RESUMEN
This paper introduces catheter-directed intravascular casting hydrogels for transarterial chemo/starvation/chemodynamic embolization (TACSCE) therapy of hepatocellular carcinoma (HCC). Comprising Mn ion-crosslinked hyaluronic acid-dopamine (HD) with glucose oxidase (for glucose decomposition to H2O2 in starvation therapy), doxorubicin (for chemotherapy), and iopamidol (for X-ray imaging), these hydrogels are fabricated for transarterial embolization therapy guided by X-ray fluoroscopy. Mn4+ (from MnO2) demonstrates strong coordination with the catechol group of HD, providing hypoxia relief through O2 generation and cellular glutathione (GSH) consumption, compared to the OH radical generation potential of Mn2+. The gelation time-controlled, catheter-injectable, and rheologically tuned multitherapeutic/embolic gel system effectively reaches distal arterioles, ensuring complete intravascular casting with fewer complications related to organic solvents. Glucose deprivation, cascade reactive oxygen species (ROS) generation, GSH depletion, and sustained release profiles of multiple drug cargos from the hydrogel system are also achieved. The combined chemo/starvation/chemodynamic efficacies of these designed hydrogel systems are confirmed in HCC cell cultures and HCC-bearing animal models. The developed radiopaque/injectable/embolic/sol-to-gel transformable systems for TACSCE therapy may offer enhanced therapeutic efficacies compared to typical transarterial embolization and transarterial chemoembolization procedures for HCC.
RESUMEN
OBJECTIVE: To evaluate the outcomes of drug-eluting bead transarterial chemoembolization (DEB-TACE) according to the size of the beads for the treatment of small hepatocellular carcinoma (HCC). MATERIALS AND METHODS: This retrospective study included 212 patients with a single HCC ≤5 cm from five tertiary institutions. One hundred and nine patients were treated with 70-150-µm doxorubicin DEBs (group A), and 103 patients received 100-300-µm doxorubicin DEBs (group B). The initial tumor response (assessed between 3 weeks and 2 months after DEB-TACE), time to local tumor progression (TTLTP), restricted mean duration of complete response (RMDCR), rate of complications, incidence of post-embolization syndrome, and length of hospital stay were compared between the two groups. Logistic regression was used to analyze prognostic factors for initial tumor response. RESULTS: The initial objective response rates were 91.7% (100/109) and 84.5% (87/103) for groups A and B, respectively (P = 0.101). In the subgroup analysis of tumors ≤3 cm, the initial objective response rates were 94.6% (53/56) and 78.0% (39/50) for groups A and B, respectively (P = 0.012). There was no significant difference in the TTLTP (median, 23.7 months for group A vs. 19.0 months for group B; P = 0.278 [log-rank], 0.190 [multivariable Cox regression]) or RMDCR at 24 months (11.4 months vs. 8.5 months, respectively; P = 0.088). In the subgroup analysis of tumors >3-cm, the RMDCR at 24 months was significantly longer in group A than in group B (11.8 months vs. 5.7 months, P = 0.024). The incidence of mild bile duct dilatation after DEB-TACE was significantly higher in group B than in group A (5.5% [6/109] vs. 18.4% [19/103], P = 0.003). CONCLUSION: DEB-TACE using 70-150-µm microspheres demonstrated a higher initial objective response rate in ≤3-cm HCCs and a longer RMDCR at 24 months in 3.1-5-cm HCCs compared to larger DEBs (100-300-µm).
