A Study on Points of Respiratory Assist Devices Using in Pre-Hospital Care Respiratory Assist Devices in Pre-Hospital Care.

BACKGROUND: In Japan, increasing the number of ambulance requests, the case with the use of respiratory assistance devices in prehospital care by paramedics is also increasing1. When patient experiences respiratory failure, the first responders frequently select a respiratory assist device (RAD) such as Bag Valve Mask (BVM), Jackson Rees (JR), or BVM with Gas Supply Valve® (BVM+GSV). This is based on both evaluation and experience as there is no study indicating which RAD is the best choice at the pre-hospital emergency site. This study clarified the precautions when using BVM, JR, and BVM+GSV in pre-hospital emergency medical care with healthy volunteers. METHODS: Twenty healthy adults were fitted with a RAD while breathing spontaneously, and changes in vital signs and ETCO2 were observed. RESULTS: The level of ETCO2 became elevated after each RAD was attached. The value was significantly higher in the JR group than in the others. CONCLUSIONS: The study showed that even in the presence of spontaneous breathing, ETCO2 increased markedly with the application of respiratory assist devices that are used in pre-hospital care for conditions such as hypoxemia and ventilatory disturbance. The increase in ETCO2 was particularly significant in the JR group, suggesting the need for caution when selecting JRs for pre-hospital care. As the number of subjects was only 20 for each RAD, studies with a larger sample size are needed.

Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model.

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. METHODS: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis. RESULTS: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4- and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy. CONCLUSION: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model.

The utility of serum osteopontin levels for predicting postoperative complications after colorectal cancer surgery.

BACKGROUND/AIM: Osteopontin (OPN) is a secretory glycoprotein, which is expressed not only in osteoblasts, but immune cells including macrophages and activated T cells. Its pleiotropic immune functions, such as bone remodeling, cancer progression, immune response, and inflammation have been reported previously. However, the association between OPN and postoperative complications (POC) after colorectal cancer (CRC) surgery has not been studied, so far. METHODS: Peripheral blood samples were collected before (pre) and immediately after surgery (post), and on postoperative days (POD) 1, 3, 5, and 7. Serum OPN levels were measured by ELISA. In total, 78 patients who underwent elective CRC surgery were divided into the No-POC (n = 54) and POC (n = 24) groups. RESULTS: The POC group had significantly higher OPN levels than the No-POC group throughout the postoperative observation period. The maximum OPN levels from pre- to postsurgical samples showed the best predictive potential for POCs (cut off: 20.75 ng/mL, area under the curve: 0.724) and were correlated with length of postoperative stays. OPN values were significantly correlated with C-reactive protein on POD3 and were identified as an independent predictive marker for POCs (odds ratio: 3.88, 95% CI: 1.175-12.798, P = 0.026). The severity of POCs was reflected in increased OPN levels. CONCLUSION: Increased postoperative OPN was associated with increased postoperative inflammatory host responses and POC after CRC surgery. Serum OPN level may be a useful biomarker for early prediction of POC and it may provide additional information for treatment decisions to prevent POC.

Effects of lysophosphatidic acid (LPA) signaling via LPA receptors on cellular functions associated with ATP reduction in osteosarcoma cells treated with ethidium bromide.

Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6) exhibits a variety of malignant properties in cancer cells. Intracellular ATP depletion leads to the development of necrosis and apoptosis. The present study aimed to evaluate the effects of LPA receptor-mediated signaling on the regulation of cancer cell functions associated with ATP reduction. Long-term ethidium bromide (EtBr) treated (MG63-EtBr) cells were established from osteosarcoma MG-63 cells. The intracellular ATP levels of MG63-EtBr cells were significantly lower than that of MG-63 cells. LPAR2, LPAR3, LPAR4 and LPAR6 gene expressions were elevated in MG63-EtBr cells. The cell motile and invasive activities of MG63-EtBr cells were markedly higher than those of MG-63 cells. The cell motile activity of MG-63 cells was increased by LPA4 and LPA6 knockdowns. In cell survival assay, cells were treated with cisplatin (CDDP) every 24 h for 3 days. The cell survival to CDDP of MG63-EtBr cells was lower than that of MG-63 cells. LPA2 knockdown decreased the cell survival to CDDP of MG-63 cells. The cell survival to CDDP of MG-63 cells was inhibited by (2 S)-OMPT (LPA3 agonist). Moreover, the cell survival to CDDP of MG-63 cells was enhanced by LPA4 and LPA6 knockdowns. These results indicate that LPA signaling via LPA receptors is involved in the regulation of cellular functions associated with ATP reduction in MG-63 cells treated with EtBr.

