Application of a First Impression Triage in the Japan Railway West Disaster

On April 25, 2005, a Japanese express train derailed into a building, resulting in 107 deaths and 549 injuries. We used “First Impression Triage (FIT)”, our new triage strategy based on general inspection and palpation without counting pulse/respiratory rates, and determined the feasibility of FIT in the chaotic situation of treating a large number of injured people in a brief time period. The subjects included 39 patients who required hospitalization among 113 victims transferred to our hospital. After initial assessment with FIT by an emergency physician, patients were retrospectively reassessed with the preexisting the modified Simple Triage and Rapid Treatment (START) methodology, based on Injury Severity Score, probability of survival, and ICU stay. FIT resulted in shorter waiting time for triage. FIT designations comprised 11 red (immediate), 28 yellow (delayed), while START assigned six to red and 32 to yellow. There were no statistical differences between FIT and START in the accuracy rate calculated by means of probability of survival and ICU stay. Overall validity and reliability of FIT determined by outcome assessment were similar to those of START. FIT would be a simple and accurate technique to quickly triage a large number of patients

Gastric cancer with autoimmune gastritis

Background: Autoimmune gastritis is known to be associated with neoplastic lesions but the relationship between autoimmunity and tumorigenesis have not been sufficiently clarified. The aim of this study is to assess the clinicopathological characteristics of gastric cancer cases associated with autoimmune gastritis. Methods: A total of 24 patients diagnosed as early gastric cancer with autoimmune gastritis were registered. Chart reviews with the data including age, gender, state of Helicobacter pylori infection, comorbidity, and concomitant gastric diseases were conducted. As for the characteristics of gastric cancer, location, size, morphological type, histopathology, invasion depth, and the presence of metachronous or simultaneous lesion were assessed. These data from autoimmune gastritis group were compared with those from 301 patients of early gastric cancer as a control group. Results: The gastric cancer associated with autoimmune gastritis was located in the upper, middle, and lower parts in 28.1%, 53.1%, and 18.8%, respectively. The morphological types are as follows: 0-I, 9.4%; 0-IIa, 28.1%; 0-IIb, 15.6%; 0-IIc, 46.9%; and 0-III, 0.0%. The mean tumor size was 21.8 mm. While 90.6% were confined to the mucosa, 9.4% showed submucosal invasion. The histological classifications are as follows: tub1, 50.0%; tub2, 15.6%; pap, 21.9%; sig, 9.4%; and por, 3.1%. More numbers of female, protruded types, larger tumor size, papillary tumor, and that in the upper location were observed in autoimmune gastritis group compared to control group. Conclusion: Early gastric cancer associated with autoimmune gastritis demonstrated different characteristics from those without autoimmune gastritis including variety of tumor morphologies and histological types with female dominancy

Staphylococcus aureus colonization in contact hypersensitivity induces a shift in cutaneous cytokine milieu from a Th1- to a Th2-type profile

Background: Colonization of atopic dermatitis lesions with Staphylococcus aureus is a frequent phenomenon and may exacerbate inflammation of the skin. The aim of the present study was to determine the effect of S. aureus on T cell-mediated immune responses in contact hypersensitivity caused by a hapten or a protein with large molecule. Methods: Staphylococcus aureus or phosphate-buffered saline was inoculated on experimental contact dermatitis induced by 2,4,6-trinitro-1-chlorobenzene (TNCB) or house dust mite antigen. At various times after inoculation, the experimental lesions were examined histologically and immunohistochemically. Furthermore, the kinetics of cytokine patterns (interferon (IFN)-γ, interleukin (IL)-2, IL-4 and IL-5) in each lesion were analyzed by reverse transcription-polymerase chain reaction. Results: In TNCB-challenged lesions inoculated with S. aureus, the levels of IL-2 mRNA decreased; in contrast, mRNA levels of IL-4 and IL-5 were upregulated. In mite antigen-challenged lesions, IL-4 and IL-5 mRNA expression was detected throughout the period of the investigation, even without S. aureus inoculation. Interferon-γ mRNA expression in mite dermatitis without S. aureus inoculation was observed only in the later period and IL-2 mRNA expression in mite dermatitis with S. aureus was suppressed and observed much later than in the control group. Conclusions: Infestation of S. aureus on skin lesions in experimental contact hypersensitivity induces a shift in the immune reaction from a Th1- to a Th2-dominant response

Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models

Hydrogen peroxide (H2O2) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H2O2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H2O2 on antitumor immunity remain unclear. To investigate the effects of H2O2, especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H2O2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H2O2/RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H2O2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H2O2/RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8+ (cluster of differentiation 8) T cells and the frequency of IFN-γ+ (interferon gamma) CD8+ T cells were higher in the noninjected/nonirradiated tumors in the H2O2/RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H2O2/RT group. Intratumoral injection of H2O2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H2O2/RT therapy combined with cancer immunotherapies, even for advanced cancers

