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1.
Ren Fail ; 43(1): 1311-1321, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34547972

ABSTRACT

Intravenous contrast media (CM) is often used in clinical practice to enhance CT scan imaging. For many years, contrast-induced nephropathy (CIN) was thought to be a common occurrence and to result in dire consequences. When treating patients with abnormal renal function, it is not unusual that clinicians postpone, cancel, or replace contrast-enhanced imaging with other, perhaps less informative tests. New studies however have challenged this paradigm and the true risk attributable to intravenous CM for the occurrence of CIN has become debatable. In this article, we review the latest relevant medical literature and aim to provide an evidence-based answer to questions surrounding the risk, outcomes, and potential mitigation strategies of CIN after intravenous CM administration.


Subject(s)
Acute Kidney Injury/chemically induced , Contrast Media/administration & dosage , Acute Kidney Injury/epidemiology , Acute Kidney Injury/prevention & control , Administration, Intravenous/adverse effects , Contrast Media/adverse effects , Humans , Injections, Intra-Arterial/adverse effects , Kidney Failure, Chronic/etiology , Randomized Controlled Trials as Topic , Risk Factors , Tomography, X-Ray Computed
2.
Pediatr Neurosurg ; 55(5): 295-298, 2020.
Article in English | MEDLINE | ID: mdl-33176321

ABSTRACT

INTRODUCTION: The intra-arterial chemotherapy (IAC) is increasingly used as a first-line therapy for retinoblastoma. The IAC has proved to be relatively safe. However, many local side effects of IAC have been described. CASE PRESENTATION: This case report describes a local side effect presenting as proptosis and myositis with vascular access difficulty of the middle meningeal artery, in a 2-year-old male with left eye diffuse multifocal stage Vb retinoblastoma complicated with retinal detachment. DISCUSSION/CONCLUSION: IAC is assured to provide as efficient results in eliminating the tumor as the systemic chemotherapy, without causing the systemic side effects. It has become an alternative to systemic chemotherapy. A better understanding of the local side effects is required.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/adverse effects , Chromosome Disorders/drug therapy , Injections, Intra-Arterial/adverse effects , Orbital Diseases/chemically induced , Retinal Neoplasms/drug therapy , Retinoblastoma/drug therapy , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Child, Preschool , Chromosome Deletion , Chromosome Disorders/complications , Chromosome Disorders/diagnostic imaging , Chromosomes, Human, Pair 13 , Exophthalmos/chemically induced , Exophthalmos/diagnostic imaging , Humans , Injections, Intra-Arterial/methods , Intravitreal Injections/methods , Male , Meningeal Arteries/diagnostic imaging , Meningeal Arteries/drug effects , Myositis/chemically induced , Myositis/diagnostic imaging , Orbital Diseases/diagnostic imaging , Retinal Neoplasms/complications , Retinal Neoplasms/diagnostic imaging , Retinoblastoma/complications , Retinoblastoma/diagnostic imaging
3.
Curr Neurovasc Res ; 17(3): 312-318, 2020.
Article in English | MEDLINE | ID: mdl-32294038

ABSTRACT

BACKGROUND: The pathogenic mechanisms involved in a disastrous scenario, following epidural steroid injections (ESI), remain unclarified. Intra-arterial injection of steroids with needlepenetrating vascular injury would be the culprit, as particulate medicine elicits a brain or spinal cord stroke-like attack. METHODS: On the other hand, the limited experimental approaches simulating an accidental steroid intra-arterial injection for ESI conflicted in their results: hemorrhage vs. ischemia. RESULTS: This article dissects the potential pathogenic mechanisms at a neurovascular unit. Noticeably, a schematic representation provides an explanation of how emboli formed by particulate steroids elicit either hemorrhagic, or ischemic lesion. CONCLUSION: In addition, the development of a rat model with intravertebral artery steroid injection is a proposal to address the unmet need in evaluating steroids and vascular injury in ESI.


