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Purpose@#BRCA1 and BRCA2 are among the most important genes involved in DNA repair via homologous recombination (HR). Germline BRCA1/2 (gBRCA1/2)-related cancers have specific characteristics and treatment options but conducting gBRCA1/2 testing and interpreting the genetic imprint are sometimes complicated. Here, we describe the concordance of gBRCA1/2 derived from a panel of clinical tumor tissues using next-generation sequencing (NGS) and genetic aspects of tumors harboring gBRCA1/2 pathogenic variants. @*Materials and Methods@#Targeted sequencing was performed using available tumor tissue from patients who underwent gBRCA1/2 testing. Comparative genomic analysis was performed according to gBRCA1/2 pathogenicity. @*Results@#A total of 321 patients who underwent gBRCA1/2 testing were screened, and 26 patients with gBRCA1/2 pathogenic (gBRCA1/2p) variants, eight patients with gBRCA1/2 variants of uncertain significance (VUS; gBRCA1/2v), and 43 patients with gBRCA1/2 wild-type (gBRCA1/2w) were included in analysis. Mutations in TP53 (49.4%) and PIK3CA (23.4%) were frequently detected in all samples. The number of single-nucleotide variants (SNVs) per tumor tissue was higher in the gBRCA1/2w group than that in the gBRCA1/2p group (14.81 vs. 18.86, p=0.278). Tumor mutation burden (TMB) was significantly higher in the gBRCA1/2w group than in the gBRCA1/2p group (10.21 vs. 13.47, p=0.017). Except for BRCA1/2, other HR-related genes were frequently mutated in patients with gBRCA1/2w. @*Conclusion@#We demonstrated high sensitivity of gBRCA1/2 in tumors analyzed by NGS using a panel of tumor tissues. TMB value and aberration of non-BRCA1/2 HR-related genes differed significantly according to gBRCA1/2 pathogenicity in patients with breast cancer.
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Purpose@#K-MASTER project is a Korean national precision medicine platform that screened actionable mutations by analyzing next-generation sequencing (NGS) of solid tumor patients. We compared gene analyses between NGS panel from the K-MASTER project and orthogonal methods. @*Materials and Methods@#Colorectal, breast, non–small cell lung, and gastric cancer patients were included. We compared NGS results from K-MASTER projects with those of non-NGS orthogonal methods (KRAS, NRAS, and BRAF mutations in colorectal cancer [CRC]; epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase [ALK] fusion, and reactive oxygen species 1 [ROS1] fusion in non–small cell lung cancer [NSCLC], and Erb-B2 receptor tyrosine kinase 2 (ERBB2) positivity in breast and gastric cancers). @*Results@#In the CRC cohort (n=225), the sensitivity and specificity of NGS were 87.4% and 79.3% (KRAS); 88.9% and 98.9% (NRAS); and 77.8% and 100.0% (BRAF), respectively. In the NSCLC cohort (n=109), the sensitivity and specificity of NGS for EGFR were 86.2% and 97.5%, respectively. The concordance rate for ALK fusion was 100%, but ROS1 fusion was positive in only one of three cases that were positive in orthogonal tests. In the breast cancer cohort (n=260), ERBB2 amplification was detected in 45 by NGS. Compared with orthogonal methods that integrated immunohistochemistry and in situ hybridization, sensitivity and specificity were 53.7% and 99.4%, respectively. In the gastric cancer cohort (n=64), ERBB2 amplification was detected in six by NGS. Compared with orthogonal methods, sensitivity and specificity were 62.5% and 98.2%, respectively. @*Conclusion@#The results of the K-MASTER NGS panel and orthogonal methods showed a different degree of agreement for each genetic alteration, but generally showed a high agreement rate.
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Purpose@#The purpose of this study is to identify the factors influencing the intention to report child abuse of emergency room nurses based on the health belief model. @*Methods@#This was a descriptive study that used a cross-sectional design. A total of 188 emergency room nurses working at general hospitals with more than 300 beds in Seoul participated in the study. Data were analyzed using descriptive statistics, t-test, ANOVA, Pearson’s correlation coefficient and multiple regression analysis with the SPSS 25.0 program. @*Results@#Correlations and regression analyses showed that the perceived severity (β=.14, p=.024), perceived barrier (β= -.25, p<.001), and self-efficacy (β=.31, p<.001) were factors influencing emergency room nurses’ intention to report child abuse, and the explanatory power of the model was 33.0%. @*conclusion@#The results of this study related to the health belief model, being a valid theoretical basis for child abuse reporting intention research, significantly suggest new research directions in the future. In addition, to increase the nurses' intention to report child abuse in the emergency room, the influencing factors identified in this study can be utilized and develop specific interventions using the health belief model.
