Equol, a soybean metabolite with estrogen-like functions, decreases lipopolysaccharide-induced human neutrophil extracellular traps in vitro.

OBJECTIVE: Neutrophil extracellular traps (NETs) defend against acute infections. However, their overexpression causes organ failure during sepsis. Control of NET formation may improve the outcomes of patients with sepsis. Equol, a soybean isoflavone, is a female hormone analog, which prevents inflammation. We evaluated the effects of equol on NET formation in human neutrophils during inflammatory stimulation in vitro. METHODS: Healthy volunteers provided blood samples. An enzyme-linked immunosorbent assay (ELISA) assessed serum equol concentrations. NET formation in neutrophils was induced by lipopolysaccharide (LPS) treatment. ELISA quantified DNA-binding elastase, and immunostaining assessed NET formation. Reverse-transcription quantitative PCR and western blotting detected G-protein-coupled receptor 30 (GPR30) or peptidyl arginine deiminase 4 (PAD4) expression. Flow cytometry assessed neutrophil phagocytic ability with inactivated Escherichia coli. RESULTS: In neutrophils derived from males with low-serum equol levels (low-serum equol group), equol significantly decreased DNA-binding elastase levels and NET formation. Equol did not decrease NETs in neutrophils from males with high-serum equol levels. GPR30 expression of neutrophils was higher in the low-serum than in the high-serum equol group. PAD4 mRNA levels and nuclear PAD4 protein expression also decreased than the vehicle control in the low-serum equol group. Equol did not alter the phagocytic ability of neutrophils. In neutrophils from young females, equol had no inhibitory effect on NET formation. CONCLUSIONS: Equol decreases LPS-induced NET formation in neutrophils from males via inhibition of PAD4 expression. Our findings provide a rationale for investigating a new therapeutic approach using equol to control neutrophil activity during sepsis.

The role of death receptor signaling pathways in mouse Sertoli cell avoidance of apoptosis during LPS- and IL-18-induced inflammatory conditions.

Lipopolysaccharide (LPS) triggers infectious acute inflammation, and interleukin (IL)-18 is an inflammasome-mediated cytokine. We previously demonstrated that endogenous IL-18 induces testicular germ cell apoptosis during acute inflammation when plasma IL-18 levels are high. Additionally, high-dose recombinant IL-18 (rIL-18) induced Leydig cell apoptosis. The blood-testis barrier formed by Sertoli cells protects testicular germ cells from both exogenous and endogenous harmful substances. However, the impact of LPS and IL-18 on Sertoli cells remained unclear. We stimulated TM4 cells, a mouse Sertoli cell line, with LPS (200 or 1000 ng/mL) or rIL-18 (0.1-100 ng/mL) at levels that induced Leydig cell apoptosis in our previous study and assessed caspase 3 cleavage and the mRNA expression of inflammatory cytokines and markers of apoptotic pathways (Tnfr1, Fasl, Fas, Fadd) after stimulation. Il6 mRNA was increased by LPS stimulation. Tnfα mRNA was increased by 200 ng/mL LPS but not 1000 ng/mL LPS. Fas was increased, but Fasl was decreased, by LPS. LPS had little influence on Tnfr1 or Fadd mRNA expression and did not induce apoptosis. Il18 mRNA was not increased, and Il18r1 was significantly decreased following LPS treatment. Treatment with rIL-18 increased Il18r1 mRNA and induced inflammation, but decreased Tnfr1 and had little influence on apoptosis, as indicated by Tnfα, Fasl, Fas, Fadd and cleaved caspase 3. These results suggested that Sertoli cells do not easily undergo apoptosis despite strong inflammatory stimuli. Additionally, Sertoli cells may resist inflammation and play a larger role in protecting testicular homeostasis than other component cells of the testis.

Understanding the Trajectory to a Diagnosis of Tetanus: A Descriptive Study.