Subject(s)
Analgesia, Epidural/adverse effects , Brain/drug effects , Injections, Intra-Arterial/adverse effects , Steroids/toxicity , Stroke/chemically induced , Analgesia, Epidural/methods , Animals , Brain/blood supply , Brain/pathology , Carotid Artery, Common/drug effects , Injections, Intra-Arterial/methods , Rats , Steroids/administration & dosage , Stroke/pathology
4.
Eur J Vasc Endovasc Surg ; 59(6): 1019-1025, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32014339

ABSTRACT

OBJECTIVE: Ultrasound guided thrombin injection (UGTI) is a minimally invasive method of treatment for iatrogenic post-catheterisation femoral pseudoaneurysms (psAs). The optimal dosing protocol for UGTI has not been established. The aim of the study was to compare the success and complication rates between two different dosing protocols (the most commonly used "standard dose protocol" and the "low dose protocol," which is the fractionated administration of smaller thrombin doses of up to 40 IU every 15 s) in patients with a psA with sac volume of ≥1 mL. METHODS: This was a retrospective cohort study, and the analysis was performed using a case matching approach based on propensity score. From June 2004 to August 2018, 384 patients who underwent femoral puncture for transcatheter procedures were diagnosed with femoral psA with a sac volume of ≥1 mL and qualified for UGTI. The patients' mean age was 68 (±10.6) years and there were 217 (56.5%) women. To compare protocols, 124 patients treated according to the low dose protocol were nearest neighbour matched according to their propensity score to 124 patients treated according to the standard dose protocol. RESULTS: The overall success rate (99.2% vs. 98.4%; p = 1) and success rate of the first UGTI attempt (87.1% vs. 86.3%; p = .85) did not differ between the low dose and standard dose groups. Complications were less common in the low dose group (7.3% vs. 16.1%; p = .03) and the median total amount of thrombin used for procedures was smaller in the low dose group (120 IU vs. 195 IU; p = .01). CONCLUSIONS: In patients with femoral psA with sac volume of ≥1 mL, the use of the low dose protocol seemed to be equally effective as the standard dose protocol and was associated with a lower complication rate and reduced thrombin dose.


Subject(s)
Aneurysm, False/drug therapy , Catheterization/adverse effects , Femoral Artery/drug effects , Postoperative Complications/epidemiology , Thrombin/administration & dosage , Aged , Aneurysm, False/diagnostic imaging , Aneurysm, False/etiology , Aneurysm, False/pathology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Femoral Artery/diagnostic imaging , Femoral Artery/injuries , Femoral Artery/pathology , Humans , Iatrogenic Disease , Injections, Intra-Arterial/adverse effects , Injections, Intra-Arterial/methods , Male , Middle Aged , Postoperative Complications/etiology , Retrospective Studies , Thrombin/adverse effects , Treatment Outcome , Ultrasonography, Interventional
5.
Cardiovasc Interv Ther ; 35(4): 371-378, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31939068

ABSTRACT

We investigated the effect of the papaverine dose increment method to confirm maximal hyperemia for fractional flow reserve (FFR) measurements. We evaluated 115 consecutive patients involving 200 lesions. FFR was measured after intracoronary papaverine injection into the left (12 mg) and right (8 mg) coronary arteries as standard doses. Except for 2 patients who had ventricular tachyarrythmia (VTA), we administered a higher papaverine dose (2 mg added to the standard dose). We compared the FFR values after using different papaverine doses. VTA incidence and electrocardiogram parameters were compared according to the papaverine doses used. The QTU interval and corrected QTU were significantly prolonged after using a higher dose compared with a standard dose. VTA occurred in one patient (0.9%) at the higher dose. There was no significant difference with a strong correlation between the FFR values in the 2 doses (r = 0.963, P < 0.001). Maximal hyperemia was achieved in most patients at the standard papaverine dose. However, 19 lesions changed ischemic diagnosis at the higher dose (12 lesions changed from ischemia negative to positive, and 7 lesions changed from positive to negative). Therefore, to confirm the appropriate ischemia diagnosis for borderline FFR values, it may be favorable to perform another FFR measurement at an incremental papaverine dose.


Subject(s)
Coronary Vessels/drug effects , Fractional Flow Reserve, Myocardial/drug effects , Hyperemia/chemically induced , Myocardial Ischemia , Papaverine/administration & dosage , Vasodilator Agents/administration & dosage , Aged , Coronary Angiography , Coronary Stenosis/diagnostic imaging , Coronary Stenosis/physiopathology , Coronary Vessels/diagnostic imaging , Coronary Vessels/physiopathology , Dose-Response Relationship, Drug , Electrocardiography , Female , Fractional Flow Reserve, Myocardial/physiology , Hemodynamics , Humans , Hyperemia/physiopathology , Injections, Intra-Arterial/adverse effects , Male , Middle Aged , Myocardial Ischemia/diagnostic imaging , Myocardial Ischemia/drug therapy , Myocardial Ischemia/physiopathology , Papaverine/adverse effects , Papaverine/therapeutic use , Percutaneous Coronary Intervention/methods , Risk Assessment , Tachycardia, Ventricular/chemically induced , Tachycardia, Ventricular/diagnosis , Vasodilator Agents/adverse effects , Vasodilator Agents/therapeutic use
7.
Ren Fail ; 41(1): 341-353, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31057054

