CG02N Analyzer Accurately Measures Fibrinogen Level in Whole Blood in the Presence of Low- or High-Dose Heparin.

Rapid fibrinogen (Fbg) evaluation is important in patients with massive bleeding during severe trauma and those undergoing major surgery. However, there are only a few studies on the point-of-care Fbg analyzer. In this study, we aimed to investigate the accuracy of Fbg level measured using CG02N, with whole blood contained in lithium-heparinized syringes with two different concentrations of heparin. Blood samples were collected in lithium-heparinized tubes, namely PREZA-PAK®II (low-dose heparin group [LG], 7 IU/mL) and Pro-Vent® Plus (high-dose heparin group [HG], 70.5 IU/mL). The Fbg levels in LG and HG were compared with those of citrated plasma Fbg (standard-Fbg). Strong correlations with respect to the Fbg level were observed between standard-Fbg and LG or HG (r = 0.968, p < 0.0001; r = 0.970, p < 0.0001, respectively). We demonstrated that the Fbg level in whole-blood samples was accurately assessed by CG02N and not affected by low- or high-dose heparin.

The current status of emergency departments in secondary emergency medical institutions in Japan: a questionnaire survey.

BACKGROUND: While emergency medicine (ER)-based emergency care is prevalent in many countries, in Japan, the "department-specific emergency care model" and the "emergency center model" are mainstream. We hypothesized that many secondary emergency medical institutions in Japan have inadequate systems. Using a questionnaire, we investigated the status of and problems in the emergency medical services system in secondary emergency medical institutions in Japan. Until date, there has not been an exhaustive survey of emergency facilities on a countrywide scale. The main objective of this study was to investigate problems in the Japanese emergency medical services system and thereby improve optimal care for emergency patients. RESULTS: A nationwide questionnaire survey involving 4063 facilities (all government-approved emergency medical facilities certified by prefectural governors) in Japan was conducted. Of the facilities that responded, all secondary emergency facilities were included in the analysis. Responses from 1289 facilities without a tertiary emergency medical care center were analyzed. Among them, 61% (792/1289) had ≤ 199 beds, and 8% were emergency department specialty training program core facilities. Moreover, 42% had an annual patient acceptance number of ≤ 500, 19% did not calculate the number of acceptances, 29% had an acceptance rate of ≥ 81%, and 25% had an acceptance rate of 61-80%. Pregnant women (63%) and children (56%) were the major types of patients that affected the acceptance rate. Factors affecting facilities with a response rate of 81% or higher were "hospitals designated for residency training" and "facilities making some efforts to improve the quality of emergency care and the emergency medical system" (logistic analysis, P < .001). CONCLUSION: Relevant authorities and core regional facilities should consider and implement specific measures for regions and hospitals with a shortage of emergency medicine specialists and physicians (e.g., development of ER-based emergency medicine and provision of education). This study may lead to further improvement in the optimal care of emergency patients through the nationwide establishment of the proposed measures as well as through grouping and integrating the structures and systems in emergency and other medical facilities.

Specific IgE Response and Omalizumab Responsiveness in Severe Allergic Asthma.

Objective: Omalizumab has demonstrated clinical efficacy in patients with severe allergic asthma sensitized to perennial allergens and/or severe pollinosis through inhibition of IgE-dependent allergic response. When considering the "one airway, one disease" concept, sensitization to pollen could predict responsiveness to omalizumab. This study aimed to assess whether the pretreatment specific IgE response could be a predictor of responsiveness to omalizumab in severe allergic asthma sensitized to perennial allergens. Methods: In this retrospective study, 41 adult patients with severe allergic asthma sensitized to perennial allergens (27 females; mean age 59 years) who had completed 52-week omalizumab treatment were enrolled. The Global Evaluation of Treatment Effectiveness was performed, and demographic characteristics and the positive ratios of specific IgE responses classified into five subgroups (pollen, dust mite, house dust, mold, and animal dander) were compared between responders and non-responders. Multivariate logistic regression analyses were performed to identify predictors of responsiveness to omalizumab. Results: Thirty-one patients (76%) were identified as responders. The number of sensitized aeroallergen subgroups and sensitization to pollens were significantly higher in responders than in non-responders (both p<0.05). Multivariate logistic regression analysis showed that sensitization to pollen (OR = 8.41, p = 0.02) was independently associated with the effectiveness of omalizumab. Conclusion: Pretreatment serum pollen-specific IgE could be a predictor of responsiveness to omalizumab.

Can Homecare Chronic Respiratory Disease Patients with Home Oxygen Treatment (HOT) in Southern Okinawa, Japan Be Evacuated Ahead of the Next Anticipated Tsunami?

