Comparison between Zone 2 and Zone 3 distal anastomoses for aortic arch replacement in terms of invasiveness.

OBJECTIVES: Zone 2 anastomosis with total cervical branch reconstruction for acute type A aortic dissection and aortic arch aneurysms became possible after stent-graft introduction. This may be an easier procedure and reduce the risk of recurrent laryngeal nerve palsy. Therefore, this study aimed to compare the outcomes between Zone 2 and Zone 3 distal anastomoses. METHODS: After evaluating the patient data in our institute between April 2016 and April 2022, the patients in whom distal anastomosis was performed at Zone 2 with a stent-graft were defined as the Zone 2 group (n = 70). The patients in whom distal anastomosis was performed at Zone 3 were defined as the Zone 3 group (n = 24). RESULTS: The incidence of new-onset recurrent nerve palsy was one patient (1.4%) in the Zone 2 group and six patients (25.0%) in the Zone 3 group (p < 0.001). The lower body perfusion arrest time was 44.3 ± 9.1 min in the Zone 2 group and 52.9 ± 12.8 min in the Zone 3 group (p = 0.005). There were no significant differences in in-hospital mortality and morbidities. Multivariable analysis showed that only age was an independent predictor of overall mortality. CONCLUSIONS: Performing distal anastomosis at Zone 2 with a frozen elephant trunk or stent-graft reduced the lower body perfusion arrest time and possibly prevented recurrent nerve palsy.

Preparation of ß-1,3-glucan mimics via modification of polymer backbone, and evaluation of cytokine production using the polymer library in immune activation.

ß-1,3-Glucans possess therapeutic potential owing to their ability to exhibit immunostimulating activity. ß-1,3-Glucans, isolated from various organisms, differ in their chemical structures, molecular weight, and branching degree, potentially forming particulate, helix, or random coil conformations in water. Therefore, this study used synthesized ß-1,3-glucan mimic polymers to investigate the difference in binding affinity for dectin-1 and induced cytokine productions based on polymer structures. The ß-1,3-glucan mimic polymers were synthesized using ß-1,3-glucan tetrasaccharyl monomer, with subsequent modifications to the polymer backbones through the introduction of hydrogen or a hydroxy group. Polymers with different structures in both ligands and polymer backbones were utilized to comprehensively investigate their binding affinity to dectin-1 and cytokine-inducing in macrophages. Hydroxylated polymers exhibited a high binding affinity for dectin-1, similar to that of schizophyllan, whereas the polymer composed of only saccharyl monomers did not bind to dectin-1. Further, when administered to macrophage RAW264 cells, polymers with branched and hydrophobic polymer backbones exhibited strong cytokine-inducing activities. Moreover, the results revealed that the essential factors for cytokine induction include the branches of ß-1,3-glucans, high (tens of thousands) molecular weights, and hydrophobicity. The results suggests that artificial polymers comprising these factors exhibit immunostimulating activity and could be developed as therapeutic agents.

Molecular basis for bacterial N-glycosylation by a soluble HMW1C-like N-glycosyltransferase.

Soluble HMW1C-like N-glycosyltransferases (NGTs) catalyze the glycosylation of Asn residues in proteins, a process fundamental for bacterial autoaggregation, adhesion and pathogenicity. However, our understanding of their molecular mechanisms is hindered by the lack of structures of enzymatic complexes. Here, we report structures of binary and ternary NGT complexes of Aggregatibacter aphrophilus NGT (AaNGT), revealing an essential dyad of basic/acidic residues located in the N-terminal all α-domain (AAD) that intimately recognizes the Thr residue within the conserved motif Asn0-X+1-Ser/Thr+2. Poor substrates and inhibitors such as UDP-galactose and UDP-glucose mimetics adopt non-productive conformations, decreasing or impeding catalysis. QM/MM simulations rationalize these results, showing that AaNGT follows a SN2 reaction mechanism in which the acceptor asparagine uses its imidic form for catalysis and the UDP-glucose phosphate group acts as a general base. These findings provide key insights into the mechanism of NGTs and will facilitate the design of structure-based inhibitors to treat diseases caused by non-typeable H. influenzae or other Gram-negative bacteria.

