Latent metabolic bone disease, skeletal dysplasia and other conditions related to low bone formation among 38 patients with subtrochanteric femoral fractures: a retrospective observational study.

Subtrochanteric femoral fracture is rare and intractable due to the possible association with low bone formation. Retrospective analysis of 38 patients with subtrochanteric femoral fractures revealed that four patients suffered from disorders related to low bone formation and there were specific treatments for two of them. PURPOSE: The main aim of this study was to detect latent metabolic bone diseases and skeletal dysplasia associated with low bone formation among patients with morphologic atypical femoral fracture (AFF). A second aim was to evaluate the frequency of recognized risk factors, such as antiresorptive agents, glucocorticoids, and age. METHODS: Clinical information was retrospectively analyzed among 38 Japanese patients who were admitted to the Department of Orthopedic Surgery and Spinal Surgery and the Division of Emergency and Critical Care Medicine at the University of Tokyo Hospital with diagnoses of subtrochanteric fractures between February 2012 and March 2022. RESULTS: Among 38 patients (including 30 females), 21 patients were aged 75 and over. Ten patients had past oral glucocorticoid use, and 18 had past antiresorptive agent use. Two patients were diagnosed with hypophosphatemic osteomalacia after the development of fractures. One patient was suspected to be a carrier of a loss-of-function variant of alkaline phosphatase, biomineralization associated (ALPL), and one other patient had previously been genetically diagnosed with pycnodysostosis. Among four patients with a diagnosis or suspicion of these metabolic bone diseases and skeletal dysplasia, four had past clinical fractures, two had past subtrochanteric femoral fractures, and two had subtrochanteric femoral fractures on both sides. CONCLUSION: If clinicians encounter patients with morphologic AFF, latent diseases related to low bone formation should be carefully differentiated because appropriate treatment may prevent delayed union and recurrent fractures. Additionally, it may be desirable to exclude these bone diseases in advance before initiating long-term use of antiresorptive agents in osteoporotic patients by screening with serum alkaline phosphatase levels to reduce the risk of morphologic AFF.

Impact of renal dysfunction on the diagnosis of acute pancreatitis using urinary trypsinogen-2: A retrospective study.

AIM: Early diagnosis of acute pancreatitis is crucial, and urinary trypsinogen has been recently reported as a useful biomarker for diagnosing acute pancreatitis. We aimed to evaluate the impact of renal dysfunction on the diagnostic performance of urinary trypsinogen-2 for acute pancreatitis. METHODS: We conducted a retrospective study using the clinical data of patients who visited the Department of Emergency and Critical Care at the University of Tokyo Hospital between 1 October, 2021, and 30 June, 2022. Patients with available data on qualitative urinary trypsinogen-2 levels were identified. We compared the urinary trypsinogen-2 levels among patients who were clinically diagnosed with acute pancreatitis. We further stratified the patients according to renal function parameters, such as serum creatinine level, blood urea nitrogen level, and estimated glomerular filtration rate, and evaluated the performance of urinary trypsinogen-2 as a biomarker for acute pancreatitis. RESULTS: Within 9 months, 35 patients were identified. Of them, 22 patients showed positive results and 13 showed negative results on the urinary trypsinogen-2 test. The sensitivity, specificity, positive predictive value, and negative predictive value were 0.80, 0.40, 0.18, and 0.92, respectively. Based on the blood urea nitrogen level and estimated glomerular filtration rate, the prevalence of false-positive results was significantly higher in patients with reduced renal function than in those with normal renal function. CONCLUSION: In patients with reduced renal function, the urinary trypsinogen-2 qualitative test results might be interpreted with caution when used for diagnosing acute pancreatitis.

Modified paratricipital approach without mobilization of the ulnar nerve prevents postoperative ulnar neuropathy in distal humerus fractures.

