Combining IL-6 and SARS-CoV-2 RNAaemia-based risk stratification for fatal outcomes of COVID-19.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic rapidly increases the use of mechanical ventilation (MV). Such cases further require extracorporeal membrane oxygenation (ECMO) and have a high mortality. OBJECTIVE: We aimed to identify prognostic biomarkers pathophysiologically reflecting future deterioration of COVID-19. METHODS: Clinical, laboratory, and outcome data were collected from 102 patients with moderate to severe COVID-19. Interleukin (IL)-6 level and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA copy number in plasma were assessed with ELISA kit and quantitative PCR. RESULTS: Twelve patients died or required ECMO owing to acute respiratory distress syndrome despite the use of MV. Among various variables, a ratio of oxygen saturation to fraction of inspired oxygen (SpO2/FiO2), IL-6, and SARS-CoV-2 RNA on admission before intubation were strongly predictive of fatal outcomes after the MV use. Moreover, among these variables, combining SpO2/FiO2, IL-6, and SARS-CoV-2 RNA showed the highest accuracy (area under the curve: 0.934). In patients with low SpO2/FiO2 (< 261), fatal event-rate after the MV use at the 30-day was significantly higher in patients with high IL-6 (> 49 pg/mL) and SARS-CoV-2 RNAaemia (> 1.5 copies/µL) compared to those with high IL-6 or RNAaemia or without high IL-6 and RNAaemia (88% vs. 22% or 8%, log-rank test P = 0.0097 or P < 0.0001, respectively). CONCLUSIONS: Combining SpO2/FiO2 with high IL-6 and SARS-CoV-2 RNAaemia which reflect hyperinflammation and viral overload allows accurately and before intubation identifying COVID-19 patients at high risk for ECMO use or in-hospital death despite the use of MV.

A Case of Central Pontine Myelinolysis Occurred During Treatment of Hyperosmolar Hyperglycemic Syndrome.

Central pontine myelinolysis (CPM) is a rare demyelinating condition which has been reported to occur in a variety of clinical settings, but most commonly in association with a rapid rise in plasma osmolality during correction of chronic hyponatremia. The clinical consequences can vary from a mild motor weakness that resolves completely over time to the devastating locked-in syndrome. In this presentation, we report a case of hyperosmolar hyperglycemic syndrome (HHS) with ponto-occipital disintegration. A 71-year-old female was transferred to our ER by an ambulance due to consciousness disorder and continuous fever for 10 days. We diagnosed septic shock caused by urinary tract infection (UTI), cerebral multiple infarctions, acute kidney injury (AKI) and HHS without treatment for diabetes. Then, we started therapeutic interventions for them based on the guideline with severe control for blood sugar (BS; primary 1635 mg/dl) under insulin therapy and hypernatremia (primary 153 mEq/l) under crystal infusion control in advanced care unit, apparently on routine lab data. However, the initial serum sodium value of 153 mEq/l was slowly compensated to 148 mEq/l in 60 hours under guideline on routine lab data, the initial compensated sodium value with osmolality was changed from 178 mEq/l to 150 mEq/l in the period. She recovered from her primary diagnosis and unconsciousness. After stabilized sepsis and HHS, we detected CPM on brain MRI due to following up multiple cerebral infarctions with left leg paralysis and verbal disorder. She gradually recovered over several months with intensive rehabilitation and eventually regained near normal functional capacity with stabilized BS. When we consider HHS with hypernatremia, it may be necessary to pay attention to not only to BS control and sodium control according to the guideline but also to osmolality changes to prevent CPM.

Environmental maintenance with effective and useful zoning to protect patients and medical staff from COVID-19 infection.

AIM: The coronavirus disease 2019 (COVID-19) pandemic has accelerated all over the world, and global health-care systems have become overwhelmed with potentially infectious patients seeking testing and care. It is essential to set up effective and useful zoning to prevent the spread of infection to and from medical staff or other patients with effective use of standard precautions with personal protective equipment (PPE). METHODS: We repurposed a general ward into an acute care unit for severe COVID-19 patients taking into consideration airflow, the direction of movement of medical staff, and prevention of the spread of infection to medical staff and other patients. We checked the daily condition and body temperature of all medical staff for 60 days. RESULTS: There was no evidence of COVID-19 infection in any medical staff or other patients during the period thanks to effective and useful zoning with PPE. CONCLUSION: Special wards and rooms should be set up for future protection of medical staff and other patients, and prevent the explosion of COVID-19 infection with effective and useful zoning with PPE.

Clinical course of 2019 novel coronavirus disease (COVID-19) in individuals present during the outbreak on the Diamond Princess cruise ship.

