Post-intensive care syndrome: Recent advances and future directions.

Post-intensive care syndrome comprises physical, cognitive, and mental impairments in patients treated in an intensive care unit (ICU). It occurs either during the ICU stay or following ICU discharge and is related to the patients' long-term prognosis. The same concept also applies to pediatric patients, and it can greatly affect the mental status of family members. In the 10 years since post-intensive care syndrome was first proposed, research has greatly expanded. Here, we summarize the recent evidence on post-intensive care syndrome regarding its pathophysiology, epidemiology, assessment, risk factors, prevention, and treatments. We highlight new topics, future directions, and strategies to overcome post-intensive care syndrome among people treated in an ICU. Clinical and basic research are still needed to elucidate the mechanistic insights and to discover therapeutic targets and new interventions for post-intensive care syndrome.

Anticoagulant therapies against sepsis-induced disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a frequent but lethal complication in sepsis. Anticoagulant therapies, such as heparin, antithrombin, activated protein C, and recombinant human-soluble thrombomodulin, were expected to regulate the progression of coagulopathy in sepsis. Although a number of randomized controlled trials (RCTs) have evaluated the survival effects of these therapies over the past few decades, there remains no consistent evidence showing a significant survival benefit of anticoagulant therapies. Currently, anticoagulant therapies are not conducted as a standard treatment against sepsis in many countries and regions. However, most of these RCTs were performed overall in patients with sepsis but not in those with sepsis-induced DIC, who were theoretically the optimal target population of anticoagulants. Actually, multiple lines of evidence from observational studies and meta-analyses of the RCTs have suggested that anticoagulant therapies might reduce mortality only when used in septic DIC. In addition, the severity of illness is another essential factor that maximally affects the efficacy of the therapy. Therefore, to provide evidence on the true effect of anticoagulant therapies, the next RCTs must be designed to enroll only patients with sepsis-induced overt DIC and a high severity of illness. To prepare these future RCTs, a novel scientific infrastructure for accurate detection of patients who can receive maximal benefit from anticoagulant therapies also needs to be established.

The potential diagnostic significance of crypt differentiation in gastric dysplasia.

AIMS: This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. METHODS AND RESULTS: The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. CONCLUSIONS: Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.

Interleukin-32 regulates downstream molecules and promotes the invasion of pancreatic cancer cells.

Pancreatic cancer is a malignant neoplasm with high invasiveness and poor prognosis. In a previous study, a highly invasive pancreatic cancer cell line was established and found to feature enhanced interleukin-32 (IL-32) expression. However, whether IL-32 promotes the invasiveness by enhancing or suppressing the expression of IL-32 through regulating downstream molecules was unclear. To investigate the effect of IL-32, cells were established with high levels of expression or downregulated IL-32; their invasive ability was measured using a real-time measurement system and the expression of some candidate downstream molecules involved in invasion was evaluated in the two cell types. The morphological changes in both cell types and the localization of IL-32 expression in pancreatic cancer tissues were studied using immunohistochemistry. Among the several splice variants of IL-32, cells transfected with the ε isoform had increased invasiveness, whereas the IL-32-suppressed cells had reduced invasiveness. Several downstream molecules, whose expression was changed in the two cell types, were monitored. Notably, changes of E-cadherin, CLDN1, CD44, CTGF and Wnt were documented. The morphologies of the two cell types differed from the original cell line. Immunohistochemically, the expression of IL-32 was observed only in tumor cells and not in normal pancreatic cells. In conclusion, IL-32 was found to promote the invasiveness of pancreatic cancer cells by regulating downstream molecules.

Utility of Ethylene-Diamine-Tetraacetic Acid Buffer Solution With Boric Acid for Immunostaining of Specimens Stored for an Extended Period.

