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Fexofenadine is useful in various allergic disease treatment.However,the pharmacokinetic variability information and quantitative factor identification of fexofenadine are very lacking.This study aimed to verify the validity of previously proposed genetic factors through fexofenadine population pharmaco-kinetic modeling and to explore the quantitative correlations affecting the pharmacokinetic variability.Polymorphisms of the organic-anion-transporting-polypeptide(OATP)1B1 and 2B1 have been proposed to be closely related to fexofenadine pharmacokinetic diversity.Therefore,modeling was performed using fexofenadine oral exposure data according to the OATP1B1-and 2B1-polymorphisms.OATP1B1 and 2B1 were identified as effective covariates of clearance(CL/F)and distribution volume(V/F)-CL/F,respectively,in fexofenadine pharmacokinetic variability.CL/F and average steady-state plasma con-centration of fexofenadine differed by up to 2.17-and 2.20-folds,respectively,depending on the OATP1B1 polymorphism.Among the individuals with different OATP2B1 polymorphisms,the CL/F and V/F differed by up to 1.73-and 2.00-folds,respectively.Ratio of the areas under the curves following single-and multiple-administrations,and the cumulative ratio were significantly different between OATP1B1-and 2B1-polymorphism groups.Based on quantitative prediction comparison through a model-based approach,OATP1B1 was confirmed to be relatively more important than 2B1 regarding the degree of effect on fexofenadine pharmacokinetic variability.Based on the established pharmacokinetic-pharmacodynamic relationship,the difference in fexofenadine efficacy according to genetic poly-morphisms of OATP1B1 and 2B1 was 1.25-and 0.87-times,respectively,and genetic consideration of OATP1B1 was expected to be important in the pharmacodynamics area as well.This population phar-macometrics study will be a very useful starting point for fexofenadine precision medicine.
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Objective@#To develop an evidence-based guideline for the diagnosis and treatment of antipsychotic-induced hyperprolactinemia by adapting existing high-quality clinical guidelines with a view to improve the clinical symptoms and long-term quality of life of patients by providing appropriate management. @*Methods@#This guideline was developed according to the ADAPTE methodology. The adaptation process included determining key health questions, systematically searching and screening guidelines, evaluating the quality and contents of these guidelines, deriving recommendations for key questions, and performing a peer review. The selection criteria for the guideline search were (1) evidence-based guidelines, (2) published within the last 5 years, and (3) written in English or Korean. @*Results@#After evaluating the quality and content, we finally selected three guidelines for adaptation. The final output of the development process was 25 recommendations for 10 key questions. We adopted the Agency for Health Research Quality methodology and presented the level of evidence from levels I to IV. In addition, we defined the recommendation grades from grade A (strongly recommended) to D (no recommendation) based on the level of evidence and clinical significance of the recommendation. @*Conclusion@#The development and dissemination of the adapted guideline is expected to increase the certainty of medical decision making and improve the quality of medical care. Further studies on the effectiveness and applicability of the developed guideline are necessary.
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The COVID-19 pandemic has increased demand for safe and effective vaccines. Research to develop vaccines against diseases including Middle East respiratory syndrome, Ebolavirus, human immunodeficiency virus, and various cancers would also contribute to global well-being. For successful vaccine development, the advancement of technologies such as antigen (Ag) screening, Ag delivery systems and adjuvants, and manufacturing processes is essential. Ag delivery systems are required not only to deliver a sufficient amount of Ag for vaccination, but also to enhance immune response. In addition, Ag types and their delivery systems determine the manufacturing processes of the vaccine product. Here, we analyze the characteristics of various Ag delivery systems: plasmids, viral vectors, bacterial vectors, nanoparticles, self-assembled particles, natural and artificial cells, and extracellular vesicles. This review provides insight into the current vaccine landscape and highlights promising avenues of research for the development and improvement of Ag delivery systems.
