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1.
Artigo em Inglês | MEDLINE | ID: mdl-38658448

RESUMO

PURPOSE: To select patients who would benefit most from sentinel lymph node biopsy (SLNB) by investigating the characteristics and risk factors of axillary lymph node metastasis (ALNM) in microinvasive breast cancer (MIBC). METHODS: This retrospective study included 1688 patients with MIBC who underwent breast surgery with axillary staging at the Asan Medical Center from 1995 to 2020. RESULTS: Most patients underwent SLNB alone (83.5%). Seventy (4.1%) patients were node-positive, and the majority had positive lymph nodes < 10 mm, with micro-metastases occurring frequently (n = 37; 55%). Node-positive patients underwent total mastectomy and axillary lymph node dissection (ALND) more than breast-conserving surgery (BCS) and SLNB compared with node-negative patients (p < 0.001). In the multivariate analysis, independent predictors of ALNM included young age [odds ratio (OR) 0.959; 95% confidence interval (CI) 0.927-0.993; p = 0.019], ALND (OR 11.486; 95% CI 5.767-22.877; p < 0.001), number of lymph nodes harvested (≥ 5) (OR 3.184; 95% CI 1.555-6.522; p < 0.001), lymphovascular invasion (OR 6.831; 95% CI 2.386-19.557; p < 0.001), presence of multiple microinvasion foci (OR 2.771; 95% CI 1.329-5.779; p = 0.007), prominent lymph nodes in preoperative imaging (OR 2.675; 95% CI 1.362-5.253; p = 0.004), and hormone receptor positivity (OR 2.491; 95% CI 1.230-5.046; p = 0.011). CONCLUSION: Low ALNM rate (4.1%) suggests that routine SLNB for patients with MIBC is unnecessary but can be valuable for patients with specific risk factors. Ongoing trials for omitting SLNB in early breast cancer, and further subanalyses focusing on rare populations with MIBC are necessary.

2.
Nat Commun ; 15(1): 1024, 2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38310093

RESUMO

Osteoarthritis (OA) is a progressive and irreversible degenerative joint disease that is characterized by cartilage destruction, osteophyte formation, subchondral bone remodeling, and synovitis. Despite affecting millions of patients, effective and safe disease-modifying osteoarthritis drugs are lacking. Here we reveal an unexpected role for the small molecule 5-aminosalicylic acid (5-ASA), which is used as an anti-inflammatory drug in ulcerative colitis. We show that 5-ASA competes with extracellular-matrix collagen-II to bind to osteoclast-associated receptor (OSCAR) on chondrocytes. Intra-articular 5-ASA injections ameliorate OA generated by surgery-induced medial-meniscus destabilization in male mice. Significantly, this effect is also observed when 5-ASA was administered well after OA onset. Moreover, mice with DMM-induced OA that are treated with 5-ASA at weeks 8-11 and sacrificed at week 12 have thicker cartilage than untreated mice that were sacrificed at week 8. Mechanistically, 5-ASA reverses OSCAR-mediated transcriptional repression of PPARγ in articular chondrocytes, thereby suppressing COX-2-related inflammation. It also improves chondrogenesis, strongly downregulates ECM catabolism, and promotes ECM anabolism. Our results suggest that 5-ASA could serve as a DMOAD.


Assuntos
Cartilagem Articular , Osteoartrite , Humanos , Masculino , Animais , Camundongos , Mesalamina/farmacologia , Mesalamina/uso terapêutico , PPAR gama/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Cartilagem Articular/metabolismo , Condrócitos/metabolismo , Modelos Animais de Doenças
3.
J Cell Physiol ; 239(4): e31196, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240115

