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1.
Nat Med ; 30(3): 699-707, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38374347

RESUMO

Regorafenib has anti-tumor activity in patients with unresectable hepatocellular carcinoma (uHCC) with potential immunomodulatory effects, suggesting that its combination with immune checkpoint inhibitor may have clinically meaningful benefits in patients with uHCC. The multicenter, single-arm, phase 2 RENOBATE trial tested regorafenib-nivolumab as front-line treatment for uHCC. Forty-two patients received nivolumab 480 mg every 4 weeks and regorafenib 80 mg daily (3-weeks-on/1-week-off schedule). The primary endpoint was the investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. The secondary endpoints included safety, progression-free survival (PFS) and overall survival (OS). ORR per RECIST version 1.1 was 31.0%, meeting the primary endpoint. The most common adverse events were palmar-plantar erythrodysesthesia syndrome (38.1%), alopecia (26.2%) and skin rash (23.8%). Median PFS was 7.38 months. The 1-year OS rate was 80.5%, and the median OS was not reached. Exploratory single-cell RNA sequencing analyses of peripheral blood mononuclear cells showed that long-term responders exhibited T cell receptor repertoire diversification, enrichment of genes representing immunotherapy responsiveness in MKI67+ proliferating CD8+ T cells and a higher probability of M1-directed monocyte polarization. Our data support further clinical development of the regorafenib-nivolumab combination as front-line treatment for uHCC and provide preliminary insights on immune biomarkers of response. ClinicalTrials.gov identifier: NCT04310709 .


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Compostos de Fenilureia , Piridinas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Linfócitos T CD8-Positivos , Leucócitos Mononucleares , Neoplasias Hepáticas/tratamento farmacológico , Nivolumabe/uso terapêutico
2.
Food Res Int ; 180: 114054, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38395548

RESUMO

Peptidomics analysis was conducted using high-resolution tandem mass spectrometry (MS2) to determine the peptide profile of snail-derived mucin extract (SM). The study was also aimed to identify an indicator peptide and validate a quantification method for this peptide. The peptide profiling and identification were conducted using discovery-based peptidomics analysis employing data-dependent acquisition, whereas the selected peptides were verified and quantified using parallel reaction monitoring acquisition. Among the 16 identified peptides, the selected octapeptide (TEAPLNPK) was quantified via precursor ion ionization (m/z 435.2400), followed by quantification of the corresponding quantifier ion fragment (m/z 639.3824) using MS2. The quantification method was optimized and validated in terms of specificity, linearity, accuracy, precision, and limit of detection/quantification. The validated method accurately quantified the TEAPLNPK content in the SM as 7.5 ± 0.2 µg/g. Our study not only identifies an indicator peptide from SM but also introduces a novel validation method, involving precursor ion ionization and quantification of specific fragments. Our findings may serve as a comprehensive workflow for the monitoring, selection, and quantification of indicator peptides from diverse food resources.


Assuntos
Mucinas , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Fluxo de Trabalho , Peptídeos/química
3.
Cell Rep Med ; 4(11): 101251, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37890486

RESUMO

Evidence on whether prior antibiotic (pATB) administration modulates outcomes of programmed cell death protein-1 (PD-1) inhibitors in advanced gastric cancer (AGC) is scarce. In this study, we find that pATB administration is consistently associated with poor progression-free survival (PFS) and overall survival (OS) in multiple cohorts consisting of patients with AGC treated with PD-1 inhibitors. In contrast, pATB does not affect outcomes among patients treated with irinotecan. Multivariable analysis of the overall patients treated with PD-1 inhibitors confirms that pATB administration independently predicts worse PFS and OS. Administration of pATBs is associated with diminished gut microbiome diversity, reduced abundance of Lactobacillus gasseri, and disproportional enrichment of circulating exhaustive CD8+ T cells, all of which are associated with worse outcomes. Considering the inferior treatment response and poor survival outcomes by pATB administration followed by PD-1 blockade, ATBs should be prescribed with caution in patients with AGC who are planning to receive PD-1 inhibitors.