An earthquake with a magnitude of 8 or 9 is predicted to occur near the Ryukyu Islands in Japan, for which the Okinawa Prefecture is preparing countermeasures. Evacuating people to a safe shelter within the tsunami arrival time is a crucial countermeasure. This study aims to understand the vulnerabilities of patients with chronic respiratory diseases in southern parts of Okinawa during a tsunami evacuation, thereby calculating evacuation distance of vulnerable patients and creating individual evacuation plans. Data for chronic respiratory patients obtained in July 2021 from the hospitals in Okinawa Prefecture include age, gender, diagnosis, residence, nearest tsunami shelter, oxygen flow at rest and walking, and maximum walking distance for 6 min based on a 6-min walk test. A quantum geographic information system was used for mapping the data. The survival potential of patients with chronic respiratory disease was evaluated by using a tsunami inundation depth of one meter and the distance within which an evacuation can be performed until the first tsunami wave reaches the nearest evacuation shelter. Results revealed a low survival potential for respiratory disease patients under the current tsunami evacuation plan. The study suggests creating an individual evacuation plan for vulnerable patients involving families and medical staff and then conducting a drill for improving the plan.

Review of pediatric abdominal trauma: operative and non-operative treatment in combined adult and pediatric trauma center.

AIM: More than 90% of pediatric solid organ abdominal injuries are treated non-operatively. It remains difficult to decide who should graduate to surgical management, more so if adult physicians must make these decisions on pediatric patients. The purpose of this study was to examine outcomes of all pediatric abdominal trauma cases in a single center, focusing on the decision-making algorithm for operative or non-operative treatment by pediatric and adult physicians. METHODS: We undertook a retrospective review of a pediatric trauma database from April 2006 to March 2016. Groups were divided into operative and non-operative, single or multi-organ injury, and adult or pediatric physician. Operative treatments included laparotomy or interventional radiology procedures. Primary outcome was survival within 30 days. RESULTS: There were 53 abdominal trauma cases; among them, 48 (90.6%) survived and 5 (9.4%) died within 30 days. The probability of survival for mortalities was less than 11%. Forty-two cases were treated non-operatively and 11 operatively. Injury Severity Score was higher in operative group (17 [9, 41]/9 [4, 16.3]). Adult physicians saw 33 patients including seven operative, whereas pediatric physicians saw 20 including four operative cases. There was no statistical difference for the management decision between adult and pediatric physicians. CONCLUSION: Our decisions for intervention were within acceptable rates. Adult physicians did not tend to operate more, but there were cases that did not fit the criteria of the algorithm. Further investigation is needed to look at which factors should be focused on to determine whether or not operative treatments are indicated.

Resuscitative endovascular balloon occlusion of the aorta performed by emergency physicians for traumatic hemorrhagic shock: a case series from Japanese emergency rooms.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA), which has been increasingly used for the management of hemorrhagic shock, is a less invasive strategy for the management of patients with very severe hemorrhage. However, its effectiveness remains controversial. METHODS: This retrospective case series included trauma patients who underwent REBOA for hemorrhagic shock due to trauma in four Japanese tertiary care emergency centers from January 2013 to March 2017. Patients in cardiac arrest at the time of REBOA and those who underwent REBOA for nontraumatic causes during the study period were excluded. RESULTS: A total of 24 patients underwent REBOA during the study period. The median age was 52 years (interquartile range (IQR) 36.5-62.5), 17 (70.8%) of the patients were male, and 23 (95.8%) had blunt trauma. The 24-h survival was 50% (n = 12), and the in-hospital survival rate was 41.7% (10/24). In all cases, REBOA was performed in emergency rooms by emergency physicians without fluoroscopic guidance. Complications of REBOA were mesenteric ischemia (n = 1, 4.2%), ischemia of the lower extremities (n = 1, 4.2%), and placement of REBOA in thoracic aortic injury (n = 3, 12.5%). CONCLUSIONS: REBOA can be an effective and feasible tool for controlling massive hemorrhage due to trauma. However, caution should be exercised regarding complications including placement of REBOA in aortic injury and limb ischemia in cases where REBOA is performed in an emergency department setting with minimal or no support from trauma surgeons.

Successful surgical treatment of traumatic sternal fracture with extensive mediastinal abscess and concomitant mitral valve endocarditis: a case report.

