Rivaroxaban, a factor Xa inhibitor, is one of the newly developed direct oral anticoagulants (DOAC). In recent times, it has been increasingly used in the prevention of pulmonary embolism in patients undergoing orthopedic surgery. This report describes a case of epidural hematoma in an elderly patient who underwent combined spinal epidural anesthesia for total knee arthroplasty; the patient received rivaroxaban postoperatively for 7 days to prevent pulmonary embolism. Additionally, the epidural hematomas developed on the 5th postoperative day but the patient recovered well with conservative treatment. Although rivaroxaban has a low need for monitoring and is easily administered, the guidelines should be carefully checked for the postoperative administration schedule in patients undergoing regional anesthesia. In addition, rivaroxaban should be used with caution, especially in elderly patients.
Aged ; Anesthesia, Conduction ; Anesthesia, Epidural ; Anticoagulants ; Appointments and Schedules ; Arthroplasty, Replacement, Knee* ; Factor Xa ; Hematoma* ; Hematoma, Epidural, Spinal ; Humans ; Orthopedics ; Pulmonary Embolism ; Rivaroxaban*

PURPOSE: Head and neck squamous cell carcinoma (HNSCC) is a deadly disease in which precision medicine needs to be incorporated. We aimed to implement next-generation sequencing (NGS) in determining actionable targets to guide appropriate molecular targeted therapy in HNSCC patients. MATERIALS AND METHODS: Ninety-three tumors and matched blood samples underwent targeted sequencing of 244 genes using the Illumina HiSeq 2500 platform with an average depth of coverage of greater than 1,000×. Clinicopathological data from patients were obtained from 17 centers in Korea, and were analyzed in correlation with NGS data. RESULTS: Ninety-two of the 93 tumors were amenable to data analysis. TP53 was the most common mutation, occurring in 47 (51%) patients, followed by CDKN2A (n=23, 25%), CCND1 (n=22, 24%), and PIK3CA (n=19, 21%). The total mutational burden was similar between human papillomavirus (HPV)–negative vs. positive tumors, although TP53, CDKN2A and CCND1 gene alterations occurred more frequently in HPV-negative tumors. HPV-positive tumors were significantly associated with immune signature-related genes compared to HPV-negative tumors. Mutations of NOTCH1 (p=0.027), CDKN2A (p < 0.001), and TP53 (p=0.038) were significantly associated with poorer overall survival. FAT1 mutations were highly enriched in cisplatin responders, and potentially targetable alterations such as PIK3CA E545K and CDKN2A R58X were noted in 14 patients (15%). CONCLUSION: We found several targetable genetic alterations, and our findings suggest that implementation of precision medicine in HNSCC is feasible. The predictive value of each targetable alteration should be assessed in a future umbrella trial using matched molecular targeted agents.
Biomarkers ; Carcinoma, Squamous Cell* ; Cisplatin ; Epithelial Cells* ; Head* ; Humans ; Korea ; Molecular Targeted Therapy ; Neck* ; Precision Medicine ; Statistics as Topic

PURPOSE: With the emergence of next-generation sequencing (NGS) technology, profiling a wide range of genomic alterations has become a possibility resulting in improved implementation of targeted cancer therapy. In Asian populations, the prevalence and spectrum of clinically actionable genetic alterations has not yet been determined because of a lack of studies examining high-throughput cancer genomic data. MATERIALS AND METHODS: To address this issue, 1,071 tumor samples were collected from five major cancer institutes in Korea and analyzed using targeted NGS at a centralized laboratory. Samples were either fresh frozen or formalin-fixed, paraffin embedded (FFPE) and the quality and yield of extracted genomic DNA was assessed. In order to estimate the effect of sample condition on the quality of sequencing results, tissue preparation method, specimen type (resected or biopsied) and tissue storage time were compared. RESULTS: We detected 7,360 non-synonymous point mutations, 1,164 small insertions and deletions, 3,173 copy number alterations, and 462 structural variants. Fifty-four percent of tumors had one or more clinically relevant genetic mutation. The distribution of actionable variants was variable among different genes. Fresh frozen tissues, surgically resected specimens, and recently obtained specimens generated superior sequencing results over FFPE tissues, biopsied specimens, and tissues with long storage duration. CONCLUSION: In order to overcome, challenges involved in bringing NGS testing into routine clinical use, a centralized laboratory model was designed that could improve the NGS workflows, provide appropriate turnaround times and control costs with goal of enabling precision medicine.
Academies and Institutes ; Asian Continental Ancestry Group ; DNA ; Humans ; Korea ; Methods ; Paraffin ; Point Mutation ; Precision Medicine ; Prevalence