Antigen modification and denaturation are recognized causes of false negatives in immunostaining. Specimens that have been stored for an extended period at room temperature show decreased immunoreactivity and may mislead the diagnosis. Studies of the molecular targeting of drugs often involve immunostaining of previous samples and, in some situations, only unstained specimens can be used. The present study aimed to develop an effective staining method to recover antigen activation in unstained specimens stored for an extended period by using ethylene-diamine-tetraacetic acid (EDTA) buffer solution with boric acid. We compared several commonly used antigen retrieval solutions and found that Tris-borate-EDTA (TBE) buffer solution with a pH ≥8.3 provided sufficient antigen retrieval. However, pH values higher than 8.3 (9.0, 10.0, and 11.0) frequently caused severe tissue damage. Thus, TBE with pH 8.3 was the most suitable antigen retrieval solution for recovering the antigenicity of specimens stored for an extended period. This procedure may allow useful immunohistochemical information, even from sections that have been stored for an extended period.

Establishment of highly invasive pancreatic cancer cell lines and the expression of IL-32.

Compared to tumors of other organs, pancreatic cancer is highly aggressive; with one of its biological features being that, despite a prominent fibrotic stroma, there is remarkable infiltration of tumor cells. This characteristic is considered to be the main reason for the poor prognosis of patients with pancreatic cancer. Therefore, in order to elucidate the factors that contribute to this high invasiveness, a selective invasion method was used to establish four highly invasive subclones from six human pancreatic cancer cell lines. The results demonstrated that two cell lines did not exhibit enhanced invasiveness. Microarray analysis revealed that, in the highly invasive cell lines, several genes were expressed at high levels, compared with the original cell lines. These highly expressed genes were recognized only in highly invasive cells. Among them, IL-32 was most strongly upregulated in the highly invasive cells, compared with cells with a low invasive potential, as well as the original cells. RT-qPCR and western blot analysis confirmed the high levels of expression of IL-32 in highly invasive cells at the RNA and protein levels. In addition, immunohistochemical analysis of resected surgical materials revealed that the tumor cells expressed IL-32 and, in particular, many IL-32 positive cells were seen at the invasive front of the tumor tissue. IL-32 is a cytokine that is widely involved in the development of cancer and has recently received considerable attention. This cytokine has multiple splice variants and shows a wide variety of behaviors, depending on the tumor type and primary organ. Although some hypotheses have been proposed to explain the activity of IL-32, a unified view has not been agreed. In the present study, through the establishment of highly invasive cells from pancreatic cancer and a comprehensive gene analysis, it is suggested that IL-32 may serve an important role as a molecule involved in the invasiveness of this neoplasm.

Intra-arterial infusion of fasudil hydrochloride to treat post-traumatic cerebral vasospasm.

BACKGROUND: The effect of intra-arterial infusion of fasudil hydrochloride in patients with post-traumatic cerebral vasospasm remains unclear. Here we report a case of intra-arterial infusion of fasudil hydrochloride for post-traumatic cerebral vasospasm. CASE PRESENTATION: A 47-year-old man was transferred to our hospital with a fractured skull and traumatic subarachnoid hemorrhage. As rhinorrhea of cerebrospinal fluid had not improved, repair surgery was carried out on day 4. Aphasia appeared on day 13. Magnetic resonance imaging and angiography showed an ischemic region in the left temporal lobe and vasospasm of the left middle cerebral artery. We immediately carried out angiography and diagnosed severe vasospasm of the M1 region of the left middle cerebral artery. After placing a microcatheter into the proximal middle cerebral artery, we injected fasudil hydrochloride intra-arterially. Vasospasm improved and aphasia resolved. CONCLUSION: In this case, intra-arterial infusion of fasudil hydrochloride was effective against post-traumatic cerebral vasospasm.

Sarcopenia Is Not a Prognostic Factor of Outcome in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy or Radiotherapy.

BACKGROUND/AIM: The objective of this study was to determine if sarcopenia was a predictor of poor prognosis in patients with cervical cancer (CC) undergoing concurrent chemoradiation therapy (CCRT) or radiation therapy (RT). MATERIALS AND METHODS: A total of 236 patients with CC undergoing CCRT or RT were retrospectively examined. We determined if clinical characteristics and survival were correlated with pretreatment sarcopenia, measured as psoas muscle index (PI) or skeletal muscle index (SMI). RESULTS: Pretreatment PI and SMI were related to parametrial involvement with CC undergoing CCRT or RT (p=0.002, and, p=0.034, respectively). The median progression-free survival (PFS) and overall survival (OS) times in patients undergoing CCRT or RT were 29.0 and 34.5 months, respectively. Neither PI nor SMI were prognostic predictors in patients with CC undergoing CCRT or RT. CONCLUSION: Sarcopenia is not a predictive factor of outcome in patients with CC undergoing CCRT or RT.

