The Survival Benefit of a Novel Trauma Workflow that Includes Immediate Whole-body Computed Tomography, Surgery, and Interventional Radiology, All in One Trauma Resuscitation Room: A Retrospective Historical Control Study.

OBJECTIVE: The aim of this study was to evaluate the impact of a novel trauma workflow, using an interventional radiology (IVR)-computed tomography (CT) system in severe trauma. BACKGROUND: In August 2011, we installed an IVR-CT system in our trauma resuscitation room. We named it the Hybrid emergency room (ER), as it enabled us to perform all examinations and treatments required for trauma in a single place. METHODS: This retrospective historical control study conducted in Japan included consecutive severe (injury severity score ≥16) blunt trauma patients. Patients were divided into 2 groups: Conventional (from August 2007 to July 2011) or Hybrid ER (from August 2011 to July 2015). We set the primary endpoint as 28-day mortality. The secondary endpoints included cause of death and time course from arrival to start of CT and surgery. Multivariable logistic regression analysis adjusted for clinically important variables was performed to evaluate the clinical outcomes. RESULTS: We included 696 patients: 360 in the Conventional group and 336 in the Hybrid ER group. The Hybrid ER group was significantly associated with decreased mortality [adjusted odds ratio (OR), 0.50 (95% confidence interval, 95% CI, 0.29-0.85); P = 0.011] and reduced deaths from exsanguination [0.17 (0.06-0.47); P = 0.001]. The time to CT initiation [Conventional 26 (21 to 32) minutes vs Hybrid ER 11 (8 to 16) minutes; P < 0.0001] and emergency procedure [68 (51 to 85) minutes vs 47 (37 to 57) minutes; P < 0.0001] were both shorter in the Hybrid ER group. CONCLUSION: This novel trauma workflow, comprising immediate CT diagnosis and rapid bleeding control without patient transfer, as realized in the Hybrid ER, may improve mortality in severe trauma.

Low-dose immunoglobulin G is not associated with mortality in patients with sepsis and septic shock.

BACKGROUND: The administration of low-dose intravenous immunoglobulin G (IVIgG) (5 g/day for 3 days; approximate total 0.3 g/kg) is widely used as an adjunctive treatment for patients with sepsis in Japan, but its efficacy in the reduction of mortality has not been evaluated. We investigated whether the administration of low-dose IVIgG is associated with clinically important outcomes including intensive care unit (ICU) and in-hospital mortality. METHODS: This is a post-hoc subgroup analysis of data from a retrospective cohort study, the Japan Septic Disseminated Intravascular Coagulation (JSEPTIC DIC) study. The JSEPTIC DIC study was conducted in 42 ICUs in 40 institutions throughout Japan, and it investigated associations between sepsis-related coagulopathy, anticoagulation therapies, and clinical outcomes of 3195 adult patients with sepsis and septic shock admitted to ICUs from January 2011 through December 2013. To investigate associations between low-dose IVIgG administration and mortalities, propensity score-based matching analysis was used. RESULTS: IVIgG was administered to 960 patients (30.8%). Patients who received IVIgG were more severely ill than those who did not (Acute Physiology and Chronic Health Evaluation (APACHE) II score 24.2 ± 8.8 vs 22.6 ± 8.7, p < 0.001). They had higher ICU mortality (22.8% vs 17.4%, p < 0.001), but similar in-hospital mortality (34.4% vs 31.0%, p = 0.066). In propensity score-matched analysis, 653 pairs were created. Both ICU mortality and in-hospital mortality were similar between the two groups (21.0% vs 18.1%, p = 0.185, and 32.9% vs 28.6%, p = 0.093, respectively) using generalized estimating equations fitted with logistic regression models adjusted for other therapeutic interventions. The administration of IVIgG was not associated with ICU or in-hospital mortality (odds ratio (OR) 0.883; 95% confidence interval (CI) 0.655-1.192, p = 0.417, and OR 0.957, 95% CI, 0.724-1.265, p = 0.758, respectively). CONCLUSIONS: In this analysis of a large cohort of patients with sepsis and septic shock, the administration of low-dose IVIgG as an adjunctive therapy was not associated with a decrease in ICU or in-hospital mortality. TRIAL REGISTRATION: University Hospital Medical Information Network Individual Clinical Trials Registry, UMIN-CTR000012543 . Registered on 10 December 2013.