We investigated the clinical course of individuals with 2019 novel coronavirus disease (COVID-19) who were transferred from the Diamond Princess cruise ship to 12 local hospitals. The conditions and clinical courses of patients with pneumonia were compared with those of patients without pneumonia. Among 70 patients (median age: 67 years) analyzed, the major symptoms were fever (64.3%), cough (54.3%), and general fatigue (24.3%). Forty-three patients (61.4%) had pneumonia. Higher body temperature, heart rate, and respiratory rate as well as higher of lactate dehydrogenase (LDH), aspartate aminotransferase (AST), and C-reactive protein (CRP) levels and lower serum albumin level and lymphocyte count were associated with the presence of pneumonia. Ground-glass opacity was found in 97.7% of the patients with pneumonia. Patients were administered neuraminidase inhibitors (20%), lopinavir/ritonavir (32.9%), and ciclesonide inhalation (11.4%). Mechanical ventilation and veno-venous extracorporeal membrane oxygenation was performed on 14 (20%) and 2 (2.9%) patients, respectively; two patients died. The median duration of intubation was 12 days. The patients with COVID-19 transferred to local hospitals during the outbreak had severe conditions and needed close monitoring. The severity of COVID-19 depends on the presence of pneumonia. High serum LDH, AST and CRP levels and low serum albumin level and lymphocyte count were found to be predictors of pneumonia. It was challenging for local hospitals to admit and treat these patients during the outbreak of COVID-19. Assessment of severity was crucial to manage a large number of patients.

The Imbalance in Medical Demand and Supply for Pediatric Victims in an Earthquake.

OBJECTIVES: We quantified an absolute imbalance of the medical risks and the support needs for children at each disaster-based hospital in Kanagawa immediately following the occurrence of a large earthquake by using the risk resource ratio (RRR) and need for medical resources (NMR). METHODS: The RRR and NMR of 33 disaster-based hospitals were estimated through dividing the estimated number of pediatric victims by the number of critically patients. We calculated the ratio of the NMR of each hospital. RESULTS: The total number of pediatric victims in Kanagawa was estimated at 8,391. The total number of vacant beds for pediatric victims was 352. The median RRR and NMR of the total number of pediatric victims were 27 and 224. The median RRR and NMR of the number of critically ill pediatric patients were 27 and 12. CONCLUSIONS: The absolute imbalance of the RRR and NMR for children in Kanagawa was quantified. This suggests that we might embark on preparedness strategies for children in advance. (Disaster Med Public Health Preparedness. 2018;13:672-676).

Creating a new index to evaluate imbalance in medical demand and supply when disasters occur.

AIM: This study examines the use of the medical risk/resource ratio (RRR) and need for medical resources (NMR) as new indicators of the imbalance in medical demand and supply in disasters. These indicators are used to quantify the medical demand-supply imbalance per disaster base hospital, examine the demand-supply imbalance in the region, and verify the need for medical support. METHODS: We calculated the RRR of each disaster base hospital by dividing the revised estimate of the number of patients with the number of empty beds. We calculated the required number of hospital beds as the NMR to restore the RRR of each disaster base hospital to two. The RRR and NMR were combined, and prioritization for medical support was classified into three levels. RESULTS: The median RRR was 23 (range, 1-101), and the median NMR was 943 (range, 0-2,124). Fifteen hospitals had a medical support priority of 1, five hospitals had a priority of 2, and 13 hospitals had a priority of 3. CONCLUSION: The medical demand-supply imbalance and amount of medical support needed can be quantified using RRR and NMR, which allows examination of the priority level for medical support.

Adrenaline aggravates lung injury caused by liver ischemia-reperfusion and high-tidal-volume ventilation in rats.

BACKGROUND: We often administer adrenaline to improve hypotension of patients undergoing systemic inflammation that is not treated with volume resuscitation. The effects of adrenaline on injured lungs during shock status have not been elucidated. We previously demonstrated that hepatic ischemia-reperfusion followed by high-tidal-volume ventilation-induced systemic inflammation, hypotension, and lung injury in rats. Using this animal model, we investigated the effects of adrenaline on lung injury and hemodynamics. METHODS: Anesthetized rats were ventilated and underwent hepatic inflow interruption for 15 min twice. After the second liver ischemia-reperfusion, the tidal volume was increased to 24 ml · kg(-1) body weight from 6 ml · kg(-1), and 12 rats in each group were observed for 360 min after reperfusion with or without continuous intravenous adrenaline administration. Extra fluid was administered according to the decline in the arterial blood pressure. RESULTS: Adrenaline administration significantly reduced the volume of intravenous resuscitation fluid. The wet-to-dry weight ratio of the lungs was higher (7.53 ± 0.37 vs. 4.63 ± 0.35, P < 0.001), the partial oxygen pressure in arterial blood was lower (213 ± 48 vs. 411 ± 33, P = 0.004), and the tumor necrosis factor-α concentration in bronchoalveolar lavage (BAL) fluid was higher (10(2.64) ± 10(0.22) vs. 10(1.91) ± 10(0.27), P = 0.015), with adrenaline. Histopathological examinations revealed marked exudation in the alveolar spaces in rats receiving adrenaline. CONCLUSIONS: Continuous administration of adrenaline partially prevented a rapid decline in blood pressure but deteriorated lung injury in a rat model of liver ischemia-reperfusion with high-tidal-volume ventilation. A possibility that adrenaline administration aggravate ventilator-induced lung injury during systemic inflammation should be considered.

