Early intubation and decreased in-hospital mortality in patients with coronavirus disease 2019.

BACKGROUND: Some academic organizations recommended that physicians intubate patients with COVID-19 with a relatively lower threshold of oxygen usage particularly in the early phase of pandemic. We aimed to elucidate whether early intubation is associated with decreased in-hospital mortality among patients with novel coronavirus disease 2019 (COVID-19) who required intubation. METHODS: A multicenter, retrospective, observational study was conducted at 66 hospitals in Japan where patients with moderate-to-severe COVID-19 were treated between January and September 2020. Patients who were diagnosed as COVID-19 with a positive reverse-transcription polymerase chain reaction test and intubated during admission were included. Early intubation was defined as intubation conducted in the setting of ≤ 6 L/min of oxygen usage. In-hospital mortality was compared between patients with early and non-early intubation. Inverse probability weighting analyses with propensity scores were performed to adjust patient demographics, comorbidities, hemodynamic status on admission and time at intubation, medications before intubation, severity of COVID-19, and institution characteristics. Subgroup analyses were conducted on the basis of age, severity of hypoxemia at intubation, and days from admission to intubation. RESULTS: Among 412 patients eligible for the study, 110 underwent early intubation. In-hospital mortality was lower in patients with early intubation than those with non-early intubation (18 [16.4%] vs. 88 [29.1%]; odds ratio, 0.48 [95% confidence interval 0.27-0.84]; p = 0.009, and adjusted odds ratio, 0.28 [95% confidence interval 0.19-0.42]; p < 0.001). The beneficial effects of early intubation were observed regardless of age and severity of hypoxemia at time of intubation; however, early intubation was associated with lower in-hospital mortality only among patients who were intubated later than 2 days after admission. CONCLUSIONS: Early intubation in the setting of ≤ 6 L/min of oxygen usage was associated with decreased in-hospital mortality among patients with COVID-19 who required intubation. Trial Registration None.

D-dimer for screening of aortic dissection in patients with ST-elevation myocardial infarction.

BACKGROUND: Acute aortic dissection (AAD) with concurrent ST-segment elevation myocardial infarction (STEMI) is relatively rare and sometimes overlooked. As D-dimer testing has been reported to have high sensitivity to diagnose AAD in a clinical scale, Aortic Dissection Detection Risk Score (ADD-RS), a point-of-care D-dimer analyzer capable of measuring in 10 min would be useful to deny AAD with concurrent STEMI. However, an optimal cut-off value of D-dimer in such population remains unclear. Therefore, the aim of this study was to elucidate the optimal D-dimer threshold in patients clinically diagnosed with STEMI. METHODS: This retrospective cohort study was conducted at two tertiary care centers between 2014 and 2019. Patients clinically diagnosed with STEMI who underwent serum D-dimer measurement on hospital arrival were included. The primary outcome was the diagnosis of AAD. The area under the receiver operating characteristic curve (AUROC) for D-dimer values to diagnose AAD was evaluated, particularly in patients with low to moderate risks of AAD (1 of ADD-RS). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated with several cut-off values. RESULTS: A total of 322 patients were included, and 28 were diagnosed with AAD. The AUROC for D-dimer to diagnose AAD was 0.970 (95% confidence interval: 0.948-0.993) in 262 patients with 1 of ADD-RS. If D-dimer ≥750 ng/mL was used as a cut-off value, sensitivity, specificity, PPV and NPV were 100%, 86.4%, 37.7%, and 100%, respectively. AAD could be denied in 209 (79.8%) patients using the cut-off value (D-dimer <750 ng/mL). CONCLUSIONS: Serum D-dimer ≥750 ng/mL exhibited high sensitivity and NPV to diagnose AAD with concurrent STEMI, while the ADD-RS originally utilized ≥500 ng/mL as a cut-off for any suspected AAD. A point-of-care D-dimer measurement with the new cut-off would be useful to rule-out AAD among patients with STEMI.

Mucosal CXCR4+ IgG plasma cells contribute to the pathogenesis of human ulcerative colitis through FcγR-mediated CD14 macrophage activation.