BACKGROUND: A traumatic sternal fracture with extensive mediastinal abscess and concomitant native valve endocarditis is an extremely rare but catastrophic situation. CASE PRESENTATION: For 2 weeks, the co-infected patient was treated with aggressive debridement for the mediastinitis, change of vacuum-assisted closure therapy dressings, vegetectomy and valve repair through lower partial sternotomy, and delayed primary wound closure. CONCLUSIONS: To the best of our knowledge, this successful staged strategy has not been previously reported. We believe that our quick decision about repeated surgical interventions and preservation of the manubrium led to a favorable result.

Fibrinogen and base excess levels as predictive markers of the need for massive blood transfusion after blunt trauma.

BACKGROUND: Assessment blood consumption and trauma-associated severe hemorrhage scores are useful for predicting the need for massive transfusion (MT) in severe trauma patients. However, fibrinogen (Fbg) and base excess (BE) levels might also be useful indicators for the need for MT. We evaluated the accuracy of prediction for MT of the scoring system vs. Fbg and BE. METHODS: The subjects of this retrospective single center observational study were patients with injury severity score ≥16 trauma, divided into a non-MT group and an MT group. We compared variables, including the scoring system (comprising vital signs and focused assessment with sonography for trauma; FAST) and Fbg between the groups. We then performed a multiple logistic regression modeling and a receiver operating characteristic analysis to clarify which value was the most useful predictive indicator for MT. RESULTS: There were 114 patients in the non-MT group and 39 in the MT group. The level of Fbg and BE were independent predictors of MT. The area under the curve values for Fbg and BE were 0.765 and 0.845, respectively, and the optimal cutoff values of Fbg and BE were 211 mg/dL and -1.4, respectively. CONCLUSIONS: Fbg and BE levels can be used as an independent predictor for MT.

New diagnostic strategy for sepsis-induced disseminated intravascular coagulation: a prospective single-center observational study.

INTRODUCTION: Inflammation and coagulation are closely interrelated pathophysiologic processes in the pathogenesis of sepsis. However, the diagnostic criteria of sepsis and disseminated intravascular coagulation (DIC) are different. This study aimed to define a biomarker panel to predict sepsis-induced DIC in emergency department patients. METHODS: Eighty-two patients who were admitted to the emergency department of a tertiary university hospital were included in this study. The inclusion criteria were as follows: (1) age >18 years; (2) ≥1 systemic inflammatory response syndrome (SIRS) criteria. Patients were excluded if they lacked biomarker data or apparent clinical manifestations. Eleven biomarkers were assayed from blood drawn on ED admission. Receiver operating curve (ROC) analysis including the area under the ROC and multivariable logistic regression were used to identify an optimal combination of biomarkers to create a diagnostic panel. The derived formula for weighting biomarker values was used to determine the severity of sepsis-induced DIC, which was divided into three categories: mild, moderate, and severe. We also investigated the ability of this classification to predict secondary outcome measures of rates of sepsis and DIC, DIC score, acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure score (SOFA) score, and 28-day all-cause mortality. RESULTS: Among the 11 biomarkers tested, the optimal 2-marker panel comprised presepsin and protein C. The area under the curve for the accuracies of predicting sepsis and DIC from these two biomarkers were 0.913 and 0.880, respectively. When patients were divided according to the severity of sepsis-induced DIC, all secondary outcomes except for mortality were significantly higher depending on the severity (P < .0001). The overall mortality rates of mild, moderate, and severe sepsis-induced DIC were 7.14%, 15.4%, and 28.6%, respectively (P = .0994). CONCLUSIONS: A biomarker panel of presepsin and protein C is predictive of the severity of sepsis-induced DIC in suspected ED patients. These criteria for sepsis-induced DIC are very simple, easy to implement, and can be used in intensive care units as a point-of-care test.

Bladder pain relief by HMGB1 neutralization and soluble thrombomodulin in mice with cyclophosphamide-induced cystitis.

High mobility group box 1 (HMGB1), one of damage-associated molecular patterns (DAMPs), plays roles in not only inflammation but also processing of somatic pain. Given that no evidence for roles of HMGB1 in visceral pain signaling is available, we asked if HMGB1 participates in bladder pain accompanying cystitis caused by cyclophosphamide in mice, using the anti-HMGB1 neutralizing antibody and recombinant human soluble thrombomodulin (rhsTM) that sequesters HMGB1 and promotes its degradation by thrombin. Cyclophosphamide, administered i.p., caused bladder pain-like nociceptive behavior and referred hyperalgesia accompanying cystitis symptoms including increased bladder weight, an indicator of edema, in mice. The cyclophosphamide-induced bladder pain and referred hyperalgesia, but not increased bladder weight, were prevented by i.p. preadministration of the anti-HMGB1 neutralizing antibody or rhsTM. HMGB1, given i.p., facilitated the bladder pain and referred hyperalgesia caused by a subeffective dose of cyclophosphamide, an effect blocked by rhsTM. In the cyclophosphamide-treated mice, HMGB1 levels greatly decreased in the bladder tissue, particularly in the urothelial cells, but did not change in the plasma. Low molecular weight heparin, known to inhibit the receptor for advanced glycation end products (RAGE), but not lipopolysaccharide from Rhodobacter sphaeroides, an inhibitor of toll-like receptor 4 (TLR4), blocked the cyclophosphamide-induced bladder pain and referred hyperalgesia. Thus, our data indicate involvement of HMGB1 in the cyclophosphamide-induced bladder pain signaling, but not cystitis itself, and suggest that targeting HMGB1 with rhsTM or blocking RAGE might serve as a novel therapeutic strategy for the management of bladder pain.

