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Recently, cases of antifreeze poisoning in companion animals, particularly cats, have surged in the Republic of Korea. Ethylene glycol (EG), the toxic primary component of antifreeze, is metabolized into glycolic acid (GA), leading to severe metabolic acidosis, acute kidney injury, and death. Traditional detection methods, although effective, are often time-consuming owing to complex sample preparation. This study involved a novel analytical method utilizing GC-MS for EG and LC-MS/MS for GA detection, which streamlined the detection process by eliminating the need for derivatization. The method was validated for accuracy and reliability, enabling the rapid and precise identification of EG and GA in biological samples. This study also included the successful application of this method in a case where initial exposure to antifreeze was not apparent, which highlighted the effectiveness of this method in diagnosing poisoning even in cases where clinical history is unclear. The development of this rapid diagnostic approach addresses the urgent need for the efficient detection of antifreeze poisoning, improving animal welfare and supporting forensic investigations.
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Etilenoglicol , Glicolatos , Animais , Etilenoglicol/intoxicação , Gatos , República da Coreia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Espectrometria de Massas em Tandem/métodos , Reprodutibilidade dos Testes , Cromatografia Líquida/métodosRESUMO
Matricellular proteins are integral non-structural components of the extracellular matrix. They serve as essential modulators of immunometabolism and tissue homeostasis, playing critical roles in physiological and pathological conditions. These extracellular matrix proteins including thrombospondins, osteopontin, tenascins, the secreted protein acidic and rich in cysteine (SPARC) family, the Cyr61, CTGF, NOV (CCN) family, and fibulins have multi-faceted functions in regulating immune cell functions, metabolic pathways, and tissue homeostasis. They are involved in immune-metabolic regulation and influence processes such as insulin signaling, adipogenesis, lipid metabolism, and immune cell function, playing significant roles in metabolic disorders such as obesity and diabetes. Furthermore, their modulation of tissue homeostasis processes including cellular adhesion, differentiation, migration, repair, and regeneration is instrumental for maintaining tissue integrity and function. The importance of these proteins in maintaining physiological equilibrium is underscored by the fact that alterations in their expression or function often coincide with disease manifestation. This review contributes to our growing understanding of these proteins, their mechanisms, and their potential therapeutic applications. [BMB Reports 2024; 57(9): 400-416].
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Proteínas da Matriz Extracelular , Homeostase , Humanos , Proteínas da Matriz Extracelular/metabolismo , Animais , Trombospondinas/metabolismo , Matriz Extracelular/metabolismo , Transdução de SinaisRESUMO
A 3-year-old boy with Glenn physiology exhibited refractory heart failure with reduced ejection fraction. To improve the patient's oxygen saturation, he underwent ventricular assist device (VAD) implantation with concomitant Fontan completion. The extracardiac conduit Fontan operation was performed with a 4-mm fenestration. For VAD implantation, Berlin Heart cannulas were positioned at the left ventricular apex and the neo-aorta. Following weaning from cardiopulmonary bypass, a temporary continuous-flow VAD, equipped with an oxygenator, was utilized for support. After a stabilization period of 1 week, the continuous-flow VAD was replaced with a durable pulsatile-flow device. Following 3 months of support, the patient underwent transplantation without complications. The completion of the Fontan procedure at the time of VAD implantation, along with the use of a temporary continuous-flow device with an oxygenator, may aid in stabilizing post-operative hemodynamics. This approach could contribute to a safe transition to a durable pulsatile VAD in patients with Glenn physiology.
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PURPOSE: To evaluate changes in ocular surface indices and tear cytokines after cataract surgery in type 2 diabetic patients. METHODS: Ocular surface indices and concentrations of tear cytokines (MCP-1, IL-6, IL-8, and VEGF) were evaluated at baseline and one week and one month postoperatively. RESULTS: Patients (30 diabetic and 30 control) were enrolled. In the diabetic group, changes in ocular symptom and tear breakup time remained until one month postoperatively (P < .05, respectively); in the control group, ocular symptom increased at one week postoperatively (P = .015). MCP-1 level in the diabetic group significantly increased postoperatively (all P < .05); however, in the control group, the IL-8 level was significantly decreased postoperatively (all P < .05). MCP-1 concentration was negatively correlated with TBUT in the diabetic group. CONCLUSION: Diabetic patients can experience more prominent changes after surgery and these changes were accompanied by an increase of several tear cytokines.
