Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.

BACKGROUND/AIMS: Severe fever with thrombocytopenia syndrome (SFTS) is a viral hemorrhagic fever with a high fatality rate. However, effective treatments for SFTS cases not responded to supportive therapy have not been established. Herein, we introduced the therapeutic plasma exchange (TPE) in SFTS patients in a tertiary hospital between 2013 and 2015. METHODS: TPE was performed in patients with rapidly progressing SFTS. Clinical, laboratory, and virological parameters were compared before and after TPE. RESULTS: Among 27 confirmed SFTS patients, two patients were treated with TPE and ribavirin combination in May 2013, then, 14 patients with rapidly progressing SFTS patients were treated with only TPE from June 2013 to September 2015: their median age was 58 years (interquartile range, 50 to 70) and eight (57.1%) were male. Body temperature, pressure-adjusted heart rate, white blood cell and platelet counts, coagulation profile, serum creatinine, and multiple organ dysfunction score improved immediately after TPE. In addition, the mean cyclic threshold value of real-time reverse transcriptase polymerase chain reaction for SFTS virus after TPE (mean ± standard deviation, 31.3 ± 2.9) was significantly higher than that before TPE (26.5 ± 2.9; p < 0.001), indicating that serum viral loads decreased after TPE. Finally, 13 of 14 TPE-treated patients (92.8%) recovered from rapidly progressing SFTS without sequelae. CONCLUSIONS SFTS patients treated with TPE showed improvements in clinical, laboratory, and virological parameters. These results suggest that TPE would be a therapeutic modality as rescue therapy in patients with rapidly progressing SFTS.

Despite a high mortality rate, no specific treatment for severe fever with thrombocytopenia syndrome (SFTS) has been established. This study compared the clinical outcomes of SFTS patients treated with plasma exchange (PE group) with those who were not treated (non-PE group) at nine Korean hospitals between May 2013 and August 2015. A total of 53 SFTS patients were included: 24 (45.3%) PE cases and 29 (54.7%) non-PE cases. The overall in-hospital mortality rate was 32.1% (17/53). The in-hospital mortality rate of the PE group did not differ from that of the non-PE group (29.3% vs. 34.5%, p=0.680). Of the 24 PE cases, 16 (66.7%) were treated with PE within 7 days of symptom onset (early PE group). The early PE group survived longer than the non-PE group (mean 28.4 days vs. 22.6 days, p=0.044). Multivariate analysis showed an inverse association between early PE implementation and 30-day mortality (adjusted hazard ratio 0.052, 95% confidence interval 0.004–0.678, p=0.024). The results of this study suggest that early PE implementation may have a beneficial effect on the clinical outcome of SFTS patients.
Fever* ; Hospital Mortality ; Humans ; Mortality ; Multivariate Analysis ; Phlebovirus ; Plasma Exchange* ; Plasma* ; Thrombocytopenia*

The authors conducted a survey on essential humanistic competency that medical students should have, and on teaching methods that will effectively develop such attributes. The participants consisted of 154 medical school professors, 589 medical students at Seoul National University College of Medicine, 228 parents, and 161 medical school and university hospital staff. They answered nine questions that the authors created. According to the results, all groups chose "morality and a sense of ethics," a "sense of accountability," "communication skills," and "empathic ability" were selected as essential qualities. According to the evaluation on the extent to which students possess each quality, participants believed students had a high "sense of accountability" and "morality," whereas they thought students had low "empathic ability," "communicate," or "collaborate with others". In terms of effective teaching methods, all sub-groups preferred extracurricular activities including small group activities, debates, and volunteer services. With regard to the speculated effect of humanism education and the awareness of the need for colleges to offer it, all sub-groups had a positive response. However the professors and students expressed a relatively passive stance on introducing humanism education as a credited course. Most participants responded that they preferred a grading method based on their rate of participation, not a relative evaluation. In order to reap more comprehensive and lasting effects of humanism education courses in medical school, it is necessary to conduct faculty training, and continuously strive to develop new teaching methods.
Adult ; Curriculum ; Female ; Health Personnel/*psychology ; *Humanism ; Humans ; Male ; Middle Aged ; Parents/psychology ; Students, Medical/*psychology ; Surveys and Questionnaires ; Young Adult