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Background@#Numerous studies have investigated risk factors for unfavorable outcomes in prosthetic breast reconstruction, such as obesity, perioperative radiotherapy, and acellular dermal matrix use. However, no reports have explored whether the use of the dominant hand influences complications in breast reconstruction. To address this gap in the literature, analyzed complication rates between the dominant and non-dominant sides after reconstruction. @*Methods@#We retrospectively reviewed the charts of 160 patients (170 breasts) who underwent breast reconstruction from February 2017 to March 2022. We analyzed the complications between beasts on the dominant and non-dominant sides according to the reconstruction method. @*Results@#During prosthetic breast reconstruction, the drainage volume and duration on the dominant side exceeded those on the non-dominant side after reconstruction (duration: 9.79 days on the dominant side vs. 9.12 days on the non-dominant side, P=0.196; volume: 771.1 mL on the dominant side vs. 654.3 mL on the non-dominant side, P=0.027). The incidence of complications such as wound dehiscence, mastectomy flap necrosis, and infection was significantly higher in the dominant hand group (infection: 6 vs. 0, P=0.014; dehiscence: 15 vs. 4, P=0.009; flap necrosis: 13 vs. 4, P=0.024). @*Conclusions@#Complications including seroma, infection, and mastectomy skin flap necrosis following prosthetic reconstruction were common in breasts on the dominant-hand side. Therefore, meticulous management and restriction of shoulder movement can aid in preventing seroma-related complications in prosthetic breast reconstruction, especially on the side of the dominant hand.
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Background@#Remifentanil can be used as adjuvants during remimazolam induction without neuromuscular blockade. We evaluated the 95% effective concentration (EC) of remifentanil effect-site concentration (Ce) for the successful insertion of an i-gel using the biased-coin up-and-down method in adult patients during remimazolam induction. @*Methods@#Forty 19–65 year-old patients scheduled to undergo surgery using i-gel were enrolled. Anesthesia was induced using remimazolam infusion (12 mg/kg/h). Simultaneously, remifentanil was infused at a predetermined Ce. After 5 min of anesthesia induction, the i-gel was inserted. The 95% EC (EC95) of remifentanil in each patient was determined using a biased-coin up-and-down method based on a successful insertion in a preceding patient. The step size of remifentanil Ce was 0.4 ng/ml. If the insertion failed, remifentanil Ce was increased in the next patient. Following successful insertions, the corresponding concentration decreased in subsequent patients with a probability of 1/19 or was maintained with a probability of 18/19. The time from remimazolam infusion initiation to a bispectral index (BIS) < 60 (time to BIS60) and hemodynamic variables were measured and recorded. @*Results@#The EC95 (95% CI) of Ce was 2.07 (1.94, 2.87) ng/ml. The overall time to BIS60 was 154.0 ± 39.9 s. No patient experienced significant hypotension or bradycardia during remimazolam induction. @*Conclusions@#The EC95 of remifentanil Ce was 2.07 (1.94, 2.87) ng/ml for successful i-gel insertion during remimazolam induction at 12 mg/kg/h without hemodynamic instability in adult patients. Future studies should measure remifentanil Ce in elderly patients or using remimazolam at various infusion doses.
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Background@#While the importance of mental health is well-recognized in the field of occupational health, implementation of effective strategies in the workplace has been limited by gaps in infrastructure, program comprehensiveness, coverage, and adherence. The authors developed a Screening, Brief Intervention, and Referral to Treatment (SBIRT) model based occupational mental health intervention, and implemented in a web-based format with a smartphone application. @*Methods@#The SBIRT-based intervention was developed by a multidisciplinary team, including occupational health physicians, nurses, psychiatrists, and software developers. The following mental health areas were included, based on outcomes of an epidemiological survey conducted: insomnia, depression, anxiety, problematic alcohol use, and suicidal risk. The viability of the two-step evaluation process utilizing a combination of the brief version and the full-length version of the questionnaire was examined using responses from the survey. The intervention was adjusted according to the survey results and expert opinions. @*Results@#The epidemiological survey included 346 employees who completed the long-form version of mental health scales. These data were the used to confirm the diagnostic value of using a combination of short-form and long-form version of the scales for screening in the SBIRT model. The model uses a smartphone application for screening, provision of psychoeducation, and for surveillance. The universal methods of the model ensure it can be implemented by all occupational managers, regardless of their specialization in mental health. In addition to the two-step screening procedure to identify employees at-risk for mental health problems, the model includes a stepped care approach, based on risk stratification, to promote mental health education, management, and follow-up for continuous care. @*Conclusion@#The SBIRT model-based intervention provides an easy-to-implement approach for the management of mental health in the workplace. Further studies are required to examine the effectiveness and feasibility of the model.