BACKGROUND/AIMS: There are only a few reports on the direct costs of severe cutaneous adverse reactions (SCARs), including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), despite the tremendous negative impact these reactions can have on patients. We estimated the direct costs of treating SCARs. METHODS: Patients admitted to a tertiary teaching hospital for the treatment of SCARs from January 1, 2005 to December 31, 2010 were included. Patients who had experienced SCARs during their admission for other medical conditions were excluded. The direct costs of hospitalization and outpatient department visits were collected. Inpatient and outpatient care costs were calculated, and factors affecting inpatient care costs were analyzed. RESULTS: The total healthcare cost for the management of 73 SCAR patients (36 with DRESS, 21 with SJS, and 16 with TEN) was 752,067 US dollars (USD). Most of the costs were spent on inpatient care (703,832 USD). The median inpatient care cost per person was 3,720 (range, 1,133 to 107,490) USD for DRESS, 4,457 (range, 1,224 to 21,428) USD for SJS, and 8,061 (range, 1,127 to 52,220) USD for TEN. Longer hospitalization significantly increased the inpatient care costs of the patients with DRESS (by 428 USD [range, 395 to 461] per day). Longer hospitalization and death significantly increased the inpatient care costs of the patients with SJS/TEN (179 USD [range, 148 to 210] per day and an additional 14,425 USD [range, 9,513 to 19,337] for the deceased). CONCLUSIONS: The management of SCARs required considerable direct medical costs. SCARs are not only a health problem but also a significant financial burden for the affected individuals.
Ambulatory Care ; Cicatrix ; Drug Hypersensitivity Syndrome ; Health Care Costs ; Hospitalization ; Hospitals, Teaching ; Humans ; Inpatients ; Korea* ; Outpatients ; Stevens-Johnson Syndrome ; Tertiary Care Centers*

PURPOSE: Although mild to moderate asthma is much more common, the morbidity and mortality of severe asthma are much higher. This study was performed to identify and analyze the clinical characteristics of severe asthma in Korea. METHODS: We registered patients with severe refractory asthma into the Severe Asthma Registry supported by the Severe Asthma Work Group of the Korean Academy of Asthma, Allergy and Clinical Immunology. Patients were enrolled since 2010 from the 15 university hospitals nationwide in Korea. Severe asthma was defined according to modified European Respiratory Society/American Thoracic Society criteria. Information on demographics, medical history, pulmonary function tests and skin prick tests was collected; the clinical characteristics of severe asthmatics were analyzed from the collected data. RESULTS: A total of 489 patients were enrolled with a mean age of 62.3; 45% are male. Sixty percent of patients received Global Initiative for Asthma step 4 treatment, and 30% received step 5 treatment. The most common comorbidities were allergic rhinitis (58.7%). Aspirin hypersensitivity was observed in 14.0%. Approximately half (53.9%) are non-smokers. Atopy was proven in 38.5% of the patients. Regarding asthma medications, inhaled corticosteroids and long-acting β-agonist combination inhalers were most commonly prescribed (96.5%), followed by leukotriene antagonists (71.0%). A recombinant anti-immunoglobulin E monoclonal antibody (omalizumab) has been used in 1.8% of the patients. The mean forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1) and FEV1/FVC were 78.7%, 67.5% and 67.9% of predicted values, respectively. The mean Asthma Control Test and quality of life questionnaire scores were 16.5 out of 25 and 59.5 out of 85, respectively. CONCLUSIONS: The baseline characteristics of severe asthma patients in the Korea Severe Asthma Registry were analyzed and reported for the first time. With this cohort, further prospective studies should be performed to search for ways to improve management of severe refractory asthma.
Adrenal Cortex Hormones ; Adult* ; Allergy and Immunology ; Aspirin ; Asthma* ; Cohort Studies ; Comorbidity ; Demography ; Forced Expiratory Volume ; Hospitals, University ; Humans ; Hypersensitivity ; Korea* ; Leukotriene Antagonists ; Male ; Mortality ; Nebulizers and Vaporizers ; Prospective Studies ; Quality of Life ; Respiratory Function Tests ; Rhinitis, Allergic ; Skin ; Vital Capacity

