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ACS Applied Bio Materials Jun 2024Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most...
Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3β/β-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.
PubMed: 38848346
DOI: 10.1021/acsabm.4c00252 -
Journal of Medical Case Reports Jun 2024Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the...
OBJECTIVE
Extravasation of infused drugs is not a rare problem in medical practice. Acyclovir is a vesicant and an antiviral medication commonly used for young children. In the present study, we presented a neonate with soft tissue damage due to acyclovir extravasation.
CASE REPORT
A female newborn (Iranian, Asian) with gestational age 37 weeks and breech presentation was born by Cesarean delivery from a mother with a recent history of Herpes simplex virus (HSV) infection (Yas Women's Hospital, Tehran, Iran). Intravenous administration of acyclovir was initiated through a peripheral catheter inserted on the dorsal side of the left hand. A few minutes after the second dose, the patient showed a diffused firm swelling, local discoloration, and induration in the dorsum of the hand. The peripheral catheter was removed immediately. Hyaluronidase was injected subcutaneously in five different regions around the catheterization site. Intermittent limb elevation and cold compression (for 10 minutes) were applied. Serial follow-ups and examinations were performed hourly to check limb inflammation, ischemia, and compartment syndrome. The limb swelling and discoloration significantly improved 4 hours after the second dose of hyaluronidase.
CONCLUSION
Early diagnosis of acyclovir extravasation and immediate management could prevent severe complications in neonates. Further studies are needed to suggest a standard approach and treatment protocol for acyclovir extravasation.
Topics: Humans; Acyclovir; Female; Infant, Newborn; Antiviral Agents; Extravasation of Diagnostic and Therapeutic Materials; Herpes Simplex; Hyaluronoglucosaminidase
PubMed: 38845030
DOI: 10.1186/s13256-024-04585-1 -
Journal of Nanobiotechnology Jun 2024Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including... (Review)
Review
Adipose-derived stem cells (ADSCs) are a subset of mesenchymal stem cells (MSCs) isolated from adipose tissue. They possess remarkable properties, including multipotency, self-renewal, and easy clinical availability. ADSCs are also capable of promoting tissue regeneration through the secretion of various cytokines, factors, and extracellular vesicles (EVs). ADSC-derived EVs (ADSC-EVs) act as intercellular signaling mediators that encapsulate a range of biomolecules. These EVs have been found to mediate the therapeutic activities of donor cells by promoting the proliferation and migration of effector cells, facilitating angiogenesis, modulating immunity, and performing other specific functions in different tissues. Compared to the donor cells themselves, ADSC-EVs offer advantages such as fewer safety concerns and more convenient transportation and storage for clinical application. As a result, these EVs have received significant attention as cell-free therapeutic agents with potential future application in regenerative medicine. In this review, we focus on recent research progress regarding regenerative medical use of ADSC-EVs across various medical conditions, including wound healing, chronic limb ischemia, angiogenesis, myocardial infarction, diabetic nephropathy, fat graft survival, bone regeneration, cartilage regeneration, tendinopathy and tendon healing, peripheral nerve regeneration, and acute lung injury, among others. We also discuss the underlying mechanisms responsible for inducing these therapeutic effects. We believe that deciphering the biological properties, therapeutic effects, and underlying mechanisms associated with ADSC-EVs will provide a foundation for developing a novel therapeutic approach in regenerative medicine.
Topics: Humans; Extracellular Vesicles; Regenerative Medicine; Adipose Tissue; Animals; Mesenchymal Stem Cells; Wound Healing; Regeneration
PubMed: 38844939
DOI: 10.1186/s12951-024-02603-4 -
Neuroimmunomodulation 2024Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune...
INTRODUCTION
Dimethyl fumarate (DMF) has shown potential for protection in various animal models of neurological diseases. However, the impact of DMF on changes in peripheral immune organs and the central nervous system (CNS) immune cell composition after ischemic stroke remains unclear.
METHODS
Eight-week-old C57BL/6J mice with photothrombosis ischemia and patients with acute ischemic stroke (AIS) were treated with DMF. TTC staining, flow cytometry, and immunofluorescence staining were used to evaluate the infarct volume and changes in immune cells in the periphery and the CNS.