Peripheral VA-ECMO and pericardial drainage connected to the ECMO circuit for cardiac tamponade from blowout rupture: a case report.

BACKGROUND: Left ventricular free wall rupture, particularly the blowout type, is still one of the most lethal complications of myocardial infarction and can cause catastrophic cardiac tamponade. Extracorporeal membrane oxygenation (ECMO) is often used to treat haemodynamic instability due to cardiac tamponade. However, elevated pericardial pressure can cause collapse of the right atrium, resulting in inadequate ECMO inflow and preventing the stabilisation of the circulation. Further, it can interfere with the venous return from the superior vena cava (SVC), increasing the intracranial pressure and reducing cerebral perfusion levels. CASE PRESENTATION: A 65-year-old man was hospitalised for out-of-hospital cardiac arrest. We used ECMO for cardiopulmonary resuscitation. After the establishment of ECMO, transthoracic echocardiography and left ventriculography revealed massive pericardial effusion. The treatment was supplemented with pericardial drainage since ECMO flow was frequently hampered by suction events. However, the blowout rupture led to the requirement of constant drainage from the pericardial catheter. To tend to this leak, we connected the venous cannula of ECMO and the pericardial drainage catheter. The surgery was performed with stable circulation without suction failure of ECMO. During the course of the intensive care management, the neurological prognosis of the patient was revealed to be poor, and the patient was shifted to palliative care. Unfortunately, the patient died on day 10 of hospitalisation. CONCLUSION: We present a case wherein the combination of pericardial drainage and ECMO was used to maintain circulation in a patient with massive pericardial effusion due to cardiac rupture.

Identification of a tomato UDP-arabinosyltransferase for airborne volatile reception.

Volatiles from herbivore-infested plants function as a chemical warning of future herbivory for neighboring plants. (Z)-3-Hexenol emitted from tomato plants infested by common cutworms is taken up by uninfested plants and converted to (Z)-3-hexenyl ß-vicianoside (HexVic). Here we show that a wild tomato species (Solanum pennellii) shows limited HexVic accumulation compared to a domesticated tomato species (Solanum lycopersicum) after (Z)-3-hexenol exposure. Common cutworms grow better on an introgression line containing an S. pennellii chromosome 11 segment that impairs HexVic accumulation, suggesting that (Z)-3-hexenol diglycosylation is involved in the defense of tomato against herbivory. We finally reveal that HexVic accumulation is genetically associated with a uridine diphosphate-glycosyltransferase (UGT) gene cluster that harbors UGT91R1 on chromosome 11. Biochemical and transgenic analyses of UGT91R1 show that it preferentially catalyzes (Z)-3-hexenyl ß-D-glucopyranoside arabinosylation to produce HexVic in planta.

Protecting-group-free glycosylation of phosphatidic acid in aqueous media.

The glycosylation of unprotected carbohydrates has emerged as an area of significant interest because it obviates the need for long reaction sequences involving protecting-group manipulations. Herein, we report the one-pot synthesis of anomeric glycosyl phosphates through the condensation of unprotected carbohydrates with phospholipid derivatives while retaining high stereo- and regioselective control. The anomeric center was activated using 2-chloro-1,3-dimethylimidazolinium chloride to facilitate condensation with glycerol-3-phosphate derivatives in an aqueous solution. A water/propionitrile mixture provided superior stereoselectivity while maintaining good yields. Under these optimized conditions, the condensation of stable isotope-labeled glucose with phosphatidic acid provided efficient access to labeled glycophospholipids as an internal standard for mass spectrometry.

UDP-glucose, cereblon-dependent proinsulin degrader.