ABSTRACT

OBJECTIVES: The aim of this study was to evaluate and compare the severity of acute kidney injury (AKI) induced by iodine contrast agent injection via the renal artery, ear vein, and femoral artery in a rabbit model. METHODS: Blood oxygenation level-dependent (BOLD) magnetic resonance (MR) scans were performed at 24 h prior to contrast injection and 1, 24, 48, and 72 h after injection. Iodixanol injection dose was 1.0, 1.5, 2.0, and 2.5 g iodine/kg, respectively. Hypoxia-inducible factor-1α (HIF-1α) expression was determined, and the BOLD-MRI parameter R2* was used to express tissue oxygenation. Increases in R2* levels reflect reductions in tissue oxygenation. Analyses including R2* value, dose response, histology, and HIF-1α were conducted. RESULT: Injection of 1.0 g iodine/kg into the left renal artery resulted in significant increases in renal R2* values after 24 h. This was equivalent to the change of R2* after 2.0 g iodine/kg femoral artery injection. Renal injury scores and HIF-1α expression scores were significantly increased at 24 h. The R2* values exhibited a positive linear correlation with histological injury scores. The maximum effects occurred 24 h after iodixanol injection and returned to baseline levels within 72 h. CONCLUSIONS: The renal injury induced by 1.0 g iodine/kg iodixanol through renal artery injection was more significant than that caused by the same dose of femoral artery and auricular vein injection, while similar to that caused by 2.0 g iodine/kg femoral artery injection.


Subject(s)
Acute Kidney Injury/diagnosis , Contrast Media/adverse effects , Acute Kidney Injury/blood , Acute Kidney Injury/chemically induced , Animals , Contrast Media/administration & dosage , Disease Models, Animal , Ear Auricle/blood supply , Femoral Artery , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Injections, Intra-Arterial/adverse effects , Injections, Intra-Arterial/methods , Injections, Intravenous/adverse effects , Injections, Intravenous/methods , Kidney/diagnostic imaging , Kidney/drug effects , Kidney/pathology , Magnetic Resonance Imaging , Male , Oxygen/blood , Rabbits , Renal Artery , Severity of Illness Index , Triiodobenzoic Acids/administration & dosage , Triiodobenzoic Acids/adverse effects
9.
J Plast Reconstr Aesthet Surg ; 72(1): 131-136, 2019 Jan.
Article in English | MEDLINE | ID: mdl-30327185

ABSTRACT

BACKGROUND: Over the past decade, cosmetic injections of dermal fillers or fat have become a popular procedure in facial rejuvenation in an overconsuming society. However, complications such as arterial embolism and occlusion can occur even with experienced injectors, especially in high-risks zones namely the glabella, the nasal dorsum or the nasolabial fold. The aim of this study was to define the vascular danger zones of the infraorbital area in order to provide guidelines helping avoid them. MATERIALS AND METHODS: The infraorbital artery, its main branches and their anastomoses with neighbouring vessels were studied in 18 fresh cadavers. Mimetic injections of inked hyaluronic acid were performed in the infraorbital area in the interest of analyzing its distribution and to determine potential vascular risks towards the infraorbital artery and its branches. RESULTS: The infraorbital artery and its branches were located in common injection regions and anastomosed to the supratrochlear artery, the dorsal nasal artery and the angular artery through the nasal branch of the infraorbital artery. Two danger zones could be depicted: injections can be risky when performed too superficially in the midcheek area, and likewise risky when performed in a periosteal layer in infraorbital hollow or tear-trough correction, because of an obvious possibility of retrograde embolism. CONCLUSION: The infraorbital artery can be involved in anatomic mechanism of arterial occlusion, further blindness and stroke, among the related neighbouring arteries. Based on the findings of this study, injections to the periosteum layer in tear-trough correction and above the periosteum on the zygomatic arch is not advised.