BACKGROUND: Chronic inflammation characterised by IgG-producing plasma cell infiltration of colonic mucosa is a histological hallmark of ulcerative colitis (UC); however, whether its function is pathogenic or protective remains unclear. OBJECTIVE: To explore the contribution of intestinal IgG plasma cells to UC pathogenesis. METHODS: We isolated lamina propria mononuclear cells (LPMCs) from intestinal mucosa of UC patients and analysed the characteristics of intestinal plasma cells (expression profiles of differentiation molecules and chemokine receptors). We investigated the involvement of IgG-immune complex (IC)-Fc gamma receptor (FcγR) signalling in intestinal inflammation by examining the cytokine production by LPMCs in response to IgG-IC stimulation. RESULTS: IgG plasma cells that were markedly increased in number in the inflamed mucosa of UC patients showed a distinct expression profile (CD19(+)CD27(low), CCR10(low)CXCR4(high)) compared with IgA plasma cells (CD19(+/-)CD27(high), CCR10(high)CXCR4(-/low)). In vitro IgG-IC stimulation activated intestinal CD14 macrophages that were increased in number in the inflamed mucosa of UC patients via FcγRI and FcγRII, and induced the extensive production of pro-inflammatory cytokines such as tumour necrosis factor (TNF) and interleukin-1ß (IL-1ß), comparable to the effect of commensal bacteria stimulation. Co-stimulation with IgG-IC and commensal bacteria increased TNF and IL-1ß production more than stimulation with the latter alone. Furthermore, IgG-IC notably up-regulated the expression of TL1A, whereas commensal bacteria specifically induced IL-23. CONCLUSIONS: Collectively, these results demonstrate a novel aspect of UC pathogenesis in which unique IgG plasma cells infiltrate the inflamed mucosa via CXCR4, and critically influence UC pathogenesis by exacerbating mucosal inflammation through the activation of 'pathogenic' intestinal CD14 macrophages via IgG-IC-FcγR signalling.

Door-to-Needle Time for Extracorporeal Cardiopulmonary Resuscitation and Neurological Outcomes in Out-of-Hospital Cardiac Arrest: A Nationwide Study.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) is an option for refractory cardiac arrest, and immediate initiation after indication is recommended. However, the practical goals of ECPR preparation (such as the door-to-needle time) remain unclear. This study aimed to elucidate the association between the door-to-needle time and neurological outcomes of out-of-hospital cardiac arrest. METHODS AND RESULTS: This is a post hoc analysis of a nationwide multicenter study on out-of-hospital cardiac arrest treated with ECPR at 36 institutions between 2013 and 2018 (SAVE-J [Study of Advanced Cardiac Life Support for Ventricular Fibrillation with Extracorporeal Circulation in Japan] II study). Adult patients without hypothermia (≥32 °C) in whom circulation was not returned at ECPR initiation were included. The probability of favorable neurological function at 30 days (defined as Cerebral Performance Category ≤2) was estimated using a generalized estimating equations model, in which institutional, patient, and treatment characteristics were adjusted. Estimated probabilities were then calculated according to the door-to-needle time with 3-minute increments, and a clinical threshold was assumed. Among 1298 patients eligible for this study, 136 (10.6%) had favorable neurological function. The estimated probability of favorable outcomes was highest in patients with 1 to 3 minutes of door-to-needle time (12.9% [11.4%-14.3%]) and remained at 9% to 10% until 27 to 30 minutes. Then, the probability dropped gradually with each 3-minute delay. A 30-minute threshold was assumed, and shorter door-to-extracorporeal membrane oxygenation/low-flow time and fewer adverse events related to cannulation were observed in patients with door-to-needle time <30 minutes. CONCLUSIONS: The probability of favorable functions after out-of-hospital cardiac arrest decreased as the door-to-needle time for ECPR was prolonged, with a rapid decline after 27 to 30 minutes. REGISTRATION: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Lacosamide Intoxication-induced Wide QRS Tachycardia Successfully Treated with Veno-arterial Extracorporeal Membrane Oxygenation.