Background and objective Tetanus is a rare but potentially fatal disease in developed countries, including Japan. It is very difficult to diagnose this condition early because of its broad symptomatology and the lack of familiarity with tetanus among both physicians and patients. In this study, we aimed to describe the clinical manifestations of tetanus and to examine as to which departments/branches of medicine patients consult in order to provide helpful information for diagnosing this challenging condition. Materials and methods This was a descriptive, retrospective study conducted at a single tertiary hospital from January 2011 to December 2021. Patients with generalized tetanus, cephalic tetanus, and local tetanus presenting to our emergency department were included in the study. We examined the clinical manifestations and departments that patients with tetanus visited first. Additionally, the initial diagnosis and diagnostic evaluation before the diagnosis were examined. Results Of the total 10 patients included in the study, nine had generalized tetanus and one had cephalic tetanus; the common initial manifestations were neck stiffness (30%), dysarthria (20%), and trismus (20%). Of note, 80% of patients also complained of dysphagia before the diagnosis. Patients first visited various departments, including a dental clinic (30%) and the department of otorhinolaryngology (20%). Only two patients were accurately diagnosed with tetanus at the first department they visited. Physicians performed head imaging for all the patients. Conclusions Based on our findings, in Japan, patients with tetanus present with symptoms that physicians interpret or suspect to be associated with disorders of the central nervous system. Meanwhile, patients themselves tend to consider the symptoms as indicative of oral or dental issues. Further prospective studies involving a larger number of participants are needed to investigate the clinical course of tetanus until the establishment of a diagnosis.

Mid-term (30- to 90-day) neurological changes in out-of-hospital cardiac arrest patients: A nationwide retrospective study (the JAAM-OHCA registry).

OBJECTIVE: Few studies have focused on mid/long-term neurological changes in out-of- hospital cardiac arrest (OHCA) survivors. Some studies suggest that there is still a slow, small, progressive improvement in cognitive function and quality of life for this population, even in the mid/long term. However, clinical data focused on mid/long-term outcomes for OHCA patients are still lacking. This study aimed to assess mid-term neurological changes in OHCA patients. We summarized patients' improved or worsened neurological changes between 30 and 90 days. Then we identified the relationship between clinical variables and 30- to 90-day neurological improvement. METHODS: A retrospective review of data (Jun 2014 - Dec 2017) from a Japanese nationwide OHCA registry was conducted. Inclusion criteria were OHCA patients ≥18 years old. Exclusion criteria were death within 30 days and missing Cerebral Performance Category (CPC) score at 30 and 90 days. We described the distributions of 30-day and 90-day CPC scores as well as the number and portion of patients whose CPC scores improved and worsened between 30 and 90 days. Additionally, factors affecting improved neurological changes over the time period were examined using multivariable logistic regression. RESULTS: Of the registry's 34,745 patients, 1868 were analyzed. Favorable neurological outcomes (CPC scores of 1 and 2) were seen in 1020/1868 patients at 90 days. CPC scores at 90 days were: CPC 1: 866 (46%), CPC 2: 154 (8.2%), CPC 3: 224 (12%), and CPC 4: 392 (20%), respectively. A total of 232 patients (CPC 5: 12%) died between 30 and 90 days. In 133 patients (7%), 90-day CPC scores improved compared to their 30-day scores. In 260 patients (14%), 90-day CPC scores worsened compared with their 30-day scores. Application of target temperature management was an independent factor for 30- to 90-day neurological improvement (adjusted odds ratio: 1.69, 95% confidence interval: 1.07-2.68). CONCLUSIONS: In our nationwide registry, 7% of resuscitated patients had improved neurological changes in the 30- to 90-day period; most of the improvements were CPC scores improving from 2 to 1. Target temperature management was an independent factor associated with CPC improvement over the 30- to 90-day period.

Can Blood Ammonia Level, Prehospital Time, and Return of Spontaneous Circulation Predict Neurological Outcomes of Out-of-Hospital Cardiac Arrest Patients? A Nationwide, Retrospective Cohort Study.

BACKGROUND: This study aimed to test if blood ammonia levels at hospital arrival, considering prehospital time and the patient's condition (whether return of spontaneous circulation [ROSC] was achieved at hospital arrival), can predict neurological outcomes after out-of-hospital cardiac arrest (OHCA). METHODS: This was a retrospective cohort study on data from a nationwide OHCA registry in Japan. Patients over 17 years old and whose blood ammonia levels had been recorded were included. The primary outcome was favorable neurological outcome at 30 days after OHCA. Blood ammonia levels, prehospital time, and the combination of the two were evaluated using the receiver operating characteristic curve to predict favorable outcomes. Then, cut-off blood ammonia values were determined based on whether ROSC was achieved at hospital arrival. RESULTS: Blood ammonia levels alone were sufficient to predict favorable outcomes. The overall cut-off ammonia value for favorable outcomes was 138 µg/dL; values were different for patients with ROSC (96.5 µg/dL) and those without ROSC (156 µg/dL) at hospital arrival. CONCLUSIONS: Our results using patient data from a large OHCA registry showed that blood ammonia levels at hospital arrival can predict neurological outcomes, with different cut-off values for patients with or without ROSC at hospital arrival.