Effects of a novel selective PPARα modulator, statin, sodium-glucose cotransporter 2 inhibitor, and combinatorial therapy on the liver and vasculature of medaka nonalcoholic steatohepatitis model.

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a disease entity with an increasing incidence, with involvement of several metabolic pathways. Various organs, including the liver, kidneys, and the vasculature, are damaged in NASH, indicating the urgent need to develop a standard therapy. Therefore, this study was conducted to investigate the effects of drugs targeting various metabolic pathways and their combinations on a high-fat diet (HFD)-induced NASH medaka model. METHODS: To investigate the effects of drugs on vascular structures, the NASH animal model was developed using the fli::GFP transgenic medaka fed with HFD at 20 mg/fish daily. The physiological changes, histological changes in the liver, vascular structures in the fin, and serum biochemical markers were evaluated in a time-dependent manner after treatment with selective peroxisome proliferator-activated receptor α modulator (pemafibrate), statin (pitavastatin), sodium-glucose cotransporter 2 inhibitor (tofogliflozin), and their combinations. Furthermore, to determine the mechanisms underlying the effects, whole transcriptome sequencing was conducted using medaka liver samples. RESULTS: Histological analyses revealed significant suppression of fat accumulation and fibrotic changes in the liver after treatment with drugs and their combinations. The expression levels of steatosis- and fibrosis-related genes were modified by the treatments. Moreover, the HFD-induced vascular damages in the fin exhibited milder changes after treatment with the drugs. CONCLUSION: The effects of treating various metabolic pathways on the medaka body, liver, and vascular structures of the NASH medaka model were evidenced. Moreover, to our knowledge, this study is the first to report whole genome sequence and gene expression evaluation of medaka livers, which could be helpful in clarifying the molecular mechanisms of drugs.

Evaluation of outcomes after EMS-witnessed traumatic out-of-hospital cardiac arrest caused by traffic collisions.

AIM: The survival rate of patients with traumatic cardiac arrest is 3% or lower. Cardiac arrest witnessed by emergency medical services (EMS) accounts for approximately 16% of prehospital traumatic cardiac arrests, but the prognosis is unknown. We aimed to compare the 1-month survival rate of cardiac arrest witnessed by EMS with that of cardiac arrest witnessed by bystanders and unwitnessed cardiac arrest in traffic trauma victims; further, the time from injury to cardiac arrest was assessed. METHODS: This analysis used the Utstein Registry in Japan and included data of 3883 patients with traumatic cardiac arrest caused by traffic collisions registered between 2014 and 2019 in Japan. RESULTS: The 1-month survival rate was 10.9% in the EMS-witnessed cardiac arrest group; this was significantly higher than that in the bystander-witnessed (7.2%) and unwitnessed (5.6%) cardiac arrest groups (P < 0.01). The median time from injury to cardiac arrest was 18 min (25% quartile: 12, 75% quartile: 26). CONCLUSION: The 1-month survival rate was significantly higher in the EMS-witnessed cardiac arrest group than in the bystander-witnessed and unwitnessed cardiac arrest groups. It is important to prevent progression to cardiac arrest in trauma patients with intact respiratory function and pulse rate at the time of contact with EMS. A system for early recognition of severe trauma is needed, and a doctor's car or helicopter can be requested as needed. We believe that early recognition and prompt intervention will improve the prognosis of prehospital traumatic cardiac arrest.

Wearing a face mask during controlled-intensity exercise is not a risk factor for exertional heatstroke: A pilot study.

