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.

Objective: : Hemorrhagic transformation (HT) can be occurred after acute cerebral infarction. HT can worse symptoms in severe cases and adversely affect long-term prognosis. As bone and vascular smooth muscle are composed of type 1 collagen, we aimed to identify a potential relationship between bone mineral density (BMD) and HT after acute cardioembolic stroke. Methods: : As an indicator of BMD, we used mean frontal skull Hounsfield unit (HU) values on brain computed tomography (CT). Multivariative hazard ratios were calculated using Cox regression analysis to identify whether the osteoporotic condition was an independent predictor of HT after acute cardioembolic stroke. Results: : This 11-year analysis enrolled 506 patients who diagnosed as acute cardioembolic infarction. The first tertile of skull HU value was an independent predictor of HT development compared to the third tertile (hazard ratio, 2.12; 95% confidence interval, 1.13–3.98; p=0.020). We observed no interactions between age and skull HU with respect to HT statistically. Conclusion : The results of this study revealed an association between osteoporotic conditions and HT development after acute cardioembolic stroke. A convenient method to measure the cancellous bone HU value of the frontal skull using brain CT images may be useful for predicting HT in patients with acute cerebral infarction.

Background: Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. Methods: The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). Results: The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. Conclusion This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.

Objective: : Hemorrhagic transformation (HT) can be occurred after acute cerebral infarction. HT can worse symptoms in severe cases and adversely affect long-term prognosis. As bone and vascular smooth muscle are composed of type 1 collagen, we aimed to identify a potential relationship between bone mineral density (BMD) and HT after acute cardioembolic stroke. Methods: : As an indicator of BMD, we used mean frontal skull Hounsfield unit (HU) values on brain computed tomography (CT). Multivariative hazard ratios were calculated using Cox regression analysis to identify whether the osteoporotic condition was an independent predictor of HT after acute cardioembolic stroke. Results: : This 11-year analysis enrolled 506 patients who diagnosed as acute cardioembolic infarction. The first tertile of skull HU value was an independent predictor of HT development compared to the third tertile (hazard ratio, 2.12; 95% confidence interval, 1.13–3.98; p=0.020). We observed no interactions between age and skull HU with respect to HT statistically. Conclusion : The results of this study revealed an association between osteoporotic conditions and HT development after acute cardioembolic stroke. A convenient method to measure the cancellous bone HU value of the frontal skull using brain CT images may be useful for predicting HT in patients with acute cerebral infarction.

Purpose: Allogeneic hematopoietic stem cell transplantation (HSCT) with optimal conditioning has helped better long-term survival in acute lymphoblastic leukemia (ALL). This study investigated the efficacy and safety of reduced-intensity conditioning (RIC) with busulfan and fludarabine in adult ALL patients unfit for myeloablation. Materials and Methods: Records of 78 patients who underwent HSCT with RIC consisting of 3.2 mg/kg/day of busulfan for 2 or 3 days and 30 mg/m2/day of fludarabine for 5 or 6 days were analyzed. Results: The median age at diagnosis was 49 years. Over a median follow-up of 22 months, 2-year estimates of relapse-free survival (RFS) and overall survival were 57.4% and 68.7%, respectively. Multivariate analysis showed a trend of improved RFS in patients with chronic graft-versus-host disease (GVHD) (hazard ratio, 0.53; 95% confidence interval, 0.26–1.08; p=0.080). The cumulative incidences of relapse and non-relapse mortality were 42.9% and 19.6%, respectively and one case of central nervous system relapse was noted. No hepatic veno-occlusive disease was reported. Grade II–IV acute GVHD and any grade chronic GVHD occurred in 21.1% and 41.7%, respectively. Conclusion RIC with busulfan and fludarabine is an effective and safe conditioning regimen for adult ALL patients unfit for myeloablation.

“Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” is the 3rd edition of clinical practice guideline (CPG) for stroke rehabilitation in Korea, which updates the 2nd edition published in 2014. Forty-two specialists in stroke rehabilitation from 21 universities and 4 rehabilitation hospitals and 4 consultants participated in this update. The purpose of this CPG is to provide optimum practical guidelines for stroke rehabilitation teams to make a decision when they manage stroke patients and ultimately, to help stroke patients obtain maximal functional recovery and return to the society. The recent two CPGs from Canada (2015) and USA (2016) and articles that were published following the 2nd edition were used to develop this 3rd edition of CPG for stroke rehabilitation in Korea. The chosen articles' level of evidence and grade of recommendation were decided by the criteria of Scotland (2010) and the formal consensus was derived by the nominal group technique. The levels of evidence range from 1++ to 4 and the grades of recommendation range from A to D. Good Practice Point was recommended as best practice based on the clinical experience of the guideline developmental group. The draft of the developed CPG was reviewed by the experts group in the public hearings and then revised. “Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” consists of ‘Chapter 1; Introduction of Stroke Rehabilitation’, ‘Chapter 2; Rehabilitation for Stroke Syndrome, ‘Chapter 3; Rehabilitation for Returning to the Society’, and ‘Chapter 4; Advanced Technique for Stroke Rehabilitation’. “Clinical Practice Guideline for Stroke Rehabilitation in Korea 2016” will provide direction and standardization for acute, subacute and chronic stroke rehabilitation in Korea.
Canada ; Consensus ; Consultants ; Humans ; Korea* ; Practice Guidelines as Topic ; Rehabilitation* ; Scotland ; Specialization ; Stroke*

OBJECTIVE: The timing of cranioplasty and method of bone flap storage are known risk factors of non-union and resorption of bone flaps. In this animal experimental study, we evaluated the efficacy of cranioplasty using frozen autologous bone flap, and examined whether the timing of cranioplasty after craniectomy affects bone fusion and new bone formation. METHODS: Total 8 rabbits (male, older than 16 weeks) were divided into two groups of early cranioplasty group (EG, 4 rabbits) and delayed cranioplasty group (DG, 4 rabbits). The rabbits of each group were performed cranioplasty via frozen autologous bone flaps 4 weeks (EG) and 8 weeks (DG) after craniectomy. In order to obtain control data, the cranioplasty immediate after craniectomy were made on the contralateral cranial bone of the rabbits (control group, CG).The bone fusion and new bone formation were evaluated by micro-CT scan and histological examination 8 weeks after cranioplasty on both groups. RESULTS: In the micro-CT scans, the mean values of the volume and the surface of new bone were 50.13+/-7.18 mm3 and 706.23+/-77.26 mm2 in EG, 53.78+/-10.86 mm3 and 726.60+/-170.99 mm2 in DG, and 31.51+/-12.84 mm3 and 436.65+/-132.24 mm2 in CG. In the statistical results, significant differences were shown between EG and CG and between DG and CG (volume : p=0.028 and surface : p=0.008). The histological results confirmed new bone formation in all rabbits. CONCLUSION: We observed new bone formation on all the frozen autologous bone flaps that was stored within 8 weeks. The timing of cranioplasty may showed no difference of degree of new bone formation. Not only the healing period after cranioplasty but the time interval from craniectomy to cranioplasty could affect the new bone formation.
Animal Experimentation ; Osteogenesis* ; Rabbits* ; Risk Factors

BACKGROUND AND OBJECTIVES: We compared the efficacy and safety of valsartan and rosuvastatin combination therapy with each treatment alone in hypercholesterolemic hypertensive patients. SUBJECTS AND METHODS: Patients who met inclusion criteria were randomized to receive 1 of the following 2-month drug regimens: valsartan 160 mg plus rosuvastatin 20 mg, valsartan 160 mg plus placebo, or rosuvastatin 20 mg plus placebo. The primary efficacy variables were change in sitting diastolic blood pressure (sitDBP) and sitting systolic blood pressure (sitSBP), and percentage change in low-density lipoprotein-cholesterol (LDL-C) in the combination, valsartan, and rosuvastatin groups. Adverse events (AEs) during the study were analyzed. RESULTS: A total of 354 patients were screened and 123 of them were finally randomized. Changes of sitDBP by least squares mean (LSM) were -11.1, -7.2, and -3.6 mm Hg, respectively, and was greater in the combination, as compared to both valsartan (p=0.02) and rosuvastatin (p<0.001). Changes of sitSBP by LSM were -13.2, -10.8, and -4.9 mm Hg, and was greater in the combination, as compared to rosuvastatin (p=0.006) and not valsartan (p=0.42). Percentage changes of LDL-C by LSM were -52, -4, and -47% in each group, and was greater in the combination, as compared to valsartan (p<0.001), similar to rosuvastatin (p=0.16). Most AEs were mild and resolved by the end of the study. CONCLUSION: Combination treatment with valsartan and rosuvastatin exhibited an additive blood pressure-lowering effect with acceptable tolerability, as compared to valsartan monotherapy. Its lipid lowering effect was similar to rosuvatatin monotherapy.
Blood Pressure ; Drug Therapy, Combination ; Humans ; Least-Squares Analysis ; Rosuvastatin Calcium ; Valsartan

In this article, on page 230, Fig. 2A needs to be corrected.