RESUMEN
Background/Aims@#Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis. @*Methods@#In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events. @*Results@#Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups.No significant difference was noted in the incidence of adverse drug reactions. @*Conclusions@#Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).
RESUMEN
Background/Aims@#The eCura system, a scoring model for stratifying the lymph node metastasis risk after noncurative endoscopic resection for early gastric cancer (EGC), has been internally validated, primarily for differentiated-type EGC. We aimed to externally validate this model for undifferentiated-type EGC. @*Methods@#This multicenter, retrospective cohort study included 634 patients who underwent additional surgery (radical surgery group, n=270) or were followed up without additional treatment (no additional treatment group, n=364) after noncurative endoscopic resection for undifferentiated-type EGC between 2005 and 2015. The lymph node metastasis and survival rates were compared according to the risk categories. @*Results@#For the radical surgery group, the lymph node metastasis rates were 2.6%, 10.9%, and 14.8% for the low-, intermediate-, and high-risk eCura categories, respectively (p for trend=0.003). For the low-, intermediate-, and high-risk categories in the no additional treatment group, the overall survival (92.7%, 68.9%, and 80.0% at 5 years, respectively, p<0.001) and cancer-specific survival rates (99.7%, 94.7%, and 80.0% at 5 years, respectively, p<0.001) differed significantly. In the multivariate analysis, the hazard ratios (95% confidence interval) in the no additional treatment group relative to the radical surgery group were 3.18 (1.41 to 7.17; p=0.005) for overall mortality and 2.60 (0.46 to 14.66; p=0.280) for cancer-specific mortality in the intermediate-tohigh risk category. No such differences were noted in the low-risk category. @*Conclusions@#The eCura system can be applied to undifferentiated-type EGC. Close follow-up without additional treatment might be considered for low-risk patients, while additional surgery is recommended for intermediate- and high-risk patients.
RESUMEN
Background/Aims@#Metachronous recurrence incidences and risk factors following endoscopic submucosal dissection (ESD) for gastric adenocarcinoma and dysplasias were investigated. @*Methods@#Retrospective review of electronic medical records of patients who underwent gastric ESD at The Catholic University of Korea, Yeouido St. Mary’s Hospital. @*Results@#A total of 190 subjects were enrolled for analysis during the study period. The mean age was 64.4 years-old and the male sex occupied 73.7%. The mean observation period following ESD was 3.45 years. The annual incidence rate of metachronous gastric neoplasms (MGN) was about 3.96%. The annual incidence rate was 5.36% for the low-grade dysplasia group, 6.47% for the high-grade dysplasia group, and 2.74% for the EGC group. MGN was more frequent in the dysplasia group than in the EGC group (p<0.05). For those with MGN development, the mean time interval from ESD to MGN was 4.1 (±1.8) years. By using the Kaplan–Meier model, the estimated mean MGN free survival time was 9.97 years (95% confidence interval, 8.53–11.40) The histological types of MGN were not related to the primary histology types. @*Conclusions@#MGN following ESD developed in 3.96% annually and MGN was more frequent in the dysplasia group. The histological types of MGN did not correlate with those of primary neoplasm.
RESUMEN
Background/Aims@#There is no clear consensus on the relative ranking of interventional and radiation techniques with indications similar to those of radiofrequency ablation (RFA) for the treatment of early hepatocellular carcinoma (HCC). We used a network meta-analysis to compare the efficacy of non-surgical treatments for early HCC. @*Methods@#We searched databases for randomized trials assessing the efficacy of loco-regional treatments for HCCs ≤5 cm with no extrahepatic spread or portal invasion. The primary outcome was the pooled hazard ratio (HR) for overall survival (OS), and secondary outcomes included overall and local progression-free survival (PFS). A frequentist network meta-analysis was performed, and the relative ranking of therapies was assessed with P-scores. @*Results@#Nineteen studies comparing 11 different strategies in 2,793 patients were included. Chemoembolization plus RFA improved OS better than RFA alone (HR 0.52, 95% confidence interval [CI] 0.33–0.82; P-score=0.951). Cryoablation, microwave ablation, laser ablation, and proton beam therapy had similar effects on OS compared with RFA. For overall PFS, but not local PFS, only chemoembolization plus RFA performed significantly better than RFA (HR 0.61, 95% CI 0.42–0.88; P-score=0.964). Injection of percutaneous ethanol or acetic acid was significantly less effective than RFA for all measured outcomes, while no differences in progression outcomes were identified for other therapies included in the network. @*Conclusions@#Our results suggest that chemoembolization combined with RFA is the best option for local treatment of early HCC. Cases with potential contraindications for RFA may benefit from a tailored approach using thermal or radiation modalities.
