Arterial and Venous Thrombosis Complicated in COVID-19: A Retrospective Single Center Analysis in Japan.

Background: Thrombosis is a characteristic complication in coronavirus disease 2019 (COVID-19). Since coagulopathy has been observed over the entire clinical course, thrombosis might be a clue to understanding the specific pathology in COVID-19. Currently, there is limited epidemiological data of COVID-19-associated thrombosis in the Japanese population and none regarding variant strains of SARS-CoV-2. Here, we elucidate the risk factors and the pattern of thrombosis in COVID-19 patients. Methods: The patients consecutively admitted to Tokyo Medical and Dental University Hospital with COVID-19 were retrospectively analyzed. SARS-CoV-2 variants of concern/interest (VOC/VOI) carrying the spike protein mutants E484K, N501Y, or L452R were identified by PCR-based analysis. All thrombotic events were diagnosed by clinical symptoms, ultrasonography, and/or radiological tests. Results: Among the 516 patients, 32 patients experienced 42 thromboembolic events. Advanced age, severe respiratory conditions, and several abnormal laboratory markers were associated with the development of thrombosis. While thrombotic events occurred in 13% of the patients with a severe respiratory condition, those events still occurred in 2.5% of the patients who did not require oxygen therapy. Elevated D-dimer and ferritin levels on admission were independent risk factors of thrombosis (adjusted odds ratio 9.39 and 3.11, 95% confidence interval 2.08-42.3, and 1.06-9.17, respectively). Of the thrombotic events, 22 were venous, whereas 20 were arterial. While patients with thrombosis received anticoagulation and antiinflammatory therapies with a higher proportion, the mortality rate, organ dysfunctions, and bleeding complications in these patients were higher than those without thrombosis. The incidence of thrombosis in COVID-19 became less frequent over time, such as during the replacement of the earlier strains of SARS-CoV-2 by VOC/VOI and during increased use of anticoagulatory therapeutics. Conclusion: This study elucidated that elevated D-dimer and ferritin levels are useful biomarkers of thrombosis in COVID-19 patients. The comparable incidence of arterial thrombosis with venous thrombosis and the development of thrombosis in less severe patients required further considerations for the management of Japanese patients with COVID-19. Further studies would be required to identify high-risk populations and establish appropriate interventions for thrombotic complications in COVID-19.

Hydrodynamic Approach for Revealing Venous Anastomotic Stenosis Formation Within a Dialysis Arteriovenous Graft.

A conventional arteriovenous graft in patients on dialysis often leads to anastomotic stenosis, which decreases the blood flow rate and increases the risk of complications. In this study, based on hydrodynamics, the pulsatile pressure at the blood vessel graft-vein junction was investigated experimentally and numerically for revealing the causes of stenosis formation and inward remodeling. In the experiments, the pulsatile pressure and displacement at the anastomotic connection were measured at a branched collapsible tube. It was revealed that the pressure becomes negative between pressure peaks of the pulsatile flow; furthermore, tube diameter changes in accordance with the pressure pulsation. Subsequently, numerical simulations revealed that a relatively large pressure difference occurs at the anastomotic connection because of flow collision and separation as compared with the other part, and the pulsatile pressure. Therefore, it is possible that vein at an anastomotic connection may change its shape under pulsating flow. Furthermore, it was found that the pressure difference slightly increased with the anastomosis angle, but the anastomosis angle did not affect the flow rate. Clinical trials in the next step are required to reveal the causal relationship between stenosis and the pulsatile pressure, but the pulsatile flow and its pressure are likely to be one factor in stenosis and inward remodeling.

Analytical Solutions of a Two-Compartment Model Based on the Volume-Average Theory for Blood Toxin Concentration during and after Dialysis.

