Tumor necrosis factor-α modifies the effects of Shiga toxin on glial cells

Shiga toxin (STX) is one of the main factors inducing hemorrhagic colitis and hemolytic-uremic syndrome (HUS) in infections with STX-producing Escherichia coli (STEC). Approximately 62% of patients with HUS showed symptoms of encephalopathy in the 2011 Japanese outbreak of STEC infections. At that time, we reported elevated serum concentrations of tumor necrosis factor (TNF)-α in patients with acute encephalopathy during the HUS phase. In the current study, we investigated whether TNF-α augments the effects of STX in glial cell lines and primary glial cells. We found that TNF-α alone or STX in combination with TNF-α activates nuclear factor-κB (NF-κB) signaling and inhibits growth of glial cells. The magnitude of the NF-κB activation and the inhibition of cell growth by the STX and TNF-α combination was greater than that obtained with TNF-α alone or STX alone. Thus, this in vitro study reveals the role of TNF-α in glial cells during STEC infections. © 2016 Elsevier B.V. All rights reserved.Embargo Period 12 month

Case report: A family of atypical hemolytic uremic syndrome involving a CFH::CFHR1 fusion gene and CFHR3-1-4-2 gene duplication

Mutations in the complement factor H (CFH) gene are associated with complement dysregulation and the development of atypical hemolytic uremic syndrome (aHUS). Several fusion genes that result from genomic structural variation in the CFH and complement factor H-related (CFHR) gene regions have been identified in aHUS. However, one allele has both CFHR gene duplication and CFH::CFHR1 fusion gene have not been reported. An 8-month-old girl (proband) presented with aHUS and was treated with ravulizumab. Her paternal grandfather developed aHUS previously and her paternal great grandmother presented with anti-neutrophil cytoplasmic antibody-associated vasculitis and thrombotic microangiopathy (TMA). However, the proband’s parents have no history of TMA. A genetic analysis revealed the presence of CFH::CFHR1 fusion gene and a CFHR3-1-4-2 gene duplication in the patient, her father, and her paternal grandfather. Although several fusion genes resulting from structural variations of the CFH–CFHR genes region have been identified, this is the first report of the combination of a CFH::CFHR1 fusion gene with CFHR gene duplication. Because the CFH–CFHR region is highly homologous, we hypothesized that CFHR gene duplication occurred. These findings indicate a novel pathogenic genomic structural variation associated with the development of aHUS

Inflation Pressure in Side Branch during Modified Jailed Balloon Technique Does Not Affect Side Branch Outcomes

Objectives. This study aimed to investigate the optimal jailed balloon inflation in the side branch during the modified jailed balloon technique for bifurcated lesions. Background. The modified jailed balloon technique is one of the effective techniques to minimize the emergence of side branch (SB) compromise by preventing plaque or carina shifting during a single stent strategy in the main vessel with provisional SB treatment. However, there are no detailed studies on the method of optimal jailed balloon inflation. Methods. We analyzed 51 consecutive patients who underwent percutaneous coronary intervention (PCI) for bifurcated lesions with a modified jailed balloon technique between September 2018 and December 2020. These 51 patients were divided into two groups according to the magnitude of inflation pressure of the jailed balloon: a higher pressure (HP) group and lower pressure (LP) group. Results. No significant differences in procedural outcomes were observed between the two groups. The findings of SB compromise were relatively common with our procedure (30.0% in the HP group; 33.3% in the LP group). The patterns of SB compromise such as dissection or stenosis increase were observed at similar frequencies between them. In particular, SB dissection was noted in the SB lesion with some plaque burden, irrespective of the magnitude of the jailed balloon inflation pressure. Univariate analysis showed that calcification in the main vessel and SB lesion length was significantly associated with SB compromise. Finally, all PCI procedures were successfully completed without any provisional stent deployment in SB. Conclusions. We speculate that lesion characteristics rather than the PCI procedural factors may be critical determinants to cause SB compromise

Percutaneous Closure Based on Physiological Assessment of an Arteriovenous Fistula in a Patient With Chronic Limb Threatening Ischaemia

Introduction: An arteriovenous fistula (AVF) is a potential complication of endovascular therapy (EVT). Arteriovenous fistula steal syndrome sometimes leads to severe limb ischaemia; however, assessment of peripheral perfusion in AVF has not yet been established. Report: A 90 year old woman diagnosed with chronic limb threatening ischaemia underwent EVT. However, subintimal angioplasty of infrapopliteal lesions resulted in AVF formation in the posterior tibial artery (PTA). Revascularisation of the anterior tibial artery and PTA was performed, but severe AVF steal syndrome persisted and wound healing was delayed. An attempt to physiologically assess the effects of AVF closure and perform an AVF closing manoeuvre, if necessary, was performed. The physiological assessment was performed by laser Doppler flowmetry (LDF) and blood flow was temporarily blocked via the AVF at the distal PTA using a 6 F guiding extension catheter. A significant increase in blood flow was observed in the perfused area of the plantar artery. Coil embolisation and covered stent implantation in the PTA completely closed the AVF. During the procedure, peripheral perfusion with LDF gradually increased in the heel and fifth toe. After AVF closure, the skin perfusion pressure values increased significantly, wound healing was accelerated, and complete healing was achieved. Discussion: Laser Doppler flowmetry measurements under simulated AVF closure using a guiding extension catheter may be useful for the physiological assessment of peripheral perfusion before percutaneous AVF closure