Detection of circulating superantigens in an intensive care unit population

AbstractObjective: Plasma concentrations of superantigens were measured in an intensive care unit (ICU) population and the relationship of superantigen positive rates with the presence of sepsis was investigated.Methods: Plasma samples were collected at least twice a week from 78 patients whose primary diagnoses were abdominal disorders (n = 27), respiratory disorders (n = 11), trauma (n = 10), burns (n = 10), cardiovascular disorders (n = 4), neurological disorders (n = 2), and others (n = 14). Five different species of superantigens, i.e., staphylococcal enterotoxins A, B, and C (SEA, SEB, and SEC), toxic shock syndrome toxin-1 (TSST-1), and streptococcal pyrogenic exotoxin A (SPEA), were measured using an enzyme-linked immunosorbent assay.Results: Significant levels of plasma superantigens were detected in 16 patients. SEA was found in seven patients, SEB in four patients, SEC in two patients, TSST-1 in six patients, and SPEA in five patients. Superantigen detection rates were 6% (1/17) in patients without systemic inflammatory response syndrome (SIRS), 0% (0/21) in SIRS patients without infection, 31% (5/16) in septic patients without shock, and 42% (10/24) in septic shock patients.Conclusions: The presence of superantigens was confirmed in part of the ICU population. The role of superantigens in the pathogenesis of sepsis remains to be determined

Metastatic Carcinoma to Subcutaneous Tissue and Skeletal Muscle: Clinicopathological Features in 11 Cases

Objective: Metastatic carcinoma to subcutaneous tissue or skeletal muscle is relatively rare. The present study aimed to clarify the clinicopathological features for confirming the diagnosis as soft tissue metastasis and determining the primary site. Methods: We reviewed records of 11 patients with soft tissue metastasis who were in our institution from 1996 to 2009. Results: In 9 of 10 patients who underwent magnetic resonance imaging, findings consisted of poorly circumscribed high-intensity lesions around the tumor on T2-weighted images, irregular peritumoral enhancement and poorly enhanced lesions at the center of the tumor on T1-weighted images. Systematic immunohistochemical examination was more valuable for diagnosing as soft tissue metastasis and confirming the primary site. The expression patterns of cytokeratins 7 and 20 and tissue-specific antibodies such as thyroid transcription factor-1, MUC5AC and CDX2 were useful diagnostic markers. The primary site could be determined in five patients with cytokeratin 7/20 immunophenotype and positivity for tissue-specific antibodies. In four cases, determination of the primary site finally became possible by comparison with the histological findings of operative specimens in past carcinoma and/or in consideration of radiological findings and the results of cytokeratin 7/20 phenotyping. Conclusions: Systematic immunohistochemical examination is helpful for confirmation of the primary origin in soft tissue metastasis of carcinoma in addition to clinical information such as the history and condition of past carcinoma, radiological findings and comparison between the histology of biopsy specimens and past carcinoma.ArticleJAPANESE JOURNAL OF CLINICAL ONCOLOGY. 41(3):358-364 (2011)journal articl

Rare complications of hyperbaric oxygen therapy

Hyperbaric oxygen therapy (HBOT) for carbon monoxide (CO) poisoning is widely performed to prevent delayed neuropsychiatric syndrome. Although HBOT can generally be performed with safety, the appropriate management of HBOT still remains unestablished. A 31-year-old man was transferred to our facility to undergo HBOT in a multiplace chamber with a diagnosis of CO poisoning. The first HBOT session ended uneventfully. During the second HBOT session, the patient suddenly experienced convulsive seizures. The accompanying doctor administered intravenous propofol to stop the convulsion and terminated the HBOT. Soon after the convulsion, the patient developed frothy secretions through the endotracheal-tube with impaired oxygenation. Head computed tomography scan showed no abnormalities, suggesting the seizure was associated with complications of HBOT. A chest X-ray revealed bilateral pulmonary edema, and echocardiography revealed normal cardiac function, indicating that the pulmonary edema resulted from HBOT or neurogenic mechanism secondary to the seizure. The patient’s respiratory status improved without recurrence of the seizure and no delayed neurological sequelae was seen afterwards. Here we report unexpected rare adverse events during HBOT. Hyperbaric oxygen therapy for acute indications should be performed in multiplace chambers, with appropriate preparation and medical equipment

