Super-Elderly Case of Acute Lower Limb Ischemia Treated with Indigo Aspiration System in Japan.

The Indigo Aspiration System (Penumbra Ltd., Alameda, CA, USA), a catheter-based device intended for the endovascular removal of clots from peripheral arteries and veins, was launched in Japan to treat acute limb ischemia after the cessation of urokinase sales. The initial application of this system in Japan was on a 96-year-old male patient. He was diagnosed with acute lower limb ischemia, which was caused by an embolism from a left common iliac artery aneurysm. The treatment significantly enhanced the perfusion to his left foot. This case report elaborates on the patient's treatment experience and discusses the indications for using the device.

Venous Screening Activities at the Site of Hokkaido East Iburi Earthquake: Report from the Result of Venous Screening in Preventive Awareness Activities.

After previous earthquakes, high prevalence of cardiovascular diseases including venous thromboembolism (VTE) has been reported. We performed venous screening at the site of Hokkaido East Iburi Earthquake which happened at 6th September 2018. VTE screening using ultrasound sonography was performed for total 7 days at Atsuma town, Mukawa town and Abira town (total 9 shelters). Deep vein thrombosis (DVT) was found in 19 of 195 evacuees (9.7%), including 8 fresh thrombus cases (4.1%). On multivariable analysis of evacuees and shelter environment factors, systolic blood pressure, use of cardboard bed and toilet environment were significant predictor of DVT. Introduction and setting-up of cardboard beds were found as an important shelter environment factor. (This is secondary publication from Jpn J Phlebol 2021; 32(1): 5-10.).

New high-throughput screening method for Chinese hamster ovary cell lines expressing low reduced monoclonal antibody levels: application of a system controlling the gas phase over cell lysates in miniature bioreactors and facilitating multiple sample setup.

Interchain disulfide bonds in monoclonal antibodies may be reduced during large-scale mAb production using Chinese hamster ovary (CHO) cells. This reaction lowers the mAb product yield and purity; however, it may be prevented by screening cell lines that are unsusceptible to reduction and using them in mAb production. Antibody reduction susceptibility may be cell line-dependent. To the best of our knowledge, however, an efficient method of screening reduction-unsusceptible CHO cell lines has not been previously reported. Here, we report a novel screening method that can simultaneously detect and identify mAb reduction susceptibility in lysates containing ≤ 48 CHO cell lines. This evaluation system was equally effective and generated similar results at all culture scales, including 250 mL, 3 L, and 1000 L. Furthermore, we discovered that reduction-susceptible cell lines contained higher total intracellular nicotinamide adenine dinucleotide phosphate (NADPH) and NADP+ concentrations than reduction-unsusceptible cell lines, regardless of whether they expressed immunoglobulin (Ig)G4 or IgG1. NADPH or NADP+ supplementation in the lysate of reduction-unsusceptible cells resulted in mAb reduction. Application of the innovative CHO cell line screening approach could mitigate or prevent reductions in large-scale mAb generation from CHO cells.

Giant Superior Mesenteric Artery Aneurysm Treated by Endovascular Treatment in a Very Elderly Female.

Superior mesenteric artery (SMA) aneurysms (SMAAs) are rare and account for approximately 7% of all visceral artery aneurysms. If the anatomical complexity permits and the patency of organ perfusion is allowed, then an endovascular approach is the first choice for minimally invasive procedures. We report the case of a 92-year-old female with a giant SMAA and challenging anatomy, including a short proximal sealing zone from the origin of the SMA and a short distal sealing zone from the hepatic artery bifurcation. In view of her advanced age, she was treated endovascularly with covered stents. Reintervention was required to correct a postoperative endoleak; however, a favorable outcome was achieved with endovascular therapy.

A case of lymphoma mimicking infected internal iliac artery aneurysm.