Asunto(s)
Antibióticos Antineoplásicos , Carcinoma Hepatocelular , Quimioembolización Terapéutica , Doxorrubicina , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/diagnóstico por imagen , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/diagnóstico por imagen , Quimioembolización Terapéutica/métodos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Doxorrubicina/administración & dosificación , Resultado del Tratamiento , República de Corea , Anciano , Antibióticos Antineoplásicos/administración & dosificación , Microesferas , AdultoRESUMEN
Ectopic varices are rare but potentially life-threatening conditions usually resulting from a combination of global portal hypertension and local occlusive components. As imaging, innovative devices, and interventional radiologic techniques evolve and are more widely adopted, interventional radiology is becoming essential in the management of ectopic varices. The interventional radiologist starts by diagnosing the underlying causes of portal hypertension and evaluating the afferent and efferent veins of ectopic varices with CT. If decompensated portal hypertension is causing ectopic varices, placement of a transjugular intrahepatic portosystemic shunt is considered the first-line treatment, although this treatment alone may not be effective in managing ectopic variceal bleeding because it may not sufficiently resolve focal mesenteric venous obstruction causing ectopic varices. Therefore, additional variceal embolization should be considered after placement of a transjugular intrahepatic portosystemic shunt. Retrograde transvenous obliteration can serve as a definitive treatment when the efferent vein connected to the systemic vein is accessible. Antegrade transvenous obliteration is a vital component of interventional radiologic management of ectopic varices because ectopic varices often exhibit complex anatomy and commonly lack catheterizable portosystemic shunts. Superficial veins of the portal venous system such as recanalized umbilical veins may provide safe access for antegrade transvenous obliteration. Given the absence of consensus and guidelines, a multidisciplinary team approach is essential for the individualized management of ectopic varices. Interventional radiologists must be knowledgeable about the anatomy and hemodynamic characteristics of ectopic varices based on CT images and be prepared to consider appropriate options for each specific situation. ©RSNA, 2024 Supplemental material is available for this article.
Asunto(s)
Hemorragia Gastrointestinal , Derivación Portosistémica Intrahepática Transyugular , Humanos , Derivación Portosistémica Intrahepática Transyugular/métodos , Hemorragia Gastrointestinal/diagnóstico por imagen , Hemorragia Gastrointestinal/terapia , Hemorragia Gastrointestinal/etiología , Várices Esofágicas y Gástricas/diagnóstico por imagen , Várices Esofágicas y Gástricas/terapia , Hipertensión Portal/diagnóstico por imagen , Hipertensión Portal/complicaciones , Várices/diagnóstico por imagen , Várices/terapia , Radiografía Intervencional/métodos , Radiología Intervencionista/métodos , Embolización Terapéutica/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Recent intravesical administration of adenoviral vectors, either as a single injection or in combination with immune checkpoint inhibitors, exemplified by cretostimogene grenadenorepvec and nadofaragene firadenovec, has demonstrated remarkable efficacy in clinical trials for non-muscle invasive bladder cancer. Despite their ability to induce an enhanced immune reaction within the lesion, the intracellular survival signaling of cancer cells has not been thoroughly addressed. METHODS: An analysis of the prognostic data revealed a high probability of therapeutic efficacy with simultaneous inhibition of mTOR and STAT3. Considering the challenges of limited pharmaco-accessibility to the bladder due to its pathophysiological structure and the partially undruggable nature of target molecules, we designed a dual siRNA system targeting both mRNAs. Subsequently, this dual siRNA system was encoded into the adenovirus 5/3 (Ad 5/3) to enhance in vivo delivery efficiency. RESULTS: Gene-targeting efficacy was assessed using cells isolated from xenografted tumors using a single-cell analysis system. Our strategy demonstrated a balanced downregulation of mTOR and STAT3 at the single-cell resolution, both in vitro and in vivo. This approach reduced tumor growth in bladder cancer xenograft and orthotopic animal experiments. In addition, increased infiltration of CD8+ T cells was observed in a humanized mouse model. We provided helpful and safe tissue distribution data for intravesical therapy of siRNAs coding adenoviruses. CONCLUSIONS: The bi-specific siRNA strategy, encapsulated in an adenovirus, could be a promising tool to augment cancer treatment efficacy and overcome conventional therapy limitations associated with "undruggability." Hence, we propose that dual targeting of mTOR and STAT3 is an advantageous strategy for intravesical therapy using adenoviruses.