Subject(s)
Esthetics , Ophthalmic Artery/anatomy & histology , Cadaver , Cosmetic Techniques/adverse effects , Dermal Fillers/adverse effects , Face , Humans , Hyaluronic Acid/administration & dosage , Hyaluronic Acid/pharmacology , Injections, Intra-Arterial/adverse effects , Rejuvenation , Risk Factors
10.
Prog. obstet. ginecol. (Ed. impr.) ; 61(4): 384-386, jul.-ago. 2018. ilus
Article in Spanish | IBECS | ID: ibc-174982

ABSTRACT

Presentamos a una gestante de 40 años, en la semana 12+6. Al obtener riesgo alto en el cribado del primer trimestre, se procedió a la biopsia corial por vía abdominal. Cuando se introdujo el anestésico local, la paciente comenzó con un dolor punzante sobre la zona de inyección, cambiando inmediatamente de color a rojo vinoso. Tras consultar con dermatología, se diagnosticó de síndrome de Nicolau, un vasoespasmo agudo por la inyección intraarterial de anestésico, que lleva a necrosis del tegumento cutáneo subsidiario a este. Dada la escasa prevalencia de esta afección, consideramos necesario elaborar una revisión bibliográfica sobre este síndrome


We present a 40-year-old pregnant woman, at week 12 + 6. By getting high risk in the first three months period screening, we abdominally proceeded to chorionic villus sampling. When the local anesthetic was introduced, the patient began with a shooting pain on the injection site, changing into a wine-red colour. After consultating with dermatology, she was diagnosed with Nicolau syndrome, an acute vasospasm by intra-arterial injection of anesthetic, leading to necrosis of the skin integument that depends on this. Given the low prevalence of this condition, we consider necessary to develop a literature review on this syndrome


Subject(s)
Humans , Female , Pregnancy , Adult , Chorionic Villi Sampling/methods , Nicolau Syndrome/diagnosis , Injections, Intra-Arterial/adverse effects , Anesthesia/adverse effects , Vasoconstriction
11.
J Cutan Pathol ; 45(5): 365-368, 2018 May.
Article in English | MEDLINE | ID: mdl-29430677

ABSTRACT

Injection drug abuse (IDA) is known to cause a spectrum of systemic and cutaneous complications. Despite the increasing incidence of IDA around the world, there is a paucity of literature discussing cutaneous complications from a dermatopathologic perspective. We present a case of a 35-year-old male with a complex medical history of Von Willebrand disease, Beçhet disease and diverticular disease. Following a sigmoidectomy/colostomy for diverticular perforation, he presented with fever and an indurated right arm displaying livedoid purpura. The right distal fingertips showed purpura with focal ulceration. A punch biopsy of the right wrist did not show evidence of inflammatory vasculitis or pyogenic infection, but instead showed a focus of polarizing, refractile material occluding a dilated arterial lumen within the mid-dermis. The patient admitted to injecting a suspension of crushed ondansetron (Zofran) tablets into the antecubital area to control post-operative nausea. It is known that direct intravascular injection of foreign material can cause distal ischemia and necrosis, either by local vasoconstriction, thrombosis, or formation of microemboli, as in this patient. Our objective is to bring awareness to this rarely reported phenomenon, and to raise clinical suspicion for IDA when confronted with such a unique vasculopathic pattern.


Subject(s)
Antiemetics/administration & dosage , Foreign Bodies/etiology , Injections, Intra-Arterial/adverse effects , Ondansetron/administration & dosage , Prescription Drug Misuse/adverse effects , Adult , Antiemetics/adverse effects , Diverticulitis, Colonic/complications , Diverticulitis, Colonic/surgery , Embolism/etiology , Foreign Bodies/pathology , Humans , Male , Ondansetron/adverse effects , Oxycodone/administration & dosage , Oxycodone/adverse effects , Postoperative Nausea and Vomiting/prevention & control , Tablets/adverse effects
12.
Indian J Pharmacol ; 50(6): 354-357, 2018.
Article in English | MEDLINE | ID: mdl-30783330

ABSTRACT

Gangrenous changes in skin due to accidental intra-arterial injection of promethazine and pentazocine have been reported. Accidental intra-arterial injection is most commonly encountered in the antecubital fossa. However, recent reports in the radial and ulnar arteries have also been encountered. We hereby report a serious, preventable adverse drug experience in the form of digital gangrene induced by inadvertent intra-arterial cocktail injection of anesthetic agents such as pentazocine, promethazine, and atropine, which seems to be in the radial artery as the lateral three digits and dorsum of the hand are affected.