RESUMEN
Purpose@#Frequent neutropenia hinders uninterrupted palbociclib treatment in patients with hormone receptor (HR)–positive breast cancer. We compared the efficacy outcomes in multicenter cohorts of patients with metastatic breast cancer (mBC) receiving palbociclib following conventional dose modification or limited modified schemes for afebrile grade 3 neutropenia. @*Materials and Methods@#Patients with HR-positive, human epidermal growth factor receptor 2–negative mBC (n=434) receiving palbociclib with letrozole as first-line therapy were analyzed and classified based on neutropenia grade and afebrile grade 3 neutropenia management as follows: group 1 (maintained palbociclib dose, limited scheme), group 2 (dose delay or reduction, conventional scheme), group 3 (no afebrile grade 3 neutropenia event), and group 4 (grade 4 neutropenia event). The primary and secondary endpoints were progression-free survival (PFS) between groups 1 and 2 and PFS, overall survival, and safety profiles among all groups. @*Results@#During follow-up (median 23.7 months), group 1 (2-year PFS, 67.9%) showed significantly longer PFS than did group 2 (2-year PFS, 55.3%; p=0.036), maintained across all subgroups, and upon adjustment of the factors. Febrile neutropenia occurred in one and two patients of group 1 and group 2, respectively, without mortality. @*Conclusion@#Limited dose modification for palbociclib-related grade 3 neutropenia may lead to longer PFS, without increasing toxicity, than the conventional dose scheme.
RESUMEN
Idiopathic pulmonary fibrosis (IPF) can be defined as a progressive chronic pulmonary disease showing scarring in the lung parenchyma, thereby resulting in increase in mortality and decrease in the quality of life. The pathophysiologic mechanism of fibrosis in IPF is still unclear. Repetitive microinjuries to alveolar epithelium with genetical predisposition and an abnormal restorative reaction accompanied by excessive deposition of collagens are involved in the pathogenesis. Although the two FDA-approved drugs, pirfenidone and nintedanib, are under use for retarding the decline in lung function of patients suffered from IPF, they are not able to improve the survival rate or quality of life. Therefore, a novel therapeutic agent acting on the major steps of the pathogenesis of disease and/or, at least, managing the clinical symptoms of IPF should be developed for the effective regulation of this incurable disease. In the present review, we tried to find a potential of managing the clinical symptoms of IPF by natural products derived from medicinal plants used for controlling the pulmonary inflammatory diseases in traditional Asian medicine. A multitude of natural products have been reported to exert an antifibrotic effect in vitro and in vivo through acting on the epithelial-mesenchymal transition pathway, transforming growth factor (TGF)-β-induced intracellular signaling, and the deposition of extracellular matrix. However, clinical antifibrotic efficacy of these natural products on IPF have not been elucidated yet. Thus, those effects should be proven by further examinations including the randomized clinical trials, in order to develop the ideal and optimal candidate for the therapeutics of IPF.
RESUMEN
In this study, artesunate, an antimalarial agent, was investigated for its potential effect on the gene expression of airway MUC5AC mucin. The human pulmonary epithelial NCI-H292 cells were pretreated with artesunate for 30 min and then stimulated with phorbol 12-myristate 13-acetate (PMA), for the following 24 h. The effect of artesunate on PMA-induced nuclear factor kappa B (NFkB) signaling pathway was also examined. Artesunate inhibited the glycoprotein production and mRNA expression of MUC5AC mucins, induced by PMA through the inhibition of degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation.These results suggest artesunate suppresses the gene expression of mucin through regulation of NF-kB signaling pathway, in human pulmonary epithelial cells.
