A Case of Femoral Artery Aneurysm Caused by Methotrexate Associated Lymphoproliferative Disease.

An 82-year-old man with left leg edema was referred to our department after an ultrasound examination by his previous physician, which revealed deep vein thrombosis (DVT) in the left superficial femoral vein and a left common femoral artery aneurysm (CFAA). The DVT was caused by the CFAA. The patient was adjudged to be at high risk of peripheral embolization due to the irregular shape of the varicose vein and a large amount of mural thrombus. Surgery was performed to replace the artificial blood vessel. The patient displayed firm adhesion to the surrounding area, marked lymph node swelling, and a large amount of mural thrombus in the mass. The superficial femoral artery (SFA) demonstrated severe intimal thickening and partial dissection. The postoperative course was good, and the patient was undergoing rehabilitation to be discharged home; however, B-cell lymphoma was suspected based on the pathology results of the mass wall submitted intraoperatively. The patient had a history of rheumatoid arthritis and was treated with methotrexate (MTX). During the course of his illness, a subcutaneous mass was found on his right forearm, and a skin biopsy revealed MTX-associated lymphoproliferative disease (MTX-LPD), which had resolved with MTX withdrawal. The histopathological results of the skin biopsy matched those of the CFAA mural thrombus, and Epstein-Barr virus-positive cells were also observed, leading to the diagnosis of MTX-LPD, which was considered to be the cause of CFAA. No MTX-LPD was identified in the vessel walls or intramural thrombus. We herein report a case of CFAA with an extremely rare etiology and clinical presentation.

A Surgical Case of Infected Popliteal Artery Aneurysm From Rare Bacteria, Eubacterium sp.

A 79-year-old man presented to our hospital with complaints of a sudden worsening of swelling in the right popliteal fossa and fever persisting for a week. Upon close examination, an infected popliteal artery aneurysm (PAA) was identified. Given the risk of rupture, the patient was advised to undergo surgery. The surgical procedure involved resecting the infectious PAA using a lateral approach. Additionally, a bypass was performed from the superficial femoral artery to the below-knee artery, utilizing the great saphenous vein located at the posterior aspect of the knee. Surgical findings revealed a popliteal artery pseudoaneurysm. Preoperative blood cultures identified Eubacterium spp., and cultures of the inoperative aneurysm specimens confirmed the presence of the same bacteria. After surgery, inflammation quickly subsided, and the patient was discharged on postoperative day (POD) 41 after receiving transvenous antibiotic therapy. Although PAA accounts for approximately 80% of all peripheral arterial aneurysms, mycotic aneurysms are relatively rare. Eubacterium spp. is part of the human intestinal or oral flora, and very few reports of bacteremia have been published. The present case of bacteremia caused by Eubacterium sp. is very rare; to the best of our knowledge, no literature has been published on this topic.

Extracellular Microvesicles Modified with Arginine-Rich Peptides for Active Macropinocytosis Induction and Delivery of Therapeutic Molecules.

Extracellular vesicles (EVs), including exosomes and microvesicles (MVs), transfer bioactive molecules from donor to recipient cells in various pathophysiological settings, thereby mediating intercellular communication. Despite their significant roles in extracellular signaling, the cellular uptake mechanisms of different EV subpopulations remain unknown. In particular, plasma membrane-derived MVs are larger vesicles (100 nm to 1 µm in diameter) and may serve as efficient molecular delivery systems due to their large capacity; however, because of size limitations, receptor-mediated endocytosis is considered an inefficient means for cellular MV uptake. This study demonstrated that macropinocytosis (lamellipodia formation and plasma membrane ruffling, causing the engulfment of large fluid volumes outside cells) can enhance cellular MV uptake. We developed experimental techniques to induce macropinocytosis-mediated MV uptake by modifying MV membranes with arginine-rich cell-penetrating peptides for the intracellular delivery of therapeutic molecules.

A patient with extensive ST elevation myocardial infarction who underwent emergent Impella CP® assisted off-pump coronary artery bypass without mechanical complication.