RESUMO

The NOD-, LRR-, and Pyrin domain-containing protein 3 (NLRP3) inflammasome plays key roles in regulating inflammation. Numerous studies show that the abnormal activation of NLRP3 associates with the initiation and progression of various diseases. Hence, the NLRP3 inflammasome may be a promising therapeutic target for these diseases. Octyl gallate (OG) is a small molecule with antioxidant, antimicrobial, antifungal, and anti-inflammatory activities; however, the mechanism underlying its anti-inflammatory activity is still unclear. Here, we developed a screening system for NLRP3-inflammasome inhibitors. A total of 3287 small molecules were screened for inhibitors of nigericin-induced NLRP3 oligomerization. OG was identified as a novel inhibitor. We show that OG directly targets the LRR domain of NLRP3 and thereby blocks the inflammatory cascade of the NLRP3 inflammasome. This contrasts with the mode-of-action of other direct NLRP3 inhibitors, which all bind to the NACHT domain of NLRP3. Interestingly, OG also inhibits the priming step by downregulating the Raf-MEK1/2-ERK1/2 axis. Thus, OG inhibits the NLRP3 inflammasome by two distinct mechanisms. Importantly, OG injection ameliorated the inflammation in mouse models of foot gout and sepsis. Our study identifies OG as a potential therapeutic agent for NLRP3-associated diseases.


Assuntos
Ácido Gálico/análogos & derivados , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Camundongos , Animais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Inflamassomos/metabolismo , Inflamação/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
5.
Medicine (Baltimore) ; 103(3): e36931, 2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38241578

RESUMO

Universal varicella vaccination (UVV), as a single dose to children aged 12 to 15 months, was introduced in Korea in 2005. A seroprevalence study is required to upgrade this UVV strategy. The fluorescent antibody to membrane antigen (FAMA) assay is the gold standard for varicella-zoster virus (VZV) immunity testing. However, no standard operating procedure (SOP) has been developed for the FAMA assay, in which either glutaraldehyde or acetone may be used for VZV-infected cell fixation. In this observational study, we aimed to investigate the age-specific seroprevalence in Korean children and adults. Additionally, with glycoprotein enzyme-linked immunosorbent assay (gpELISA) as the reference, we evaluated the performance of the FAMA assay using acetone-fixed cells. Four hundred sera were analyzed using the FAMA assay (acetone-fixed cells) and gpELISA, comprising 50 subjects from each age category. In the FAMA assay, the seropositivity rate decreased from 82.0% in the 1 to 4-year-old group to 58.0% in the 5 to 9-year-old group (95% confidence interval [CI]: 69.2-90.2 and 44.2-70.6, respectively; P = .009), while that in the gpELISA decreased from 80.0% to 52.0% (95% CI: 67.0-88.8 and 38.5-65.2, respectively; P = .003). In both methods, the seropositivity rates ranged from 95% to 100% in the population aged ≥ 20 years. We observed a significant correlation between the 2 methods, with a correlation coefficient of 0.795 (P < .001). In receiver operating characteristic analysis using the gpELISA results as a reference, the area under the curve for the FAMA assay was very high at 0.995 (95% CI: 0.990-1.000; P < .001). Compared to the gpELISA, the sensitivity, specificity, and kappa value of the FAMA assay were 99.4%, 79.3%, and 0.84 (nearly perfect), respectively. The seropositivity rate of the 5 to 9-year-old group indicated waning immunity over time and supported implementation of a second dose in the UVV program. The results of the FAMA assay were comparable to those of the gpELISA. Although further study is needed to standardize procedures, our results suggest that the FAMA assay using acetone-fixed cells can be used widely and can be included in a universal FAMA assay SOP.


Assuntos
Varicela , Herpesvirus Humano 3 , Adulto , Criança , Humanos , Lactente , Pré-Escolar , Estudos Soroepidemiológicos , Acetona , Anticorpos Antivirais , Ensaio de Imunoadsorção Enzimática/métodos , Glicoproteínas , Vacinação , Varicela/epidemiologia
6.
Vaccines (Basel) ; 12(1)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38276680