Assuntos
Antibacterianos , Microbioma Gastrointestinal , Inibidores de Checkpoint Imunológico , Neoplasias Gástricas , Humanos , Antibacterianos/administração & dosagem , Linfócitos T CD8-Positivos , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/imunologia
4.
Cells ; 12(14)2023 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-37508518

RESUMO

One major challenge associated with lung cancer organoids (LCOs) is their predominant derivation from surgical specimens of patients with early-stage lung cancer. However, patients with advanced lung cancer, who are in need of chemotherapy, often cannot undergo surgery. Therefore, there is an urgent need to successfully generate LCOs from biopsy specimens. Conventional lung biopsy techniques, such as transthoracic needle biopsy and forceps biopsy, only yield small amounts of lung tissue, resulting in a low success rate for culturing LCOs from biopsy samples. Furthermore, potential complications, like bleeding and pneumothorax, make it difficult to obtain sufficient tissue. Another critical issue is the overgrowth of normal lung cells in later passages of LCO culture, and the optimal culture conditions for LCOs are yet to be determined. To address these limitations, we attempted to create LCOs from cryobiopsy specimens obtained from patients with lung cancer (n = 113). Overall, the initial success rate of establishing LCOs from cryobiopsy samples was 40.7% (n = 46). Transbronchial cryobiopsy enables the retrieval of significantly larger amounts of lung tissue than bronchoscopic forceps biopsy. Additionally, cryobiopsy can be employed for peripheral lesions, and it is aided via radial endobronchial ultrasonography. This study significantly improved the success rate of LCO culture and demonstrated that the LCOs retained characteristics that resembled the primary tumors. Single-cell RNA sequencing confirmed high cancer cell purity in early passages of LCOs derived from patients with advanced lung cancer. Furthermore, the three-dimensional structure and intracellular components of LCOs were characterized using three-dimensional holotomography. Finally, drug screening was performed using a specialized micropillar culture system with cryobiopsy-derived LCOs. LCOs derived from cryobiopsy specimens offer a promising solution to the critical limitations of conventional LCOs. Cryobiopsy can be applied to patients with lung cancer at all stages, including those with peripheral lesions, and can provide sufficient cells for LCO generation. Therefore, we anticipate that cryobiopsy will serve as a breakthrough strategy for the clinical application of LCOs in all stages of lung cancer.


Assuntos
Criocirurgia , Neoplasias Pulmonares , Humanos , Broncoscopia/métodos , Criocirurgia/métodos , Neoplasias Pulmonares/patologia , Pulmão/patologia , Organoides/patologia
5.
Rheumatology (Oxford) ; 62(11): 3690-3699, 2023 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-36929924

RESUMO

OBJECTIVES: To investigate computer-aided quantitative scores from high-resolution CT (HRCT) images and determine their longitudinal changes and clinical significance in patients with idiopathic inflammatory myopathies (IIMs)-related interstitial lung disease (IIMs-ILD). METHODS: The clinical data and HRCT images of 80 patients with IIMs who underwent serial HRCT scans at least twice were retrospectively analysed. Quantitative ILD (QILD) scores (%) were calculated as the sum of the extent of lung fibrosis, ground-glass opacity, and honeycombing. The individual time-estimated ΔQILD between two consecutive scans was derived using a linear approximation of yearly changes. RESULTS: The baseline median QILD (interquartile range) scores in the whole lung were 28.1% (19.1-43.8). The QILD was significantly correlated with forced vital capacity (r = -0.349, P = 0.002) and diffusing capacity for carbon monoxide (r = -0.381, P = 0.001). For ΔQILD between the first two scans, according to the visual ILD subtype, QILD aggravation was more frequent in patients with usual interstitial pneumonia (UIP) than non-UIP (80.0% vs 44.4%, P = 0.013). Multivariable logistic regression analyses identified UIP was significantly related to radiographic ILD progression (ΔQILD >2%, P = 0.015). Patients with higher baseline QILD scores (>28.1%) had a higher risk of lung transplantation or death (P = 0.015). In the analysis of three serial HRCT scans (n = 41), dynamic ΔQILD with four distinct patterns (improving, worsening, convex and concave) was observed. CONCLUSION: QILD changes in IIMs-ILD were dynamic, and baseline UIP patterns seemed to be related to a longitudinal progression in QILD. These may be potential imaging biomarkers for lung function, changes in ILD severity and prognosis in IIMs-ILD.


