Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). Conclusion Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Purpose: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. Materials and Methods: Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). Results: Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. Conclusion There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Background: Sterility and safety assurance of hematopoietic stem cell (HSC) products is critical in transplantation. Microbial contamination can lead to product disposal and increases the risk of unsuccessful clinical outcomes. Therefore, it is important to implement and maintain good practice guidelines and regulations for the HSC collection and processing unit in each hospital. We aimed to share our experiences and suggest strategies to improve the quality assurance of HSC processing. Methods: We retrospectively analyzed microbial culture results of 11,743 HSC products processed over a 25-year period (January 1996 to May 2021). Because of reorganization of the HSC management system in 2008, the 25-year period was divided into periods 1 (January 1996 to December 2007) and 2 (January 2008 to May 2021). We reviewed all culture results of the HSC products and stored aliquot samples and collected culture results for peripheral blood and catheter samples. Results: Of the 11,743 products in total, 35 (0.3%) were contaminated by microorganisms, including 19 (0.5%) of 3,861 products during period 1 and 16 (0.2%) of 7,882 products during period 2. Penicillium was the most commonly identified microorganism (15.8%) during period 1 and coagulase-negative Staphylococcus was the most commonly identified (31.3%) during period 2. HSC product contamination occurred most often during HSC collection and processing. Conclusions The contamination rate decreased significantly during period 2, when the HSC management system was reorganized. Our results imply that handling HSC products by trained personnel and adopting established protocols, including quality assurance programs, aid in decreasing the contamination risk.

We assessed the success rate of empirical antifungal therapy with itraconazole and evaluated risk factors for predicting the failure of empirical antifungal therapy. A multicenter, prospective, observational study was performed in patients with hematological malignancies who had neutropenic fever and received empirical antifungal therapy with itraconazole at 22 centers. A total of 391 patients who had abnormal findings on chest imaging tests (31.0%) or a positive result of enzyme immunoassay for serum galactomannan (17.6%) showed a 56.5% overall success rate. Positive galactomannan tests before the initiation of the empirical antifungal therapy (P=0.026, hazard ratio [HR], 2.28; 95% confidence interval [CI], 1.10-4.69) and abnormal findings on the chest imaging tests before initiation of the empirical antifungal therapy (P=0.022, HR, 2.03; 95% CI, 1.11-3.71) were significantly associated with poor outcomes for the empirical antifungal therapy. Eight patients (2.0%) had premature discontinuation of itraconazole therapy due to toxicity. It is suggested that positive galactomannan tests and abnormal findings on the chest imaging tests at the time of initiation of the empirical antifungal therapy are risk factors for predicting the failure of the empirical antifungal therapy with itraconazole. (Clinical Trial Registration on National Cancer Institute website, NCT01060462)
14-alpha Demethylase Inhibitors/adverse effects/therapeutic use ; Adolescent ; Adult ; Aged ; Antifungal Agents/adverse effects/*therapeutic use ; Aspergillosis/complications/*drug therapy ; Candidiasis/complications/*drug therapy ; Coccidioidomycosis/complications/drug therapy ; Febrile Neutropenia/complications/drug therapy ; Female ; Hematologic Neoplasms/complications/drug therapy/*microbiology ; Humans ; Itraconazole/adverse effects/*therapeutic use ; Male ; Mannans/blood ; Middle Aged ; Prospective Studies ; Treatment Outcome ; Young Adult

In order to present the optimal neuroscience tutorial material for medical students and researchers, this study is aimed to make neuro-digital slide and neuro-atlas based on the histological specimens of human spinal cord and brain stem. Cadavers which had agreed for organ donation for research purpose were used in this study. Brains and spinal cords were extracted within 24 hours after death, and then fixed with 10% neutral buffered formalin. Paraffin blocks were made with the following regions; 8 regions from the spinal cord (the levels of the upper cervical segment, the cervical enlargement, the upper thoracic segment, the mid thoracic segment, the lower thoracic segment, the upper lumbar segment, the lumbar enlargement, the sacral segment), 14 regions from the brain stem (the levels of the spinomedullary junction, the pyramidal decussation, the medial lemniscus decussation, the obex, the mid-olivary medulla, the upper medulla, the pontomedullary junction, the lower pons, the mid pons, the upper pons, the isthmus rhombencephali, the inferior colliculus, the superior colliculus, the posterior commissure). Using virtual microscope software, we made digital neuro-slides which can be used anywhere and anytime regardless of equipment of microscope. To help understanding anatomy and functions of nervous tissue, we also made neuro-atlas based on the digital slide images. As results, the outline and detailed structures of nuclei and tracts are easily discriminated and also matched with marks and nomenclatures of neuro-atlas. Moreover, the cytoarchitecture of each nucleus and histological features can be well distinguished. We hope that this product would be used as a useful neuroscience tutorial material for the medical and paramedical school students, clinical trainees like interns and residents, and also neuroscience researchers.
Brain ; Brain Stem ; Formaldehyde ; Humans ; Inferior Colliculi ; Neurosciences ; Paraffin ; Pons ; Pyramidal Tracts ; Spinal Cord ; Students, Medical ; Superior Colliculi ; Tissue and Organ Procurement