RESUMO

Since the 2000s, sporadic outbreaks of whooping cough have been reported in advanced countries, where the acellular pertussis vaccination rate is relatively high, and in developing countries. Small-scale whooping cough has also continued in many countries, due in part to the waning of immune protection after childhood vaccination, necessitating the development of an improved pertussis vaccine and vaccination program. Currently, two different production platforms are being actively pursued in Korea; one is based on the aP (acellular pertussis) vaccine purified from B. pertussis containing pertussis toxoid (PT), filamentous hemagglutin (FHA) and pertactin (PRN), and the other is based on the recombinant aP (raP), containing genetically detoxified pertussis toxin ADP-ribosyltransferase subunit 1 (PtxS1), FHA, and PRN domain, expressed and purified from recombinant E. coli. aP components were further combined with diphtheria and tetanus vaccine components as a prototype DTaP vaccine by GC Pharma (GC DTaP vaccine). We evaluated and compared the immunogenicity and the protective efficacy of aP and raP vaccines in an experimental murine challenge model: humoral immunity in serum, IgA secretion in nasal lavage, bacterial clearance after challenge, PTx (pertussis toxin) CHO cell neutralization titer, cytokine secretion in spleen single cell, and tissue resident memory CD4+ T cell (CD4+ TRM cell) in lung tissues. In humoral immunogenicity, GC DTaP vaccines showed high titers for PT and PRN and showed similar patterns in nasal lavage and IL-5 cytokine secretions. The GC DTaP vaccine and the control vaccine showed equivalent results in bacterial clearance after challenge, PTx CHO cell neutralization assay, and CD4+ TRM cell. In contrast, the recombinant raP vaccine exhibited strong antibody responses for FHA and PRN, albeit with low antibody level of PT and low titer in PTx CHO neutralization assay, as compared to control and GC DTaP vaccines. The raP vaccine provided a sterile lung bacterial clearance comparable to a commercial control vaccine after the experimental challenge in murine model. Moreover, raP exhibited a strong cytokine response and CD4+ TRM cell in lung tissue, comparable or superior to the experimental and commercial DTaP vaccinated groups. Contingent on improving the biophysical stability and humoral response to PT, the raP vaccine warrants further development as an effective alternative to aP vaccines for the control of a pertussis outbreak.

7.
J Rheum Dis ; 31(1): 49-53, 2024 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-38130956

RESUMO

Neonatal lupus can occur in infants born to mother with autoimmune disorders through transplacental auto-antibodies. Clinical manifestations in neonatal lupus include cutaneous lesions and hematologic or hepatobiliary findings resembling those seen in systemic lupus erythematosus. In autoimmune state, macrophage activation syndrome (MAS) represent a critical and potentially fatal complication that can result in mortality if not immediately identified and managed with the appropriate care. Here we present a 33-day-old girl diagnosed with neonatal lupus and serious MAS. She was delivered by a primipara mother who did not exhibit any autoimmune symptoms. The patient visited the hospital due to fever and pancytopenia. Laboratory data were compatible with MAS, including pancytopenia, high level of ferritin, soluble interleukin-2, and decreased natural killer cell activity. In addition, autoimmune study showed positive results for anti-nuclear antibody (ANA), anti-Sjogren syndrome antigen A (SSA), and SSB, The autoimmune study for mother also showed positive results for ANA, anti-SSA, and SSB. The patient recovered after she received high dose steroid and supportive care. Our case indicates that neonatal lupus should be taken into consideration when fever, erythematous skin rash, and pancytopenia are observed in infants, even if their mothers have no prior history of autoimmune conditions.

8.
Front Biosci (Landmark Ed) ; 28(11): 307, 2023 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-38062845

RESUMO

Since Toll-like receptors (TLRs) recognize the earliest signs of infection or cell damage, they play fundamental roles in innate immunity. This review summarizes the numerous studies on the expression of TLRs in patients with Coronavirus disease 2019 (COVID-19). We show that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can stimulate at least six of the ten TLRs in humans and that this can shape the severity of COVID-19. Specifically, TLR2, TLR4, and TLR9 appear to play pathogenic roles while TLR3, TLR7, and TLR8 may be protective. Most have mutations that could partly explain the susceptibility phenotypes of COVID-19. Further understanding the roles of TLRs in COVID-19 immunopathogenesis could reveal prognostic biomarkers and help drive the development of novel and effective therapeutics for COVID-19.


Assuntos
COVID-19 , Humanos , SARS-CoV-2/metabolismo , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo , Imunidade Inata
9.
Exp Mol Med ; 55(12): 2576-2585, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38036734

RESUMO

Osteoarthritis (OA) is a degenerative joint disease. While it is classically characterized by articular cartilage destruction, OA affects all tissues in the joints and is thus also accompanied by local inflammation, subchondral bone changes, and persistent pain. However, our understanding of the underlying subchondral bone dynamics during OA progression is poor. Here, we demonstrate the contribution of immunoglobulin superfamily 11 (IgSF11) to OA subchondral bone remodeling by using a murine model. In particular, IgSF11 was quickly expressed by differentiating osteoclasts and upregulated in subchondral bone soon after destabilization-of-the-medial-meniscus (DMM)-induced OA. In mice, IgSF11 deficiency not only suppressed subchondral bone changes in OA but also blocked cartilage destruction. The IgSF11-expressing cells in OA subchondral bone were found to be involved in osteoclast maturation and bone resorption and colocalized with receptor-activator of nuclear-factor κ-B (RANK), the key osteoclast differentiation factor. Thus, our study shows that blocking early subchondral bone changes in OA can ameliorate articular cartilage destruction in OA.


