Myeloid Progenitor Inhibitory Factor-1 (CCL23) Inhibits Lung Leukocyte Recruitment in a Primate Cardiopulmonary Bypass-Induced Pulmonary Ischaemia Model.

BACKGROUND: Bone marrow (BM)-derived polymorphonuclear leukocytes (PMNs) and monocytes (MO) induced by cardiopulmonary bypass (CPB) are highly proteolytic and cause postoperative lung injury. Although CCL23/Myeloid progenitor inhibitory factor-1 is a human CC chemokine with potent suppressor effects on myeloid progenitor cells, in vivo inhibitory effects on BM-derived leukocyte kinetics associated with CPB are unknown. METHODS: Two-hour CPB was surgically performed in cynomolgus monkeys and BM-derived leukocytes kinetics were monitored postoperatively by flow cytometry with 5'-bromo-2'-deoxyuridine (BrdU) and cytokine ELISA. Monkeys were given CCL23 (n=5) or saline (control, n=5) intravenously daily for 3 days before BrdU labelling and peripheral blood/bronchoalveolar lavage fluid (BALF) timepoint sampling to reveal BrdU-labelled cells. Levels of cytokines, CD11b, and L-selectin were considered leukocytic activation markers. RESULTS: The CCL23 treatment significantly prolonged BM transit of leukocytes (PMNs, 118.4±11.7-95.5±4.1 hours [control]; MO, 91.6±5.0-62.0±3.0 hours [control]) and reduced their alveolar appearance. The BM pool size of MO was decreased by CCL23 but PMNs were unaffected. CD11b, L-selectin expression of PMNs and MO during CPB, and post-surgical increases of interleukin (IL)-6, IL-8, TNF-α, MCP-1, and PMN elastase in the BALF were not suppressed. CONCLUSIONS: CCL23 treatment slows turnover of PMN and MO progenitors in BM and suppresses their circulatory release and lung recruitment. CCL23 has inhibitory effects specifically on the CPB-induced BM response and could hold value for preventing CPB-induced lung injury.

Validation of the Japan Coma Scale for the prediction of mortality in children: analysis of a nationwide trauma database.

Objective: The Japan Coma Scale (JCS) is widely used in clinical practice to evaluate levels of consciousness in Japan. There have been several studies on the usefulness of JCS in adults. However, its usefulness in evaluating children has not been reported. Therefore, this study aimed to assess the usefulness of the JCS for the prediction of mortality in children. Methods: This is a multicenter cohort study which used data from a national trauma registry (Japan Trauma Data Bank). This study included patients under 16 years of age who were treated between 2004 and 2015.The primary outcome measure was in-hospital mortality. Two models were used to examine each item of the Glasgow Coma Scale (GCS) and the JCS. Model A included the discrete levels of each index. In model B, data regarding age, sex, vital signs on arrival to hospital, the Injury Severity Score, and blunt trauma were added to each index. The effectivity of the JCS score was then evaluated using the area under the curve (AUC) for discrimination, a calibration plot, and the Hosmer-Lemeshow test for calibration. Results: A total of 9045 patients were identified. The AUCs of the GCS and JCS were 0.929 (95% confidence interval (CI) 0.904 to 0.954) and 0.930 (95% CI 0.906 to 0.954) in model A and 0.975 (95% CI 0.963 to 0.987) and 0.974 (95% CI 0.963 to 0.985) in model B, respectively. The results of the Hosmer-Lemeshow test were 0.00 (p=1.00) and 0.00 (p=1.00) in model A and 4.14 (p=0.84) and 8.55 (p=0.38) in model B for the GCS and JCS, respectively. Conclusions: We demonstrated that the JCS is as valid as the GCS for predicting mortality. The findings of this study indicate that the JCS is a useful and relevant tool for pediatric trauma care and future research.

Urticaria-like decompression illness in a caisson worker treated successfully in a monoplace chamber.

Background: Although decompression illness is rare for nondivers, it can happen in an environment involving rapid decompression. Recompression is the recommended treatment. We herein report a decompression illness case with cutis marmorata and osteonecrosis in both legs during pneumatic caisson work. Case Presentation: A 59-year-old compressed air worker suffered sudden dyspnea during pneumatic caisson work. He had rash on his trunk and limbs. He was diagnosed with decompression illness, and hyperbaric oxygen therapy was performed twice. He had no neurological dysfunction nor sequalae on discharge, but magnetic resonance imaging follow-up revealed osteonecrosis in both legs. Conclusion: A detailed medical history should be taken when treating patients with dyspnea at work. Cutis marmorata often precedes more severe symptoms. Early introduction of hyperbaric oxygen therapy is desirable.

