Seong-Ho Kim

Sepsis is a life-threatening condition and remains a major cause of mortality. The aim of this study was to evaluate the role of biomarkers in the diagnosis of sepsis and septic shock in patients admitted to the emergency department (ED). Medical records of patients who underwent measurement of serum biomarkers including lactic acid, C-reactive protein, procalcitonin (PCT), and presepsin in the ED between May 2019 and May 2020 were retrospectively reviewed. Patients were subdivided into 3 groups; non-sepsis, sepsis, and septic shock according to the new definition using the sequential organ failure assessment score. The mean age was 69.3 years, and 55.8% of the study population was female. Of 249 subjects, 98 patients confined to sepsis group, and 35.7% of them were septic shock. In the multivariable analysis, a high level of PCT was an independent predictor of sepsis (odds ratio [OR], 1.028; 95% confidence interval [CI], 1.006–1.051; P = .011) along with a simplified acute physiology score III (SAPS III) (OR, 1.082; 95% CI, 1.062–1.103, P < .001). PCT was also an independent risk factor for septic shock (OR, 1.043; 95% CI, 1.016–1.071, P = .02). In the receiver operating characteristic curve analysis, the area under the curve of PCT to predict sepsis and septic shock were 0.691 (P < .001) and 0.734 (P < .001), respectively. The overall 30-days mortality rate was 8.8%, and the mortality rate was significantly higher in the sepsis group (sepsis vs non-sepsis, 15.3% vs 4.6%; P = .004). In the multivariate Cox analysis, a higher level of lactic acid (hazard ratio [HR], 1.328; 95% CI, 1.061–1.663, P = .013), predisposing chronic pulmonary diseases (HR, 7.035; 95% CI, 1.687–29.341, P = .007), and a high SAPSIII value (HR, 1.046; 95% CI, 1.015–1.078, P = .003) were independent risk factors for mortality in sepsis patients. PCT was a useful biomarker for predicting sepsis and septic shock in the ED. A higher level of lactic acid, predisposing chronic pulmonary diseases, and a high SAPS III score were associated with a greater mortality risk in patients with sepsis.

Pleuroparenchymal fibroelastosis (PPFE) is a rare idiopathic interstitial pneumonia characterized by predominantly upper lobe involvement with pleural fibrosis and subjacent parenchymal fibrosis. Recently, there have been increasing reports of PPFE, and PPFE might coexist with other interstitial lung diseases in the lower lobe and upper lobe. However, cases of unilateral PPFE are scarce. A 75-year-old Korean male presented to our hospital with chronic dry cough and exertional dyspnea. The patient’s symptoms started 6 mo previously and had been gradually worsening. At the time of presentation, he felt dyspnea when walking at his own pace. Radiologic findings suggested PPFE, but the lesion was localized in the upper lobe of the right lung. After multidisciplinary discussion, a transbronchial lung biopsy in the right upper lobe revealed collapsed alveoli with parenchymal fibroelastosis, and elastic van Gieson staining demonstrated septal elastosis with intra-alveolar collagenosis, which met the histopathologic criteria of definite PPFE. After multidisciplinary discussion in an experienced interstitial lung disease center, we confirmed the diagnosis of unilateral PPFE. Furthermore, we confirmed the progression of PPFE on radiologic findings during the follow-up period. Clinicians should consider PPFE, even in cases with unilateral, predominantly upper lung involvement in interstitial lung disease patients through multidisciplinary discussion.

Growing evidence suggests that early life stress (ELS) has long-lasting effects on glucocorticoid receptor (GR) expression and behavior via epigenetic changes of the GR exon 1₇ promoter. However, it remains unclear whether ELS regulates histone modifications of the GR exon 1₇ promoter across the life span. We investigated the effects of maternal separation (MS) on histone acetylation and methylation of GR exon 1₇ promoter in the hippocampus, according to the age of adults. Depression-like behavior and epigenetic regulation of GR expression were examined at young and middle adulthood in mice subjected to MS from postnatal day 1 to 21. In the forced swimming test, young adult MS mice showed no effect on immobility time, but middle-aged MS mice significantly increased immobility time. Young adult and middle-aged MS mice showed decreased GR expression. Their two ages showed decreased histone acetylation with increased histone deacetylases (HDAC5) levels, decreased permissive methylation, and increased repressive methylation at the GR exon 1₇ promoter. The extent of changes in gene expression and histone modification in middle adulthood was greater than in young adulthood. These results indicate that MS in early life causes long-term negative effects on behavior via histone modification of the GR gene across the life span.

Milnacipran is a reuptake inhibitor of both serotonin and noradrenaline, used in the treatment of fibromyalgia with severe depression. However, few studies have been conducted on the efficacies of milnacipran drug on the functional connectivity of the neural network. The authors aimed to find the correlation between the drug efficacy and the changes in neural network in fibromyalgia patients. Resting-state-functional magnetic resonance imaging (rs-fMRI) were obtained before and after milnacipran drug administration. Graph theory indexes and small-worldness were calculated using preprocessed blood-oxygen-level-dependent signals from the rs-fMRI scans of 14 brain regions-of-interest. Statistical analyses were conducted to compare the topological network parameters. Significant changes in the neural network indexes appeared in three of the 14 brain regions-of-interest. In the pain network, the average path length on the left side of Brodmann area 32 was shortened. In the default mode network, functional connectivity changes were observed in the left lateral parietal cortex and medial prefrontal cortex. In the left lateral parietal cortex, the degree and betweenness centrality increased, whereas the clustering coefficient decreased. In the medial prefrontal cortex, local efficiency decreased. The small-worldness declined after milnacipran medication. The present results demonstrate that functional connectivity indexes in the brains of female fibromyalgia patients obtained from rs-fMRI data can be used as potential prognosis markers of milnacipran drug treatment.