The pyrimidine antimetabolite 5-fluorouracil (5-FU) is a chemotherapeutic agent used widely for various tumors. Common side effects of 5-FU are related to its effects on the bone marrow and gastrointestinal epithelium. Neurotoxicity caused by 5-FU is uncommon, although acute and delayed forms have been reported. Wernicke's encephalopathy is an acute, neuropsychiatric syndrome resulting from thiamine deficiency, and has significant morbidity and mortality. Central nervous system neurotoxicity such as Wernicke's encephalopathy following chemotherapy with 5-FU has been reported rarely, although it has been suggested that 5-FU can produce adverse neurological effects by causing thiamine deficiency. We report a patient with Wernicke's encephalopathy, reversible with thiamine therapy, associated with 5-FU-based chemotherapy.
Acute Disease ; Antimetabolites, Antineoplastic/*adverse effects ; Female ; Fluorouracil/*adverse effects ; Humans ; Magnetic Resonance Imaging ; Middle Aged ; Nasopharyngeal Neoplasms/drug therapy/radiotherapy ; Thiamine/therapeutic use ; Thiamine Deficiency/*complications/diagnosis ; Wernicke Encephalopathy/*chemically induced/diagnosis

BACKGROUND: This study evaluated the clinical characteristics and risk factors associated with community and hospital onset MRSA isolated from patients admitted to a tertiary care teaching hospital. METHODS: The study was carried out on MRSA isolated from clinical specimens of patients admitted into the wards and the intensive care unit in a 2,200-bed tertiary care teaching hospital from January 1st through December 31st, 2007. In order to identify the risk factors associated with MRSA acquisition, the medical records were reviewed. All statistics were computed using SPSS version 14.0. RESULTS: Of the 835 MRSA isolates, 179 (21.4%) were CO-MRSA and 656 (78.6%) were HO-MRSA. Of the 179 CO-MRSA isolates, 6 (3.4%) were CA-MRSA. Multiple logistic regression analysis showed that a history of using medical device or antibiotics within 1 year before the isolation of MRSA were significant risk factors for HO-MRSA, and a history of hospitalization within 1 year before the isolation of MRSA was a significant risk factor for CO-MRSA. Analysis on the antibiotics administered within 1 year before the isolation of MRSA showed that levofloxacin, macrolides, 1st generation cephalosporins, 3rd generation cephalosporins, 4th generation cephalosporins, vancomycin, metronidazole, and carbapenem were all significant risk factors for HO-MRSA and that TMP/SMX was a significant risk factor for CO-MRSA. Of the 6 (3.4%) CA-MRSA isolates, 1 (16.7%) was the pathogen responsible for soft tissue infection. No patients died from the CA-MRSA infection. CONCLUSION: MRSA isolated from clinical specimens of patients admitted into the wards and the ICU in a tertiary care teaching hospital was usually HO-MRSA, CO-MRSA and HO-MRSA usually had at least one of the risk factors associated with MRSA acquisition, and CO-MRSA was mainly HACO-MRSA.
Anti-Bacterial Agents ; Cephalosporins ; Hospitalization ; Hospitals, Teaching ; Humans ; Intensive Care Units ; Logistic Models ; Macrolides ; Medical Records ; Methicillin Resistance ; Methicillin-Resistant Staphylococcus aureus ; Metronidazole ; Ofloxacin ; Risk Factors ; Soft Tissue Infections ; Tertiary Healthcare ; Vancomycin

BACKGROUND: Most of adult patients with chronic immune thrombocytopenic purpura (ITP) that was refractory or relapsed to high-dose corticosteroid have been treated with splenectomy as a 2nd line treatment. However, these patients may have increased morbidity and mortality according to the operation and the increased risk of infection for a lifetime after splenectomy. Despite of the above risks, 30~40% of these patients can't maintain remission. Furthermore, the remission rate after splenectomy is relatively lower in patients with corticosteroid-refractory chronic ITP than that in those patients with corticosteroid-responsiveness. We studied whether danazol, an attenuated androgen, is useful or safe as 2nd line treatment for chronic ITP instead of splenectomy and which factors are associated with the response to danazol. METHODS: Among the patients with chronic ITP who failed corticosteroid therapy in our hospital, 28 patients who received danazol as the 2nd line treatment were analyzed retrospectively. A complete response was defined that the platelet count was increased to 150 x 10(3)/microL, and a partial response was defined that the platelet count was increased above 50 x 10(3)/microL or there was an increased platelet count of more than 20 x 10(3)/microL from the pre-treatment platelet count when the platelet count was above 50 x 10(3)/microL at the time of danazol therapy. RESULTS: The median age of patients was 44 years (range: 19~67) and the number of male patients was 9 (32.1%) and the number of females was 19 (67.9%). The starting daily doses of danazol were variable from 200 to 600mg, though most of the patients were treated with 400mg daily (18 cases, 64.3%). The median duration of danazol therapy was 201.5 days (range: 13~973) and the median duration from ITP diagnosis to danazol treatment was 56 days (range: 20~2,430). Among the accrued 28 patients, 22 patients showed a response to danazol (78.5%); there were 6 patients (21.4%) with a complete response and 16 patients (57.1%) with a partial response. The median duration from danazol treatment to response was 30 days (range: 0~180). The median response duration of danazol treatment was 330 days (95% CI: 182~478) by the Kaplan-Meiyer method. For the danazol-responsive patients, 9 patients (40.9%) remained in remission and 13 patients (59.1%) relapsed. Grade 3~4 toxicity was observed in two patients and three patients stopped danazol because of adverse effects. Hepatotoxicity was the most common toxicity. CONCLUSION: Our findings suggest that danazol is a beneficial, safe choice as the 2nd line treatment for patients with chronic ITP that was refractory or relapsed to corticosteroid.
Adult ; Danazol* ; Diagnosis ; Female ; Humans ; Male ; Mortality ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic* ; Retrospective Studies ; Splenectomy