Comparison of accuracy of presepsin and procalcitonin concentrations in diagnosing sepsis in patients with and without acute kidney injury.

BACKGROUND: Levels of the biomarkers presepsin and procalcitonin are affected by renal function. We evaluated the accuracies of presepsin and procalcitonin levels for diagnosing sepsis in patients with and without acute kidney injury (AKI). METHODS: We evaluated patients with presepsin and procalcitonin data, and classified them into AKI and non-AKI groups based on the Kidney Disease Improving Global Outcomes criteria. Each group was then subdivided according to sepsis status for each stage of AKI. Receiver operating characteristic curve analyses were used to investigate the accuracies of biomarker levels for diagnosing sepsis. RESULTS: In the non-AKI group, the area under the curves (AUCs) for procalcitonin and presepsin levels were 0.897 and 0.880, respectively (p = .525) and optimal cut-off values were 0.10 ng/ml (sensitivity: 85.1%, specificity: 79.1%) and 240 pg/ml (sensitivity: 80.9%, specificity: 83.2%), respectively. In the stage 3 subgroup, the AUC for procalcitonin (0.946) was significantly higher than that for presepsin (0.768, p < .001). The optimal cut-off values for diagnosing sepsis were 4.07 ng/ml (sensitivity: 87.2%, specificity: 93.5%) for procalcitonin and 500 pg/ml (sensitivity: 89.7%, specificity: 59.7%) for presepsin. CONCLUSIONS: In patients with severe AKI, the accuracy of the diagnosis of sepsis with procalcitonin was significantly higher than with presepsin.

Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability.

BACKGROUND: The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. MATERIALS AND METHODS: A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). RESULTS: Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. CONCLUSIONS: This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

Tsumura-Suzuki obese diabetic mice-derived hepatic tumors closely resemble human hepatocellular carcinomas in metabolism-related genes expression and bile acid accumulation.

BACKGROUND AND AIMS: Tsumura-Suzuki obese diabetic (TSOD) is a good model of metabolic syndrome showing typical lesions found in nonalcoholic fatty liver disease and nonalcoholic steatohepatitis, and develops spontaneous hepatic tumors with a high frequency. Majority of the developing tumors overexpress glutamine synthetase (GS), which is used as a marker of hepatocellular carcinoma (HCC). The aim of this study is to assess the status of expression of metabolism-related genes and the level of bile acids in the TSOD mice-derived tumors and to determine the association with metabolic dysregulation between human HCC and TSOD mice-derived tumors. METHODS: GS-positive hepatic tumors or adjacent normal tissues from 71-week-old male TSOD mice were subjected to immunohistochemical staining, quantitative RT-PCR (qRT-PCR), quantitation of cholic acid and taurocholic acid. RESULTS: We found that downregulation of the rate-limiting enzyme for betaine synthesis (BADH), at both mRNA and protein levels in GS-positive TSOD mice-derived tumors. Furthermore, the bile acid receptor FXR and the bile acid excretion pump BSEP (Abcb11) were found to be downregulated, whereas BAAT and Akr1c14, involved in primary bile acid synthesis and bile acid conjugation, were found to be upregulated at mRNA level in GS-positive TSOD mice-derived tumors. BAAT and Akr1c14 were also overexpressed at protein levels. Total cholic acid was found to be increased in GS-positive TSOD mice-derived tumors. CONCLUSION: Our results strongly support the significance of TSOD mice as a model of spontaneously developing HCC.

Endoglin (CD105) and SMAD4 regulate spheroid formation and the suppression of the invasive ability of human pancreatic cancer cells.

