Serum H‐ficolin levels: Clinical association with interstitial lung disease in patients with systemic sclerosis

Ficolins, a group of oligomeric lectins consisting of three isoforms (H‐, L‐ and M‐ficolin), contribute to innate immunity via activating the complement pathway and/or acting directly as opsonins against pathogens and apoptotic cells. Because apoptotic cells likely drive the development of systemic sclerosis (SSc) partly through innate immunity, we assessed the clinical association of serum H‐ficolin levels in SSc patients. Despite no difference in serum H‐ficolin levels between SSc and control subjects, SSc patients with decreased serum H‐ficolin levels tended to have a higher prevalence of interstitial lung disease (ILD). More importantly, serum H‐ficolin levels inversely correlated with ground‐glass opacity score on chest computed tomography in SSc‐ILD patients. Therefore, H‐ficolin‐related innate immunity may be involved in SSc‐ILD development.     

Reversible Periventricular Hyperintensity Lesions in Cerebral Amyloid Angiopathy: A Case Mimicking Cerebral Amyloid Angiopathy-related Inflammation

A 59-year-old man with progressive cognitive decline and mood disturbances was admitted to the hospital. Brain magnetic resonance imaging revealed marked white matter hyperintensity (WMH) and widespread lobar cerebral microbleeds. Because he had untreated hypertension, we started antihypertensive treatment and found a significantly improved cognitive function and WMH regression. We diagnosed him with cerebral amyloid angiopathy (CAA) based on the modified Boston Criteria with the rare apolipoprotein E (ApoE) ε2/ε4 genotype. The mechanism underlying reversible leukoencephalopathy in CAA may be related to the loss of autoregulation of brain circulation: cerebrovascular amyloid β deposits damaged the blood-brain barrier of the capillaries, which led to vasogenic edema induced by blood pressure surges.     

Fatty liver with metabolic disorder,such as metabolic dysfunction‐associated fatty liver disease,indicates high risk for developing diabetes mellitus

IntroductionNonalcoholic fatty liver disease (NAFLD) is diagnosed after excluding other liver diseases. The pathogenesis of NAFLD when complicated by other liver diseases has not been established completely. Metabolic dysfunction‐associated fatty liver disease (MAFLD) involves more metabolic factors than NAFLD, regardless of complications with other diseases. This study aimed to clarify the effects of fatty liver occurring with metabolic disorders, such as MAFLD without diabetes mellitus (DM), on the development of DM.Materials and MethodsWe retrospectively assessed 9,459 participants who underwent two or more annual health check‐ups. The participants were divided into the MAFLD group (fatty liver disease with overweight/obesity or non‐overweight/obesity complicated by metabolic disorders), simple fatty liver group (fatty liver disease other than MAFLD group), metabolic disorder group (metabolic disorder without fatty liver disease), and normal group (all other participants).ResultsThe DM onset rates in the normal, simple fatty liver, metabolic disorder, and MAFLD groups were 0.51, 1.85, 2.52, and 7.36%, respectively. In the multivariate analysis, the MAFLD group showed a significantly higher risk of DM onset compared with other three groups (P < 0.01). Additionally, the risk of DM onset was significantly increased in fatty liver disease with overweight/obesity or pre‐diabetes (P < 0.01).ConclusionsFatty liver with metabolic disorders, such as MAFLD, can be used to identify patients with fatty liver disease who are at high risk of developing DM. Additionally, patients with fatty liver disease complicated with overweight/obesity or prediabetes are at an increased risk of DM onset and should receive more attention.     

Possible pro‐inflammatory role of heparin‐binding epidermal growth factor‐like growth factor in the active phase of systemic sclerosis

Heparin‐binding epidermal growth factor (EGF)‐like growth factor (HB‐EGF) is a member of the EGF family growth factors, which affects multiple aspects of the wound healing process such as epithelialization, wound contraction and angiogenesis. In our study, we measured the serum HB‐EGF levels of 51 systemic sclerosis (SSc) patients, which showed a significant increase compared with those of 20 normal subjects. Further analysis revealed a positive correlation between the HB‐EGF level and pulmonary ground‐glass score but no correlation between the former and pulmonary fibrosis score. Other findings include: a significant increase of serum sialylated carbohydrate antigen KL‐6 levels and significant shortness of disease duration in the diffuse cutaneous SSc patients with elevated HB‐EGF levels; and significantly higher HB‐EGF levels in the presence of Raynaud's phenomenon, in that of telangiectasia, and in the absence of contracture of phalanges in all SSc patients. We then evaluated HB‐EGF mRNA levels of fibroblasts harvested from skin samples of the SSc patients and those of foreskin‐derived fibroblasts treated with transforming growth factor‐β, both of which were significantly higher than each control. In conclusion, we speculate that HB‐EGF plays a pro‐inflammatory role in the active skin and lung lesions of SSc.     