Assuntos
Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Miosite , Humanos , Estudos Retrospectivos , Doenças Pulmonares Intersticiais/diagnóstico por imagem , Pulmão/diagnóstico por imagem , Miosite/diagnóstico por imagem
6.
Exp Mol Med ; 55(3): 653-664, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36941461

RESUMO

We do not yet understand exactly how corticosteroids attenuate hyperinflammatory responses and alleviate high-risk coronavirus disease 2019 (COVID-19). We aimed to reveal the molecular mechanisms of hyperinflammation in COVID-19 and the anti-inflammatory effects of corticosteroids in patients with high-risk COVID-19. We performed single-cell RNA sequencing of peripheral blood mononuclear cells (PBMCs) from three independent COVID-19 cohorts: cohort 1 was used for comparative analysis of high-risk and low-risk COVID-19 (47 PBMC samples from 28 patients), cohort 2 for longitudinal analysis during COVID-19 (57 PBMC samples from 15 patients), and cohort 3 for investigating the effects of corticosteroid treatment in patients with high-risk COVID-19 (55 PBMC samples from 13 patients). PBMC samples from healthy donors (12 PBMC samples from 12 donors) were also included. Cohort 1 revealed a significant increase in the proportion of monocytes expressing the long noncoding RNAs NEAT1 and MALAT1 in high-risk patients. Cohort 2 showed that genes encoding inflammatory chemokines and their receptors were upregulated during aggravation, whereas genes related to angiogenesis were upregulated during improvement. Cohort 3 demonstrated downregulation of interferon-stimulated genes (ISGs), including STAT1, in monocytes after corticosteroid treatment. In particular, unphosphorylated STAT-dependent ISGs enriched in monocytes from lupus patients were selectively downregulated by corticosteroid treatment in patients with high-risk COVID-19. Corticosteroid treatment suppresses pathologic interferon responses in monocytes by downregulating STAT1 in patients with high-risk COVID-19. Our study provides insights into the mechanisms underlying COVID-19 aggravation and improvement and the effects of corticosteroid treatment.


Assuntos
COVID-19 , Leucócitos Mononucleares , Humanos , Leucócitos Mononucleares/metabolismo , Interferons , Monócitos/metabolismo , Corticosteroides/farmacologia , Corticosteroides/uso terapêutico , Fator de Transcrição STAT1/genética , Fator de Transcrição STAT1/metabolismo
7.
Arthritis Rheumatol ; 75(7): 1176-1186, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36787119

RESUMO

OBJECTIVE: To demonstrate the immune landscape of blood and synovial cells in the setting of ankylosing spondylitis (AS) through the analysis of both single-cell transcriptome and surface protein expression, and to unveil the molecular characteristics of pathogenic Th17 cells. METHODS: This study included 40 individuals with active AS, 20 individuals with stable AS, 40 patients with active rheumatoid arthritis, and 20 healthy controls. Surface phenotype and intracellular staining were assessed using flow cytometry after peripheral blood mononuclear cells and synovial fluid mononuclear cells were stimulated with T cell receptor. Single-cell transcriptomes of 6 patients with active AS were studied along with cellular indexing of transcriptomes and epitopes by sequencing. We also assessed the outcome of targeting OX40 and glucocorticoid-induced tumor necrosis factor receptor (GITR) on the surface of Th17 cells in a mouse model of curdlan-injected SKG mice in which anti-GITR ligand and/or anti-OX40 ligand were used. RESULTS: We identified pathogenic Th17 cells as polyfunctional interleukin-17A (IL-17A)- and interferon-γ (IFNγ)-producing memory CD4+ T cells, with clinically supportive evidence for their pathogenic roles at sites of inflammation in AS. Transcriptome and flow cytometric analyses revealed that the coexpression of TNFRSF4 (OX40) and TNFRSF18 (GITR) is increased in pathogenic Th17 cells. Suppression of ligand receptor interactions in vivo through OX40 and GITR effectively suppressed clinical arthritis and decreased pathogenic Th17 cells in the curdlan-injected SKG mouse model. CONCLUSION: Our results have implications for the understanding of pathogenic Th17 cells in AS patients and suggest potential therapeutic targets.