AIM: This study aimed to measure the influence of wearing face masks on individuals' physical status in a hot and humid environment. METHODS: Each participant experienced different physical situations: (i) not wearing a mask (control), (ii) wearing a surgical mask, (iii) wearing a sport mask. An ingestible capsule thermometer was used to measure internal core body temperature during different exercises (standing, walking, and running, each for 20 min) in an artificial weather room with the internal wet-bulb globe temperature set at 28°C. The change in the participants' physical status and urinary liver fatty acid-binding protein (L-FABP) were measured. RESULTS: Six healthy male volunteers were enrolled in the study. In each participant, significant changes were observed in the heart rate and internal core temperatures after increased exercise intensity; however, no significant differences were observed between these parameters and urinary L-FABP among the three intervention groups. CONCLUSION: Mask wearing is not a risk factor for heatstroke during increased exercise intensity.

Functional Capacity Index: cultural adaptation and measurement of validity and reliability.

OBJECTIVE: To carry out a cultural adaptation of the Functional Capacity Index (FCI) into Portuguese and to verify its reliability and validity in traffic accident victims. METHOD: Methodological study for cultural adaptation of the FCI. Reliability and validity were verified in a convenience sample of traffic accident victims, in São Paulo city. Data from the patient's medical record were collected retrospectively in 2015. Reliability verified by Cronbach's alpha coefficient and validity by Spearman's correlation and Mann-Whitney test. RESULTS: The FCI in Portuguese was applied to 50 traffic accident victims. The internal consistency reached Cronbach's alpha values >0.70. The FCI correlated with the Katz index, did not correlate with the severity of trauma and the FCI of trauma patients was higher compared to those without trauma. CONCLUSION: The FCI in Portuguese showed satisfactory internal consistency, allowing the measurement of functional capacity, discriminating against people with and without traumatic injuries.

Rapid progression of colonic mucinous adenocarcinoma with immunosuppressive condition: A case report and review of literature.

BACKGROUND: Colorectal mucinous adenocarcinoma is a rare subtype of colorectal cancer and is characterized by an abundance of mucin in the tumor. In addition, the colorectal mucinous adenocarcinoma often demonstrates poor differentiation in the histology of tumor cells and poor prognosis compared with those with adenocarcinoma. Here, we present the case of a young woman with colonic mucinous adenocarcinoma showing significantly rapid progression within four months of immunosuppressant therapy for Henoch-Schönlein purpura. CASE SUMMARY: Here we report a rare case of ascending colon mucinous adenocarcinoma with lymph node and liver metastases which developed and progressed rapidly within four months during the treatment of Henoch-Schönlein purpura using corticosteroids. The systemic screening examinations showed no tumors before the immunosuppressant therapy. Fortunately, the patient was successfully treated with chemotherapy. CONCLUSION: While no direct evidence that the immunosuppressants accelerated the tumor development, the case presenta tion and review of the literature demonstrated that surveillance for malignancies before and during treatment with immunosuppressive agents is essential.

Rare complication of hepatocellular carcinoma in Wilson's disease.

The complication of hepatocellular carcinoma (HCC) in Wilson's disease is rare. Wilson's disease treatment using D-penicillamine (DPA) is useful to prevent HCC occurrence; however, it also causes iron accumulation and synergistic radical formation in the liver, which may enhance carcinogenesis. Reported herein is a case of HCC in Wilson's disease treated with DPA for 36 years. The tumor was surgically resected and histologically diagnosed with moderately differentiated HCC surrounded by cirrhotic tissue with fatty infiltration. Rhodanine staining revealed a slight positively stained area in both tumor and surrounding tissues. Information obtained from this case and literature review highlight the feature of HCC in Wilson's disease.

A prediction model using 2-propanol and 2-butanone in urine distinguishes breast cancer.