Insulin secretion is regulated in multiple steps, and one of the main steps is in the endoplasmic reticulum (ER). Here, we show that UDP-glucose induces proinsulin ubiquitination by cereblon, and uridine binds and competes for proinsulin degradation and behaves as sustainable insulin secretagogue. Using insulin mutagenesis of neonatal diabetes variant-C43G and maturity-onset diabetes of the young 10 (MODY10) variant-R46Q, UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1) protects cereblon-dependent proinsulin ubiquitination in the ER. Cereblon is a ligand-inducible E3 ubiquitin ligase, and we found that UDP-glucose is the first identified endogenous proinsulin protein degrader. Uridine-containing compounds, such as uridine, UMP, UTP, and UDP-galactose, inhibit cereblon-dependent proinsulin degradation and stimulate insulin secretion from 3 to 24 h after administration in ß-cell lines as well as mice. This late and long-term insulin secretion stimulation is designated a day sustainable insulin secretion stimulation. Uridine-containing compounds are designated as proinsulin degradation regulators.

UDP-Glucose: A Cereblon-Dependent Glucokinase Protein Degrader.

We previously reported that glucokinase is ubiquitinated and degraded by cereblon with an unknown endogenous glucokinase protein degrader. Here, we show that UDP-glucose is a glucokinase protein degrader. We identified that both glucose and UDP-glucose bind to glucokinase and that both uridine and UDP-glucose bind to cereblon in a similar way to thalidomide. From these results, UDP-glucose was identified as a molecular glue between cereblon and glucokinase. Glucokinase produces glucose-6-phosphate in the pancreas and liver. Especially in ß-cells, glucokinase is the main target of glucose for glucose-induced insulin secretion. UDP-glucose administration ubiquitinated and degraded glucokinase, lowered glucose-6-phosphate production, and then reduced insulin secretion in ß-cell lines and mice. Maturity-onset diabetes of the young type 2 (MODY2) glucokinaseE256K mutant protein was resistant to UDP-glucose induced ubiquitination and degradation. Taken together, glucokinase ubiquitination and degradation signaling might be impaired in MODY2 patients.

Strategic 2-step surgery using thoracic endovascular aortic repair for an infected thoracic aortic aneurysm.

An 81-year-old man with multiple comorbidities developed infected thoracic aortic aneurysm, and we employed a strategic 2-step surgical approach combining thoracic endovascular aortic repair and local debridement with an omental flap during the active phase of infection. No signs of reinfection were observed at the 1-year follow-up. This strategy can be a safe and less invasive alternative to conventional open surgery in patients with high surgical risk.

Antimicrobial activities of amphiphilic cationic polymers and their efficacy of combination with novobiocin.

Today, drug-resistant bacteria represent a significant problem worldwide. In fact, bacteria are becoming resistant even to newly developed antibiotics. Therefore, there is an urgent need to develop antibiotics to which bacteria cannot become resistant. In this study, antimicrobial polymers to which bacteria cannot develop resistance were prepared from 6-aminohexyl methacrylamide and N-isopropyl acrylamide. The polymers with molecular weights of the order of 105 showed little antimicrobial activity against Staphylococcus aureus and Escherichia coli as well as low toxicity. On the other hand, polymers with lower molecular weights (of the order of 104) did show antimicrobial activity against S. aureus and E. coli. These polymers were combined with novobiocin to investigate the combined usage effects against E. coli. The combined usage of novobiocin and the low-molecular-weight polymers reduced the minimum inhibitory concentration, which was less than 0.0625 µg/mL against E. coli. This result indicates that the combination is useful for increasing the efficacy of antibiotics and broadening their antimicrobial spectrum. Furthermore, the results showed the possibility that the antimicrobial polymers serve not only as antibiotics to which bacteria have not developed resistance but also as adjuvants for other antibiotics.

A three-dimensional biomodel of type A aortic dissection for endovascular interventions.