Benefit profile of anticoagulant therapy in sepsis: a nationwide multicentre registry in Japan.

BACKGROUND: Little evidence supports anticoagulant therapy as effective adjuvant therapy to reduce mortality overall in sepsis. However, several studies suggest that anticoagulant therapy may reduce mortality in specific patients. This study aimed to identify a subset of patients with high benefit profiles for anticoagulant therapy against sepsis. METHODS: This post hoc subgroup analysis of a nationwide multicentre retrospective registry was conducted in 42 intensive care units in Japan. Consecutive adult patients with sepsis were included. Treatment effects of anticoagulants, e.g. antithrombin, recombinant thrombomodulin, heparin, and protease inhibitors, were evaluated by stratifying patients according to disseminated intravascular coagulation (DIC) and Sequential Organ Failure Assessment (SOFA) score. Intervention effects of anticoagulant therapy on in-hospital mortality and bleeding complications were analysed using Cox regression analysis stratified by propensity scores. RESULTS: Participants comprised 2663 consecutive patients with sepsis; 1247 patients received anticoagulants and 1416 received none. After adjustment for imbalances, anticoagulant administration was significantly associated with reduced mortality only in subsets of patients diagnosed with DIC, whereas similar mortality rates were observed in non-DIC subsets with anticoagulant therapy. Favourable associations between anticoagulant therapy and mortality were observed only in the high-risk subset (SOFA score 13-17; adjusted hazard ratio 0.601; 95 % confidence interval 0.451, 0.800) but not in the subsets of patients with sepsis with low to moderate risk. Although the differences were not statistically significant, there was a consistent tendency towards an increase in bleeding-related transfusions in all SOFA score subsets. CONCLUSIONS: The analysis of this large database indicates anticoagulant therapy may be associated with a survival benefit in patients with sepsis-induced coagulopathy and/or very severe disease. TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR ID: UMIN000012543 ). Registered on 10 December 2013.

Impact on survival of whole-body computed tomography before emergency bleeding control in patients with severe blunt trauma.

INTRODUCTION: Whole-body computed tomography (CT) has gained importance in the early diagnostic phase of trauma care. However, the diagnostic value of CT for seriously injured patients is not thoroughly clarified. This study assessed whether preoperative CT beneficially affected survival of patients with blunt trauma who required emergency bleeding control. METHODS: This retrospective study was conducted from January 2004 to December 2010 in two tertiary trauma centers in Japan. The primary inclusion criterion was patients with blunt trauma who required emergency bleeding control (surgery or transcatheter arterial embolization). CT before emergency bleeding control was performed at the attending physician's discretion based on individual patient condition (for example, hemodynamic stability or certain abnormalities in the primary survey). We assessed covariates associated with 28-day mortality with multivariate logistic regression analysis and evaluated standardized mortality ratio (SMR, ratio of observed to predicted mortality by Trauma and Injury Severity Score (TRISS) method) in two subgroups of patients who did or did not undergo CT. RESULTS: The inclusion criterion was fulfilled by 152 patients with a median Injury Severity Score of 35.3. During the early resuscitation phase, 132 (87%) patients underwent CT and 20 (13%) did not. Severity of injury was significantly higher in the non-CT versus CT group patients. Observed mortality rate was significantly lower in the CT versus non-CT group (18% vs. 80%, P <0.001). Multivariate adjustment for the probability of survival (Ps) by TRISS method confirmed CT as an independent predictor for 28-day mortality (adjusted OR, 7.22; 95% CI, 1.76 to 29.60; P = 0.006). In the subgroup with less severe trauma (TRISS Ps ≥50%), SMR in the CT group was 0.63 (95% CI, 0.23 to 1.03; P = 0.066), indicating no significant difference between observed and predicted mortality in the CT group. In contrast, in the subgroup with more severe trauma (TRISS Ps <50%), SMR was 0.65 (95% CI, 0.41 to 0.90; P = 0.004) only in the CT group, whereas the difference between observed and predicted mortality was not significant in the non-CT group, suggesting a possible beneficial effect of CT on survival only in trauma patients at high risk of death. CONCLUSION: CT performed before emergency bleeding control might be associated with improved survival, especially in severe trauma patients with TRISS Ps of <50%.

