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OBJECTIVES: In the treatment of chronic limb-threatening ischemia (CLTI), complete wound healing is an important goal. Although foot perfusion status seems to be important for wound healing, the global limb anatomic staging system (GLASS) of the Global Vascular Guidelines (GVG) does not include pedal artery status for the staging process due to the lack of sufficient evidence of its importance. This study aimed to clarify the importance of pedal perfusion status after bypass surgery. METHODS: Among the 153 CLTI cases that underwent bypass distal to popliteal arteries from 2014 to 2018, 117 CLTI limbs with wounds and with sufficient pedal angiographic data were enrolled. They were classified into two groups, based on the wound status 6 months postoperatively; early wound healing group (EWG, N=78), which achieved complete wound healing within 6 months postoperatively, and prolonged healing or unhealed wounds group (PWG, N=39), which failed to achieve wound healing within 6 months. Various factors associated with wound healing, including the wound, ischemia, and foot infection (WIfI) classification, intraoperative graft flow, and pedal angiographic data, were analyzed. Regarding pedal angiographic data, in addition to the GLASS inframalleolar/pedal disease descriptor (IPD), newly formed classification system of the pedal circulation status in association with the location of wounds was included: pedal circulation status was classified into two groups as visualized arterial perfusion towards wounds (visualized perfusion) and non-visualized arterial perfusion towards wounds (non-visualized perfusion). RESULTS: Univariate analysis showed preoperative albumin (Odds ratio [OR], 0.47; 95% confidence interval [CI], 0.24-0.94; P=.027), higher WIfI clinical stage (OR, 3.88; 95%CI, 1.74-10.1; P=.0005), higher IPD (OR, 2.16; 95%CI, 1.16-4.02; P=.012), and non-visualized perfusion to wounds (OR, 5.74: 95%CI, 2.45-14.0; P < .0001) as significant for prolonged wound healing. Multivariate analysis showed higher WIfI stage (OR, 5.04; 95%CI, 1.74-14.6; P=.0029) and non-visualized perfusion to wounds (OR, 4.34; 95%CI, 1.71-11.0; P=.0021) as significant, while IPD was not detected as significant. Regarding blood supply to the foot, although graft flow was significantly lower in IPD-P2 than IPD-P0/P1, graft flow was similar regardless of the status of angiographic circulation to wounds, suggesting that distribution of blood supply to the wound would be more important than total amount of blood supply to the foot for wound healing. CONCLUSIONS: WIfI clinical stage and pedal circulatory environment were important factors for wound healing after bypass surgery. Pedal anatomical classification system including perfusion status would be important for decision making in CLTI treatment.
Subject(s)
Arthritis, Rheumatoid , Humans , Arthritis, Rheumatoid/drug therapy , Arthritis, Rheumatoid/complications , Female , Aged , Japan , East Asian PeopleABSTRACT
BACKGROUND: Pseudo-Kaposi sarcoma (PKS) is a rare vascular proliferative disease, caused by arteriovenous malformation (AVM) and chronic venous insufficiency. The lesions are characterized by purple or reddish-brownish papules, plaques, and nodules. Although benign, it is clinically similar to Kaposi's sarcoma (KS), a malignant disease, and must be differentiated by histopathological examination. We report a rare case of PKS with chronic limb-threatening ischemia (CLTI). CASE PRESENTATION: An 83-year-old man with diabetes mellitus (DM) presented to a local dermatology department with a complaint of a right second toe ulcer and was, thereby, referred to our department due to arterial bleeding during skin biopsy to exclude malignant diseases. Although the pulsation of dorsalis pedis artery of the affected limb was palpable, the skin perfusion pressure was only 20 and 30 mmHg on the dorsum and planter surface, respectively, indicating severe ischemia of toe and forefoot. Ultrasonography and computed tomography revealed an AVM around the right second metatarsophalangeal joint and occlusion of the right dorsalis pedis artery in the middle, indicating CLTI in the background. Pathological findings of the skin biopsy found capillary blood vessel proliferation, hemosiderin deposition, and extravascular red blood cell leakage in the dermal layer, which could be found in KS. However, CD34 was normally stained in the vascular endothelium, and human herpesvirus-8 staining was negative, resulting in the pathological diagnosis of PKS, a proliferative vascular lesion associated with AVM. The ulcer was spontaneously epithelialized, but 2 years later the ulcer recurred and infection developed, necessitating treatment for abnormal blood flow. Transarterial embolization using N-butyl 2-cyanoacrylate for the AVM controlled abnormal perfusion once; however, the procedure exacerbated perfusion of the toe, resulting in foot ulcer progression. Forefoot amputation with surgical excision of AVM was performed, and thereby, wound healing was achieved. CONCLUSION: This is a rare case of PKS with CLTI complicated with AVM. As there is currently no established consensus on the treatment of PKS, the approach to treatment strategy should be tailored to the specific condition of each patient.
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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.
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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.).
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
Subject(s)
Colitis, Ulcerative , Fasciitis , Adult , Colitis, Ulcerative/complications , Colitis, Ulcerative/drug therapy , Fasciitis/complications , Fasciitis/etiology , Humans , Magnetic Resonance Imaging , Male , Myalgia/complications , PrednisoloneABSTRACT
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.
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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.
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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.
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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.
Subject(s)
Antibodies, Monoclonal , Chromatography, Affinity/methods , Filtration/methods , Viruses/isolation & purification , Animals , CHO Cells , Cricetinae , Cricetulus , Recombinant Proteins/standardsABSTRACT
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.
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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.
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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.