to determine the association between AKI and vitamin D therapy and to identify risk factors for AKI using the Japanese Adverse Drug Event Report database. We used reporting odds ratios (RORs) to detect signals and evaluate risk factors using multiple logistic regression analysis. Among 298,891 reports from April 2004 to September 2023, 1071 implicated active vitamin D 3 analogs as suspect drugs for adverse events. There was a significant association between AKI and active vitamin D 3 analogs (ROR [95% confidence interval {CI}], eldecalcitol: 16.75 [14.23–19.72], P  < 0.001; alfacalcidol: 5.29 [4.07–6.87], P  < 0.001; calcitriol: 4.46 [1.88–10.59], P  < 0.001). The median duration of administration before AKI onset was 15.4 weeks. Multiple logistic regression analysis showed a significant association between AKI and age ≥ 70 years (odds ratio [95% CI], 1.47 [1.04–2.07]; P  = 0.028), weight < 50 kg (1.55 [1.12–2.13]; P  = 0.007), hypertension (1.90 [1.42–2.54]; P  < 0.001), and concomitant use of nonsteroidal anti-inflammatory drugs (1.58 [1.10–2.25], P  = 0.012) and magnesium oxide (1.96 [1.38–2.78]; P  < 0.001). Our results suggest that active vitamin D 3 analogs are associated with AKI development. Physicians prescribing these medications to patients with risk factors should consider the possibility of AKI, especially during the first 6 months.

Background There is a limited evidence for humidified high-flow nasal cannula (HHFNC) use on inter-hospital transport. Despite this, its use during transport is increasing in children with respiratory distress worldwide. In 2015 HHFNC was implemented on a specialized pediatric retrieval team serving for Victoria. The aim of this study is to investigate the effect of the HHFNC implementation on the retrieval team on the paediatric intensive care unit (PICU) length of stay and respiratory support use. Methods We performed a cohort study using a comparative interrupted time-series approach controlling for patient and temporal covariates, and population-adjusted analysis. We studied 3022 children admitted to a PICU in Victoria with respiratory distress January 2010–December 2019. Patients were divided in pre-intervention era (2010–2014) and post-intervention era (2015–2019). Results 1006 children following interhospital transport and 2016 non-transport children were included. Median (IQR) age was 1.4 (0.7–4.5) years. Pneumonia (39.1%) and bronchiolitis (34.3%) were common. On retrieval, HHFNC was used in 5.0% (21/420) and 45.9% (269/586) in pre- and post-intervention era. In an unadjusted model, median (IQR) PICU length of stay was 2.2 (1.1–4.2) and 1.7 (0.9–3.2) days in the pre- and post-intervention era in transported children while the figures were 2.4 (1.3–4.9) and 2.1 (1.2–4.5) days in non-transport children. In the multivariable regression model, the intervention was associated with the reduced PICU length of stay (ratio 0.64, 95% confidential interval 0.49–0.83, p  = 0.001) with the predicted reduction of PICU length of stay being − 10.6 h (95% confidential interval − 16.9 to − 4.3 h), and decreased respiratory support use (− 25.1 h, 95% confidential interval − 47.9 to − 2.3 h, p  = 0.03). Sensitivity analyses including a model excluding less severe children showed similar results. In population-adjusted analyses, respiratory support use decreased from 4837 to 3477 person-hour per year in transported children over the study era, while the reduction was 594 (from 9553 to 8959) person-hour per year in non-transport children. With regard to the safety, there were no escalations of respiratory support mode during interhospital transport. Conclusions The implementation of HHFNC on interhospital transport was associated with the reduced PICU length of stay and respiratory support use among PICU admissions with respiratory distress.

Aim Pelvic ring fractures (PRFs) due to high‐energy trauma often result in severe bleeding and high mortality. Pelvic circumferential compression devices (PCCD) are widely used to stabilize PRF and decrease bleeding. However, evidence supporting their effectiveness is still inconclusive. Methods We conducted an observational study using the Japan Trauma Data Bank (JTDB) from 2019 to 2021. Patients with blunt lower body trauma aged 15 years or older were included. We used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to evaluate the association of PCCD and mortality. Results Of the 74,393 patients in the database, 235 PCCD group and 23,429 control group were analyzed. After PSM, 231 patients in both groups were enrolled. Crude analysis indicated significantly higher in‐hospital mortality in the PCCD group (odds ratio (OR) = 3.8 [95% CI = 2.51–5.75]). However, PSM and IPTW analysis indicated that PCCD was associated with decreased in‐hospital mortality (PSM: OR = 0.79 [0.43–1.42]; IPTW: OR = 0.73 [0.62–0.86]). In a subgroup analysis of the IPTW analysis, PCCD fitting resulted in increased in‐hospital mortality in the group without PRF (OR = 2.08 [1.91–2.27]), a decrease in stable PRF (OR = 0.74 [0.6–0.91]), and a further decrease in unstable PRF (OR = 0.18 [0.12–0.27]). Additional factors, such as a fall from a height, a fall downstairs, and pre‐hospital PCCD placement also influenced the treatment effect. Conclusion The present, large, registry‐based study found that PCCD reduced mortality in patients with a lower body injury, especially those with an unstable PRF.