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1.
Mil Med Res ; 11(1): 39, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902798

ABSTRACT

BACKGROUND: Despite the efficacy of absolute ethanol (EtOH), its radiolucency introduces several risks in interventional therapy for treating vascular malformations. This study aims to develop a novel radiopaque ethanol injection (REI) to address this issue. METHODS: Iopromide is mixed with ethanol to achieve radiopacity and improve the physicochemical properties of the solution. Overall, 82 male New Zealand white rabbits are selected for in vivo radiopacity testing, peripheral vein sclerosis [animals were divided into the following 5 groups (n = 6): negative control (NC, saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), low-dose REI (L-D REI, 0.125 ml/kg), moderate-dose REI (M-D REI, 0.250 ml/kg), and high-dose REI (H-D REI 0.375 ml/kg)], pharmacokinetic analyses (the blood sample was harvested before injection, 5 min, 10 min, 20 min, 40 min, 1 h, 2 h, 4 h, and 8 h after injection in peripheral vein sclerosis experiment), peripheral artery embolization [animals were divided into the following 5 groups (n = 3): NC (saline, 0.250 ml/kg), positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)], kidney transcatheter arterial embolization [animals were divided into the following 4 groups (n = 3): positive control (EtOH, 0.250 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg); each healthy kidney was injected with saline as negative control], and biosafety evaluations [animals were divided into the following 5 groups (n = 3): NC (0.250 ml/kg), high-dose EtOH (0.375 ml/kg), L-D REI (0.125 ml/kg), M-D REI (0.250 ml/kg), and H-D REI (0.375 ml/kg)]. Then, a prospective cohort study involving 6 patients with peripheral venous malformations (VMs) is performed to explore the clinical safety and effectiveness of REI. From Jun 1, 2023 to August 31, 2023, 6 patients [age: (33.3 ± 17.2) years] with lingual VMs received sclerotherapy of REI and 2-month follow-up. Adverse events and serious adverse events were evaluated, whereas the efficacy of REI was determined by both the traceability of the REI under DSA throughout the entire injection and the therapeutic effect 2 months after a single injection. RESULTS: The REI contains 81.4% ethanol (v/v) and 111.3 mg/ml iodine, which can be traced throughout the injection in the animals and patients. The REI also exerts a similar effect as EtOH on peripheral venous sclerosis, peripheral arterial embolization, and renal embolization. Furthermore, the REI can be metabolized at a similar rate compared to EtOH and Ultravist® and did not cause injury to the animals' heart, liver, spleen, lungs, kidneys and brain. No REI-related adverse effects have occurred during sclerotherapy of VMs, and 4/6 patients (66.7%) have achieved complete response at follow-up. CONCLUSION: In conclusion, REI is safe, exerts therapeutic effects, and compensates for the radiolucency of EtOH in treating VMs. TRIAL REGISTRATION: The clinical trial was registered as No. ChiCTR2300071751 on May 24 2023.


Subject(s)
Ethanol , Vascular Malformations , Animals , Rabbits , Ethanol/therapeutic use , Ethanol/pharmacology , Male , Vascular Malformations/therapy , Vascular Malformations/drug therapy , Humans , Contrast Media/pharmacokinetics , Contrast Media/pharmacology , Contrast Media/therapeutic use , Iohexol/analogs & derivatives
2.
Comput Biol Med ; 172: 108132, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38508058

ABSTRACT

BACKGROUND: So far, baseline Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI) has played a key role for the application of sophisticated artificial intelligence-based models using Convolutional Neural Networks (CNNs) to extract quantitative imaging information as earlier indicators of pathological Complete Response (pCR) achievement in breast cancer patients treated with neoadjuvant chemotherapy (NAC). However, these models did not exploit the DCE-MRI exams in their full geometry as 3D volume but analysed only few individual slices independently, thus neglecting the depth information. METHOD: This study aimed to develop an explainable 3D CNN, which fulfilled the task of pCR prediction before the beginning of NAC, by leveraging the 3D information of post-contrast baseline breast DCE-MRI exams. Specifically, for each patient, the network took in input a 3D sequence containing the tumor region, which was previously automatically identified along the DCE-MRI exam. A visual explanation of the decision-making process of the network was also provided. RESULTS: To the best of our knowledge, our proposal is competitive than other models in the field, which made use of imaging data alone, reaching a median AUC value of 81.8%, 95%CI [75.3%; 88.3%], a median accuracy value of 78.7%, 95%CI [74.8%; 82.5%], a median sensitivity value of 69.8%, 95%CI [59.6%; 79.9%] and a median specificity value of 83.3%, 95%CI [82.6%; 84.0%], respectively. The median and CIs were computed according to a 10-fold cross-validation scheme for 5 rounds. CONCLUSION: Finally, this proposal holds high potential to support clinicians on non-invasively early pursuing or changing patient-centric NAC pathways.


