TXB-001, a newly-developed polymer-conjugated anthracycline: Significantly lower adverse effects in animal models of alopecia and hand-foot syndrome.

Anthracycline anti-cancer drugs have been widely used in the treatment of several cancers; however, their use is limited by adverse effects (AEs). Alopecia is a common AE that is minimally invasive, but adversely affects mental health and reduces quality of life (QoL). Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL, a liposomal formulation of doxorubicin (DOX). Although it is not a life-threatening condition, HFS affects function and reduces QoL. TXB-001 is a new candidate polymer-conjugated anthracycline anti-cancer drug, and modified and optimized polymerized pirarubicin (THP), known as P-THP, is expected to have low toxicity and high efficacy. The anti-cancer effects of TXB-001 were examined using the 4T1 mouse model. An alopecia mouse model and HFS rat model were used to evaluate the alopecia- and HFS-inducing effects of TXB-001 and compare their severity with existing anthracycline anti-cancer drugs. A pharmacokinetic analysis of plasma as well as chest, palmar, and plantar skin samples after the single intravenous administration of DOXIL and TXB-001 to rats was also performed. The results obtained revealed that TXB-001 exerted similar anti-cancer effects to those of DOXIL in mice, weaker alopecia-inducing effects than DOX, DOXIL, and THP in mice, and no or markedly weaker HFS-like changes than DOXIL, which induced significant histopathological changes. The results of the pharmacokinetic analysis showed the accumulation of DOXIL, but not TXB-001, in skin, particularly palmar and plantar skin samples, and these differences were considered to contribute to their HFS-inducing effects.

Ultrasound and computed tomography findings of hepatic portal venous gas associated with acute appendicitis in a paediatric patient: A case report.

Introduction: Hepatic portal venous gas is a rare and life-threatening condition characterised by the presence of gas in the portal vein. Hepatic portal venous gas is frequently associated with intestinal ischaemia and necrosis. We present the case of a paediatric patient with acute appendicitis with hepatic portal venous gas detected using ultrasonography. Case report: A 5-year-old boy was admitted to our hospital with a respiratory tract infection. The boy started vomiting on day 2 of hospitalisation. He did not complain of any symptoms due to developmental retardation. We performed bedside point-of-care ultrasound, which detected hepatic portal venous gas, although the appendix could not be detected due to an acoustic shadow associated with bowel gas. Contrast-enhanced computed tomography revealed perforated appendicitis and pneumatosis intestinalis associated with paralytic ileus. An emergency laparoscopic appendectomy was performed. He was discharged on day 25 of hospitalisation after antibiotic therapy. Discussion: The present case suggests that the mechanism of hepatic portal venous gas was paralytic ileus, which caused gas-forming bacterial proliferation. The gas produced by bacteria and/or the gas-forming bacteria entered the bowel wall, which caused pneumatosis intestinalis. The bubbles in the intestinal wall floated in the portal system and were detected as hepatic portal venous gas. Perforated appendicitis and paralytic ileus seemed to be caused by a delayed diagnosis of appendicitis. The point-of-care ultrasound examination was useful for detecting hepatic portal venous gas and for helping establish the diagnosis of appendicitis. Conclusion: Hepatic portal venous gas is a rare finding associated with appendicitis in children. In addition, point-of-care ultrasound is useful for detecting hepatic portal venous gas in paediatric patients.

Reversible suspension culture of human vascular smooth muscle cells using the functional biopolymer FP003.

Human vascular smooth muscle cells (SMCs) are adherent cells, and they cannot survive without scaffolds in suspension culture. Here, we aimed to establish a suspension culture of SMCs using the functional biopolymer FP003 and to investigate the proliferation status of the cells. When SMCs were suspension cultured with FP003, their proliferation was inhibited with a viability of 75% until day 15. When SMCs were re-plated on plastic plates after suspension culture with FP003 for 48 h, the SMCs proliferated as in a normal plate culture. The SMCs cultured in suspension with FP003 showed a relatively low phosphorylation of retinoblastoma protein, low expression of cyclin D1, high proportion of G0/G1 phase cells, low proportion of S phase cells, and no obvious signs of apoptosis, indicating that this culture system inhibited progression from the G1 to S phase. This growth arrest was a reversible property that showed no significant changes in the expressions of the marker proteins α-smooth muscle actin and smooth muscle myosin heavy chain. These results suggest that human SMCs can be stably cultured in suspension with FP003 without losing their characteristics when they are cultured on plastic plates again.