Recombinant human soluble thrombomodulin prevents peripheral HMGB1-dependent hyperalgesia in rats.

BACKGROUND AND PURPOSE: High-mobility group box 1 (HMGB1), a nuclear protein, is actively or passively released during inflammation. Recombinant human soluble thrombomodulin (rhsTM), a medicine for treatment of disseminated intravascular coagulation (DIC), sequesters HMGB1 and promotes its degradation. Given evidence for involvement of HMGB1 in pain signalling, we determined if peripheral HMGB1 causes hyperalgesia, and then asked if rhsTM modulates the HMGB1-dependent hyperalgesia. EXPERIMENTAL APPROACH: Mechanical nociceptive threshold and swelling in rat hindpaw were determined by the paw pressure test and by measuring paw thickness, respectively, and HMGB1 levels in rat hindpaw plantar tissue, dorsal root ganglion (DRG) and serum were determined by Western blotting or elisa. KEY RESULTS: Intraplantar (i.pl.) administration of HMGB1 rapidly evoked paw swelling and gradually caused hyperalgesia in rats. Systemic administration of rhsTM abolished HMGB1-induced hyperalgesia, and partially blocked paw swelling. LPS, administered i.pl., rapidly produced mild paw swelling, and gradually caused hyperalgesia. The anti-HMGB1 neutralizing antibody abolished LPS-induced hyperalgesia, but partially inhibited paw swelling. rhsTM at a high dose, 10 mg kg(-1) , prevented both hyperalgesia and paw swelling caused by LPS. In contrast, rhsTM at low doses, 0.001-1 mg kg(-1) , abolished the LPS-induced hyperalgesia, but not paw swelling. HMGB1 levels greatly decreased in the hindpaw, but not DRG. Serum HMGB1 tended to increase after i.pl. LPS in rats pretreated with vehicle, but not rhsTM. CONCLUSION AND IMPLICATIONS: These data suggest that peripheral HMGB1 causes hyperalgesia, and that rhsTM abolishes HMGB1-dependent hyperalgesia, providing novel evidence for therapeutic usefulness of rhsTM as an analgesic.

Limaprost reduces motor disturbances by increasing the production of insulin-like growth factor I in rats subjected to spinal cord injury.

Calcitonin gene-related peptide (CGRP) released from sensory neurons increases the production of a neuroprotective substance insulin-like growth factor I (IGF-I), and sensory neuron stimulation contributes to a reduction of spinal cord injury (SCI) by inhibiting inflammatory responses in rats. Because receptors for prostaglandin E2 (EP receptors) are present on sensory neurons, it is possible that prostaglandin E1 analog limaprost reduces SCI by increasing IGF-I production through sensory neuron stimulation. We examined this possibility in rats subjected to compression-trauma-induced SCI. Limaprost increased the CGRP release from dorsal root ganglion (DRG) neurons isolated from rats, and this increase was reversed by pretreatment with the EP4 receptor antagonist ONO-AE3-208. Spinal cord tissue levels of CGRP and IGF-I were increased after the induction of SCI, peaking at 2 h postinduction. The intravenous administration of limaprost enhanced increases of spinal cord tissue levels of CGRP, IGF-I, and IGF-I mRNA at 2 h after the induction of SCI. Increases of spinal cord tissue levels of tumor necrosis factor, caspase-3, myeloperoxidase, and the number of apoptotic nerve cells were inhibited by the administration of limaprost. Motor disturbances of hind legs in animals subjected to the compression-trauma-induced SCI were reduced by the administration of limaprost. These effects of limaprost were reversed completely by pretreatment with a specific transient receptor potential vanilloid 1 inhibitor SB366791 and by sensory denervation. These observations strongly suggest that limaprost may increase the IGF-I production by stimulating sensory neurons in the spinal cord, thereby ameliorating compression-trauma-induced SCI through attenuation of inflammatory responses.