Subject(s)
Breast Neoplasms , Neoadjuvant Therapy , Humans , Female , Neoadjuvant Therapy/methods , Artificial Intelligence , Contrast Media/therapeutic use , Treatment Outcome , Magnetic Resonance Imaging/methods , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology
3.
Clin Hemorheol Microcirc ; 87(3): 323-331, 2024.
Article in English | MEDLINE | ID: mdl-38277286

ABSTRACT

BACKGROUND: No studies have been retrieved comparing perfluorobutane with sulfur hexafluoride for microwave ablation (MWA) in small hepatocellular carcinoma(sHCC). OBJECTIVE: To retrospective investigate the value of perfluorobutane ultrasonography contrast agent in ultrasonography (US)-guided MWA of sHCC. METHODS: We conducted a retrospective clinical controlled study about US-guided percutaneous MWA in patients with sHCC, and in patients undergoing intra-operative treatment with perfluorobutane or sulfur hexafluoride. In both groups, a contrast agent was injected to clear the tumor and then a needle was inserted. A 5-point needle prick difficulty score was developed to compare needle prick difficulty in the two groups of cases. RESULTS: A total of 67 patients were included: 25 patients in group perfluorobutane, aged 41-82 (60.64±9.46), tumor size 1.1-2.8 (1.78±0.45) cm. 42 patients in group sulfur hexafluoride, aged 38-78 (62.26±9.27), with tumor size of 1.1-3.0 (1.89±0.49) cm. There was no significant difference in age or tumor size in both groups (P > 0.05). Puncture difficulty score (5-point): 2.0-2.7 (2.28±0.29) in group perfluorobutane, and 2.0-4.7 (2.95±0.85) in group sulfur hexafluoride, and the difference between the two groups was statistically significant (P < 0.05). Enhanced imaging results within 3 months after surgery: complete ablation rate was 100% (25/25) in the group perfluorobutane, 95.2% (40/42 in the group sulfur hexafluoride), with no significant difference between the two groups (P > 0.05). CONCLUSION: Perfluorobutane kupffer phase can make the operator accurately deploy the ablation needle and reduce the difficulty of operation.


Subject(s)
Carcinoma, Hepatocellular , Fluorocarbons , Liver Neoplasms , Microwaves , Humans , Carcinoma, Hepatocellular/surgery , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/surgery , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/pathology , Middle Aged , Male , Female , Aged , Retrospective Studies , Microwaves/therapeutic use , Fluorocarbons/therapeutic use , Adult , Aged, 80 and over , Ultrasonography/methods , Contrast Media/therapeutic use
4.
J Neurol ; 271(4): 1747-1766, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38286842

ABSTRACT

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory syndrome with characteristic clinical, radiological, and pathological features, and can be effectively treated with corticosteroid-based immunotherapies. The exact pathogenesis of CLIPPERS remains unclear, and specific diagnostic biomarkers are not available. According to the 2017 diagnostic criteria, probable CLIPPERS should be considered in middle-aged patients with subacute onset of pontocerebellar symptoms and typical punctuate and curvilinear gadolinium enhancement lesions ("salt-and-pepper" appearance) located in the hindbrain (especially pons) on magnetic resonance imaging. In addition, CLIPPERS-mimics, such as central nervous system (CNS) lymphoma, and several antibody-associated autoimmune CNS diseases (e.g., myelin oligodendrocyte glycoprotein antibody-associated disease, autoimmune glial fibrillary acidic protein astrocytopathy, and anti-N-methyl-D-aspartate receptor encephalitis), should be extensively excluded. The prerequisite for definite CLIPPERS is the perivascular T-cell-predominant inflammatory infiltration observed on pathological analysis. A biopsy is strongly suggested when clinical/radiological red flags are present. Most patients with CLIPPERS respond well to corticosteroids and have a good prognosis. Long-term low-dose corticosteroid maintenance therapy or corticosteroids coupled with immunosuppressants are recommended to prevent the recurrence of the syndrome. The potential progression of CLIPPERS to lymphoma has been suggested in some cases; therefore, at least 2-year clinical and radiological follow-up is essential. Here, we critically review the recent developments and provided an update on the clinical characteristics, diagnostic criteria, differential diagnoses, and therapeutic management of CLIPPERS. We also discuss the current controversies in this context that can be resolved in future research studies.


Subject(s)
Central Nervous System Neoplasms , Lymphoma , Middle Aged , Humans , Contrast Media/therapeutic use , Gadolinium , Inflammation/complications , Steroids/therapeutic use , Adrenal Cortex Hormones/therapeutic use , Magnetic Resonance Imaging/methods , Pons/pathology , Central Nervous System Neoplasms/pathology , Lymphoma/complications
5.
Neuropediatrics ; 55(2): 117-123, 2024 04.
Article in English | MEDLINE | ID: mdl-38181817

ABSTRACT

INTRODUCTION: We report a case study of two male pediatric patients presenting with anterior uveitis and elevated renal function parameters. Both were diagnosed with tubulointerstitial nephritis and uveitis syndrome and subsequently developed diffuse cerebral symptoms such as headache, fatigue, and diziness. METHODS: Magnetic resonance images (MRIs) of the brain showed T2-hyperintense lesions with and without gadolinium enhancement leading to brain biopsy and diagnosis of small-vessel central nervous system (CNS) vasculitis in both cases. Both patients were treated according to BrainWorks small-vessel vasculitis protocol and symptoms vanished over the course of treatment. Follow-up MRIs up to 12 months after initiation of therapy showed no signs of recurrence indicating a monophasic disease. CONCLUSION: Small-vessel CNS vasculitis can occur simultaneously to other autoimmune diseases (ADs) in the scope of polyautoimmunity. As clinical findings of CNS vasculitis are often unspecific, neurological symptoms in nonneurological ADs should be adressed thoroughly. Under suspicion of small-vessel CNS vasculitis brain biopsy is still the gold standard and only secure way of definitive diagnosis.