BACKGROUND: Malignant lymphoma rarely mimics an infected arterial aneurysm and a ruptured arterial aneurysm because of similar imaging findings, leading to misdiagnosis. The hematomas of ruptured aneurysms are radiologically difficult to distinguish from those of malignant lymphoma in emergency settings. Hence, a definitive diagnosis is crucial to avoid unnecessary surgery. CASE PRESENTATION: A man in his 80s with hematuria and shock vital had right internal iliac artery aneurysm (IIAA) and perianeurysmal fluid retention, which appeared to be a ruptured or an infected aneurysm. Treatment was initiated for infected IIAA instead of for ruptured IIAA. Systemic inflammatory response syndrome developed, and the infectious sources were assessed. Pacemaker lead and urinary tract infections were identified and treated; however, blood pressure was unstable. The aneurysm was treated with endovascular aortic aneurysm repair following antibiotic therapy; however, fluid retention increased, and inflammatory status and hematuria deteriorated. Open surgical conversion was performed to manage the infected lesions. Although an iliopsoas abscess was detected during surgery and nephrectomy and ureterectomy were performed to control the hematuria, analysis of the removed tissues led to the pathological diagnosis of diffuse large B-cell lymphoma (DLBCL). CONCLUSIONS: We encountered a case of DLBCL with imaging findings mimicking an infected internal iliac artery aneurysm, and definitive diagnosis was made more than 2 months after the initial examination. Definitively diagnosing malignant lymphoma around an iliac artery aneurysm based merely on symptoms and imaging findings is extremely difficult. Thus, histological examination should be actively performed in atypical infected aneurysms.

Anti-glycine receptor antibody-positive progressive encephalomyelitis with rigidity and myoclonus initially presenting with one-sided stiff face: A case report.

Background: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a subtype of stiff-person syndrome, a rare cerebrospinal disease that causes brainstem symptoms, myoclonus, muscle rigidity, and hyperekplexia. Case presentation: A 71-year-old man experienced left-sided stiff face, and was subsequently admitted to our hospital because of the appearance of left-dominant lower limb myoclonus. Muscle rigidity followed 3 days later. Magnetic resonance imaging revealed no abnormality. An electrophysiological examination showed a toughness of the antagonistic muscle following evocation of the Achilles tendon reflex, and a tonic phenomenon affecting the left facial muscles during the blink reflex. The patient's serum was positive for anti-glycine receptor (anti-GlyR) antibody, suggesting PERM. The patient was administered steroids, immunoglobulin therapy, and immunosuppressive drugs. He gradually improved after these therapies and became able to walk using a walker. Conclusions: We conclude that this was a rare case of anti-GlyR antibody-positive PERM with unilateral brainstem symptoms, myoclonus, and muscle rigidity.

Wound Healing on the Cutting Plane of Ankle Bones after Incomplete Revascularization for Chronic Limb-Threatening Ischemia in an Elderly Patient: A Case Report.

Chronic limb-threatening ischemia (CLTI) is an important issue for elderly patients with peripheral artery disease. Here, we present the case of a 91-year-old man with CLTI, residing in a rural district. The onset of CLTI rapidly deprived him of ambulation because of a foot infection. Given that he had difficulty with long-distance transportation, limb salvage for extensive tissue loss was performed at a district facility, based on his and his family's request. Finally, skin grafting on the cutting plane of the right ankle bones resulted in wound healing in six months after incomplete revascularization and multiple minor amputations.

Traumatic Superficial Femoral Arteriovenous Fistula with Pulsatile Mass and Leg Pain 60 Years after Stabbing Injury.

Post-traumatic arteriovenous fistula (AVF) is a vascular injury complication and can present with vessel dilation, forming pulsatile varices, venous hypertension, distal ischemia, and congestive heart failure. We present a case of only pulsatile mass and leg pain caused by a 60-year-old post-traumatic AVF. Computed tomography angiography showed an AVF between the superficial femoral artery and superficial femoral vein. Surgical repair with AVF ligation was successfully performed. Traumatic AVF caused vascular and heart failure in the future; therefore, post-traumatic AVF is better eliminated as soon as possible.