RESUMEN
The current study aimed to reveal the potential effect of meclofenamate, a nonsteroidal anti-inflammatory drug, on the gene expression of airway MUC5AC mucin. Human pulmonary mucoepidermoid NCI-H292 cells were pretreated with meclofenamate for 30 min and stimulated with phorbol 12-myristate 13-acetate (PMA) for 24 h. Thereafter, the effect of meclofenamate on the PMAinduced nuclear factor kappa B (NF-kB) signaling pathway was assessed. Meclofenamate inhibited glycoprotein production and mRNA expression of MUC5AC mucins induced by PMA by inhibiting the degradation of inhibitory kappa Bα (IkBα) and NF-kB p65 nuclear translocation. These results suggest meclofenamate suppresses mucin gene expression by regulating NF-kB signaling pathway in human pulmonary epithelial cells.
RESUMEN
Background@#During the coronavirus disease 2019 (COVID-19) pandemic, the everyday use of face masks massively increased to prevent the spread of infection. Many people complain of ear pain and erosion when wearing a mask for extended periods of time. If prolonged mask usage is uncomfortable for ordinary people, a question arises—how much more inconvenient must mask wearing be for patients with a full-thickness skin graft (FTSG) donor site in the retroauricular region? Herein, we evaluated complications related to face mask use in 27 patients with a retroauricular FTSG donor site, with the goal of clarifying whether the retroauricular region is still an appropriate FTSG donor site in the context of the COVID-19 pandemic. @*Methods@#Complications in 27 patients treated by FTSGs harvested from the retroauricular region from 2019 to 2021 were investigated. A questionnaire comparing the normal and the operated sides was administered. Pain, itching, soreness, deformity, and symmetry were further investigated. @*Results@#Pain and itching were the only observed complications. The operated side was slightly more painful than the normal side in four patients (14.8%), and four patients (14.8%) reported itching on the operated side. However, all patients who experienced complications stated that the pain or itching did not interfere with mask wearing. Most symptomatic patients were older than 60 years of age (23.8%, p=0.185) and wore masks for longer periods of time (28.5%, p=0.326). @*Conclusion@#Few retroauricular donor site-related complications occurred, and none of these complications caused inconvenience in daily life. Therefore, in the COVID-19 pandemic, the use of the retroauricular region as an FTSG donor site remains appropriate.
RESUMEN
Purpose@#Surgeons have become increasingly interested in reduced-port gastrectomy to minimize trauma while maintaining oncologic safety. Although gastroduodenostomy has the benefits of better nutritional outcomes and fewer postoperative complications than other types of reconstruction, gastroduodenostomy is not a preferred option for reducedport distal gastrectomy because of technical difficulties. In this study, we describe our intracorporeal modified deltashaped gastroduodenostomy technique, which is easily applicable during 2-port distal gastrectomy. @*Methods@#We retrospectively reviewed our database of 30 consecutive patients with gastric cancer who underwent 2-port distal gastrectomy with intracorporeal modified delta-shaped gastroduodenostomy from October 2016 to May 2021. In this reduced-port approach, we used a Tropian Single port (TROPIAN TECH) via a 25-mm transumbilical incision and a 12-mm port at the right flank. All anastomoses were performed using a 60-mm endolinear stapler. We used 3 additional sutures to provide proper traction and support for the anastomosis. @*Results@#Mean ± standard deviation of operation time was 148.9 ± 34.7 minutes; reconstruction time was 13.2 ± 4.6 minutes; estimated blood loss was 29.3 ± 44.4 mL; and length of hospital stay was 4.5 ± 1.2 postoperative days. A total of 11 patients (36.7%) had a Clavien-Dindo grade I or grade II complication, and there were no grade IIIa or higher complications. @*Conclusion@#Intracorporeal modified delta-shaped gastroduodenostomy was safely performed via a 2-port approach, resulting in acceptable surgical outcomes and no major complications.
