Bite wound and mauling of a zookeeper by a gorilla.

The majority of bite wounds that we encounter in the emergency department are caused by dogs, cats and humans, but bite injuries can be caused by a variety of animals. Here, we describe a case of bite wound and trauma caused by a large gorilla (Western lowland gorilla) weighing over 170 kg. Gorilla bites are rare, and the patient had an open fracture of the right distal radioulna in addition to multiple bite wounds. Treatment required careful consideration of gorilla antigenicity and a literature review to guide the selection of appropriate antimicrobial agents. Furthermore, trauma inflicted by large animals tends to require systemic traumatological screening, and patients can develop acute stress disorder because of a fear of being attacked again; therefore, early psychiatric intervention is important.

Changes in carbon dioxide production and oxygen uptake evaluated using indirect calorimetry in mechanically ventilated patients with sepsis.

BACKGROUND: Several clinical guidelines recommend monitoring blood lactate levels and central venous oxygen saturation for hemodynamic management of patients with sepsis. We hypothesized that carbon dioxide production (VCO2) and oxygen extraction (VO2) evaluated using indirect calorimetry (IC) might provide additional information to understand the dynamic metabolic changes in sepsis. METHODS: Adult patients with sepsis who required mechanical ventilation in the intensive care unit (ICU) of our hospital between September 2019 and March 2020 were prospectively enrolled. Sepsis was diagnosed according to Sepsis-3. Continuous measurement of VCO2 and VO2 using IC for 2 h was conducted within 24 h after tracheal intubation, and the changes in VCO2 and VO2 over 2 h were calculated as the slopes by linear regression analysis. Furthermore, temporal lactate changes were evaluated. The primary outcome was 28-day survival. RESULTS: Thirty-four patients with sepsis were enrolled, 26 of whom survived 76%. Significant differences in the slope of VCO2 (- 1.412 vs. - 0.446) (p = 0.012) and VO2 (- 2.098 vs. - 0.851) (p = 0.023) changes were observed between non-survivors and survivors. Of note, all eight non-survivors and 17 of the 26 survivors showed negative slopes of VCO2 and VO2 changes. For these patients, 17 survivors had a median lactate of - 2.4% changes per hour (%/h), whereas non-survivors had a median lactate of 2.6%/hr (p = 0.023). CONCLUSIONS: The non-survivors in this study showed temporal decreases in both VCO2 and VO2 along with lactate elevation. Monitoring the temporal changes in VCO2 and VO2 along with blood lactate levels may be useful in predicting the prognosis of sepsis.

Subcutaneous injection of organophosphate (Fenitrothion)-Management of preventing the appearance of toxic symptoms: A case report.

There is a risk of unnecessary extensive incision because of swelling after the subcutaneous injection; however, removing completely the injected organophosphate by making a skin incision before the appearance of toxic symptoms could reduce sequelae.

Early diagnosis and antibiotic treatment for fulminant Clostridium difficile infection.

In fulminant Clostridium difficile infection (CDI), early diagnosis is important, and early diagnosis could save fulminant CDI patients that do not qualify for surgery due to severe complicating conditions by conservative antibiotic therapy.

Recombinant thrombomodulin prevents acute lung injury induced by renal ischemia-reperfusion injury.

Acute kidney injury (AKI) complicated by acute lung injury has a detrimental effect on mortality among critically ill patients. Recently, a renal ischemia-reperfusion (IR) model suggested the involvement of histones and neutrophil extracellular traps (NETs) in the development of distant lung injury after renal IR. Given that recombinant thrombomodulin (rTM) has anti-inflammatory roles by binding to circulating histones, we aimed to clarify its effect on distant lung injury induced by AKI in a murine bilateral renal IR model. Both pretreatment and delayed treatment with rTM significantly decreased pulmonary myeloperoxidase activity, but they did not affect renal dysfunction at 24 h after renal IR. Additionally, rTM mitigated the renal IR-augmented expression of proinflammatory cytokines (tumor necrosis factor-α, interleukin-6, and keratinocyte-derived chemokine), and vascular leakage, as well as the degree of lung damage. Intense histone accumulation and active NET formation occurred in both the kidneys and the lungs; however, rTM significantly decreased the histone and NET accumulation only in the lungs. Administration of rTM may have protective impact on the lungs after renal IR by blocking histone and NET accumulation in the lungs, although no protection was observed in the kidneys. Treatment with rTM may be an adjuvant strategy to attenuate distant lung injury complicating AKI.