Asunto(s)
Factor de Transcripción STAT3 , Serina-Treonina Quinasas TOR , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/terapia , Humanos , Factor de Transcripción STAT3/metabolismo , Animales , Ratones , Serina-Treonina Quinasas TOR/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Administración Intravesical , Femenino , Línea Celular Tumoral , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The human gastrointestinal (GI) tract houses a diverse microbial community, known as the gut microbiome comprising bacteria, viruses, fungi, and protozoa. The gut microbiome plays a crucial role in maintaining the body's equilibrium and has recently been discovered to influence the functioning of the central nervous system (CNS). The communication between the nervous system and the GI tract occurs through a two-way network called the gut-brain axis. The nervous system and the GI tract can modulate each other through activated neuronal cells, the immune system, and metabolites produced by the gut microbiome. Extensive research both in preclinical and clinical realms, has highlighted the complex relationship between the gut and diseases associated with the CNS, such as Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. This review aims to delineate receptor and target enzymes linked with gut microbiota metabolites and explore their specific roles within the brain, particularly their impact on CNS-related diseases.
Asunto(s)
Carcinoma Hepatocelular , Hepatectomía , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/cirugía , Carcinoma Hepatocelular/radioterapia , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/cirugía , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Resultado del Tratamiento , Carga Tumoral , Factores de Tiempo , Radioterapia AdyuvanteAsunto(s)
Colesteatoma del Oído Medio , Fístula , Enfermedades del Laberinto , Canales Semicirculares , Humanos , Canales Semicirculares/patología , Canales Semicirculares/diagnóstico por imagen , Colesteatoma del Oído Medio/cirugía , Colesteatoma del Oído Medio/complicaciones , Colesteatoma del Oído Medio/patología , Fístula/cirugía , Enfermedades del Laberinto/patología , Enfermedades del Laberinto/diagnóstico por imagen , Enfermedades del Laberinto/etiología , Masculino , Femenino , Persona de Mediana EdadRESUMEN
Introduction: Dysphagia is a common complication in patients with cervical spinal cord injury (C-SCI) and can cause various pulmonary complications, such as aspiration pneumonia and mechanical airway obstruction increasing mortality and morbidity. This study evaluated the clinical factors that predict dysphagia in patients with traumatic and non-traumatic C-SCI. Methods: Ninety-eight patients with C-SCI were retrospectively enrolled in this study and were divided into those with and without dysphagia. Clinical factors such as age, sex, tracheostomy, spinal cord independence measure, pulmonary function test (PFT) including forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and FVC/FEV1, American Spinal Cord Injury Association score, Berg Balance Scale, and surgical approach were investigated retrospectively. Results: Multivariate logistic regression analysis revealed that FVC and the presence of tracheostomy were significantly correlated with dysphagia in patients with C-SCI (p < 0.05). FVC and the presence of tracheostomy are useful tools for detecting dysphagia in patients with C-SCI. Conclusion: Considering the results of our study, early PFTs, especially FVC, in patients with C-SCI and early initiation of dysphagia management and treatment in patients with C-SCI and tracheostomy will be advantageous in lowering the mortality and morbidity due to pulmonary aspiration in these patients.