BACKGROUND: In distal humerus fracture surgery, postoperative ulnar neuropathy is a common complication. The present study assessed the utility of the modified paratricipital approach for preventing ulnar neuropathy. This approach preserved the continuity of the attachment of the triceps with the ulnar nerve and allowed anterior subluxation of the ulnar nerve onto the hardware to be avoided. METHODS: From December 2018 to March 2020, 13 patients who underwent surgery for distal humerus fracture through the modified paratricipital approach at our hospital were prospectively enrolled in the study. Ulnar neuropathy, Mayo Elbow Performance Score (MEPS), and Range of motion (ROM) were evaluated. RESULTS: No postoperative ulnar neuropathy was observed. At the final follow-up, the mean Mayo Elbow Performance score was 97.7 (range, 85-100). The mean arc motion was 132.7° (range, 115°-145°) with a mean flexion contracture of 4.2° (range, 0°-10°) and mean flexion of 136.2° (range, 120°-145°). Hardware breakage leading to a loss of reduction occurred in one case, but the other fractures united. CONCLUSIONS: Our results demonstrated the effectiveness of the modified paratricipital approach for preventing postoperative ulnar neuropathy. The modified paratricipital approach is a safe and reliable method of performing distal humerus fracture surgery.

Microbiome composition comparison in oral and atherosclerotic plaque from patients with and without periodontitis.

There is no conclusive evidence regarding a causal relationship between periodontitis and atherosclerosis. In this study, we examined the microbiome in the oral cavity and atheromatous plaques from atherosclerosis patients with or without periodontitis to investigate the role of oral bacteria in the formation of atheromatous plaques. We chose four patients with and without periodontitis, who had undergone carotid endarterectomy. Bacterial samples were extracted from the tongue surface, from periodontal pocket (during the oral examination), and from the atheromatous plaques (APs). We investigated the general and oral conditions from each patient and performed next-generation sequencing (NGS) analysis for all bacterial samples. There were no significant differences between both groups concerning general conditions. However, the microbiome patterns of the gingival pocket showed differences depending on the absence or presence of periodontitis, while those of the tongue surface were relatively similar. The microbiome pattern of the atheromatous plaques was entirely different from that on the tongue surface and gingival pocket, and oral bacteria were seldom detected. However, the microbiome pattern in atheromatous plaques was different in the presence or absence of periodontitis. These results suggested that oral bacteria did not affect the formation of atheromatous plaques directly.

Prion protein interacts with the metabotropic glutamate receptor 1 and regulates the organization of Ca2+ signaling.

Cellular prion protein (PrP) is a membrane protein that is highly conserved among mammals and mainly expressed on the cell surface of neurons. Despite its reported interactions with various membrane proteins, no functional studies have so far been carried out on it, and its physiological functions remain unclear. Neuronal cell death has been observed in a PrP-knockout mouse model expressing Doppel protein, suggesting that PrP might be involved in Ca2+ signaling. In this study, we evaluated the binding of PrP to metabotropic glutamate receptor 1 (mGluR1) and found that wild-type PrP (PrP-wt) and mGluR1 co-immunoprecipitated in dual-transfected Neuro-2a (N2a) cells. Fluorescence resonance energy transfer analysis revealed an energy transfer between mGluR1-Cerulean and PrP-Venus. In order to determine whether PrP can modulate mGluR1 signaling, we performed Ca2+ imaging analyses following repetitive exposure to an mGluR1 agonist. Agonist stimulation induced synchronized Ca2+ oscillations in cells coexpressing PrP-wt and mGluR1. In contrast, N2a cells expressing PrP-ΔN failed to show ligand-dependent regulation of mGluR1-Ca2+ signaling, indicating that PrP can bind to mGluR1 and modulate its function to prevent irregular Ca2+ signaling and that its N-terminal region functions as a molecular switch during Ca2+ signaling.

Application of amplicon-based targeted sequencing with the molecular barcoding system to detect uncommon minor EGFR mutations in patients with treatment-naïve lung adenocarcinoma.