Assuntos
Reabsorção Óssea , Cartilagem Articular , Osteoartrite , Animais , Camundongos , Osso e Ossos , Reabsorção Óssea/genética , Modelos Animais de Doenças , Osteoartrite/genética , Osteoartrite/complicações , Osteoclastos
10.
Biomedicines ; 11(10)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37893216

RESUMO

Osteoarthritis (OA) is the most common joint disease that causes local inflammation and pain, significantly reducing the quality of life and normal social activities of patients. Currently, there are no disease-modifying OA drugs (DMOADs) available, and treatment relies on pain relief agents or arthroplasty. To address this significant unmet medical need, we aimed to develop monoclonal antibodies that can block the osteoclast-associated receptor (OSCAR). Our recent study has revealed the importance of OSCAR in OA pathogenesis as a novel catabolic regulator that induces chondrocyte apoptosis and accelerates articular cartilage destruction. It was also shown that blocking OSCAR with a soluble OSCAR decoy receptor ameliorated OA in animal models. In this study, OSCAR-neutralizing monoclonal antibodies were isolated and optimized by phage display. These antibodies bind to and directly neutralize OSCAR, unlike the decoy receptor, which binds to the ubiquitously expressed collagen and may result in reduced efficacy or deleterious off-target effects. The DMOAD potential of the anti-OSCAR antibodies was assessed with in vitro cell-based assays and an in vivo OA model. The results demonstrated that the anti-OSCAR antibodies significantly reduced cartilage destruction and other OA signs, such as subchondral bone plate sclerosis and loss of hyaline cartilage. Hence, blocking OSCAR with a monoclonal antibody could be a promising treatment strategy for OA.

11.
J Rheum Dis ; 30(4): 272-277, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37736588

RESUMO

Multisystem inflammatory syndrome in children (MIS-C) is a serious post-infectious complication of COVID-19 characterized by hyperinflammation and multi-organ dysfunction including shock. Shock is also seen in a severe form of Kawasaki disease (KD) called KD shock syndrome (KDSS). Here, we present one MIS-C and one KDSS case and compare similarities and differences between them. Both MIS-C (case 1) and KDSS (case 2) showed hyperinflammation, KD-related features, gastrointestinal problems, hypotension, and coagulopathy. The extent of systemic inflammation and organ dysfunction was more severe in KDSS than in MIS-C. Case 1 was diagnosed as MIS-C because SARS-CoV-2 was confirmed, and case 2 was diagnosed as KDSS because no pathogen was identified in microbiological studies. We believe that the most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger. Organ dysfunction is a hallmark of MIS-C and KDSS, but not KD, so MIS-C shares more clinical phenotypes with KDSS than with KD. Comparison of MIS-C and KDSS will be an interesting and important topic in the field of KD-like hyperinflammatory disease research.

12.
J Med Virol ; 95(9): e29108, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37715715

RESUMO

Live varicella vaccines are known to provide robust immunity against varicella zoster virus (VZV) infections. However, problems with viral attenuation have led to pathogenic VZV vaccine strains causing varicella-like rash and herpes zoster in immunocompetent children after immunization. We report the first fatal case of VZV infection caused by OKA/SK strain contained in the vaccine administrated as a booster shot in an immunocompetent child, which has been independently developed from any currently available varicella vaccines that are OKA strain or MAV/06 strain based. The patient died due to sudden pulmonary alveolar hemorrhage as a secondary complication of VZV pneumonitis. Sequencing of the four SNPs unique to the OKA/SK strain (SNP loci 14 035T; 32 626C; 58 777G; 70 319G) enabled discrimination of the strain responsible for the disseminated infection. OKA/SK strain does not have any SNPs in ORF62 postulated to be responsible for the attenuation of varicella vaccines which have been safely and effectively used world-wide or locally, and exclusively enriches a virulent factor in ORF31 identified in parental OKA strain, thus possibly resulting in disseminated VZV infection leading to mortality. Therefore, actions need to be taken to prevent vaccine related morbidity and mortality in children.