RESUMEN
Sarcopenia, the progressive decline in skeletal muscle mass and function, is observed in various conditions, including cancer and aging. The complex molecular biology of sarcopenia has posed challenges for the development of FDA-approved medications, which have mainly focused on dietary supplementation. Targeting a single gene may not be sufficient to address the broad range of processes involved in muscle loss. This study analyzed the gene expression signatures associated with cancer formation and 5-FU chemotherapy-induced muscle wasting. Our findings suggest that dimenhydrinate, a combination of 8-chlorotheophylline and diphenhydramine, is a potential therapeutic for sarcopenia. In vitro experiments demonstrated that dimenhydrinate promotes muscle progenitor cell proliferation through the phosphorylation of Nrf2 by 8-chlorotheophylline and promotes myotube formation through diphenhydramine-induced autophagy. Furthermore, in various in vivo sarcopenia models, dimenhydrinate induced rapid muscle tissue regeneration. It improved muscle regeneration in animals with Duchenne muscular dystrophy (DMD) and facilitated muscle and fat recovery in animals with chemotherapy-induced sarcopenia. As an FDA-approved drug, dimenhydrinate could be applied for sarcopenia treatment after a relatively short development period, providing hope for individuals suffering from this debilitating condition.
Asunto(s)
Autofagia , Transcriptoma , Animales , Autofagia/efectos de los fármacos , Ratones , Humanos , Biosíntesis de Proteínas/efectos de los fármacos , Modelos Animales de Enfermedad , Músculo Esquelético/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/patología , Perfilación de la Expresión Génica , Sarcopenia/tratamiento farmacológico , Sarcopenia/metabolismo , Sarcopenia/patología , Distrofia Muscular de Duchenne/tratamiento farmacológico , Distrofia Muscular de Duchenne/genética , Distrofia Muscular de Duchenne/metabolismo , Distrofia Muscular de Duchenne/patologíaRESUMEN
The present study describes an unusual case of bilateral sudden hearing loss associated with iron deficiency anemia. Although hematologic disorders such as anemia or leukemia have been reported to be associated with sudden hearing loss, bilateral sudden hearing loss, which was presented as the first manifestation of iron deficiency anemia, has not been reported. A 74-year-old man presented with simultaneous bilateral sudden hearing loss without vertigo. A complete blood count test revealed a hemoglobin level of 6.4 g/dL and a ferritin level of 14.5 mg/mL, indicating iron deficiency anemia. Postcontrast 3D FLAIR MRI showed enhancement of the bilateral cochlea, vestibules, and lateral semicircular and posterior semicircular canals. After treatment, the patient's hearing loss partially improved.
RESUMEN
PURPOSE: The Cobb angle is a standard measurement to qualify and track the progression of scoliosis. However, the Cobb angle has high inter- and intra-observer variability. Consequently, its measurement varies with vertebrae and may even differ when the same vertebra is measured. Therefore, it is not constant and differs with measurements. This study aimed to develop a deep learning model that automatically measures the Cobb angle. The deep learning model for identifying vertebrae on spine radiographs was developed. METHODS: The dataset consisted of 297 images that were divided into two subsets for training and validation. Two hundred and twenty-seven images (76.4%) were used to train the model, while 70 images (23.6%) were used as the validation dataset. Absolut error between the measurements by the observer and developed deep learning model and intraclass correlation coefficient (ICC). RESULTS: The average absolute error between the measurements was 1.97° with a standard deviation of 1.57°. In addition, 95.9% of the angles had an absolute error of less than 5°. The ICC was calculated to assess the model's reliability further. The ICC was 0.981, indicating excellent reliability. CONCLUSIONS: The authors believe the model will be useful in clinical practice by relieving clinicians of the burden of having to manually compute the Cobb angle. Further studies are needed to enhance the accuracy and versatility of this deep learning model.