A novel method for predicting the unbound valproic acid concentration.

In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07-0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA [µM] - 2 × SA [µM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPA values, the constructed formula showed a weak trend with CtVPA or SA. The formula based on (CtVPA [µM] - 2 × SA [µM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.

Left Distal Transradial Approach for the Treatment of a Sacral Extradural Arteriovenous Fistula: A Technical Note and Literature Review.

BACKGROUND: Sacral extradural arteriovenous fistula (SEAVF) is relatively rare, and its etiology is unknown. They are mostly fed by the lateral sacral artery (LSA). For endovascular treatment, both the stability of the guiding catheter and accessibility of the microcatheter to the fistula, distal to the LSA are required for sufficient embolization of the fistulous point. Cannulation of these vessels requires either crossover at the aortic bifurcation or retrograde cannulation using the transfemoral approach. However, atherosclerotic femoral and tortuous aortoiliac vessels can make the procedure technically difficult. Although the right transradial approach (TRA) can reduce this difficulty by straightening the access route, a potential risk remains for cerebral embolism because it passes the aortic arch. Herein, we present a case of successful embolization of a SEAVF using a left distal TRA. METHODS: We report a case of a 47-year-old man with SEAVF treated with embolization using a left distal TRA. Lumbar spinal angiography showed a SEAVF with an intradural vein through the epidural venous plexus fed by the left LSA. A 6-French guiding sheath was cannulated into the internal iliac artery via the descending aorta using the left distal TRA. A microcatheter could be advanced into the extradural venous plexus over the fistula point from the intermediate catheter placed at the LSA. Embolization with coils and n-butyl cyanoacrylate was successfully performed. RESULTS: The SEAVF completely disappeared on neuroimaging, and the patient gradually recovered. CONCLUSIONS: Left distal TRA could be a useful, safe, and less invasive option for the embolization of SEAVF, especially for patients with high-risk factors for aortogenic embolism or puncture site complications.

A search for acrolein scavengers among food components.

Brain stroke is a major cause of being bedridden for elderly people, and preventing stroke is important for maintaining quality of life (QOL). Acrolein is a highly reactive aldehyde and causes tissue damage during stroke. Decreasing acrolein toxicity ameliorates tissue injury during brain stroke. In this study, we tried to identify food components which decrease acrolein toxicity. We found that 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine decreased acrolein toxicity. These compounds neutralized acrolein by direct interaction. However, the interaction between acrolein and taurine was not so strong. Approximately 30 mM taurine was necessary to interact with 10 µM acrolein, and 2 g/kg taurine was necessary to decrease the size of mouse brain infarction. Taurine also slightly increased polyamine contents, which are involved in decrease in the acrolein toxicity. Mitochondrial potential damage by acrolein was also protected by taurine. Our results indicate that daily intake of foods containing 2-furanmethanethiol, cysteine methyl and ethyl esters, alliin, lysine and taurine may prevent severe injury in brain stroke and improve the quality of life for elderly people.

Relationship between elevated bilirubin levels and enhanced warfarin effects during biliary obstruction.

OBJECTIVES: A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin. METHODS: Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction. RESULTS: Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ = -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR. CONCLUSIONS: PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

In vitro analysis of factors affecting the continuous hemodiafiltration clearance of teicoplanin.

BACKGROUND: In the treatment of sepsis, continuous hemodiafiltration (CHDF) and the administration of antibiotics such as teicoplanin (TEIC) are frequently performed in parallel. We aimed to clarify the factors influencing the CHDF clearance (CLCHDF ) of TEIC using a polymethylmethacrylate (PMMA) membrane or a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST). We also investigated whether the adsorption of TEIC onto the hemofilters inhibits the adsorption of interleukin (IL)-6 onto the membranes. METHODS: TEIC, human serum albumin (HSA), and IL-6 were incubated with pieces of hemofilter membranes and adsorption rates were calculated. The CLCHDF , diafiltration rate, and adsorption rate of TEIC were calculated using an in vitro CHDF circuit model. RESULTS: The adsorption rates of TEIC onto the pieces of PMMA and AN69ST membranes ranged from 15.0% to 100% and from -10% to 5%, respectively. The adsorption rate of IL-6 was similar with or without TEIC. The CLCHDF and adsorption rate of TEIC under PMMA-CHDF depended on HSA, but not on effluent flow rate (Qe). The CLCHDF under AN69ST-CHDF depended on HSA and Qe. The observed CLCHDF under AN69ST-CHDF was similar to the predicted value (the product of Qe and the plasma unbound fraction). The observed CLCHDF under PMMA-CHDF was 2.0-7.8 times greater than the predicted value. CONCLUSIONS: Adsorption mainly contributes to the CLCHDF of TEIC using PMMA membranes, whereas diafiltration mainly contributes to the CLCHDF of TEIC using AN69ST membranes. TEIC adsorption might not affect the adsorption of IL-6 onto PMMA membrane.