Assuntos
Varicela , Vacina contra Herpes Zoster , Herpes Zoster , Vacinas Virais , Criança , Humanos , Varicela/complicações , Vacina contra Varicela/efeitos adversos , Vacinas Atenuadas , Antígenos Virais
13.
Children (Basel) ; 10(9)2023 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-37761488

RESUMO

This study aimed to investigate the characteristics of COVID-19-associated multisystem inflammatory syndrome in children (MIS-C) and Kawasaki disease shock syndrome (KDSS) and to compare the similarities and differences between the two diseases. The incidence of KDSS and MIS-C was also estimated. Medical records of patients diagnosed with MIS-C or KDSS at four hospitals from January 2013 to December 2022 were retrospectively reviewed. Thirty-one patients were enrolled in the study in either an MIS-C group (n = 22) or a KDSS group (n = 9). The incidence of KDSS in KD was 0.8% (9/1095) and the incidence of MIS-C versus KD was 10.2% (22/216). Compared with the MIS-C group, the KDSS group had longer hospital stays and more severe systemic inflammation (e.g., anemia, elevated C-reactive protein, hypoalbuminemia, and pyuria) and organ dysfunction (e.g., number of involved organs, shock, vasoactive infusion, and intensive care unit admission). All patients in the MIS-C group, but none in the KDSS group, including two patients during the COVID-19 pandemic, had laboratory evidence of SARS-CoV-2 infection. MIS-C and KDSS shared demographic, clinical, and laboratory characteristics; organ dysfunction; treatment; and outcomes. Overall severity was more severe in patients with KDSS than in those with MIS-C. The most important difference between MIS-C and KDSS was whether SARS-CoV-2 was identified as an infectious trigger.

14.
Gut Pathog ; 15(1): 40, 2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37596621

RESUMO

BACKGROUND: The effect of fecal stream diversion on the gut microbiota is still uncertain. The present study was designed to assess the effect of fecal stream diversion on the composition of the gut microbiota in patients with colorectal cancer. We included patients undergoing left-sided colorectal cancer surgery with (ileostomy group) or without (control group) diverting ileostomy. Fecal samples were collected from 10 patients in each group before surgery (t1) and after ileostomy repair in the ileostomy group and 6-12 months after the initial surgery in the control group (t2). The fecal microbiota was assessed using 16S rRNA sequencing, and changes in the composition of the fecal microbiota were compared between the two groups. RESULTS: Alpha diversity analysis revealed that the complexity of fecal microbiota decreased between t1 and t2 only in the ileostomy group. Beta diversity analysis also showed dissimilarity between t1 and t2 only in the ileostomy group. The composition of the microbiota was similar between the two groups at t1. However, at t2, the ileostomy group had lower proportion of beneficial bacteria (Lachnospiraceae, 3.8% vs. 29.9%, p < 0.001; Ruminococcaceae, 0.6% vs. 18.4%, p < 0.001; Blautia, 0.1% vs. 9.1%, p < 0.001; Faecalibacterium, 0.2% vs. 7.5%, p < 0.001) and a higher proportion of harmful bacteria (Proteobacteria, 17.9% vs. 5.1%, p = 0.006; Clostridium, 16.2% vs. 1.1%, p = 0.013; Streptococcus, 17.7% vs. 1.6%, p = 0.002) than the control group. CONCLUSIONS: Fecal stream diversion was closely associated with less diversity and dysbiosis of the gut microbiota.