Bilateral disseminated herpes zoster in an immunocompetent host.

Herein we report a rare case of disseminated herpes zoster(HZ) infection involving two widely separated bilateral dermatomes in an immunocompetent host. HZ involving two widely separated areas simultaneously is referred to as HZ duplex bilateralis. It is very rare, with an incidence of less than 0.1 percent of all HZ cases, and usually develops in immunocompromised patients.

Uterine rupture successfully treated with a damage-control strategy of hysterectomy and resuscitative endovascular balloon occlusion of the aorta-assisted cardiopulmonary resuscitation.

Background: Uterine rupture is a major cause of postpartum hemorrhage (PPH) that requires surgery. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is also helpful for PPH. However, the effectiveness of REBOA in PPH with cardiac arrest is unknown. Case Presentation: A 40-year-old woman developed hemorrhagic shock due to uterine rupture after an induced delivery. She developed cardiac arrest, but was rescued by cardiopulmonary resuscitation (CPR), REBOA, a hysterectomy, and pelvic gauze packing. The hemodynamics were too unstable to move to the operating room. Then we initiated the CPR assisted with REBOA and decided to activate massive transfusion and perform laparotomy in the emergency room. She was finally discharged home without neurological sequelae. Conclusion: Our damage control strategy, including REBOA-assisted CPR, contributed to saving the life of a patient with a life-threatening PPH.

Successful bronchial artery embolization using hydrogel coils for hemoptysis during extracorporeal membrane oxygenation.

A 58-year-old woman with bronchiectasis presented with massive hemoptysis and severe respiratory failure, which required long-term extracorporeal membrane oxygenation with continuous heparin infusion. Bronchial artery embolization using hydrogel coils, which provide a greater volume occlusion than bare platinum coils, was performed; hemoptysis stopped and she fully recovered. No recanalization was observed on follow-up computed tomography angiography 2 months postbronchial artery embolization, and there had been no recurrence of bleeding at the time of this report (at least 6 months). Although continuous anticoagulation during extracorporeal membrane oxygenation might hinder complete vessel occlusion by metallic coils or induce early recanalization (because the homeostatic mechanism of coils depends on the patient's coagulability), our experience showed that bronchial artery embolization using hydrogel coils was effective and safe. Additionally, this case presents a successful example of anticoagulation management for patients with hemoptysis on extracorporeal membrane oxygenation who undergo bronchial artery embolization using coils.

Mice with a targeted mutation of patched2 are viable but develop alopecia and epidermal hyperplasia.