In this study, we investigated the ability of pancreatic cancer cell lines to form spheroids with the aim of identifying factors involved in cell invasiveness, a property that leads to a poor prognosis in pancreatic cancer. For this purpose, 8 cell lines derived from human pancreatic cancer tissues were cultured in non-adherent culture conditions to form spheroids, as well as normal monolayers. The morphology of the cells was observed and spheroid diameters measured. mRNA expression was compared between cells cultured under both culture conditions. The gene knockdown of endoglin (ENG) and SMAD4, components of the transforming growth factor-ß (TGF-ß) signaling system, using siRNAs was conducted in spheroids in order to identify affected protein signaling factors, determine the morphological changes occurring over time and to measure the invasive capacity of the cells constituting spheroids. The cell lines exhibited differences in their spheroid-forming abilities. The expression of SMAD4 and ENG concomitantly increased in the cells that formed spheroids. SMAD4 was transported into the nucleus when spheroids were formed. The expression of ENG was decreased in the cells in which SMAD4 was knocked down; by contrast, the expression of BMP and activin membrane-bound inhibitor (BAMBI) and noggin (NOG), further components of the TGF-ß signaling system, increased. In the cells in which ENG was knocked down, the decreased mRNA expression of TGF-ß receptor type 2 (TGFBR2) and SMAD9 was observed, as well as a change in the expression of pSMAD1/5/9, and a tendency of spheroids to decrease in size. Spheroids cultured on Matrigel exhibited a tendency towards a reduction in size over time, as well as a tendency to invade into the Matrigel. In particular, the cells in which ENG was knocked down exhibited spheroids which were reduced in size, and also exhibited an increase in invasiveness, and a decrease in adhesiveness. Thus, our data indicate that in pancreatic cancer cells, the expression of ENG may be controlled by a pathway mediated by SMAD4. In addition, ENG was found to be related to the spheroid-forming ability of cells and to be involved in the invasive capacity of pancreatic cancer cells.

Sarcopenia Is an Important Prognostic Factor in Patients With Cervical Cancer Undergoing Concurrent Chemoradiotherapy.

OBJECTIVE: This study aimed to investigate the correlation of sarcopenia findings with prognostic factors in patients with cervical cancer (CC) undergoing concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively collected data on body composition and clinicopathological features from the medical records of 60 patients with CC who underwent CCRT and analyzed correlations between prognosis and changes in body composition as measured by computed tomography (skeletal muscle and iliopsoas muscle [IM]). Statistical analyses were performed using the Mann-Whitney U test. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. Cox proportional hazard regression was used for univariate and multivariate analyses. RESULTS: The median follow-up for all patients who were alive at the last follow-up was 33.5 months (range, 1-104 months). The PFS and OS rates were worse for patients with at least 15.0% than for those with less than 15.0% loss of skeletal muscle and IM from baseline (P < 0.001 for both). Furthermore, multivariate analyses showed that at least 15.0% loss of IM was an independent prognostic factor for PFS and OS (P = 0.002 for both). CONCLUSIONS: Sarcopenia (≥15.0% loss of IM from baseline) was revealed to be an important prognostic factor in patients with CC undergoing CCRT.

Efficacy of direct hemoperfusion with a polymyxin B-immobilized fiber column in miliary tuberculosis.

Case: A 75-year-old woman presented with a 10-day history of intermittent fever, general fatigue, and progressive dyspnea. Although she had a low PaO2/FIO2 ratio, the cause of acute respiratory distress syndrome was not clear until day 9 in hospital. Outcome: We treated the patient with direct hemoperfusion with a polymyxin B-immobilized fiber column incidentally; the PaO2/FIO2 ratio improved following this therapy. Acid-fast bacilli, which were not seen in the sputum on admission, were detected in cultures from sputum, urine, bone marrow, liver biopsy, and blood samples, with a real-time polymerase chain reaction assay confirming tuberculosis. She was immediately transferred to a specialized tuberculosis hospital, and after a 3-month treatment, was discharged. Conclusion: Treatment with polymyxin B-immobilized fiber column may provide good results for pulmonary oxygenation in acute respiratory distress syndrome caused by tuberculosis.

The Influence of Adverse Effects on Quality of Life of Survivors of Gynecologic Cancer.