Accurate prediction of blood toxin concentration during and after dialysis will greatly contribute to the determination of dialysis treatment conditions. Conventional models, namely single-compartment model and two-compartment model, have advantages and disadvantages in terms of accuracy and practical application. In this study, we attempted to derive the mathematical model that predicts blood toxin concentrations during and after dialysis, which has both accuracy and practicality. To propose the accurate model, a new two-compartment model was mathematically derived by adapting volume-averaging theory to the mass transfer around peripheral tissues. Subsequently, to propose a practical model for predicting the blood toxin concentration during dialysis, an analytical solution expressed as algebraic expression was derived by adopting variable transformation. Furthermore, the other analytical solution that predicts rebound phenomena after dialysis was also derived through similar steps. The comparisons with the clinical data revealed that the proposed analytical solutions can reproduce the behavior of the measured blood urea concentration during and after dialysis. The analytical solutions proposed as algebraic expressions will allow a doctor to estimate the blood toxin concentration of a patient during and after dialysis. The proposed analytical solutions may be useful to consider the treatment conditions for dialysis, including the rebound phenomenon.

Efficacy of multidisciplinary team approach with extracorporeal membrane oxygenation for COVID-19 in a low volume ECMO center.

Veno-venous extracorporeal membrane oxygenation (VV ECMO) is an effective and proven adjunct support for various severe respiratory failures requiring invasive mechanical ventilation and cardiovascular support. In response to the rapidly increasing number of COVID-19 patients in Japan, we launched an ECMO support team comprised of multidisciplinary experts including physicians, nurses, perfusionists, and bioethicists in preparation for the threat of a pandemic. From April 2 to July 15, 2020, Tokyo Medical and Dental University hospital treated 104 PCR confirmed COVID-19 patients. Among those, 34 patients were admitted to intensive care unit (ICU) and 5 patients required VV ECMO. All management related to ECMO was decided by the ECMO support team in addition to participation of the ECMO support team in daily multidisciplinary rounds in the ICU. Median age was 54 years old. Duration from onset to mechanical ventilation (MV) and MV to ECMO were 8 and 7 days, respectively. Four patients (80%) were successfully weaned off from ECMO. One patient died after 81 days of ECMO run. Four patients were discharged and recovered to their prehospital quality of life without major disability. We achieved a high survival rate using ECMO in our low volume ECMO institution during the COVID-19 pandemic. Multidisciplinary decision-making and a team approach for the unclear pathology with an emerging infectious disease was effective and contributed to the survival rate.

AN69ST membranes adsorb nafamostat mesylate and affect the management of anticoagulant therapy: a retrospective study.

BACKGROUND: In Japan, nafamostat mesylate (NM) is frequently used as an anticoagulant during continuous renal replacement therapy (CRRT). The dialyzer membrane AN69ST has been reported to adsorb NM and affect the management of anticoagulant therapy. However, the adsorbed amount has not yet been quantitatively assessed. Therefore, in this study, we evaluated the pre- and post-hemofilter prolongation of the activated clotting time (ACT) in patients with AN69ST and PS membranes. We also measured the adsorption of NM in three types of CRRT membranes using an experimental model. METHODS: In a study of patients who underwent CRRT using AN69ST or PS membranes in 2015 at the Advanced Emergency and Critical Care Center, Okayama University Hospital, pre- and post-hemofilter ACT measurements were extracted retrospectively, and the difference was calculated. In addition, AN69ST (sepXiris100), PS (HEMOFEEL SHG-1.0), and PMMA membranes (HEMOFEEL CH-1.0N) were used in an in vitro model of a dialysis circuit, and the concentrations of NM were measured in pre- and post-hemofilter membranes and filtrates. RESULTS: The ACT difference was significantly lower in the group using AN69ST membranes (p < 0.01). In the in vitro model (n = 4) with adsorption and filtration, the post-hemofilter and filtrate concentrations of NM in AN69ST membranes were significantly lower than those in the PS and PMMA membranes (p < 0.01). The NM adsorption clearance of the AN69ST membrane was significantly higher than that of the PS and PMMA membranes. CONCLUSIONS: The AN69ST membrane had higher NM adsorption than the PS and PMMA membranes. This may have resulted in the lower ACT difference in patients undergoing CRRT using the AN69ST membrane than in patients undergoing CRRT using PS or PMMA membranes.

Citrobacter braakii bacteremia-induced septic shock after colonoscopy preparation with polyethylene glycol in a critically ill patient: a case report.

