Brain Hypothermia Therapy and Targeted Temperature Management for Acute Encephalopathy in Children: Status and Prospects.

In adult intensive care, brain hypothermia therapy (BHT) was reported to be effective in neuroprotection after resuscitation and cardiac arrest. By contrast, in neonatal intensive care, the pathophysiology of brain damage caused by hypoxic-ischemic encephalopathy (HIE) is attributed to circulatory disturbances resulting from ischemia/reperfusion, for which neonatal brain cryotherapy is used. The International Liaison Committee on Resuscitation, 2010, recommends cerebral cryotherapy for HIE associated with severe neonatal pseudoparenchyma death. The usefulness of BHT for neuroprotection in infants and children, especially in pediatric acute encephalopathy, is expected. Theoretically, BHT could be useful in basic medical science and animal experiments. However, there are limitations in clinical planning for treating pediatric acute encephalopathy. No international collaborative study has been conducted, and no clinical evidence exists for neuroprotection using BHT. In this review, we will discuss the pathogenesis of neuronal damage in hypoxic and hypoperfused brains; the history of BHT, its effects, and mechanisms of action; the success of BHT; cooling and monitoring methods of BHT; adverse reactions to BHT; literature on BHT. We will review the latest literature on targeted temperature management, which is used for maintaining and controlling body temperature in adults in intensive care. Finally, we will discuss the development of BHT and targeted temperature management as treatments for pediatric acute encephalopathy.

Does early excision or skin grafting of severe burns improve prognosis? A retrospective cohort study.

The present study aimed to investigate the appropriate timing of excision or skin grafting of burn wounds in patients with severe burns. We retrospectively analyzed data from the Diagnosis Procedure Combination Database, a nationwide inpatient database in Japan. Patients with severe burns (burn index ≥10) who underwent excision or skin grafting within 7 days from September 2010 to March 2019 were included. We defined the early surgery group as patients who underwent excision or skin grafting within 2 days of admission and the delayed surgery group as those who underwent surgery within 3-7 days of admission. Propensity score matching was used to compare the in-hospital mortality between the two groups, yielding a cohort of 389 pairs. A total of 2362 eligible patients were categorized into the early surgery group (n = 626) and delayed surgery group (n = 1736). The overall in-hospital mortality was 19.6%. In-hospital mortality did not differ significantly between the early surgery (15.9%) and the delayed surgery groups (17.2%; p = 0.70). These results suggest that excision or skin grafting within 2 days of admission was not associated with improved in-hospital mortality compared with surgery thereafter for patients with severe burns.

Additive effectiveness of acrylonitrile-co-methallyl sulfonate surface-treated membranes in the treatment of pneumonia: A propensity score-matched retrospective cohort study.

BACKGROUND: The acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane has cytokine adsorption capacity and is used for treating sepsis. This study aimed to compare the effects of continuous renal replacement therapy (CRRT) using the AN69ST membrane with those of CRRT using other membranes for patients with pneumonia-associated sepsis. METHODS: This retrospective, propensity score-matched, cohort study was based on a nationwide Japanese inpatient database. We included data from adults hospitalized with a primary diagnosis of pneumonia, who received CRRT using either the AN69ST membrane or another membrane within 2 days of admission, and who were discharged from the hospitals between September 2014, and March 2017. Propensity score matching was used to compare in-hospital mortality between the two groups. RESULTS: Eligible patients (N = 2393) were categorized into an AN69ST group (N = 631) and a non-AN69ST group (N = 1762). The overall in-hospital mortality rate was 38.9%. Among the 545 propensity-matched patient pairs, the in-hospital mortality rate was significantly lower in the AN69ST group than in the non-AN69ST group (35.8 vs. 41.8%, p = 0.046). CONCLUSIONS: Among patients with pneumonia-associated sepsis treated with CRRT, CRRT with the AN69ST membrane was associated with a significantly lower in-hospital mortality than CRRT with standard membranes.

Characteristics of patients who received helicopter emergency medical services in Japan from 2012 to 2019: a retrospective analysis of data from Tochigi Prefecture.