RESUMEN
Purpose@#Because the global geriatric population continues to increase, the assessment of emergency surgical outcomes in elderly patients with acute peritonitis will become more important. @*Methods@#A retrospective review was conducted on the data of 174 elderly patients who underwent emergency surgery for intestinal perforation or intestinal infarction between June 2010 and November 2022. We conducted an analysis of the risk factors associated with postoperative complications and mortality by evaluating the characteristics of patients and their surgical outcomes. @*Results@#In our study, most patients (94.3%) had preexisting comorbidities, and many patients (84.5%) required transfer to the intensive care unit following emergency surgery. Postoperative complications were observed in 84 individuals (48.3%), with postoperative mortality occurring in 29 (16.7%). Multivariate analysis revealed preoperative acute renal injury, hypoalbuminemia, and postoperative ventilator support as significant predictors of postoperative mortality. @*Conclusion@#When elderly patients undergo emergency surgery for intestinal perforation or infarction, it is important to recognize that those with preoperative acute renal injury, hypoalbuminemia, and a need for postoperative ventilator support have a poor prognosis. Therefore, these patients require intensive care from the early stages of treatment.
RESUMEN
Purpose@#The prognostic significance and treatment of lateral pelvic lymph node metastasis (mLPLN) in rectal cancer patients receiving neoadjuvant chemoradiotherapy (nCRT) are not well understood. In this study, we evaluated the impact of mLPLN identified in imaging modality on outcomes. @*Methods@#Between January 2008 and December 2016, 1,535 patients who underwent radical resection following nCRT were identified. The association between mLPLN and disease-free survival (DFS), overall survival (OS), local recurrencefree survival (LRFS), and pelvic recurrence-free survival (PRFS) was analyzed, along with risk factors associated with OS and DFS. @*Results@#Overall, 329 (21.4%) of the 1,535 patients experienced disease recurrence; 71 (4.6%) had local recurrence, 25 (1.6%) had pelvic recurrence, and 312 (20.3%) had distant recurrence. The pre- and post-nCRT mLPLN (–) groups had better DFS, LRFS, PRFS, and OS than the (+) groups. LPLN sampling (LPLNs) was implemented in 24.0% of the pre-nCRT mLPLN (+) group and in 28.8% of the post-nCRT mLPLN (+) group. There was no significant difference in OS and LRFS between LPLNs group and no LPLNs group in pre- and post-nCRT mLPLN (+) groups. Pre-nCRT mLPLN was associated with poor OS (hazard ratio [HR], 1.43; P = 0.009) and post-nCRT mLPLN was associated with poor DFS (HR, 1.49; P = 0.002). @*Conclusion@#Pre- and post-nCRT mLPLN (+) have different prognostic effects. Post-nCRT mLPLN appears to be more important for disease control. However, pre-nCRT mLPLN should not be disregarded when devising a treatment strategy since it is an independent risk factor for OS.
RESUMEN
Purpose@#This study aimed to evaluate the predictive value of lymph node yield (LNY) for survival outcomes according to tumor response after preoperative chemoradiotherapy (PCRT) in patients with rectal cancer. @*Methods@#This study was a retrospective study conducted in a tertiary center. A total of 1,240 patients with clinical stage II or III rectal cancer who underwent curative resection after PCRT between 2007 and 2016 were included. Patients were categorized into the good response group (tumor regression grade [TRG], 0–1) or poor response group (TRG, 2–3). Propensity score matching was performed for age, sex, and pathologic stage between LNY of ≥12 and LNY of <12 within tumor response group. The primary outcome was 5-year disease-free survival (DFS) and overall survival (OS). @*Results@#LNY and positive lymph nodes were inversely correlated with TRG. In good responders, 5-year DFS and 5-year OS of patients with LNY of <12 were better than those with LNY of ≥12, but there was no statistical significance. In poor responders, the LNY of <12 group had worse survival outcomes than the LNY of ≥12 group, but there was also no statistical significance. LNY of ≥12 was not associated with DFS and OS in multivariate analysis. @*Conclusion@#LNY of <12 showed contrasting outcomes between the good and poor responders in 5-year DFS and OS. LNY of 12 may not imply adequate oncologic surgery or proper staging in rectal cancer patients treated by PCRT. Furthermore, a decrease in LNY should be comprehended differently according to tumor response.