Recombinant Thrombomodulin on Neutrophil Extracellular Traps in Murine Intestinal Ischemia-Reperfusion.

BACKGROUND: In multiple-organ dysfunction, an injury affecting one organ remotely impacts others, and the injured organs synergistically worsen outcomes. Recently, several mediators, including extracellular histones and neutrophil extracellular traps, were identified as contributors to distant organ damage. This study aimed to elucidate whether these mediators play a crucial role in remote organ damage induced by intestinal ischemia-reperfusion. This study also aimed to evaluate the protective effects of recombinant thrombomodulin, which has been reported to neutralize extracellular histones, on multiple-organ dysfunction after intestinal ischemia-reperfusion. METHODS: Intestinal ischemia was induced in male C57BL/6J mice via clamping of the superior mesenteric artery. Recombinant thrombomodulin (10 mg/kg) was administered intraperitoneally with the initiation of reperfusion. The mice were subjected to a survival analysis, histologic injury scoring, quantitative polymerase chain reaction analysis of tumor necrosis factor-α and keratinocyte-derived chemokine expression, Evans blue dye vascular permeability assay, and enzyme-linked immunosorbent assay analysis of histones in the jejunum, liver, lung, and kidney after 30- or 45-min ischemia. Neutrophil extracellular trap formation was evaluated by immunofluorescence staining. RESULTS: Recombinant thrombomodulin yielded statistically significant improvements in survival after 45-min ischemia (ischemia-reperfusion without vs. with 10 mg/kg recombinant thrombomodulin: 0% vs. 33%, n = 21 per group, P = 0.001). Recombinant thrombomodulin reduced the histologic injury score, expression of tumor necrosis factor-α and keratinocyte-derived chemokine, and extravasation of Evans blue dye, which were augmented by 30-min ischemia-reperfusion, in the liver, but not in the intestine. Accumulated histones and neutrophil extracellular traps were found in the livers and intestines of 30-min ischemia-reperfusion-injured mice. Recombinant thrombomodulin reduced these accumulations only in the liver. CONCLUSIONS: Recombinant thrombomodulin improved the survival of male mice with intestinal ischemia-reperfusion injury. These findings suggest that histone and neutrophil extracellular trap accumulation exacerbate remote liver injury after intestinal ischemia-reperfusion. Recombinant thrombomodulin may suppress these accumulations and attenuate liver injury.

Damage-associated molecular patterns in intensive care unit patients with acute liver injuries: A prospective cohort study.

Acute liver injury (ALI) is frequently detected in an intensive care unit (ICU) and reportedly affects prognosis. Experimental animal studies suggested that increased extracellular histone and high morbidity group box-1 (HMGB1) levels might contribute to ALI development. Whether these damage-associated molecular patterns (DAMPs) play a crucial role in ALI remains unclear in the human clinical setting.We consecutively enrolled the patients admitted to our ICU. The patients with ALI were included in the analysis together with those without ALI by using frequency matching. Extracellular histone, HMGB1, soluble thrombomodulin (sTM), and interleukin-6 (IL-6) levels were measured in plasma collected at ICU admission. ALI was defined as an acute elevation in serum aminotransferase levels to >200 IU/L.A total of 805 patients were enrolled. Twenty ALI and forty non-ALI patients were analyzed. Plasma histone levels were significantly higher in the ALI group than in the non-ALI group, whereas HMGB1 levels were significantly lower in the ALI group. Furthermore, sTM was significantly increased in the ALI patients, whereas IL-6 levels were comparable between the groups. Multivariate logistic regression analysis demonstrated that histones were independently associated with ALI. There was no significant impact of ALI on in-hospital mortality.Extracellular histones showed an independent association with ALI. Histone elevation might be one of the possible pathogenic mechanisms in the development of ALI of ICU patients.

A critically ill patient after a colchicine overdose below the lethal dose: a case report.

BACKGROUND: Although 0.8 mg/kg is considered a lethal dose of colchicine, fatal cases of patients who followed a critical disease course after an intake below this lethal dose have been reported. CASE PRESENTATION: An 18-year-old Japanese woman who had taken an overdose of prescription colchicine (15 mg; 0.2 mg/kg) was brought to our emergency out-patient department. Although her colchicine intake was below 0.8 mg/kg (considered the lethal dose), she reached a critical state and underwent three phases characterizing colchicine poisoning (gastrointestinal symptoms, multiple organ failure, and recovery). Her condition was critical, with a Sequential Organ Failure Assessment score of a maximum of 14. CONCLUSIONS: Patients might reach a critical stage after colchicine ingestion at a non-lethal dose. Thus, it might be necessary to review which dose of colchicine should be considered lethal.