Edaravone prevents lung injury induced by hepatic ischemia-reperfusion.

BACKGROUND: Lung injury is a major clinical concern after hepatic ischemia-reperfusion (I/R), due to the production of reactive oxygen species in the reperfused liver. We investigated the efficacy of edaravone, a potent free-radical scavenger, for attenuating lung injury after hepatic I/R. MATERIALS AND METHODS: Adult male Sprague-Dawley rats were assigned to sham + normal saline (NS), I/R + NS, or I/R + edaravone group. Rats in the I/R groups were subjected to 90 min of partial hepatic I/R. Five minutes before reperfusion, 3 mg/kg edaravone was administered to the I/R + edaravone group. After 6 h of reperfusion, we evaluated lung histopathology and wet-to-dry ratio. We also measured malondialdehyde (MDA), an indicator of oxidative stress, in the liver and the lung, as well as cytokine messenger RNA expressions in the reperfused liver and plasma cytokine concentrations. RESULTS: Histopathology revealed lung damages after 6 h reperfusion of partial ischemic liver. Moreover, a significant increase in lung wet-to-dry ratio was observed. MDA concentration increased in the reperfused liver, but not in the lungs. Edaravone administration attenuated the lung injury and the increase of MDA in the reperfused liver. Edaravone also suppressed the reperfusion-induced increase of interleukin-6 messenger RNA expressions in the liver and plasma interleukin-6 concentrations. CONCLUSIONS: Edaravone administration before reperfusion of the ischemic liver attenuates oxidative stress in the reperfused liver and the subsequent lung injury. Edaravone may be beneficial for preventing lung injury induced by hepatic I/R.

[Three cases of inhalation of household pyrethroid and metoxadiazone insecticides with remarkable dyspnea].

Household insecticides containing pyrethroids as their active ingredient are widely used in Japan. We encountered three cases of dyspnea caused by insecticides containing pyrethroids and metoxadiazone. The first case was a 52-year-old woman who suffered with dyspnea after breathing interior air following use of a fumigating insecticide. Although bronchoscopy revealed laryngotracheal edema, symptoms improved following administration of hydrocortisone and midazolam. Although the second case was a 63-year-old man who suffered with dyspnea as a result of direct aerosol insecticide inhalation due to missuse, symptoms had dissipated when the patient arrived at the hospital. The third case was a 20-year-old man with allergies who presented with dyspnea due to exposure to an aerosol insecticide three days after use. An allergic mechanism was thought to be involved. Reports of respiratory symptoms and allergic reactions caused by inhalation of pyrethroids are rare. Although the levels of exposure were low in all three cases compared to oral lethal dosage, these cases presented with serious respiratory symptoms, thus suggesting the need for further considerations regarding latent cases and safety.

Spectral analyses of electroencephalography and heart rate variability during sleep in normal subjects.

We investigated the relationship between electroencephalogram (EEG) activity and autonomic nervous system function using spectral analyses of EEG and heart rate variability (HRV) in healthy subjects during sleep. Eleven subjects were enrolled in this study. From EEG, the spectral edge frequencies (SEFs including SEF50, SEF90 and SEF95) were calculated. From electrocardiogram (ECG), the spectral powers of low-frequency band (LF: 0.04-0.15 Hz), high-frequency band (HF: 0.15-0.4 Hz) and the ratio of LF to HF (LF/HF) were calculated. During sleep, each set of data was obtained as the average of a 5-min measurement. We found that SEFs and LF/HF or LF decreased simultaneously and periodically, suggesting simultaneous depression of EEG activity and relative sympathetic activity, and SEFs significantly correlated with LF/HF and LF in all subjects during sleep, but not with HF. The existence of a clear correlation of SEFs with LF or LF/HF may offer a simple approach to estimate the relationship between EEG activity and autonomic nervous system function during sleep.