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Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.
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A 75-year-old male was diagnosed with idiopathic pulmonary fibrosis and treated with pirfenidone. He presented with an erythematous thick scaly patch on his face, neck, and both hands and arms. He had a history of significant exposure to sunlight without using sunscreen. All lesions were restricted to sun-exposed areas and appeared one month ago.Histopathological examination revealed necrotic keratinocytes, epidermal spongiosis, liquefaction degeneration of the basal layer, interface dermatitis, solar elastosis, and upper dermal perivascular lympho-histiocytic infiltration. Based on clinical and histopathological findings, the skin lesion could be diagnosed as photosensitive drug eruption induced by pirfenidone. Pirfenidone was discontinued for a month, and the patient was treated with oral and topical corticosteroids. Consequently, the skin lesion almost fully cleared, leaving mild postinflammatory hyperpigmentation. Although there are many reports of photosensitivity reactions to pirfenidone, dermatologists are still not familiar with this drug. Through this case presentation, clinicians should be aware of the potential phototoxic effects of pirfenidone and provide the necessary precautionary information to patients who take pirfenidone.
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Background@#Cesarean section under spinal anesthesia may cause anxiety and hypotension. Administration of sedative drugs after delivery can diminish these side-effects, but may increase hemodynamic instability. We evaluated the effect of the administration of 0.7 μg/kg dexmedetomidine and compared it with that of 0.03 mg/kg midazolam for usefulness of sedation of the parturient after delivery during cesarean section. @*Methods@#After obtaining written consent and the ethics board approval, 60 parturients aged 20–43 years who underwent elective cesarean delivery under spinal anesthesia were recruited. A total of 0.5% hyperbaric bupivacaine (8–10 mg) and intrathecal fentanyl (10 μg) was given to induce anesthesia. Parturients were then randomly allocated to receive either midazolam (0.03 mg/kg; group M) or dexmedetomidine 0.7 (μg/kg; group D) after delivery. The primary outcome measure was patient satisfaction score. Secondary outcomes included vital signs; vasopressor dosage; incidence of shivering, nausea, and vomiting; incidence of bradycardia; time to sensory and motor recovery; postoperative nausea and vomiting score; and postoperative pain visual analog scale at 6, 24, and 48 h. @*Results@#Satisfaction scores for sedation were similar between the two groups. The systolic blood pressure, heart rate, oximetry saturation, and tympanic temperature were comparable between the two groups. The predicted mean systolic blood pressure of group D was 106.3 mmHg and that of group M was 107.5 mmHg. Both groups showed comparable adverse intraoperative and postoperative outcomes. @*Conclusions@#Dexmedetomidine and midazolam showed similar hemodynamic effects and patient satisfaction in parturients under spinal anesthesia.
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The development of drug-resistant influenza and new pathogenic virus strains underscores the need for antiviral therapeutics. Currently, neuraminidase (NA) inhibitors are commonly used antiviral drugs approved by the US Food and Drug Administration (FDA) for the prevention and treatment of influenza. Here, we show that vitisin B (VB) inhibits NA activity and suppresses H1N1 viral replication in MDCK and A549 cells. Reactive oxygen species (ROS), which frequently occur during viral infection, increase virus replication by activating the NF-κB signaling pathway, downmodulating glucose-6-phosphate dehydrogenase (G6PD) expression, and decreasing the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) antioxidant response activity. VB decreased virus-induced ROS generation by increasing G6PD expression and Nrf2 activity, and inhibiting NF-κB translocation to the nucleus through IKK dephosphorylation. In addition, VB reduced body weight loss, increased survival, decreased viral replication and the inflammatory response in the lungs of influenza A virus (IAV)-infected mice. Taken together, our results indicate that VB is a promising therapeutic candidate against IAV infection, complements existing drug limitations targeting viral NA. It modulated the intracellular ROS by G6PD, Nrf2 antioxidant response pathway, and NF-κB signaling pathway. These results demonstrate the feasibility of a multi-targeting drug strategy, providing new approaches for drug discovery against IAV infection.