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In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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Objectives@#Postoperative opioid use and pain are related to postoperative delirium. This study aims to compare the incidence of delirium in patients with and without patient-controlled intravenous analgesia (PCIA) among liver transplant recipients. @*Methods@#The medical records of 253 patients who received liver transplantation (LT) from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided into two groups: the patients who had used PCIA (P group, n = 71) and those who did not use PCIA (C group, n = 182) after LT in intensive care unit (ICU). The patient data were collected, which included demographic data, and details about perioperative management and postoperative complications. @*Results@#There was no difference in the model for end-stage liver disease (MELD) score between the two groups. Postoperative delirium occurred in 10 / 71 (14.08 %) in the P group and 26 / 182 (14.29 %) in the C group after LT, respectively (P = 0.97). After propensity score matching, no differences were observed in the incidence of delirium (P = 0.359) and the time from surgery to discharge (P = 0.26) between the two groups. @*Conclusions@#Patients with PCIA after LT exhibited no relationship with postoperative delirium. Therefore, it is necessary to actively control postoperative pain using PCIA.
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In 2017, Korean Society of Medical Oncology (KSMO) published the Korean management guideline of metastatic prostate cancer. This paper is the 2nd edition of the Korean management guideline of metastatic prostate cancer. We updated recent many changes of management in metastatic prostate cancer in this 2nd edition guideline. The present guideline consists of the three categories: management of metastatic hormone sensitive prostate cancer; management of metastatic castration resistant prostate cancer; and clinical consideration for treating patients with metastatic prostate cancer. In category 1 and 2, levels of evidence (LEs) have been mentioned according to the general principles of evidence-based medicine. And grades of recommendation (GR) was taken into account the quality of evidence, the balance between desirable and undesirable effects, the values and preferences, and the use of resources and GR were divided into strong recommendations (SR) and weak recommendations (WR). A total of 16 key questions are selected. And we proposed recommendations and described key evidence for each recommendation. The treatment landscape of metastatic prostate cancer is changing very rapid and many trials are ongoing. To verify the results of the future trials is necessary and should be applied to the treatment for metastatic prostate cancer patients in the clinical practice. Especially, many prostate cancer patients are old age, have multiple underlying medical comorbidities, clinicians should be aware of the significance of medical management as well as clinical efficacy of systemic treatment.
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Objectives@#Postoperative opioid use and pain are related to postoperative delirium. This study aims to compare the incidence of delirium in patients with and without patient-controlled intravenous analgesia (PCIA) among liver transplant recipients. @*Methods@#The medical records of 253 patients who received liver transplantation (LT) from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided into two groups: the patients who had used PCIA (P group, n = 71) and those who did not use PCIA (C group, n = 182) after LT in intensive care unit (ICU). The patient data were collected, which included demographic data, and details about perioperative management and postoperative complications. @*Results@#There was no difference in the model for end-stage liver disease (MELD) score between the two groups. Postoperative delirium occurred in 10 / 71 (14.08 %) in the P group and 26 / 182 (14.29 %) in the C group after LT, respectively (P = 0.97). After propensity score matching, no differences were observed in the incidence of delirium (P = 0.359) and the time from surgery to discharge (P = 0.26) between the two groups. @*Conclusions@#Patients with PCIA after LT exhibited no relationship with postoperative delirium. Therefore, it is necessary to actively control postoperative pain using PCIA.