Predictive Factors of the Fatality of Motor Vehicle Passengers Involved in Far-Side Lateral Collisions: A National Crash Database Study

Although the risks faced by passengers in near-side lateral collisions are understood, and despite the presence of side airbags for injury prevention, passengers involved in far-side lateral collisions also suffer serious and fatal injuries. The objective of this study was to determine the independent predictive factors of fatality of motor vehicle passengers involved in far-side lateral collisions. Using 2010 records from the National Automotive Sampling System/Crashworthiness Data System (NASS/CDS), we selected 86 fatal and 325 non-fatal passengers with an Abbreviated Injury Scale (AIS) score of 2 or more. The background and injury severity of the passengers and collision characteristics were compared between the two groups. In a multivariable logistic regression analysis, variables independently associated with fatalities were female sex (Ref, male) (odds ratio [OR], 0.396), age (OR, 1.029), body mass index (OR, 1.057), total delta-V (OR, 1.031), head AIS score (OR, 1.679), chest AIS score (OR, 1.330), and abdomen AIS score (OR, 1.294). This is the first report to determine factors affecting fatality in passengers involved in far-side lateral collisions. Improving the safety of the vehicle interior, such as by including additional seatbelt systems or a side airbag that deploys between seats, might help to avoid fatalities, and reduce injury severity

Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2‐mutation carriers

The aldehyde degrading function of the ALDH2 enzyme is impaired by Glu504Lys polymorphisms (rs671, termed A allele), which causes alcohol flushing in east Asians, and elevates the risk of esophageal cancer among habitual drinkers. Recent studies suggested that the ALDH2 variant may lead to higher levels of DNA damage caused by endogenously generated aldehydes. This can be a threat to genome stability and/or cell viability in a synthetic manner in DNA repair-defective settings such as Fanconi anemia (FA). FA is an inherited bone marrow failure syndrome caused by defects in any one of so far identified 22 FANC genes including hereditary breast and ovarian cancer (HBOC) genes BRCA1 and BRCA2. We have previously reported that the progression of FA phenotypes is accelerated with the ALDH2 rs671 genotype. Individuals with HBOC are heterozygously mutated in either BRCA1 or BRCA2, and the cancer-initiating cells in these patients usually undergo loss of the wild-type BRCA1/2 allele, leading to homologous recombination defects. Therefore, we hypothesized that the ALDH2 genotypes may impact breast cancer development in BRCA1/2 mutant carriers. We genotyped ALDH2 in 103 HBOC patients recruited from multiple cancer centers in Japan. However, we were not able to detect any significant differences in clinical stages, histopathological classification, or age at clinical diagnosis across the ALDH2 genotypes. Unlike the effects in hematopoietic cells of FA, our current data suggest that there is no impact of the loss of ALDH2 function in cancer initiation and development in breast epithelium of HBOC patients

Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction

心房細動の遺伝的基盤を解明 --大規模ゲノムデータによる病態解明と遺伝的リスクスコア構築--. 京都大学プレスリリース. 2023-01-20.Atrial fibrillation (AF) is a common cardiac arrhythmia resulting in increased risk of stroke. Despite highly heritable etiology, our understanding of the genetic architecture of AF remains incomplete. Here we performed a genome-wide association study in the Japanese population comprising 9, 826 cases among 150, 272 individuals and identified East Asian-specific rare variants associated with AF. A cross-ancestry meta-analysis of >1 million individuals, including 77, 690 cases, identified 35 new susceptibility loci. Transcriptome-wide association analysis identified IL6R as a putative causal gene, suggesting the involvement of immune responses. Integrative analysis with ChIP-seq data and functional assessment using human induced pluripotent stem cell-derived cardiomyocytes demonstrated ERRg as having a key role in the transcriptional regulation of AF-associated genes. A polygenic risk score derived from the cross-ancestry meta-analysis predicted increased risks of cardiovascular and stroke mortalities and segregated individuals with cardioembolic stroke in undiagnosed AF patients. Our results provide new biological and clinical insights into AF genetics and suggest their potential for clinical applications