Assuntos
Espondilite Anquilosante , Camundongos , Animais , Espondilite Anquilosante/genética , Transcriptoma , Glucocorticoides , Linfócitos T CD4-Positivos , Células Th17 , Leucócitos Mononucleares/metabolismo , Ligantes , Receptores do Fator de Necrose Tumoral , Fator de Necrose Tumoral alfa
8.
Artigo em Inglês | MEDLINE | ID: mdl-35627518

RESUMO

Knee arthroplasties are strongly associated with blood transfusion to compensate for perioperative bleeding. The purpose of this study was to evaluate trends of transfusion associated with knee arthroplasties using nationwide data of the National Health Insurance Service-National Sample Cohort (NHIS-NSC). Using data from the nationwide claims database of the Health Insurance Review Assessment Service managed by the NHIS, 50,553 knee arthroplasties under three categories (total knee replacement arthroplasty, uni-knee replacement arthroplasty, and revision arthroplasty) from 2012 to 2018 were identified. Overall transfusion rate, transfusion count, proportion of each type of transfusion, and cost associated with each type of operation were investigated. Overall transfusion rate was 83.4% (5897/7066) in 2012, 82.7% (5793/7001) in 2013, 79.6% (5557/6978) in 2014, 75.9% (5742/7557) in 2015, 73.1% (6095/8337) in 2016, 68.2% (4187/6139) in 2017, and 64.6% (4271/6613) in 2018. The proportion of each type of transfusion was 1.8% for fresh frozen plasma, 0.5% for platelets, and 97.7% for red blood cells. The average cost of transfusion was $109.1 ($123 in 2012, $124 in 2013, $123.3 in 2014, $110.6 in 2015, $100 in 2016, $92.9 in 2017, and $90.1 in 2018). In this nationally representative study of trends in transfusion associated with knee arthroplasty, we observed significantly high rates of blood transfusion among patients undergoing knee arthroplasties. Although the overall rate of transfusion had declined, the allogeneic transfusion rate was still high from 2012 to 2018 in Korea. Thus, surgeons need to develop various patient blood management plans and minimize the use of allogeneic transfusion when performing knee arthroplasties.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Transfusão de Sangue , Humanos , Programas Nacionais de Saúde , Reoperação
9.
J Rheum Dis ; 29(4): 254-260, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37476427

RESUMO

Deficiency of adenosine deaminase 2 (DADA2) is an autoinflammatory disease caused by pathogenic variants of the ADA2 gene and has similar clinical features to polyarteritis nodosa (PAN). We, herein, report a case of DADA2 in Korea that was diagnosed in a patient with childhood-onset PAN. The patient had a truncal ataxia and facial palsy caused by thalamic infarction at 34 months of age. Livedo reticularis with Raynaud phenomenon and abdominal pain with fever were followed. Radiologic examination showed multiple infarctions in brain and kidney. She was diagnosed with PAN using skin biopsy and angiography. She had severe hemorrhagic strokes despite medical treatments. Her disease activity was controlled after adding a tumor necrosis factor-α inhibitor. Molecular analysis revealed compound heterozygous pathogenic variants of ADA2 gene. This is the first case of DADA2 in Korea. Genetic analysis for ADA2 gene should be considered in patients with childhood-onset PAN.