The profile of Japanese Association for Acute Medicine - out-of-hospital cardiac arrest registry in 2014-2015.

AIM: To describe the registry design of the Japanese Association for Acute Medicine - out-of-hospital cardiac arrest (JAAM-OHCA) Registry as well as its profile on hospital information, patient and emergency medical service characteristics, and in-hospital procedures and outcomes among patients with OHCA who were transported to the participating institutions. METHODS: The special committee aiming to improve the survival after OHCA by providing evidence-based therapeutic strategies and emergency medical systems from the JAAM has launched a multicenter, prospective registry that enrolled OHCA patients who were transported to critical care medical centers or hospitals with an emergency care department. The primary outcome was a favorable neurological status 1 month after OHCA. RESULTS: Between June 2014 and December 2015, a total of 12,024 eligible patients with OHCA were registered in 73 participating institutions. The mean age of the patients was 69.2 years, and 61.0% of them were male. The first documented shockable rhythm on arrival of emergency medical services was 9.0%. After hospital arrival, 9.4% underwent defibrillation, 68.9% tracheal intubation, 3.7% extracorporeal cardiopulmonary resuscitation, 3.0% intra-aortic balloon pumping, 6.4% coronary angiography, 3.0% percutaneous coronary intervention, 6.4% targeted temperature management, and 81.1% adrenaline administration. The proportion of cerebral performance category 1 or 2 at 1 month after OHCA was 3.9% among adult patients and 5.5% among pediatric patients. CONCLUSIONS: The special committee of the JAAM launched the JAAM-OHCA Registry in June 2014 and continuously gathers data on OHCA patients. This registry can provide valuable information to establish appropriate therapeutic strategies for OHCA patients in the near future.

Interface design dividing physical findings into medical and trauma findings facilitates clinical document entry in the emergency department: A prospective observational study.

PURPOSE: The interface design and its effect on workflow are key determinants of the usability of electronic medical records (EMRs) in the emergency department (ED). However, whether the overall clinical care can be improved by dividing the interface design of physical findings into medical and trauma findings is unknown. We previously developed an EMR system in which the checkpoints were separated into different sections according to the body part. Herein, we modified this EMR system by remaking the interface design specifically for trauma patients, and evaluated its performance. METHODS: This study was undertaken in a single-center ED between October 2014 and September 2015. In the modified EMR system, all trauma findings are displayed together on the screen, according to the Japan Advanced Trauma Evaluation and Care. We compared the time to final documentation entry and the length of ED stay between the previous (used in the first 6 months) and current systems (used in the latter 6 months). Furthermore, we stratified the patients by triage levels. RESULTS: The study involved 2141 patients (934 and 1207 assessed using the previous and modified EMR systems, respectively). The modified EMR in trauma patients significantly decreased the time to final documentation entry from 131.5 [interquartile range, 86.8-207.3] to 115 [78.8-161] min (p = 0.049). When stratifying trauma patients by triage level, significantly shorter clinical documentation times were observed with the modified EMR system in levels 2 (emergency) and 3 (urgent). CONCLUSIONS: Using different interfaces for trauma findings shortened the time for clinical documentation for trauma patients.

Early-phase Innate Immune Suppression in Murine Severe Sepsis Is Restored with Systemic Interferon-ß.

BACKGROUND: Sepsis is a leading cause of death in the intensive care unit. Immune modulatory therapy targeting sepsis-associated proinflammatory responses has not shown survival benefit. Here, the authors evaluated innate immunity at the early stage of murine mild or severe peritoneal sepsis induced by cecal ligation and puncture, and the effect of systemic interferon-ß, a potent inflammatory mediator, on severe sepsis as well as its mechanism of action. METHODS: Mild and severe sepsis was induced in C57BL/6 mice by cecal ligation and puncture with 22- and 18-gauge needles for puncture, respectively. Interferon-ß (700 U/g) was subcutaneously administered either before or 12 h after cecal ligation and puncture for the severe sepsis group. RESULTS: Severe sepsis resulted in significantly lower 6-day survival rates than mild sepsis (n = 48, 25% vs. n = 11, 81.8%, P = 0.002), significantly less phagocytic capacity of peritoneal exudate cells, and lower CXC chemokine receptor-2 expression on circulating neutrophils at 24 h after cecal ligation and puncture. Interferon-ß administration 12 h after cecal ligation and puncture associated with significantly improved survival (n = 34, 52.9%, P = 0.017) increased the number and function of peritoneal exudate cells, peritoneal/systemic inflammatory cytokine/chemokine concentrations, and CXC chemokine receptor-2 on neutrophils, compared with the severe sepsis controls. However, those responses were not observed in the prophylactic interferon-ß group (n = 24). Interferon-ß increased lipopolysaccharide-induced interleukin-6 messenger RNA/protein expression of lipopolysaccharide-tolerant murine peritoneal macrophages, which was not observed in nontolerant cells. CONCLUSIONS: In severe sepsis, immune suppression occurs within 24 h and is associated with worse mortality. Interferon-ß given after the onset of peritonitis restores impaired innate immunity in vivo and in vitro.