Potential Fatal Complication of Neurofibromatosis Type 1: Acute Upper Airway Obstruction Due to Ruptured Transverse Cervical Artery Aneurysm.

Neurofibromatosis type 1 (NF1) can cause vascular complications even in undiagnosed NF1 patients. A ruptured aneurysm of the branches of the subclavian artery is a rare but life-threatening event, and the hemorrhage can cause upper airway obstruction. We present a case of NF1 patient with a ruptured transverse cervical artery aneurysm, which led to a nearly obstructed airway. A 52-year-old man who was not previously diagnosed with NF1 presented with sudden pain from the left shoulder to the neck. Since childhood, he has had multiple cutaneous neurofibromas and café-au-lait macules, and freckling in the bilateral axillae. His swollen left side of the neck and left shoulder suggested a hematoma, which compressed the upper airway. Contrast-enhanced computed tomography revealed a cervical hematoma caused by a ruptured aneurysm of the transverse cervical artery. We performed awake fiberoptic intubation because a difficult airway was predicted and surgical airway management may have been impossible due to the anterior cervical hematoma. His airway was secured, and his aneurysm was successfully treated by coil embolization. Based on his cutaneous findings, he was finally diagnosed with NF1. Those who have café-au-lait macules and cutaneous neurofibromas may present with acute cervical hematoma, and it is important to consider the possibility of ruptured aneurysms in the neck region. When patients develop an acute cervical hematoma that causes an acute upper airway obstruction, emergency physicians should consider awake fiberoptic intubation to secure the airway.

State-of-the-art methods for the treatment of severe hemorrhagic trauma: selective aortic arch perfusion and emergency preservation and resuscitation-what is next?

Trauma is a primary cause of death globally, with non-compressible torso hemorrhage constituting an important part of "potentially survivable trauma death." Resuscitative endovascular balloon occlusion of the aorta has become a popular alternative to aortic cross-clamping under emergent thoracotomy for non-compressible torso hemorrhage in recent years, however, it alone does not improve the survival rate of patients with severe shock or traumatic cardiac arrest from non-compressible torso hemorrhage. Development of novel advanced maneuvers is essential to improve these patients' survival, and research on promising methods such as selective aortic arch perfusion and emergency preservation and resuscitation is ongoing. This review aimed to provide physicians in charge of severe trauma cases with a broad understanding of these novel therapeutic approaches to manage patients with severe hemorrhagic trauma, which may allow them to develop lifesaving strategies for exsanguinating trauma patients. Although there are still hurdles to overcome before their clinical application, promising research on these novel strategies is in progress, and ongoing development of synthetic red blood cells and techniques that reduce ischemia-reperfusion injury may further maximize their effects. Both continuous proof-of-concept studies and translational clinical evaluations are necessary to clinically apply these hemostasis approaches to trauma patients.

Incidence and related factors of hypoxia associated with elderly femoral neck fractures in the emergency department setting.