Subject(s)
Nephritis, Interstitial , Uveitis , Vasculitis, Central Nervous System , Humans , Male , Child , Contrast Media/therapeutic use , Gadolinium/therapeutic use , Uveitis/complications , Uveitis/diagnosis , Vasculitis, Central Nervous System/complications , Vasculitis, Central Nervous System/diagnosis
6.
Ultrasound Med Biol ; 50(3): 352-357, 2024 03.
Article in English | MEDLINE | ID: mdl-38072718

ABSTRACT

OBJECTIVE: The aim of the work described here was to explore the value of contrast-enhanced ultrasound (CEUS) quantitative parameters in predicting the response of combined immune checkpoint inhibitor (ICI) and anti-angiogenesis therapies for unresectable hepatocellular carcinoma (HCC). METHODS: Sixty-six HCC patients who underwent combined ICI and anti-angiogenesis therapies were prospectively enrolled. A CEUS examination was performed at baseline, and tumor perfusion parameters were obtained with perfusion quantification software. The differences in CEUS quantitative parameters between the responder and non-responder groups were compared, and the correlations between CEUS parameters and progression-free survival (PFS) was evaluated. RESULTS: The objective response rate (ORR) was 21.2%. The values of rising time (RT) ratio, time to peak ratio, fall time ratio, peak enhancement ratio, wash-in rate ratio, wash-in perfusion index ratio and wash-out rate ratio differed significantly differed between the responder and non-responder groups (all p values < 0.05). Multivariable logistic regression analysis revealed that the RT ratio was the only independent factor associated with the ORR (odds ratio = 0.007, 95% confidence interval: 0.000-0.307, p = 0.010). The median RT ratios of the responder and non-responder groups were 36.9 and 58.9, respectively (p = 0.006). The appropriate cutoff point of the RT ratio was 80.1, determined with the X-tile program. Survival analysis indicated high PFS for the patients with a lower RT ratio (high RT ratio vs. low RT ratio = 4.4 mo vs. not reached, p = 0.001). CONCLUSION: CEUS quantitative parameters may predict the efficacy of ICI and anti-angiogenesis combined therapies for HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/diagnostic imaging , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/diagnostic imaging , Liver Neoplasms/drug therapy , Liver Neoplasms/pathology , Immune Checkpoint Inhibitors/therapeutic use , Contrast Media/therapeutic use , Immunotherapy , Ultrasonography , Retrospective Studies
7.
Arq Bras Cir Dig ; 36: e1777, 2023.
Article in English | MEDLINE | ID: mdl-38088723

ABSTRACT

BACKGROUND: Adhesive small bowel obstruction is one of the most common causes of surgical emergencies, representing about 15% of hospital admissions. Defining the need and timing of surgical intervention still remains a challenge. AIMS: To report the experience of using meglumine-based water-soluble contrast in a tertiary hospital in southern Brazil, comparing with the world literature. METHODS: Patients suspected of having adhesive small bowel obstruction, according to their clinical conditions, underwent an established protocol, consisting of the administration of water-soluble contrast, followed by plain abdominal radiograph within 12 hours and by a new clinical evaluation. The protocol was initiated after starting conservative management, including fasting and placement of a nasogastric tube, as well as intravenous fluid reposition. RESULTS: A total of 126 patients were submitted to the protocol. The water-soluble contrast test sensitivity and specificity after the first radiograph were 94.6 and 91.0%, respectively; after the second radiograph, these values were 92.3 and 100%. The general test values for sensitivity and specificity were 91.9 and 100%, respectively. CONCLUSIONS: The measure parameters evaluated in this study were similar to those found in the literature, contributing to endorse the importance of this test in the evaluation of patients with adhesive small bowel obstruction. The particular relevance of this study was the similar results that were found using a different type of meglumine-based contrast, which is available in Brazil.


Subject(s)
Diatrizoate Meglumine , Intestinal Obstruction , Humans , Diatrizoate Meglumine/therapeutic use , Tissue Adhesions/diagnostic imaging , Contrast Media/therapeutic use , Intestinal Obstruction/diagnostic imaging , Intestinal Obstruction/surgery , Meglumine/therapeutic use , Water
8.
Kardiologiia ; 63(12): 31-38, 2023 Dec 26.
Article in Russian, English | MEDLINE | ID: mdl-38156487