Pediatric delirium is associated with increased brain injury marker levels in cardiac surgery patients.

Despite global consensus on the importance of screening pediatric delirium, correlations between pediatric delirium during acute brain injury and adult delirium are unclear. Therefore, we hypothesized that similar pediatric biomarkers reflect acute brain injury as in adult delirium. We observed pediatric cardiac surgery patients from neonatal age to 18 years, who were admitted to our pediatric intensive care unit after cardiovascular operations between October 2019 to June 2020, up to post-operative day 3 (4 days total). We recorded age, sex, risk score (Risk Adjustment in Congenital Heart Surgery [RACHS-1]), midazolam/dexmedetomidine/fentanyl dosage, and pediatric Sequential Organ Failure Assessment (pSOFA). Richmond Agitation-Sedation Scale (RASS), Cornell Assessment of Pediatric Delirium (CAPD), Face, Leg, Activity, Consolability (FLACC) behavioral scale, and Withdrawal Assessment Tool (WAT-1) scales were used and serum sampling for neuron specific enolase (NSE) was conducted. Consciousness status was considered hierarchical (coma > delirium > normal) and associations between conscious status and NSE were conducted by hierarchical Bayesian modeling. We analyzed 134 data points from 40 patients (median age 12 months). In the multi-regression model, NSE was positively associated with coma [posterior odds ratio (OR) = 1.1, 95% credible interval (CrI) 1.01-1.19] while pSOFA [posterior OR = 1.63, 95% CrI 1.17-2.5], midazolam [posterior OR = 1.02, 95% CrI 1.01-1.04], and dexmedetomidine [posterior OR = 9.52, 95% CrI 1.02-108.85] were also associated. We also evaluated consciousness state probability at each NSE concentration and confirmed both that consciousness was hierarchically sorted and CAPD scores were also associated with NSE [posterior OR = 1.32, 95% CrI 1.09-1.58]. "Eye contact" (r = 0.55) was the most correlated component with NSE within the pain, withdrawal syndrome, and PD items. PD within the hierarchy of consciousness (coma, delirium, normal) and CAPD scores are associated with brain injury marker levels. Using pediatric delirium assessment tools for monitoring brain injury, especially eye contact, is a reliable method for observing PD.

Relationship Between Prehospital Time and 24-h Mortality in Road Traffic-Injured Patients in Laos.

BACKGROUND: Road traffic injury has long been regarded as a "time-dependent disease." However, shortening the prehospital time might not improve the outcome in developing countries given the current quality of in-hospital care. We aimed to examine the relationship between the prehospital time and 24-h mortality among road traffic victims in Laos. METHODS: A prospective observational study was conducted using the trauma registry data on traffic-injured patients who were transported by ambulance to a trauma center in the capital city of Laos from May 2018 to April 2019. The analysis focused on patients with non-mild conditions, whose outcomes could be affected by the prehospital time. To examine the relationship between a prehospital time of <60 min and 24-h mortality, a generalized estimating equation model was used incorporating the inverse probability weights utilizing the propensity score for the prehospital time. RESULTS: Of 701 patients, 73% were men, 91% were riding 2- or 3-wheel motor vehicles during the crash, and 68% had a prehospital time of <60 min. A total of 35 patients died within 24 h after the crash. Compared with those who survived, individuals who died tended to have head and torso injuries. The proportions of 24-h mortality were 4.7% and 5.4% in patients whose prehospital time was <60 min and ≥60 min, respectively. No significant relationship was found between the prehospital time and 24-h mortality. CONCLUSION: A shorter prehospital time was not associated with the 24-h survival among road traffic victims in Laos.

A desmoplastic fibroblastoma that developed in the anterior mediastinum: a case report.

