Asymmetric bromolactonization of prochiral cyclohexadiene derivatives with N-bromosuccimide proceeded in the presence of (DHQD)(2)PHAL as a chiral catalyst to afford the corresponding bromolactones ...with up to 93% ee. This reaction was also applicable to the kinetic resolution of a racemic cyclic ene-carboxylic acid, where the starting material was recovered with high enantioselectivity.
Background:The hypothesis of this study is that latent class analysis could identify the subphenotypes of out-of-hospital cardiac arrest (OHCA) patients associated with the outcomes and allow us to ...explore heterogeneity in the effects of extracorporeal cardiopulmonary resuscitation (ECPR).Methods and Results:This study was a retrospective analysis of a multicenter prospective observational study (CRITICAL study) of OHCA patients. It included adult OHCA patients with initial shockable rhythm. Patients from 2012 to 2016 (development dataset) were included in the latent class analysis, and those from 2017 (validation dataset) were included for evaluation. The association between subphenotypes and outcomes was investigated. Further, the heterogeneity of the association between ECPR implementation and outcomes was explored. In the study results, a total of 920 patients were included for latent class analysis. Three subphenotypes (Groups 1, 2, and 3) were identified, mainly characterized by the distribution of partial pressure of O2(PO2), partial pressure of CO2(PCO2) value of blood gas assessment, cardiac rhythm on hospital arrival, and estimated glomerular filtration rate. The 30-day survival outcomes were varied across the groups: 15.7% in Group 1; 30.7% in Group 2; and 85.9% in Group 3. Further, the association between ECPR and 30-day survival outcomes by subphenotype groups in the development dataset was as varied. These results were validated using the validation dataset.Conclusions:The latent class analysis identified 3 subphenotypes with different survival outcomes and potential heterogeneity in the effects of ECPR.
We aimed to investigate the association between serum lactate levels during cardiopulmonary resuscitation (CPR) and survival in patients with out-of-hospital cardiac arrest (OHCA). From the database ...of a multicenter registry on OHCA patients, we included adult nontraumatic OHCA patients transported to the hospital with ongoing CPR. Based on the serum lactate levels during CPR, the patients were divided into four quartiles: Q1 (≤ 10.6 mEq/L), Q2 (10.6-14.1 mEq/L), Q3 (14.1-18.0 mEq/L), and Q4 (> 18.0 mEq/L). The primary outcome was 1-month survival. Among 5226 eligible patients, the Q1 group had the highest 1-month survival (5.6% 74/1311), followed by Q2 (3.6% 47/1316), Q3 (1.7% 22/1292), and Q4 (1.0% 13/1307) groups. In the multivariable logistic regression analysis, the adjusted odds ratio of Q4 compared with Q1 for 1-month survival was 0.24 (95% CI 0.13-0.46). 1-month survival decreased in a stepwise manner as the quartiles increased (p for trend < 0.001). In subgroup analysis, there was an interaction between initial rhythm and survival (p for interaction < 0.001); 1-month survival of patients with a non-shockable rhythm decreased when the lactate levels increased (p for trend < 0.001), but not in patients with a shockable rhythm (p for trend = 0.72). In conclusion, high serum lactate level during CPR was associated with poor 1-month survival in OHCA patients, especially in patients with non-shockable rhythm.
Objectives
The Pediatric Emergency Care Applied Research Network (PECARN) head trauma prediction rules are used to assist computed tomography (CT) decision‐making for children with minor head trauma. ...Although the PECARN rules have been validated in North America and Europe, they have not yet been validated in Asia. In Japan, there are no clinical decision rules for children with minor head trauma. The rate of head CT for children with minor head trauma in Japan is high since CT is widely accessible across the country. The objective of this study was to evaluate the diagnostic accuracy of the PECARN rules for identifying clinically important traumatic brain injuries (ciTBI) in children with minor head trauma in Japan.