Impella (Abiomed Inc., Danvers, MA, USA) assisted off-pump coronary artery bypass has been increasingly reported in recent years. However, there have been no reports of the procedures performed for acute myocardial infarction in which the patient is hemodynamically unstable. We report a case of a 73-year-old man with cardiogenic shock due to extensive ST elevation acute myocardial infarction that worsened despite Impella CP® support. Because of the fragile myocardium in the acute phase of myocardial infarction, Impella assisted off-pump coronary artery bypass graft causes a high risk of myocardial injury, but we were able to safely perform the procedure by ingenious techniques. Learning objective: When performing Impella-assisted off-pump coronary artery bypass for extensive acute myocardial infarction patients, the high risk of mechanical complications due to myocardial fragility must be considered. The position of Impella should be carefully monitored intraoperatively, and elevation of cardiac apex should be kept to a minimum to prevent myocardial damage caused by Impella.

Maturation and development of fetal pig intestinal tissue in immunodeficient mice.

PURPOSE: This study aimed to compare the degree of maturation and development of fetal pig segmental intestinal tissue with that of spheroids created by in-vitro reaggregation of dissociated fetal intestinal cells after transplantation into immunodeficient mice. METHODS: Fetal pig small intestines were transplanted as segmental grafts into the omentum and subrenal capsules of immunodeficient mice or enzymatically treated to generate single cells. Spheroids made by in-vitro reaggregation of these cells were transplanted into the subrenal capsules of immunodeficient mice. The segmental grafts and spheroids were harvested four and eight weeks after transplantation, and the structural maturity and in-vivo development of these specimens were histologically evaluated. RESULTS: The spheroids were engrafted and supplied blood vessels from the host mice, but an intestinal layered structure was not clearly observed, and there was almost no change in size. On the other hand, the segmental grafts formed deep crypts in the mucus membrane, the inner circular layer, and outer longitudinal muscles. The crypts of the transplanted grafts harvested at eight weeks were much deeper, and the smooth muscle layer and the enteric nervous system were more mature than those of grafts harvested at the fourth week, although the intestinal peristaltic wave was not observed. CONCLUSIONS: Spheroids created from fetal small intestinal cells could not form layered structures or mature sufficiently. Conversely, segmental tissues structurally matured and developed after in-vivo transplantation and are therefore potential grafts for transplantation.

Maturation and development of fetal pig intestinal tissue in immunodeficient mice

Purpose: This study aimed to compare the degree of maturation and development of fetal pig segmental intestinal tissue with that of spheroids created by in-vitro reaggregation of dissociated fetal intestinal cells after transplantation into immunodeficient mice. Methods: Fetal pig small intestines were transplanted as segmental grafts into the omentum and subrenal capsules of immunodeficient mice or enzymatically treated to generate single cells. Spheroids made by in-vitro reaggregation of these cells were transplanted into the subrenal capsules of immunodeficient mice. The segmental grafts and spheroids were harvested four and eight weeks after transplantation, and the structural maturity and in-vivo development of these specimens were histologically evaluated. Results: The spheroids were engrafted and supplied blood vessels from the host mice, but an intestinal layered structure was not clearly observed, and there was almost no change in size. On the other hand, the segmental grafts formed deep crypts in the mucus membrane, the inner circular layer, and outer longitudinal muscles. The crypts of the transplanted grafts harvested at eight weeks were much deeper, and the smooth muscle layer and the enteric nervous system were more mature than those of grafts harvested at the fourth week, although the intestinal peristaltic wave was not observed. Conclusions: Spheroids created from fetal small intestinal cells could not form layered structures or mature sufficiently. Conversely, segmental tissues structurally matured and developed after in-vivo transplantation and are therefore potential grafts for transplantation.

Delayed Giant Pseudoaneurysm With Left-to-Right Shunt Following Postinfarct Ventricular Septal Perforation Repair.