BACKGROUND: In lung cancer, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor sensitizing mutations co-existing with rare minor EGFR mutations are known as compound mutations. These minor EGFR mutations can lead to acquired resistance after EGFR tyrosine kinase inhibitor treatment, so determining the mutation status of patients is important. However, using amplicon-based targeted deep sequencing based on next-generation sequencing to characterize mutations is prone to sequencing error. We therefore assessed the benefit of incorporating molecular barcoding with high-throughput sequencing to investigate genomic heterogeneity in treatment-naïve patients who have undergone resection of their non-small cell lung cancer (NSCLC) EGFR mutations. METHODS: We performed amplicon-based targeted sequencing with the molecular barcoding system (MBS) to detect major common EGFR mutations and uncommon minor mutations at a 0.5% allele frequency in fresh-frozen lung cancer samples. RESULTS: Profiles of the common mutations of EGFR identified by MBS corresponded with the results of clinical testing in 63 (98.4%) out of 64 cases. Uncommon mutations of EGFR were detected in seven cases (10.9%). Among the three types of major EGFR mutations, patients with the G719X mutation had a significantly higher incidence of compound mutations than those with the L858R mutation or exon 19 deletion (p = 0.0052). This was validated in an independent cohort from the Cancer Genome Atlas dataset (p = 0.018). CONCLUSIONS: Our findings demonstrate the feasibility of using the MBS to establish an accurate NSCLC patient genotype. This work will help understand the molecular basis of EGFR compound mutations in NSCLC, and could aid the development of new treatment modalities.

Panel-based next-generation sequencing identifies prognostic and actionable genes in childhood acute lymphoblastic leukemia and is suitable for clinical sequencing.

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although the cure rate of ALL has greatly improved, a considerable number of patients suffer from relapse of leukemia. Therefore, ALL remains the leading cause of death from cancer during childhood. To improve the cure rate of these patients, precisely detecting patients with high risk of relapse and incorporating new targeted therapies are urgently needed. This study investigated inexpensive, rapid, next-generation sequencing of more than 150 cancer-related genes for matched diagnostic, remission, and relapse samples of 17 patients (3 months to 15 years old) with relapsed ALL. In this analysis, we identified 16 single-nucleotide variants (SNVs) and insertion/deletion variants and 19 copy number variants (CNVs) at diagnosis and 28 SNVs and insertion/deletion variants and 22 CNVs at relapse. With these genetic alterations, we could detect several B cell precursor ALL patients with high-risk gene alterations who were not stratified into the highest-risk group (5/8, 62.5%). We also detected potentially actionable genetic variants in about half of the patients (8/17, 47.1%). Among them, we found that one patient harbored germline TP53 mutation as a secondary finding. This inexpensive, rapid method can be immediately applied as clinical sequencing and could lead to better management of these patients and potential improvement in the survival rate in childhood ALL.

Comparative mutational evaluation of multiple lung cancers by multiplex oncogene mutation analysis.

In patients presenting with synchronous or metachronous multiple lung cancer (MLC), it is important to distinguish between multiple primary lung cancer (MP) and intrapulmonary metastasis (IM). The present study was aimed at investigating the mutational profiles of synchronous/metachronous MLC and to compare the classification of paired tumors by multiplex gene mutation analysis with the histopathological evaluation. We carried out targeted sequencing of 20 lung cancer-related oncogenes using next-generation sequencing (NGS) in 82 tumors from 37 MLC patients who underwent surgical resection at our department. The patients were diagnosed as MP or IM cases based on the Martini and Melamed criteria, histopathological and gene mutational evaluations. Matching mutations between paired tumors was observed in 20 (54%) patients, who were diagnosed as IM cases by mutational evaluation. Patients who could not be clearly diagnosed by histopathological evaluation were classified as equivocal cases. Among the histopathological IM cases (n = 7), six (86%) were confirmed as IM cases also by mutational evaluation, and most of the paired tumors of these cases (n = 5) harbored multiple matching mutations. Among the histopathological MP cases (n = 17), mutational evaluation yielded a discordant diagnosis in eight (47%) cases. Of these, the paired tumors of four cases harbored multiple matching mutations, suggesting that the mutational diagnosis might be more suitable in these patients. Our findings suggest that multiplex mutational analysis could be a useful complementary tool for distinguishing between MP and IM in addition to histopathological evaluation.