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Catarata , Diabetes Mellitus Tipo 2 , Humanos , Citocinas , Diabetes Mellitus Tipo 2/complicações , Interleucina-8 , CórneaRESUMO
A formal screening of self-complementary adeno-associated virus (scAAV) vector serotypes in canine joint tissues has not been performed to date. Selecting appropriate serotypes is crucial for successful treatment due to their varying levels of tissue tropism. The objective of this study is to identify the most optimal scAAV vector serotype that maximizes transduction efficiencies in canine cell monolayer cultures (chondrocytes, synoviocytes, and mesenchymal stem cells) and tissue explant cultures (cartilage and synovium). Transduction efficiencies of scAAV serotypes 1, 2, 2.5, 3, 4, 5, 6, 8, and 9 were evaluated in each culture type in three different vector concentrations by encoding a green fluorescent protein. It was found that scAAV2 and 2.5 showed the overall highest transduction efficiency among serotypes with dose-response. Since possible immune response against conventional AAV2 was previously reported in dogs, the chimeric scAAV2.5 may be more suitable to use. Evaluation of the safety and efficacy of the scAAV2.5 vector with an appropriate therapeutic gene in vivo is indicated.
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Dependovirus , Vetores Genéticos , Cães , Animais , Sorogrupo , Transdução Genética , Vetores Genéticos/genética , Dependovirus/genética , Dependovirus/metabolismoRESUMO
PURPOSE: To investigate the effects of deep learning-based imaging reconstruction (DLR) on the image quality of MRI of rectal cancer after chemoradiotherapy (CRT), and its accuracy in diagnosing pathological complete responses (pCR). METHODS: We included 39 patients (men: women, 21:18; mean age ± standard deviation, 59.1 ± 9.7 years) with mid-to-lower rectal cancer who underwent a long-course of CRT and high-resolution rectal MRIs between January 2020 and April 2021. Axial T2WI was reconstructed using the conventional method (MRIconv) and DLR with two different noise reduction factors (MRIDLR30 and MRIDLR50). The signal-to-noise ratio (SNR) of the tumor was measured. Two experienced radiologists independently made a blind assessment of the complete response on MRI. The sensitivity and specificity for pCR were analyzed using a multivariable logistic regression analysis with generalized estimating equations. RESULTS: Thirty-four patients did not have a pCR whereas five (12.8%) had pCR. Compared with the SNR of MRIconv (mean ± SD, 7.94 ± 1.92), MRIDLR30 and MRIDLR50 showed higher SNR (9.44 ± 2.31 and 11.83 ± 3.07, respectively) (p < 0.001). Compared to MRIconv, MRIDLR30 and MRIDLR50 showed significantly higher specificity values (p < 0.036) while the sensitivity values were not significantly different (p > 0.301). The sensitivity and specificity for pCR were 48.9% and 80.8% for MRIconv; 48.9% and 88.2% for MRIDLR30; and 38.8% and 86.7% for MRIDLR50, respectively. CONCLUSION: DLR produced MR images with higher resolution and SNR. The specificity of MRI for identification of pCR was significantly higher with DLR than with conventional MRI.
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Aprendizado Profundo , Imageamento por Ressonância Magnética , Neoplasias Retais , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Imageamento por Ressonância Magnética/métodos , Terapia Neoadjuvante , Neoplasias Retais/diagnóstico por imagem , Neoplasias Retais/terapia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Although there are growing demands for stem cell-based therapy for companion animals in various diseases, a few clinical trials have been reported. Moreover, most of them are the results from only one or a few times of stem cell injection. OBJECTIVES: The aim of this study is to describe a long-term treatment with allogeneic adipose-derived stem cells (ASCs) in a dog with rheumatoid arthritis (RA), which is a rare canine disease. METHODS: The dog with RA received intravascular injection of allogeneic ASCs derived from two healthy donors once a month for 11 months. To assess therapeutic effects of ASCs, orthopedic examination and clinical evaluation was performed. Cytokines of tumor necrosis factor-α and interleukin-6 in the plasma were measured using ELISA analysis. RESULTS: Despite this repeated and long-term administration of allogeneic ASCs, there were no side effects such as immunorejection responses or cell toxicity. The orthopedic examination score for the dog decreased after ASCs treatment, and the clinical condition of the dog and owner's satisfaction were very good. CONCLUSIONS: Although ASCs has been suggested as one of the options for RA treatment because of its anti-inflammatory and immunosuppressive functions, it has never been used to treat RA in dogs. The present report describes a case of canine RA treated with allogeneic ASCs for long-term in which the dog showed clinical improvement without adverse effects.