BACKGROUND: Desmoplastic fibroblastoma (also known as collagenous fibroma) is a benign, slowly growing soft-tissue tumor. Most desmoplastic fibroblastomas develop in the limbs, neck, or trunk. A mediastinal origin is quite rare. CASE PRESENTATION: A 32-year-old Asian female was referred to us for the diagnosis and treatment of an anterior mediastinal tumor. The tumor was 80 mm in the largest diameter and was located on the pericardium. No invasion was evident. She underwent resection of the tumor via video-assisted thoracoscopic resection. The tumor was totally encapsulated, and its pedicle was on the pericardium. The resected specimen was very rigid, making it difficult to remove from the intercostal space. Histologically, the tumor was composed of a paucicellular dense collagenous tissue. Mitosis was rarely observed, and cellular atypia was not evident, suggesting that the tumor was benign. We diagnosed the tumor as a desmoplastic fibroblastoma by morphology and immunohistochemistry. CONCLUSIONS: Desmoplastic fibroblastoma of the mediastinum is an extremely rare disease. Preoperative diagnosis is difficult. Early surgical resection is suitable for diagnosis and treatment planning.

Mechanism of Drug Tolerant Persister Cancer Cells: The Landscape and Clinical Implication for Therapy.

A minor population of cancer cells may evade cell death from chemotherapy and targeted therapy by entering a reversible slow proliferation state known as the drug tolerant persister (DTP) state. This DTP state can allow cancer cells to survive drug therapy long enough for additional mechanisms of acquired drug resistance to develop. Thus, cancer persistence is a major obstacle to curing cancers, where insight into the biology of DTP cells and therapeutic strategies targeting this mechanism can have considerable clinical implications. There is emerging evidence that DTP cells adapt to new environments through epigenomic modification, transcriptomic regulation, flexible energy metabolism, and interactions with the tumor microenvironment. Herein, we review and discuss the various proposed mechanisms of cancer persister cells and the molecular features underlying the DTP state, with insights into the potential therapeutic strategies to conquer DTP cells and prevent cancer recurrence or therapeutic failures.

Impact of adverse events on patient outcomes in a Japanese intensive care unit: a retrospective observational study.

AIM: We investigated adverse events (AEs) in a Japanese intensive care unit (ICU) and evaluated the impact of cause-specific AEs on mortality and length of stay. DESIGN: A retrospective observational study in the ICU of an academic hospital. METHODS: We reviewed medical records with the Global Trigger Tool. RESULTS: Of the 246 patients, 126 (51%) experienced one or more AEs with an incidence of 201 per 1000 patient-days and 115 per 100 admissions. A total of 294 AEs were detected with 119 (42%) adverse drug events, 67 (24%) procedural complications, 63 (22%) surgical complications, 26 (9%) nosocomial infections, 5 (2%) therapeutic errors and 4 (1%) diagnostic errors. Adverse event (AE) presence was associated with length of ICU stay (ß = 2.85, 95% confidence interval [CI]: 1.09-4.61). Adverse drug events, procedural complications and nosocomial infections were strongly associated with length of ICU stay (ß = 2.38, 95% CI: 0.77-3.98; ß = 3.75, 95% CI: 2.03-5.48; ß = 6.52, 95% CI: 4.07-8.97 respectively).

Development of the Japanese version of the Intensive Care Unit Trigger Tool to detect adverse events in critically ill patients.

AIM: The Intensive Care Unit Trigger Tool (ICUTT) was developed to detect adverse events (AEs) in intensive care unit (ICU) patients. The purpose of this study was to determine the validity and reliability of the Japanese version of the ICUTT (ICUTT-J). METHODS: The translation of ICUTT was carried out based on the guideline for translation of instruments. Subsequently, two review teams independently reviewed 50 patients' medical records using the ICUTT-J, and agreement regarding the presence and number of AEs was evaluated to ensure reliability. RESULTS: The ICUTT-J was submitted to the authors of the original ICUTT, who confirmed it as being equivalent to the original version. The item-content validity index and scale-content validity index were 1.00 and 1.00, respectively. Interrater reliability showed moderate agreement of κ = 0.52 in terms of the presence of AEs and linear weighting of κ = 0.49 (95% confidence interval, 0.28, 0.71) in terms of the number of AEs. CONCLUSION: This study's findings suggest that the ICUTT-J is valid and moderately reliable for use in ICUs.

Adequacy of hand positioning by medical personnel during chest compression in a simulation study.