Asymmetric Synthesis and Cytotoxicity Evaluation of Right-Half Models of Antitumor Renieramycin Marine Natural Products.

A general protocol for the asymmetric synthesis of 3-N-arylmethylated right-half model compounds of renieramycins was developed, which enabled structure⁻activity relationship (SAR) study of several 3-N-arylmethyl derivatives. The most active compound (6a) showed significant cytotoxic activity against human prostate cancer DU145 and colorectal cancer HCT116 cell lines (IC50 = 11.9, and 12.5 nM, respectively).

Development and validation of a new ICD-10-based trauma mortality prediction scoring system using a Japanese national inpatient database.

INTRODUCTION: To develop and validate a new trauma mortality prediction scoring system based on International Statistical Classification of Diseases (ICD)-10 codes, using a Japanese administrative claims and discharge abstract database. METHODS: This retrospective observational study used the Japanese Diagnosis Procedure Combination database. Injuries were categorised into 33 groups with 5 additional groups based on injury sites and types. A multivariable logistic regression analysis was performed for in-hospital mortality in a derivation cohort after adjusting for the 38 groups, patient's sex, age and Charlson Comorbidity Index score. Each variable was assigned a score that was equal to the value of the regression coefficient. The new severity score was defined as the sum of the scores. The new scoring system was tested in a validation cohort. RESULTS: The mortality rates were 2.4% (9270/393 395) and 2.5% (8778/349 285) in the derivation and validation cohorts, respectively. The area under the receiver operating curve (AUROC) of the new scoring system was 0.887 (95% CI 0.884 to 0.890) in the validation cohort. Subgroup analyses showed that the scoring system retained high predictive performance both for patients <65 years (AUROC 0.934, 95% CI 0.928 to 0.939) and for elderly patients at the age of ≥65 years (AUROC 0.825, 95% CI 0.820 to 0.829). CONCLUSIONS: A new ICD-10-based injury severity scoring system was developed and validated. Further studies are required to validate the scoring system in other databases.

Outcomes of Argatroban Treatment in Patients With Atherothrombotic Stroke: Observational Nationwide Study in Japan.

BACKGROUND AND PURPOSE: Argatroban, a selective thrombin inhibitor, is recommended for the use in patients with atherothrombotic stroke by the Japanese Guidelines for the Management of Patients with Acute Ischemic Stroke. We performed a nationwide Japanese study to investigate whether argatroban improved early stroke outcomes in patients with acute atherothrombotic stroke. METHODS: This retrospective observational study, using the Diagnosis Procedure Combination database in Japan, included patients who were hospitalized from July 1, 2010, to March 31, 2012, with a diagnosis of atherothrombotic stroke within 1 day of stroke onset. Patients were divided into 2 groups: those receiving argatroban on admission (argatroban group), and those who did not receive argatroban during hospitalization (control group). To balance the baseline characteristics and concomitant treatments during hospitalization between the 2 groups, one-to-one propensity-score matching analyses were performed. The main outcomes were the modified Rankin Scale score at discharge and the occurrence of hemorrhagic complications during hospitalization. An ordinal logistic regression analysis evaluated the association between argatroban use and modified Rankin Scale at discharge. RESULTS: After propensity-score matching, 2289 pairs of patients were analyzed. There were no significant differences in modified Rankin Scale at discharge between the argatroban and the control groups (adjusted odds ratio, 1.01; 95% confidence interval, 0.88-1.16). The occurrence of hemorrhagic complications did not differ significantly between the argatroban and the control groups (3.5% versus 3.8%; P=0.58). CONCLUSIONS: The present study suggested that argatroban was safe, but had no added benefit in early outcomes after acute atherothrombotic stroke.