11.
Surg Endosc ; 36(2): 1369-1378, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-33689013

RESUMO

BACKGROUND: Histologically incomplete resection of large colorectal polyps is frequently encountered; however, the long-term outcomes or surveillance timing is not well known. We evaluated the incidence rate and time of recurrence of these cases during a long-term follow-up. METHODS: We performed a retrospective analysis of patients who underwent endoscopic resection for large (≥10 mm in size) non-pedunculated colorectal polyps at a tertiary academic hospital. Patients who had positive or indeterminate lateral margin in the histology and underwent completed surveillance colonoscopy first at 3-12 months and finally at ≥2 years after initial resection were included. RESULTS: Of 169 polyps (148 patients), 37 (21.9%) and 132 (78.1%) polyps had positive and indeterminate lateral margins, respectively. The median time intervals of the first and last surveillance from the initial resection were 6 (3-12) and 48 (24-114) months, respectively. The recurrence rate was 9.5% (16/169) during follow-up, and the mean time to recurrence was 31.9 months. Thirteen (81.3%) polyps recurred after ≥12 months. Most (14/16, 87.5%) recurrent polyps were benign, and 2 cases had advanced cancer. The only factor that was significantly associated with recurrence in the univariate and multivariate analyses was ≥3 piecemeal resections (odds ratio in the multivariate analysis, 16.92; 95% CI, 1.19-241.81; p = 0.037). CONCLUSION: During the long-term follow-up, the only factor that was significantly associated with recurrence was ≥3 piecemeal resections, and most recurrences occurred after ≥12 months. Thus, a histologically incomplete resection with ≤2 piecemeal resections and no findings of suspected submucosal cancer may be considered as complete resection, and these patients may undergo first surveillance colonoscopy after 1-2 years.


Assuntos
Pólipos do Colo , Neoplasias Colorretais , Ressecção Endoscópica de Mucosa , Pólipos do Colo/patologia , Pólipos do Colo/cirurgia , Colonoscopia , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Ressecção Endoscópica de Mucosa/efeitos adversos , Humanos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/etiologia , Estudos Retrospectivos
12.
BMC Pediatr ; 21(1): 453, 2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34654403

RESUMO

BACKGROUND: Severe protein C deficiency is a rare and inherited cause of thrombophilia in neonates. Protein C acts as an anticoagulant, and its deficiency results in vascular thrombosis. Herein, we report a case of protein C deficiency with a homozygous pathogenic variant in a term neonate, with good outcomes after proper treatment. CASE PRESENTATION: A four-day-old male newborn was transferred to the Seoul National University Hospital on account of dark red to black skin lesions. He was born full-term with an average birth weight without perinatal problems. There were no abnormal findings in the prenatal tests, including intrauterine sonography. The first skin lesion was observed on his right toes and rapidly progressed to proximal areas, such as the lower legs, left arm, and buttock. Under the impression of thromboembolism or vasculitis, we performed a coagulopathy workup, which revealed a high D-dimer level of 23.05 µg/ml. A skin biopsy showed fibrin clots in most capillaries, and his protein C activity level was below 10%, from which we diagnosed protein C deficiency. On postnatal day 6, he experienced an apnea event with desaturation and an abnormal right pupillary light reflex. Brain computed tomography showed multifocal patchy intracranial hemorrhage and intraventricular hemorrhage with an old ischemic lesion. Ophthalmic examination revealed bilateral retinal traction detachments with retinal folds. Protein C concentrate replacement therapy was added to previous treatments including steroids, prostaglandin E1, and anticoagulation. After replacement therapy, there were no new skin lesions, and the previous lesions recovered with scarring. Although there were no new brain hemorrhagic infarctions, there was ongoing ischemic tissue loss, which required further rehabilitation. Ophthalmic surgical interventions were performed to treat the bilateral retinal traction detachments with retinal folds. Molecular analysis revealed a homozygous pathogenic variant in the PROC gene. CONCLUSION: Severe protein C deficiency can manifest as a fatal coagulopathy in any organ. Early diagnosis and proper treatment, including protein C concentrate replacement, may improve outcomes without serious sequelae.