AIM: Femoral neck fractures in elderly patients needing oxygen therapy are often encountered in the emergency department. This single-center, retrospective, observational study aimed to examine the frequency, cause, and factors related to hypoxia in elderly patients with femoral neck fractures. METHODS: We analyzed data from 241 patients admitted to Okayama Saiseikai General Hospital (Okayama, Japan) from April 2016 to March 2019. Hypoxia was defined as PaO2 / FiO2 ratio under 300. The independent factors for hypoxia were determined by multiple logistic regression analysis. RESULTS: There were 194 patients who met the study inclusion criteria, 148 in the non-hypoxia group and 46 in the hypoxia group. The hypoxia group included patients with pneumonia (n = 3), chronic obstructive pulmonary disease (n = 2), pulmonary edema (n = 1), and pulmonary embolization (n = 1). The cause of hypoxia was undetermined in 39 cases. However, occult fat embolism syndrome was suspected in 29 of these 39 cases based on Gurd and Wilson criteria after considering clinical examination results. Barthel indexes were significantly lower in the hypoxia group on discharge. Age (adjusted odds ratio [OR] 1.07; 95% confidence interval [CI], 1.00-1.14; P = 0.038), D-dimer (adjusted OR 1.02; 95% CI, 1.00-1.03; P = 0.005), and transtricuspid pressure gradient (adjusted OR 1.03; 95% CI, 1.00-1.07; P = 0.015) were independently associated with the hypoxia. CONCLUSION: We found that hypoxia, including undetermined hypoxia, was commonly encountered in the emergency department. Hypoxia in elderly patients with femoral neck fractures was associated with age, D-dimer, and transtricuspid pressure gradient and needs further investigation.

Glycogenic hepatopathy following attempted suicide by long-acting insulin overdose in patient with type 1 diabetes.

Patients with poorly controlled insulin-dependent type 1 or type 2 diabetes rarely present with glycogenic hepatopathy, which is characterized by hepatomegaly and liver enzyme abnormalities. Glycogenic hepatopathy occurs as a consequence of excessive accumulation of glycogen in hepatocytes caused by insulin. We report a young male patient with type 1 diabetes mellitus who developed glycogenic hepatopathy following a suicide attempt by insulin overdose via subcutaneous injection. The patient's medication/nutrition compliance and adherence to insulin were poorly controlled due to comorbid schizophrenia. Our patient required a large amount of continuous glucose to maintain euglycemia for persistent intractable hypoglycemia induced by overdose of long-acting insulin. On admission day 4, the patient presented elevated transaminases, hepatomegaly, and lactic acidosis. Computed tomography revealed swollen liver parenchyma with a diffusely high absorption. The patient gradually recovered without any medical intervention except for adequate control of blood sugar and was moved to a psychiatric ward on day 8 for schizophrenia management. This report may help emergency physicians be aware of the common symptoms, clinical course, and pathophysiology of glycogenic hepatopathy. Doctors should include glycogenic hepatopathy in the differential diagnosis of abnormal liver enzymes and hepatomegaly for those with poorly controlled insulin-dependent diabetes mellitus or unstable blood sugar levels due to insulin overdose like our patient.

Therapeutic strategies for ischemia reperfusion injury in emergency medicine.

Ischemia reperfusion (IR) injury occurs when blood supply, perfusion, and concomitant reoxygenation is restored to an organ or area following an initial poor blood supply after a critical time period. Ischemia reperfusion injury contributes to mortality and morbidity in many pathological conditions in emergency medicine clinical practice, including trauma, ischemic stroke, myocardial infarction, and post-cardiac arrest syndrome. The process of IR is multifactorial, and its pathogenesis involves several mechanisms. Reactive oxygen species are considered key molecules in reperfusion injury due to their potent oxidizing and reducing effects that directly damage cellular membranes by lipid peroxidation. In general, IR injury to an individual organ causes various pro-inflammatory mediators to be released, which could then induce inflammation in remote organs, thereby possibly advancing the dysfunction of multiple organs. In this review, we summarize IR injury in emergency medicine. Potential therapies include pharmacological treatment, ischemic preconditioning, and the use of medical gases or vitamin therapy, which could significantly help experts develop strategies to inhibit IR injury.

The psoas muscle index as a predictor of mortality and morbidity of geriatric trauma patients: experience of a major trauma center in Kobe.

PURPOSE: An association between the prognoses of trauma and sarcopenia has not been well documented. The purpose of this study was to compare the outcomes of elderly Japanese trauma patients with sarcopenia and those without sarcopenia. METHODS: The medical records of patients aged ≧ 65 years old and Injury Severity Scores above 15 treated for trauma between 2010 and 2017 were reviewed, retrospectively. We measured the psoas muscle index (PMI), defined as the psoas muscle area at the third lumbar vertebra level divided by the body surface area. Patients of each gender with a PMI less than the lower interquartile range were included in the sarcopenia group. A questionnaire was mailed to the patients or their families to collect data on 1-year mortality and activities of daily living. RESULTS: There were 405 patients included in this study: 304 in the non-sarcopenia group (Group NS) and 101 in the sarcopenia group (Group S). Mortality was significantly higher in Group S than in Group NS (NS; 7.9% vs. S; 15.8%, OR, 2.20; 95% CI, 1.12-4.32; p = 0.027). Only 175 of the questionnaires were completed and the responses did not reveal any significant differences between the groups. CONCLUSIONS: Sarcopenia as defined by the PMI may be used as an indicator for mortality risk for geriatric trauma patients.