RESULTS
DMF reduced the infarct volume on day 1 after PT. DMF reduced the percentages of peripheral immune cells, such as neutrophils, dendritic cells, macrophages, and monocytes, on day 1, followed by NK cells on day 3 and B cells on day 7 after PT. In the CNS, DMF significantly reduced the percentage of monocytes in the brain on day 3 after PT. In addition, DMF increased the number of microglia in the peri-infarct area and reduced the number of neurons in the peri-infarct area in the acute and subacute phases after PT. In AIS patients, B cells decreased in patients receiving alteplase in combination with DMF.
CONCLUSION
DMF can change the immune environment of the periphery and the CNS, reduce infarct volume in the acute phase, promote the recruitment of microglia and preserve neurons in the peri-infarct area after ischemic stroke.
Topics: Animals; Dimethyl Fumarate; Ischemic Stroke; Mice, Inbred C57BL; Mice; Male; Humans; Female; Prognosis; Middle Aged; Aged; Disease Models, Animal
PubMed: 38843787
DOI: 10.1159/000539589 -
Ophthalmic Genetics Jun 2024Familial Exudative Vitreoretinopathy (FEVR) is a heritable retinal vascular disease characterized by incomplete vascularization of the peripheral retina resulting in...
INTRODUCTION
Familial Exudative Vitreoretinopathy (FEVR) is a heritable retinal vascular disease characterized by incomplete vascularization of the peripheral retina resulting in ischemia. Fifty percent of FEVR cases 10 are due to known pathogenic genetic variants, and disease phenotype can vary greatly. FEVR is a clinical diagnosis, however, genetic testing can play a key role in screening for FEVR in genetically susceptible populations, thus leading to early treatment and improved patient outcomes.
CASE
A 2-year-old male with no known past ocular or medical history was diagnosed with FEVR upon examination under anesthesia and multimodal retinal imaging. Genetic testing identified a () variant of uncertain significance, 15 which has been linked to FEVR in recent studies. Despite close follow-up and treatment, the patient experienced a funnel retinal detachment in the right eye approximately one year after diagnosis.
DISCUSSION
This case in conjunction with recent literature suggests that variants are likely associated with FEVR. Further investigations are necessary to identify the frequency of variants among patients with FEVR. Robust understanding of FEVR's heterogenous genetic profile will lead to improved treatment modalities 20 and patient outcomes.
PubMed: 38836470
DOI: 10.1080/13816810.2024.2357303 -
European Heart Journal. Case Reports Jun 2024Buerger disease, also known as Winiwarter-Buerger disease or thromboangiitis obliterans (TAO), is a non-specific inflammation of small- and medium-sized arteries with...
BACKGROUND
Buerger disease, also known as Winiwarter-Buerger disease or thromboangiitis obliterans (TAO), is a non-specific inflammation of small- and medium-sized arteries with thrombus obliteration and without atherosclerotic changes. Patients with TAO can develop chronic limb-threatening ischaemia (CLTI) and are at risk of limb amputation despite smoking cessation and exercise therapy recommendations.
CASE SUMMARY
A 72-year-old Japanese man presented with painful discolouration of toes and renal impairment. He was diagnosed with Rutherford classification Stage 6 CLTI with immunoglobulin A nephropathy. He refused limb amputation. Clinical symptoms reduced after treatment with low-intensity pulsed ultrasound (LIPUS). LIPUS is a non-invasive option to alleviate peripheral arterial disease symptoms. Despite the initiation of conventional therapy measures, there was a worsening of the limb condition. The non-invasive investigational treatment option of LIPUS was initiated after the poor clinical outcomes of the conventional therapy measures. The patient's symptoms in the bilateral lower limbs, ulcers, and the blue-coloured toes gradually lessened. After 1 year of treatment with LIPUS, he had achieved better walking independence with improved quality of life.
DISCUSSION
Low-intensity pulsed ultrasound is a non-invasive option for therapeutic angiogenesis with the potential to improve ischaemic limb conditions in patients with peripheral arterial disease and to avoid major amputation procedures.