Thoracic endovascular aortic repair is widely used for type B aortic dissection. However, there is no favorable stent-graft for type A aortic dissection. A significant limitation for device development is the lack of an experimental model for type A aortic dissection. We developed a novel three-dimensional biomodel of type A aortic dissection for endovascular interventions. Based on Digital Imaging and Communication in Medicine data from the computed tomography image of a patient with a type A aortic dissection, a three-dimensional biomodel with a true lumen, a false lumen, and an entry tear located at the ascending aorta was created using laser stereolithography and subsequent vacuum casting. The biomodel was connected to a pulsatile mock circuit. We conducted four tests: an endurance test for clinical hemodynamics, wire insertion into the biomodel, rapid pacing, and simulation of stent-graft placement. The biomodel successfully simulated clinical hemodynamics; the target blood pressure and cardiac output were achieved. The guidewire crossed both true and false lumens via the entry tear. The pressure and flow dropped upon rapid pacing and recovered after it was stopped. This simulation biomodel detected decreased false luminal flow by stent-graft placement and detected residual leak. The three-dimensional biomodel of type A aortic dissection with a pulsatile mock circuit achieved target clinical hemodynamics, demonstrated feasibility for future use during the simulated endovascular procedure, and evaluated changes in the hemodynamics.

Bail-Out Pull-Through Pull-Back Technique for Accidental Coverage of the Left Common Carotid Artery During Thoracic Endovascular Aortic Repair.

PURPOSE: We describe a pull-through pull-back technique to revascularize the left common carotid artery (LCCA) that was unintentionally covered during thoracic endovascular aortic repair (TEVAR). CASE REPORT: A 69-year-old man presented with back pain secondary to acute type B aortic dissection with an intimal tear in the proximal descending aorta. Serial computed tomography (CT) revealed an enlarged descending aorta and proximal progression of the aortic dissection. He underwent left carotid-subclavian artery bypass and TEVAR, 10 days after admission. The Valiant Navion stent graft without a bare stent was deployed proximally; however, the LCCA was unintentionally covered by the stent graft during this procedure. A pull-through form was created between the left axillary and femoral arteries using a 0.035-inch guide wire. The pull-through guide wire was gently pulled, and the greater curvature of the proximal end of the stent graft was displaced distally. Angiography confirmed restoration of antegrade blood flow into the LCCA. The patient's postoperative course was uneventful. Follow-up CT performed 6 months postoperatively confirmed preserved blood flow into the LCCA without endoleak nor stent migration. CONCLUSION: The pull-through pull-back technique is a feasible troubleshooting strategy for accidental coverage of supra-aortic vessels during TEVAR.

Cardiopulmonary Bypass Surgery in a Patient with Unexpected Heparin-Induced Thrombocytopenia.

We report a case of a 77-year-old woman with massive pulmonary embolism associated with heparin-induced thrombocytopenia. Before developing a pulmonary embolism, the patient underwent gastrectomy due to gastric cancer and received subcutaneous heparin calcium for deep venous thrombosis prophylaxis for 5 d. Then, thrombectomy with cardiopulmonary bypass using full heparinization was successfully performed. The patient was definitively diagnosed with this condition postoperatively, based on elevated serum antibody levels, in addition to pre- and postoperative thrombocytopenia and thrombosis. Intravenous heparin therapy was switched to argatroban. Although it is uncommon, clinicians should consider this condition in patients with a history of heparin exposure.

Antibacterial Activity of Membrane-Permeabilizing Bactericidal Cyclodextrin Derivatives.

Antimicrobial peptides that act by disrupting bacterial membranes are attractive agents for treating drug-resistant bacteria. This study investigates a membrane-disrupting peptide mimic made of a cyclic oligosaccharide cyclodextrin scaffold that can be chemically polyfunctionalized. An antibacterial functional group on the peptide was simplified to an alkylamino group that combines cationic and hydrophobic moieties, the former to interact with the anionic bacterial membrane and the latter with the membrane interior. The cyclodextrins equipped with eight alkylamino groups on the molecules using a poly-click reaction exhibited antibacterial activity against Gram-positive and Gram-negative bacteria, including drug-resistant pathogens such as carbapenem-resistant Enterobacteriaceae. Several lines of evidence showed that these agents disrupt bacterial membranes, leading to rapid bacterial cell death. The resulting membrane perturbation was directly visualized using high-speed atomic force microscopy imaging. In Gram-negative bacteria, the membrane-permeabilizing action of these derivatives allowed the entry of co-treated traditional antibiotics, which were then active against these bacteria.

