Impact of Pelvic Fracture Sites on Fibrinogen Depletion in Patients with Blunt Trauma: A Single-Center Cohort Study

Background: We aimed to examine the association of pelvic fracture sites with the minimum fibrinogen level within 24 h after hospital arrival. Methods: We conducted a single-center cohort study using health records review. We included patients with pelvic fractures transported by ambulance to a tertiary-care hospital from January 2012 to December 2018 and excluded those transported from other hospitals or aged younger than 16 years. The pelvic fracture was diagnosed and confirmed by trauma surgeons and/or radiologists. We classified the fracture sites of the pelvis as ilium, pubis, ischium, acetabulum, sacrum, sacroiliac joint diastasis, and pubic symphysis diastasis, and each side was counted separately except for pubic symphysis diastasis. We performed linear regression analysis to evaluate the association between pelvic fracture sites and the minimum fibrinogen level within 24 h of arrival. Results: We analyzed 120 pelvic fracture patients. Their mean age was 47.3 years, and 69 (57.5%) patients were men. The median Injury Severity Score was 24, and in-hospital mortality was 10.8%. The mean minimum fibrinogen level within 24 h of arrival was 171.4 mg/dL. Among pelvic fracture sites, only sacrum fracture was statistically significantly associated with the minimum fibrinogen level within 24 h of arrival (estimate, −34.5; 95% CI, −58.6 to −10.4; p = 0.005). Conclusions: Fracture of the sacrum in patients with pelvic fracture was associated with lower minimum fibrinogen levels within 24 h of hospital arrival and the requirement of blood transfusion

Genetic analysis of a Japanese cerebrotendinous xanthomatosis family: identification of a novel mutation in the adrenodoxin binding region of the CYP 27 gene

AbstractCerebrotendinous xanthomatosis (CTX), an autosomal recessive lipid-storage hereditary disorder, is caused by mutations in the sterol 27-hydroxylase gene (CYP 27). A 24-year-old female Japanese CTX patient and her parents were studied for a CYP 27 mutation. Multiple xanthomas were the main complaint of the patient and plasma cholestanol level was markedly elevated. Sterol analysis of a xanthoma biopsy confirmed cholesterol and cholestanol deposition, and the cholestanol accounted for 8.1% of the total setrols. Sterol 27-hydroxylase activity in fibroblasts derived from the patient was undetectable, while the activities in fibroblasts from her mother and father were 54% and 41% of the normal level, respectively. Direct sequence analysis showed a missense mutation of A for G substitution in the CYP 27 gene at codon 362 (CGT 362Arg to CAT 362His) with a homozygous pattern in the patient, and a heterozygous pattern in the parents. The mutation, which eliminates a normal HgaI endonuclease site at position 1195 of the cDNA and is located at the adrenodoxin binding region of the gene, is most probably responsible for the decreased sterol 27-hydroxylase activity in this Japanese CTX family. The combined data strongly support that the primary enzymatic defect in CTX is the disruption of sterol 27-hydroxylase and that the disease is inherited in an autosomal recessive trait

Trends and outcomes of blunt renal trauma management: A nationwide cohort study in Japan

Nakao, S., Katayama, Y., Hirayama, A. et al. Trends and outcomes of blunt renal trauma management: a nationwide cohort study in Japan. World J Emerg Surg 15, 50 (2020). https://doi.org/10.1186/s13017-020-00329-

Real-World Pharmacokinetics, Effectiveness, and Safety of Atezolizumab in Patients With Unresectable Advanced or Recurrent NSCLC: An Exploratory Study of J-TAIL

Introduction: This study validated real-world pharmacokinetic (PK) data using an established population PK (PopPK) model for atezolizumab in Japanese patients with NSCLC and explored the relationship between PK parameters, effectiveness, and adverse events (AEs) for the 1200 mg once every three weeks regimen. Methods: A subgroup of 262 of 1039 patients from J-TAIL consented to this exploratory research for PK evaluation of atezolizumab monotherapy for unresectable advanced/recurrent NSCLC (August 2018 to October 2019; 197 institutions). We evaluated plasma concentrations before the start of the third cycle of atezolizumab infusion classified into quartiles 1 to 4, their association with effectiveness, and the association between atezolizumab maximum plasma concentrations (Cmax) calculated using the existing PopPK model and AEs of special interest (AESIs). Results: Overall, 175 of 262 patients were included; baseline characteristics were similar to those of patients enrolled in J-TAIL (Eastern Cooperative Oncology Group performance status ≥ 2, 12.0%; age ≥ 75 y, 28.9%; atezolizumab as more than or equal to third-line treatment, 57.5%). Atezolizumab plasma concentrations were similar to previously reported data among Japanese/non-Japanese patients. The overall survival was significantly shorter in patients with lower atezolizumab plasma concentrations in Q1 versus Q2 to Q4, although progression-free survival remained the same. The PK data adequately fit the PopPK model, with the frequency of AESIs increasing as the calculated Cmax at cycle 1 increased. Conclusions: In real-world Japanese patients with unresectable advanced/recurrent NSCLC, PKs were similar to previous reports. Certain patient populations had shorter overall survival, and atezolizumab plasma concentrations in cycle 3 were lower in this population. Elevated Cmax at cycle 1 may be associated with an increased frequency of AESIs

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL)

Introduction: The efficacy and safety of atezolizumab in previously treated patients with NSCLC have been established in the registrational phase 3 OAK trial. In this study, we evaluated the effectiveness and safety of atezolizumab monotherapy in a large real-world cohort to confirm the reproducibility of the results of the registrational trial. Methods: This was a multicenter, prospective, single-arm observational study. Consecutive patients with previously treated NSCLC scheduled to receive atezolizumab monotherapy were enrolled. The primary end point was the 18-month overall survival (OS) rate. The incidence of adverse events (AEs) and immune-related AEs was evaluated. Results: Overall, 1002 patients were included in the safety analysis set and 1000 in the full analysis set. Median follow-up was 11.5 months. Of the full analysis set, 62% were ineligible for the OAK trial (OAK-unlike subpopulation). The 18-month OS rate was 41.1%, with a median OS of 13.0 months (95% confidence interval: 12.2–15.1). The 18-month OS rate was 49.4% and 36.1% in OAK-like and OAK-unlike subpopulations, respectively; that in patients with Eastern Cooperative Oncology Group performance status greater than or equal to 2 was 14.3%. The incidence of AEs overall, in the OAK-like, and OAK-unlike subpopulations was 43.9%, 46.2%, and 42.5%; that of immune-related AEs was 19.0%, 20.1%, and 18.3%, respectively. Conclusions: The findings suggest that atezolizumab may be effective and safe for previously treated patients with NSCLC in real-world settings; however, atezolizumab administration should be considered carefully regarding the benefit–risk balance for the OAK-unlike subpopulation, especially in patients with Eastern Cooperative Oncology Group performance status greater than or equal to 2