RESUMEN
Purpose@#Behçet’s disease (BD) is a chronic inflammatory immune-mediated disease involving multiorgan systems. Gastrointestinal (GI) manifestations of BD include abdominal pain, vomiting, GI bleeding, fistula formation, obstruction, and perforation that might require surgery. Recently, anti-tumor necrosis factor-alpha (anti-TNF-α) therapy has been shown to have favorable outcomes in patients with intestinal BD who are refractory to conventional therapy. This study sought to figure out the risk factors for undergoing surgery during anti-TNF-α therapy in patients with intestinal BD. @*Materials and Methods@#In this retrospective analysis of intestinal BD patients who were treated with anti-TNF-α, we collected the baseline patient data including comorbidities, clinical, endoscopic, and radiologic characteristics, and the Disease Activity Index for Intestinal Behçet’s Disease at the time of anti-TNF-α initiation. Each potential risk factor was compared. For multivariate analysis, Cox regression was used. @*Results@#A total of 62 patients were considered eligible for analysis, and 15 of them (24.1%) underwent surgery. In univariate analysis, the presence of extraintestinal manifestation, such as joint symptoms and erythrocyte sedimentation rate (ESR), were significantly associated with surgery during therapy. In multivariate analysis, drug response within 4 weeks [hazard ratio (HR), 64.59], skin and joint manifestation (HR, 10.23 and HR, 6.22), geographic ulcer (HR, 743.97), and ESR >42.5 mm/h (HR, 9.16) were found to be factors predictive of undergoing surgery during anti-TNF-α therapy. @*Conclusion@#We found five risk factors predictive of surgery in patients with intestinal BD receiving anti-TNF-α therapy, which can guide physicians in selecting appropriate patients between anti-TNF-α therapy and early surgery.
RESUMEN
Objective@#The study aimed to evaluate the changes in mandibular width after sagittal split ramus osteotomy (SSRO) in patients with mandibular asymmetric prognathism using cone-beam computed tomography (CBCT). @*Methods@#Seventy patients who underwent SSRO for mandibular setback surgery were included in two groups, symmetric (n = 35) and asymmetric (n = 35), which were divided according to the differences in their right and left setback amounts. The mandibular width was evaluated three-dimensionally using CBCT images taken immediately before surgery (T1), 3 days after surgery (T2), and 6 months after surgery (T3). Repeated measures analysis of variance was applied to verify the differences in mandibular width statistically. @*Results@#Both groups showed a significant increase in the mandibular width at T2, followed by a significant decrease at T3. No significant difference was observed between T1 and T3 in any of the measurements. No significant differences were found between the two groups (p > 0.05). Conclusions: After mandibular asymmetric setback surgery using SSRO, the mandibular width increased immediately but returned to its original width 6 months after surgery.
RESUMEN
Background/Aims@#This study evaluated the long-term cardiovascular complications among Korean patients with hypertension and compared them with that of controls without hypertension. @*Methods@#The Korean Hypertension Cohort (KHC) enrolled 11,043 patients with hypertension and followed them for more than 10 years. Age- and sex-matched controls without hypertension were enrolled at a 1:10 ratio. We compared the incidence of cardiovascular events and death among patients and controls without hypertension. @*Results@#The mean age was 59 years, and 34.8% and 16.5% of the patients belonged to the high and moderate cardiovascular risk groups, respectively. During the 10-year follow-up, 1,591 cardiovascular events (14.4%) with 588 deaths (5.3%) occurred among patients with hypertension and 7,635 cardiovascular events (6.9%) with 4,826 deaths (4.4%) occurred among controls. Even the low-risk population with hypertension showed a higher cardiovascular event rate than the population without hypertension. Although blood pressure measurements in the clinic showed remarkable inaccuracy compared with those measured in the national health examinations, systolic blood pressure (SBP) ≥ 150 mmHg was significantly associated with a higher risk of cardiovascular events. @*Conclusions@#This long-term follow-up study confirmed the cardiovascular event rates among Korean hypertensive patients were substantial, reaching 15% in 10 years. SBP levels ≥ 150 mmHg were highly associated with occurrence of cardiovascular event rates.