Oral antibiotics and a low-residue diet reduce the incidence of anastomotic leakage after left-sided colorectal surgery: a retrospective cohort study.

PURPOSE: Anastomotic leakage is a potential complication after colorectal surgery. We investigated the effects of oral antibiotics and a low-residue diet on the incidence of anastomotic leakage after left-sided colorectal surgery. METHODS: Outcomes were retrospectively compared between 64 patients who underwent mechanical bowel preparation alone (group A) and 183 patients who underwent mechanical bowel preparation with addition of oral kanamycin and metronidazole (group B) on the day before left-sided colorectal surgery. After surgery, patients in group A received a normal diet containing dietary fiber and those in group B received a low-residue diet. The primary outcome was the incidence of anastomotic leakage. Secondary outcomes were rates of other postoperative complications, length of postoperative hospital stay, and laboratory data. RESULTS: Anastomotic leakage, surgical site infection, and diarrhea were less common in group B than in group A (4.9% vs 18.8%, 6.6% vs 23.4%, and 25.7% vs 43.8%, respectively). Postoperative C-reactive protein levels were significantly lower in group B. The median postoperative hospital stay was significantly shorter in group B than in group A (8 days vs 9 days, P = 0.010). Adaptive double least absolute shrinkage and selection operator regression revealed that use of preoperative oral antibiotics and a postoperative low-residue diet were associated with lower incidence of anastomotic leakage (odds ratio 0.163, 95% confidence interval 0.062-0.430; P < 0.001). CONCLUSION: Oral antibiotics and a low-residue diet reduced the incidence of anastomotic leakage and shortened the postoperative hospital stay by 1 day.

Decrease of voriconazole trough levels during therapy with enteral nutrition: a case report.

BACKGROUND: Voriconazole (VRCZ) is the first-line therapy for chronic pulmonary aspergillosis and is available in both intravenous and oral formulations. The bioavailability of the oral form is estimated to be over 90% in healthy volunteers. Some drugs are reported to interact with enteral nutrition (EN), but there are few reports about the trough levels of VRCZ during EN therapy. Here, we describe changes in the VRCZ trough levels in a patient receiving continuous EN therapy. CASE PRESENTATION: The patient was a 58-year-old man with esophageal cancer and a history of partial pulmonary resection due to aspergilloma. He was taking oral VRCZ tablets and his VRCZ trough level was about 2 µg/mL before esophageal cancer surgery. Following esophagectomy, VRCZ was restarted on postoperative day 16. Crushed VRCZ tablets were administered via a jejunostomy tube because of swallowing difficulty. He was also receiving EN, which was interrupted only during the administration of VRCZ. When we checked his VRCZ level 5 days after restarting VRCZ, the trough level was 0.80 µg/mL. After increasing the VRCZ dose, reducing EN, and changing the administration route from jejunostomy tube to oral, his trough level increased to 1.87 µg/mL. CONCLUSIONS: A decrease in the VRCZ trough level was observed when VRCZ was administered via a jejunostomy tube while the patient was receiving continuous EN. Careful monitoring of VRCZ levels is needed in such cases.

Initial Experience with Left Transradial Neurointerventions for Cerebral Aneurysms Using the 6-French Simmons Guiding Sheath.