Lacosamide is an antiepileptic drug that acts on voltage-gated sodium channels and was approved as an antiepileptic by the Food and Drug Administration in 2008. Although the efficacy and safety of lacosamide have been established in many previous trials, some case reports have shown that it may lead to cardiovascular side effects, especially in patients with electrical conduction system disorders. We herein report a case of life-threatening cardiac arrhythmia caused by lacosamide intoxication that was successfully treated with veno-arterial extracorporeal membrane oxygenation.

Early restricted oxygen therapy after resuscitation from cardiac arrest (ER-OXYTRAC): protocol for a stepped-wedge cluster randomised controlled trial.

INTRODUCTION: Cardiac arrest is a critical condition, and patients often experience postcardiac arrest syndrome (PCAS) even after the return of spontaneous circulation (ROSC). Administering a restricted amount of oxygen in the early phase after ROSC has been suggested as a potential therapy for PCAS; however, the optimal target for arterial partial pressure of oxygen or peripheral oxygen saturation (SpO2) to safely and effectively reduce oxygen remains unclear. Therefore, we aimed to validate the efficacy of restricted oxygen treatment with 94%-95% of the target SpO2 during the initial 12 hours after ROSC for patients with PCAS. METHODS AND ANALYSIS: ER-OXYTRAC (early restricted oxygen therapy after resuscitation from cardiac arrest) is a nationwide, multicentre, pragmatic, single-blind, stepped-wedge cluster randomised controlled trial targeting cases of non-traumatic cardiac arrest. This study includes adult patients with out-of-hospital or in-hospital cardiac arrest who achieved ROSC in 39 tertiary centres across Japan, with a target sample size of 1000. Patients whose circulation has returned before hospital arrival and those with cardiac arrest due to intracranial disease or intoxication are excluded. Study participants are assigned to either the restricted oxygen (titration of a fraction of inspired oxygen with 94%-95% of the target SpO2) or the control (98%-100% of the target SpO2) group based on cluster randomisation per institution. The trial intervention continues until 12 hours after ROSC. Other treatments for PCAS, including oxygen administration later than 12 hours, can be determined by the treating physicians. The primary outcome is favourable neurological function, defined as cerebral performance category 1-2 at 90 days after ROSC, to be compared using an intention-to-treat analysis. ETHICS AND DISSEMINATION: This study has been approved by the Institutional Review Board at Keio University School of Medicine (approval number: 20211106). Written informed consent will be obtained from all participants or their legal representatives. Results will be disseminated via publications and presentations. TRIAL REGISTRATION NUMBER: UMIN Clinical Trials Registry (UMIN000046914).

Blast Injuries by an Improvised Explosive Device in Japan: A Case Report.

Blast injuries caused by an improvised explosive device (IED) are becoming more common in civilian settings. However, physicians may not be familiar with the treatment and management of blast-injured victims. To the best of our knowledge, this is the first case report of a blast injury caused by an IED in Japan. A 64-year-old man was admitted to our hospital's emergency department after sustaining a blast injury. His vital signs were stable, but he had multiple small wounds with embedded foreign bodies that were consistent with injuries sustained by IED victims. The patient was treated for his injuries and was moved to another hospital on day 37. Knowledge about blast injuries caused by IEDs and management strategies for mass casualties are both necessary.

Threshold of increase in oxygen demand to predict mechanical ventilation use in novel coronavirus disease 2019: A retrospective cohort study incorporating restricted cubic spline regression.