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Purpose@#Numerous studies have reported the effects of interrupting prolonged sitting with aerobic exercise on vascular and postprandial function, but the effects of resistance exercise for interrupting prolonged sitting remain unclear. We tested the hypothesis that intermittent resistance activity breaks would attenuate prolonged sittinginduced vascular and postprandial metabolic dysfunction. @*Methods@#Fourteen healthy adults (age, 24±2 years; body mass index, 22.0±2.4 kg/m2 ) completed two trials in a randomized cross-over design. During a 4-hour sitting after a high-fat meal, the participants underwent either resistance activity (RA) with 10 repetitions of five exercises every hour or uninterrupted sitting as a control trial (SIT). Plasma glucose, triglycerides, and brachial artery blood pressure, along with blood flow and shear rate in the superficial femoral artery and carotid artery were measured at baseline and every hour during the 4-hour sitting period. Brachial artery flow-mediated dilation (FMD) was measured at baseline, 2 hours, and 4 hours after the start of the sitting. @*Results@#Plasma glucose and triglycerides increased after a high-fat meal in both RA and SIT groups without a significant interaction effect. In addition, while SIT group decreased brachial artery FMD (7.2%±2.0% to 6.5%±2.7% to 5.1%±2.6%), RA did not attenuate a decrease in FMD (7.6%±3.4% to 7.3%±3.1% to 6.7%±2.7%, interaction p=0.581). @*Conclusion@#Our findings indicate that interrupting prolonged sitting with intermittent RA did not attenuate the negative effects of sitting on vascular function and postprandial metabolism in young healthy adults.
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Purpose@#Regular aerobic exercise improves exercise capacity and quality of life in children with congenital heart disease (CHD), but it remains unclear whether aerobic exercise would improve vascular function in children with CHD. We tested the hypothesis that acute bout of virtual reality (VR) exergame would improve vascular function in children with CHD. @*Methods@#In a single-arm study, eight children (age, 9±1 years; five males) with CHD participated in VR exergame (30 minutes at 40% of heart rate reserve) using a stationary cycle ergometer with a head mount display. Endothelial function and arterial stiffness as surrogate markers of vascular function were assessed via reactive hyperemia index (RHI) and augmentation index (AIx) using peripheral arterial tonometry at baseline and 30 minutes after VR exergame. @*Results@#Compared to baseline, VR exergame improved in RHI (1.08 [0.96–1.30] to 1.16 [1.09–1.36], p＜ 0.05) and natural log transformed RHI (0.07 [−0.04–0.26] to 0.15 [0.09–0.31], p＜ 0.05). However, no significant changes were observed for decrease AIx (−1.00 [−9.00–9.50] to −7.00 [−14.00–8.75], p=0.547) and AIx@75 (−6.50 [9.75–3.50] to −4.50 [−13.00–4.50], p=0.735) (all index values are reported as median [interquartile range]). @*Conclusion@#These findings suggest that a single bout of VR exergame has the potential to improve vascular endothelial function in children with CHD.