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Artrite Reumatoide , Doenças do Cão , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Tecido Adiposo , Animais , Artrite Reumatoide/patologia , Artrite Reumatoide/terapia , Artrite Reumatoide/veterinária , Doenças do Cão/terapia , Cães , Transplante de Células-Tronco Hematopoéticas/veterináriaRESUMO
As pyrazole and its derivatives have a wide range of biological activities, including anticancer activity, the design of novel pyrazole derivatives has emerged as an important research field. This study describes a novel pyrazole derivative that exerts antitumor and radiosensitizing activities in breast cancer both in vitro and in vivo. We synthesized a novel pyrazole compound N,N-dimethyl-N'-(3-(1-(4-(trifluoromethyl)phenyl)-1H-pyrazol-4-yl)phenyl)azanesulfonamide (PCW-1001) and showed that it inhibited several oncogenic properties of breast cancer both in vitro and in vivo. PCW-1001 induced apoptosis in several breast cancer cell lines. Transcriptome analysis of PCW-1001-treated cells showed that it regulates genes involved in the DNA damage response, suggesting its potential use in radiotherapy. Indeed, PCW-1001 enhanced the radiation sensitivity of breast cancer cells by modulating the expression of DNA damage response genes. Therefore, our data describe a novel pyrazole compound, PCW-1001, with antitumor and radiosensitizer activities in breast cancer.
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Alteration in stress response seems to affect the development of psychiatric disorders. In this study, we aimed to investigate whether baseline peripheral biomarkers could predict the reduction of stress response among patients with major depressive disorder (MDD) and panic disorder (PD). Patients with MDD (n = 41) and PD (n = 52) and healthy controls (HC, n = 59) were selected and regularly followed up with five visits for 12 weeks. The severity of stress at every visit was assessed using the Stress Response Inventory (SRI), and peripheral biomarkers were measured by blood tests at baseline and 2, 4, 8, and 12 weeks. Interleukin (IL)-6, IL-10, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, C-reactive protein (CRP), adiponectin, and leptin levels were analyzed using enzyme-linked immunosorbent assays. Reduction of stress response was defined as the difference in SRI score between baseline and 12 weeks divided by the baseline score. SRI scores were significantly (p < 0.0001) higher in patients with MDD and PD than in HC at every visit after adjusting for variables. In multivariable linear regression, adiponectin levels at baseline were significantly associated with reduction of stress response in patients with PD. When adiponectin increased 1 mg/l, stress response decreased 0.781 points (ß = -0.781, S.E. = 0.220, p = 0.001). Among the subscales of SRI, somatization had a moderate negative correlation with adiponectin levels (r = -0.469). There was no significant association between baseline peripheral biomarkers and reduction of stress response in patients with MDD. Our study showed an inverse association between baseline adiponectin levels and stress response changes in patients with PD, but not in patients with MDD. Thus, differentiated approaches for assessing and treating stress responses of patients with PD and MDD might be helpful. Larger and longitudinal studies are necessary to establish the role and mechanism of action of adiponectin in regulating stress responses in PD.
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OBJECTIVES: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. METHODS: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. RESULTS: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). CONCLUSIONS: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.
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COVID-19 , Púrpura Trombocitopênica Idiopática , Trombocitopenia , Trombose , Vacinas , Trombose Venosa , Ad26COVS1 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , ChAdOx1 nCoV-19 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/epidemiologia , Púrpura Trombocitopênica Idiopática/etiologia , SARS-CoV-2 , Trombocitopenia/etiologia , Trombose/epidemiologia , Trombose/etiologia , Trombose Venosa/induzido quimicamente , Trombose Venosa/etiologiaRESUMO
On October 2020, the US Food and Drug Administration (FDA) approved remdesivir as the first drug for the treatment of coronavirus disease 2019 (COVID-19), increasing remdesivir prescriptions worldwide. However, potential cardiovascular (CV) toxicities associated with remdesivir remain unknown. We aimed to characterize the CV adverse drug reactions (ADRs) associated with remdesivir using VigiBase, an individual case safety report database of the World Health Organization (WHO). Disproportionality analyses of CV-ADRs associated with remdesivir were performed using reported odds ratios and information components. We conducted in vitro experiments using cardiomyocytes derived from human pluripotent stem cell cardiomyocytes (hPSC-CMs) to confirm cardiotoxicity of remdesivir. To distinguish drug-induced CV-ADRs from COVID-19 effects, we restricted analyses to patients with COVID-19 and found that, after adjusting for multiple confounders, cardiac arrest (adjusted odds ratio [aOR]: 1.88, 95% confidence interval [CI]: 1.08-3.29), bradycardia (aOR: 2.09, 95% CI: 1.24-3.53), and hypotension (aOR: 1.67, 95% CI: 1.03-2.73) were associated with remdesivir. In vitro data demonstrated that remdesivir reduced the cell viability of hPSC-CMs in time- and dose-dependent manners. Physicians should be aware of potential CV consequences following remdesivir use and implement adequate CV monitoring to maintain a tolerable safety margin.