OBJECTIVE: The objective of this observational study was to investigate correlations between adverse effects (lower-extremity lymphedema [LEL], dysuria, and severe gastrointestinal symptoms) and quality of life (QOL) (physical well-being [PWB], social well-being, emotional well-being [EWB], and functional well-being) before treatment, at least 6 weeks after treatment (posttreatment1), and 3 or 6 months after treatment (posttreatment2) of patients with gynecologic cancer (GC). METHODS: From August 2012 to October 2016, questionnaire responses and clinical data of 75 patients with GC were collected and assessed by treatment received. The χ test was used to determine the significance of correlations. RESULTS: Participants with LEL had significantly poorer QOL than did those without it in the domains of PWB at posttreatment1 (P = 0.026) and EWB at posttreatment2 (P = 0.020). Moreover, patients with 2 adverse effects (LEL plus dysuria or severe gastrointestinal symptoms) had significantly poorer QOL than did those with no or single adverse effect in the domains of PWB at posttreatment1 and posttreatment2 (posttreatment1: P = 0.049, P = 0.001; posttreatment2: P = 0.002, P = 0.028) and poorer QOL compared with those with no adverse effect in the domain of EWB at posttreatment1 (P = 0.017). CONCLUSIONS: Poorer QOL in emotional and physical domains is associated with adverse effects of treatment in patients with GC. It is important to consider the effects of radical therapy not only on survival but also on the QOL of survivors.

Facilitatory effect of insulin treatment on hepatocellular carcinoma development in diabetes.

BACKGROUND: To evaluate the effect of insulin treatment on the incidence and/or severity of hepatocellular carcinoma (HCC) in a mouse model of HCC based on diabetes. METHODS: We recently reported that neonatal streptozotocin (STZ) treatment causes type 1 diabetes and subsequent HCC in ddY, Institute for Animal Reproduction (DIAR) mice. Newborn male DIAR mice were divided into three groups based on STZ and insulin (INS) treatment. STZ was subcutaneously injected (60 mg/g) into the STZ-treated group (DIAR-nSTZ mice, N = 13) and the STZ/insulin-treated group (DIAR-nSTZ/INS mice, N = 20). A physiologic solution was injected into the control group (DIAR-control mice, N = 8) 1.5 days after birth. Insulin was subcutaneously injected into the DIAR-nSTZ/INS mice according to the following protocol: 2 IU/day at 4-5 weeks of age, 3 IU/day at 5-7 weeks of age, and 4 IU/day at 7-12 weeks of age. All mice were fed a normal diet and were subjected to physiological and histopathological assessments at 12 weeks of age. RESULTS: DIAR-nSTZ mice had significantly lower body weight and higher blood glucose levels than DIAR-control mice, whereas no significant differences were observed between DIAR-nSTZ/INS mice and control mice. At 12 weeks of age, lower weight of paratesticular fat and higher levels of total cholesterol, triglyceride, and free fatty acids were observed in DIAR-nSTZ mice compared to DIAR-control mice, whereas there were no significant differences between DIAR-nSTZ/INS mice and DIAR-control mice. In the livers of DIAR-nSTZ mice, HCC was observed in 15% of cases, and dysplastic nodules were observed in 77% of cases. In the livers of DIAR-nSTZ/INS mice, HCC was observed in 39% of cases and dysplastic nodules were observed in 61% of cases (p = 0.011). Moreover, the average tumor size was significantly larger in STZ/INS-treated mice than in STZ-treated mice. Immunohistochemical analysis demonstrated that the expression of ERK1/2, downstream substrates of insulin signaling that activate cell proliferation, was significantly higher in STZ/INS-treated mice compared to STZ-treated mice. CONCLUSIONS: Insulin treatment promoted, rather than inhibited, the progression of liver carcinogenesis in DIAR-nSTZ mice. Hyperinsulinemia rather than hyperglycemia can accelerate the progression of HCC via insulin signaling.

Pretreatment prognostic nutritional index is a significant predictor of prognosis in patients with cervical cancer treated with concurrent chemoradiotherapy.

