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Find video protocols related to scientific articles indexed in Pubmed.
A novel 8-joint ultrasound score is useful in daily practice for rheumatoid arthritis.
Mod Rheumatol
PUBLISHED: 11-18-2014
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Objectives. To investigate the optimal number and combination of joints to be assessed by power Doppler ultrasonography (PDUS) in daily practice for rheumatoid arthritis (RA). Methods. PDUS were performed in 24 joints, including all proximal interphalangeal, metacarpophalangeal (MCP), and bilateral wrist and knee joints in 234 patients with RA. PD signals were scored semiquantitatively from 0 to 3 in each joint, and total PD score-24 was calculated by summing them up as comprehensive assessment. Results. Positive PD signals were more frequently found in bilateral wrist, knee, and the second and third MCP joints than the other joints. The individual PD scores of these 8 joints also showed higher correlation coefficients with total PD score-24 (rs ? 0.4). Among the sum PD scores of various selected joint combinations, the score of the combination of 8 joints (total PD score-8), including bilateral second and third MCP, wrist, and knee joints, showed the highest sensitivity and negative predictive value (98.1% and 96.2%, respectively). Total PD score-8 showed high correlation with the total PD score-24 (rs = 0.97, p < 0.01). Conclusions. Total PD score-8 is simple and efficient enough for monitoring disease activity and judging imaging remission of RA in daily practice.
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Measurement of eNO with portable analyzer might improve the management of persistent cough at primary care practice in Japan.
Clin Respir J
PUBLISHED: 09-29-2014
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There are some controversial reports that investigated the usefulness of exhaled nitric oxide (eNO) to predict the efficacy of inhaled corticosteroids (ICS) in chronic cough patients. Therefore, we retrospectively analyzed the usefulness of eNO measurement with portable analyzer to predict the requirement of ICS therapy in persistent cough (defined as lasting for 3 weeks or more) patients in Japan and investigated whether it might improve the management of persistent cough at primary care practice.
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Prognostic significance of serum beta-2 microglobulin level in Hodgkin lymphoma treated with ABVD-based therapy.
Med. Oncol.
PUBLISHED: 08-21-2014
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The levels of serum beta-2 microglobulin (?2MG) are determined mainly from lymphoid tissue. To examine its prognostic value in Hodgkin lymphoma (HL), we conducted a retrospective analysis. We analyzed 67 patients with HL diagnosed and treated at seven institutes of the Yokohama City University Hematology Group between 1998 and 2011. The patients included 40 males and 27 females with a median age of 41 years (range 16-81 years). The HL subtypes were nodular sclerosis classical HL in 37 patients, mixed cellular classical HL in 23, lymphocyte-rich classical HL in 6, and nodular lymphocyte-predominant HL in 1. The 4-year overall survival (OS) rate of all 67 patients was 89 %. Patients with ?2MG levels ? 2.5 mg/L (n = 18) showed inferior progression-free survival (PFS; 4-year PFS rate, 42 %) and inferior OS (4-year OS rate, 60 %) compared to patients who had ?2MG levels <2.5 mg/L (n = 49; 4-year PFS rate, 87 %; 4-year OS rate, 98 %; P < 0.001). In multivariate analysis, only a serum ?2MG level ? 2.5 mg/L was a significant adverse prognostic factor in regard to PFS (P = 0.04; relative risk 3.57). However, it was not significant prognostic factor for OS (P = 0.16) in the multivariate analysis. The serum ?2MG level at diagnosis is a useful prognostic marker in patients with HL.
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Serum ferritin level is prognostic of patient outcome in extranodal NK/T cell lymphoma, nasal type.
Med. Oncol.
PUBLISHED: 08-10-2014
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The objective of the current study was to assess the prognostic factors in patients with extranodal natural killer (NK)/T cell lymphoma, nasal type (ENKL). We retrospectively analyzed 35 patients who were diagnosed with ENKL between 1998 and 2011. The median patient age was 63 years, and the male/female ratio was 22:13; twenty patients had localized ENKL, and 26 had a good Eastern Cooperative Oncology Group performance status (score 0 or 1). B symptoms were present in 17 patients. Twenty-five patients presented with nasal or paranasal lesions, or both. With a median follow-up duration among patients still alive at their last follow-up of 47 months (range 8-93 months), the 3-year overall survival (OS) rate was 44.5 %. Multivariate analysis revealed that advanced disease stage (P = 0.002), the presence of extranasal disease (P = 0.013), and serum ferritin levels greater than 300 ng/ml (P < 0.001) were significant and independent (negative) prognostic factors. High serum ferritin levels were associated with the presence of B symptoms, elevated lactate dehydrogenase levels, and high soluble interleukin-2 receptor levels, but not with clinical stage. Patients with high ferritin levels had a remarkably low remission rate (23 %) and a short OS time (median: 4 months). Serum ferritin level at the time of diagnosis of ENKL was a useful prognostic factor.