PubMed: 38835990
DOI: 10.1093/ehjcr/ytae246 -
Journal of Vascular Surgery Jun 2024We compared the efficacy of percutaneous deep venous arterialization (pDVA) in patients with no-option chronic limb-threatening ischemia in the hospital vs in...
OBJECTIVE
We compared the efficacy of percutaneous deep venous arterialization (pDVA) in patients with no-option chronic limb-threatening ischemia in the hospital vs in office-based laboratory (OBL) settings.
METHODS
A retrospective chart review was performed of all patients who underwent pDVA using off-the-shelf devices from January 2018 to March 2023 in a hospital and an OBL. We identified 73 eligible patients, 41 from a hospital setting (59% male; median age, 72 years; interquartile range, 18 years) and 32 from an OBL setting (59% males; 67 years; interquartile range, 16 years). All eligible patients were deemed to have no-option critical limb ischemia, had at least one patent proximal tibial artery available for the creation of an arteriovenous anastomosis, and were classified as having Rutherford classification IV or higher peripheral arterial disease. Patients were ineligible if classified as Rutherford classification III or lower, had active infection, did not have at least one appropriate venous target, and/or had rapidly progressing wounds requiring immediate major amputation. The primary outcome was major amputation-free survival (AFS). Secondary outcomes included technical success, limb salvage, survival, primary patency, reintervention rate, adverse events, and partial and complete wound healing. Outcomes were evaluated using Kaplan-Meier method, log-rank, and two-stage procedure tests.
RESULTS
Technical success was achieved in 70 patients (96%) with 1 hospital (2.4%) and 2 OBL (6.3%) patients lost to follow-up. Major AFS estimates at 6 months, 1 year, and 2 years were 51.4%, 40.4%, and 30.2% in the hospital group and 69.4%, 54.0%, and 49.5% in the OBL group, respectively. Partial wound healing estimates at 6 months, 1 year, and 2 years were 27.5%, 71.7%, and 81.2% in the hospital group and 62.7% at all time points in the OBL group. Complete wound healing estimates at 6 months, 1 year, and 2 years were 6.7%, 33.3%, and 33.3% in the hospital group and 5.3%, 37.7%, and 41.6% in the OBL group, respectively. There was no significant difference in major AFS (P = .13), limb salvage (P = .07), survival (P = .69), primary patency (P = .53), partial (P = .08), or complete wound healing (P = .79) between groups. Reintervention was performed in 8 hospital (20.5%) and 14 OBL (45.2%) patients.
CONCLUSIONS
pDVA is a feasible and safe procedure for no-option critical limb ischemia in the hospital and OBL setting without significant differences in outcomes at ≤2 years.
PubMed: 38830436
DOI: 10.1016/j.jvs.2024.05.051 -
Journal of Radiology Case Reports May 2023A 52-year-old male developed right knee pain after hiking in Guatemala. On his return he underwent a knee MRI for an indication of medial knee pain, which demonstrated a...
A 52-year-old male developed right knee pain after hiking in Guatemala. On his return he underwent a knee MRI for an indication of medial knee pain, which demonstrated a medial meniscal tear. However, the MRI demonstrated marked tortuosity and dense calcification of the popliteal artery, confirmed on subsequent radiographs. Review of previous CT studies of the abdomen and lower extremities showed severe ectasia and arterial calcification in the femoral and popliteal arteries bilaterally, but no calcifications in the aorta and common iliac arteries. Dual energy CT studies of the extremities demonstrated extensive periarticular soft tissue calcification throughout the wrists, hands, ankle and feet without evidence of uric acid. Review of the electronic medical records revealed a diagnosis of Arterial Calcification due to Deficiency of CD73 (ACDC), a rare genetic disorder presenting with debilitating pain in the wrists and hands, claudication of the calves, thighs and buttocks, progressing to chronic ischemia of the feet which may be limb-threatening. The patient was enrolled in an NIH trial of bisphosphonates and dual-antiplatelet therapy with stabilization of symptoms. This case discusses the imaging findings of this rare condition, differential diagnosis to consider, and current management.