OBJECTIVE: The use of a transradial approach utilizing a Simmons-shaped catheter for neurointervention has been steadily increasing. Although the right radial artery is commonly used, in interventional cardiology, the left transradial approach offers clear clinical benefits for right-handed patients. To the best of our knowledge, no previous studies have examined intracranial aneurysm embolization with the routine use of the left transradial approach. The aim of this study was to evaluate the technical feasibility of left transradial intracranial aneurysm embolization. METHODS: We conducted a retrospective review of a prospective database of consecutive patients who had undergone left transradial intracranial aneurysm coiling using a 6-French Simmons guiding sheath between January and August 2021. The following outcome variables were then analyzed: whether the catheterization was successful, the angiographical results, and the presence of any procedure-related complications. RESULTS: In total, 25 patients underwent left transradial coiling for 15 anterior and 10 posterior circulation aneurysms. The Simmons guiding sheath could be successfully shaped and cannulated into the targeted vessel in all patients. All aneurysms were completely embolized without any complications. Immediate postoperative angiograms showed Raymond 1 in 10 aneurysms (40.0%), Raymond 2 in 12 (48.0%), and Raymond 3a in 3 (12.0%). None of the patients required crossover to the right radial or femoral arteries, and no radial artery spasms or occlusions were observed. CONCLUSION: The results of this study suggest that the left transradial approach for intracranial aneurysm coiling is not only safe, effective, and technically feasible, but also provides improved comfort to right-handed patients.

Analysis of the variable factors affecting changes in the blood concentration of cyclosporine before and after transfusion of red blood cell concentrate.

BACKGROUND: The blood concentration of cyclosporine (CyA) is frequently elevated following the transfusion of red blood cell concentrate (RCC) to patients after allogeneic hematopoietic stem cell transplantation (HSCT). The aim of this retrospective study was to identify the variable factors affecting changes in the blood concentration of CyA before and after transfusion of RCC. METHODS: We enrolled 105 patients (age, 5-66 years) who received both CyA and transfusion after HSCT. The ratio of the measurement after transfusion to the measurement before transfusion was calculated for the hematocrit and blood concentration/dose ratio of CyA (termed the HCT ratio and the CyA ratio, respectively). RESULTS: The blood concentration/dose ratio of CyA was increased after transfusion compared with before transfusion (P < 0.001). The HCT ratio was significantly correlated with the CyA ratio (P = 0.23, P < 0.001). The HCT ratio, concomitant medication that could elevate CyA concentration after RCC transfusion, and difference in the alkaline phosphatase level between before and after transfusion (ΔALP) were explanatory variables associated with the variation in the CyA ratio. There was no correlation between the CyA concentration after transfusion and the change in the estimated glomerular filtration rate. CONCLUSIONS: A change in the blood concentration/dose ratio of CyA was found to be associated with a change in the HCT, concomitant medication that could elevate CyA concentration after RCC transfusion, and ALP levels. If the HCT level rises significantly after RCC transfusion, clinicians and pharmacists should pay attention to changes in the blood CyA concentration.

Contribution of diafiltration and adsorption to vancomycin clearance in a continuous hemodiafiltration circuit model in vitro.

BACKGROUND: Vancomycin (VCM) is eliminated mainly by diafiltration under continuous hemodiafiltration (CHDF), but the contribution of adsorption to CHDF clearance (CLCHDF ) of VCM using a polyacrylonitrile and sodium methallyl sulfonate copolymer membrane coated with polyethylenimine (AN69ST) or a polymethylmethacrylate (PMMA) membrane is unknown. This study sought to investigate the contribution of diafiltration and adsorption to the CLCHDF of VCM using AN69ST and PMMA membranes in vitro. METHODS: An in vitro CHDF circuit model was developed. The initial concentration of VCM was 50 µg/mL and human serum albumin (HSA) was prepared at a concentration of 0, 2.5, or 5.0 g/dL. The effluent flow rate (Qe) was set at 800, 1500, or 3000 mL/h. The CLCHDF , diafiltration rate, and adsorption rate of VCM were calculated. RESULTS: Total CLCHDF of VCM using the AN69ST membrane increased and decreased with increasing Qe and HSA concentration, respectively. Diafiltration and adsorption rates were 82.1 ± 9.8% and 12.1 ± 6.1% under all conditions, respectively. Total CLCHDF using the PMMA membrane increased with increasing Qe. Diafiltration and adsorption rates were 89.2 ± 20.4% and 4.6 ± 17.0% under all conditions, respectively. The observed CLCHDF values significantly correlated with the predicted CLCHDF , calculated according to a previous study as the product of Qe and the plasma unbound fraction. CONCLUSIONS: Diafiltration predominantly contributed to CLCHDF of VCM using AN69ST and PMMA membranes. When diafiltration rather than adsorption mainly contributes to the CLCHDF of VCM, the CLCHDF could be predicted from the Qe and HSA concentration, at least in vitro.