Lateral approach to distal peroneal artery without fibular resection.

Bypass to the peroneal artery has sometimes been effective for pedal gangrene. However, the difficulty of approaching the terminal segment of the peroneal artery because of its anatomic features has been a clinical issue. Surgical access to this area can be achieved via a lateral approach with fibular resection. Although severe complications associated with fibular resection have rarely been reported, a less invasive surgical procedure would enable faster postoperative recovery and reduce the incidence of wound-related complications. We have described our experience with successful terminal peroneal artery bypass via a lateral approach without fibular resection in a 38-year-old male patient with chronic limb-threatening ischemia.

[A case of localized fasciitis with ulcerative colitis].

A 36-year-old man with ulcerative colitis presented with bloody stools at the beginning of October 2020. His condition had been stable without treatment since diagnosis 4 years prior. He was administered 4,000 mg of salazosulfapyridine orally and the bloody stools resolved. Fifteen days after treatment, he was admitted to our hospital with swelling and pain in his right lower leg. Laboratory results revealed an elevated erythrocyte sedimentation rate (43 mm/hr) and mildly elevated C-reactive protein levels (4.08 mg/dl). His D-dimer level was also elevated at 7.6 µg/ml. MRI using fat saturated T2-weighted imaging demonstrated marked hyperintensity in the fascia of the lower leg flexor and blood vessels of interstitial. In gadolinium-enhanced T1-weighted images, the deep veins were found to be dilated and the vein walls and their surrounding areas strongly contrasted, suggestive of localized fasciitis. No abnormalities were found on biopsy of his right gastrocnemius muscle on the 5th day after admission. Two days after the muscle biopsy, the patient began experiencing swelling and pain in his left lower leg. The high intensity lesions in his right leg were reduced on MRI performed the same day, but that of the fascia between the left gastrocnemius and soleus muscles was noted. We administered 60 mg (1.0 mg/kg/day) of prednisolone orally on day 9 and the pain and swelling in both legs promptly resolved. The prednisolone was tapered to 5 mg/day and as of the time of writing, resolution of pain and swelling has been maintained. Gastrocnemius myalgia syndrome, which causes pain and localized fasciitis, is often reported as a complication of Crohn's disease but is rare in conjunction with ulcerative colitis. It is important that clinicians are aware of this syndrome so it can be recognized early and successfully treated.

The Impact of Chronic Limb-Threatening Ischemia on Cardiac Surgery.

Purpose: The effect of chronic limb threatening ischemia (CLTI) on advanced cardiac disease, which requires surgical treatment, has rarely been reported. The purpose of this study was to review the outcomes of cardiac surgery in patients with CLTI and determine the risk factors, with a particular focus on the severity of CLTI. Patients: The baseline characteristics and outcomes of 33 patients who were treated for CLTI and underwent cardiac surgery were retrospectively analyzed. The states of CLTI were evaluated based on the Wound, Ischemia, and foot Infection (WIfI) classification system, and 33 patients were divided into the low-WIfI group (stages 1-2, n = 13) and high-WIfI group (stages 3-4, n = 20). Results: The in-hospital mortality rate was 0% in low-WIfI group and 35% in high-WIfI group (p = 0.027). Postoperative complications, particularly severe infections, occurred more frequently among high-WIfI group than low-WIfI group (70.0% vs. 23.1%, p < 0.01). Multivariable analysis identified foot infection grade as a WIfI classification factor and lower albumin levels as factors significantly associated with postoperative complications. The 1-year and 2-year survival rates were 84.6% and 67.7% in low-WIfI group and 45% and 28.1% in high-WIfI group, respectively (p = 0.011). Conclusions: Cardiac surgery in patients with high WIfI stage was an extremely high-risk procedure. In such patients, lowering the WIfI stage by lower extremity revascularization and/or debridement of diseased parts prior to cardiac surgery can be considered.

