Search

Abstract: The antibody (Ab) array format provides a unique opportunity to pan and characterize multiple leukocyte subsets in parallel. However, the questions of reproducibility and robustness of leukocyte panning on Ab arrays need to be answered for this technology to become an immunophenotyping tool. The present study sought to address several of these questions, including: (1) purity of leukocyte subsets captured on Ab regions, (2) dynamics of leukocyte binding, (3) elimination of non-specific cell adhesion, and (4) standardization of cell washing conditions. Abs for CD4 T-cells, CD8 T-cells, CD36 monocytes, and CD16b neutrophils were dispensed onto standard glass slides containing a thin film of poly(ethylene glycol) (PEG) hydrogel. PEG gel coating was highly effective in eliminated non-specific cell adhesion on the surface. Incubation of the Ab arrays with red blood cell (RBC) depleted whole blood resulting in antigen-specific panning of leukocyte subsets on the respective Ab domains. A flow through chamber was employed to determine optimal shear stress conditions for removal of non-specifically attached cells. The purity of the four subsets remaining on the surface after washing was determined by Wright staining and immunofluorescence, and was found to be as follows: CD4 T-cells (99.2±0.3%), CD8 T-cells (98.7±0.3%), CD36 monocytes (97.2±0.9%), and CD16b neutrophils (99.1±0.6%). In conclusion, the methods described in this study allow to separate whole blood into pure leukocyte subsets with minimal sample preparation and handling. These approaches will be valuable in the future development of Ab arrays as tools for quantitative immunophenotyping of leukocytes. [Copyright &y& Elsevier]

The Japanese Urological Association's guidelines for the treatment of renal trauma were published in 2016. In conjunction with its revision, herein, we present the new guidelines for overall urotrauma. Its purpose is to provide standard diagnostic and treatment recommendations for urotrauma, including iatrogenic trauma, to preserve organ function and minimize complications and fatality. The guidelines committee comprised urologists with experience in urotrauma care, selected by the Trauma and Emergency Medicine Subcommittee of the Specialty Area Committee of the Japanese Urological Association, and specialists recommended by the Japanese Association for the Surgery of Trauma and the Japanese Society of Interventional Radiology. The guidelines committee established the domains of renal and ureteral, bladder, urethral, and genital trauma, and determined the lead person for each domain. A total of 30 clinical questions (CQs) were established for all domains; 15 for renal and ureteral trauma and five each for the other domains. An extensive literature search was conducted for studies published between January 1, 1983 and July 16, 2020, based on the preset keywords for each CQ. Since only few randomized controlled trials or meta‐analyses were found on urotrauma clinical practice, conducting a systematic review and summarizing the evidence proved challenging; hence, the grade of recommendation was determined according to the 2007 "Minds Handbook for Clinical Practice Guidelines" based on a consensus reached by the guidelines committee. We hope that these guidelines will be useful for clinicians in their daily practice, especially those involved in urotrauma care. [ABSTRACT FROM AUTHOR]

Background: The efficacies of fresh frozen plasma and coagulation factor transfusion have been widely evaluated in trauma-induced coagulopathy management during the acute post-injury phase. However, the efficacy of red blood cell transfusion has not been adequately investigated in patients with severe trauma, and the optimal hemoglobin target level during the acute post-injury and resuscitation phases remains unclear. Therefore, this study aimed to examine whether a restrictive transfusion strategy was clinically non-inferior to a liberal transfusion strategy during the acute post-injury phase. Methods: This cluster-randomized, crossover, non-inferiority multicenter trial was conducted at 22 tertiary emergency medical institutions in Japan and included adult patients with severe trauma at risk of major bleeding. The institutions were allocated a restrictive or liberal transfusion strategy (target hemoglobin levels: 7–9 or 10–12 g/dL, respectively). The strategies were applied to patients immediately after arrival at the emergency department. The primary outcome was 28-day survival after arrival at the emergency department. Secondary outcomes included transfusion volume, complication rates, and event-free days. The non-inferiority margin was set at 3%. Results: The 28-day survival rates of patients in the restrictive (n = 216) and liberal (n = 195) strategy groups were 92.1% and 91.3%, respectively. The adjusted odds ratio for 28-day survival in the restrictive versus liberal strategy group was 1.02 (95% confidence interval: 0.49–2.13). Significant non-inferiority was not observed. Transfusion volumes and hemoglobin levels were lower in the restrictive strategy group than in the liberal strategy group. No between-group differences were noted in complication rates or event-free days. Conclusions: Although non-inferiority of the restrictive versus liberal transfusion strategy for 28-day survival was not statistically significant, the mortality and complication rates were similar between the groups. The restrictive transfusion strategy results in a lower transfusion volume. Trial registration number:umin.ac.jp/ctr: UMIN000034405, registration date: 8 October 2018. [ABSTRACT FROM AUTHOR]