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Purpose@#Next-generation sequencing (NGS) can facilitate precision medicine approaches in metastatic colorectal cancer (mCRC) patients. We investigated the molecular profiling of Korean mCRC patients under the K-MASTER project which was initiated in June 2017 as a nationwide precision medicine oncology clinical trial platform which used NGS assay to screen actionable mutations. @*Materials and Methods@#As of 22 January 2020, total of 994 mCRC patients were registered in K-MASTER project. Targeted sequencing was performed using three platforms which were composed of the K-MASTER cancer panel v1.1 and the SNUH FIRST Cancer Panel v3.01. If tumor tissue was not available, cell-free DNA was extracted and the targeted sequencing was performed by Axen Cancer Panel as a liquid biopsy. @*Results@#In 994 mCRC patients, we found 1,564 clinically meaningful pathogenic variants which mutated in 71 genes. Anti-EGFR therapy candidates were 467 patients (47.0%) and BRAF V600E mutation (n=47, 4.7%), deficient mismatch repair/microsatellite instability–high (n=15, 1.5%), HER2 amplifications (n=10, 1.0%) could be incorporated with recently approved drugs. The patients with high tumor mutation burden (n=101, 12.7%) and DNA damaging response and repair defect pathway alteration (n=42, 4.2%) could be enrolled clinical trials with immune checkpoint inhibitors. There were more colorectal cancer molecular alterations such as PIK3CA, KRAS G12C, atypical BRAF, and HER2 mutations and even rarer but actionable genes that approved or ongoing clinical trials in other solid tumors. @*Conclusion@#K-MASTER project provides an intriguing background to investigate new clinical trials with biomarkers and give therapeutic opportunity for mCRC patients.
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Background/Aims@#Stress is closely related to the deterioration of digestive disease. Melatonin has potent anti-inflammatory properties. The objective of this study was to determine the effect of water stress (WS) and sleep deprivation (SD) on intestinal microbiota and roles of melatonin in stressful condition. @*Methods@#We used C57BL/6 mice and specially designed water bath for stress and SD for 10 days. We measured melatonin concentrations in serum, feces, and colon tissues by high-performance liquid chromatography. Genomic DNA was extracted from feces and amplified using primers targeting V3 to V4 regions of bacterial 16S ribosomal RNA genes. @*Results@#Compared to the control, melatonin concentration was lower in the WS and SD. Fecal concentration was 0.132 pg/mL in control, 0.062 pg/mL in WS, and 0.068 pg/mL in SD. In colon tissue, it was 0.45 pg/mL in control, 0.007 pg/mL in WS, and 0.03 pg/mL in SD. After melatonin treatment, melatonin concentrations in feces and colon tissue were recovered to the level of control. Metagenomic analysis of microbiota showed abundance in colitogenic microbiota in WS and SD. Melatonin injection attenuated this harmful effect. WS and SD showed decreased Lactobacillales and increased Erysipelotrichales and Enterobacteriales. Melatonin treatment increased Akkermansia muciniphila and Lactobacillus and decreased Bacteroides massiliensis and Erysipelotrichaceae. @*Conclusions@#This study showed that stress and SD could affect intestinal dysbiosis and increase colitogenic microbiota, which could contribute to the aggravating digestive disease. Melatonin concentrations in feces and colon tissue decreased under WS and SD. Melatonin treatment brought recovery of melatonin concentration in colon tissue and modulating dysbiosis of intestinal microbiota.
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Background@#There are various reports on the effects of the anesthetic method on neurologic complications. A population-based study was conducted to estimate the effect of anesthetic method on the incidence of postoperative delirium in patients that underwent total hip replacement arthroplasty in South Korea. @*Methods@#The Korean National Health Insurance claims database was used to retrospectively identify and analyze 24,379 cases of total hip replacement arthroplasty, defined as patients having a claim record with the operation code ‘N0711,’ from January 2008 to December 2017. Patients were divided into two groups, a general anesthesia group (n = 9,921) and a regional anesthesia group (n = 14,458). The incidence of delirium was assessed in cases when patients used medications for delirium, such as haloperidol, chlorpromazine, olanzapine, and risperidone. @*Results@#Of the 9,921 patients receiving general anesthesia and 14,458 receiving regional anesthesia, 142 (1.43%) and 209 (0.86%) experienced postoperative delirium after total hip replacement arthroplasty, respectively. There was no significant difference between the groups (P = 0.92). In logistic regression analysis, sex (P = 0.038) and patients with acquired immune deficiency syndrome (P = 0.008) were predictors of postoperative delirium. @*Conclusions@#Our results revealed that the anesthetic method was not associated with the incidence of postoperative delirium. In addition, the results suggest that male patients and patients with acquired immune deficiency syndrome undergoing total hip replacement arthroplasty carefully managed for postoperative delirium after surgery.
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Background/Aims@#The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients’ old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. @*Methods@#We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. @*Results@#Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p 4 cycles of first line chemotherapy and subsequent second line chemotherapy. @*Conclusions@#PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.