ABSTRACT

Aim      A 12-month evaluation of the potentialities of the angiotensin II receptor inhibitor olmesartan (Olme) and the angiotensin receptor and neprilysin inhibitor (ARNI) sacubitril/valsartan in patients with arterial hypertension (AH) and dyslipidemia in the dynamics of the following indicators of chronic heart failure (CHF): N-terminal pro-brain natriuretic peptide (NT-proBNP), left ventricular ejection fraction (LVEF), LV global longitudinal strain (LV GLS) in diffuse myocardial fibrosis (MF) previously diagnosed by magnetic resonance imaging (MRI).Material and methods  Olmesartan medoxomil (n=56) and sacubitril/valsartan (n=63) were used for 12 months in patients with hypertension, dyslipidemia and NYHA functional class II-III CHF with mid-range LVEF (CHFmrEF). MF was diagnosed by the following MRI criteria: late gadolinium enhancement and an increased proportion of extracellular matrix (33% or more). The frequency of persisting late gadolinium enhancement and the increased proportion of extracellular matrix (33% or more) was evaluated at 12 months; changes in systolic blood pressure (SBP), diastolic blood pressure (DBP), NT-proBNP, and LV GLS were evaluated after 3, 6, and 12 months of follow-up.Results Baseline parameters did not differ between groups. The late gadolinium enhancement and increased proportion of extracellular matrix were present at baseline in all patients of both groups (100%; p=1.0). Already at 3 months, statistically significant decreases in SBP and DBP were observed in both groups. In addition, the LV GLS monitoring showed LV GLS significantly increased in both groups after 3 months and continued changing after 6 and 12 months. The NT-proBNP concentration significantly decreased in both groups already after 3 months and continued to decrease after 6 and 12 months. At 6 and 12 months, sacubitril/valsartan was superior to olmesartan in reducing SBP and NT-proBNP and in restoring LV GLS. At 12 months, the incidence of persisting, abnormal late gadolinium enhancement and increased proportion of extracellular matrix was significantly less in the ARNI group.Conclusion      Olmesartan was demonstrated effective in the multi-modality therapy of CHFmrEF and MF in patients with AH and dyslipidemia. ARNI was superior to olmesartan in this regard, but further research of this issue is required.


Subject(s)
Dyslipidemias , Heart Failure , Hypertension , Ventricular Dysfunction, Left , Humans , Stroke Volume , Contrast Media/therapeutic use , Gadolinium/therapeutic use , Angiotensin Receptor Antagonists/therapeutic use , Ventricular Function, Left , Valsartan/therapeutic use , Tetrazoles/therapeutic use , Heart Failure/diagnosis , Heart Failure/drug therapy , Heart Failure/etiology , Aminobutyrates/pharmacology , Aminobutyrates/therapeutic use , Biphenyl Compounds/therapeutic use , Hypertension/complications , Hypertension/diagnosis , Hypertension/drug therapy , Drug Combinations , Fibrosis
9.
ACS Appl Mater Interfaces ; 15(38): 44773-44785, 2023 Sep 27.
Article in English | MEDLINE | ID: mdl-37721368

ABSTRACT

Supramolecular self-assembly has gained increasing attention to construct multicomponent drug delivery systems for cancer diagnosis and therapy. Despite that these self-assembled nanosystems present surprising properties beyond that of each subcomponent, the spontaneous nature of co-self-assembly causes significant difficulties in control of the synthesis process and consequently leads to unsatisfactory influences in downstream applications. Hence, we utlized an in situ dynamic covalent reaction based on thiol-disulfide exchange to slowly produce disulfide macrocycles, which subsequently triggered the co-self-assembly of an anticancer drug (doxorubicin, DOX) and a magnetic resonance imaging (MRI) contrast agent of ultrasmall iron oxide nanoparticles (IO NPs). It showed concentration regulation of macrocyclic disulfides, DOX, and IO NPs by a dynamic covalent self-assembly (DCS) strategy, resulting in a stable codelivery nanosystem with high drug loading efficiency of 37.36%. More importantly, disulfide macrocycles in the codelivery system could be reduced and broken by glutathione (GSH) in tumor cells, thus leading to disassembly of nanostructures and intellgent release of drugs. These stimuli-responsive performances have been investigated via morphologies and molecular structures, revealing greatly enhanced dual-modal MRI abilities and smart drug release under the trigger of GSH. Moreover, the codelivery system conjugated with a targeting molecule of cyclic Arg-Gly-Asp (cRGD) exhibited significant biocompatibility, MR imaging, and chemotherapeutic anticancer effect in vitro and in vivo. These results indicated that in situ dynamic covalent chemistry enhanced the control over co-self-assembly and paved the way to develop more potential drug delivery systems.