Assuntos
Deficiência de Proteína C , Anticoagulantes , Homozigoto , Humanos , Recém-Nascido , Hemorragias Intracranianas , Masculino , Proteína C/genética , Deficiência de Proteína C/complicações , Deficiência de Proteína C/diagnóstico , Deficiência de Proteína C/genética
13.
Nat Commun ; 12(1): 4567, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315893

RESUMO

Few studies have used a longitudinal approach to describe the immune response to SARS-CoV-2 infection. Here, we perform single-cell RNA sequencing of bronchoalveolar lavage fluid cells longitudinally obtained from SARS-CoV-2-infected ferrets. Landscape analysis of the lung immune microenvironment shows distinct changes in cell proportions and characteristics compared to uninfected control, at 2 and 5 days post-infection (dpi). Macrophages are classified into 10 distinct subpopulations with transcriptome changes among monocyte-derived infiltrating macrophages and differentiated M1/M2 macrophages, notably at 2 dpi. Moreover, trajectory analysis reveals gene expression changes from monocyte-derived infiltrating macrophages toward M1 or M2 macrophages and identifies a macrophage subpopulation that has rapidly undergone SARS-CoV-2-mediated activation of inflammatory responses. Finally, we find that M1 or M2 macrophages show distinct patterns of gene modules downregulated by immune-modulatory drugs. Overall, these results elucidate fundamental aspects of the immune response dynamics provoked by SARS-CoV-2 infection.


Assuntos
COVID-19/genética , COVID-19/metabolismo , Macrófagos/metabolismo , Macrófagos/fisiologia , Animais , Líquido da Lavagem Broncoalveolar , Furões
14.
Mol Cells ; 44(6): 377-383, 2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34187969

RESUMO

Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) is a novel virus that causes coronavirus disease 2019 (COVID-19). To understand the identity, functional characteristics and therapeutic targets of the virus and the diseases, appropriate infection models that recapitulate the in vivo pathophysiology of the viral infection are necessary. This article reviews the various infection models, including Vero cells, human cell lines, organoids, and animal models, and discusses their advantages and disadvantages. This knowledge will be helpful for establishing an efficient system for defense against emerging infectious diseases.


Assuntos
COVID-19/virologia , Modelos Teóricos , Organoides/virologia , SARS-CoV-2/patogenicidade , Animais , COVID-19/imunologia , COVID-19/patologia , Gatos , Linhagem Celular Tumoral , Galinhas/virologia , Chlorocebus aethiops/virologia , Cricetinae , Cães , Furões/virologia , Humanos , Camundongos , Organoides/imunologia , Organoides/patologia , Coelhos , SARS-CoV-2/crescimento & desenvolvimento , Suínos/virologia , Células Vero
15.
Semin Arthritis Rheum ; 51(4): 685-691, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34139521

RESUMO

OBJECTIVES: To determine the association of first, second, and third-line biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib with drug survival among seropositive rheumatoid arthritis (RA) patients. METHODS: The study population was composed of 8,018 seropositive RA patients who were prescribed bDMARDs or tofacitinib between January 2014 and January 2019 from the Korean Health Insurance Review and Assessment Service database. First, second, and third-line choice of tumor necrosis factor inhibitors (TNFi) including etanercept, infliximab, adalimumab, and golimumab, as well as non-TNFi including tocilizumab, rituximab, tofacitinib, and abatacept were assessed. Multivariate Cox proportional hazards regression was used to determine the adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for drug failure according to bDMARD or tofacitinib choice starting from the initial prescription date. RESULTS: Compared to first etanercept users, patients with first tocilizumab (aHR 0.56, 95% CI 0.46-0.68), tofacitinib (aHR 0.27, 95% CI 0.18-0.42), or abatacept (aHR 0.83, 95% CI 0.69-0.99) had lower risk of drug failure. Second choice of tocilizumab (aHR 0.38, 95% CI 0.25-0.55), tofacitinib (aHR 0.23, 95% CI 0.15-0.37), or abatacept (aHR 0.54, 95% CI 0.35-0.84) was associated with lower drug failure risk compared to second etanercept users. Finally, third choice of tocilizumab (aHR 0.32, 95% CI 0.16-0.62) or tofacitinib (aHR 0.35, 95% CI 0.19-0.63) was associated with lower drug failure risk compared to third TNFi users. CONCLUSION: First and second-line tocilizumab, tofacitinib, or abatacept may lead to improved drug survival. Third-line use of tocilizumab or tofacitinib may be beneficiary in reducing drug failure risk among seropositive RA patients.