Left ventricular pseudoaneurysm with a left-to-right shunt is extremely rare, requiring surgery if symptomatic; however, surgery has a high risk. Here, the case of a 77-year-old man with heart failure symptoms is reported, in which he develops a giant left ventricular pseudoaneurysm 16 months after ventricular septal perforation repair as a result of acute myocardial infarction, with mild shunt blood flow from the pseudoaneurysm to the right ventricle. Intraoperative findings showed a free wall rupture along the area where the patch was secured during the initial surgery. The patient was discharged on postoperative day 13, and postoperative examination revealed no abnormalities.

Preparing Size-Controlled Liposomes Modified with Polysaccharide Derivatives for pH-Responsive Drug Delivery Applications.

The liposome particle size is an important parameter because it strongly affects content release from liposomes as a result of different bilayer curvatures and lipid packing. Earlier, we developed pH-responsive polysaccharide-derivative-modified liposomes that induced content release from the liposomes under weakly acidic conditions. However, the liposome used in previous studies size was adjusted to 100-200 nm. The liposome size effects on their pH-responsive properties were unclear. For this study, we controlled the polysaccharide-derivative-modified liposome size by extrusion through polycarbonate membranes having different pore sizes. The obtained liposomes exhibited different average diameters, in which the diameters mostly corresponded to the pore sizes of polycarbonate membranes used for extrusion. The amounts of polysaccharide derivatives per lipid were identical irrespective of the liposome size. Introduction of cholesterol within the liposomal lipid components suppressed the size increase in these liposomes for at least three weeks. These liposomes were stable at neutral pH, whereas the content release from liposomes was induced at weakly acidic pH. Smaller liposomes exhibited highly acidic pH-responsive content release compared with those from large liposomes. However, liposomes with 50 mol% cholesterol were not able to induce content release even under acidic conditions. These results suggest that control of the liposome size and cholesterol content is important for preparing stable liposomes at physiological conditions and for preparing highly pH-responsive liposomes for drug delivery applications.

Inkjet-Based Intracellular Delivery System that Effectively Utilizes Cell-Penetrating Peptides for Cytosolic Introduction of Biomacromolecules through the Cell Membrane.

In the drug delivery system, the cytosolic delivery of biofunctional molecules such as enzymes and genes must achieve sophisticated activities in cells, and microinjection and electroporation systems are typically used as experimental techniques. These methods are highly reliable, and they have high intracellular transduction efficacy. However, a high degree of proficiency is necessary, and induced cytotoxicity is considered as a technical problem. In this research, a new intracellular introduction technology was developed through the cell membrane using an inkjet device and cell-penetrating peptides (CPPs). Using the inkjet system, the droplet volume, droplet velocity, and dropping position can be accurately controlled, and minute samples (up to 30 pL/shot) can be carried out by direct administration. In addition, CPPs, which have excellent cell membrane penetration functions, can deliver high-molecular-weight drugs and nanoparticles that are difficult to penetrate through the cell membrane. By using the inkjet system, the CPPs with biofunctional cargo, including peptides, proteins such as antibodies, and exosomes, could be accurately delivered to cells, and efficient cytosolic transduction was confirmed.

Biocompatible Polymer-Grafted TiO2 Nanoparticle Sonosensitizers Prepared Using Phosphonic Acid-Functionalized RAFT Agent.

Sonodynamic therapy is widely used in clinical studies including cancer therapy. The development of sonosensitizers is important for enhancing the generation of reactive oxygen species (ROS) under sonication. Herein, we have developed poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)-modified TiO2 nanoparticles as new biocompatible sonosensitizers with high colloidal stability under physiological conditions. To fabricate biocompatible sonosensitizers, a grafting-to approach was adopted with phosphonic-acid-functionalized PMPC, which was prepared by reversible addition-fragmentation chain transfer (RAFT) polymerization of 2-methacryloyloxyethyl phosphorylcholine (MPC) using a newly designed water-soluble RAFT agent possessing a phosphonic acid group. The phosphonic acid group can conjugate with the OH groups on the TiO2 nanoparticles. We have clarified that the phosphonic acid end group is more crucial for creating colloidally stable PMPC-modified TiO2 nanoparticles under physiological conditions than carboxylic-acid-functionalized PMPC-modified ones. Furthermore, the enhanced generation of singlet oxygen (1O2), an ROS, in the presence of PMPC-modified TiO2 nanoparticles was confirmed using a 1O2-reactive fluorescent probe. We believe that the PMPC-modified TiO2 nanoparticles prepared herein have potential utility as novel biocompatible sonosensitizers for cancer therapy.