15.
Nutr Res Pract ; 17(3): 475-486, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37266110

RESUMO

BACKGROUND/OBJECTIVES: This study aimed to evaluate the effect of preoperative immunonutrition on the composition of fecal microbiota following a colon cancer surgery. MATERIALS/METHODS: This study was a secondary analysis of a randomized controlled trial assessing the impact of preoperative immunonutrition on the postoperative outcomes of colon cancer surgery. Patients with primary colon cancer were enrolled and randomly assigned to receive additional preoperative immunonutrition or a normal diet alone. Oral nutritional supplementation (400 mL/day) with arginine and ω-3 fatty acids were administered to patients in the immunonutrition group for 7 days prior to surgery. Thirty-two fecal samples were collected from 16 patients in each group, and the composition of fecal microbiota was compared between the 2 groups. RESULTS: At the phylum level, no significant difference was observed in the composition of microbiota between the 2 groups (Firmicutes, 69.1% vs. 67.5%, P = 0.624; Bacteroidetes, 19.3% vs. 18.1%, P = 0.663; Actinobacteria, 6.7% vs. 10.6%, P = 0.080). The Firmicutes/Bacteroidetes ratio (4.43 ± 2.32 vs. 4.55 ± 2.51, P = 0.897) was also similar between the 2 groups. At the genus level, the proportions of beneficial bacteria such as Faecalibacterium spp. (8.1% vs. 6.4%, P = 0.328) and Prevotella spp. (6.9% vs. 4.8%, P = 0.331) were higher, while that of Clostridium spp. was lower (0.5% vs. 1.2%, P = 0.121) in the immunonutrition group, but the difference was not significant. CONCLUSIONS: Immunonutrition showed no significant association with the composition of fecal microbiota. The relationship between immunonutrition and the fecal microbiota should be investigated further in large-scale studies.

16.
Sci Rep ; 13(1): 8127, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37208344

RESUMO

Wafer map defect pattern classification is essential in semiconductor manufacturing processes for increasing production yield and quality by providing key root-cause information. However, manual diagnosis by field experts is difficult in large-scale production situations, and existing deep-learning frameworks require a large quantity of data for learning. To address this, we propose a novel rotation- and flip-invariant method based on the labeling rule that the wafer map defect pattern has no effect on the rotation and flip of labels, achieving class discriminant performance in scarce data situations. The method utilizes a convolutional neural network (CNN) backbone with a Radon transformation and kernel flip to achieve geometrical invariance. The Radon feature serves as a rotation-equivariant bridge for translation-invariant CNNs, while the kernel flip module enables the model to be flip-invariant. We validated our method through extensive qualitative and quantitative experiments. For qualitative analysis, we suggest a multi-branch layer-wise relevance propagation to properly explain the model decision. For quantitative analysis, the superiority of the proposed method was validated with an ablation study. In addition, we verified the generalization performance of the proposed method to rotation and flip invariants for out-of-distribution data using rotation and flip augmented test sets.

17.
Breast Cancer Res Treat ; 200(1): 47-61, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37184775

RESUMO

PURPOSE: The clinical behavior, prognosis, and management of microinvasive breast cancer (MiBC) is controversial. We aimed to clarify its significance across different subtypes and the role of human epidermal growth factor receptor 2 (HER2) expression in MiBC. METHODS: We analyzed 1530 patients with T1mi (tumor size ≤ 0.1 cm), node-negative breast cancer who underwent breast conserving surgery or total mastectomy between 2001 and 2020 at the Asan Medical Center (AMC). RESULTS: When divided into four subtypes, hormone receptor (HR)+/HER2-, HR+ /HER2+ , HR-/HER2+ , and HR-/HER2-, HR-/HER2+ had the highest prevalence rate of 38.5% in MiBC patients. In a median follow-up period of 74 months (0-271 months), 103 (6.7%) patients had recurrent tumor, and 95 (6.2%) had local recurrence. Disease-free survival (DFS) and local recurrence-free survival (LRFS) were worst in the HR-/HER2+ group. The five-year DFS for the HR-/HER2+ group was 92.2%, while it was 97.1% for the HR+/HER2- group (p = 0.024 The five-year LRFS for HER2- patients were better than that of HER2+ MiBC patients, which were 97.1 and 93.8%, respectively (p = 0.010). Univariate and multivariate Cox regression analyses showed that the HR-/HER2+ group had relatively higher risk of recurrence compared to the HR+/HER2- group (hazard ratio [HR] = 2.332, 95% confidence interval [CI] 1.412-3.852, p = 0.001 unadjusted; HR = 3.346, 95% CI 1.408-7.953, p = 0.006 adjusted). CONCLUSION: HER2 overexpression was significantly associated with adverse clinicopathologic parameters and increased local recurrence risk in MiBC. Therefore, more understanding of the clinical behavior of HER2 in MiBC will enable tailoring of adjuvant therapy for these patients.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Relevância Clínica , Biomarcadores Tumorais/metabolismo , Mastectomia , Recidiva Local de Neoplasia/tratamento farmacológico , Receptor ErbB-2/metabolismo , Prognóstico , Intervalo Livre de Doença
18.
Polymers (Basel) ; 15(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36987323