AIM: During chest compressions (CCs), the hand position at the lower half of the sternum is not strictly maintained, unlike depth or rate. This study was conducted to determine whether medical staff could adequately push at a marked location on the lower half of the sternum, identify where the inappropriate hand position was shifted to, and correct the inappropriate hand position. METHODS: This simulation-based, prospective single-center study enrolled 44 medical personnel. Pressure and hand position during CC were ascertained using a flexible pressure sensor. The participants were divided into four groups by standing position and the hand in contact with the sternum: right-left (R-l), right-right (R-r), left-right (L-r), and left-left (L-l). We compared the groups and the methods: the manual method (MM), the thenar method, and the hypothenar method (HM). RESULTS: Among participants using the MM, 80% did not push adequately at the marked location on the lower half of the sternum; 60%-90% of the inadequate positions were shifted to the hypothenar side. CCs with the HM facilitated stronger pressure, and the position was minimally shifted to the hypothenar side. CONCLUSION: Medical staff could not push at an appropriate position during CCs. Resuscitation courses should be designed to educate personnel on the appropriate position for application of maximal pressure while also evaluating the position during CCs.

Levetiracetam versus fosphenytoin as a second-line treatment after diazepam for status epilepticus: study protocol for a multicenter non-inferiority designed randomized control trial.

BACKGROUND: Status epilepticus (SE) is an emergency condition for which rapid and secured cessation is important. Phenytoin and fosphenytoin, the prodrug of phenytoin with less severe adverse effects, have been recommended as second-line treatments. However, fosphenytoin causes severe adverse events, such as hypotension and arrhythmia. Levetiracetam reportedly has similar efficacy and higher safety for SE; however, evidence to support its use for adult SE is lacking. In the present study, a non-inferiority designed multicenter randomized controlled trial (RCT) is being conducted to compare levetiracetam with fosphenytoin after diazepam as a second-line treatment for SE. METHODS: This multicenter, prospective, and open-label RCT is conducted in emergency departments. Between December 23, 2019, and March 31, 2023, 176 patients with convulsive SE transported to an emergency room will be randomized into a fosphenytoin group and levetiracetam group at a ratio of 1:1. The definition of SE is "continuous seizures longer than 5 min or discrete seizures longer than 2 min with intervening consciousness disturbance." In both groups, diazepam is initially administered at 1-20 mg, followed by intravenous fosphenytoin at 22.5 mg/kg or intravenous levetiracetam at 1000-3000 mg. The primary outcome is the seizure cessation rate within 30 min. Seizure recurrence within 24 h, severe adverse events, and intubation rate within 24 h are secondary outcomes. DISCUSSION: The present study was approved and conducted as an initiative study of the Japanese Association for Acute Medicine. If non-inferiority is identified, the society will pursue an application for the national health insurance coverage of levetiracetam for SE via a public knowledge-based application. TRIAL REGISTRATION: Japan Registry of Clinical Trials jRCTs031190160 . Registered on December 13, 2019.

Medicine at mass gatherings: current progress of preparedness of emergency medical services and disaster medical response during 2020 Tokyo Olympic and Paralympic Games from the perspective of the Academic Consortium (AC2020).

Mass gatherings are events characterized by "the concentration of people at a specific location for a specific purpose over a set period of time that have the potential to strain the planning and response resources of the host country or community." Previous reports showed that, as a result of the concentration of people in the limited area, injury and illness occurred due to several factors. The response plan should aim to provide timely medical care to the patients and to reduce the burden on emergency hospitals, and to maintain a daily emergency medical services system for residents of the local area. Although a mass gathering event will place a significant burden on the local health-care system, it can provide the opportunity for long-term benefits of public health-care and improvement of daily medical service systems after the end of the event. The next Olympic and Paralympic Games will be held in Tokyo, during which mass gatherings will occur on a daily basis in the context of the coronavirus disease (COVID-19) epidemic. The Academic Consortium on Emergency Medical Services and Disaster Medical Response Plan during the Tokyo Olympic and Paralympic Games in 2020 (AC2020) was launched 2016, consisting of 28 academic societies in Japan, it has released statements based on assessments of medical risk and publishing guidelines and manuals on its website. This paper outlines the issues and countermeasures for emergency and disaster medical care related to the holding of this big event, focusing on the activities of the academic consortium.

Closed reduction and minimally invasive surgical treatment of type IIIa fragility fractures of the pelvis associated with ipsilateral periprosthetic femur fracture: A case report.

Patients with fragility fractures of the pelvic ring (FFP) are elderly and, from the perspective of surgical invasion, percutaneous and stable fixation may be a superior surgical method than open reduction and internal fixation (ORIF). While in the case of FFP type IIIa, ORIF, as a rule, typically requires open reduction of the displaced ilium via an anterior intrapelvic approach and/or lateral window of the ilioinguinal approach. We have reported here the case of an 89-year-old woman who suffered from FFP type IIIa with ipsilateral periprosthetic femur fracture that was surgically treated. The iliac fracture was approached in a minimally invasive manner using the traction operation while preparing for femoral shaft fracture surgery, which did not require open reduction, and showed favorable outcomes.