Safe and noninvasive methods for breast cancer screening with improved accuracy are urgently needed. Volatile organic compounds (VOCs) in biological samples such as breath and blood have been investigated as noninvasive novel markers of cancer. We investigated volatile organic compounds in urine to assess their potential for the detection of breast cancer. One hundred and ten women with biopsy-proven breast cancer and 177 healthy volunteers were enrolled. The subjects were divided into two groups: a training set and an external validation set. Urine samples were collected and analyzed by gas chromatography and mass spectrometry. A predictive model was constructed by multivariate analysis, and the sensitivity and specificity of the model were confirmed using both a training set and an external set with reproducibility tests. The training set included 60 breast cancer patients (age 34-88 years, mean 60.3) and 60 healthy controls (age 34-81 years, mean 58.7). The external validation set included 50 breast cancer patients (age 35-85 years, mean 58.8) and 117 healthy controls (age 18-84 years, mean 51.2). One hundred and ninety-one compounds detected in at least 80% of the samples from the training set were used for further analysis. The predictive model that best-detected breast cancer at various clinical stages was constructed using a combination of two of the compounds, 2-propanol and 2-butanone. The sensitivity and specificity in the training set were 93.3% and 83.3%, respectively. Triplicated reproducibility tests were performed by randomly choosing ten samples from each group, and the results showed a matching rate of 100% for the breast cancer patient group and 90% for the healthy control group. Our prediction model using two VOCs is a useful complement to the current diagnostic tools. Further studies inclusive of benign tumors and non-breast malignancies are warranted.

Breast Cancer Detection from a Urine Sample by Dog Sniffing: A Preliminary Study for the Development of a New Screening Device, and a Literature Review.

BACKGROUND: Breast cancer is a leading cause of cancer death worldwide. Several studies have demonstrated that dogs can sniff and detect cancer in the breath or urine sample of a patient. This study aims to assess whether the urine sample can be used for breast cancer screening by its fingerprints of volatile organic compounds using a single trained sniffer dog. This is a preliminary study for developing the "electronic nose" for cancer screening. METHODS: A nine-year-old female Labrador Retriever was trained to identify cancer from urine samples of breast cancer patients. Urine samples from patients histologically diagnosed with primary breast cancer, those with non-breast malignant diseases, and healthy volunteers were obtained, and a double-blind test was performed. Total of 40 patients with breast cancer, 142 patients with non-breast malignant diseases, and 18 healthy volunteers were enrolled, and their urine samples were collected. RESULTS: In 40 times out of 40 runs of a double-blind test, the trained dog could correctly identify urine samples of breast cancer patients. Sensitivity and specificity of this breast cancer detection method using dog sniffing were both 100%. CONCLUSIONS: The trained dog in this study could accurately detect breast cancer from urine samples of breast cancer patients. These results indicate the feasibility of a method to detect breast cancer from urine samples using dog sniffing in the diagnosis of breast cancer. Although the methodological standardization is still an issue to be discussed, the current result warrants further study for developing a new breast cancer screening method based on volatile organic compounds in urine samples.

Functional Capacity Index: cultural adaptation and measurement of validity and reliability / Functional Capacity Index: adaptação cultural e mensuração da validade e confiabilidade

ABSTRACT Objective To carry out a cultural adaptation of the Functional Capacity Index (FCI) into Portuguese and to verify its reliability and validity in traffic accident victims. Method Methodological study for cultural adaptation of the FCI. Reliability and validity were verified in a convenience sample of traffic accident victims, in São Paulo city. Data from the patient's medical record were collected retrospectively in 2015. Reliability verified by Cronbach's alpha coefficient and validity by Spearman's correlation and Mann-Whitney test. Results The FCI in Portuguese was applied to 50 traffic accident victims. The internal consistency reached Cronbach's alpha values >0.70. The FCI correlated with the Katz index, did not correlate with the severity of trauma and the FCI of trauma patients was higher compared to those without trauma. Conclusion The FCI in Portuguese showed satisfactory internal consistency, allowing the measurement of functional capacity, discriminating against people with and without traumatic injuries

RESUMEN Objetivo Realizar adaptación cultural del Índice de Capacidad Funcional (FCI) al portugués y verificar su fiabilidad y validez en víctimas de accidentes de tráfico. Método Estudio metodológico para adaptación cultural de FCI. Fiabilidad y validez se verificaron en muestra de conveniencia de víctimas de accidentes de tránsito, en la ciudad de São Paulo. Datos del registro del paciente se recopilaron retrospectivamente en 2015. Fiabilidad verificada por coeficiente alfa de Cronbach y validez por correlación de Spearman y prueba de Mann-Whitney. Resultados FCI en portugués se aplicó a 50 víctimas de accidentes de tránsito. Consistencia interna alcanzó valores alfa de Cronbach >0,70. FCI se correlacionó con índice de Katz, no se correlacionó con gravedad del trauma y FCI de pacientes con trauma fue mayor en comparación con aquellos sin trauma. Conclusión FCI en portugués mostró consistencia interna satisfactoria, permitiendo medir capacidad funcional, discriminando personas con y sin lesiones traumáticas.