Subject(s)
Anesthetics/administration & dosage , Fingers/pathology , Gangrene/etiology , Injections, Intra-Arterial/adverse effects , Medication Errors , Amputation, Surgical , Atropine/administration & dosage , Female , Fingers/surgery , Gangrene/diagnosis , Gangrene/surgery , Humans , Middle Aged , Pentazocine/administration & dosage , Promethazine/administration & dosage
13.
Hand (N Y) ; 12(5): 507-511, 2017 09.
Article in English | MEDLINE | ID: mdl-28832211

ABSTRACT

BACKGROUND: Sublingual buprenorphine/naloxone, a common treatment for opioid dependence, is frequently abused by intravenous injection. Inadvertent intra-arterial injection of buprenorphine/naloxone can produce acute ischemic insult to the hand due to gelatin embolism. Our purpose was to review a series of these patients in order to describe the clinical entity, review the outcomes, and propose a rational treatment algorithm. METHODS: Clinical records of all patients evaluated by the hand surgery team between 2011 and 2015 for ischemia of the hand after buprenorphine/naloxone injection were reviewed. Treatment, complications, and amount of tissue loss were recorded. Patients presenting within 48 hours of the injection were treated with intravenous heparin for 5 days, followed by oral aspirin and clopidogrel for 30 days. Those presenting after 48 hours were treated with aspirin and clopidogrel only. RESULTS: Ten patients presented during the review period. Average follow-up time was 13 weeks. Eight had ischemia of the radial side of the hand, 1 of the ulnar side, and 1 had bilateral ischemia. Three patients were treated with intravenous heparin and 5 with oral agents. Two presented with dry gangrene and did not receive anticoagulation. All patients experienced tissue loss. There was no difference in outcome regardless of treatment. CONCLUSIONS: With the increasing use of sublingual buprenorphine/naloxone in opioid dependency, ischemic hand injuries will be seen with greater frequency. Whereas outcomes did not vary with treatment modality in this series, further study is needed to determine the most effective treatment of these injuries.


Subject(s)
Buprenorphine, Naloxone Drug Combination/adverse effects , Hand/blood supply , Injections, Intra-Arterial/adverse effects , Ischemia/chemically induced , Narcotic Antagonists/adverse effects , Opioid-Related Disorders/complications , Adult , Aspirin/therapeutic use , Clopidogrel/therapeutic use , Female , Fibrinolytic Agents/therapeutic use , Heparin/therapeutic use , Humans , Ischemia/drug therapy , Male , Middle Aged , Opiate Substitution Treatment/adverse effects , Opioid-Related Disorders/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Retrospective Studies , Young Adult
14.
J Ayub Med Coll Abbottabad ; 29(2): 230-233, 2017.
Article in English | MEDLINE | ID: mdl-28718237

ABSTRACT

BACKGROUND: Accidental intra-arterial drug injections usually occur as an iatrogenic complication but it is also found in drug abusers as a result of attempted intravenous (IV) injections. It is estimated that accidental intra-arterial injections are found in 1:3500-1:56000 patients visiting emergency department. METHODS: This was cross sectional study performed in cardiovascular department Lady reading Hospital Peshawar from 1.1.2013 to 31.8.2015. Accidental intra-arterial injection was defined as intravenous injection in upper limb for any illness which is followed by sudden severe pain in limb followed by bluish discoloration of any part of limb. Data was analysed using SPSS-20. Frequency and percentage were calculated for categorical variables like while Means±SD was calculated for numerical variables. Chi square test was used to compare Categorical variables. RESULTS: Total 30 patients were studied in whom 17 were male. Mean age of the study population was 43.2±17.9 years. All patients after admission were put on intravenous Heparin alone or in combination with Dexamethason, Beraprost and Nifedifin on discretion of visiting consultant. Injection diclofenac were found more frequently as cause of limb ischemia (43 %). Amputation of digits or part of limb was noted in 7 (23.1 %) cases. CONCLUSIONS: Accidental intra-arterial injection can lead to limb ischemia and even limb loss so while injecting IV drugs, care should be taken to use venous site away from arterial sites.


Subject(s)
Injections, Intra-Arterial/adverse effects , Ischemia/etiology , Upper Extremity , Adult , Cross-Sectional Studies , Humans , Iatrogenic Disease , Middle Aged , Pain/etiology , Upper Extremity/blood supply , Upper Extremity/physiopathology
15.
Int J Cardiol ; 244: 77-83, 2017 Oct 01.
Article in English | MEDLINE | ID: mdl-28622945