BACKGROUND: Polyethylene glycol (PEG) is widely used for bowel cleaning in preparation for colonoscopy because of its safety. Septic shock after PEG preparation is an extremely rare complication. Herein, we describe a case of septic shock that occurred immediately after colonoscopy preparation with PEG. CASE PRESENTATION: A 75-year-old Japanese male who had previously developed diabetes after total pancreatectomy received PEG in preparation for colonoscopy. He had been admitted to the emergency intensive care unit 4 days earlier due to hematochezia presenting with shock. He ingested PEG to prepare for a colonoscopy examination, which was performed to identify the source of his bleeding over a 5-h period, but suddenly exhibited septic shock and markedly elevated procalcitonin levels. A blood culture subsequently revealed Citrobacter braakii. Immediate resuscitation and intensive care with appropriate antibiotics improved his condition. CONCLUSIONS: Clinicians should be aware of the possibility of deteriorating conditions after bowel preparation with PEG among severely ill patients with recent episodes of hemorrhagic shock.

Intracranial Pressure Monitoring for Pediatric Acute Encephalopathy.

Newly published clinical practice guidelines recommend intracranial pressure (ICP) monitoring in critical care for the management of pediatric acute encephalopathy (pAE), but the utility of ICP monitoring for pAE has been poorly studied. We recently performed direct ICP monitoring for two patients. We observed that although the direct ICP monitoring had clinical benefits with less body weight gain and no vasopressor use in both cases, this monitoring technique is still invasive. Future studies should determine the utility of non-invasive ICP monitoring systems in pAE to further improve the quality of intensive-care management.

Recurrent apnea in an infant with pertussis due to household transmission.

Bordetella pertussis causes life-threatening apnea in infants. Lymphocytosis is an important clue for diagnosis and for determining the severity of pertussis. Antibiotics do not shorten or ameliorate the disease and only decrease the risk of transmission. Antepartum maternal immunization is important for preventing pertussis in infants.

The Clinical Application of Hydrogen as a Medical Treatment.

In recent years, it has become evident that molecular hydrogen is a particularyl effective treatment for various disease models such as ischemia-reperfusion injury; as a result, research on hydrogen has progressed rapidly. Hydrogen has been shown to be effective not only through intake as a gas, but also as a liquid medication taken orally, intravenously, or locally. Hydrogen's effectiveness is thus multifaceted. Herein we review the recent research on hydrogen-rich water, and we examine the possibilities for its clinical application. Now that hydrogen is in the limelight as a gaseous signaling molecule due to its potential ability to inhibit oxidative stress signaling, new research developments are highly anticipated.

Soft tissue hematoma of the neck due to thyroid rupture with unusual mechanism.

INTRODUCTION: Massive bleeding from the thyroid gland causing airway compromise secondary to indirect neck trauma is rare. PRESENTATION OF CASE: An 89-year-old woman was transferred to our emergency department due to anterior neck pain after a traffic accident. She had been propelled forward and struck her head on the front mirror during emergency braking. Airway patency was confirmed at the first contact. Although her vital signs were stable at presentation, she gradually suffered from respiratory distress and severe dyspnea, implying airway compression, therefore requiring endotracheal intubation. Computed tomography (CT) revealed a large, encapsulated hematoma in the left thyroid gland lobe extending to the upper mediastinum. Contrast-enhanced CT demonstrated an extravasation of the contrast agent around the left superior thyroid artery. The left thyroid artery was ligated and the hematoma was removed immediately. She had a favorable course without further complications and was discharged 36days after admission. DISCUSSION: Airway management is the most important consideration in patients with thyroid injury. Treatment should be customized depending on the degree of respiratory distress resulting from of either involvement of the direct airway or secondary compression. CONCLUSION: Although hemorrhage from the thyroid gland without blunt trauma is rare, emergency physicians should regard possible thyroid gland rupture in patients with swelling of the neck or acute respiratory failure after direct/indirect trauma to the neck. Observation or operative management for limited or expanding hematoma are appropriately based on fundamental neck trauma principles.

A case of cricothyroidotomy for facial trauma in a patient taking antiplatelet agents after a simple ground-level fall.