Methods
We conducted a retrospective cohort study at a tertiary care pediatric hospital in Japan (30,000 patients/year). We enrolled all children younger than 18 years with minor head trauma (Glasgow Coma Scale ≥ 14) who presented to the emergency department within 24 hours of their injury between January and December 2013. We retrospectively classified the children into three risk categories according to the PECARN rules. The PECARN rules were considered negative when children were classified into the very‐low‐risk category. The primary outcome was considered positive when a child had ciTBI defined as head injury resulting in death, neurosurgery, intubation for > 24 hours, or hospital admission ≥ 2 nights with evidence of TBI on CT.
Results
Among 2,208 children included in the study, 24 (1.1%) had ciTBI. Sensitivities and specificities of the PECARN rules to predict ciTBI were 85.7% (12/14; 95% confidence interval CI = 57.2 to 98.2) and 73.5% (572/778; 95% CI = 70.3 to 76.6), respectively, for children < 2 years old, and 100% (10/10; 95% CI = 58.7 to 100) and 73.5% (1033/1406; 95% CI = 71.0 to 75.7) for children ≥ 2 years old, respectively. There were 10 cases of physically abused children < 2 years old, and six (60%) of them had ciTBI. Also, two cases of physically abused children with ciTBI were classified as very low risk. If we did not include physically abused children, the sensitivity of the PECARN rule for children < 2 years old improved from 85.7% to 100% (8/8).
Conclusions
The PECARN rules were less sensitive for physically abused children, although the rules showed excellent applicability for the cohort without physical abuse. Thoughtful consideration may be needed for cases of nonaccidental trauma. Further prospective studies are required to verify the applicability of the PECARN rules for children with minor head trauma in Japan.
Background:The aim of our study was to investigate in detail the temporal trends in in-hospital characteristics, actual management, and survival, including neurological status, among adult ...out-of-hospital cardiac arrest (OHCA) patients in recent years.Methods and Results:From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all OHCA patients aged ≥18 years for whom resuscitation was attempted, and who were transported to participating hospitals between the years 2013 and 2017. The primary outcome measure was 1-month survival with favorable neurological outcome after OHCA. Temporal trends in in-hospital management and favorable neurological outcome among adult OHCA patients were assessed. Of the 11,924 patients in the database, we included a total of 10,228 adult patients from 16 hospitals. As for in-hospital advanced treatments, extracorporeal cardiopulmonary resuscitation (ECPR) use increased from 2.4% in 2013 to 4.3% in 2017 (P for trend <0.001). However, the proportion of adult OHCA patients with favorable neurological outcome did not change during the study period (from 5.7% in 2013 to 4.4% in 2017, adjusted odds ratio (OR) for 1-year increment: 0.98 (95% confidence interval: 0.94–1.23)).Conclusions:In this target population, in-hospital management such as ECPR increased slightly between 2013 and 2017, but 1-month survival with favorable neurological outcome after adult OHCA did not improve significantly.
Extracorporeal cardiopulmonary resuscitation (ECPR) is performed in refractory out-of-hospital cardiac arrest (OHCA) patients, and the eligibility has been conventionally determined based on three ...criteria (initial cardiac rhythm, time to hospital arrival within 45 minutes, and age <75 years) in Japan. Owing to limited information, this study descriptively determined neurological outcomes after applying the three criteria among OHCA patients who underwent ECPR.
This study conducted a post-hoc analysis of data from the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study. This was a multi-institutional prospective observational study of OHCA patients in Osaka Prefecture, Japan. All adult (aged ≥18 years) OHCA patients with internal medical causes treated with ECPR between 1 July 2012 and 31 December 2019 were evaluated. We described one-month neurological favourable outcomes based on the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age <75 years), and we compared them using the chi-square test.
Among 18,379 patients screened from the CRITICAL study database, we included 517 OHCA patients treated by ECPR; 311 (60.2%) patients met all three criteria. Favourable neurological outcomes were as follows: patients meeting no or one criterion: 2.3% (1/43), those meeting two criteria: 8% (13/163), and those meeting all criteria: 16.1% (50/311) (P-value = 0.004).
In this study, approximately 60% of patients treated by ECPR met the three criteria (initial shockable, time to hospital arrival within 45 minutes, and age <75 years), and the greater the number of criteria met, the better were the neurological outcomes achieved.