RESUMEN
BACKGROUND: Neurodegenerative diseases, including Parkinson's disease, Amyotropic Lateral Sclerosis (ALS) and Alzheimer's disease, present significant challenges for therapeutic development due to drug delivery restrictions and toxicity concerns. Prevailing strategies often employ adeno-associated viral (AAV) vectors to deliver neuroprotective survival genes directly into the central nervous system (CNS). However, these methods have been limited by triggering immunogenic responses and risk of tumorigenicity, resulting from overexpression of survival genes in peripheral blood mononuclear cells (PBMC), thereby increasing the risk of tumorigenicity in specific immune cells. Thus, by coding selectively suppressive microRNA (miRNA) target sequences in AAV genome, we designed CNS-targeted neuroprotective gene expression vector system without leakage to blood cells. METHODS: To minimize the potential for transgene contamination in the blood, we designed a CNS-specific AAV system. Our system utilized a self-complementary AAV (scAAV), encoding a quadruple repeated target sequence of the hematopoietic cell-specific miR142-3p at the 3' untranslated region (UTR). As a representative therapeutic survival gene for Parkinson's disease treatment, we integrated DX2, an antagonistic splice variant of the apoptotic gene AIMP2, known to be implicated in Parkinson's disease, into the vector. RESULTS: This configuration ensured that transgene expression was stringently localized to the CNS, even if the vector found its way into the blood cells. A single injection of scAAV-DX2 demonstrated marked improvement in behavior and motor activity in animal models of Parkinson's disease induced by either Rotenone or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Importantly, comprehensive preclinical data adhering to Good Laboratory Practice (GLP) standards revealed no adverse effects in the treated animals. CONCLUSIONS: Our CNS-specific vector system, which encodes a survival transgene DX2, signifies a promising avenue for safe gene therapy, avoiding unintended expression of survival gene in blood cells, applicable to various neurodegenerative diseases.
Asunto(s)
Enfermedad de Parkinson , Animales , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Leucocitos Mononucleares , Encéfalo/metabolismo , Terapia Genética/métodos , Transgenes , Vectores Genéticos , Dependovirus/genéticaRESUMEN
Kidney fibrosis is a major mechanism underlying chronic kidney disease (CKD). N6-methyladenosine (m6A) RNA methylation is associated with organ fibrosis. We investigated m6A profile alterations and the inhibitory effect of RNA methylation in kidney fibrosis in vitro (TGF-ß-treated HK-2 cells) and in vivo (unilateral ureteral obstruction [UUO] mouse model). METTL3-mediated signaling was inhibited using siRNA in vitro or the METTL3-specific inhibitor STM2457 in vivo and in vitro. In HK-2 cells, METTL3 protein levels increased in a dose- and time-dependent manner along with an increase in the cellular m6A levels. In the UUO model, METTL3 expression and m6A levels were significantly increased. Transcriptomic and m6A profiling demonstrated that epithelial-to-mesenchymal transition- and inflammation-related pathways were significantly associated with RNA m6A methylation. Genetic and pharmacologic inhibition of METTL3 in HK-2 cells decreased TGF-ß-induced fibrotic marker expression. STM2457-induced inhibition of METTL3 attenuated the degree of kidney fibrosis in vivo. Furthermore, METTL3 protein expression was significantly increased in the tissues of CKD patients with diabetic or IgA nephropathy. Therefore, targeting alterations in RNA methylation could be a potential therapeutic strategy for treating kidney fibrosis.
Asunto(s)
Riñón , Metiltransferasas , Insuficiencia Renal Crónica , Animales , Humanos , Ratones , Riñón/patología , Metiltransferasas/genética , Insuficiencia Renal Crónica/genética , ARN Interferente Pequeño , Factor de Crecimiento Transformador beta , FibrosisRESUMEN
BACKGROUND: While gelatin sponge particles and calibrated microspheres are commonly used as embolic materials in conventional transarterial chemoembolization (cTACE), direct comparisons between these embolic agents are rare. AIM: To compare the efficacy and safety of superselective cTACE using Embosphere® or Marine gel® in patients with early-stage hepatocellular carcinoma (HCC). METHODS: This retrospective study included 70 patients with small (< 4 cm) HCC who underwent cTACE with Embosphere® (n = 33) or Marine gel® (n = 37) as the embolic agent at a single center between March 2021 and July 2022. The radiologic images and clinical data were retrospectively reviewed, with an emphasis on tumor response, procedure-related complications, and local tumor recurrence. The primary index tumor was assessed on a 1-mo follow-up image, and local progression-free survival was obtained using the Kaplan-Meier method and was compared by the log-rank test. RESULTS: The median tumor size of both groups was 1.5 cm, and 69 patients achieved a complete response one month after cTACE. The cumulative local recurrence rate at 12 mo was 15.5% in the Embosphere® group and 14.4% in the Marine gel® group. The local progression-free survival was not significantly different between the two groups (P = 0.83). In the multivariate analysis, high serum alpha-fetoprotein was the only significant poor prognostic factor for local tumor progression (P = 0.01). Postembolization syndrome occurred in 36.4% of the Embosphere® group and 35.1% of the Marine gel® group, and there were no cases of biloma, biliary duct dilation, or liver abscess in either group. CONCLUSION: Calibrated gelatin sponge particles (Marine gel®) and calibrated microspheres (Embosphere®) have similar outcomes in terms of tumor response for superselective cTACE of small HCC.