RESUMO Objetivo Realizar adaptação cultural do Functional Capacity Index (FCI) para língua portuguesa e verificar sua confiabilidade e validade em vítimas de acidente de trânsito. Método Estudo metodológico para adaptação cultural do FCI. Confiabilidade e validade foram verificadas em amostra de conveniência de acidentados de trânsito, no município de São Paulo. Dados do prontuário do paciente foram coletados retrospectivamente em 2015. Confiabilidade verificada pelo coeficiente alfa de Cronbach e validade pela correlação de Spearman e teste de Mann-Whitney. Resultados O FCI em português foi aplicado em 50 vítimas de acidente de trânsito. A consistência interna alcançou valores de alfa de Cronbach >0,70. O FCI correlacionou com índice de Katz, não correlacionou com a gravidade do trauma e o FCI de pacientes de trauma foi superior em comparação aos sem trauma. Conclusão O FCI em português mostrou consistência interna satisfatória, permitindo mensurar a capacidade funcional, discriminando pessoas com e sem lesões traumáticas.

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis: A case report.

BACKGROUND: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized. CASE SUMMARY: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness. CONCLUSION: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy.

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

NIR Photodynamic Destruction of PDAC and HNSCC Nodules Using Triple-Receptor-Targeted Photoimmuno-Nanoconjugates: Targeting Heterogeneity in Cancer.

Receptor heterogeneity in cancer is a major limitation of molecular targeting for cancer therapeutics. Single-receptor-targeted treatment exerts selection pressures that result in treatment escape for low-receptor-expressing tumor subpopulations. To overcome this potential for heterogeneity-driven resistance to molecular targeted photodynamic therapy (PDT), we present for the first time a triple-receptor-targeted photoimmuno-nanoconjugate (TR-PIN) platform. TR-PIN functionalization with cetuximab, holo-transferrin, and trastuzumab conferred specificity for epidermal growth factor receptor (EGFR), transferrin receptor (TfR), and human epidermal growth factor receptor 2 (HER-2), respectively. The TR-PINs exhibited up to a 24-fold improvement in cancer cell binding compared with EGFR-specific cetuximab-targeted PINs (Cet-PINs) in low-EGFR-expressing cell lines. Photodestruction using TR-PINs was significantly higher than the monotargeted Cet-PINs in heterocellular 3D in vitro models of heterogeneous pancreatic ductal adenocarcinoma (PDAC; MIA PaCa-2 cells) and heterogeneous head and neck squamous cell carcinoma (HNSCC, SCC9 cells) containing low-EGFR-expressing T47D (high TfR) or SKOV-3 (high HER-2) cells. Through their capacity for multiple tumor target recognition, TR-PINs can serve as a unique and amenable platform for the effective photodynamic eradication of diverse tumor subpopulations in heterogeneous cancers to mitigate escape for more complete and durable treatment responses.

Intravenous Immunoglobulin Attenuates Cecum Ligation and Puncture-Induced Acute Lung Injury by Inhibiting Apoptosis of Alveolar Epithelial Cells.