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[T315I positive promyelocytic crisis of chronic myeloid leukemia].
Rinsho Ketsueki
PUBLISHED: 07-01-2014
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Promyelocytic crisis (PMC) of chronic myelogenous leukemia (CML) is relatively rare. We report a patient who progressed to PMC with a T315I mutation during the initial treatment with dasatinib for CML. He obtained hematological remission after combination therapy with all-trans retinoic acid and chemotherapy for PMC, and PML-RARA was not detected by FISH analysis. Arsenic trioxide (ATO) and imatinib therapy induced a second complete cytogenetic response, and PML-RARA mRNA detected by real-time quantitative RT-PCR dropped below the detection limit. Finally, allogeneic stem cell transplantation was performed. This case suggests that combination therapy with imatinib and ATO achieves favorable outcomes for PMC.
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Minimum Clinically Important Difference in Diffusing Capacity of the Lungs for Carbon Monoxide Among Patients with Severe and Very Severe Chronic Obstructive Pulmonary Disease.
COPD
PUBLISHED: 06-11-2014
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Abstract Background: The minimum clinically important difference (MCID) for diffusing capacity of the lungs for carbon monoxide (DLCO) has not yet been solidly established. Methods: We used the dataset of surgical cohort of National Emphysema Treatment Trial. Briefly, severe and very severe chronic obstructive pulmonary disease (COPD) patients who were candidate for volume reduction surgery and who could provide sufficient data at 12-month follow-up were included. We used two anchor methods using 6-minute walk distance (6MWD. MCID = 40 m) and forced expiratory volume in 1 sec (FEV1. MCID = 100 ml) as anchors, and two distribution methods. We proposed MCID with a median of estimated values. We estimated MCID for DLCO in raw value and % change from the baseline independently. Results: The surgical cohort included 356 patients, whose average age was 66.6 ± 5.5 years, and the average % predicted FEV1 was 27.8 ± 7.3%. The estimated MCID for DLCO in raw value and % change from the baseline were as follows: anchor method (average, 6MWD) 1.2 ml/min/mmHg, 17%; anchor method (average, FEV1) 0.7 ml/min/mmHg, 11%; anchor method (receiver operating characteristic, 6MWD) 1.1 ml/min/mmHg, 10%; anchor method (receiver operating characteristic, FEV1) 1.2 ml/min/mmHg, 3%; distribution method (0.3 units of standard deviation), 0.9 ml/min/mmHg, 11%; distribution method (standard error of measurement), 1.1 ml/min/mmHg. The median of these values was 1.1 ml/min/mmHg and 11%. Conclusion: We estimated the group-level MCID for DLCO for patients with severe and very severe COPD patients as 1.1 ml/min/mmHg and 11% of baseline DLCO.
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Intrathecal methotrexate prophylaxis and central nervous system relapse in patients with diffuse large B-cell lymphoma following rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone.
Leuk. Lymphoma
PUBLISHED: 06-11-2014
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This study evaluated the efficacy of central nervous system (CNS) prophylaxis using intrathecal methotrexate (IT-MTX) in patients with diffuse large B-cell lymphoma (DLBCL). We retrospectively studied 322 patients who achieved first complete remission (CR) after rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. The CNS prophylaxis consisted of four doses of IT-MTX (15 mg) with hydrocortisone (25 mg) administered after CR was achieved. Forty patients (12%) received CNS prophylaxis (group A) and 282 patients (88%) did not (group B). Three patients in group A (8%) and eight in group B (3%) experienced isolated CNS relapse during the first CR, although this difference was not statistically significant (p = 0.14). Ten of 11 CNS relapses occurred in the brain parenchyma with (n = 3) or without (n = 7) leptomeningeal involvement, and the remaining patient had exclusive leptomeningeal involvement. In patients with DLBCL attaining CR after R-CHOP, IT-MTX administration was insufficient to prevent CNS relapse.