BACKGROUND: The standard morphological evaluation has been widely used for embryo selection, but it has limitations. This study aimed to investigate the correlation between morphologic grading and euploidy rate of in vitro fertilization (IVF) preimplantation genetic screening (PGS) and compare the pregnancy rates in young and old ages. METHODS: This is a retrospective study using the medical records of patients who underwent IVF procedures with PGS between January 2016 and February 2017 in a single center. The embryo grades were categorized into 4 groups: excellent, good, fair, and poor. Basic characteristics, euploidy rates, clinical pregnancy (CP) rates and ongoing pregnancy rates were analyzed. RESULTS: The excellent group had significantly higher rate of euploid embryos than fair group (47.82% vs. 29.33%; P = 0.023) and poor group (47.82% vs. 29.60%; P = 0.005). When the four groups were recategorized into two groups (excellent and good vs. fair and poor), they also showed significant difference in euploidy rates (44.52% vs. 29.53%; P = 0.002). When the patients were divided into two groups by age 35, the CP rates for those under and over 35 years old were 44.74% and 47.83%, respectively, which showed no significant difference. CONCLUSION: The significant differences among the euploidy rates of different morphologic embryo grades demonstrated the positive correlations between the morphologic grading of the embryo and the euploidy rate of PGS. Additionally, there was no significant difference between the younger and older patients' CP rates. These findings emphasize the fact that old age patients might benefit from PGS whatever the indication of PGS is.
Blastocyst* ; Embryonic Structures ; Fertilization in Vitro* ; Genetic Testing* ; Humans ; In Vitro Techniques* ; Medical Records ; Pregnancy ; Pregnancy Rate ; Retrospective Studies

PURPOSE: We conducted a randomized, multicenter, phase III trial to compare S-1 plus docetaxel (DS) with S-1 plus cisplatin (SP) as adjuvant chemotherapy for stage III gastric cancer patients. MATERIALS AND METHODS: Stage III gastric cancer patients who had received curative gastrectomy with D2 lymphadenectomy were randomized into equal groups to receive adjuvant chemotherapy of eight cycles of DS (S-1 70 mg/m2/day on days 1-14 plus docetaxel 35 mg/m2on days 1 and 8) every 3 weeks or SP (S-1 70 mg/m2/day on days 1-14 plus cisplatin 60 mg/m2on day 1) every 3 weeks. The primary endpoint was 3-year disease-free survival (DFS) rate. RESULTS: Between November 2010 and July 2013, 153 patients (75 patients to DS and 78 patients to SP) were enrolled from 8 institutions in Korea. After the capecitabine plus oxaliplatin was approved based on the CLASSIC study, itwas decided to close the study early. With a median follow-up duration of 56.9 months, the 3-year DFS rate between two groups was not significantly different (49.14% in DS group vs. 52.5% in SP group). The most common grade 3-4 adverse event was neutropenia (42.7% in DS and 38.5% in SP, p=0.351). SP group had more grade 3-4 anemia (1.3% vs. 11.5%, p=0.037), whereas grade 3-4 hand-foot syndrome (4.1% vs. 0%, p=0.025) and mucositis (10.7% vs. 2.6%, p=0.001) were more common in DS group. Fifty-one patients (68%) in DS group and 52 (66.7%) in SP group finished planned treatment. CONCLUSION: Our findings suggest that SP or DS is an effective and tolerable option for patients with curatively resected stage III gastric cancer.
Anemia ; Capecitabine ; Chemotherapy, Adjuvant* ; Cisplatin ; Disease-Free Survival ; Follow-Up Studies ; Gastrectomy ; Hand-Foot Syndrome ; Humans ; Korea ; Lymph Node Excision ; Mucositis ; Neutropenia ; Stomach Neoplasms*