Effect of prehospital epinephrine on out-of-hospital cardiac arrest: a report from the national out-of-hospital cardiac arrest data registry in Japan, 2011-2012.

PURPOSE: The effect of prehospital epinephrine on neurological outcome in out-of-hospital cardiac arrest (OHCA) is still controversial. We sought to determine whether prehospital epinephrine administration was associated with improved outcomes in adult OHCA. METHODS: A nationwide, population-based, propensity score-matched study of OHCA patients from January 1, 2011, to December 31, 2012, in Japan was conducted. We included adult OHCA patients treated by emergency medical service personnel without an excessive delay. The primary outcome was neurologically favorable survival 1 month after OHCA. RESULTS: A total of 237,068 patients (16,616 with a shockable rhythm and 220,452 with a non-shockable rhythm) were included in the final cohort. A total of 4024 out of the 16,616 shockable OHCAs and 29,393 out of the 220,452 non-shockable OHCAs received prehospital epinephrine. In the propensity score-matched cohort, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival (shockable OHCA 7.6 vs. 17.9 %, OR 0.38 [95%CI 0.33-0.43]; non-shockable OHCA 0.6 vs. 1.2 %, OR 0.47 [95%CI 0.39-0.56]). In the subgroup analyses, prehospital epinephrine was significantly associated with poor neurological outcome in all subgroups. In the ancillary analyses, although the neurological outcome was worse as the number of epinephrine doses increased or the time to epinephrine increased, patients had a greater chance of a favorable neurological outcome only when a single dose of epinephrine was administered within 15 min of the emergency call in shockable OHCA. CONCLUSIONS: Among adult OHCA patients, prehospital epinephrine was associated with a decreased chance of neurologically favorable survival. Situations in which prehospital epinephrine is effective may be extremely limited.

Potential Survival Benefit of Polymyxin B Hemoperfusion in Septic Shock Patients on Continuous Renal Replacement Therapy: A Propensity-Matched Analysis.

BACKGROUND/AIMS: We assessed the survival benefit of polymyxin B hemoperfusion (PMX) in septic shock patients starting continuous renal replacement therapy (CRRT), who are known to have an increased rate of mortality. METHODS: Adult patients in the Japanese diagnosis procedure combination database satisfying the following criteria were enrolled: hospitalized in 2007-2012; diagnosed as having sepsis; required noradrenaline and/or dopamine; and started CRRT in intensive care unit. Propensity scores for receiving PMX were created from patient and hospital characteristics. RESULTS: Of 3,759 eligible patients, 1,068 received PMX. Propensity-score matching produced a matched cohort of 978 pairs. The 28-day mortality was 40.2% (393/978) in the PMX group and 46.8% (458/978) in the control group (p = 0.003). Logistic regression analysis revealed a significant association between the use of PMX and decreased 28-day mortality (adjusted OR 0.75; 95% CI 0.62-0.91). CONCLUSION: This large retrospective study suggests that septic shock patients starting CRRT may benefit from PMX.

Erythropoietin concentration in acute kidney injury is associated with insulin-like growth factor-binding protein-1.

AIM: Erythropoietin (EPO) production is stimulated by hypoxia in the kidney. Ischaemic injury plays a crucial role in the pathogenesis of acute kidney injury (AKI). However, EPO concentrations in critically ill patients complicated with AKI have not been evaluated sufficiently. This study was conducted to clarify the factors associated with plasma EPO concentrations in AKI. METHODS: This study prospectively enrolled 98 critically ill adult patients treated at the adult mixed ICU. Plasma EPO, insulin-like growth factor-binding protein-1 (IGFBP-1), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6 (IL-6) and urinary N-acetyl-ß-D-glucosaminidase (NAG) were measured on ICU admission. RESULTS: Acute kidney injury occurred in 42 (42.9%) patients. Significantly higher plasma EPO in the AKI group was detected than in the non-AKI group (16.13 (9.87-28.47) mIU/mL versus 27.81 (10.16-106.02) mIU/mL, P < 0.05). Plasma IGFBP-1 in the AKI group was also significantly higher than in the non-AKI group (19 208 (8820-50 780) pg/mL versus 63 199 (25 289-147 489) pg/mL, P < 0.05). Plasma EPO concentration was negatively correlated with haemoglobin in the non-AKI group with statistical significance, but not in the AKI group. Multiple logistic regression analysis revealed that plasma EPO in the AKI group was associated significantly with plasma IGFBP-1 and complication of diabetes mellitus, but not the haemoglobin concentration, partial pressure of arterial oxygen (PaO2 ), and IL-6. CONCLUSIONS: Not low arterial oxygen tension, haemoglobin concentration, and inflammation evaluated by IL-6 but plasma IGFBP-1 was significantly associated with plasma EPO concentration in AKI, suggesting an unknown mechanism related to systemic stress conditions for EPO regulation in AKI.