Huge abdominal cerebrospinal fluid pseudocyst following ventriculoperitoneal shunt: a case report.

INTRODUCTION: Abdominal pseudocysts comprising cerebrospinal fluid are an uncommon but significant complication in patients with ventriculoperitoneal shunt. We present a successfully treated 12-year-old boy with a history of ventriculoperitoneal shunting and a huge abdominal cerebrospinal fluid pseudocyst. CASE PRESENTATION: A12-year-old Japanese boy presented with a deteriorated consciousness and a palpable and elastic large lower abdominal mass. Computed tomography of his abdomen demonstrated a collection of homogenous low-density fluid near the catheter tip of the ventriculoperitoneal shunt. Cerebral computed tomography revealed an increased ventricular size. Based on the clinical diagnosis of abdominal pseudocyst, the peritoneal shunt catheter was secured and divided into two parts by cutting it on the chest; then, the proximal side of the peritoneal shunt catheter was externalized for extraventricular drainage. The cyst was percutaneously aspirated with ultrasound guidance, and the distal side of the peritoneal shunt catheter was removed. The distal side of the peritoneal shunt catheter was reinserted in another position into his abdomen after 3-week extraventricular drainage management. CONCLUSION: Emergency physicians should know about this potential complication as an important differential diagnosis resulting from acute abdominal complaints in patients with ventriculoperitoneal shunts.

Association of Japan Coma Scale score on hospital arrival with in-hospital mortality among trauma patients.

BACKGROUND: The Japan Coma Scale (JCS) score has been widely used to assess patients' consciousness level in Japan. JCS scores are divided into four main categories: alert (0) and one-, two-, and three-digit codes based on an eye response test, each of which has three subcategories. The purpose of this study was to investigate the utility of the JCS score on hospital arrival in predicting outcomes among adult trauma patients. METHODS: Using the Japan Trauma Data Bank, we conducted a nationwide registry-based retrospective cohort study. Patients 16 years old or older directly transported from the trauma scene between January 2004 and December 2017 were included. Our primary outcome was in-hospital mortality. We examined outcome prediction accuracy based on area under the receiver operating characteristic curve (AUROC) and multiple logistic regression analysis with multiple imputation. RESULTS: A total of 222,540 subjects were included; their in-hospital mortality rate was 7.1% (n = 15,860). The 10-point scale JCS and the total sum of Glasgow Coma Scale (GCS) scores demonstrated similar performance, in which the AUROC (95% CIs) showed 0.874 (0.871-0.878) and 0.878 (0.874-0.881), respectively. Multiple logistic regression analysis revealed that the higher the JCS score, the higher the predictability of in-hospital death. When we focused on the simple four-point scale JCS score, the adjusted odds ratio (95% confidence intervals [CIs]) were 2.31 (2.12-2.45), 4.81 (4.42-5.24), and 27.88 (25.74-30.20) in the groups with one-digit, two-digit, and three-digit scores, respectively, with JCS of 0 as a reference category. CONCLUSIONS: JCS score on hospital arrival after trauma would be useful for predicting in-hospital mortality, similar to the GCS score.

Case of Nontraumatic Rectus Sheath Hematoma from Muscle Training Mimicking Acute Abdomen.

Rectus sheath hematoma is an unusual but well-known clinical problem. Our hospital admitted a 54-year-old woman complaining of harsh right-sided hypogastric pain that started while muscle training. Computed tomography of the abdomen and pelvis demonstrated a right rectus sheath hematoma. As the hematoma did not increase, the patient was conservatively treated. Despite increased awareness of rectus sheath hematoma, its early diagnosis and treatment still present a challenge to emergency physicians. Swift acknowledgement of this rare cause of abdominal pain may avoid more intrusive examination, unnecessary hospitalization, and laparotomy. Careful consideration of the patient's medical history and a high index of suspicion are needed to diagnose this complication.

