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Cureus Aug 2023Lemierre's syndrome is a rare, life-threatening complication of an acute oropharyngeal infection. It is generally characterised by pharyngitis secondary to , causing... (Review)
Review
Lemierre's syndrome is a rare, life-threatening complication of an acute oropharyngeal infection. It is generally characterised by pharyngitis secondary to , causing thrombophlebitis of the internal jugular vein and sepsis, with subsequent formation of septic emboli that can rapidly spread to different organ sites. The condition is associated with high mortality if treatment with antibiotics is delayed, and recent evidence suggests that patients are at significant risk of in-hospital morbidity and long-term neurological sequelae. Although it is agreed that antibiotics are the mainstay of treatment, there is currently no consensus on the use of anticoagulation in the condition. This review article aims to summarise our current understanding of Lemierre's syndrome with regard to its definition, epidemiology, microbiology, presentation, diagnosis, and treatment.
PubMed: 37724228
DOI: 10.7759/cureus.43685 -
Blood Advances Sep 2023Factor XII (FXII) knockdown attenuates catheter thrombosis in rabbits. Because histidine-rich glycoprotein (HRG) modulates FXIIa activity, we hypothesized that HRG...
Factor XII (FXII) knockdown attenuates catheter thrombosis in rabbits. Because histidine-rich glycoprotein (HRG) modulates FXIIa activity, we hypothesized that HRG depletion would promote catheter thrombosis. To test this, rabbits were given either antisense oligonucleotides (ASOs) against HRG or FXII, a control ASO, or saline. The activated partial thromboplastin time (aPTT), prothrombin time (PT), and catheter-induced thrombin generation were determined in blood collected before and after treatment. Compared with the controls, the HRG- and FXII-directed ASOs reduced hepatic messenger RNA and plasma levels of HRG and FXII, respectively, by >90%. Although HRG knockdown shortened the aPTT by 2.5 fold, FXII knockdown prolonged it by fourfold; neither of the ASOs affected the PT. Catheter segments shortened the lag time and increased peak thrombin in the plasma from control rabbits; effects were significantly enhanced and attenuated in the plasma from rabbits given the HRG- and FXII-directed ASOs, respectively. Catheters were then inserted into the right external jugular vein of the rabbits, and the time for catheter occlusion was determined. The catheter occlusion times with the control ASO or saline were 62 ± 8 minutes and 60 ± 11 minutes, respectively. The occlusion time was significantly reduced to 34 ± 9 minutes, with HRG knockdown and significantly prolonged to 128 ± 19 minutes with FXII knockdown. HRG levels are decreased with sepsis or cancer, and such patients are prone to catheter thrombosis. Because HRG modulates catheter thrombosis, our findings suggest that HRG supplementation may prevent this problem.
Topics: Animals; Rabbits; Blood Coagulation; Catheters; Factor XII; Thrombin; Thrombosis
PubMed: 37042966
DOI: 10.1182/bloodadvances.2022009236 -
Translational Pediatrics Aug 2023Congenital heart disease (CHD) affects around 1.35 million neonates worldwide per annum, and surgical repair is necessary in approximately 25% of cases. Xenografts,... (Review)
Review
Congenital heart disease (CHD) affects around 1.35 million neonates worldwide per annum, and surgical repair is necessary in approximately 25% of cases. Xenografts, usually of bovine or porcine origin, are often used for the surgical reconstruction. These xenografts elicit an immune response due to significant immunological incompatibilities between host and donor. Current techniques to dampen the initial hyperacute rejection response involve aldehyde fixation to crosslink xenoantigens, such as galactose-α1,3-galactose and N-glycolylneuraminic acid. While this temporarily masks the epitopes, aldehyde fixation is a suboptimal solution, degrading over time, resulting in cytotoxicity and rejection. The immune response to foreign tissue eventually leads to chronic inflammation and subsequent graft failure, necessitating reintervention to replace the defective bioprosthetic. Decellularisation to remove immunoincompatible material has been suggested as an alternative to fixation and may prove a superior solution. However, incomplete decellularisation poses a significant challenge, causing a substantial immune rejection response and subsequent graft rejection. This review discusses commercially available grafts used in surgical paediatric CHD intervention, looking specifically at bovine jugular vein conduits as a substitute to cryopreserved homografts, as well as decellularised alternatives to the aldehyde-fixed graft. Mechanisms of biological prosthesis rejection are explored, including the signalling cascades of the innate and adaptive immune response. Lastly, emerging strategies of intervention are examined, including the use of tissue from genetically modified pigs, enhanced crosslinking and decellularisation techniques, and augmentation of grafts through recellularisation or functionalisation with human surface proteins.
PubMed: 37692547
DOI: 10.21037/tp-23-80