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Monofosfato de Adenosina/análogos & derivados , Alanina/análogos & derivados , Antivirais/efeitos adversos , Tratamento Farmacológico da COVID-19 , Doenças Cardiovasculares/induzido quimicamente , Farmacovigilância , SARS-CoV-2 , Monofosfato de Adenosina/efeitos adversos , Alanina/efeitos adversos , Bases de Dados Factuais , Humanos , Miócitos Cardíacos/efeitos dos fármacos , Estudos Retrospectivos , Organização Mundial da SaúdeRESUMO
OBJECTIVE: Flattening in the anteroposterior direction (AP flattening) of the terminal ileum (TI) or sigmoid colon (SC) lying across the psoas muscle, on magnetic resonance enterography (MRE), might mimic bowel inflammation in the coronal view. This study investigated the prevalence of AP flattening and the factors associated with its development. MATERIALS AND METHODS: A total of 364 surgery-naïve patients with Crohn's disease (CD) who had undergone MRE were retrospectively reviewed. AP flattening was defined as a luminal collapse in the anteroposterior direction, with a bowel width in the axial plane < 1/4 of the normal diameter without reduction of bowel width in coronal images. The prevalence of AP flattening of the TI and SC on MRE in patients with bowel segments lying across the psoas muscle was determined. We further compared the rate of AP flattening between MRE and computed tomography enterography (CTE) in a subcohort of patients with prior CTE. The factors associated with AP flattening were analyzed using multivariable logistic regression in a subcohort of patients with endoscopic findings of TI. RESULTS: Three hundred and twenty-two and 363 patients, respectively, had TI and SC lying across the psoas muscle. The prevalence of AP flattening on MRE was 7.5% (24/322) in TI and 5.2% (19/363) in SC. The prevalences were significantly higher on MRE than on CTE in both the TI (7.3% [12/164] vs. 0.6% [1/164]; p = 0.003) and SC (5.8% [11/190] vs. 1.6% [3/190]; p = 0.039). AP flattening of the TI was independently and strongly associated with the absence of CD inflammation on endoscopy, with an adjusted odds ratio of 0.066 (p = 0.003) for the presence versus the absence (reference) of inflammation. CONCLUSION: AP flattening of the TI or SC lying across the psoas muscle was uncommon and predominantly observed on MRE of the bowel without CD inflammation.
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Doença de Crohn , Colo Sigmoide/diagnóstico por imagem , Doença de Crohn/diagnóstico por imagem , Humanos , Íleo , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Músculos Psoas/diagnóstico por imagem , Estudos RetrospectivosRESUMO
Foot-and-mouth disease (FMD) is a highly contagious disease caused by FMD virus (FMDV) in cloven-hoofed animals. Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are representative receptors in the cytoplasm for the detection of viral RNA and trigger antiviral responses, leading to the production of type I interferon. Although MDA5 is a crucial receptor for sensing picornavirus RNA, the interplay between MDA5 and FMDV is relatively unknown compared to the interplay between RIG-I and FMDV. Here, we observed that the FMDV infection inhibits MDA5 protein expression. Of the non-structural proteins, the Lb and 3C proteinases (Lbpro and 3Cpro) were identified to be primarily responsible for this inhibition. However, the inhibition by 3Cpro was independent of proteasome, lysosome and caspase-dependent pathway and was by 3C protease activity. A direct interaction between 3Cpro and MDA5 protein was observed. In conclusion, this is the first report that 3Cpro inhibits MDA5 protein expression as a mechanism to evade the innate immune response during FMDV infection. These results elucidate the pathogenesis of FMDV and provide fundamental insights for the development of a novel vaccine or therapeutic agent.