IFN-ß Improves Sepsis-related Alveolar Macrophage Dysfunction and Postseptic Acute Respiratory Distress Syndrome-related Mortality.

IFN-ß is reported to improve survival in patients with acute respiratory distress syndrome (ARDS), possibly by preventing sepsis-induced immunosuppression, but its therapeutic nature in ARDS pathogenesis is poorly understood. We investigated the therapeutic effects of IFN-ß for postseptic ARDS to better understand its pathogenesis in mice. Postseptic ARDS was reproduced in mice by cecal ligation and puncture to induce sepsis, followed 4 days later by intratracheal instillation of Pseudomonas aeruginosa to cause pneumonia with or without subcutaneous administration of IFN-ß 1 day earlier. Sepsis induced prolonged increases in alveolar TNF-α and IL-10 concentrations and innate immune reprogramming; specifically, it reduced alveolar macrophage (AM) phagocytosis and KC (CXCL1) secretion. Ex vivo AM exposure to TNF-α or IL-10 duplicated cytokine release impairment. Compared with sepsis or pneumonia alone, pneumonia after sepsis was associated with blunted alveolar KC responses and reduced neutrophil recruitment into alveoli despite increased neutrophil burden in lungs (i.e., "incomplete alveolar neutrophil recruitment"), reduced bacterial clearance, increased lung injury, and markedly increased mortality. Importantly, IFN-ß reversed the TNF-α/IL-10-mediated impairment of AM cytokine secretion in vitro, restored alveolar innate immune responsiveness in vivo, improved alveolar neutrophil recruitment and bacterial clearance, and consequently reduced the odds ratio for 7-day mortality by 85% (odds ratio, 0.15; 95% confidence interval, 0.03-0.82; P = 0.045). This mouse model of sequential sepsis → pneumonia infection revealed incomplete alveolar neutrophil recruitment as a novel pathogenic mechanism for postseptic ARDS, and systemic IFN-ß improved survival by restoring the impaired function of AMs, mainly by recruiting neutrophils to alveoli.

Efficacy of levetiracetam versus fosphenytoin for the recurrence of seizures after status epilepticus.

Benzodiazepines are used as first-line treatments for status epilepticus. Fosphenytoin (FPHT) is recommended for second-line therapy; however, intravenous injection of levetiracetam (LEV) may also be effective against status epilepticus. Herein, we compared the efficacy and safety of LEV as a second-line treatment for status epilepticus with FPHT in Japanese patients.Patients with status epilepticus were selected from the database of the Emergency and Critical Care Center of Hitachi General Hospital. The subjects were patients whose status epilepticus was successfully stopped by diazepam, and in whom FPHT or LEV was administered after diazepam. As LEV injections recently became clinically available in Japan, the choice of drug was determined by the treatment period. Thus, 21 patients who were intravenously injected with LEV as a second-line therapy and 42 matched patients (historical controls) who were treated with FPHT (1:2) were selected.The subjects had a mean age of 64.0 ±â€Š2.2 years, and included 48 males and 15 females. The status epilepticus control rates of the FPHT and LEV groups did not differ significantly (81.0% [34/42] vs 85.1% [18/21], respectively; P  =  .69). As for serious adverse events, a reduction in blood pressure was observed in the FPHT group, but not in the LEV group. The oral anticonvulsant switching rates of the 2 groups were similar, but the same-drug switching rates of the FPHT and LEV groups were 8.1% and 77.8%, respectively.The efficacy of intravenous LEV injections after status epilepticus was equivalent to that of FPHT, and the incidence of adverse events was lower in the LEV group. LEV is effective and safe at preventing recurrent seizures after status epilepticus following benzodiazepine treatment.