Stent-Graft Removal and Extra-Anatomical Bypass for the Treatment of Stent-Graft Infection after Endovascular Aneurysm Repair.

Stent-graft infection is a rare but potentially life-threatening complication of endovascular aortic repair. There are currently no consensus guidelines for treating stent-graft infections, but surgical treatment is generally considered preferable due to the low overall survival rate of patients receiving conservative therapy; however, the revascularization method remains controversial. We report a case in which stent-graft infection after endovascular aneurysm repair was successfully treated by stent-graft removal and extra-anatomical bypass (EAB). EAB is an effective method of revascularization for stent-graft infection.

Successful endovascular therapy involving direct puncture for spontaneous internal iliac artery aneurysm rupture.

Neurofibromatosis type 1 (NF-1) is associated with fatal vascular complications. A 40-year-old woman with NF-1 who had previously undergone left iliac artery ligation and femorofemoral bypass grafting for internal iliac artery (IIA) aneurysm rupture was transported to our hospital for the treatment of a newly developed IIA aneurysm. Although endovascular therapy was difficult owing to the previous surgery, we successfully performed embolization of the aneurysm and its feeding vessels via direct percutaneous puncture under ultrasound guidance. Aneurysm enhancement had completely disappeared at 2 months postoperatively. We have reported a novel approach of direct percutaneous puncture for IIA aneurysm embolization in a patient with NF-1.

Virus clearance by activated carbon for therapeutic monoclonal antibody purification.

In our previous study, activated carbon (AC) was employed in the purification process of therapeutic monoclonal antibody (mAb) as a replacement for Protein A affinity chromatography. In addition, we established an innovative column-free flow-through purification process using AC filter. In these investigations, the effective clearance of impurities (high-molecular-weight species, low-molecular-weight species, host cell proteins, and DNA) was observed compared to the conventional Protein A platform purification process. In this study, virus removal capability of our established AC process (AC filter) was investigated using two model viruses, Murine Leukemia Virus (MuLV) and Minute Virus of Mice (MVM) with the combination of two filtration methods (single-pass filtration and re-circulation filtration) using three kinds of mAbs. We found effective clearance of both MuLV and MVM (>3 log reduction factor, LRF) in all mAbs. Not only filtration method but also re-circulation duration didn't affect LRF, and >3 LRF of virus removal could be achieved by only single-pass filtration. From these results, it is expected that AC will be a promising candidate for the virus removal unit operation for mAb purification processes.

Calcified amorphous tumor located on a severely calcified mitral annulus in a patient with normal renal function.

A calcified amorphous tumor (CAT) of the heart is a rare, nonneoplastic, intracavitary cardiac mass. Histological examination shows that it contains calcified and amorphous fibrous material with underlying chronic inflammation. Surgical excision is generally recommended to avoid future embolism. The risk of embolism has been reported to be especially high in mitral-annular-calcification-related CAT, which constitutes a subgroup of CAT that is often associated with end-stage renal disease. A case of a CAT attached to the anterior annulus of the mitral valve that was easily removed with a light touch of the forceps through aortotomy is reported.

Endovascular Reintervention for Stent-Graft Dislocation after Open Surgical Conversion for Thoracoabdominal Aortic Aneurysm Treated by Thoracic Endovascular Aortic Repair.

Complex anatomical restrictions can lead to further interventions after the emergence of a postoperative aneurysm enlargement in thoracic endovascular aortic repair (TEVAR) for a thoracoabdominal aortic aneurysm (TAAA). A 75-year-old male underwent a TEVAR for a Crawford extent I TAAA. The main device and the distal extension were placed using a fenestrated technique, outside of the instructions for use. The aneurysm expanded because of an endoleak and stent graft migration; and was surgically repaired by fully salvaging the previous endografts 38 months after the first TEVAR. However, the distal extension, which was the proximal anastomosis site with a prosthetic graft, became completely dislocated from the main device eight months after the open surgical conversion, resulting again in the enlargement of the aneurysm. An additional TEVAR was successfully performed to correct the dislocated stent graft. An appropriate treatment strategy is crucial to prevent multiple reinterventions for TAAA with complex anatomical restrictions.