Subject(s)
Antineoplastic Agents , Nanoparticles , Neoplasms , Humans , Disulfides/chemistry , Nanoparticles/chemistry , Antineoplastic Agents/chemistry , Neoplasms/diagnostic imaging , Neoplasms/drug therapy , Doxorubicin/chemistry , Drug Delivery Systems/methods , Magnetic Resonance Imaging , Glutathione , Contrast Media/therapeutic use
10.
Ultrasound Med Biol ; 49(9): 2169-2176, 2023 09.
Article in English | MEDLINE | ID: mdl-37451952

ABSTRACT

OBJECTIVE: It is known that in patients with renal cell carcinoma (RCC), the invasiveness of the tumor is closely related to the treatment and prognosis. Currently, histologic diagnosis of RCC is typically established after surgical removal of tumors or after biopsy. The use of non-invasive imaging modalities to predict the invasiveness of RCC is of great clinical value, particularly before surgery. In this study, the differences in conventional ultrasound (US) and contrast-enhanced ultrasound (CEUS) features between invasive and non-invasive RCC were analyzed with the aim of providing more accurate and valuable information for diagnosis and treatment to clinically optimize the treatment plan in a non-invasive manner and improve the prognosis of patients. METHODS: Conventional US and CEUS features of 163 patients (total of 164 RCCs), obtained from the Lanzhou University Second Hospital in the period ranging from March 2021 to September 2022, were retrospectively analyzed. Patients were categorized into two groups: invasive group (n = 44) and non-invasive group (n = 120), with surgical pathology as reference standard. Receiver operating characteristic curves were drawn to evaluate the feasibility of differentiation. RESULTS: The possibility of an intrarenal lesion/kidney ratio >50% in the invasive group (13/44, 29.5%) was significantly higher than that in the non-invasive group (8/120, 6.7%) (p < 0.001). The absence of perilesional rim-like enhancement was more likely to imply invasive RCC (30/44, 68.2%) than non-invasive RCC (100/120, 83.3%) (p = 0.049) and was an independent predictor of invasive RCC. As for CEUS quantitative features, there were statistically significant differences in peak intensity (p = 0.009) or peak enhancement (p = 0.010), taking the largest range of lesion as the region of interest. CONCLUSION: Conventional US and CEUS features may help in the differentiation of invasive RCC from non-invasive RCC and have potential application value in the pre-operative prediction of RCC invasiveness.


Subject(s)
Carcinoma, Renal Cell , Kidney Neoplasms , Humans , Carcinoma, Renal Cell/diagnostic imaging , Carcinoma, Renal Cell/surgery , Kidney Neoplasms/diagnostic imaging , Kidney Neoplasms/surgery , Retrospective Studies , Contrast Media/therapeutic use , Kidney/pathology , Ultrasonography/methods
11.
Eur Rev Med Pharmacol Sci ; 27(13): 6132-6139, 2023 07.
Article in English | MEDLINE | ID: mdl-37458675

ABSTRACT

OBJECTIVE: Spinal cord injury (SCI) is still one of the most challenging problems in neurosurgical practice. One of the major obstacles to neural regeneration following trauma is the formation of glial scarring and post-traumatic cysts which acts against proper growth of axons through the site of injury. Cerebrospinal fluid (CSF) delivery of bioactive agents into cystic cavities could represent a promising therapeutic strategy. In the present study, we investigated specifically the dynamics of intradural delivery of contrast medium and its relocation into post-traumatic cysts in an experimental model of spinal cord cryoinjury in rats. MATERIALS AND METHODS: 32 male Sprague Dawley SPF rats were submitted to injury as previously described. Omnipaque-240 was injected either into the cisterna magna or at the level of the cauda equina. Subsequently, cerebral CT scan examinations were performed in order to check the CSF dynamics of the contrast medium. RESULTS: There was a steady accumulation of contrast medium into post-traumatic cysts as early as five minutes after injection. A dosage of 65 mg of iodine per kilogram ensured an adequate feeling of the cysts at an average of 30 minutes. CONCLUSIONS: Our data indicate that intraspinal injection of bioactive agents can easily reach the site of injury and fill post-traumatic cysts. This could represent an interesting potential therapeutic protocol for SCI.


Subject(s)
Cysts , Spinal Cord Injuries , Rats , Male , Animals , Rats, Sprague-Dawley , Spinal Cord/diagnostic imaging , Spinal Cord Injuries/therapy , Axons , Contrast Media/therapeutic use
12.
Clin Neurol Neurosurg ; 232: 107885, 2023 09.
Article in English | MEDLINE | ID: mdl-37459794

ABSTRACT

BACKGROUND: Cladribine was approved for the treatment of multiple sclerosis (MS). Real-world data is very limited. OBJECTIVES: To study the effectiveness and the safety of Cladribine treatment in only one group of MS patients after treatment with Cladribine for two years. METHODS: This observational, longitudinal prospective study. Eligible subjects were relapsing remitting MS patients who had at least two-year follow-up after Cladribine treatment. The primary endpoint was the proportion of relapse free patients. Secondary endpoints were ARR, change in EDSS scores, the proportion of patients with CDP, MRI activity, and NEDA-3 status, also the rate of occurrence of AEs. Patients were assessed for primary and secondary endpoints at the end of two years of follow-up. RESULTS: Of a total of seventy-two patients, 59 (81.9 %) were females, mean age of 36.32 + 10.06 years old, mean disease duration 7.21 + 6.19. Most patients (n = 32; 44.4 %) were naïve to any treatment. Forty patients (55.6 %) completed two courses of treatment. The primary endpoint showed that most of our cohort was relapse free (85 % versus 25 %; P < 0.001), Secondary endpoints showed that ARR was significantly reduced 0.15 + 0.36 versus 0.85 + 0.53; P < 0.01). Most of the cohort 90 % have no progression of disability. Few subjects had new T2 lesions (7.5 % versus 70.8 %; P < 0.001 and gadolinium enhancement 5 % versus 66.7 %; P < 0.001) in MRI compared to baseline. No evidence of disease activity 3 (NEDA-3) was achieved in 30 (75 %) patients. It was achieved in 87.5 % of naive patients versus 66.7 % in patients who received prior disease modification drugs before Cladribine initiation. Infections 6 (n = 6; 8.4 %) lymphocytopenia (n = 3; 4.2 %), and elevated liver enzymes (n = 1; 1.4 %) were reported. CONCLUSION: Cladribine treatment reduced significantly relapse rate and MRI activity. It was safe and tolerable. Early initiation of cladribine is associated with favorable outcomes.