BACKGROUND: Helicopter Emergency Medical Services (HEMS) has been in operation in Japan since 2001, allowing patients almost anywhere in the nation to receive on-scene emergency treatment from physicians. However, there is insufficient literature on the characteristics of the patients who use Japanese HEMS. Thus, this study aimed to investigate the overall characteristics of patients receiving HEMS care within a single prefecture in Japan. METHODS: We retrospectively analyzed the data of 5163 patients-in Tochigi Prefecture-who received HEMS care from 2012 to 2019. Descriptive statistics were used to analyze the following aspects of care: diagnosis, severity, background characteristics, geographical and environmental variables, immediate pre-hospital intervention, transportation type, and short-term clinical outcomes. RESULTS: Among 7370 HEMS requests received during the study period, treatment was provided to 5163 patients (1.8 cases per day; 3489 men [67.6%]). Nearly 55% (n = 2856) of patients were aged above 60 years. Age peaks were observed at 0-9 years and 60-69 years. The median distance from the base hospital to the site was 26.7 km. The age-standardized rate of HEMS treatment was 30.3 patients per 100,000 people. Cases of trauma and cardiovascular diseases were the most common (65.3%). Most individuals aged 0-9 years and 60-69 years had neurological disease (seizures accounted for 80.5% of this group) and cardiovascular disease, respectively. The number of patients was similar across all four seasons. After immediate pre-hospital intervention, 81.6% of patients receiving HEMS care were transferred by the helicopter ambulance (53.4% and 28.2% to the base hospital and to other hospitals, respectively). Overall, 56.6% of patients receiving HEMS care were transferred to the base hospital, and the short-term recovery rate was above 75%. Intravenous drip and oxygen administration were the most common pre-hospital interventions (93.1% and 72.7%, respectively). CONCLUSIONS: This study is the first to describe the overall characteristics of HEMS patients using comprehensive data of all HEMS patients in one prefecture in Japan. Further research using both local- and national-level data is needed to accelerate the understanding of the benefits of HEMS.

A case of renal trauma successfully treated by close monitoring of intravesical pressure and subsequent intervention.

Management of abdominal compartment syndrome (ACS) due to renal injury is important. A 21-year-old man was taken to an emergent care unit with grade IV right kidney trauma and hypovolemic shock due to a road traffic injury. Despite twice targeted transcatheter arterial embolization of a renal artery, intravesical pressure increased and blood pressure was difficult to maintain. After right nephrectomy and ligated the bleeding lumbar arteries and veins to avoid ACS, the patient's general condition improved, and he did not develop ACS. Monitoring of intravesical pressure may be useful for deciding treatment strategy.

Transmission of toxigenic Corynebacterium ulcerans infection with airway obstruction from cats to a human.

BACKGROUND: Infections caused by Corynebacterium ulcerans, a zoonotic pathogen, have been reported worldwide. This microorganism is known to produce the diphtheria toxin and cause diphtheria-like illness. CASE PRESENTATION: A 63-year-old woman with a history of diabetes and hypertension developed cold and flu-like symptoms, which gradually progressed into respiratory distress. Therefore, the patient was intubated for dyspnea with pseudomembrane formation. A toxin-producing strain of C. ulcerans was identified, also detected in the patient's domestic cats. Multilocus sequence typing confirmed all strains, including the patient's isolate, as ST337. CONCLUSION: Multilocus sequence typing revealed zoonotic transmission of C. ulcerans from domestic cats to a human.

Characteristics of Emergency Neurological Patients Who Were Transported by Helicopter Emergency Medical Services in Tochigi, Japan.

In Japan, reports on the association of individual characteristics, and geographical distance and time with clinical outcomes for neurological emergencies involving helicopter emergency medical services (HEMS) are scarce. Using Tochigi HEMS data (2010-2018), we assessed the characteristics of 1,170 emergency neurological patients (e.g., stroke, neurotrauma, and seizure) at the base hospital, which covered 58% of all HEMS patients in the prefecture. After initial treatment in the emergency room, emergency physicians confirmed the clinical outcomes of each patient compared to those at the incident sites (recovery/non-recovery). We calculated the geographic distance from the base hospital to each incident site, and estimated and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for non-recovery against distance. The mean distance between the incident site and base hospital was 22.0 ± 11.7 km, and 77.4% of patients recovered following initial treatment. Two peak age groups were observed among emergency neurological diseases, including seizures in patients who were aged < 5 years and stroke and neurotrauma in patients who were aged 70-80 years. The percentages of stroke, traumatic head and brain injury, and seizure were 35.8%, 29.2%, and 22.8%, respectively. The incidence of stroke (aOR = 11.8, 95% CI 6.86-20.3) and neurotrauma (aOR = 4.86, 95% CI 2.78-8.51) independently predicted a poor prognosis. However, no significant association was observed with the distance from the base hospital. Therefore, in the Tochigi prefecture, geographical disparities may not affect the short-term prognosis of patients with neurological emergencies who were transported by HEMS.