Challenges for the Development of Extracellular Vesicle-Based Nucleic Acid Medicines.

Nucleic acid drugs, such as siRNAs, antisense oligonucleotides, and miRNAs, exert their therapeutic effects by causing genetic changes in cells. However, there are various limitations in their delivery to target organs and cells, making their application to cancer treatment difficult. Extracellular vesicles (EVs) are lipid bilayer particles that are released from most cells, are stable in the blood, and have low immunogenicity. Methods using EVs to deliver nucleic acid drugs to target organs are rapidly being developed that take advantage of these properties. There are two main methods for loading nucleic acid drugs into EVs. One is to genetically engineer the parent cell and load the target gene into the EV, and the other is to isolate EVs and then load them with the nucleic acid drug. Target organ delivery methods include passive targeting using the enhanced permeation and retention effect of EVs and active targeting in which EVs are modified with antibodies, peptides, or aptamers to enhance their accumulation in tumors. In this review, we summarize the advantages of EVs as a drug delivery system for nucleic acid drugs, the methods of loading nucleic acid drugs into EVs, and the targeting of EVs to target organs.

Clinical Application of Laser Speckle Flowgraphy to Assess Changes in Blood Flow to the Foot After a Lumbar Sympathetic Ganglion Block: A Case Report.

BACKGROUND: The lumbar sympathetic ganglion block (LSGB) has been used as a diagnostic and therapeutic procedure for treating pain conditions such as neuropathic and ischemia-related pain, affecting the lower extremities. In general, an increase in skin temperature is useful in confirming the effectiveness of the sympathetic nerve block in clinical settings. However, the assessment of skin temperature in patients with peripheral arterial disease (PAD) occasionally provides false negatives. CASE PRESENTATION: A novel technology, laser speckle flowgraphy (LSFG) enables noninvasive quantitative and qualitative blood flow assessments. LSFG is a novel neuro-monitor for quantitative blood flow detection in the optic nerve head during cardiac surgery. Herein, we report on measuring foot blood flow using LSFG before and after LSGB in a PAD patient. This research aimed to determine whether LSFG could detect any improvement in the dynamics of foot blood flow after an LSGB in a situation where changes in skin temperature alone could not determine the procedure's outcome. CONCLUSION: LSFG can be used to assess blood flow changes in a foot with PAD, following a LSGB.

Collateral artery bypass in the infrapopliteal segment.

A 74-year-old man with diabetes and end-stage renal failure on regular dialysis required revascularization for gangrene of multiple toes and a heel ulcer on the right foot with chronic limb-threatening ischemia. However, the anterior tibial artery, posterior tibial artery, and peroneal artery, which are the usual targets below the knee, showed obstruction or calcification and were considered inappropriate bypass targets. Instead, a collateral artery developed along the area of the posterior tibial artery, and bypass surgery was performed with this artery. This is a case report showing successful collateral artery bypass grafting in the distal infrapopliteal segment.

A Case of Isolated Infragenicular Arterial Lesions Successfully Treated with Open Endarterectomy.

A 68-year-old man with a history of superior mesenteric arterial thromboembolism due to chronic atrial fibrillation had experienced intermittent claudication (IC) of his left leg for 3 years. Computed tomography angiography showed focal occlusive lesions in the left distal popliteal artery and proximal segments of the infrapopliteal arteries. Endarterectomy was performed for these localized arterial lesions, and a drastic symptomatic improvement of IC after revascularization was achieved. The endarterectomized segments remained patent for 4 years after the surgery. Endarterectomy could be a useful alternative to bypass surgery and endovascular therapy for the treatment of localized infragenicular arterial lesions.