RESUMEN
BACKGROUND: Parthanatos represents a critical molecular aspect of Parkinson's disease, wherein AIMP2 aberrantly activates PARP-1 through direct physical interaction. Although AIMP2 ought to be a therapeutic target for the disease, regrettably, it is deemed undruggable due to its non-enzymatic nature and predominant localization within the tRNA synthetase multi-complex. Instead, AIMP2 possesses an antagonistic splice variant, designated DX2, which counteracts AIMP2-induced apoptosis in the p53 or inflammatory pathway. Consequently, we examined whether DX2 competes with AIMP2 for PARP-1 activation and is therapeutically effective in Parkinson's disease. METHODS: The binding affinity of AIMP2 and DX2 to PARP-1 was contrasted through immunoprecipitation. The efficacy of DX2 in neuronal cell death was assessed under 6-OHDA and H2O2 in vitro conditions. Additionally, endosomal and exosomal activity of synaptic vesicles was gauged in AIMP2 or DX2 overexpressed hippocampal primary neurons utilizing optical live imaging with VAMP-vGlut1 probes. To ascertain the role of DX2 in vivo, rotenone-induced behavioral alterations were compared between wild-type and DX2 transgenic animals. A DX2-encoding self-complementary adeno-associated virus (scAAV) was intracranially injected into 6-OHDA induced in vivo animal models, and their mobility was examined. Subsequently, the isolated brain tissues were analyzed. RESULTS: DX2 translocates into the nucleus upon ROS stress more rapidly than AIMP2. The binding affinity of DX2 to PARP-1 appeared to be more robust compared to that of AIMP2, resulting in the inhibition of PARP-1 induced neuronal cell death. DX2 transgenic animals exhibited neuroprotective behavior in rotenone-induced neuronal damage conditions. Following a single intracranial injection of AAV-DX2, both behavior and mobility were consistently ameliorated in neurodegenerative animal models induced by 6-OHDA. CONCLUSION: AIMP2 and DX2 are proposed to engage in bidirectional regulation of parthanatos. They physically interact with PARP-1. Notably, DX2's cell survival properties manifest exclusively in the context of abnormal AIMP2 accumulation, devoid of any tumorigenic effects. This suggests that DX2 could represent a distinctive therapeutic target for addressing Parkinson's disease in patients.