An Autopsy Case of Primary Biliary Cholangitis with Histological Submassive Hepatic Necrosis Caused by Acute Hepatitis E Virus Infection.

A 59-year-old woman who had been diagnosed with cirrhotic primary biliary cholangitis (PBC) 5 years earlier was admitted for severe jaundice (total bilirubin: 30.1 mg/dL). We suspected that her cirrhotic PBC had deteriorated acutely for some reason. Her general condition deteriorated quickly, and she passed away on day 18 of admission. Hepatitis E virus (HEV)-IgA antibodies were positive, and Genotype 3b HEV involvement was confirmed from a blood sample taken on admission. Histopathological findings revealed cirrhosis and submassive loss and necrosis of hepatocytes. Clinicians should consider the possibility of acute HEV infection as a trigger for acute PBC exacerbation.

[Preoperative Metallic Stent Placement and Neoadjuvant Chemotherapy for Locally Advanced Sigmoid Colon Cancer with Obstruction and Invasion of the Psoas Muscle-A Case Report].

A 77-year-old man was diagnosed with obstructive sigmoid colon cancer invading the psoas major and iliac muscles. To avoid the postoperative paralysis of the lower limb, a self-expandable metallic stent(SEMS)was placed, and systemic chemotherapy was administered subsequently. After 4 courses of SOX, Hartmann's procedure was performed. The patient did not develop lower limb paralysis and is alive without recurrence 2 years and 3 months postoperatively. This case suggests that preoperative metallic SEMS placement and neoadjuvant chemotherapy could be an effective treatment for locally advanced colon cancer with obstruction and invasion of the adjacent tissues.

Clinical Effect of the Acrylonitrile-Co-Methallyl Sulfonate Surface-Treated Membrane as a Cytokine Adsorption Therapy for Sepsis due to Acute Panperitonitis: A Retrospective Cohort Study.

INTRODUCTION: Sepsis is a systemic inflammatory response syndrome caused by infectious diseases, with cytokines possibly having an important role in the disease mechanism. Acrylonitrile-co-methallyl sulfonate surface-treated (AN69ST) membrane is expected to improve the outcomes of patients with sepsis through cytokine adsorption. OBJECTIVE: This study aimed to investigate the clinical effect of the AN69ST membrane in comparison to standard continuous renal replacement therapy (CRRT) membranes for panperitonitis due to lower gastrointestinal perforation. METHODS: Using the Diagnosis Procedure Combination database, we identified adult patients with sepsis due to panperitonitis receiving any CRRT. Propensity score matching was used to compare patients who received CRRT with the AN69ST membrane (AN69ST group) and those who received CRRT with other membranes (non-AN69ST group). The primary outcome measure was in-hospital mortality. RESULTS: A total of 528 and 1,445 patients were included in the AN69ST group and in the non-AN69ST group, respectively. Propensity score matching resulted in 521 pairs. There was no significant difference in in-hospital mortality (32.1 vs. 35.5%; p = 0.265) and 30-day mortality (41.3 vs. 42.8%, p = 0.074) between the AN69ST group and the non-AN69ST group. CONCLUSION: There is no significant difference in-hospital mortality between CRRT with the AN69ST membrane and CRRT with standard CRRT membranes for panperitonitis due to lower gastrointestinal perforation. These results indicate that the AN69ST membrane is not superior to the standard CRRT membrane.

Ulinastatin did not reduce mortality in elderly multiple organ failure patients: a retrospective observational study in a single center ICU.