Recombinant thrombomodulin for secondary thrombotic thrombocytopenic purpura.

In the pathogenesis of thrombotic thrombocytopenic purpura (TTP), reductions in the enzyme activity of ADAMTS13, which cuts ultralarge von Willebrand multimers, generates shear stress on the microvascular endothelium, leading to platelet aggregation and the formation of a thrombus. ADAMTS13 activity is markedly decreased in typical TTP, but is only mildly reduced in secondary TTP, which concomitantly develops with primary disease. The latter develops with septic disseminated intravascular coagulation (DIC) and often causes organ failure. Recombinant thrombomodulin (rTM) is a drug that is used to treat DIC and may also remit TTP because it improves vascular endothelial dysfunction. Therefore, we herein investigated the efficacy of rTM in patients treated for the pathology of secondary TTP. Patients who were admitted to the Emergency and Critical Care Center of our hospital and met the following conditions were extracted and retrospectively analyzed: hemolytic anemia accompanied by fragmented red blood cells (Hb < 12 g/dL or lower); thrombocytopenia (<100 × 10/µL); and ADAMTS13 activity <50%. Sixteen patients were included and accompanied by Kidney Disease: Improving Global Outcomes (KDIGO) stage 2 or more severe nephropathy and DIC. Eleven and 5 patients treated with and without rTM (the rTM and non-rTM treatment groups, respectively) were compared, and no significant difference was noted in their basic characteristics, such as background disease and severity. No significant difference was observed in survival rates; however, the platelet count, which is an important outcome of treatments for TTP, significantly increased in the rTM treatment group: 3.3 ±â€Š2.6→11.3 ±â€Š14.6 versus 3.5 ±â€Š3.7→5.7 ±â€Š3.9 (×1000/µL) (P = 0.034). Thrombotic thrombocytopenic purpura originally requires invasive treatments and its prognosis is not favorable. Blood thrombomodulin levels also markedly increase due to vascular endothelial dysfunction, whereas rTM alleviates vascular endothelial dysfunction in TTP patients with high blood TM levels, suggesting the importance of administering rTM. Thus, rTM may be effective for secondary TTP and may be adopted as adjuvant therapy.

Switching therapy from intravenous beta blocker to bisoprolol transdermal patch for atrial fibrillation tachycardia.

Beta-blockers are important for severe-status patients with atrial fibrillation-related tachycardia. Beta 1-selective intravenous injection are routinely used, but long-term administration is difficult due to cost-performance- or management-related issues. A bisoprolol patch, a beta-blocker to be percutaneously absorbed, recently became commercially available in Japan. As it may facilitate effective absorption and a mild elevation of the blood concentration, we retrospectively analyzed 16 patients with atrial fibrillation-related tachycardia who were admitted to the Intensive Care Unit of Hitachi General Hospital Emergency and Critical Care Center, and underwent switching therapy from landiolol to a bisoprolol patch. For switching, the bisoprolol patch (4 mg) was attached to each patient. The bisoprolol patch was introduced 88 h after the start of landiolol administration, when the rate was approximately 3 µg/kg/min. Landiolol injection was combined with bisoprolol for 15.4 ± 17.5 h. Switching therapy was successful in all subjects. The introduction of the bisoprolol patch did not induce any significant changes in the blood pressure or heart rate. After the completion of landiolol administration, there were also no significant changes in either parameter. There were no adverse events. In severe-status patients, switching therapy from landiolol injection to the bisoprolol patch can be conducted safely, and might be useful for heart-rate control.

Continuous veno-venous hemodialysis and filtration for extensive burn with severe hypernatremia.

Case: A 51-year-old man presented with severe burns, with a burn index of 33.5. Relaxation incisions were made in the trunk and right arm. Ringer's solution (12,000 mL) was used as initial fluid therapy for the first 24 h. The patient's serum Na level gradually increased to 170 mEq/L; infusion was carried out to correct the hypernatremia. Continuous veno-venous hemodialysis and filtration succeeded in maintaining the serum Na level at approximately 145 mEq/L. Outcome: After the initiation of continuous veno-venous hemodialysis and filtration, the skin graft survival rate improved markedly with the normalization of the Na level, and the patient recovered smoothly. He was discharged on foot. Conclusion: Hypernatremia, frequently observed in patients with extensive burns, is considered to be markedly disadvantageous for the survival of skin grafts. Continuous veno-venous hemodialysis and filtration may be one of the options for the treatment of refractory hypernatremia in severe burns.