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Background/Aims@#Patients with pancreatic cancer (PC) generally have poor clinical outcomes. Early determination of their prognosis is crucial for developing a therapeutic strategy. Recently, various inflammatory markers have been validated as prognostic indicators for many cancers, including PC. However, few studies have evaluated these markers together. Thus, the purpose of this study was to comprehensively evaluate the value of inflammatory markers as prognostic indicators in patients with advanced PC treated with gemcitabine-based chemotherapy as the first line regimen. @*Methods@#This was a single-center retrospective study evaluating 302 patients with advanced PC who began first line treatment between November 2004 and August 2016. These patients were monitored until June 2017. Survival rates were assessed with univariate and multivariate analyses. Continuous variables were separated using the normal range or ideal cut-off levels determined by receiver operating curve analyses. @*Results@#Among inflammatory markers evaluated, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and C-reactive protein (CRP) to albumin ratio (CRP-albumin ratio) were independent predictors of overall survival (hazard ratio, 1.712, 1.345, and 1.454, respectively). Difference in survival rates was significant (p < 0.001) among three groups divided by the number of marker-related risks. @*Conclusions@#Baseline inflammatory markers including NLR, PLR, and CRP-albumin ratio are useful in predicting survival rates in patients with PC. Combining these three markers is proven to be valuable.
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Purpose@#The purpose of this study was to identify the concordant or discordant genomic profiling between primary and matched metastatic tumors in patients with colorectal cancer (CRC) and to explore the clinical implication. @*Materials and Methods@#Surgical samples of primary and matched metastatic tissues from 158 patients (335 samples) with CRC at Korea University Anam Hospital were evaluated using the Ion AmpliSeq Cancer Hotspot Panel. We compared genetic variants and classified them as concordant, primary-specific, and metastasis-specific variants. We used a combination of principal components analysis and clustering to find genomic groups. Kaplan-Meier curves were used to appraise survival between genomic groups. We used machine learning to confirm the correlation between genetic variants and metastatic sites. @*Results@#A total of 282 types of deleterious non-synonymous variants were selected for analysis. Of a total of 897 variants, an average of 40% was discordant. Three genomic groups were yielded based on the genomic discrepancy patterns. Overall survival differed significantly between the genomic groups. The poorest group had the highest proportion of concordant KRAS G12V and additional metastasis-specific SMAD4. Correlation analysis between genetic variants and metastatic sites suggested that concordant KRAS mutations would have more disseminated metastases. @*Conclusion@#Driver gene mutations were mostly concordant; however, discordant or metastasis-specific mutations were present. Clinically, the concordant driver genetic changes with additional metastasis-specific variants can predict poor prognosis for patients with CRC.
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BACKGROUND: Postoperative nausea and vomiting (PONV) frequently occurs following bimaxillary orthognathic surgeries. Compared to opioids, Nefopam is associated with lower incidences of PONV, and does not induce gastrointestinal tract injury, coagulopathy, nephrotoxicity, or fracture healing dysfunction, which are common side effects of Nonsteroidal anti-inflammatory drugs. We compared nefopam- and fentanyl-induced incidence of PONV in patients with access to patient-controlled analgesia (PCA) following bimaxillary orthognathic surgeries. METHODS: Patients undergoing bimaxillary orthognathic surgeries were randomly divided into nefopam and fentanyl groups. Nefopam 120 mg or fentanyl 700 µg was mixed with normal saline to a final volume of 120 mL. Patients were given access to nefopam or fentanyl via PCA. Postoperative pain intensity and PONV were measured at 30 minutes and 1 hour after surgery in the recovery room and at 8, 24, 48, and 72 hours after surgery in the ward. The frequency of bolus delivery was compared at each time point. RESULTS: Eighty-nine patients were enrolled in this study, with 48 in the nefopam (N) group and 41 in the fentanyl (F) group. PONV occurred in 13 patients (27.7%) in the N group and 7 patients (17.1%) in the F group at 8 hours post-surgery (P = 0.568), and there were no significant differences between the two groups at any of the time points. VAS scores were 4.4 ± 2.0 and 3.7 ± 1.9 in the N and F groups, respectively, at 8 hours after surgery (P = 0.122), and cumulative bolus delivery was 10.7 ± 13.7 and 8.6 ± 8.5, respectively (P = 0.408). There were no significant differences in pain or bolus delivery at any of the remaining time points. CONCLUSION: Patients who underwent bimaxillary orthognathic surgery and were given nefopam via PCA did not experience a lower rate of PONV compared to those that received fentanyl via PCA. Furthermore, nefopam and fentanyl did not provide significantly different postoperative pain control.