Topics: Humans; Male; Middle Aged; Vascular Calcification; 5'-Nucleotidase; GPI-Linked Proteins; Diagnosis, Differential; Tomography, X-Ray Computed; Magnetic Resonance Imaging; Popliteal Artery
PubMed: 38828028
DOI: 10.3941/jrcr.v17i12.5175 -
Indian Journal of Thoracic and... May 2024Embolism is a common complication in infective endocarditis which may lead to serious complications, such as stroke, intestinal ischemia, and peripheral embolization. A... (Review)
Review
Embolism is a common complication in infective endocarditis which may lead to serious complications, such as stroke, intestinal ischemia, and peripheral embolization. A comprehensive literature search was performed and the registry at our centre, including 390 cases of infective endocarditis, diagnosed between 2010 and 2020, was investigated. Large registries show that 20-40% of patients with infective endocarditis (IE) are affected by embolism. In many instances, embolism is present already at the time of diagnosis. The rate of embolism during the hospital stay in our data was 11%. However, only 2% developed clinical embolism during or following surgery. According to recent guidelines, previous embolism, and the presence of vegetations > 10 mm present an indication for surgical treatment. Routine imaging revealed non-symptomatic cerebral embolism in 8.5% of surgical patients. However, it is not clear whether detection of non-symptomatic embolism and consecutive surgical treatment improves the prognosis of infective endocarditis.
PubMed: 38827555
DOI: 10.1007/s12055-023-01616-2 -
Scandinavian Journal of Surgery : SJS :... Jun 2024In retrospective studies, wound healing and leg salvage have been better if revascularization is targeted to the crural artery supplying arterial flow to the wound... (Comparative Study)
Comparative Study
BACKGROUND AND AIMS
In retrospective studies, wound healing and leg salvage have been better if revascularization is targeted to the crural artery supplying arterial flow to the wound angiosome. No data exist on how revascularization changes the blood flow in foot angiosomes. The aim of this study was to evaluate the change in perfusion after infrapopliteal artery revascularization in all foot angiosomes and to compare directly revascularized (DR) angiosomes to the indirectly revascularized (IR) angiosomes.
METHODS
In this prospective study, foot perfusion was measured with indocyanine green fluorescence imaging (ICG-FI) before and after either surgical or endovascular below-knee revascularization. According to angiograms, we divided the foot angiosomes into DR and IR angiosomes. Furthermore, in a subanalysis, the IR angiosomes were graded as IR_Coll+ angiosomes if there were strong collaterals arising from the artery which was revascularized, and as IR_Coll- angiosomes if strong collaterals were not seen.
RESULTS
A total of 72 feet (28 bypass, 44 endovascular revascularizations) and 282 angiosomes were analyzed. Surgical and endovascular revascularization increased perfusion significantly in both DR and IR angiosomes. After bypass surgery, the increase in DR angiosomes was 55 U and 53 U in IR angiosomes; there were no significant difference in the perfusion increase between IR and DR angiosomes. After endovascular revascularization, perfusion increased significantly more, 40 U, in DR angiosomes compared to 26 U in IR angiosomes (p < 0.05). In the subanalysis of IR angiosomes, perfusion increased significantly after surgical bypass regardless of whether strong collaterals were present or not. After endovascular revascularization, however, a significant perfusion increase was noted in the IR_Coll+ but not in the IR_Coll- subgroup.
CONCLUSION
Open revascularization increased perfusion equally in DR and IR angiosomes, whereas endovascular revascularization increased perfusion significantly more in DR than in IR angiosomes. Strong collateral network may help increase perfusion in IR angiosomes.
Topics: Humans; Prospective Studies; Aged; Male; Female; Foot; Middle Aged; Endovascular Procedures; Regional Blood Flow; Diabetic Foot; Peripheral Arterial Disease; Popliteal Artery; Aged, 80 and over; Treatment Outcome; Vascular Surgical Procedures
PubMed: 38825887
DOI: 10.1177/14574969241242205