Several lines of evidence imply that brain-derived neurotrophic factor (BDNF) is involved in the pathophysiology of fibromyalgia (FM); in this regard, patients with FM have altered blood and cerebrospinal fluid levels of BDNF. In this study, we explored the association between BDNF gene polymorphisms and FM susceptibility and the severity of symptoms. In total, 409 patients with FM and 423 healthy controls in 10 medical centers were enrolled from the Korean nationwide FM survey. The alleles and genotypes at 10 positions in the BDNF gene were genotyped. The allele and genotype frequencies of BDNF rs11030104 differed significantly between the patients with FM and the controls (P = 0.031). The GG genotype of rs11030104 had a protective effect against FM (P = 0.016), and the G allele of rs11030104 was negatively associated with the presence of FM compared with the A allele (P = 0.013). In comparison, although the allele and genotype frequencies of BDNF rs12273539 did not differ between the two groups, the TT genotype of BDNF rs12273539 was associated with susceptibility to FM (P = 0.038). Haplotype analyses implied that some BDNF haplotypes have a protective effect against FM. Finally, several genotypes and haplotypes of the BDNF gene contributed to specific symptoms of FM. This study is the first to evaluate the associations between BDNF gene polymorphisms and FM. Our results imply that some BDNF single-nucleotide polymorphisms and haplotypes are associated with susceptibility to, and contribute to the symptoms of, FM.

Objectives This study aimed to evaluate the relationship between radiographic knee osteoarthritis and vertebral fractures (VFs) in an Asian population. Methods This cross-sectional study involved data from 1,829 participants of the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee osteoarthritis was defined as Kellgren-Lawrence (KL) grades >= 2. Prevalent VF was defined as a loss of >= 4 cm of height from the peak height. BMD was measured using dual-energy X-ray absorptiometry, in the lumbar spine and femoral neck. Results In both sexes, the prevalence of VFs increased with age, and was higher in the knee osteoarthritis group than in the control group (in men 13.2 % in osteoarthritis group and 7.9 % in control group; in women 27.7 % in osteoarthritis group and 14.7 % in control group). Age-adjusted BMD at the lumbar spine and femoral neck was significantly higher in the knee osteoarthritis group. In multivariable analysis, KL grade 4 was significantly associated with vertebral fractures in men. In women, there was a significant trend for a positive association between KL grades and vertebral fractures. Conclusions Despite high systemic BMD, knee osteoarthritis was positively associated with VFs. These results suggest that bone quality, and consequently bone strength, may be decreased at the systemic level in knee osteoarthritis.

This study aimed to evaluate the relationship between radiographic knee osteoarthritis and vertebral fractures (VFs) in an Asian population.

Objective: Sarcopenic obesity is a body composition category in which obesity is accompanied by low skeletal muscle mass, offsetting the increase in body weight caused by increased adipose tissue. The purpose of this study was to analyze the association between knee osteoarthritis (OA) and 4 different categories of body composition: normal, sarcopenic nonobesity, nonsarcopenic obesity, and sarcopenic obesity.Methods: This was a cross‐sectional study using the data from 2,893 participants in the Fifth Korean National Health and Nutrition Examination Survey. Radiographic knee OA was defined as a Kellgren/Lawrence grade of ≥2. Appendicular skeletal muscle mass (ASM) and whole‐body fat mass were measured using dual x‐ray absorptiometry. Sarcopenia was defined as a skeletal muscle mass index (ASM/body weight [%]) below –2SD of the value in sex‐matched young reference groups. Nonsarcopenic obesity was defined as a body mass index (BMI) ≥27.5 kg/m².Results: The prevalence of each body composition category was as follows: 83.5% normal, 4.3% sarcopenic nonobesity, 9.2% nonsarcopenic obesity, and 3.0% sarcopenic obesity. Compared with nonsarcopenic obesity participants, participants with sarcopenic obesity were significantly older, had lower ASM, higher whole‐body fat mass, and higher waist circumference. However, there was no significant difference in body weight or BMI. In multivariate analysis, sarcopenic obesity was more closely associated with radiographic knee OA (OR 3.51 [95% confidence interval (95% CI) 2.15–5.75]) than was nonsarcopenic obesity (OR 2.38 [95% CI 1.80–3.15]). Sarcopenic nonobesity showed no significant association with knee OA.Conclusion: Sarcopenic obesity was more closely associated with knee OA than was nonsarcopenic obesity, although both groups had equivalent body weight. This finding supports the importance of the systemic metabolic effect of obesity in knee OA.

Lee S, et al. J Rheum Dis. 2012 Dec;19(6):355-358. http://dx.doi.org/10.4078/jrd.2012.19.6.355