Hedgehog (Hh) signaling plays pivotal roles in tissue patterning and development in Drosophila melanogaster and vertebrates. The Patched1 (Ptc1) gene, encoding the Hh receptor, is mutated in nevoid basal cell carcinoma syndrome, a human genetic disorder associated with developmental abnormalities and increased incidences of basal cell carcinoma (BCC) and medulloblastoma (MB). Ptc1 mutations also occur in sporadic forms of BCC and MB. Mutational studies with mice have verified that Ptc1 is a tumor suppressor. We previously identified a second mammalian Patched gene, Ptc2, and demonstrated its distinct expression pattern during embryogenesis, suggesting a unique role in development. Most notably, Ptc2 is expressed in an overlapping pattern with Shh in the epidermal compartment of developing hair follicles and is highly expressed in the developing limb bud, cerebellum, and testis. Here, we describe the generation and phenotypic analysis of Ptc2(tm1/tm1) mice. Our molecular analysis suggests that Ptc2(tm1) likely represents a hypomorphic allele. Despite the dynamic expression of Ptc2 during embryogenesis, Ptc2(tm1/tm1) mice are viable, fertile, and apparently normal. Interestingly, adult Ptc2(tm1/tm1) male animals develop skin lesions consisting of alopecia, ulceration, and epidermal hyperplasia. While functional compensation by Ptc1 might account for the lack of a strong mutant phenotype in Ptc2-deficient mice, our results suggest that normal Ptc2 function is required for adult skin homeostasis.

Design and Evaluation of New Unified Criteria for Disseminated Intravascular Coagulation Based on the Japanese Association for Acute Medicine Criteria.

BACKGROUND: Current disseminated intravascular coagulation (DIC) criteria are insufficient for predicting mortality. Hemostatic endothelial molecular markers are useful for DIC diagnoses. We aimed to design new DIC criteria involving these markers based on the recently published Japanese Association for Acute Medicine (JAAM) DIC criteria, which exhibit higher sensitivity for mortality. MATERIALS AND METHODS: Patients with severe sepsis or septic shock admitted to a tertiary referral hospital in Japan between September 2009 and November 2011 were included. Clinical data, including hemostatic endothelial molecular markers, were measured within 12 hours after admission. Receiver operating characteristic analyses were conducted for 8 candidate variables to identify the mortality-related markers. Then, we designed new unified criteria based on the JAAM DIC criteria and involving the identified optimal markers. RESULTS: Of the 79 patients, 66 (83.5%) survived and 13 (16.5%) died. Protein C activity correlated best with mortality with a very high prognostic value (area under the curves [AUCs] = 0.850; P < .001), followed by plasminogen activator inhibitor 1 (AUC = 0.828; P < .001). The unified criteria, consisting of the JAAM DIC criteria plus these 2 markers, exhibited greater prognostic value for mortality (sensitivity, 84.6%; specificity, 80.3%). Moreover, DIC-positive patients using the unified criteria had significantly higher disease severity, as indicated by the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores. CONCLUSION: Our unified criteria involving hemostatic endothelial molecular markers reflected not only mortality but also the severity of illness in patients with severe sepsis.

Characteristics, treatments, and outcomes of severe sepsis of 3195 ICU-treated adult patients throughout Japan during 2011-2013.

Severe sepsis is a major concern in the intensive care unit (ICU), although there is very little epidemiological information regarding severe sepsis in Japan. This study evaluated 3195 patients with severe sepsis in 42 ICUs throughout Japan. The patients with severe sepsis had a mean age of 70 ± 15 years and a mean Acute Physiology and Chronic Health Evaluation II score of 23 ± 9. The estimated survival rates at 28 and 90 days after ICU admission were 73.6 and 56.3 %, respectively.

Antithrombin Supplementation and Mortality in Sepsis-Induced Disseminated Intravascular Coagulation: A Multicenter Retrospective Observational Study.