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Proteases Virais 3C/metabolismo , Vírus da Febre Aftosa/imunologia , Evasão da Resposta Imune , Imunidade Inata , Helicase IFIH1 Induzida por Interferon/metabolismo , Animais , Caspases/metabolismo , Catálise , Proteína DEAD-box 58/metabolismo , Regulação para Baixo , Células HEK293 , Humanos , Interferons/genética , Interferons/metabolismo , Lisossomos/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Transdução de Sinais , Suínos , Transcrição GênicaRESUMO
Previous studies have investigated the role of inflammatory markers in suicidality of patients with major depressive disorder (MDD) or panic disorder (PD). However, few studies have investigated associations between serum inflammatory cytokine levels and suicidality. We hypothesized that MDD and PD status might be significantly associated with serum inflammatory cytokines and that we could predict levels of improvement in suicide ideation intensity using serum inflammatory biomarkers in patients with MDD and PD. For this study, 41 patients with MDD, 52 patients with PD, and 59 healthy control (HC) subjects were enrolled. Psychological measurements and serum inflammatory markers such as interleukin (IL) -6, -10, interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and C reactive protein (CRP) were examined. A total of five visits were completed during 12 weeks. After controlling for confounding factors, log-transformed IL-6 (ln_IL-6) at baseline (MDD: 0.297 ± 0.626; PD: 0.342 ± 0.723; HC: -0.121 ± 0.858; p = 0.007, >0.0017, 0.05/30) and mean ln_IL-6 (MDD: 0.395 ± 0.550, PD: 0.249 ± 0.544, HC: -0.139 ± 0.622, p = 0.002, >0.0017, 0.05/30) levels were trends towards significantly higher in patients with MDD and PD than in HC. In MDD patients, a higher level of basal ln_TNF-α was a significant predictor of ΔSSI (changes in SSI scores between baseline and week 12) even after controlling for changes of depression symptoms and baseline SSI scores (standardized ß = 0.541, p = 0.002 < 0.0028, 0.05/18). In conclusion, we could predict ΔSSI using baseline inflammatory biomarkers for patients with MDD.
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Transtorno Depressivo Maior , Transtorno de Pânico , Biomarcadores , Seguimentos , Humanos , Ideação SuicidaRESUMO
BACKGROUND: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) treated with pralatrexate have previously shown superior overall survival (OS) compared to those who underwent conventional chemotherapy (CC, 15.4 vs. 4.07 months). We conducted an economic evaluation of pralatrexate from a societal perspective in Korea based on data from the PROPEL phase II study. METHODS: Using a Markov model with a weekly cycle, we simulated the experience of patients with R/R PTCL receiving pralatrexate or CC for 15 years. The model consists of five health states; initial treatment, treatment pause, subsequent treatment, stem cell transplantation (SCT) success, and death. Comparative effectiveness was based on PROPEL phase II single-arm study and its matched historical control analysis. Costs included drug, drug administration, monitoring, adverse event management, and SCT costs. RESULTS: The incremental cost-effectiveness ratio of the base case was $39,153 per quality-adjusted life-year (QALY) gained. The results of one-way sensitivity analysis ranged from $33,949 to $51,846 per QALY gained, which remained within an implicit willingness-to-pay (WTP) threshold of anticancer drugs in Korea. CONCLUSIONS: Pralatrexate is a cost-effective intervention with improved OS and incremental costs within the WTP limit. Pralatrexate could function as a new therapeutic option for patients suffering from life-threatening R/R PTCL.
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Aminopterina/análogos & derivados , Linfoma de Células T Periférico/tratamento farmacológico , Linfoma de Células T Periférico/economia , Aminopterina/economia , Aminopterina/farmacologia , Aminopterina/uso terapêutico , Estudos de Casos e Controles , Análise Custo-Benefício , Feminino , Humanos , Masculino , Recidiva Local de NeoplasiaRESUMO
Although MASTL (microtubule-associated serine/threonine kinase-like) is an attractive target for anticancer treatment, MASTL inhibitors with antitumor activity have not yet been reported. In this study, we have presented a novel MASTL inhibitor, MKI-1, identified through in silico screening and in vitro analysis. Our data revealed that MKI-1 exerted antitumor and radiosensitizer activities in in vitro and in vivo models of breast cancer. The mechanism of action of MKI-1 occurred through an increase in PP2A activity, which subsequently decreased the c-Myc protein content in breast cancer cells. Moreover, the activity of MKI-1 in the regulation of MASTL-PP2A was validated in a mouse oocyte model. Our results have demonstrated a new small-molecule inhibitor of MASTL, MKI-1, which exerts antitumor and radiosensitizer activities through PP2A activation in breast cancer in vitro and in vivo.