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BACKGROUND/OBJECTIVES@#Habitual coffee consumption was inversely associated with type 2 diabetes (T2D) and hyperglycemia in observational studies, but the causality of the association remains uncertain. This study tested a causal association of genetically predicted coffee consumption with T2D using the Mendelian randomization (MR) method. @*SUBJECTS/METHODS@#We used five single-nucleotide polymorphisms (SNPs) as instrumental variables (IVs) associated with habitual coffee consumption in a previous genome-wide association study among Koreans. We analyzed the associations between IVs and T2D, fasting blood glucose (FBG), 2h-postprandial glucose (2h-PG), and glycated haemoglobin (HbA1C) levels. The MR results were further evaluated by standard sensitivity tests for possible pleiotropism. @*RESULTS@#MR analysis revealed that increased genetically predicted coffee consumption was associated with a reduced prevalence of T2D; ORs per one-unit increment of logtransformed cup per day of coffee consumption ranged from 0.75 (0.62–0.90) for the weighted mode-based method to 0.79 (0.62–0.99) for Wald ratio estimator. We also used the inverse-variance-weighted method, weighted median-based method, MR-Egger method, and MR-PRESSO method. Similarly, genetically predicted coffee consumption was inversely associated with FBG and 2h-PG levels but not with HbA1c. Sensitivity measures gave similar results without evidence of pleiotropy. @*CONCLUSIONS@#A genetic predisposition to habitual coffee consumption was inversely associated with T2D prevalence and lower levels of FBG and 2h-PG profiles. Our study warrants further exploration.
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A 13-year-old neutered male Maltese dog presented to our hospital with lethargy and anorexia. Laboratory abnormalities included severe non-regenerative anemia (hematocrit, 12.9%; reticulocyte count 12.8 K/μL). The cytology of bone marrow revealed erythroid hypercellularity with mild myelofibrosis. Therefore, late-stage precursor-targeted immune-mediated anemia (PIMA) was diagnosed. Multimodal treatment including 2 immunosuppressant drugs (prednisolone and mycophenolate mofetil), antithrombic drug (clopidogrel), and blood transfusion was performed. The dog showed complete remission from PIMA, and the total duration of follow-up was 622 days. This is the first case report of canine PIMA managed successfully with prednisolone and mycophenolate mofetil in Korea.
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Objectives@# This study aimed to examine the effect of eating habits and dietary attitudes on dessert consumption among university students in Gwangju Province, South Korea. @*Methods@# A survey was conducted from May to June 2022. Out of 300 distributed questionnaires, 261 valid responses were included in the analysis. The survey assessed dessert selection, satisfaction, consumer attitudes and behaviors, as well as factors influencing satisfaction. @*Results@# Both genders reported purchasing desserts 2 to 3 times per week, primarily after lunch, due to the convenience of dessert accessibility. Males favored ice cream, bakery items, and fruits, while females preferred bakery items, ice cream, and fruits in that sequence. ‘Having fun’ was identified as the most common motivation for dessert consumption post-meal. Notable gender disparities emerged regarding perceptions of dessert consumption, including its role in stress relief, potential for nutritional imbalance, positive effects, and preferences for seasonal menus. Significant gender-based differences also manifested in intentions to purchase dessert, responsiveness to price changes, and inclination to recommend desserts to others. @*Conclusions@# This study offers foundational data on university students’ dessert purchasing behaviors, perceptions, and satisfaction levels, intending to inform strategies promoting healthier dietary habits.
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Purpose@#: Intensive care unit (ICU) diaries have been implemented across the international ICU community. This study aimed to comprehend the meaning and nature of the lived experience of patients’ families using the ICU diary in Korea. @*Methods@#: This qualitative study adopted van Manen’s hermeneutic phenomenology. The participants comprised eight women and two men who were the family members of patients in the ICU for more than three days. Data were collected using in-depth interviews and observation from July 2018 to January 2019. @*Results@#: Patients’ families who experienced the ICU diary recognized it with six beings according to time: a good idea, forgotten stuff, burdensome work, touching service, my stuff, and a thing in the memory. The ICU diary had three essential meanings for the families: communication, solace and hope, and a record of life. These findings were rearranged according to van Manen’s fundamental existential, and the lived things and lived others were remarkably confirmed. @*Conclusion@#: Patients’ families experienced various ICU diary forms over time and recognized an ICU diary as a means of communication. Therefore, the ICU diary is expected to be used as an intervention between families and healthcare providers in the ICU to support mutual communication.