RESUMO

The development of waterborne polyurethane (WPU) has been stimulated as an alternative to solvent-based polyurethanes due to low-VOC alternatives and reduced exposure to solvents. However, their relatively low mechanical performance and degradation have presented challenges in their wide application. Here, we developed environmentally-friendly bio polyol-based WPU nanocomposite dispersions and films, and presented the optimal process conditions for their manufacture. Additionally, the condition was established without using harmful catalysts or ethyl methyl ketone (MEK) during the polymerization. Moreover, regenerated cellulose nanoparticles (RCNs) were employed as natural chain-extenders in order to improve the biodegradability and mechanical performances of the nanocomposite films. The RCNs have a lower crystallinity compared to cellulose nanocrystals (CNCs), allowing them to possess high toughness without interfering with the elastomeric properties of polyurethane. The prepared CWPU/RCNs nanocomposite films exhibited high toughness of 58.8 ± 3 kgf∙mm and elongation at break of 240 ± 20%. In addition, depending on the molar ratio of NCO/OH, the polyurethane particle size is variously controlled from 70 to 230 nm, enabling to fabricate their dispersions with various transmittances. We believe that our findings not only open a meaningful path toward green elastomers with biodegradability but provides the design concept for bio-elastomers in order to develop industrial elastomers with mechanical and thermal properties.

19.
Trials ; 24(1): 152, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36855158

RESUMO

BACKGROUND: Minimally invasive surgery has become popular as a surgical approach for colorectal cancer because it has fewer complications related to the abdominal incision and perioperative complications. However, the incidence of incisional hernias in laparoscopic surgery has been reported to be similar to that in open surgery. We developed a new method, the non-muscle-cutting periumbilical transverse incision, for a small incision in laparoscopic colon cancer surgery. This study aims to evaluate the effectiveness of the non-muscle-cutting periumbilical transverse incision in comparison with the midline incision in reducing the incidence of an incisional hernia in patients undergoing laparoscopic colon cancer surgery. METHODS: This is an open-label, multi-centre, parallel, superiority, and randomised trial. Altogether, 174 patients will be allocated in a 1:1 ratio to either the midline incision or the non-muscle-cutting periumbilical transverse incision group, after stratifying by the location of the tumour (right- or left-sided). The primary outcome of this study is the incidence of incisional hernias (both symptomatic and radiologic hernias) at 12 months after surgery. The secondary outcomes include operative outcomes, 30-day postoperative complications, pathological results, and patient-reported outcomes (short form-12 health survey questionnaire and body image questionnaire). Both primary (intention-to-treat) and secondary (as-treated principles) analyses will be performed for all outcomes. The statistical significance level was set at p < 0.05 (two-sided testing). DISCUSSION: This trial may show that the non-muscle-cutting periumbilical transverse incision will reduce the incidence of incisional hernias compared to the midline incision. TRIAL REGISTRATION: Clinical Research Information Service (CRiS) of Republic of Korea, KCT0006082 . Registered on April 12, 2021.


Assuntos
Neoplasias do Colo , Hérnia Incisional , Humanos , Hérnia Incisional/epidemiologia , Hérnia Incisional/etiologia , Hérnia Incisional/prevenção & controle , Neoplasias do Colo/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Imagem Corporal , Inquéritos Epidemiológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
20.
Int J Prosthodont ; 36(1): 71-73, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36853227

RESUMO

This manuscript presents a more accurate methodology, in comparison to extant approaches, that enables errorless congruence between an implant scanbody and its counterparts in the scanbody library of a dental computer-aided design (CAD) application. The proposed method deletes corners and difficult intraoral scanning regions and selects only the remaining flat and wide scanbody planes in the library. Achieving overlap between the portions of the actual scanbody data without distortion using an intraoral scanner is a novel development that is expected to represent a new standard in scanbody library alignment.


Assuntos
Desenho Assistido por Computador , Implantes Dentários
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