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Treatment options for children with end-stage heart failure are limited. We report the first case of a successful pediatric heart transplantation bridged with a durable left ventricular assist device in Korea. A 10-month-old female infant with dilated cardiomyopathy and left ventricular non-compaction was listed for heart transplantation. During the waiting period, the patient's status deteriorated. Therefore, we decided to provide support with a durable left ventricular assist device as a bridge to transplantation. The patient was successfully bridged to heart transplantation with effective support and without any major adverse events.
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OBJECTIVES: To determine the diagnostic accuracy of magnetic resonance tumor regression grade (mrTRG) for pathological complete response (pCR) and its correlation with pathological findings. METHODS: Original studies that investigated the correlation of mrTRG with pathological tumor regression grade and pathological T stage were identified in MEDLINE and EMBASE up until August 31, 2018, according to PRISMA guidelines. The search terms included colorectal cancer, chemoradiation therapy, magnetic resonance imaging, and response or regression. Meta-analytic summary sensitivity and specificity for pathologic complete response (pCR) and pathologic T1 or lower than T1 stage (≤ypT1) were calculated using a bivariate random-effects model. The sensitivity and specificity were calculated in both mrTRG 1 and mrTRG 1 or 2, respectively. RESULTS: Six studies with 916 patients were included. The meta-analytic summary sensitivity and specificity of mrTRG 1 for pCR were 32.3% (95% CI, 18.2-50.6%) and 93.5% (95% CI, 91.5-95.1%), while for ≤ypT1 they were 31.8% (95% CI, 16.2-53.0%) and 94.7% (95% CI, 91.9-96.5%). On the contrary, sensitivity and specificity of mrTRG 1 or 2 for pCR were 69.9% (95% CI, 60.2-78.1%) and 62.2% (95% CI, 56.2-67.8%), while those for ≤ypT1 were 71.4% (95% CI, 61.6-79.6%) and 67.7% (95% CI, 59.8-74.7%). CONCLUSIONS: mrTRG 1 showed high specificity for pCR and ≤ypT1, but suboptimal sensitivity. mrTRG 1 or 2 showed higher sensitivity for pCR and ≤ypT1, but lower specificity. Because of the suboptimal sensitivity of mrTRG 1, it might be limited as a criterion for less aggressive treatment after neoadjuvant chemoradiotherapy. KEY POINTS: ⢠Magnetic resonance tumor regression grade 1 shows high specificity for pCR and ≤ypT1, but suboptimal sensitivity. ⢠Magnetic resonance tumor regression grade 1 or 2 shows higher sensitivity for pCR and ≤ypT1, but lower specificity than magnetic resonance tumor regression grade 1 alone.
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Algoritmos , Imageamento por Ressonância Magnética/métodos , Estadiamento de Neoplasias/métodos , Neoplasias Retais/patologia , Quimiorradioterapia/métodos , Humanos , Terapia Neoadjuvante/métodos , Neoplasias Retais/terapia , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Since the introduction of 2 rotavirus (RV) vaccines in Korea, the vaccination rate has reached over 80% with out-of-pocket spending in the private market. We investigated the socioeconomic impact of RV vaccines in Korea to assess their value and public health contribution. METHODS: By using National Health Insurance Service claims data, we compared the epidemiologic and economic characteristics of rotavirus gastroenteritis (RVGE) before and after the introduction of RV vaccines. For each year of the study period, the annual prevalence and national costs of RVGE were estimated based on children under 5 years with at least 1 National Health Insurance Service claims record with a diagnosis of RVGE. RESULTS: Compared with the prevaccination period, the prevalence of RVGE decreased in the postvaccination period by 48.9% from 2097 per 100,000 children in 2006 to 1072 per 100,000 children in 2015, implying an increase in the vaccination rate and the prevention effect of the vaccines. The highest reduction was observed among those 12 to <24 months of age (-73.4%), presumably due to the benefit of full vaccination, while children under 2 months, ineligible for the RV vaccine, showed an increase (41.7%). The number of hospitalized RVGE cases per year decreased by 69.0%. The national economic burden of RVGE decreased by 28.6%. CONCLUSIONS: The substantial reduction in the socioeconomic burden of RVGE after the introduction of RV vaccines confirms their benefit to society. This study would help health policy makers make empirical decisions on incorporating the vaccination into national immunization programs.