Asunto(s)
Enfermedad de Parkinson , Parthanatos , Animales , Humanos , Inhibidores de Poli(ADP-Ribosa) Polimerasas , Proteínas Nucleares/metabolismo , Peróxido de Hidrógeno , Oxidopamina , Enfermedad de Parkinson/genética , Enfermedad de Parkinson/terapia , Rotenona , Línea Celular TumoralRESUMEN
PURPOSE: To evaluate the safety and effectiveness of ablative radioembolization for large hepatocellular carcinoma (HCC) while preserving a small future liver remnant (FLR). MATERIALS AND METHODS: Twenty-five patients with large HCC of ≥5 cm requiring treatment for >60% of the total liver volume and having well-preserved liver function were treated with ablative glass microsphere radioembolization at a single institution from January 2017 to December 2021. Radioembolization was performed with a mean absorbed dose of >150 Gy, and the FLR per nontumor liver volume (NTLV) was set at >30%. Changes in liver function, adverse events, duration of response (DoR) in a treated area, time-to-progression (TTP), and overall survival (OS) were retrospectively investigated. RESULTS: The largest tumor diameter and planned dose per treated volume were 11.4 cm ± 3.9 and 242.3 Gy ± 63.6 (169.4 Gy ± 45.9 per whole liver volume), respectively. All patients remained at Child-Pugh Class A for 90 days. No patient experienced Grade 3â4 hyperbilirubinemia or new ascites. One patient (lung dose, 27.8 Gy) developed radiation pneumonitis requiring transient steroid treatment. According to the posttreatment dosimetry, the tumorous and nontumorous liver absorbed doses were 418.8 Gy ± 227.4 and 69.0 Gy ± 32.1, respectively. The median DoR in a treated area and TTP were 22.0 and 17.1 months, respectively. The 5-year OS rate was 83.2%. CONCLUSIONS: Ablative radioembolization of large HCC of ≥5 cm can be performed safely and effectively in patients with preserved liver function when FLR/NTLV exceeds 30%.
Asunto(s)
Carcinoma Hepatocelular , Embolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Carcinoma Hepatocelular/radioterapia , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/radioterapia , Hepatectomía , Estudios Retrospectivos , Radioisótopos de Itrio/efectos adversos , Embolización Terapéutica/efectos adversos , Microesferas , Resultado del TratamientoRESUMEN
PURPOSE: This study aims to test the hypothesis that idarubicin-based transarterial chemoembolization (IDA-TACE), using one of the most potent chemotherapeutic agents, could yield oncologic outcomes equivalent to or marginally improved over doxorubicin-based TACE (DOX-TACE). MATERIALS AND METHODS: This single-center, prospective, phase II, randomized controlled, non-inferiority, double-blind trial will enroll 128 treatment-naïve patients with HCC (≤ 5 tumors, 1-5 cm in diameter) for conventional TACE. Participants will be randomly assigned (1:1) to either IDA-TACE or DOX-TACE, with stratification by Child-Pugh class. Superselective conventional TACE will be performed using cone-beam CT and small-bore microcatheters. Patient evaluations, including dynamic imaging and blood tests, will occur at 1, 3, and 6 months post-initial treatment. The primary outcome measure is the objective response rate (ORR) according to mRECIST at 6 months. Secondary outcomes include 3-month and 6-month tumor responses, time-to-progression, the incidence of treatment-related serious adverse events within 30 days, and the incidence and severity of any adverse events. STATISTICS: Non-inferiority will be claimed if the upper limit of a one-sided 97.5% confidence interval for the proportion difference (i.e., "6-month ORR of DOX-TACE" - "6-month ORR of IDA-TACE") falls below 0.15 in both intention-to-treat and per-protocol analyses. The proportion difference and its confidence interval will be calculated by the Cochran-Mantel-Haenszel method to obtain a weighted average of stratum-specific proportion differences. EXPECTED GAIN OF KNOWLEDGE: If IDA-TACE demonstrates outcomes comparable to DOX-TACE, this study could provide compelling evidence that various cytotoxic agents yield similar contributions in TACE, considering the minor role of chemotherapeutic agents in TACE. TRIAL REGISTRATION: ClinicalTrials.gov ( https://clinicaltrials.gov/ ). Identifier: NCT06114082. World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) ( https://trialsearch.who.int/Default.aspx ). Identifier: KCT0008166.