Assuntos
Antirreumáticos , Artrite Reumatoide , Preparações Farmacêuticas , Abatacepte/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Estudos de Coortes , Humanos
16.
Healthcare (Basel) ; 9(3)2021 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-33800397

RESUMO

The purpose of this study is to evaluate the utility of QR (quick response) codes in explaining the proper method for orthotic use after orthopedic surgery. A questionnaire survey was adopted to evaluate patient satisfaction with education and training in orthotic applications after orthopedic surgery. The study periods were 1 April to 30 April 2017, and 1 October to 31 October 2017. The oral training involving the conventional orthoses was conducted in April, and the videos with the orthosis on the QR code were captured in October. The QR code containing the data was distributed and the education was conducted. A total of 68 patients (QR-code group: 33) participated in the questionnaire survey. After the QR code application, the number of retraining cases increased from 62.9 to 93.9% (p-value < 0.01). The mean scores of the four items measuring the comprehension increased from 10.97 to 14.39. The satisfaction level rose from 7.14 to 9.30, and the performance increased from 7.14 to 9.52 (p-value < 0.01). The QR code is expected to be a valuable method for explaining the orthotic application after orthopedic surgery, and especially when repeated explanations are needed for elderly patients.

17.
J Foot Ankle Surg ; 60(4): 724-728, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33773921

RESUMO

The objective of this study was to determine the anatomical relationship between the calcaneus and its neighboring bones. Furthermore we tested a prediction model that enables to estimate safe screw length during the surgery of calcaneus fractures. A total of 169 feet were used for the study based on CT scans. We measured two horizontal and two parallel lines. The coronal length of the cuboid bone (CL) was a horizontal line anterior to the calcaneocuboidal joint, and W1 of calcaneus was a horizontal line posterior to the articular surface of the calcaneocuboidal joint. The subtalar articular length (STA) was a parallel line above the talocalcaneal joint, and W2 of calcaneus was a parallel line below to the talocalcaneal joint. Relationship of each measurement was determined through correlation analysis. A prediction model was developed based on observed correlations and the quality analyzed and validated. The CL and W1 had a significant positive correlation (r = 0.899, p < .001). The STA and W2 also had a significant positive correlation (r = 0.939, p < .001). Based on these correlations, the prediction model was made. In the quality analysis, the values of concordance correlation coefficient (CCC) for W1 and W2 were 0.894, and 0.937 respectively. In the validation analysis, the values of CCC for W1, W2 were 0.79, and 0.8, respectively. This study made it possible to predict the anatomical reference point using preoperative coronal length of the calcaneus to guide safety margin of screw length, and thereby to prevent the iatrogenic injuries on medial neurovascular structures of the calcaneus.


Assuntos
Traumatismos do Tornozelo , Calcâneo , Fraturas Ósseas , Fixação Interna de Fraturas , Humanos , Tomografia Computadorizada por Raios X
18.
Medicine (Baltimore) ; 100(5): e23839, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33592840

RESUMO

ABSTRACT: Non-tuberculous mycobacteria (NTM) comprise mycobacteria, with the exceptions of Mycobacterium (M.) leprae and the M. tuberculosis complex. Septic arthritis caused by NTM is so rare that there is no standardized treatment.Between April and September 2012, 27 patients were infected with M. massiliense in a single clinic following injection of steroid in the knee joint. Clinical data of 9 patients who received arthroscopic treatment in Seoul Hospital of Soonchunhyang University were analyzed retrospectively.Arthroscopic irrigation and debridement were performed average 2.6 times (1-3 times). As 6 out of 9 cases (67%) had joint contracture of the knee joint, arthroscopic adhesiolysis, and brisement were performed. After surgical procedures, Hospital for Special Surgery and Lysholm knee score showed improvement compared before the surgery, but a radiographic result evaluated by Kellgren-Lawrence revealed that 6 cases got deteriorated to stage 4 in the 4-year follow-up.NTM septic arthritis had a higher recurrence and a higher contracture incidence than septic arthritis caused by tuberculous mycobacteria or other bacteria. Treatment was possible with repeated arthroscopic debridement and intravenous antibiotics.