Aim: Our aim was to evaluate the effect of ulinastatin on 28-day mortality in patients who developed multiple organ failure (MOF) related to their acute illness and were admitted to the intensive care unit (ICU). Methods: We carried out a retrospective observational study of MOF patients in a general ICU of a tertiary care hospital in Japan from January 2009 to December 2012. The primary outcome was 28-day all-cause mortality. Secondary outcomes were ventilator-free days, ICU-free days, and vasopressor-free days at day 28. We investigated the association between ulinastatin treatment and outcomes using multivariable regression analysis. Results: A total of 212 MOF patients were included, 79 (37%) of whom received ulinastatin. The median age was 70 years (interquartile range, 60-77) and median APACHE II score was 25 (interquartile range, 19-29). Overall 28-day mortality was 20%. There were no significant differences between the ulinastatin group and the control group in age, gender, or APACHE II score. The ulinastatin group had higher prevalence of sepsis (44% versus 22%, P = 0.001). Multivariable logistic regression analysis showed that ulinastatin was not associated with 28-day mortality (odds ratio = 1.22; 95% confidence interval, 0.54-2.79). Moreover, ulinastatin did not reduce the mortality in patients with sepsis (odds ratio = 1.92; 95% confidence interval, 0.52-7.13). However, ICU-free days and ventilator-free days was significantly fewer in the ulinastatin group than control group. Conclusions: In this retrospective observational study, ulinastatin was not associated with mortality in elderly patients with established MOF, although it might be related to patient's utility.

Interruption of enteral nutrition in the intensive care unit: a single-center survey.

BACKGROUND: Interruption of enteral nutrition (EN) in the intensive care unit (ICU) occurs frequently for various reasons including feeding intolerance and the conduct of diagnostic and therapeutic procedures. However, few studies have investigated the details of EN interruption practices including reasons for and duration of interruptions. There is no standard protocol to minimize EN interruptions. METHODS: This is a retrospective review of 100 patients in the ICU staying more than 72 h and receiving EN in a 12-bed, medical/surgical ICU in a tertiary care center in 2013. Data collected include total time designated for EN; the number of EN interruption episodes; reason for each interruption categorized as diagnostic study, therapeutic intervention, or gastrointestinal (GI) event, and their individual subcategories; duration of each interruption; and the presence of written orders for interruptions. RESULTS: One hundred patients staying in the ICU for at least 72 h and receiving EN were included. There were 567 episodes of EN interruption over a median ICU length of stay of 17.1 (interquartile range 8.0-22.0) days. There were a median of three EN interruption episodes per patient. EN interruption was performed for undetermined reasons (166 episodes, 29%), airway manipulation (103 episodes, 18%), GI events (78 episodes, 14%), and intermittent dialysis (71 episodes, 13%). Median duration of EN interruption in all patients was 5.5 (3.0-10.0) h. The cumulative interruption time corresponds to 19% of the total time designated for EN. Duration of EN interruption varied according to reason, including airway manipulation (9.0 [5.0-21.0] h), tracheostomy (9.5 [7.5-14.0] h), and GI events (6.5 [3.0-14.0] h). The average calorie deficits due to interruptions were 11.5% of daily target calories. Only 60 episodes (12%) had clear written orders for interruption. CONCLUSIONS: Based on this single-center retrospective chart review, interruption of EN in the ICU is frequent, reasons for and duration of interruption varied, and airway procedures are associated with a relatively longer duration of interruption. Documentation and orders were frequently missing. These results warrant development of a protocol for EN interruption.

Investigation and treatment of pulmonary embolism as a potential etiology may be important to improve post-resuscitation prognosis in non-shockable out-of-hospital cardiopulmonary arrest: report on an analysis of the SOS-KANTO 2012 study.

Background: The prognosis of non-shockable out-of-hospital cardiac arrest is worse than that of shockable out-of-hospital cardiac arrest. We investigated the associations between the etiology and prognosis of non-shockable out-of-hospital cardiac arrest patients who experienced the return of spontaneous circulation after arriving at hospital. Methods and Results: All subjects were extracted from the SOS-KANTO 2012 study population. The subjects were 3,031 adults: (i) who had suffered out-of-hospital cardiac arrest, (ii) for whom there were no pre-hospital data on ventricular fibrillation/pulseless ventricular tachycardia until arrival at hospital, (iii) who experienced the return of spontaneous circulation after arriving at hospital. We compared the patients' prognosis after 1 and 3 months between various etiological and presumed cardiac factors. The proportion of the favorable brain function patients that developed pulmonary embolism or incidental hypothermia was significantly higher than that of the patients with presumed cardiac factors (1 month, P < 0.0001 and P < 0.0001, respectively; 3 months, P = 0.0018 and P < 0.0001, respectively). In multiple logistic regression analysis, pulmonary embolism and incidental hypothermia were found to be significant independent prognostic factors for 1- and 3-month survival and the favorable brain function rate. Conclusions: In patients who suffer non-shockable out-of-hospital cardiac arrest, but who experience the return of spontaneous circulation after arriving at hospital, the investigation and treatment of pulmonary embolism as a potential etiology may be important for improving post-resuscitation prognosis.