To clarify whether genetic and common infectious backgrounds are distinct, according to anti-aquaporin 4 (AQP4) antibody status in Japanese patients with neuromyelitis optica (NMO).
We analysed human ...leucocyte antigen (HLA)-DRB1 and HLA-DPB1 alleles, and IgG antibodies against Helicobacter pylori, Chlamydia pneumoniae, varicella zoster virus and Epstein-Barr virus nuclear antigen (EBNA) in 116 patients with NMO, including 39 patients with neuromyelitis optica spectrum disorder (NMOSD), 145 multiple sclerosis (MS) patients and 367 unrelated healthy controls. 77 NMO/NMOSD patients were seropositive for AQP4 antibody while 39 were seronegative.
Compared with healthy controls, NMO/NMOSD patients showed a significantly lower frequency of DRB1*0901 and significantly higher frequencies of DRB1*1602 and DPB1*0501, which conferred susceptibility to anti-AQP4 antibody positive NMO/NMOSD, but not antibody negative NMO/NMOSD. DRB1*0901 was a common protective allele, irrespective of the presence or absence of anti-AQP4 antibody. Anti-H pylori and anti-C pneumoniae antibodies were more commonly detected in anti-AQP4 antibody positive NMO/NMOSD patients than healthy controls. Antibody negative NMO/NMOSD patients did not differ from healthy controls regarding the presence of these antibodies. The presence or absence of antibodies against varicella zoster virus and EBNA did not vary among the groups. The frequencies of antibodies against these four pathogens were not significantly different between MS patients and healthy controls.
Our results suggest that HLA-DRB1*1602 and DPB1*0501 alleles and H pylori and Chlamydia pneumonia infection are risk factors only for anti-AQP4 antibody positive NMO/NMOSD but not for anti-AQP4 antibody negative NMO/NMOSD.
Yoshimura and Yoon present a case of a 60-year-old man suffering from invasive pneumococcal infection with hyposplenism. The patient presented to the emergency department with fever, dyspnea and ...ecchymosis on his trunk and face that had spread rapidly to his entire body within six hours, after one day of malaise. He had severe acute epiglottitis five years previously, and cellulitis and appendicitis in childhood. He had no history of splenectomy or hyposplenism and had never received a pneumococcal vaccination. Urgent computed tomography showed a hypoplastic spleen. They diagnosed invasive pneumococcal infection and administered a full dose of linezolid.
Fingolimod efficiently reduces multiple sclerosis (MS) relapse by inhibiting lymphocyte egress from lymph nodes through down-modulation of sphingosine 1-phosphate (S1P) receptors. We aimed to clarify ...the alterations in peripheral blood T cell subsets associated with MS relapse on fingolimod.
Blood samples successively collected from 23 relapsing-remitting MS patients before and during fingolimod therapy (0.5 mg/day) for 12 months and 18 healthy controls (HCs) were analysed for T cell subsets by flow cytometry. In MS patients, the percentages of central memory T (CCR7+CD45RO+) cells (TCM) and naïve T (CCR7+CD45RO-) cells decreased significantly, while those of effector memory T (CCR7-CD45RA-) and suppressor precursor T (CD28-) cells increased in both CD4+T and CD8+T cells from 2 weeks to 12 months during fingolimod therapy. The percentages of regulatory T (CD4+CD25highCD127low) cells in CD4+T cells and CCR7-CD45RA+T cells in CD8+T cells also increased significantly. Eight relapsed patients demonstrated greater percentages of CD4+TCM than 15 non-relapsed patients at 3 and 6 months (p=0.0051 and p=0.0088, respectively). The IL17-, IL9-, and IL4-producing CD4+T cell percentages were significantly higher at pre-treatment in MS patients compared with HCs (p<0.01 for all), while the IL17-producing CD4+T cell percentages tended to show a transient increase at 2 weeks of fingolimod therapy (pcorr=0.0834).
The CD4+TCM percentages at 2 weeks to 12 months during fingolimod therapy are related to relapse.
Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we ...investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio AOR 0.97, 95% confidence interval CI 0.95–0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94–0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.
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