Identification of factors affecting meropenem pharmacokinetics in critically ill patients: Impact of inflammation on clearance.

INTRODUCTION: The purpose of this study was to explore factors influencing meropenem pharmacokinetics (PKs) in critically ill patients by developing a population PK model and to determine the optimal dosing strategy. METHODS: This prospective observational study involved 12 critically ill patients admitted to the intensive care unit and treated with meropenem 1 g infused over 1 h every 8 h. Blood samples were collected on days 1, 2, and 5 immediately prior to dosing, and at 1, 2, 4, and 6 h after the start of infusion. Population PK parameters were estimated using nonlinear mixed-effects model software. RESULTS: Meropenem PK was adequately described using a two-compartment model. Typical values of total and inter-compartmental clearance were 9.30 L/h and 9.70 L/h, respectively, and the central and peripheral compartment volumes of distribution were 12.61 L and 7.80 L, respectively. C-reactive protein (CRP) was identified as significant covariate affecting total meropenem clearance. The probability of target attainment (PTA) predicted by Monte Carlo simulations varied according to the patients' CRP. The PTA of 100% time above the minimum inhibitory concentration ≤2 mg/L for bacteria was achieved after a dose of 1 and 2 g infused over 4 h every 8 h in patients with CRP of 30 and 5 mg/dL, respectively. CONCLUSION: The findings of this study suggest that CRP might be helpful in managing meropenem dosing in critically ill patients. Higher doses and extended infusion may be required to achieve optimal pharmacodynamic targets.

Evaluation of association between parameters related to penetration into cerebrospinal fluid and the microbiological efficacy of vancomycin in patients with bacterial meningitis.

Vancomycin (VM) is used as empirical therapy for bacterial meningitis (BM). We investigated the relationship of the microbiological efficacy of VM for BM with VM minimum inhibitory concentration (MICVM), serum VM trough concentration (VMser) and cerebrospinal fluid (CSF) protein (P)/serum albumin (SA) ratio, which may reflect the extent of blood-brain barrier (BBB) disruption. Twelve BM patients were enrolled and VM was microbiologically effective in seven (58.3%). VMser, MICVM, and CSF-P/SA ratio were not associated with the microbiological efficacy of VM. The microbiological efficacy of VM was significantly associated with CSF-P/SA ratio multiplied by VMser relative to the MICVM (η = 0.61, p = 0.04). These results indicate that the parameter combining VMser, MICVM, and the extent of BBB disruption could be associated with the microbiological efficacy of VM in BM patients.

Left Transradial Neurointerventions Using the 6-French Simmons Guiding Sheath: Initial Experiences with the Interchange Technique.

BACKGROUND: The transradial approach using a Simmons-shaped catheter has been increasingly used for diagnostic cerebral angiography and neurointervention. In the transradial approach for neurointervention, the right radial artery is mainly used. However, in interventional cardiology, there are apparent clinical benefits with the left transradial approach for right-handed patients. To our knowledge, no studies have reported on neurointervention with the routine use of the left transradial approach. We therefore devised a novel technique for cases with an unachievable form of the Simmons shape using the standard technique, which we named the "interchange technique." The purpose of this study was to evaluate the technical feasibility of the left transradial neurointervention. METHODS: This study is a retrospective review of our prospective database of consecutive patients who underwent a left transradial neurointervention, using a 6-French Simmons guiding sheath, performed from January through April 2021. The outcome variables studied were successful catheterization and procedure-related complications. RESULTS: Twenty-one patients underwent a left transradial neurointervention including cerebral aneurysm coiling, carotid artery stenting, and meningioma embolization. The Simmons shape could not be formed with the standard technique for 3 patients, for whom we successfully formed the Simmons shape with our new interchange technique. The procedure was completely achieved in all 21 patients. No patients required crossover to the right radial or femoral arteries, and there were no radial artery spasms or occlusions or any procedural complications. CONCLUSIONS: The left transradial approach for neurointervention is a technically feasible, safe, and effective alternative while providing more comfort to right-handed patients.

Analysis of postprocedural microembolic infarctions and global oxygen extraction fraction during balloon-protected carotid artery stenting: Preliminary study.