Ozagrel for Patients With Noncardioembolic Ischemic Stroke: A Propensity Score-Matched Analysis.

BACKGROUND AND PURPOSE: Ozagrel sodium (ozagrel), a thromboxane A2 synthesis inhibitor, is used for ischemic stroke patients in several countries, despite a lack of strict evidence of its benefits. We investigated whether ozagrel was beneficial for patients with atherothrombotic stroke or lacunar infarction. METHODS: This was a retrospective observational study using the Diagnosis Procedure Combination database in Japan. We identified patients with atherothrombotic stroke or lacunar infarction who were admitted to 781 hospitals from July 1, 2010 to March 31, 2012. Propensity score-matched analyses were performed separately for patients with atherothrombotic stroke and those with lacunar infarction, which balanced differences in baseline characteristics between patients who received ozagrel (ozagrel group) and those who did not (control group) in each stroke subtype. The modified Rankin Scale scores at discharge and occurrence of hemorrhagic complications after admission were compared between the ozagrel and control groups. RESULTS: After the propensity score matching, 2726 pairs of patients with atherothrombotic stroke and 1612 pairs of patients with lacunar infarction were analyzed. Ordinal logistic regression analyses showed that ozagrel use was not significantly associated with modified Rankin Scale score at discharge in patients with atherothrombotic stroke (odds ratio: .99; 95% confidence interval: .88-1.11) or in those with lacunar infarction (odds ratio: 1.00; 95% confidence interval: .87-1.16). The occurrence of hemorrhagic complications did not differ significantly between the ozagrel and control groups. CONCLUSION: The present study suggested that ozagrel was safe to use but did not improve functional outcomes in patients with atherothrombotic or lacunar infarction.

Detection of K-ras gene mutation by liquid biopsy in patients with pancreatic cancer.

BACKGROUND: Cell-free circulating tumor DNA (ctDNA) in serum has been considered to be a useful candidate for noninvasive cancer diagnosis. The current study was designed to estimate the clinical usefulness of genetic analysis for ctDNA by digital polymerase chain reaction in patients with pancreatic cancer. METHODS: The authors compared K-ras mutations detected in endoscopic ultrasound-guided fine-needle aspiration biopsy tissue DNA and in ctDNA from 75 patients with pancreatic cancer. K-ras mutations in the serum of 66 independent, consecutive patients with pancreatic cancer were also analyzed and the authors compared the results with survival rates. RESULTS: The frequencies of the mutations in tissue samples at G12V, G12D, and G12R in codon 12 were 28 of 75 samples (37.3%), 22 of 75 samples (29.3%), and 6 of 75 samples (8.0%), respectively. Conversely, the rates of the mutations in ctDNA were 26 of 75 samples (34.6%), 29 of 75 samples (38.6%), and 4 of 75 samples (5.3%), respectively. Overall, the K-ras mutation rates in tissue and ctDNA were 74.7% and 62.6%, respectively, and the concordance rate between them was 58 of 75 samples (77.3%). Survival did not appear to differ by the presence of K-ras mutations in tissue DNA, but the survival of patients with K-ras mutations in ctDNA was significantly shorter than that of patients without mutations in both a development set (P = .006) and an independent validation set (P = .002). The difference was especially evident in cases with a G12V mutation. CONCLUSIONS: Analysis of ctDNA is a new useful procedure for detecting mutations in patients with pancreatic cancer. This noninvasive method may have great potential as a new strategy for the diagnosis of pancreatic cancer as well as for predicting survival.