Assuntos
Artrite Infecciosa/cirurgia , Artroscopia/métodos , Injeções Intra-Articulares/efeitos adversos , Infecções por Mycobacterium não Tuberculosas/cirurgia , Mycobacterium abscessus , Idoso , Artrite Infecciosa/induzido quimicamente , Artrite Infecciosa/microbiologia , Surtos de Doenças , Feminino , Humanos , Articulação do Joelho/microbiologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium não Tuberculosas/induzido quimicamente , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos , Resultado do Tratamento
19.
Medicina (Kaunas) ; 57(2)2021 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-33530595

RESUMO

Background: Calcaneal bone cysts rarely occur and most of them are known to be benign. Among them, simple bone cysts (SBCs) third most commonly occur in the calcaneus and of the many surgical treatment options, endoscopic curettage is recently gaining popularity among surgeons due to its advantages of minimal invasiveness and optimal visualization. As for portal placement for endoscopy, two lateral portals are considered a standard technique, but no rationale has been established for SBCs with abnormal geometry. This case report suggests an SBC with secondary aneurysmal change located outside the Ward's triangle, as well as an appropriate endoscopic approach. Case Presentation: An 18-year-old male high school student presented with a main complaint of pain at the hind foot level for the past one year, without significant improvement from conservative treatment. An endoscopic curettage through the lesion specific two posterior portals and bone graft using allogeneic cancellous bone were performed. SBC with a secondary aneurysmal bone cyst was diagnosed on pathology. At a one-year follow-up, the patient was painless and had returned to his regular activities. Physical and radiographic examinations revealed that the lesion was completely healed without any evidence of recurrence. Conclusion: For calcaneal bone cysts located at the posterior aspect of the calcaneus, eccentrically medial and abnormally long anterior-posteriorly, we suggest an endoscopic procedure using lesion specific portals such as two posterior portals.


Assuntos
Cistos Ósseos , Calcâneo , Adolescente , Cistos Ósseos/diagnóstico por imagem , Cistos Ósseos/cirurgia , Calcâneo/diagnóstico por imagem , Calcâneo/cirurgia , Curetagem , Endoscopia , Humanos , Masculino , Recidiva Local de Neoplasia
20.
Artigo em Inglês | MEDLINE | ID: mdl-33401516

RESUMO

(1) Background: Ingrown toenail is a common disorder of the toe that induces severe toe pain and limits daily activities. The Winograd method, the most widely used operative modality for ingrown toenails, has been modified over years to include wedge resection of the nail fold and complete ablation of the germinal matrix. We evaluated the outcomes of original Winograd procedure without wedge resection with electrocautery-aided matrixectomy. (2) Methods: We retrospectively analyzed the outcomes of patients who underwent surgery for ingrown toenails at a university hospital for two years from November 2015 to October 2017. Surgery was performed in 76 feet with a mean operation time of 9.34 min. (3) Results: The minimal interval from surgery to return to regular activities was 13.26 (range 7 to 22) days. Recurrence and postoperative wound infections were found in 3 (3.95%) and 2 (2.63%) patients, respectively. Evaluation of patient satisfaction at one-year follow-up showed that 40 (52.63%) patients were very satisfied, 33 (43.42%) were satisfied, 3 (3.95%) were dissatisfied, and none of them were very dissatisfied. The average follow-up duration was 14.66 (range 12 to 25) months. (4) Conclusions: Therefore, it is believed that this less-invasive and simple procedure could be easily performed by clinicians, with satisfactory patient outcomes.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Unhas Encravadas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Unhas Encravadas/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
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