Phase wavefront perturbation calculation model for spectroscopic refractive index matching of hybrid materials.

A low-cost flexible spectroscopic refractive index matching (SRIM) material with bandpass filtering properties without incidence angle and polarization dependence by randomly dispersing inorganic C a F 2 particles in organic polydimethylsiloxane (PDMS) materials was proposed in our previous study. Since the micron size of the dispersed particles is much larger than the visible wavelength, the calculation based on the commonly used finite-difference time-domain (FDTD) method to simulate light propagation through the SRIM material is too bulky; however, on the other hand, the light tracing method based on Monte Carlo theory in our previous study cannot adequately explain the process. Therefore, a novel approximate calculation model, to the best of our knowledge, based on phase wavefront perturbation is proposed that can well explain the propagation of light through this SRIM sample material and can also be used to approximate the soft scattering of light through composite materials with small refractive index differences, such as translucent ceramics. The model simplifies the complex superposition of wavefront phase disturbances and the calculation of scattered light propagation in space. The scattered and nonscattered light ratios; the light intensity distribution after transmission through the spectroscopic material; and the influence of absorption attenuation of the PDMS organic material on the spectroscopic performance are also considered. The simulation results based on the model are in great agreement with the experimental results. This work is important to further improve the performance of SRIM materials.

Effect of Poly(Vinyl Alcohol) Concentration and Chain Length on Polymer Nanogel Formation in Aqueous Dispersion Polymerization.

Nanotechnology has attracted increasing interest in various research fields for fabricating functional nanomaterials. In this study, we investigated the effect of poly(vinyl alcohol) (PVA) addition on the formation and thermoresponsive properties of poly(N-isopropyl acrylamide)-based nanogels in aqueous dispersion polymerizations. During dispersion polymerization, PVA appears to play three roles: (i) it bridges the generated polymer chains during polymerization, (ii) it stabilizes the formed polymer nanogels, and (iii) it regulates the thermoresponsive properties of the polymer nanogels. By regulating the bridging effect of PVA via changing the PVA concentration and chain length, the size of the obtained polymer gel particles was maintained in the nanometer range. Furthermore, we found that the clouding-point temperature increased when using low-molecular weight PVA. We believe that the knowledge gained in this study regarding the effect of PVA concentration and chain length on nanogel formation will aid in the future fabrication of functional polymer nanogels.

The Comparison of Postoperative Umbilical Port Site-Related Complications Between Transumbilical and Periumbilical Incision After Laparoscopic Surgery in Children.

Introduction: No studies have directly compared postoperative umbilical port site (UPS)-related complications between transumbilical and periumbilical incisions (TUI and PUI) after laparoscopic surgery in children. Patients and Methods: We conducted a retrospective review of 324 children of ≤15 years of age who underwent laparoscopic repair (LR) for inguinal hernia, via either a TUI or PUI, between 2010 and 2020. UPS-related complications, such as wound infection and umbilical deformity, were compared between TUI and PUI. We also investigated the risk factors for the development of UPS-related complications after LR. Results: TUIs and PUIs were used for 228 and 96 children, respectively. The incidence rates of postoperative wound infection and umbilical deformity in the PUI group were higher in comparison to the TUI group; although not to a statistically significant extent (7.3% versus 5.3%, P = .451, 6.3% versus 4.8%, P = .593). One case of incisional hernia at the UPS was seen in the TUI group. In the univariate analysis, sex, age, weight for age Z-score, nutrition status, insertion and closure time, total operative time, American Society of Anesthesiologists score, blood loss, and comorbidities were not significantly associated with the development of UPS-related complications after LR. Conclusion: The incidence of UPS-related complications in TUI and PUI was not significantly different. Due to the low incidence of UPS-related complications, it was difficult to draw conclusions regarding contributing factors; however, meticulous care should be taken to avoid UPS-related complications when closing the UPS (Ethical approval No. 2019-24).