This study investigated whether pretreatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and prognostic nutritional index (PNI) are prognostic factors in patients with cervical cancer who undergo concurrent chemoradiotherapy (CCRT) and radiotherapy (RT). A total of 131 patients who underwent CCRT and RT for cervical cancer were retrospectively investigated and the correlations of NLR, PLR and PNI with clinical parameters and prognosis were assessed in CCRT and RT. The CCRT and RT groups had a median progression-free survival (PFS) of 41.82 and 24.72 months, respectively, and an overall survival of 49.70 and 29.56 months, respectively. At a cut-off value of NLR≥2.85, the PFS and OS in patients with higher NLR undergoing RT were significantly shorter compared with those in patients with lower NLR (P=0.029 and P=0.017, respectively). At a cut-off value for PNI of ≤48.55 in patients undergoing CCRT and ≤45.80 in patients undergoing RT, the PFS and OS in patients with lower PNI were significantly shorter compared with those in patients with higher PNI (PFS and OS with CCRT, P<0.001 and P<0.001, respectively; PFS and OS with RT, P=0.002 and P=0.008, respectively). Multivariate analyses also identified low PNI as an independent prognostic factor for PFS and OS in patients receiving CCRT. Therefore, low PNI was shown to predict poor prognosis in patients with cervical cancer.

Augmented renal clearance in Japanese intensive care unit patients: a prospective study.

BACKGROUND: Augmented renal clearance (ARC) of circulating solutes and drugs has been recently often reported in intensive care unit (ICU) patients. However, only few studies on ARC have been reported in Japan. The aims of this pilot study were to determine the prevalence and risk factors for ARC in Japanese ICU patients with normal serum creatinine levels and to evaluate the association between ARC and estimated glomerular filtration rate (eGFR) calculated using the Japanese equation. METHODS: We conducted a prospective observational study from May 2015 to April 2016 at the emergency ICU of a tertiary university hospital; 111 patients were enrolled (mean age, 67 years; interquartile range, 53-77 years). We measured 8-h creatinine clearance (CLCR) within 24 h after admission, and ARC was defined as body surface area-adjusted CLCR ≥ 130 mL/min/1.73 m2. Multiple logistic regression analysis was performed to identify the risk factors for ARC. Moreover, a receiver operating curve (ROC) analysis, including area under the receiver operating curve (AUROC) was performed to examine eGFR accuracy and other significant variables in predicting ARC. RESULTS: In total, 43 patients (38.7 %) manifested ARC. Multiple logistic regression analysis was performed for age, body weight, body height, history of diabetes mellitus, Acute Physiology and Chronic Health Evaluation II scores, admission categories of post-operative patients without sepsis and trauma, and serum albumin, and only age was identified as an independent risk factor for ARC (odds ratio, 0.95; 95 % confidence interval [CI], 0.91-0.98). Moreover, the AUROC of ARC for age and eGFR was 0.81 (95 % CI, 0.72-0.89) and 0.81 (95 % CI, 0.73-0.89), respectively. The optimal cutoff values for detecting ARC were age and eGFR of ≤63 years (sensitivity, 72.1 %; specificity, 82.4 %) and ≥76 mL/min/1.73 m2 (sensitivity, 81.4 %; specificity, 72.1 %), respectively. CONCLUSIONS: ARC is common in Japanese ICU patients, and age was an independent risk factor for ARC. In addition, age and eGFR calculated using the Japanese equation were suggested to be useful screening tools for identifying Japanese patients with ARC.

Aberrant iron metabolism might have an impact on progression of diseases in Tsumura Suzuki obese diabetes mice, a model of spontaneous metabolic syndrome.

Tsumura Suzuki obese diabetes (TSOD) mice spontaneously develop obesity and type 2 diabetes with aberrant accumulation of excessive iron in the spleen. Aberrantly accumulated iron may cause oxidative stress and result in various symptoms of metabolic syndrome in the mice. We investigated iron metabolism and oxidative stress in TSOD mice. Male TSOD and control mice were killed at 2, 3, 6, and 8 months of age, and blood and tissue samples were collected. The serum levels of ferritin and oxidized low-density lipoprotein (OxLDL) were measured. Total glutathione concentrations of liver and spleen were also measured. Serum ferritin and OxLDL were higher in TSOD mice than in control mice at 2 and 6 months. In addition, the glutathione concentrations in TSOD mice were lower in the liver and higher in the spleen at 3 and 6 months than those in control mice. These results suggest that abnormal iron metabolism and imbalanced oxidative stress occurs in young and old TSOD mice. We propose herein that TSOD mice might be a unique and valuable model for investigating the role of iron metabolism in pathogenesis of metabolic syndrome.