PURPOSE: To evaluate the influence of axial length on the recurrence of wet age-related macular degeneration (AMD) after anti-vascular endothelial growth factor therapy. METHODS: A retrospective review of the medical records for 45 eyes of 45 patients, who were diagnosed with neovascular AMD and treated with three ranibizumab injections per month, was performed. Axial length was compared between eyes with (recurrence group) and without (no recurrence group) recurrence of fluid during a 12-month follow-up period. In eyes with recurrence, the association between axial length and the time between the third injection and the first recurrence was also evaluated. RESULTS: The axial length was measured at a mean of 20.6 ± 10.1 months after the diagnosis of neovascular AMD. The mean axial length at that time was 23.33 ± 0.90 mm. The mean axial length was 23.29 ± 0.96 mm in the recurrence group (n = 30) and 23.40 ± 0.79 mm in the no-recurrence group (n = 15). There was no difference in the axial length between the two groups (p = 0.709). In the recurrence group, the period between the third injection and the first recurrence was not associated with axial length (p =0.582). CONCLUSIONS: There was no significant difference in axial length between eyes with and without recurrence after initial treatment for wet AMD. In addition, the time to first recurrence was not significantly associated with axial length. Because the present study was retrospective and the sample size was small, further prospective studies with a better design are needed to more accurately assess the influence of axial length.
Choroidal Neovascularization ; Diagnosis ; Endothelial Growth Factors ; Follow-Up Studies ; Humans ; Macular Degeneration ; Medical Records ; Prospective Studies ; Ranibizumab ; Recurrence ; Retrospective Studies ; Sample Size

BACKGROUND AND OBJECTIVES: Aortic valve replacement (AVR) is the treatment of choice in severe symptomatic aortic stenosis (AS) patients. However, a substantial number of elderly patients refuse AVR and treated medically. We investigated their long-term prognosis. METHODS: From January 2005 to December 2016, we analyzed elderly patients with severe symptomatic AS who refused to have AVR. RESULTS: After screening of total 534 patients, we analyzed total 180 severe symptomatic AS patients (78±7 years old, 96 males). Hypertension was the most common cardiovascular risk factor (72%) and the most common symptom was dyspnea (66%). Calculated aortic stenosis area was 0.73±0.20 cm2 and mean left ventricular ejection fraction (LVEF) was 57.8±12.2%. Total 102 patients died during follow-up period (39.1±31.0 months). One-, 3-, and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Of them, 87 died from cardiac causes, and 1-, 3-, and 5-year cardiac mortality rate was 18.0±2.9%, 38.2±3.8%, and 50.7±4.3%, respectively. Their all-cause mortality and cardiac mortality were significantly higher than those of controls. Univariate analysis showed that age, anemia, LVEF, and Log N-terminal pro B-type natriuretic peptide (NT-proBNP) were significant parameters in all-cause mortality (p < 0.001, p=0.001, p=0.039, and p=0.047, respectively) and in cardiac mortality (p < 0.001, p < 0.001, p=0.046, and p=0.026, respectively). Multivariate analysis showed that age and anemia were significant prognostic factors for cardiac and all-cause mortality. CONCLUSIONS: In elderly severe symptomatic AS patients who treated medically, their 1-, 3- and 5-year all-cause mortality rate was 21.1±3.0%, 43.1±3.8%, and 56.5±4.2%, respectively. Age and anemia were significant prognostic factors for cardiac and all-cause mortality.
Aged ; Anemia ; Aortic Valve Stenosis ; Aortic Valve ; Drug Therapy ; Dyspnea ; Follow-Up Studies ; Humans ; Hypertension ; Mass Screening ; Mortality ; Multivariate Analysis ; Natriuretic Peptide, Brain ; Prognosis ; Risk Factors ; Stroke Volume

A 78-year-old male cadaver showed bilateral anomalous muscles on the dorsum of the hand. An extensor digitorum brevis manus was noted on the dorsum of the right hand. It originated from the distal end of the radius and the radiocarpal joint ligaments and inserted into the metacarpophalangeal joint of the third digit. On the dorsum of the left hand, an extensor digiti medii proprius was identified. It originated from the distal third of the ulna near the extensor indicis proprius and the interosseous membrane and inserted into the metacarpophalangeal joint of the third digit. Awareness of these combined muscular variation would be helpful in understanding the identification of digital extensors and in requiring careful consideration for the reconstruction surgery of the hand.
Aged ; Cadaver ; Forearm ; Hand ; Humans ; Joints ; Ligaments ; Male ; Membranes ; Metacarpophalangeal Joint ; Muscles ; Radius ; Ulna