Ultrasound-guided subclavian venipuncture is more rapidly learned than the anatomic landmark technique in simulation training.

PURPOSE: Both ultrasound-guided subclavian venipuncture (US-SV) and landmark-guided subclavian venipuncture (LM-SV) are important in critical care, because the clinical utility of ultrasound guidance is still debated. Education of residents and medical students should include both techniques. The aim of this study is to compare learning these two techniques in a simulation environment. METHODS: This study was approved by the research ethics review committee. Trainees included residents and medical students who were instructed using the "Videos in Clinical Medicine" for LM-SV, or a dedicated slide series for US-SV, using the long-axis in-plane with needle-guide technique. After the lecture, trainees attempted to perform venipuncture in a simulator. All participants performed both techniques. The procedure time from initial skin puncture to detecting back-flow of fluid from the simulated vein was measured. A procedure time over 3 min, arterial puncture, or pneumothorax was counted as a failure. The end-point for each trainee was three successive successful venipunctures without a failure. A trainee who reached the end-point was considered as having acquired adequate skill. Statistical analysis of the procedure time comparing the techniques was done using the Mann-Whitney U test. RESULTS: Twenty trainees participated in this training. Adequate skill to perform US-SV was achieved within three tries, but up to nine attempts were needed for LM-SV. One arterial puncture occurred during LM-SV. No pneumothoraxes occurred during the simulation training. CONCLUSIONS: US-SV was learned more quickly than LM-SV in a simulation model.

Therapeutic hypothermia with the use of intracranial pressure monitoring for acute disseminated encephalomyelitis with brainstem lesion: a case report.

Acute disseminated encephalomyelitis confined to the brainstem is associated with poor prognosis. We describe a case of a 10-year-old boy with acute disseminated encephalomyelitis in the brainstem that developed after influenza A infection. A 10-year-old boy presented with fever and prolonged disturbance of consciousness and was admitted to our hospital. Magnetic resonance imaging (MRI) of the midbrain, with T2-weighted and fluid-attenuated inversion recovery images, suggested acute disseminated encephalomyelitis accompanied by a brainstem lesion. Lumbar puncture showed pleocytosis and increased protein content, including myelin basic protein, interleukin-6, and immunoglobulin G, all suggestive of acute disseminated encephalomyelitis. Treatments such as methylprednisolone pulse therapy, intravenous immunoglobulin, and therapeutic hypothermia were performed. Although the patient presented with anisocoria with increased intracranial pressure monitoring during hypothermia, prompt therapy with d-mannitol and dopamine was effective. Our case results suggest that hypothermia could be included in the choice of therapy for acute disseminated encephalomyelitis with brainstem lesions.

Effects of an aqueous extract of cocoa on nitric oxide production of macrophages activated by lipopolysaccharide and interferon-gamma.

OBJECTIVE: Macrophages are the primary targets of bacterial lipopolysaccharide (LPS). The effects of cocoa extract on production of nitric oxide (NO) by murine J774.1 macrophages activated by LPS and interferon-gamma (IFN-gamma) were examined. METHODS: Cocoa was suspended in heated water and centrifuged, and the supernatant was then filtered. Nitrite was measured as a quantitative indicator of NO by spectrophotometry. LPS (1.0 mg/mL) and IFN-gamma (100 U/mL) were added to cultured macrophages with 0.05% cocoa extract, 0.25% cocoa extract, or pure water. NO synthesis by macrophages was significantly inhibited by cocoa extract (P < 0.01). RESULTS: The inhibitory effect increased with concentration of the extract (P < 0.01). IFN-gamma (100 U/mL) and, later, LPS (100 microgram/mL) were added, together with 2.0% cocoa or pure water, to cultured macrophages. An inhibitory effect on NO production was observed on addition of only IFN-gamma, but more significant effects were obtained with addition of LPS (P < 0.01) and addition of both was most effective (P < 0.01). CONCLUSIONS: These data suggested that cocoa extract contains a suppressor of NO production in murine macrophages activated by LPS and IFN-gamma. This effect does not appear to be caused merely by neutralization of LPS.