RESUMEN
Background/Aims@#The gastric extranodal marginal zone B-cell lymphomas of mucosa-associated lymphoid tissue (gastric MALT lymphoma) are mostly related to Helicobacter pylori infections. However, chromosomal aberration involving translocation t(11;18) is also frequently reported in these patients. @*Methods@#The study was a retrospective review and analysis of electronic medical records to assess the factors which affect complete remission (CR) in patients with gastric MALT lymphoma. Based on the medical records, subjects with gastric MALT lymphoma were enrolled consecutively from January 2004 to December 2021. @*Results@#Among the 77 subjects who were found with gastric MALT lymphoma in the database, 65 cases with complete records were analyzed. Of these, 66.2% (43/65) were H. pylori positive. Genetic analyses for t(11:18) were done on 41 subjects. The t(11:18) chromosomal translocation with MALT1:BIRC3 fusion was found in 31.7% (13/41) of the subjects. With H. pylori eradication therapy, 75% (21/28) of the subjects without t(11:18) achieved CR. However, only 23.1% (3/13) subjects with t(11:18) could achieve CR (p-value=0.009). In the H. pylori-positive group, 85.7% (18/21) subjects without t(11:18) achieved CR with eradication therapy, but 71.4% (5/7) subjects with t(11:18) failed to achieve CR (p-value=0.004). In the H. pylori-negative group, 42.3% (3/7) of the subjects without t(11:18) achieved CR with eradication therapy. However, 83.3% (5/6) of H. pylori-negative subjects with t(11:18) failed to achieve CR with eradication therapy and needed additional radiotherapy (p-value=0.396). @*Conclusions@#H. pylori negativity and the presence of t(11:18) were both risk factors for failure to achieve CR with H. pylori eradication therapy as the first line of treatment.
RESUMEN
Background@#Peripheral blood mononuclear cells (PBMCs) are commonly used to assess in vitro immune responses. However, PBMC isolation is a time-consuming procedure, introduces technical variability, and requires a relatively large volume of blood. By contrast, whole blood assay (WBA) is faster, cheaper, maintains more physiological conditions, and requires less sample volume, laboratory training, and equipment. @*Objectives@#Herein, this study aimed to develop a porcine WBA for in vitro evaluation of immune responses. @*Methods@#Heparinized whole blood (WB) was diluted (non-diluted, 1/2, 1/8, and 1/16) in RPMI-1640 media, followed by phorbol myristate acetate and ionomycin. After 24 h, cells were stained for interferon (IFN)-γ secreting T-cells followed by flow cytometry, and the supernatant was analyzed for tumor necrosis factor (TNF)-α. In addition, diluted WB was stimulated by lipopolysaccharide (LPS) and polyinosinic:polycytidylic acid (poly I:C), reference strain KCTC3557 (RS), field isolate (FI), of heat-killed (HK) Streptococcus suis, and porcine reproductive and respiratory syndrome virus (PRRSV). @*Results@#The frequency of IFN-γ + CD3 + T-cells and concentration of TNF-α in the supernatant of WB increased with increasing dilution factor and were optimal at 1/8. WB TNF-α and interleukin (IL)-10 cytokine levels increased significantly following stimulation with LPS or poly I:C. Further, FI and RS induced IL-10 production in WB. Additionally, PRRSV strains increased the frequency of IFN-γ + CD4 - CD8 + cells, and IFN-γ was non-significantly induced in the supernatant of re-stimulated samples. @*Conclusions@#We propose that the WBA is a rapid, reliable, and simple method to evaluate immune responses and WB should be diluted to trigger immune cells.