Background: Critical coronavirus disease 2019 (COVID-19) has a high fatality rate, especially in hemodialysis (HD) patients, with this poor prognosis being caused by systemic hyperinflammation; cytokine storms. Steroid pulse therapy or tocilizumab (TCZ) have insufficient inhibitory effects against cytokine storms in critical cases. This study evaluated the clinical effects and safety of combining steroid pulse therapy and TCZ. Methods: From September 2020 to May 2021, 201 patients with COVID-19 were admitted to our hospital. Before February 2021, patients with an oxygen demand exceeding 8 L/min were intubated and treated with standard therapy (dexamethasone and antiviral therapy). After February 2021, patients underwent high-flow nasal cannula oxygen therapy and were treated with TCZ (8 mg/kg) and methylprednisolone (mPSL) (500 mg/day [≤ 75 kg], 1000 mg/day [> 75 kg]) for 3 days. We compared background characteristics, laboratory findings, and prognosis between non-HD and HD patients and between patients who received and did not receive TCZ and mPSL pulse therapy. Results: Among non-HD patients, the TCZ + mPSL pulse group had significantly higher survival rates and lower secondary infection rates (p < 0.05), than the standard therapy group. All HD patients in the standard therapy group with oxygen demand exceeding 8 L/min died. Contrastingly, all patients in the TCZ + mPSL pulse group survived, with their oxygen demand decreasing to 0–1 L/min within 3 weeks post-administration. Conclusion: TCZ combined with mPSL pulse therapy improved the survival rate without significant adverse events in critical HD and non-HD patients with COVID-19 by strongly suppressing systemic hyperinflammation. [ABSTRACT FROM AUTHOR]

A 60-year-old man presented with dyspnea four days after the second dose of the coronavirus disease (COVID-19) vaccine. Imaging revealed extensive ground-glass opacification. Blood tests were notable for elevated KL-6 levels. Bronchoalveolar lavage fluid analysis showed increased lymphocyte-dominant inflammatory cells and decreased CD4/CD8 ratio. These findings were consistent with the diagnosis of drug-induced interstitial lung disease (DIILD). To the best of our knowledge, this has never been reported in previous literature. Treatment with glucocorticoids relieved his symptoms. This paper highlights that although extremely rare, COVID-19 vaccine could cause DIILD, and early diagnosis and treatment are crucial to improve patient outcomes. [ABSTRACT FROM AUTHOR]

Our goal was to analyze minimum inhibitory concentration (MIC) data for Staphylococcus aureus isolated from surgical infections (SIs) and to look for correlations among the clinically available antimicrobials that were tested. Clinical isolates from SIs were collected by a multicenter surveillance group involving 34 institutions in Japan. During the period April 1998 to March 2007, 312 strains of S. aureus [71 methicillin susceptible (MSSA) and 241 methicillin resistant (MRSA)] were consecutively obtained from these institutions. MIC data for 18 clinically available antimicrobial agents [ABPC, CEZ, CTM, CMX, CPR, FMOX, CFPM, CZOP, IPM, MEMP, GM, ABK, MINO, CLDM, FOM, LVFX, VCM, and TEIC (abbreviations defined in Tables 2 and 3)] against these isolates was analyzed using a principal component analysis (PCA). PCA revealed that four principal components explained 71.1% of the total variance. The first component consisted of major contributions from MEPM and IPM. The second component consisted of major contributions from MINO. These two-first axes, which were strong and explained 54.2% of the total variance, were able to classify the clinical isolates into four clusters. Furthermore, the proportion of the four clusters provided the characteristics of the S. aureus that were clinically isolated at each institute. PCA is a clinically applicable method for analyzing MIC patterns. Such analyses might contribute to the establishment of a practical classification of antimicrobial agents and to the identification of the characteristic antimicrobial resistance patterns at each institute. [ABSTRACT FROM AUTHOR]