Inflammation has recently been implicated in cancer formation and progression. As tissue transglutaminase (TG2) has been associated with both inflammatory signaling and tumor cell behavior, we propose that TG2 may be an important link inducing interleukin-6 (IL-6)-mediated cancer cell aggressiveness, including cancer stem cell-like characteristics and distant hematogenous metastasis. We evaluated the effect of differential TG2 and IL-6 expression on in vivo distant metastasis of human ovarian cancer cells. IL-6 production in human ovarian cancer cells was dependent on their TG2 expression levels. The size and efficiency of tumor sphere formation were correlated with TG2 expression levels and were dependent on TG2-mediated IL-6 secretion in human ovarian cancer cells. Primary tumor growth and propagation in the peritoneum and distant hematogenous metastasis into the liver and lung were also dependent on TG2 and downstream IL-6 expression levels in human ovarian cancer cells. In this report, we provide evidence that TG2 is an important link in IL-6-mediated tumor cell aggressiveness, and that TG2 and downstream IL-6 could be important mediators of distant hematogenous metastasis of human ovarian cancer cells. Intervention specific to TG2 and/or downstream IL-6 in ovarian cancer cells could provide a promising means to control tumor metastasis.
Axis, Cervical Vertebra* ; Humans* ; Inflammation ; Interleukin-6 ; Liver ; Lung ; Neoplasm Metastasis* ; Ovarian Neoplasms* ; Peritoneum

Middle East Respiratory Syndrome (MERS) is an acute viral respiratory illness with high mortality caused by a new strain of betacoronavirus (MERS-CoV). Since the report of the first patient in Saudi Arabia in 2012, large-scale outbreaks through hospital-acquired infection and inter-hospital transmission have been reported. Most of the patients reported in South Korea were also infected in hospital settings. Therefore, to eliminate the spread of MERS-CoV, infection prevention and control measures should be implemented with rigor. The present guideline has been drafted on the basis of the experiences of infection control in the South Korean hospitals involved in the recent MERS outbreak and on domestic and international infection prevention and control guidelines. To ensure efficient MERS-CoV infection prevention and control, care should be taken to provide comprehensive infection control measures including contact control, hand hygiene, personal protective equipment, disinfection, and environmental cleaning.
Delivery of Health Care* ; Disease Outbreaks ; Disinfection ; Hand Hygiene ; Humans ; Infection Control* ; Korea ; Middle East* ; Mortality ; Quarantine ; Saudi Arabia

Hypochondroplasia (HCH) is an autosomal dominant inherited skeletal dysplasia, usually caused by a heterozygous mutation in the fibroblast growth factor receptor 3 gene (FGFR3). A 27-year-old HCH woman with a history of two consecutive abortions of HCH-affected fetuses visited our clinic for preimplantation genetic diagnosis (PGD). We confirmed the mutation in the proband (FGFR3:c.1620C>A, p.N540K), and established a nested allele-specific PCR and sequence analysis for PGD using single lymphocyte cells. We performed this molecular genetic analysis to detect the presence of mutation among 20 blastomeres from 18 different embryos, and selected 9 embryos with the wild-type sequence (FGFR3:c.1620C). A successful pregnancy was achieved through a frozen-thawed cycle and resulted in the full-term birth of a normal neonate. To the best of our knowledge, this is the first report of a successful pregnancy and birth using single-cell allele-specific PCR and sequencing for PGD in an HCH patient.
Blastomeres ; Bone and Bones ; Dwarfism ; Embryonic Structures ; Female ; Fetus ; Humans ; Infant, Newborn ; Limb Deformities, Congenital ; Lordosis ; Lymphocytes ; Molecular Biology ; Parturition ; Polymerase Chain Reaction ; Pregnancy ; Preimplantation Diagnosis ; Prostaglandins D ; Receptor, Fibroblast Growth Factor, Type 3 ; Sequence Analysis