OBJECTIVE: To identify the factors affecting the complete fetal loss following multifetal pregnancy reduction (MFPR). DESiGN: Retrospective clinical study. METHODS: A total of 256 consecutive treatments of MFPR in iVF-ET cycles performed between 1992 through 2000 in Samsung Cheil hospital were analyzed. MFPR was done around 8 weeks of gestation by transvaginal ultrasono-guided aspiration in multiple pregnancies and reduced to singleton or twins. Stepwise logistic regression was performed to identify the factors affecting the final outcome of pregnancy after MFPR. Dependent variable was complete fetal loss and the independent variables were maternal age, paternal age, initial number of gestational sac (iGSNO), initial number of fetal heart beat, the number of remaining live fetus after MFPR, and chorionicity. RESULTS: The total survival rate was 87.9%, and total fetal loss rate after MFPR was 12.1%. Total fetal loss occurred within four weeks from MFPR procedure was 1.95%. Total loss occurred after four weeks of procedure and before 24 gestational weeks was 8.2%. Seventy nine percent (202/256) of pregnancies delivered after 34 weeks of gestation. The survival rate of pregnancies reduced to singleton was significantly higher than that of pregnancies reduced to twins (93.5% vs. 86.7%, p<0.05). The mean (+/-SEM) gestational age at delivery was 36.2+/-1.0 and 34.1+/-0.5 weeks for pregnancies reduced to singletons and twins, respectively (p=0.065). Logistic regression analysis revealed that the maternal age, the number of initial gestational sac (iGSNO), and the number of remaining live fetus after MFPR significantly affected the rate of total fetal loss (Z = 0.174'age + 0.596'iGSNO + 1.324'remaining fetuses-12.07), (p<0.05). CONCLUSiONS: MFPR seems to be a relatively safe and efficient method to improve the obstetric outcome in high order multiple pregnancy. Because the maternal age, the number of initial gestational sac and the remaining live fetuses after MFPR affect the total fetal loss rate, restriction of the number of transferred embryos according to the age and MFPR to singleton fetus could be considered for the better obstetric outcome in iVF pregnancy.
Chorion ; Embryonic Structures ; Female ; Fetal Heart ; Fetus ; Gestational Age ; Gestational Sac ; Humans ; Logistic Models ; Maternal Age ; Paternal Age ; Pregnancy ; Pregnancy Reduction, Multifetal* ; Pregnancy, Multiple ; Retrospective Studies ; Survival Rate

OBJECTIVE: The relationship was studied between expression of c-erbB-2 oncoprotein and topoisomerase II-alpha as proliferating marker in precancerous lesions and invasive squamous carcinomas of the uterine cervix. METHODS: Total 81 formalin-fixed, paraffin-embedded sections of low-grade intrasquamous lesion (22 cases), high-grade intraepithelial lesions (42 cases) and invasive squamous cell carcinomas (17 cases) in the uterine cervix were stained by immunohistochemistry for expression of the c-erbB-2 oncoprotein and topoisomerase II-alpha. RESULTS: The expression of c-erbB-2 oncoprotein and staining index (mean+/-S.D) of topoisomerase II-alpha were statistically significant between precancerous lesions and invasive carcinoma. The expression of c-erbB-2 oncoprotein has correlation with staining index (mean+/-S.D) of topoisomerase II-alpha. CONCLUSION: There results suggest that the expression of c-erbB-2 protein has relationship with progression of squamous lesions and topoisomerase II-alpha is an useful proliferating marker in the uterine cervix. And, the expression of c-erbB-2 protein has correlation with expression of topoisomerase II-alpha.
Carcinoma, Squamous Cell* ; Cervix Uteri* ; DNA Topoisomerases, Type I* ; DNA* ; Female ; Immunohistochemistry ; Receptor, erbB-2