RESUMEN
Purpose@#Patients with triple-negative breast cancer (TNBC) have an increased risk of distant metastasis compared to those with other subtypes. In this study, we aimed to identify the genes associated with distant metastasis in TNBC and their underlying mechanisms. @*Methods@#We established patient-derived xenograft (PDX) models using surgically resected breast cancer tissues from 31 patients with TNBC. Among these, 15 patients subsequently developed distant metastases. Candidate metastasis-associated genes were identified using RNA sequencing. In vitro wound healing, proliferation, migration, and invasion assays and in vivo tumor xenograft and metastasis assays were performed to determine the functional importance of aldo-keto reductase family 1 member C2 (AKR1C2). Additionally, we used the METABRIC dataset to investigate the potential role of AKR1C2 in regulating TNBC subtypes and their downstream signaling activities. @*Results@#RNA sequencing of primary and PDX tumors showed that genes involved in steroid hormone biosynthesis, including AKR1C2, were significantly upregulated in patients who subsequently developed metastasis. In vitro and in vivo assays showed that silencing of AKR1C2 resulted in reduced cell proliferation, migration, invasion, tumor growth, and incidence of lung metastasis. AKR1C2 was upregulated in the luminal androgen receptor (LAR) subtype of TNBC in the METABRIC dataset, and AKR1C2 silencing resulted in the downregulation of LAR classifier genes in TNBC cell lines. The androgen receptor (AR) gene was a downstream mediator of AKR1C2-associated phenotypes in TNBC cells. AKR1C2 expression was associated with gene expression pathways that regulate AR expression, including JAK-STAT signaling or interleukin 6 (IL-6). The levels of phospho-signal transducer and activator of transcription and IL-6, along with secreted IL-6, were significantly downregulated in AKR1C2-silenced TNBC cells. @*Conclusion@#Our data indicate that AKR1C2 is an important regulator of cancer growth and metastasis in TNBC and may be a critical determinant of LAR subtype features.
RESUMEN
Background@#Patella baja with patellar tendon shortening due to traumatic or ischemic injury is a widely known complication after primary total knee arthroplasty (TKA). Pseudo-patella baja may arise from the elevation of the joint line after excessive distal femoral resection. The maintenance of original patellar height is important in revision TKA because postoperative patella baja and pseudo-patella baja can cause inferior biomechanical and clinical results. We investigated the incidence and risk factors of patella baja and pseudo-patella baja after revision TKA. @*Methods@#We retrospectively reviewed data for 180 revision TKAs. Patella baja was defined as a truly low-lying patella with an Insall-Salvati ratio (ISR) of < 0.8 and a Blackburne-Peel ratio (BPR) of < 0.54. Pseudo-patella baja was defined as a relatively lowlying patella compared to the joint line within the normal range of ISR and with a BPR of < 0.54. Clinically, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and range of motion (ROM) were evaluated. Risk factors increasing the incidence of patella baja and pseudo-patella baja after revision TKA were evaluated using multiple regression analysis. @*Results@#Before revision TKA, 169 knees did not exhibit patella baja or pseudo-patella baja, while 9 knees showed patella baja and 2 knees exhibited pseudo-patella baja. At 2 years after revision TKAs, 25 knees (13.9%) showed patella baja and 23 knees (12.8%) exhibited pseudo-patella baja. Despite no differences in the postoperative WOMAC score between groups with and without patella baja and pseudo-patella baja, the postoperative ROM was significantly smaller in the group with patella baja (113.3°) or pseudo patella baja (110.5°) than in the normal group (122.0°). Infection as the cause of revision TKA increased the risk of patella baja (odds ratio, 10.958; p < 0.001), and instability increased the risk of pseudo-patella baja (odds ratio, 11.480; p < 0.001). @*Conclusions@#Infection and instability resulted in increases in the incidence of patella baja and pseudo-patella baja after revision TKA. Information about the risk factors of patella baja and pseudo-patella baja will help TKA surgeons plan the height of the patella after revision TKA and improve clinical outcomes.