OBJECTIVES: Dysregulation of the central noradrenergic system may be involved in the pathophysiology of attention-deficit hyperactivity disorder (ADHD). The aim of this study was to examine the differences in pre- and post-treatment cerebral perfusion according to the MspI polymorphisms of the alpha-2A-adrenergic receptor gene (ADRA2A) in children with ADHD. METHODS: Thirty seven drug-naive ADHD children (8.9+1.8 years old, M=32, F=5) were genotyped. Baseline single-photon emission computed tomography (SPECT) and clinical assessments were performed for ADHD children. After treatment with methylphenidate for eight weeks, SPECT and clinical assessment were repeated. RESULTS: No differences in baseline clinical assessments or cerebral perfusion were observed according to the MspI genotype. However, after treatment, ADHD children with the G/G genotype at the MspI polymorphism showed hyperperfusion in the right cerebellar declive (p=.001, uncorrected) and hypoperfusion in the left lentiform nucleus and left cingulate gyrus (p<.001 and p=.001, uncorrected), compared to children without the G/G genotype. CONCLUSION: Although the results of this study should be interpreted cautiously, they suggest a possible role of the MspI polymorphisms of the ADRA2A gene in methylphenidate-induced changes in cerebral perfusion.
Brain ; Child ; Corpus Striatum ; Genotype ; Gyrus Cinguli ; Humans ; Methylphenidate ; Perfusion ; Pharmacogenetics ; Receptors, Adrenergic, alpha-2 ; Tomography, Emission-Computed ; Tomography, Emission-Computed, Single-Photon

BACKGROUND: Staphylococcus aureus is a major bacteremia-causing pathogen in hemodialysis patients, frequently colonizing patient skin and mucosa. Active infection control is necessary to prevent methicillin-resistant S. aureus (MRSA) infection in hospitals; however, the spread of community-associated MRSA has recently become a concern for MRSA infection control. We evaluated the nasal colonization of MRSA among hemodialysis patients and the molecular characterization of the MRSA isolates. METHODS: Nasal swabs were obtained from 482 hemodialysis patients in 7 nationwide hospitals in November 2009, and cultured for MRSA colonization. Swabs were inoculated and cultured in 6.5% NaCl tryptic soy broth, then subcultured on MRSASelect medium (Bio-Rad, Hercules, CA) for 20-24 h. Multiplex PCR was performed to analyze staphylococcal cassette chromosome mec (SCCmec) types of MRSA isolates. RESULTS: Of 482 hemodialysis patients, 57 (11.8%) carried MRSA, ranging from 6.7% to 19.0%. Among the 57 MRSA isolates, we identified 3 (5.3%) SCCmec II, 1 (1.8%) SCCmec IIA, 30 (52.6%) SCCmec IIB, 1 (1.8%) SCCmec III, 6 (10.5%) SCCmec IV, and 16 (28.1%) SCCmec IVA subtypes. CONCLUSION: The MRSA carriage rate (11.8%) of hemodialysis patients in this study was high. The SCCmec IIB subtype, a healthcare-associated strain, was the predominant strain, although SCCmec IV isolates, typically found in community-associated MRSA infections, were also frequently observed. To prevent healthcare-associated MRSA infections in hemodialysis patients, standardized infection control measures should be performed, and efforts to reduce MRSA carriage rates should be considered.
Colon* ; Humans ; Infection Control ; Methicillin Resistance* ; Methicillin-Resistant Staphylococcus aureus* ; Mucous Membrane ; Multiplex Polymerase Chain Reaction ; Renal Dialysis* ; Skin ; Staphylococcus aureus