Supplemental doses of antithrombin (AT) are widely used to treat sepsis-induced disseminated intravascular coagulation (DIC) in Japan. However, evidence on the benefits of AT supplementation for DIC is insufficient. This multicenter retrospective observational study aimed to clarify the effect of AT supplementation on sepsis-induced DIC using propensity score analyses. Data from 3,195 consecutive adult patients admitted to 42 intensive care units for severe sepsis treatment were retrospectively analyzed; 1,784 patients were diagnosed with DIC (n = 715, AT group; n = 1,069, control group). Inverse probability of treatment-weighted propensity score analysis indicated a statistically significant association between AT supplementation and lower in-hospital all-cause mortality (n = 1,784, odds ratio [95% confidence intervals]: 0.748 [0.572-0.978], P = 0.034). However, quintile-stratified propensity score analysis (n = 1,784, odds ratio: 0.823 [0.646-1.050], P = 0.117) and propensity score matching analysis (461 matching pairs, odds ratio: 0.855 [0.649-1.125], P = 0.263) did not show this association. In the early days after intensive care unit admission, the survival rate was statistically higher in the propensity score-matched AT group than in the propensity score-matched control group (P = 0.007). In DIC patients without concomitant heparin administration, similar results were observed. In conclusion, AT supplementation may be associated with reduced in-hospital all-cause mortality in patients with sepsis-induced DIC. However, the statistical robustness of this connection was not strong. In addition, although the number of transfusions needed in patients with AT supplementation increased, severe bleeding complications did not.

A case of cutaneous odontogenic sinus.

Despite the fact that cutaneous sinus tracts of odontogenic origin are well documented, the condition is still commonly misdiagnosed, because chronic periapical periodontitis may be asymptomatic and is rarely open to the skin. A 75-year-old Japanese woman presented to our clinic with the chief complaint of a left cheek skin lesion with mild pain. Physical examination revealed a subcutaneous nodule covered with erythematous skin on her left buccal region. Cultures from the subcutaneous nodule grew Bacteroides species and Peptostreptococcus micros but did not yield acid-fast bacilli, fungi, or Actinomyces. Stains of smeared pus showed a considerable number of Gram-negative rods. The histopathological examination revealed a focal abscess formation in the lower dermis and subcutaneous tissue. Dental evaluation, including an orthopantogram, showed a radiolucent alveolar area at the left lower first molar apex, suggesting a periapical abscess. Antibiotic therapy for three weeks associated with surgical root canal therapy eliminated the subcutaneous nodule. A high degree of suspicion is required to correctly diagnose a lower facial lesion as being of odontogenic origin, and prompt dental evaluation should be considered.

Genetic polymorphisms of killer cell immunoglobulin-like receptors are associated with susceptibility to psoriasis vulgaris.

To elucidate the association between killer cell immunoglobulin-like receptors (KIRs) and psoriasis vulgaris (PV), we typed 14 KIR genes in 96 Japanese cases and 50 healthy controls using PCR with sequence-specific primers (PCR-SSP). Here we report an interesting association between certain KIRs and Japanese cases with PV. The frequencies of KIR2DS1 and KIR2DL5 were significantly increased in PV cases compared with controls (KIR2DS1, 43 of 96 (45%) in cases vs 14 of 50 (28%) in controls; KIR2DL5, 46 of 96 (48%) in cases vs 15 of 50 (30%) in controls, p<0.05 for both), and the frequency of carriage of at least one presumed "B" haplotype, inferred from patterns including KIR2DL2, KIR2DL5, and/or various combinations of activating KIRs, was also statistically increased in the PV cases (53 of 96 (55%) in cases vs 18 of 50 (36%) in controls, p<0.04). The increase in KIR2DS1 has also been observed in psoriatic arthritis, another HLA-Cw6-associated disease (Martin et al, 2002). Accordingly, KIR2DS1 may be a common denominator of both diseases.

Successful treatment of pyogenic granuloma with injection of absolute ethanol.

Pyogenic granuloma (PG) is a small, almost always solitary, sessile or pedunculated, raspberry-like vegetation of exuberant granulation tissue. Conservative treatment by techniques such as cryosurgery, laser surgery, and electrodesiccation are usually adequate, whereas excisional treatment can often result in noticeable scars. We attempted a different approach using an injection of absolute ethanol in five patients with recurrence due to inadequate cryosurgery. This therapy is less invasive than surgical excision and appears to be an alternative therapy for PG.