High prevalence of metallo-beta-lactamase and 16S rRNA methylase coproduction among imipenem-resistant Pseudomonas aeruginosa isolates in Brazil

Rates of metallo-β-lactamase and 16S rRNA methylase production were investigated in 51 imipenem-resistant Pseudomonas aeruginosa clinical isolates collected from hospitals in São Paulo, Brazil. Of them, 57% and 75% produced SPM-1 and RmtD, respectively. Of note, 51% produced both enzymes, suggesting that their coproduction is already common in this geographic area.Treatment of infections due to Pseudomonas aeruginosa is becoming increasingly complicated by its tendency to acquire resistance to multiple classes of antimicrobials (12). The agents typically used to treat these infections include antipseudomonal penicillins, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides. The production of metallo-β-lactamases (MBLs) contributes substantially to panresistant phenotypes in P. aeruginosa because they confer resistance to all classes of β-lactam antimicrobials except aztreonam (10). Various MBLs including IMP, VIM, SPM, and GIM types have been reported for P. aeruginosa (12). Of note, SPM-type MBLs have been found only in Brazil thus far (13).Methylation of 16S rRNA has emerged as a mechanism of high-level aminoglycoside resistance among gram-negative pathogens in recent years (3). Five such methylases, ArmA and RmtA through RmtD, have been reported to date. The most recently identified methylase is RmtD, which we reported previously for a panresistant P. aeruginosa strain isolated near São Paulo, Brazil (4). This enzyme confers high-level resistance to most aminoglycosides in clinical use. In this particular strain, the coproduction of RmtD and SPM-1 played a substantial role in the panresistant phenotype. The present study was conducted to determine the prevalence of coproduction of these enzymes among P. aeruginosa clinical isolates in Brazil.Nonrepetitive imipenem-resistant P. aeruginosa isolates from a total of 49 patients hospitalized at seven hospitals in the São Paulo area in 2005 and 2006 were collected. One patient had two isolates with different pulsed-field gel electrophoresis (PFGE) patterns, and another patient had two isolates with identical PFGE patterns but markedly different susceptibility patterns. Thus, 51 imipenem-resistant P. aeruginosa isolates were included in the study. Sites of the specimens were as follows: 28 from urine, 8 from blood, 7 secretions from various sites, 3 from cerebrospinal fluid, 2 from catheter tip, 1 from bronchoalveolar lavage fluid, 1 from ascitic fluid, and 1 from nasal swab.The MICs of imipenem, meropenem, aztreonam, amikacin, gentamicin, arbekacin, ciprofloxacin, and colistin were obtained using either the standard agar dilution method or Etest (AB Biodisk, Solna, Sweden) (2). The MICs of imipenem were 32 μg/ml or higher for all the isolates, verifying the high degree of resistance to this agent in this collection. For meropenem, MICs were 8 μg/ml or higher. When the phenotypic test using sodium mercaptoacetic acid was performed to detect MBL production (1), 29 of 51 isolates (57%) yielded a positive result.PFGE was performed with SpeI (New England Biolabs, Beverly, MA) as the restriction enzyme for the genomic DNA. Electrophoresis was performed with the CHEF III DR system (Bio-Rad, Hercules, CA). The pulses were increased linearly from 5.3 to 34.9 s for 24 h at 14°C. Seventeen pulsotypes were observed among the 51 isolates by PFGE. Eight of the pulsotypes comprising 32 isolates from six hospitals were possibly related to each other (“pulsotype A,” consisting of subtypes A1 through A8), whereas the other nine pulsotypes were unrelated (pulsotypes B through J) according to criteria described previously by Tenover et al. (Table ​(Table11 and Fig. ​Fig.1)1) (14). Pulsotype A was thus the most prevalent genotype in hospitals in this area.Open in a separate windowFIG. 1.PFGE patterns of the study isolates. The pulsotypes were aligned using Bionumerics software version 4.0 (Applied Maths, Sint-Martens-Latem, Belgium).

TABLE 1.

Characteristics of study isolates