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Humanos , Analgesia Controlada pelo Paciente , Analgésicos Opioides , Fentanila , Consolidação da Fratura , Trato Gastrointestinal , Incidência , Nefopam , Cirurgia Ortognática , Dor Pós-Operatória , Anafilaxia Cutânea Passiva , Náusea e Vômito Pós-Operatórios , Estudos Prospectivos , Sala de RecuperaçãoRESUMO
“Precision†trials, using reasonably integrated biomarker targets and molecularly selective anticancer agents, have become a major concern for both patients and their physicians. As next-generation sequencing, which is a parallel analysis method, becomes quicker, easier, and more accurate, precision medicine-based approaches are becoming more generalized in determining treatments for cancer patients. However, it is not applicable to all cancer patients because of current high prices, limited reimbursement coverage, low prevalence of driver genetic mutations, and lack of treatable drugs. To solve these problems, the Republic of Korea has been operating the Cancer Precision Medicine Diagnosis and Treatment (K-MASTER) Enterprise since its establishment in June 2017. The aim of the project was to conduct large-scale genomic analyses, appropriate matching targeted clinical trials, and data management, which incorporates genomic and clinical information. In this review, we introduce the goals and composition of this project and describe the progress of the project to date.
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BACKGROUND: Maintenance of tracheal intubation is associated with use of sedatives, stress due to mechanical ventilation, or respiratory complications. The aim of this study is to compare the incidence of delirium between early and late extubation groups after liver transplantation (LT). METHODS: Medical records from 247 patients who received LT from January 2010 to July 2017 in a single university hospital were retrospectively reviewed. Patients were divided with 2 groups: Those who underwent early extubation after LT (E group, n = 52) and those who underwent extubation within few hours of intensive care unit (ICU) admission after surgery (C group, n = 195). The patients’ demographic data, perioperative managements and postoperative complications were collected. Early extubation was defined as performing extubation in the operating room after LT. A propensity score matching analysis was performed to reduce the effects of selection bias. RESULTS: Among them, 4/52 (7.69%) in E group and 30/195 (15.38%) in C group occurred postoperative delirium after LT, respectively (P = 0.180). After propensity score matching, there was no difference of the period of hospitalization in ICU (P = 0.961), time to discharge after surgery (P = 0.117) and incidence of delirium between groups (P = 1.000). CONCLUSIONS: Although this study is a retrospective study and limited by the small number of subjects, early extubation does not affect the incidence of delirium after LT. Therefore, further prospective studies on this were needed.
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Humanos , Extubação , Delírio , Hospitalização , Hipnóticos e Sedativos , Incidência , Unidades de Terapia Intensiva , Intubação , Transplante de Fígado , Fígado , Registros Médicos , Salas Cirúrgicas , Complicações Pós-Operatórias , Pontuação de Propensão , Estudos Prospectivos , Respiração Artificial , Estudos Retrospectivos , Viés de SeleçãoRESUMO
BACKGROUND: Static parameters such as central venous pressure and pulmonary artery occlusion pressure, have limitation in evaluation of patients' volume status. Dynamic parameters such as stroke volume variation (SVV), have been used to evaluate intraoperative hemodynamic volume status, in various operations. We examined if SVV is also effective for patients undergoing operation with prone position for fluid management. METHODS: Eighteen patients that received spinal surgery under prone position November 2015 to May 2016, were enrolled. Patients were kept at an SVV value less than 14% during surgery. Changes of pre-, post-operative volume status were evaluated, using transthoracic echocardiography. RESULTS: Mean fluid administered was 1,731.97 ± 792.38 ml. Left ventricular end-diastolic volume was 72.85 ± 13.50 ml before surgery, and 70.84 ± 15.00 ml after surgery (P value = 0.594). Right ventricular end-diastolic area was 15.56 ± 1.71 cm² before surgery, and 13.52 ± 2.65 cm² after surgery (P value = 0.110). Inferior vena cava diameter was 14.99 ± 1.74 mm before surgery, and 13.57 ± 2.83 mm after surgery (P value = 0.080). CONCLUSIONS: We can confirm that fluid management based on SVV is effective, even in prone position surgery. So, SVV, that can be measured by continuous arterial pressure, can be considered a guideline for effective fluid management in spinal surgery.