Current state of continuous renal replacement therapy for acute kidney injury in Japanese intensive care units in 2011: analysis of a national administrative database.

BACKGROUND: Nationwide data for the prevalence and outcomes of patients receiving continuous renal replacement therapy (CRRT) in intensive care units (ICUs) are scarce. This study assessed the status of CRRT in Japanese ICUs using a nationwide administrative claim database. METHODS: Data were extracted from the Japanese Diagnosis Procedure Combination database for 2011. From a cohort of critically ill patients aged 12 years or older who were admitted to ICUs for 3 days or longer, acute kidney injury (AKI) patients treated with CRRT were identified. The period prevalence of CRRT and in-hospital mortality were calculated. Logistic regression analysis identified factors associated with in-hospital mortality. RESULTS: Of 165 815 ICU patients, 6478 (3.9%) received CRRT for AKI. The most frequent admission diagnosis category was diseases of the circulatory system (n = 3074). The overall in-hospital mortality rate of the CRRT-treated AKI patients was 50.6%. Clustering patients into four groups by background revealed the lowest in-hospital mortality rate of 41.5% for the cardiovascular surgery group (n = 1043) compared with 53.5% for the nonsurgical cardiovascular group (n = 2031), 51.7% for the sepsis group (n = 1863) and 51.6% for other cases (n = 1541). Multiple logistic regression analysis showed a significant association of these four group classifications with in-hospital mortality in addition to age, hospital characteristics (type and volume), time from hospital admission to CRRT initiation and interventions performed on the day of CRRT initiation. CONCLUSIONS: Using a large Japanese nationwide database, this study revealed remarkably high in-hospital mortality of CRRT-treated AKI patients, although the period prevalence of CRRT for AKI in ICUs was low.

The contributions of emergency physicians to out-of-hospital cardiopulmonary arrest: an analysis of the national Utstein Registry data.

BACKGROUND: Emergency physicians are likely to play an important role in the "chain of survival." The relationship between the number of emergency physicians and out-of-hospital cardiopulmonary arrest (OHCA) prognosis is not well understood. OBJECTIVE: We assessed the impact of the number of emergency physicians on the outcomes of OHCA. METHODS: In a nationwide, population-based, observational study, we enrolled 120,721 adults aged ≥ 18 years with OHCA, from January 1, 2010 to December 31, 2010. We used the countrywide Utstein Registry database coupled with health statistics data surveyed by the Ministry of Health, Labour and Welfare. The primary endpoint was favorable neurological outcomes 1 month after OHCA. RESULTS: During the study period, OHCA occurred in 25,580 people (21.2%) in an area with the number of emergency physicians/100,000 population < 1.5, in 62,299 people (51.6%) in an area with ≥ 1.5 and < 3.0 emergency physicians/100,000 population, in 30,948 people (25.6%) in an area with ≥ 3.0 and < 4.5 emergency physicians/100,000 population, and in 1894 people (1.6%) in an area with ≥ 4.5 emergency physicians/100,000 population. Patient prognosis became more favorable as the number of emergency physicians increased (1-month survival: 5.08% vs. 5.81% vs. 5.90% vs. 8.82%, p < 0.0001; and favorable neurological outcomes: 2.64% vs. 2.84% vs. 3.23% vs. 3.54%, p < 0.0001; for emergency physicians/100,000 population of < 1.5, ≥ 1.5 and < 3.0, ≥ 3.0 and < 4.5, and ≥ 4.5, respectively). The adjusted odds ratio for favorable neurological outcomes per increase of one emergency physician/100,000 population was 1.06 (95% confidence interval 1.01-1.11, p = 0.0163). CONCLUSION: An increased number of emergency physicians/100,000 population is likely to be associated with improved outcomes.