Subject(s)
Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Female , Humans , Adult , Middle Aged , Male , Cladribine/therapeutic use , Multiple Sclerosis/drug therapy , Prospective Studies , Follow-Up Studies , Longitudinal Studies , Contrast Media/therapeutic use , Gadolinium/therapeutic use , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Immunosuppressive Agents/therapeutic use
13.
Int J Mol Sci ; 24(9)2023 May 04.
Article in English | MEDLINE | ID: mdl-37175958

ABSTRACT

Contrast-induced acute kidney injury (CI-AKI) is manifested by an abrupt decline in kidney function as a consequence of intravascular exposure to contrast media. With the increased applicability of medical imaging and interventional procedures that utilize contrast media for clinical diagnosis, CI-AKI is becoming the leading cause of renal dysfunction. The pathophysiological mechanism associated with CI-AKI involves renal medullary hypoxia, the direct toxicity of contrast agents, oxidative stress, apoptosis, inflammation, and epigenetic regulation. To date, there is no effective therapy for CI-AKI, except for the development of strategies that could reduce the toxicity profiles of contrast media. While most of these strategies have failed, evidence has shown that the proper use of personalized hydration, contrast medium, and high-dose statins may reduce the occurrence of CI-AKI. However, adequate risk predication and attempts to develop preventive strategies can be considered as the key determinants that can help eliminate CI-AKI. Additionally, a deeper understanding of the pathophysiological mechanism of CI-AKI is crucial to uncover molecular targets for the prevention of CI-AKI. This review has taken a step further to solidify the current known molecular mechanisms of CI-AKI and elaborate the biomarkers that are used to detect early-stage CI-AKI. On this foundation, this review will analyze the molecular targets relating to apoptosis, inflammation, oxidative stress, and epigenetics, and, thus, provide a strong rationale for therapeutic intervention in the prevention of CI-AKI.


Subject(s)
Acute Kidney Injury , Contrast Media , Humans , Contrast Media/therapeutic use , Epigenesis, Genetic , Acute Kidney Injury/therapy , Oxidative Stress , Inflammation , Risk Factors
14.
BMC Womens Health ; 23(1): 233, 2023 05 06.
Article in English | MEDLINE | ID: mdl-37149639

ABSTRACT

BACKGROUND: In women with unexplained infertility, tubal flushing with oil-based contrast during hysterosalpingography leads to significantly more live births as compared to tubal flushing with water-based contrast during hysterosalpingography. However, it is unknown whether incorporating tubal flushing with oil-based contrast in the initial fertility work-up results to a reduced time to conception leading to live birth when compared to delayed tubal flushing that is performed six months after the initial fertility work-up. We also aim to evaluate the effectiveness of tubal flushing with oil-based contrast during hysterosalpingography versus no tubal flushing in the first six months of the study. METHODS: This study will be an investigator-initiated, open-label, international, multicenter, randomized controlled trial with a planned economic analysis alongside the study. Infertile women between 18 and 39 years of age, who have an ovulatory cycle, who are at low risk for tubal pathology and have been advised expectant management for at least six months (based on the Hunault prediction score) will be included in this study. Eligible women will be randomly allocated (1:1) to immediate tubal flushing (intervention) versus delayed tubal flushing (control group) by using web-based block randomization stratified per study center. The primary outcome is time to conception leading to live birth with conception within twelve months after randomization. We assess the cumulative conception rate at six and twelve months as two co-primary outcomes. Secondary outcomes include ongoing pregnancy rate, live birth rate, miscarriage rate, ectopic pregnancy rate, number of complications, procedural pain score and cost-effectiveness. To demonstrate or refute a shorter time to pregnancy of three months with a power of 90%, a sample size of 554 women is calculated. DISCUSSION: The H2Oil-timing study will provide insight into whether tubal flushing with oil-based contrast during hysterosalpingography should be incorporated in the initial fertility work-up in women with unexplained infertility as a therapeutic procedure. If this multicenter RCT shows that tubal flushing with oil-based contrast incorporated in the initial fertility work-up reduces time to conception and is a cost-effective strategy, the results may lead to adjustments of (inter)national guidelines and change clinical practice. TRIAL REGISTRATION NUMBER: The study was retrospectively registered in International Clinical Trials Registry Platform (Main ID: EUCTR2018-004153-24-NL).