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Humanos , Pressão Arterial , Pressão Venosa Central , Ecocardiografia , Hidratação , Hemodinâmica , Decúbito Ventral , Artéria Pulmonar , Volume Sistólico , Acidente Vascular Cerebral , Veia Cava InferiorRESUMO
“Precision” trials, using reasonably integrated biomarker targets and molecularly selective anticancer agents, have become a major concern for both patients and their physicians. As next-generation sequencing, which is a parallel analysis method, becomes quicker, easier, and more accurate, precision medicine-based approaches are becoming more generalized in determining treatments for cancer patients. However, it is not applicable to all cancer patients because of current high prices, limited reimbursement coverage, low prevalence of driver genetic mutations, and lack of treatable drugs. To solve these problems, the Republic of Korea has been operating the Cancer Precision Medicine Diagnosis and Treatment (K-MASTER) Enterprise since its establishment in June 2017. The aim of the project was to conduct large-scale genomic analyses, appropriate matching targeted clinical trials, and data management, which incorporates genomic and clinical information. In this review, we introduce the goals and composition of this project and describe the progress of the project to date.
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Humanos , Antineoplásicos , Diagnóstico , Sequenciamento de Nucleotídeos em Larga Escala , Métodos , Terapia de Alvo Molecular , Medicina de Precisão , Prevalência , República da CoreiaRESUMO
Iatrogenic postintubation tracheal injury is a rare but potentially fatal complication associated with anesthesia. However, as signs of tracheal injury including subcutaneous emphysema, pneumomediastinum, pneumothorax, and respiratory distress may also be related to surgical technique, diagnosis may be confused and treatment of tracheal injury can be delayed. We report a case of postintubation tracheal laceration, whose diagnosis was delayed because of symptoms were confused with subcutaneous emphysema after septorhinoplasty including osteotomy. As symptoms deteriorated in spite of conventional management, patient underwent evaluation to determine other causes and eventually postintubation tracheal injury was detected. Therefore, even if there is no problem during tracheal intubation, it is necessary to consider postintubation tracheal injury in patients with subcutaneous emphysema that worsens despite appropriate treatment after septorhinoplasty including osteotomy.
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Humanos , Anestesia , Diagnóstico Tardio , Diagnóstico , Intubação , Intubação Intratraqueal , Lacerações , Enfisema Mediastínico , Osteotomia , Pneumotórax , Enfisema SubcutâneoRESUMO
PURPOSE: Fibroblast growth factor (FGF) signals are important in carcinogenesis and progression of prostate cancer. Dovitinib is an oral, pan-class inhibitor of vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, and fibroblast growth factor receptor (FGFR). We evaluated the efficacy and toxicity of dovitinib in men with metastatic castration resistant prostate cancer (mCRPC). MATERIALS AND METHODS: This study was a single-arm, phase II, open-label, multicenter trial of dovitinib 500 mg/day (5-days-on/2-days-off schedule). The primary endpoint was 16-week progression-free survival (PFS). Secondary endpoints were overall survival (OS), toxicity and prostate-specific antigen (PSA) response rate. Biomarker analyses for VEGFR2, FGF23, and FGFR2 using multiplex enzyme-linked immunosorbent assay was performed. RESULTS: Forty-four men were accrued from 11 hospitals. Eighty percent were post-docetaxel. Median PSA was 100 ng/dL, median age was 69, 82% had bone metastases, and 23% had liver metastases. Median cycles of dovitinib was 2 (range, 0 to 33). Median PFS was 3.67 months (95% confidence interval [CI], 1.36 to 5.98) and median OS was 13.70 months (95% CI, 0 to 27.41). Chemotherapy-naïve patients had longer PFS (17.90 months; 95% CI, 9.23 to 28.57) compared with docetaxel-treated patients (2.07 months; 95% CI, 1.73 to 2.41; p=0.001) and the patients with high serum VEGFR2 level over median level (7,800 pg/mL) showed longer PFS compared with others (6.03 months [95% CI, 4.26 to 7.80] vs. 1.97 months [95% CI, 1.79 to 2.15], p=0.023). Grade 3 related adverse events were seen in 40.9% of patients. Grade 1-2 nausea, diarrhea, fatigue, anorexia, and all grade thrombocytopenia are common. CONCLUSION: Dovitinib showed modest antitumor activity with manageable toxicities in men with mCRPC. Especially, patients who were chemo-naïve benefitted from dovitinib.