＜Editors' Choice＞ Neck pain after cervical laminoplasty is associated with postoperative atrophy of the trapezius muscle.

Cervical laminoplasty is a safe and effective treatment for cervical myelopathy. However, it has a higher frequency of postoperative axial pain than other methods. A variety of causes of postoperative axial pain have been reported, but these have not been fully elucidated. This study aimed to investigate the association between postoperative axial pain and changes in the posterior neck muscles before and after surgery. The study included 93 patients with cervical myelopathy who underwent surgery at our institute between June 2010 and March 2013. The patients with greater preoperative and 1-year postoperative neck pain visual analog scale scores comprised the neck pain group. The cross-sectional area of the cervical posterior extensor muscles and the trapezius muscle were measured by magnetic resonance imaging before and 1 year after surgery at the C3/4, C4/5, and C5/6 levels to compare with neck pain. The total cross-sectional area atrophy rate (C3/C4, C4/C5, and C5/C6) of the trapezius muscle was significantly larger in patients with neck pain (12.8 ± 13.2) than in those without (6.2 ± 14.4; p<0.05). The cross-sectional area atrophy rate of the trapezius muscle at only the C5/6 level was significantly higher in patients with neck pain (16.7 ± 11.7) compared to those without (3.3 ± 14.4; p<0.001). No significant differences were found in the cross-sectional areas of the cervical posterior extensor muscles. Trapezius atrophy, especially at the lower cervical vertebrae, was associated with neck pain after cervical laminoplasty.

Association between Postoperative Neck Pain and Intraoperative Transcranial Motor-Evoked Potential Waveforms of the Trapezius Muscles in Patients with Cervical Myelopathy Who Underwent Cervical Laminoplasty.

STUDY DESIGN: Retrospective study. PURPOSE: Cervical laminoplasty is safe and effective for treating cervical myelopathy but has a higher frequency of postoperative axial pain compared to other methods. Several studies have reported on the causes of postoperative axial pain, but none have fully elucidated them. This study aimed to investigate the association between postoperative neck pain and intraoperative transcranial motor-evoked potential (MEP) waveforms of the trapezius muscles using transcranial MEPs. OVERVIEW OF LITERATURE: Few studies have investigated the association between postoperative neck pain and intraoperative transcranial MEP waveforms of the trapezius muscles in patients with cervical laminoplasty. METHODS: A total of 79 patients with cervical myelopathy who underwent cervical laminoplasty at our facility between June 2010 and March 2013 were included in this study. Intraoperative control and final waveform were evaluated based on the trapezius muscle MEPs by measuring the latency and amplitude. A neck pain group comprised patients with higher neck pain Visual Analog Scale scores from preoperative value to 1 year postoperatively. The cross-sectional areas of the trapezius muscles and the MEP latencies and amplitudes were compared between patients with and without neck pain. RESULTS: The latency and amplitude of the control waveforms were not significantly different between groups. The neck pain group had a significantly shorter final waveform latency (neck pain: 23.6±2.5, no neck pain: 25.8±4.5; p =0.019) and significantly larger amplitude (neck pain: 2,125±1,077, no neck pain: 1,630±966; p =0.041) than the no neck pain group. CONCLUSIONS: Postoperative neck pain was associated with the final waveform latency and amplitude of the trapezius muscle MEPs during cervical laminoplasty. Intraoperative electrophysiological trapezius muscle abnormalities could cause postoperative neck pain.

Cationic lipid potentiated the adjuvanticity of polysaccharide derivative-modified liposome vaccines.