Sandwich repair for postinfarction ventricular septal rupture and left ventricular rupture.

A 77-year-old woman who presented with chest pain was diagnosed with acute anterior myocardial infarction. Echocardiography revealed pericardial effusion, and she underwent sutureless repair for postinfarction left ventricular free wall rupture. Echocardiography performed 2 days postoperatively revealed ventricular septal rupture and left ventricular acute dilatation. Hemodynamic instability with ventricular tachycardia and rapid decline of kidney function developed. Four days after the primary surgery, we performed successful sandwich repair for ventricular septal rupture and the dilatation. Her postoperative course was uneventful, and postoperative evaluation did not show a residual shunt or left ventricular dilatation.

Total arch and descending aorta replacement via left thoracotomy for infected post-thoracic endovascular aortic repair type B aortic dissection.

A 38-year-old man underwent thoracic endovascular aortic repair for impending rupture of acute type B aortic dissection. Computed tomography revealed abscess formation around the proximal descending aorta 4 weeks after endovascular treatment. He underwent one-stage total arch and descending aorta replacement and omental wrapping via left thoracotomy. At the 6-month follow-up, his postoperative course was uneventful.

Double-patch and glue repair of a postinfarction left ventricular pseudoaneurysm.

An 85-year-old man with appetite loss, lightheadedness, and leg edema was referred to our institution. Computed tomography and transthoracic echocardiography revealed a left ventricular pseudoaneurysm with a maximal diameter of 80 mm and severe mitral regurgitation. Coronary angiography showed 90% stenosis and total occlusion of the left circumflex artery at segments 11 and 12, respectively. He was diagnosed with postinfarction left ventricular pseudoaneurysm and underwent patch repair using two bovine pericardium patches and biological glue, mitral valve replacement, and coronary artery bypass grafting. His postoperative course was uneventful.

Clinical outcomes of a fenestrated frozen elephant trunk technique for acute type A aortic dissection.

OBJECTIVES: We investigated the outcomes of a fenestrated frozen elephant trunk (FET) technique performed without reconstruction of one or more supra-aortic vessels for aortic repair in patients with acute type A aortic dissection. METHODS: We investigated 22 patients who underwent the fenestrated FET technique for acute type A aortic dissection at our hospital between December 2017 and April 2020. The most common symptom was chest pain and/or back pain. Nine patients presented with malperfusion and 1 with cardiac arrest, preoperatively. A FET was deployed under hypothermic circulatory arrest and manually fenestrated under direct vision. Single fenestration was made in the FET in 15 patients, 2 fenestrations in 5 patients and a total fenestrated technique in 2 patients. Concomitant procedures were performed in 5 patients. RESULTS: The cardiopulmonary bypass, aortic cross-clamp and hypothermic circulatory arrest times were 181 ± 49, 106 ± 43 and 37 ± 7 min, respectively. In-hospital mortality, stroke, or recurrent nerve injury did not occur in any patient. One patient developed paraparesis, which completely recovered at discharge. During the follow-up period (mean 18 ± 7 months), 1 patient died of heart failure. Fenestration site occlusion did not occur. Follow-up computed tomography (mean 12 ± 6 months postoperatively) revealed that the maximal aortic diameter remained unchanged at the levels of the distal end of the FET, the 10th thoracic vertebra and the coeliac artery; however, the aortic diameter was significantly reduced at the level of the pulmonary artery bifurcation. CONCLUSIONS: The fenestrated FET technique is a simple, safe and effective procedure for selected patients with acute type A aortic dissection.