INTRODUCTION: Cricothyroidotomy is an emergency procedure that can be used to secure the airway in situations in which intubation and ventilation are not possible. PRESENTATION OF CASE: We describe a case of 79-year-old male presenting with facial trauma combined with massive upper airway bleeding and swelling in which cricothyroidotomy was required to open the airway in an elderly male patient taking antiplatelet agents who suffered a simple ground-level fall. DISCUSSION: Although emergency airway management is often required in patients with Le Fort fractures, mandibular condyle fractures exhibit a significant relationship with ground-level falls, which are not usually associated with emergency airway management. Prophylactic intubation should be considered prior to transfer or deterioration in a trauma patient with dual antiplatelet drugs and fractures of bilateral mandibular condyle. CONCLUSION: Clinicians should be aware of the life-threatening injuries that can be caused by simple ground-level falls in patients taking antiplatelet agents.

Three cases of heparin-induced thrombocytopenia associated with polytrauma.

Case: We present three cases in which patients that had suffered polytrauma developed heparin-induced thrombocytopenia after the start of heparin treatment for thrombosis. All three patients had high injury severity scores and required major surgery. They all started receiving unfractionated heparin for deep venous thrombosis with or without an asymptomatic pulmonary embolism. The patients were clinically diagnosed with heparin-induced thrombocytopenia after their platelet counts fell or exhibited a delayed recovery. Outcome: Heparin-induced thrombocytopenia and the associated thromboses were successfully treated by discontinuing all forms of heparin treatment and administering argatroban followed by warfarin. Conclusion: Early recognition and clinical diagnosis of heparin-induced thrombocytopenia is necessary for clinicians in cases in which severely injured trauma patients show reductions or delayed recovery in their platelet counts in combination with thrombosis after starting heparin treatment.

Characteristics and Costs of Ladder Fall Injuries: A Report from a Single Emergency Center in Okayama.

We sought to identify the incidence, injury patterns, and financial burden of ladder fall injuries to provide a reference for reinforcing guidelines on the prevention of such injuries. We enrolled the patients who were injured in a ladder-related fall and required intensive care between April 2012 and March 2014 at Okayama University Hospital, a tertiary care hospital in Okayama City:9 patients injured in 7 stepladder falls and 2 straight ladder falls. The median patient age was 69 years, and 8 were males. Six falls occurred in non-occupational settings. Head injuries predominated, and the injury severity score ranged from 2 to 35 (mean＝21±12). At the time of discharge from the intensive care unit, one patient had died and 5 patients had some neurological disabilities. The case fatality rate was 11%. The total cost of care during the review period was ï¿¥16,705,794, with a mean cost of ï¿¥1,856,199 per patient. Ladder fall injuries are associated with a high rate of neurological sequelae and pose a financial burden on the health insurance system. A prevention education campaign targeting at older-aged males in non-occupational settings may be a worthwhile health service investment in this community.

An unusual case of a patient who presented with haemorrhagic shock following massive subcutaneous haematomas of the lower back due to blunt trauma.

An 83-year-old woman with no significant medical history was transferred to our tertiary hospital after being hit by a car and presenting with haemorrhagic shock. Immediate fluid resuscitation was performed; physical, chest/pelvic X-ray and echographic examinations did not detect any major sources of bleeding. However, a contrast-enhanced CT scan revealed multiple regions of significant contrast extravasation in an extensive part of the subcutaneous tissue of the patient's lower back, which is an unusual source of bleeding. Transcatheter arterial embolisation of the lumbar and internal iliac arteries and their branches was carried out. In addition, haemostatic resuscitation was performed for damage control resuscitation, which successfully resolved the patient's haemorrhagic shock.

Superior ophthalmic vein thrombosis associated with severe facial trauma: a case report.