Antigen carriers that can selectively deliver antigens to antigen presenting cells and which can simultaneously activate these cells (adjuvant property) are necessary for efficient cancer immunotherapy or vaccination. Delivery of a model antigen into dendritic cell cytosol has been achieved by pH-responsive polymer-modified liposomes via destabilization of endosomal membranes responding to acidic pH, which impelled antigen-specific cellular immunity. Furthermore, ß-glucan-based pH-responsive polysaccharides have shown not only cytosolic antigen delivery performance but also adjuvant property, which further heightened cellular immune responses. Because pH-responsive polysaccharides have anionic carboxy groups, cationic lipid was introduced to liposomes in this study to improve the modification efficiency of pH-responsive polysaccharides and to improve their adjuvanticity and immunity-inducing functions. Introduction of cationic lipids increased the amounts of polysaccharide derivatives on the liposome and increased the cellular association of the liposomes to dendritic cells. Liposomes containing ß-glucan-based pH-responsive polysaccharides and cationic lipids increased cytokine production from dendritic cells much more than other polysaccharide derivatives did. Furthermore, through improvement of intra-tumoral immunosuppression and induction of antigen-specific cellular immunity, administering these liposomes impelled tumor suppression even with a small antigen dose. These results suggest that introducing cationic lipids and using pH-responsive polysaccharides having intrinsically adjuvant function are effective for producing liposomal nanovaccines showing strong immunity-inducing function.

Reversible Stabilization of Nanofiber-Polyplexes through Introducing Cross-Linkages.

Non-viral gene delivery systems are typically designed vector systems with contradictory properties, namely sufficient stability before cellular uptake and instability to ensure the release of nucleic acid cargoes in the transcription process after being taken up into cells. We reported previously that poly-(L-lysine) terminally bearing a multi-arm PEG (maPEG-PLL) formed nanofiber-polyplexes that suppressed excessive DNA condensation via steric repulsion among maPEGs and exhibited effective transcriptional capability in PCR amplification experiments and a cell-free gene expression system. In this study, the reversible stabilization of a nanofiber-polyplex without impairing the effective transcriptional capability was investigated by introducing cross-links between the PLL side chains within the polyplex using a cross-linking reagent with disulfide (SS) bonds that can be disrupted under reducing conditions. In the presence of dextran sulfate and/or dithiothreitol, the stability of the polyplex and the reactivity of the pDNA were evaluated using agarose gel electrophoresis and real-time PCR. We succeeded in reversibly stabilizing nanofiber-polyplexes using dithiobis (succinimidyl propionate) (DSP) as the cross-linking reagent. The effect of the reversible stabilization was confirmed in experiments using cultured cells, and the DSP-crosslinked polyplexes exhibited gene expression superior to that of polyethyleneimine polyplexes, which are typical polyplexes.

Preoperative Sarcopenia Assessment Using Pectoralis Muscle Mass Indicated Poor Mid-term Cardiac Surgery Prognosis.

BACKGROUND: Many studies have defined sarcopenia based on psoas muscle mass using abdominal computed tomography (CT). We hypothesized that sarcopenia can be assessed by measuring pectoralis muscle mass on chest CT and aimed to examine its relationship with the postoperative prognosis of cardiac surgery. METHODS: This retrospective study included 189 patients who underwent cardiac surgery via median sternotomy between July 2020 and June 2022. We excluded patients <70 years old, urgent/emergent cases, no chest CT within 90 days before surgery, and cases in which evaluation of the pectoralis muscle was impossible with CT. The pectoralis muscle area (PMA) was measured using a preoperative chest CT. The sarcopenia cut-off value was defined as the lowest sex-specific tertile in PMA at the level of the 4th thoracic vertebrae. RESULTS: Eighty patients were included. The lower tertile were classified as the sarcopenia group (SG) (n = 26) and the rest as the non-sarcopenia group (NSG) (n = 54). In the SG, 1-year survival was significantly worse than that in NSG (NSG: 92.7% vs. SG: 54.9%, p < 0.0001). In the multivariate model, sarcopenia was an independent risk factor for mid-term all-cause death (hazard ratio, 4.89; 95% confidence interval: 1.14-21.0, p = 0.033). CONCLUSION: Preoperative sarcopenia defined using PMA was associated with poor mid-term survival after elective cardiac surgery via median sternotomy. The pectoralis muscle mass observed through a chest CT could be used for preoperative risk scoring in older patients undergoing cardiac surgery.