Effective pre-hospital care for out-of-hospital cardiac arrest caused by respiratory disease.

BACKGROUND: The relationship between pre-hospital care and the prognosis of out-of-hospital cardiac arrest (OHCA) caused by respiratory disease is unclear. This study aimed to assess the impact of pre-hospital care on the prognosis of OHCA caused by respiratory disease. METHODS: In a nationwide, population-based, observational study, we enrolled 121,081 adults aged ≥18 years who experienced OHCA from January 1, 2010, to December 31, 2010. The primary endpoint was favourable neurological outcomes. RESULTS: Of the 120,256 eligible adult OHCA patients, 7,071 (5.9%) experienced OHCA caused by respiratory disease. Of these 7,071 patients, 3,911 (55.3%) received no cardiopulmonary resuscitation (CPR), 2,403 (34.0%) received chest-compression-only CPR, and 757 (10.7%) received conventional CPR by a bystander. There was no significant difference between the three types of bystander CPR with regard to the neurological outcome (no CPR: OR 0.68, 95%CI 0.39-1.24, p=0.1951; chest-compression-only CPR: OR 0.68, 95%CI 0.37-1.29, p=0.2295; and conventional CPR: as a reference). Pre-hospital administration of epinephrine (OR 0.37, 95%CI 0.13-0.85, p=0.0170) and the implementation of advanced airway management (OR 0.32, 95%CI 0.19-0.52, p<0.0001) were associated with poor neurological outcomes. CONCLUSIONS: Even in OHCA caused by respiratory disease, not only pre-hospital epinephrine administration but also pre-hospital advanced airway management and rescue breathing in bystander CPR may not be critical.

Postoperative polymyxin B hemoperfusion and mortality in patients with abdominal septic shock: a propensity-matched analysis.

OBJECTIVES: To examine the effect of postoperative polymyxin B hemoperfusion on mortality in patients with abdominal septic shock triggered by lower gastrointestinal tract perforation, identifying subpopulations of patients who may benefit from this treatment. DESIGN: Propensity-matched analysis. SETTING: We used a nationwide inpatient database in Japan. PATIENTS: We included patients who are 18 years old or older hospitalized during a period of 34 months between July 2007 and October 2011, who had open abdominal surgery on the day of admission (day 0) for perforation of lower gastrointestinal tract, and who required noradrenaline and/or dopamine. We excluded patients who died on day 0 or 1 and patients starting polymyxin B hemoperfusion on day 2 or later. MEASUREMENTS AND MAIN RESULTS: The main outcome was 28-day mortality. Of 2,925 eligible patients, 642 received one or two polymyxin B hemoperfusion sessions, starting the first one on day 0 or 1. Propensity score matching created a matched cohort of 1,180 patients (590 pairs with and without polymyxin B hemoperfusion). The 28-day mortality was 17.1% (101 of 590) in the polymyxin B hemoperfusion group and 16.3% (96 of 590) in the control group (p = 0.696). Subgroup analyses by number of polymyxin B hemoperfusion sessions (one or two), timing of polymyxin B hemoperfusion initiation (day 0 or 1), the use of noradrenaline, and number of dysfunctional organs (one to six) did not show any significant difference in 28-day mortality between the groups. Multiple logistic did not show a significant association between the use of polymyxin B hemoperfusion and 28-day mortality (adjusted odds ratio, 1.10; 95% CI, 0.80-1.51; p = 0.569). Age, end-stage renal disease requiring maintenance hemodialysis, the use of noradrenaline, and number of dysfunctional organs were positively associated with 28-day mortality. CONCLUSIONS: In this retrospective study, postoperative polymyxin B hemoperfusion did not show any survival benefit for the overall study population or any of the studied subgroups of patients with abdominal septic shock. A large multicentered prospective randomized trial is warranted to identify the true role of polymyxin B hemoperfusion in sepsis caused by Gram-negative bacteria.