Asunto(s)
Carcinoma Hepatocelular , Quimioembolización Terapéutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamiento farmacológico , Quimioembolización Terapéutica/métodos , Ensayos Clínicos Fase II como Asunto , Doxorrubicina/uso terapéutico , Idarrubicina/uso terapéutico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamiento farmacológico , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Estudios de Equivalencia como AsuntoRESUMEN
BACKGROUND: Despite the application of various therapeutic methods, pain caused by complex regional pain syndrome (CRPS) is not sufficiently managed and often progresses to a chronic stage. For the systematic and effective treatment of CRPS, we developed an algorithm for multimodal medication therapy based on the established pathophysiology of CRPS to control CRPS-related pain. OBJECTIVE: In this study, we present the outcomes of our novel algorithm for multimodal medication therapy for patients with CRPS, consisting of three major components: multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapy. METHODS: We retrospectively investigated patients with CRPS who received multimodal therapy. Pain severity scores were evaluated using a numerical rating scale at four time points (P1, pain at initial consultation; P2, pain after oral medication; P3, pain after ketamine treatment; and P4, pain after lidocaine treatment). The effect of the multimodal medication therapy algorithm on pain management was evaluated at each time point. RESULTS: In patients with CRPS, multimodal oral medication, intravenous ketamine, and intravenous lidocaine therapies led to significantly improved pain control (p< 0.05). Additionally, the combination of these three therapies (through the multimodal medication therapy algorithm) resulted in significant pain relief in patients with CRPS (p< 0.05). CONCLUSIONS: Our multimodal medication therapy algorithm effectively controlled pain in patients with CRPS. However, further prospective studies with large sample sizes and randomized controlled trials are needed for more accurate generalization.
Asunto(s)
Algoritmos , Analgésicos , Síndromes de Dolor Regional Complejo , Ketamina , Lidocaína , Dimensión del Dolor , Humanos , Femenino , Masculino , Síndromes de Dolor Regional Complejo/tratamiento farmacológico , Estudios Retrospectivos , Ketamina/administración & dosificación , Ketamina/uso terapéutico , Persona de Mediana Edad , Lidocaína/administración & dosificación , Lidocaína/uso terapéutico , Adulto , Analgésicos/uso terapéutico , Analgésicos/administración & dosificación , Manejo del Dolor/métodos , Anestésicos Locales/administración & dosificación , Anestésicos Locales/uso terapéutico , Terapia Combinada , Resultado del Tratamiento , Administración Oral , Anciano , Administración IntravenosaRESUMEN
PURPOSE: This study aimed to verify the value of arterial spin labeling (ASL) collateral perfusion estimation for predicting functional outcomes in acute anterior circulation ischemic stroke. METHODS: This secondary analysis of an ongoing prospective observational study included data from participants with acute ischemic stroke due to steno-occlusion of the internal carotid artery and/or the middle cerebral artery within 8 h of symptom onset. We compared the collateral map, which is a 5-phase collateral imaging derived from dynamic contrast-enhanced magnetic resonance angiography, and ASL to validate the ASL collateral perfusion estimation. Multiple logistic regression analyses were conducted to identify independent predictors of favorable functional outcomes. RESULTS: One hundred forty-eight participants (68 ± 13 years, 96 men) were evaluated. The ASL collateral perfusion grade was positively correlated with the collateral perfusion grade of the collateral map (P < .001). Younger age (OR = 0.53, 95% CI = 0.36-0.78, P = .002), lower baseline NIHSS score (OR = 0.85, 95% CI = 0.78-0.92, P < .001), intermediate ASL collateral perfusion grade (OR = 4.02, 95% CI = 1.43-11.26, P = .008), good ASL collateral perfusion grade (OR = 26.37, 95% CI = 1.06-655.01, P = .046), and successful reperfusion (OR = 5.84, 95% CI = 2.08-16.42, P < .001) were independently associated with favorable functional outcomes. CONCLUSION: ASL collateral perfusion estimation provides prognostic information, which can be helpful in guiding management decisions.