INTRODUCTION: Superior ophthalmic vein thrombosis is a rare entity, but is associated with significant morbidities. We describe a case in which superior ophthalmic vein thrombosis occurred shortly after severe facial trauma. CASE PRESENTATION: A 77-year-old Japanese man was transferred to our tertiary hospital after a motor vehicle accident. Le Fort III facial bone fractures and a minor cerebral contusion were detected. Follow-up computed tomography scans detected dilatation of his left superior ophthalmic vein on day 3 and thrombosis on day 12; however, no causative carotid cavernous fistula was observed. As he did not present with any symptoms other than slight conjunctival congestion, a conservative management strategy was adopted along with anticoagulant therapy against deep venous thrombosis. The superior ophthalmic vein thrombosis resolved spontaneously and the conjunctival congestion also improved. CONCLUSIONS: Superior ophthalmic vein thrombosis should be taken into consideration and managed properly after severe facial injuries, and further investigation of its cause is necessary to prevent morbidities.

Prevalence, risk factors, and short-term consequences of traumatic brain injury-associated hyponatremia.

Hyponatremia, a common electrolyte disorder associated with traumatic brain injuries (TBIs), has high mortality and morbidity rates. The aim of this study was to identify the risk factors for hyponatremia associated with TBI. We retrospectively analyzed the cases of TBI patients who were admitted to the emergency intensive care unit at Okayama University Hospital between October 2011 and September 2014. A total of 82 TBI patients were enrolled. The incidences of hyponatremia (serum sodium level of＜135mEq/L) and severe hyponatremia (serum sodium level of＜130mEq/L) within the first 14 days after admission were 51% (n＝42) and 20% (n＝16), respectively. After admission, hyponatremia took a median period of 7 days to develop and lasted for a median of 3 days. Multivariate analysis demonstrated that higher fluid intake from days 1 to 3 and the presence of cranial fractures were risk factors for hyponatremia. The 58 patients with hyponatremia experienced fewer ventilator-free days, longer intensive care unit stays, and less favorable outcomes compared to the 24 patients without hyponatremia;however, these differences were not significant. Further studies are needed to determine the optimal management strategy for TBI-associated hyponatremia in the intensive care unit setting.

Septic shock due to Aeromonas hydrophila bacteremia in a patient with alcoholic liver cirrhosis: a case report.

INTRODUCTION: Aeromonas hydrophila sometimes causes bacteremia, which can be fatal in compromised patients, such as those with liver cirrhosis. We present a case of septic shock due to Aeromonas hydrophila bacteremia in a patient with liver cirrhosis, which was successfully treated with rapid resuscitation and critical care. CASE PRESENTATION: A 71-year-old Japanese man with liver cirrhosis was transported to our emergency center by ambulance after presenting with gait difficulties and fever. On arrival, he exhibited shock and severe lactic acidosis, which was suggestive of sepsis, and was immediately resuscitated and administered empiric antibiotic therapy. He also displayed catecholamine-resistant hypotension, which was successfully treated with critical care including supportive therapies, such as polymyxin B hemoperfusion and cytokine-absorbing hemofiltration. Aeromonas hydrophila was detected in his initial blood cultures. CONCLUSIONS: Aeromonas septicemia should be considered in patients with alcoholic liver cirrhosis who have profound shock. In addition to goal-directed therapy and the prompt administration of empiric antibiotic therapy, aggressive critical care involving multiple supportive therapies can save such patients.

Mean lung pressure during adult high-frequency oscillatory ventilation: an experimental study using a lung model.

In adult high-frequency oscillatory ventilation (HFOV), stroke volume (SV) and mean lung pressure (PLung) are important for lung protection. We measured the airway pressure at the Y-piece and the lung pressure during HFOV using a lung model and HFOV ventilators for adults (R100 and 3100B). The lung model was made of a 20-liter, airtight rigid plastic container (adiabatic compliance: 19.3 ml/cmH2O) with or without a resistor (20 cmH2O/l/sec). The ventilator settings were as follows: mean airway pressure (MAP), 30 cmH2O; frequency, 5-15 Hz (every 1 Hz); airway pressure amplitude (AMP), maximum;and % of inspiratory time (IT), 50% for R100, 33% or 50% for 3100B. The measurements were also performed with an AMP of 2/3 or 1/3 maximum at 5, 10 and 15 Hz. The PLung and the measured MAP were not consistently identical to the setting MAP in either ventilator, and decreasing IT decreased the PLung in 3100B. In conclusion, we must pay attention to the possible discrepancy between the PLung and the setting MAP during adult HFOV.