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Nasotracheal intubation is commonly performed under general anesthesia in oral and maxillofacial surgery. For the convenience of surgery, nasal Ring-Adair-Elwyn (RAE) tubes are mainly used. Because the nasal RAE tubes were bent in an “L” shape, the insertion depth was limited. Particularly, it is necessary to accurately determine the appropriate depth of the RAE tubes in children. Several types of nasal RAE tubes are used in the medical market, which vary in material and length. We performed endotracheal intubation using a nasal RAE tube for double-jaw surgery, but air leakage persisted even when the air pressure in the cuff was increased. When checked with a laryngoscope, it was confirmed that the tube was pushed out, and the cuff was caught on the vocal cords, causing air leakage. Since inserting the tube deeply did not solve the problem, replacing it with a nasal RAE tube (Polar TM , Preformed Tracheal Tube, Smith Medical, Inc., USA) did not cause air leakage; thus, we reported this case.
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The objective of this study was to compare recommendations of the Korean Medication Algorithm Project for Bipolar Disorder 2022 (KMAP-BP 2022) with other recently published guidelines for treating bipolar disorder. We reviewed a total of six recently published global treatment guidelines and compared treatment recommendation of the KMAP-BP 2022 with those of other guidelines. For initial treatment of mania, there were no significant differences across treatment guidelines. All guidelines recommended mood stabilizer (MS) or atypical antipsychotic (AAP) monotherapy or a combination of an MS with an AAP as a first-line treatment strategy in a same degree for mania. However, the KMAP-BP 2022 recommended MS + AAP combination therapy for psychotic mania, mixed mania and psychotic depression as treatment of choice. Aripiprazole, quetiapine and olanzapine were the first-line AAPs for nearly all phases of bipolar disorder across guidelines. Some guideline suggested olanzapine is a second-line options during maintenance treatment, related to concern about long-term tolerability. Most guidelines advocated newer AAPs (asenapine, cariprazine, long-acting injectable risperidone, and aripiprazole once monthly) as first-line treatment options for all phases while lamotrigine was recommended for depressive and maintenance phases. Lithium and valproic acid were commonly used as MSs in all phases of bipolar disorder. KMAP-BP 2022 guidelines were similar to other guidelines, reflecting current changes in prescription patterns for bipolar disorder based on accumulated research data. Strong preference for combination therapy was characteristic of KMAP-BP 2022, predominantly in the treatment of psychotic mania, mixed mania and psychotic depression.
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While the guidelines for adjuvant chemotherapy (AC) for colon cancer are relatively standardized, those for early rectal cancer are still lacking. We therefore evaluated the role of AC in clinical stage II rectal cancer treatment after preoperative chemoradiotherapy (CRT). Patients diagnosed with early rectal cancer (defined by clinical stage T3/4, N0) who completed CRT followed by surgery were enrolled in this retrospective study. To evaluate the role of AC, we analyzed the risk of recurrence and survival based on clinicopathologic parameters and adjuvant chemotherapy. Of the 112 patients, 11 patients (9.8%) experienced recurrence and five patients (4.8%) died. In a multivariate analysis, circumferential resection margin involvement (CRM+) on magnetic resonance imaging at diagnosis, CRM involvement following neoadjuvant therapy (ypCRM+), tumor regression grade (≤G1) and no-AC were considered poor prognostic factors for recurrence free survival (RFS). In addition, ypCRM+ and no-AC were associated with poor overall survival (OS) in the multivariate analysis. AC including 5-FU monotherapy demonstrated the benefits of reduced recurrence and prolonged survival in clinical stage II rectal cancer, even in pathologic stage following neoadjuvant therapy (ypStage) 0-I. Further prospective studies are needed to verify the benefit of each regimen of AC and the development of a method that can accurately predict CRM status before surgery, and a vigorous treatment that can induce CRM non-involvement (CRM−) should be considered even in early stages of rectal cancer.
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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.