ABSTRACT

AIMS: Systematic review of literature to evaluate safety of intracoronary (i.c.) pharmacologic testing with acetylcholine (ACh), or ergonovine (ERGO), to induce coronary artery spasm. METHODS AND RESULTS: Review of all relevant publications using MEDLINE and EMBASE databases yielded 10 publications, totalling 9,444 patients. Prevalence of provoked spasm varied from 2.3% to 54.7% of patients tested in the selected studies. The wide variability in prevalence was due to heterogeneity of study populations and provocation protocols. No deaths were reported. Overall occurrence of major (0.8%) and minor (4.7%) complications for i.c. pharmacologic testing was low. Compared to ERGO, ACh showed significantly higher rate of major (1.09% vs 0.15%; p<0.001) and minor complications (5.87% vs 2.36%; p<0.001). CONCLUSION: Provocative testing with i.c. ACh or ERGO are safe and can facilitate the diagnosis of inducible coronary artery spasm during diagnostic coronary angiography. These tests should be part of the routine armamentarium of interventional cardiologists.


Subject(s)
Acetylcholine/administration & dosage , Coronary Angiography/methods , Coronary Vasospasm/chemically induced , Coronary Vasospasm/diagnostic imaging , Ergonovine/administration & dosage , Acetylcholine/adverse effects , Ergonovine/adverse effects , Humans , Injections, Intra-Arterial/adverse effects , Oxytocics/administration & dosage , Oxytocics/adverse effects , Vasodilator Agents/administration & dosage , Vasodilator Agents/adverse effects
18.
J Addict Med ; 11(1): 77-79, 2017.
Article in English | MEDLINE | ID: mdl-28027191

ABSTRACT

Intravenous injection of drugs is associated with a host of medical complications, notably soft-tissue infections. On the contrary, intra-arterial injections of drugs have also been reported, largely restricted to inadvertent injections. Here we describe a patient who engaged in repeated intra-arterial injections of heroin when she exhausted most of her venous access, and presented acutely with a radial artery occlusion requiring thrombolytic therapy. Clinicians should have a high index of suspicion for intra-arterial injection in injection drug users who present with limb pain, ischemia, and motor/sensory deficits. Given the reluctance patients may have in discussing their injection practices, clinicians should proactively discuss and counsel patients about safe injection practices and the dangers of intra-arterial injections.


Subject(s)
Arterial Occlusive Diseases/etiology , Heroin Dependence/complications , Injections, Intra-Arterial/adverse effects , Radial Artery/pathology , Adult , Arterial Occlusive Diseases/drug therapy , Female , Humans , Thrombolytic Therapy
19.
Cell Transplant ; 26(2): 283-292, 2017 02 16.
Article in English | MEDLINE | ID: mdl-27725029

ABSTRACT

Glioblastoma multiforme (GBM) is the most common and most severe form of malignant gliomas. The prognosis is poor with current combinations of pharmaceutical, radiotherapy, and surgical therapy. A continuous search for new treatments has therefore been ongoing for many years. Therapy with tumor-infiltrating lymphocytes (TILs) is a clinically promising strategy to treat various cancers, including GBM. An endovascular intra-arterial injection of TILs as a method of delivery may, instead of intravenous infusion, result in better retention of effector cells within the tumor. Prior to clinical trials of intra-arterial injections with any cells, preclinical safety data with special emphasis on embolic-ischemic events are necessary to obtain. We used native rabbits as a model for intra-arterial injections with routine clinical catheter material and a clinical angiography suite. We selectively infused a total dose of 20 million activated T cells at a cell concentration of 4,000 cells/µl over 8 min of injection time. The rabbits were evaluated for ischemic lesions by 9.4 T magnetic resonance imaging (MRI) (n = 6), and for tracking of injected cells, single-photon emission computed tomography/computed tomography (SPECT/CT) was used (n = 2). In this study, we show that we can selectively infuse activated T cells to a CNS volume of 3.5 cm3 (estimated from the volumetric MRI) without catastrophic embolic-ischemic adverse events. We had one adverse event with a limited basal ganglia infarction, probably due to catheter-induced mechanical occlusion of one of the lateral lenticulostriatal arteries. The cells pass through the native brain without leaving SPECT signals. The cells then, over the first hours, end up in the liver to a large extent and to a lesser degree by the spleen, pancreas, and kidneys. Virtually no uptake could be detected in the lungs. This indicates a difference in biodistribution as opposed to other cell types when infused intravenously.


Subject(s)
Brain/metabolism , Injections, Intra-Arterial/adverse effects , Injections, Intra-Arterial/methods , Magnetic Resonance Imaging/methods , T-Lymphocytes/physiology , Tomography, Emission-Computed, Single-Photon/methods , Tomography, X-Ray Computed/methods , Animals , Female , Glioblastoma/metabolism , Humans , Rabbits
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