Successful use of extracorporeal membrane oxygenation for airway-obstructing lung adenocarcinoma.

Endobronchial-invasive lung cancers are generally diagnosed at advanced stages and may require emergency treatment for airway obstruction. Stent implantation is a common intervention for such obstructed airways but certain subsets of patients cannot receive adequate treatment without respiratory support. Veno-venous extracorporeal membrane oxygenation (ECMO) is a salvage therapy for respiratory failure but its usefulness in managing patients with advanced lung cancer remains unclear given the poor prognosis. In recent years, molecular targeted agents for patients with driver mutations offer rapid responses and may be administered even while under critical care. In this report, we describe the case of 39-year-old female who presented to our emergency department with severe respiratory distress. A computed tomography scan revealed a large mediastinal tumor invading the tracheal carina causing severe stenosis of the left main bronchus and right main pulmonary artery. ECMO support was required as the respiratory condition remained unstable despite high pressure ventilation. Under ECMO support, the patient underwent bronchial stent implantation and was successfully weaned off ECMO. The tumor was histologically diagnosed as pulmonary adenocarcinoma with anaplastic lymphoma kinase gene rearrangement. Treatment with a tyrosine kinase inhibitor, alectinib, induced a marked tumor reduction within a short period. The patient recovered well and is now in remission one year later. This case indicates that intensive respiratory support with ECMO may become a bridge through the critical period for selected patients with respiratory failure secondary to advanced lung cancer. KEY POINTS: SIGNIFICANT FINDINGS OF THIS STUDY: ECMO was important to maintain oxygenation during airway intervention for acute respiratory failure due to critical lung adenocarcinoma with ALK gene rearrangement. WHAT THIS STUDY ADDS: With the development of targeted therapies and the improvement in therapeutic bronchoscopy, intensive respiratory support with ECMO may be helpful especially in selected lung cancer patients with oncogenic driver mutations.

Fatal acute hypernatremia resulting from a massive intake of seasoning soy sauce.

BACKGROUND: Hypernatremia due to salt poisoning is clinically rare and standard care procedures have not been established. We report a case of salt poisoning due to massive intake of seasoning soy sauce. CASE PRESENTATION: A 40-year-old woman presented to the emergency department with seizures and remarkable hypernatremia with a serum sodium concentration of 183 mEq/L. The initial brain computed tomography scan showed brain shrinkage, which could occur during the acute phase of hypernatremia. We reduced her serum sodium level rapidly, rather than at the recommended slow rate. On day 3, the patient's brain computed tomography scan showed widespread low-density areas and edema. The patient died 8 days after admission. CONCLUSION: After reviewing instances of resuscitation following salt intoxication, aggressive rapid correction of serum sodium concentration should only be considered in acute phases of hypernatremia within a few hours from ingestion, and 2-3 h could be one of the criteria.

Delayed union of a surgically treated fragility fracture of the pelvis: A case report.

INTRODUCTION: There are no universally accepted treatment strategies for fragility fractures of the pelvis (FFPs). The incidence of delayed union or non-union of Type IIIa FFP is still unknown. PRESENTATION OF CASE: We describe a case of delayed union of a Type IIIa FFP. A 96-year-old female patient who lives independently accidentally fell when exiting a car. The diagnosis of Type IIIa FFP with displaced left ilium and left pubic rami fracture. Surgical repair was performed using an anterior intrapelvic approach with constructs made using two reconstruction contoured plates to bridge the medial edge and middle part of the fracture. This case was revealed delayed union. The periodic CT examinations were performed to determine the progress of bone union. The patient returned to most social activities including living independently and the Modified Majeed score was 94 at 12 months post-operation. DISCUSSION: For the case of TypeⅢa FFP, soft tissue is spread over a wide area. When the fracture site of ilium was exposed, the cortical bone was found to be thin with poor blood flow. There is a possibility that the blood flow was hindered by subperiosteal elevation of the iliacus muscle from the internal iliac fossa in this case. CONCLUSION: Non-union of the iliac wings is relatively rare following high-energy pelvic ring fractures. The incidence of delayed union or non-union of Type IIIa FFP remains unknown; therefore, careful follow-up of patients who undergo treatment is necessary to reduce the risk of delayed union.