Subject(s)
Infertility, Female , Female , Humans , Pregnancy , Contrast Media/therapeutic use , Fallopian Tubes/diagnostic imaging , Hysterosalpingography/adverse effects , Infertility, Female/etiology , Multicenter Studies as Topic , Pregnancy Rate , Randomized Controlled Trials as Topic
15.
J Mater Chem B ; 11(21): 4799-4807, 2023 05 31.
Article in English | MEDLINE | ID: mdl-37194355

ABSTRACT

It is crucially important to explore the additional metal-endowed functions of supramolecular organic frameworks (SOFs) for expanding their applications. In this work we have reported the performance of a SOF (designated as Fe(III)-SOF) as a theranostic platform via magnetic resonance imaging (MRI)-guided chemotherapy. The Fe(III)-SOF may be used as an MRI contrast agent for cancer diagnosis because the building unit (iron complex) contains high spin iron(III) ions. Additionally, the Fe(III)-SOF may also be used as a drug carrier because it possesses stable internal voids. We loaded doxorubicin (DOX) into the Fe(III)-SOF to obtain a DOX@Fe(III)-SOF. The Fe(III)-SOF showed good loading content (16.3%) and high loading efficiency (65.2%) for DOX. Additionally, the DOX@Fe(III)-SOF had a relatively modest relaxivity value (r2 = 19.745 mM-1 s-1) and exhibited the strongest negative contrast (darkest) at 12 h of post-injection. Furthermore, the DOX@Fe(III)-SOF effectively inhibited tumor growth and showed high anticancer efficiency. In addition, the Fe(III)-SOF was biocompatible and biosafe. Therefore, the Fe(III)-SOF was an excellent theranostic platform and may have potential applications in tumor diagnosis and treatment in the future. We believe that this work will initiate extensive research endeavors not only on the development of SOFs, but also on the construction of theranostic platforms based on SOFs.


Subject(s)
Iron , Neoplasms , Humans , Precision Medicine , Doxorubicin/pharmacology , Doxorubicin/therapeutic use , Neoplasms/drug therapy , Contrast Media/therapeutic use , Magnetic Resonance Imaging/methods
16.
JNMA J Nepal Med Assoc ; 61(260): 390-396, 2023 Apr 01.
Article in English | MEDLINE | ID: mdl-37208871

ABSTRACT

Adhesion is a leading cause of small bowel obstruction. Adhesive small bowel obstruction has significant challenges in diagnosis, treatment and prevention with considerable impact on morbidity and socioeconomic burden. Small bowel obstruction caused by adhesion or any other aetiology is clinically indistinguishable due to similar clinical presentation. Computed Tomography scans and water-soluble contrast studies are more specific in diagnosis and possess value in predicting the need for surgery. Surgical management is indicated only in complicated cases or failed conservative treatments with the majority resolving with non-operative management. However, there is no clear-cut consensus about the timing of operative intervention. Meticulous surgical practice is the keystone in preventing adhesion formation despite the availability of numerous pharmacological and surgical strategies. This review aims to update the current knowledge of the pathophysiology of adhesion formation, treatment options and various prevention modalities of adhesive small bowel obstruction. Keywords: diagnosis; laparotomy; prevention; surgery.


Subject(s)
Intestinal Obstruction , Humans , Intestinal Obstruction/diagnosis , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Tissue Adhesions/complications , Tissue Adhesions/diagnosis , Tissue Adhesions/surgery , Contrast Media/therapeutic use , Intestine, Small/pathology , Intestine, Small/surgery , Conservative Treatment
17.
Ultrasound Med Biol ; 49(7): 1638-1646, 2023 07.
Article in English | MEDLINE | ID: mdl-37100671

ABSTRACT

OBJECTIVE: This prospective study was aimed at evaluating the role of automated breast ultrasound (ABUS) and contrast-enhanced ultrasound (CEUS) in the early prediction of treatment response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. METHODS: Forty-three patients with pathologically confirmed invasive breast cancer treated with NAC were included. The standard for evaluation of response to NAC was based on surgery within 21 d of completing treatment. The patients were classified as having a pathological complete response (pCR) and a non-pCR. All patients underwent CEUS and ABUS 1 wk before receiving NAC and after two treatment cycles. The rising time (RT), time to peak (TTP), peak intensity (PI), wash-in slope (WIS) and wash-in area under the curve (Wi-AUC) were measured on the CEUS images before and after NAC. The maximum tumor diameters in the coronal and sagittal planes were measured on ABUS, and the tumor volume (V) was calculated. The difference (∆) in each parameter between the two treatment time points was compared. Binary logistic regression analysis was used to identify the predictive value of each parameter. RESULTS: ∆V, ∆TTP and ∆PI were independent predictors of pCR. The CEUS-ABUS model achieved the highest AUC (0.950), followed by those based on CEUS (0.918) and ABUS (0.891) alone. CONCLUSION: The CEUS-ABUS model could be used clinically to optimize the treatment of patients with breast cancer.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/diagnostic imaging , Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neoadjuvant Therapy/methods , Prospective Studies , Treatment Outcome , Contrast Media/therapeutic use
18.
ACS Nano ; 17(7): 6649-6663, 2023 04 11.
Article in English | MEDLINE | ID: mdl-36989423