QT dispersion, defined as the maximal-minus-minimal QT interval on a 12-lead electrocardiogram, has emerged as a non-invasive measurement for quantifying the spatial inhomogeneity of ventricular repolarization under various conditions, including acute stress. Because burn injuries elicit acute stress reactions, it was hypothesized that QT dispersion increases with the severity of the burn injury. To test the hypothesis, 13 burned patients (age range of 22–76 years, nine males, ranging from 4.0 to 75.0% of total body surface area burned) in whom a measurable 12-lead electrocardiogram had been obtained within 4 h after arrival at the emergency department were identified retrospectively, and their QTc intervals, i.e. QT intervals corrected for heart rate by the standard Bazett formula, were measured. QTc dispersion (QTcd) was then calculated, and correlations were assessed with burn severity (burn index, BI; prognostic burn index, PBI). Of the 13 patients, nine patients had a prolonged QTcd (>40 ms), and linear correlation analyses showed significant positive correlations between QTcd and both BI and PBI (r=0.61 and 0.62, respectively). In conclusion, QT dispersion was greater in the burned patients, and although the pathophysiology was unclear from the present study, the findings suggested that acute stress contributed to the spatial inhomogeneity of ventricular repolarization. [Copyright &y& Elsevier]

Background: Strategies to predict delayed airway obstruction in patients with inhalation injury have not been extensively studied. This study aimed to develop a novel scale, predicting the need for Delayed Intubation after inhalation injury (PDI) score.Methods: We retrospectively identified patients with inhalation injury at four tertiary care centers in Japan between 2012 and 2018. We included patients aged 15 or older and excluded those intubated within 30 min after hospital arrival. Predictors for delayed intubation were identified with univariate analyses and scored on the basis of odds ratios. The PDI score was evaluated with the area under the receiver operating characteristic (AUROC) curve and compared with other scaling systems for burn injuries.Results: Data from 158 patients were analyzed; of these patients, 18 (11.4%) were intubated during the delayed phase. Signs of respiratory distress, facial burn, and pharyngolaryngeal swelling observed on laryngoscopy, were identified as predictors for delayed intubation. The discriminatory power of the PDI (AUROC curve = 0.90; 95% confidence interval, 0.83 to 0.97; p < 0.01) was higher than that of the other scaling systems.Conclusions: We developed a novel scale for predicting delayed intubation in inhalation injury. The score should be further validated with other population. [ABSTRACT FROM AUTHOR]

We aimed to determine the characteristics of quantitative pupillary response parameters other than amplitude of pupillary light reflex (PLR) early after return of spontaneous circulation (ROSC) and their implications for predicting neurological outcomes early after cardiac arrest (CA). Fifty adults resuscitated after non-traumatic out-of-hospital CA from four emergency hospitals were enrolled. Pupil diameters, PLR, constriction velocity (CV), maximum CV (MCV), dilation velocity (DV), latency of constriction, and Neurological Pupil index (NPi) were quantitatively measured at 0, 6, 12, 24, 48, and 72 h post-ROSC using an automated pupillometer. Change over time of each parameter was compared between favorable (Cerebral Performance Category [CPC] 1 or 2) and unfavorable neurological outcome (CPC 3–5) groups. Prognostic values of 90-day favorable outcome by these parameters and when combined with clinical predictors (witness status, bystander cardiopulmonary resuscitation, initial shockable rhythm, implementation of target temperature management) were tested. Thirteen patients achieved favorable outcome. CV, MCV, DV (P < 0.001), and NPi (P = 0.005) were consistently greater in the favorable group than in the unfavorable outcome group. Change over time was not statistically different between the groups in all parameters. CV, MCV, DV (ρ = 0.96 to 0.97, P < 0.001, respectively), and NPi (ρ = 0.65, P < 0.001) positively correlated with PLR. The prognostic value of 0-hour CV (area under the curve, AUC [95% confidence interval]: 0.92 [0.80–1.00]), DV (0.84 [0.68–0.99]), and NPi (0.88 [0.74–1.00]) was equivalent to that of PLR (0.84 [0.69–0.98]). Prognostic values improved to AUC of 0.95–0.96 when 0-hour PLR, CV, DV, or NPi was combined with clinical predictors. The 0-hour CV, MCV, and NPi showed equivalent prognostic values to PLR alone/in combination with clinical predictors. Using PLR among several quantitative pupillary response parameters for early neurological prognostication of post-CA patients is a simple and effective strategy. [ABSTRACT FROM AUTHOR]

Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) has the potential to be an alternative to open aortic cross-clamping (ACC). However, its practical indication remains unknown. We examined the usage trend of REBOA and ACC in Japan for severe torso trauma and investigated whether these procedures were associated with the time of death distribution based on a large database from the Japan Trauma Data Bank (JTDB). Methods: The JTDB from 2004 to 2014 was reviewed. Eligible patients were restricted to those with severe torso trauma, which was defined as an abbreviated injury scale score of ≥4. Patients were classified into groups according to the aortic occlusion procedures. The primary outcomes were the rates of REBOA and ACC use according to the clinical situation. We also evaluated whether the time of death distribution for the first 8 h differed based on these procedures. Results: During the study period, a total of 21,533 patients met our inclusion criteria. Overall, REBOA was more commonly used than ACC for patients with severe torso trauma (2.8% vs 1.5%). However, ACC was more frequently used in cases of thoracic injury and cardiac arrest. Regarding the time of death distribution, the cumulative curve for death in REBOA cases was elevated much more slowly and mostly flat for the first 100 min. Conclusions: REBOA is more commonly used compared to ACC for patients with severe torso trauma in Japan. Moreover, it appears that REBOA influences the time of death distribution in the hyperacute phase. [ABSTRACT FROM AUTHOR]

Aim: To clarify whether quantitative assessment of pupillary light reflexes (PLR) can predict the outcome of post-cardiac arrest (CA) patients during the first 72 h after the return of spontaneous circulation (ROSC).Methods: Fifty adults resuscitated after non-traumatic out-of-hospital CA (OHCA) (mean age 64.1 years old, 36 males) were enrolled in four emergency hospitals. PLR was sequentially measured at 0, 6, 12, 24, 48, and 72 h after ROSC by an automated portable infrared pupillometry. PLR values for each time point were compared between both survivors and non-survivors, and patients with either favourable (Cerebral Performance Category (CPC) 1 or 2) or unfavourable neurological outcomes.Results: Twenty-three patients survived for 90 days after CA, and 13 patients achieved favourable neurological outcomes. The PLR values of the survivors and patients with favourable neurological outcomes were consistently greater than those of non-survivors (P < 0.001) and those with unfavourable neurological outcomes (P < 0.001), respectively. The change in PLR over time was not statistically different between the outcome groups. The 0-hour PLR best predicted both 90-day survival (AUC = 0.82, cutoff 3%, sensitivity 0.87, specificity 0.80) and favourable neurological outcomes (AUC = 0.84, cutoff 6%, sensitivity 0.92, specificity 0.74). No patient with a 6-hour PLR less than 3% survived for 90 days after CA.Conclusions: Quantitatively measured PLR was consistently greater in survivors and patients with favourable neurological outcomes during the 72 h after ROSC. Quantitative assessment of PLR at as early as 0 h has a potential role for prognostication in post-CA patients. [ABSTRACT FROM AUTHOR]

Introduction: Because Japan has high suicide rates and low violent crime rates, it is likely that most abdominal stab wounds (ASWs) in Japan are self-inflicted. Although physical examination is one of the most important factors in surgical decision making, such evaluations can be difficult in patients with self-inflicted ASWs due to patient agitation and uncooperative behavior. Therefore, the self-inflicted nature of an injury may strongly affect clinical practice, particularly in Japan, but its influence remains uncertain. We hypothesized that the rates of exploratory laparotomy and nontherapeutic laparotomy (NTL) would be higher in self-inflicted patients.Methods: We reviewed ASW patients from 2004 to 2014 in the Japan Trauma Data Bank. The rates of exploratory laparotomy and NTL were compared between self-inflicted and non-self-inflicted ASWs.Results: Of the 1705 eligible patients, 1302 patients (76.4%) had self-inflicted ASWs, and 403 patients (23.6%) had non-self-inflicted ASWs. Self-inflicted patients had a significantly higher rate of psychiatric history, but lower injury severity. The in-hospital mortality rate was similar between the two groups (4.5% vs. 5.2%, p = 0.576). Self-inflicted patients had significantly higher rates of exploratory laparotomy and NTL (69.1% vs. 56.7%, p < 0.001, 22.5% vs. 13.6%, p = 0.03, respectively). Self-inflicted patients were also associated with significantly longer hospital stays (10.0 [5.0-21.0] vs. 9.0 [4.0-18.0] days, P = 0.045). In a multivariable analysis, self-inflicted patients were independently associated with exploratory laparotomy (odds ratio [OR], 2.05; 95% confidence interval [CI]: 1.55-2.72) and NTL (OR, 1.61; 95% CI: 1.01-2.56).Conclusion: ASWs in Japan were predominantly self-inflicted. The clinical patterns of self-inflicted ASWs had some unique features. Patients with self-inflicted ASWs had higher rates of laparotomy and NTL. Further studies are needed to develop a useful protocol specific to self-inflicted ASWs. [ABSTRACT FROM AUTHOR]