Activated CTLA-4-independent immunosuppression of Treg cells disturbs CTLA-4 blockade-mediated antitumor immunity

Combination therapy with anti-cytotoxic T lymphocyte-associated protein 4 (CTLA-4) and anti-programmed death-1 (PD-1) monoclonal antibodies (mAbs) has dramatically improved the prognosis of patients with multiple types of cancer, including renal cell carcinoma (RCC). However, more than half of RCC patients fail to respond to this therapy. Regulatory T cells (Treg cells) are a subset of highly immunosuppressive CD4(+) T cells that promote the immune escape of tumors by suppressing effector T cells in the tumor microenvironment (TME) through various mechanisms. CTLA-4 is constitutively expressed in Treg cells and is regarded as a key molecule for Treg-cell-mediated immunosuppressive functions, suppressing antigen-presenting cells by binding to CD80/CD86. Reducing Treg cells in the TME with an anti-CTLA-4 mAb with antibody-dependent cellular cytotoxicity (ADCC) activity is considered an essential mechanism to achieve tumor regression. In contrast, we demonstrated that CTLA-4 blockade without ADCC activity enhanced CD28 costimulatory signaling pathways in Treg cells and promoted Treg-cell proliferation in mouse models. CTLA-4 blockade also augmented CTLA-4-independent immunosuppressive functions, including cytokine production, leading to insufficient antitumor effects. Similar results were also observed in human peripheral blood lymphocytes and tumor-infiltrating lymphocytes from patients with RCC. Our findings highlight the importance of Treg-cell depletion to achieve tumor regression in response to CTLA-4 blockade therapies

Establishment of an Animal Model of Bisphosphonate-Related Osteonecrosis of the Jaws in Spontaneously Diabetic Torii Rats.

BACKGROUND:We evaluated the side effects of bisphosphonate (BP) on tooth extraction socket healing in spontaneously diabetic Torii (SDT) rats, an established model of non-obese type 2 diabetes mellitus, to develop an animal model of BP-related osteonecrosis of the jaws (BRONJ). MATERIALS AND METHODS:Male Sprague-Dawley (SD) rats and SDT rats were randomly assigned to the zoledronic acid (ZOL)-treated groups (SD/ZOL or SDT/ZOL) or to the control groups (SD/control or SDT/control). Rats in the SD/ZOL or SDT/ZOL groups received an intravenous bolus injection of ZOL (35 μg/kg) every 2 weeks. Each group consisted of 6 rats each. Twenty-one weeks after ZOL treatment began, the left maxillary molars were extracted. The rats were euthanized at 2, 4, or 8 weeks after tooth extraction, and the total maxillae were harvested for histological and histochemical studies. RESULTS:In the oral cavity, bone exposure persisted at the tooth extraction site in all rats of the SDT/ZOL group until 8 weeks after tooth extraction. In contrast, there was no bone exposure in SD/control or SDT/control groups, and only 1 of 6 rats in the SD/ZOL group showed bone exposure. Histologically, necrotic bone areas with empty lacunae, microbial colonies, and less invasion by inflammatory cells were observed. The number of tartrate-resistant acid phosphatase-positive osteoclasts was lower in the SDT/ZOL group than in the SD/control group. The mineral apposition rate was significantly lower in the SDT/ZOL group compared with the SD/control group. CONCLUSIONS:This study demonstrated the development of BRONJ-like lesions in rats and suggested that low bone turnover with less inflammatory cell infiltration plays an important role in the development of BRONJ

New Biomarkers for Prediction of Disseminated Intravascular Coagulation in Patients With Sepsis

Complication of disseminated intravascular coagulation (DIC) is a determinant of the prognosis for patients with sepsis. The purpose of this study was to find DIC-related peptides in blood for prediction and early diagnosis of DIC in patients with sepsis. The participants were 20 patients with sepsis (age: 68.9 ± 11.4 years) and they were divided into 2 groups with (n = 8) and without (n = 12) a complication of DIC. Peptides in the serum of the patients were inclusively analyzed by a new method for peptidome analysis using a target plate, BLOTCHIP. By differential analysis of peptides in the blood from patients in the groups with and without DIC, we selected 13 mass spectrometry (MS) peaks as candidate marker peptides for prediction of DIC. By subsequent MS/MS structural analysis, 8 peptides were successfully identified as marker peptides for DIC in patients with sepsis. The peptides were fragments of serum amyloid A-2 protein, α2-HS-glycoprotein, fibrinogen α chain, fibrinogen β chain, serum albumin, collagen α1 (I) chain, collagen α1 (III) chain, and coagulation factor XIII A chain. In receiver–operating characteristic analysis for the relationships between the marker peptides and DIC, the area under the curve for each of these peptides was 0.594 to 0.760. We identified 8 blood marker peptides for prediction of DIC complication in patients with sepsis. Further studies by direct measurements of the serum peptide levels in larger numbers of patients with sepsis-induced DIC are needed to confirm the findings of this study