BACKGROUND: Rapid deterioration of oxygenation occurs in novel coronavirus disease 2019 (COVID-19), and prediction of mechanical ventilation (MV) is needed for allocation of patients to intensive care unit. Since intubation is usually decided based on varying clinical conditions, such as required oxygen changes, we aimed to elucidate thresholds of increase in oxygen demand to predict MV use within 12 h. METHODS: A single-center retrospective cohort study using data between January 2020 and January 2021was conducted. Data were retrieved from the hospital data warehouse. Adult patients diagnosed with COVID-19 with a positive polymerase chain reaction (PCR) who needed oxygen during admission were included. Hourly increments in oxygen demand were calculated using two consecutive oxygen values. Covariates were selected from measurements at the closest time points of oxygen data. Prediction of MV use within 12 h by required oxygen changes was evaluated with the area under the receiver operating curves (AUCs). A threshold for increased MV use risk was obtained from restricted cubic spline curves. RESULTS: Among 66 eligible patients, 1835 oxygen data were analyzed. The AUC was 0.756 for predicting MV by oxygen demand changes, 0.888 by both amounts and changes in oxygen, and 0.933 by the model adjusted with respiratory rate, PCR quantification cycle (Ct), and days from PCR. The threshold of increments of required oxygen was identified as 0.44 L/min/h and the probability of MV use linearly increased afterward. In subgroup analyses, the threshold was lower (0.25 L/min/h) when tachypnea or frequent respiratory distress existed, whereas it was higher (1.00 L/min/h) when viral load is low (Ct ≥20 or days from PCR >7 days). CONCLUSIONS: Hourly changes in oxygen demand predicted MV use within 12 h, with a threshold of 0.44 L/min/h. This threshold was lower with an unstable respiratory condition and higher with a low viral load.

Hospital Preparedness for COVID-19: The Known and The Known Unknown.

In late March 2020, we faced a nosocomial outbreak of novel coronavirus disease 2019 (COVID-19) at Keio University Hospital, Tokyo, Japan. Presently, COVID-19 is an unprecedented worldwide biohazard, and a nosocomial outbreak can occur in any hospital at any time. Therefore, we reviewed the literature regarding hospital preparedness, the initial management of COVID-19, and the surveillance of healthcare workers (HCWs) to find information that would be generally useful for physicians when confronted with COVID-19. In terms of hospital preparedness, each hospital should develop an incident management system and establish a designated multidisciplinary medical team. To initiate case management, COVID-19 should be suspected based on patient symptoms and/or high-risk history and then should be confirmed by viral testing, such as reverse transcription polymerase chain reaction (RT-PCR) analysis. Although some patients will become critically ill, the guidelines for respiratory failure and septic shock for non-COVID-19 cases can be followed for supportive treatment. Antiviral medications should be carefully selected because the available information is confused by the large volume of preprint literature and unreliable data. HCWs who have come into contact with patients with COVID-19 can generate new in-hospital clusters of COVID-19 cases. Quarantine following contact tracking with risk stratification is effective in preventing transmission, and the essentials of medical surveillance include monitoring different types of symptoms, delegation of supervision, and continuation of surveillance regardless of the RT-PCR results. Preparation for COVID-19 is recommended before the first COVID-19 case is encountered.

Rapid collapse of the inferior vena cava in a patient with cardiac arrest induced by anaphylactic shock after iodinated contrast medium injection.

Anaphylactic shock to contrast media can progress to cardiac arrest despite appropriate treatment. During anaphylactic shock to contrast media, rapid vasodilation and a massive fluid shift can occur. Here we report a patient who developed cardiac arrest induced by anaphylactic shock to iodinated contrast medium and exhibited rapid collapse of the inferior vena cava (IVC) on enhanced abdominal computed tomography (CT) images. The patient underwent postsurgical unenhanced and contrast-enhanced abdominal CT follow-up of cecum cancer. She had neither allergy nor medical history except for the cancer. She did not complain of any symptoms immediately after completion of the CT. However, she developed anaphylactic shock and pulseless electrical activity cardiac arrest only 2 minutes after finishing the CT despite appropriate treatment. Emergency physicians successfully treated the patient using advanced life support and targeted temperature management. She recovered with good overall and cerebral performance (Overall Performance Category (OPC) 1 and Cerebral Performance Category (CPC) 1). On the contrast-enhanced CT images, she exhibited rapid collapse of the IVC, although it was normal on the unenhanced CT images. The collapsed IVC is a good indicator of hypovolemia in patients with trauma. In this case, we considered that rapid vasodilation and a massive volume shift might have caused the collapsed IVC. This finding suggests the importance of aggressive volume resuscitation as well as epinephrine injection in patients with anaphylactic shock to contrast media. Furthermore, this finding occurred before the onset of clinical symptoms, and there is a possibility that it could be used as an indicator of anaphylactic shock to contrast media.