We compared the effects of Ringer's lactate (RL) and acetate (RA) solutions on parameters of splanchnic dysoxia such as PgCO2 (PCO2 of gastric mucosa) and pHi (pH of gastric mucosa) using a gastric tonometer, in addition to blood markers such as the serum arterial level of lactate, base excess, ketone body ratio, and antithrombin during the first 72h of the resuscitation period in patients with burns covering 30% or more of their body surface. A prospective study was conducted in the university tertiary referral centers. There were no significant differences in the average age, TBSA (total burn surface area), and resuscitative fluid volume during the first and second 24h between the two groups. In the RA group, PCO2 gap values calculated employing the formula: PgCO2 −PaCO2 (arterial PCO2), and pH gap calculated by: pHa (arterial pH)−pHi, improved to the normal ranges at 24h postburn, which was significantly faster than in the RL group. On the other hand, there were no significant differences in blood parameters between the two groups over the course. These results suggest that fluid resuscitation with RA may more rapidly ameliorate splanchnic dysoxia, as evidenced by gastric tonometry, compared to that with RL. [Copyright &y& Elsevier]

Abstract: Critically ill patients are commonly associated with systemic inflammatory response syndrome (SIRS) and are at a greater risk of developing acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Under these conditions, large amounts of various cytokines are produced, which either directly or indirectly induce tissue injury and finally organ dysfunctions, through the activation of neutrophils and as a result of release of cytotoxic molecules, especially neutrophil elastase (NE). In the present study, we determined plasma neutrophil elastase–alpha-1 antitrypsin complex (NE–AT) and elastase digests of cross-linked fibrin (e-XDP) in critically ill patients to elucidate the significance of NE in the initiation and progression of ALI and ARDS in the presence or absence of SIRS. We found significantly increased levels of plasma NE–AT in the patients with ARDS, especially when the definition of SIRS was met. Among ALI/ARDS groups, plasma NE–AT, but not e-XDP, correlated significantly with the decrease in PaO2/FIO2 ratio and the duration of ALI/ARDS. Furthermore, NE–AT, but not e-XDP, significantly increased in subgroups whose PaO2/FIO2 ratio decreased by more than 20%. Such correlations and differences between the subgroups were not observed in the non-ALI patients. From these results, we speculate that NE–AT, but not e-XDP, may be predictive of progressive lung injury in the early stage of ALI and ARDS. [Copyright &y& Elsevier]

QT dispersion, defined as the maximal-minus-minimal QT interval on a 12-lead electrocardiogram, has emerged as a non-invasive measurement for quantifying the spatial inhomogeneity of ventricular repolarization under various conditions, including acute stress. Because burn injuries elicit acute stress reactions, it was hypothesized that QT dispersion increases with the severity of the burn injury. To test the hypothesis, 13 burned patients (age range of 22-76 years, nine males, ranging from 4.0 to 75.0% of total body surface area burned) in whom a measurable 12-lead electrocardiogram had been obtained within 4h after arrival at the emergency department were identified retrospectively, and their QTc intervals, i.e. QT intervals corrected for heart rate by the standard Bazett formula, were measured. QTc dispersion (QTcd) was then calculated, and correlations were assessed with burn severity (burn index, BI; prognostic burn index, PBI). Of the 13 patients, nine patients had a prolonged QTcd (>40 ms), and linear correlation analyses showed significant positive correlations between QTcd and both BI and PBI (r=0.61 and 0.62, respectively). In conclusion, QT dispersion was greater in the burned patients, and although the pathophysiology was unclear from the present study, the findings suggested that acute stress contributed to the spatial inhomogeneity of ventricular repolarization. [ABSTRACT FROM AUTHOR]

Anaphylactoid reactions to iodinated contrast media can cause life-threatening events and even death. A 44-year-old woman presented with cardiopulmonary arrest (CPA) immediately following the administration of nonionic iodinated contrast media for an intravenous pyelography. Her cardiac rhythm during CPA was asystole. She was successfully resuscitated by the radiologists supported by paged emergency physicians using the prompt intravenous administration of 1 mg of epinephrine. Neither laryngeal edema nor bronchial spasm was observed during the course of treatment, and she was discharged on the 4th day without any complications. The patient did not have a history of allergy, but had experienced a myocardial infarction and aortitis. She had undergone 11 angiographies and had been taking a β-adrenergic receptor antagonist. Planned emergency medical backup is advisable to ensure resuscitation in the event of an anaphylactoid reaction to the use of contrast media in-hospital settings. [Copyright &y& Elsevier]