Orbital Emphysema as a Consequence of Forceful Nose-Blowing: Report of a Case.

Orbital emphysema occurs when air enters the soft tissue surrounding the orbit. Although orbital blowout fractures are often caused by face trauma, nontraumatic orbital fractures can also occur but have been rarely described. Here, a case of orbital and palpebral emphysema caused by forceful nose-blowing is presented. Examination uncovered gross swelling of the right eye and discernable subcutaneous emphysema. The patient had normal eye movement and visual acuity. Orbital computed tomography (CT) revealed orbital emphysema secondary to an orbit floor fracture into the maxillary sinus, resulting from high intranasal pressure upon blowing her nose. The patient received conservative management with antibiotics and was given instructions not to sneeze or blow her nose. She fully recovered and all her symptoms completely resolved.

Atypical case of posterior reversible encephalopathy syndrome related to late onset postpartum eclampsia: A case report.

RATIONALE: Eclampsia, an obstetric emergency frequently seen in pregnant or puerperal women, is a risk factor for posterior reversible encephalopathy syndrome (PRES). Most cases of eclampsia occur postpartum. We report a woman with PRES associated with eclampsia 10 weeks post-delivery, the latest onset ever reported. PATIENT CONCERNS: A 23-year-old healthy woman presented headache and nausea 10 weeks after delivery. Two days later, she generalized tonic-clonic seizure. Her brain MRI presented the foci which is typical of PRES. DIAGNOSIS: The patient was diagnosed as PRES associated with eclampsia. INTERVENTIONS: The patient received levetiracetam and edaravone. OUTCOMES: Her clinical course was uneventful and she fully recovered without neurological complications LESSONS:: The possible diagnosis of late onset postpartum eclampsia, even weeks post-delivery, should be considered, since initiation of early treatment averts severe complications and decreases mortality. Sharing our experience may increase awareness of PRES induced by late-onset postpartum eclampsia.

Gastric Emphysema in a Critically Ill Patient Successfully Treated without Surgery.

Gastric emphysema is a relatively rare clinical entity caused by injury to the gastric mucosa. A 62-year-old Japanese male with a history of heavy alcohol consumption and smoking was admitted to the emergency intensive care unit due to severe hypercapnic respiratory acidosis. His body mass index was only 12.6. Ten days after initiation of enteral feeding, he complained of abdominal pain. Computed tomography revealed intraluminal air in the distended gastric wall. Esophagogastroduodenoscopy showed diffuse edema, redness, and erosion throughout the stomach. Based on the findings of narrow angle and short distance of the aorta-superior mesenteric artery, the patient was diagnosed with gastric emphysema associated with superior mesenteric artery syndrome. He was successfully managed nonoperatively with treatments including intravenous antibiotics, gastric decompression, and bowel rest. Physicians should be aware of this unusual condition in such critically ill patients complaining of abdominal pain and needing close monitoring and observation to exclude gastric necrosis or perforation.

Oxygen management in mechanically ventilated patients: A multicenter prospective observational study.

PURPOSE: To observe arterial oxygen in relation to fraction of inspired oxygen (FIO2) during mechanical ventilation (MV). MATERIALS AND METHODS: In this multicenter prospective observational study, we included adult patients required MV for >48h during the period from March to May 2015. We obtained FIO2, PaO2 and SaO2 from commencement of MV until the 7th day of MV in the ICU. RESULTS: We included 454 patients from 28 ICUs in this study. The median APACHE II score was 22. Median values of FIO2, PaO2 and SaO2 were 0.40, 96mmHg and 98%. After day two, patients spent most of their time with a FIO2 between 0.3 and 0.49 with median PaO2 of approximately 90mmHg and SaO2 of 97%. PaO2 was ≥100mmHg during 47.2% of the study period and was ≥130mmHg during 18.4% of the study period. FIO2 was more likely decreased when PaO2 was ≥130mmHg or SaO2 was ≥99% with a FIO2 of 0.5 or greater. When FIO2 was <0.5, however, FIO2 was less likely decreased regardless of the value of PaO2 and SaO2. CONCLUSIONS: In our multicenter prospective study, we found that hyperoxemia was common and that hyperoxemia was not corrected.