ABSTRACT

Cartilage tissue exhibits early degenerative changes with onset of osteoarthritis (OA). Early diagnosis is critical as there is only a narrow time window during which therapeutic intervention can reverse disease progression. Computed tomography (CT) has been considered for cartilage imaging as a tool for early OA diagnosis by introducing radio-opaque contrast agents like ioxaglate (IOX) into the joint. IOX, however, is anionic and thus repelled by negatively charged cartilage glycosaminoglycans (GAGs) that hinders its intra-tissue penetration and partitioning, resulting in poor CT attenuation. This is further complicated by its short intra-tissue residence time owing to rapid clearance from joints, which necessitates high doses causing toxicity concerns. Here we engineer optimally charged cationic contrast agents based on cartilage negative fixed charge density by conjugating cartilage targeting a cationic peptide carrier (CPC) and multi-arm avidin nanoconstruct (mAv) to IOX, such that they can penetrate through the full thickness of cartilage within 6 h using electrostatic interactions and elicit similar CT signal with about 40× lower dose compared to anionic IOX. Their partitioning and distribution correlate strongly with spatial GAG distribution within healthy and early- to late-stage arthritic bovine cartilage tissues at 50-100× lower doses than other cationic contrast agents used in the current literature. The use of contrast agents at low concentrations also allowed for delineation of cartilage from subchondral bone as well as other soft tissues in rat tibial joints. These contrast agents are safe to use at current doses, making CT a viable imaging modality for early detection of OA and staging of its severity.


Subject(s)
Cartilage, Articular , Osteoarthritis , Rats , Animals , Cattle , Contrast Media/therapeutic use , Cartilage, Articular/diagnostic imaging , Tomography, X-Ray Computed/methods , Ioxaglic Acid/therapeutic use , Cations , Osteoarthritis/diagnostic imaging , Early Diagnosis
19.
Eur J Radiol ; 162: 110756, 2023 May.
Article in English | MEDLINE | ID: mdl-36907069

ABSTRACT

PURPOSE: To clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). METHODS: We enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. RESULTS: Tumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV (<26.0 %), sensitivity, specificity, accuracy, positive predictive value, and negative value for predicting response group were 71.4 %, 85.0 %, 83.6 %, 35.7 % and 96.2 %, respectively. CONCLUSION: PDAC with lower DECT-ECV can potentially show better response to NAC. DECT-ECV might be a useful biomarker for predicting response to NAC in patients with PDAC.


Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Humans , Neoadjuvant Therapy , Pancreatic Neoplasms/diagnostic imaging , Pancreatic Neoplasms/drug therapy , Pancreatic Neoplasms/surgery , Carcinoma, Pancreatic Ductal/diagnostic imaging , Carcinoma, Pancreatic Ductal/drug therapy , Carcinoma, Pancreatic Ductal/surgery , Tomography, X-Ray Computed/methods , Retrospective Studies , Contrast Media/therapeutic use , Pancreatic Neoplasms
20.
ACS Appl Mater Interfaces ; 15(8): 10477-10491, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36790347

ABSTRACT

Imaging-guided percutaneous microwave thermotherapy has been regarded as an important alternative nonsurgical therapeutic strategy for hepatocellular carcinoma (HCC) that provides excellent local tumor control and favorable survival benefit. However, providing a high-resolution, real-time, and noninvasive imaging technique for intraoperative guidance and controlling postoperative residual tumor recurrence are urgent needs for the clinical setting. In this study, a cisplatin (CDDP)-loaded nanocapsule (NPs@CDDP) with microwave responsive property was prepared to simultaneously serve as a contrast agent of emerging thermoacoustic imaging and a sensitizing agent of microwave thermo-chemotherapy. Accompanying the enzymolysis in the tumor microenvironment, the NPs@CDDP responsively release l-arginine (l-Arg) and CDDP. l-Arg with excellent microwave-absorbing property allowed it to serve as a thermoacoustic imaging contrast agent for accurately delineating the tumor and remarkably increasing tumor temperature under ultralow power microwave irradiation. Apart from the chemotherapeutic effect, CDDP elevated the intracellular H2O2 level through cascade reactions and further accelerated the continuous transformation of l-Arg to nitric oxide (NO), which endowed the NPs@CDDP with NO-generation capability. Notably, the high concentration of intracellular NO was proved to aggravate lipid peroxidation and greatly improved the efficacy of microwave thermo-chemotherapy. Thereby, NPs@CDDP was expected to serve as a theranostic agent integrating the functions of tumor microenvironment-responsive drug delivery system, contrast agent of thermoacoustic imaging, thermal sensitizing agent, and NO nanogenerator, which was promising to provide a potential imaging-guided therapeutic strategy for HCC.


Subject(s)
Antineoplastic Agents , Carcinoma, Hepatocellular , Liver Neoplasms , Humans , Carcinoma, Hepatocellular/drug therapy , Nitric Oxide/therapeutic use , Liver Neoplasms/drug therapy , Microwaves , Contrast Media/therapeutic use , Hydrogen Peroxide , Cisplatin/therapeutic use , Antineoplastic Agents/therapeutic use , Tumor Microenvironment
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