BACKGROUND: Atherosclerotic carotid stenosis with impaired cerebral perfusion is a risk factor for cerebral ischemia. In major carotid stenoocclusive diseases, increased oxygen extraction fraction (OEF) is associated with ischemic stroke. Balloon-protected carotid artery stenting (CAS) is valuable for high-grade carotid stenosis. However, while balloon-protected CAS can effectively reduce the occurrence of ischemic complications by blocking carotid flow, cerebral hypoperfusion may result in simultaneous cerebral ischemia. We sought to evaluate whether increased OEF during balloon-protected CAS can predict postprocedural microembolic infarction (MI). METHODS: Eighty-four patients who underwent balloon-protected CAS were enrolled. Initial, intraprocedural, and postprocedural OEFs were calculated from the cerebral arteriovenous oxygen differences obtained from blood sampled just before the temporary occlusion and reperfusion of the internal carotid artery during and after the procedure. MIs were evaluated by diffusion-weighted imaging (DWI). Patients were classified into two groups based on the presence or absence of new MIs, and the relationship between the OEF and postprocedural MIs was analyzed. RESULTS: New DWI-positive lesions were found in 37 cases (44.0%). Age, signal intensity ratio (SIR) of carotid plaque on T1-weighted black blood magnetic resonance imaging, and intraprocedural OEF were significantly higher in the DWI-positive group. The high SIR and intraprocedural OEF were significantly associated with the development of postprocedural MIs in multivariate analysis. MIs were correlated with the increase in OEF. CONCLUSION: Increased intraprocedural OEF, obtained by blood sampling during balloon-protected CAS, could predict the incidence of postprocedural MIs. Patients with carotid stenosis could be hemodynamically compromised by carotid flow blockage during balloon-protected CAS.

Analysis of the acrolein-modified sites of apolipoprotein B-100 in LDL.

We have reported that acrolein-conjugated low-density lipoprotein (Acro-LDL) uptake by scavenger receptor class A type 1 (SR-A1) can mediate macrophage foam cell formation. The purpose of this study was to determine which amino acid residues of apoB protein in LDL are conjugated with acrolein. Acro-apoB was prepared by incubation of LDL with acrolein (10 to 60 µM) at 37 °C for 7 days. Identification of acrolein-conjugated amino acid residues in apoB was performed using LC-MS/MS. The levels of acrolein-conjugated amino acid residues of apoB as well as crosslinking apoB increased in proportion to acrolein concentration. The level of LDL uptake by macrophages was parallel with the acrolein-conjugated monomer apoB. Acrolein-conjugated amino acid residues in apoB were C212, K327, K742, K949, K1087, H1923, K2634, K3237 and K3846. The NH2-teriminal four amino acid residues (C212, K327, K742 and K949) were located at the scavenger receptor SR-A1 recognition site, suggesting that these four acrolein-conjugated amino acids are involved in the rapid uptake of Acro-LDL by macrophages. It is proposed that the rapid uptake of LDL by macrophages is dependent on acrolein conjugation of four amino acids residues at the scavenger receptor recognition site of apoB in LDL.

Delayed Iatrogenic Dissection Caused by a Carotid Stent: A Case Report.

Iatrogenic dissection (ID) is a well-known complication of neuroendovascular treatments. ID is predominantly attribute to endothelial injury by the manipulation of wires and/or catheters, and is generally detected in angiography during the procedure. We present a rare case with delayed ID due to deployment of a carotid stent. A 71-year-old man presented with transient motor weakness in the right extremity. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) showed previous multiple cerebral infarctions without a diffusion sign, stenosis with vulnerable plaque in the left common carotid artery (CCA), and an extremely flexed internal carotid artery (ICA). On dual antiplatelet medication, carotid artery stenting (CAS) was completed with favorable dilation of the carotid lumen. Computed tomography angiography 4 days after the procedure revealed high-grade stenosis at the ICA adjacent to the distal edge of the deployed stent. ID with intramural hematoma was diagnosed on MRI. The ID was conservatively treated and remarkably diminished 4 months after the procedure. The patient was asymptomatic during the entire clinical course. This delayed ID was considered to be due to an endothelial injury caused by the distal edge and the constant radial force of the open-cell stent against the flexed vessel and exacerbated by dual antiplatelet therapy. Even in a patient with favorable arterial dilation in CAS procedure, the possibility of a delayed ID should always be considered.