PURPOSE: Intravenous immunoglobulin (IVIG) therapy has been used to treat sepsis, but its mechanisms of action remain unclear. Sepsis causes multiple organ failure, such as acute lung injury (ALI), which involves apoptosis of alveolar epithelial cells. In this study, we hypothesized that IVIG suppresses apoptosis in alveolar epithelial cells and evaluated mortality, cytokine levels, histological changes in the lung, and alveolar epithelial cell apoptosis after IVIG administration, in mice with experimentally induced sepsis. METHODS: Mice received an injection of vehicle (saline) or immunoglobulin (100 mg/kg or 400 mg/kg) into the tail vein, after which they underwent cecal ligation and puncture. A sham-operated group was used as the normal control. Survival was assessed in all groups after 72 hours. Plasma levels of TNF-α and IL-6, histopathological changes and wet-to-dry ratio in lung, and alveolar epithelial cell apoptosis were evaluated in all groups at 4 hours after surgery. RESULTS: In the vehicle group, histopathological injury of the lung was severe, and apoptosis of alveolar epithelial cells was significant. Survival and plasma cytokine levels were better in the IVIG treatment groups than in the vehicle group. IVIG 400 mg/kg suppressed apoptosis of alveolar epithelial cells and reduced ALI. CONCLUSION: IVIG suppressed inflammatory cytokine levels and improved survival. Lung histopathology and alveolar epithelial cell apoptosis were improved by IVIG treatment, in a dose-dependent manner. Suppressing apoptosis in alveolar epithelial cells appears to be a mechanism by which IVIG improves survival.

Serum D-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1.

Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood D-/L-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum D-/L-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased D-/L-serine ratio did not associate with activity of a D-serine degrading enzyme, D-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum D-serine increase. In vitro study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of D-serine preferably to L-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum D-serine accumulation.

Blood Galectin-3 Levels Predict Postoperative Complications after Colorectal Cancer Surgery.

BACKGROUND: Recent studies suggested that galectin-3 may act as a pro-inflammatory damage-associated molecular pattern. The aim of this study is to investigate the association between blood galectin-3 and postoperative complications (POC) after colorectal cancer (CRC) surgery. METHODS: Blood samples were taken from 35 patients with CRC before surgery, immediately after surgery, and on postoperative days (POD) 1, 3, 5, and 7. Blood galectin-3 and interleukin-6 levels were measured by commercially available ELISA. Patients were divided into those with (POC group) and without POC (no-POC group). RESULTS: Significantly higher galectin-3 levels were observed pre- and postoperatively in the POC group (n=10) compared with those of the no-POC group (n=25). Galectin-3 levels on POD1 showed the best predictive potential for POC (cut-off: 3.18 pg/mL, area under the curve: 0.868). CONCLUSIONS: These results indicate that increased perioperative blood galectin-3 levels may be associated with POC after CRC surgery.

Colonic stent-induced mechanical compression may suppress cancer cell proliferation in malignant large bowel obstruction.

BACKGROUND: The short-term safety and efficacy of insertion of a self-expandable metallic colonic stent (SEMS) followed by elective surgery, "bridge to surgery (BTS)", for malignant large bowel obstruction (MLBO) have been well described; however, the influence on long-term oncological outcomes is unclear. The aim of this study was to evaluate changes in oncological characteristics in colorectal cancer (CRC) tissues after SEMS insertion, focusing on growth factors, cell cycle and apoptosis. METHODS: From January 2013 to September 2014, a total of 25 patients with MLBO who underwent BTS at our single institution were retrospectively included. Paired CRC tissue samples before (endoscopic biopsy) and after SEMS insertion (surgically resected) were collected from each patient. EGFR, VEGF, Ki-67, p27kip1 and TUNEL expression were determined by immunohistochemistry. RESULTS: No clinical or subclinical perforations evaluated by mechanical ulceration pathologically were observed. Epithelial exfoliation, tumour necrosis, infiltration of inflammatory cells and fibrosis were observed in SEMS-inserted surgically-resected specimens. Overall, 84% (21/25) and 60% (15/25) of patients exhibited no change or a decrease in staining category, respectively, for EGFR and VEGF expression after SEMS insertion. A significant decrease in Ki-67 expression was observed in surgically-resected specimens compared with endoscopic biopsy specimens (P < 0.01). The upstream cell cycle inhibitor, p27kip1, was significantly increased after SEMS insertion (P = 0.049). CONCLUSIONS: Although the long-term safety of BTS should be determined in a future clinical trial, mechanical compression by SEMS may suppress cancer cell proliferation and this result could provide some insights into the issue.