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Intrapulmonary Schwannoma Diagnosed With Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration: Case Report.
Arch. Bronconeumol.
PUBLISHED: 06-08-2014
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A 47-year-old woman was referred to our hospital for further examination of a lung tumor. CT of the chest revealed a round, well-defined 2.4-cm nodule in S2, adjacent to right superior lobe bronchus. Endobronchial ultrasonography showed a well-defined, hypoechoic tumor with echogenic capsule and posterior acoustic enhancement. Diagnosis of schwannoma was confirmed from the specimen obtained by endobronchial ultrasound-guided transbronchial needle aspiration. She underwent tumorectomy due to the possibility of obstructive pneumonia. Pathology diagnosis from the surgical specimen was also schwannoma. Endobronchial ultrasound-guided transbronchial needle aspiration and findings with endobronchial ultrasonography might be helpful in the diagnosis of intrapulmonary schwannoma.
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Evidence suggesting that oral corticosteroids increase mortality in stable chronic obstructive pulmonary disease.
Respir. Res.
PUBLISHED: 03-25-2014
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Oral corticosteroids were used to control stable chronic obstructive pulmonary disease (COPD) decades ago. However, recent guidelines do not recommend long-term oral corticosteroids (LTOC) use for stable COPD patients, partly because it causes side-effects such as respiratory muscle deterioration and immunosuppression. Nonetheless, the impact of LTOC on life prognosis for stable COPD patients has not been clarified.
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Statins reduce all-cause mortality in chronic obstructive pulmonary disease: a systematic review and meta-analysis of observational studies.
Respir. Res.
PUBLISHED: 03-19-2014
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Recent observational studies have suggested that use of statins reduces mortality in patients suffering from chronic obstructive pulmonary disease. However, no meta-analysis has reported the pooled hazard ratio of statins to all-cause mortality.
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Analysis of various factors on the relapse of acute neurological attacks in Behçet's disease.
Mod Rheumatol
PUBLISHED: 03-19-2014
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Abstract Objectives. To investigate the influences of various factors on the relapse of acute neurological attacks in patients with Behçet's disease (BD). Methods. Sixty-one patients, who met the international classification criteria for BD, had attacks of acute neuro-Behçet's disease (NBD) and could be followed up at least for 2 months, including 60 patients in our multicenter retrospective survey on BD patients in 2011. The factors associated with relapse of acute neurological attacks were assessed. Results. Twenty-one of 61 patients had been taking cyclosporine A (CyA) at the onset of acute NBD. All the 21 patients with CyA and 33 of the 40 patients without CyA had eye involvement. There were no significant differences in demographic features, clinical symptoms, MRI findings, the need for, and responses to corticosteroid therapy including pulse therapy between patients with CyA and those without CyA. CyA was withdrawn in 19 of 21 patients with CyA. Of note, patients with CyA showed significantly lower relapse rates than those without CyA (HR 0.1283, 95% CI: 0.0788-0.7836, p = 0.0186 as calculated by log-rank test). Moreover, colchicine was found to reduce the relapse rates in patients with acute NBD without CyA (HR 0.2771, 95% CI: 0.0827-0.9422, p = 0.0450 [log-rank test]). Conclusion. These results indicate that CyA-related acute neurological manifestations are almost identical with CyA-unrelated acute events of NBD, except for the paucity of relapse on withdrawal of CyA. The data also demonstrate that colchicine is effective to prevent relapses of acute neurological attacks especially in patients with CyA-unrelated acute NBD.
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Post-therapy (18)F-fluorodeoxyglucose positron emission tomography for predicting outcome in patients with peripheral T cell lymphoma.
Ann. Hematol.
PUBLISHED: 02-27-2014
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The International Harmonization Project on Lymphoma recommends (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) for the routine assessment of treatment efficacy in patients with FDG-avid lymphomas such as Hodgkin's and diffuse large B cell lymphomas. The utility of FDG-PET in predicting outcomes in patients with peripheral T cell lymphomas (PTCL) has not been fully elucidated. We retrospectively determined the predictive value of FDG-PET after first-line treatment (post-PET) for outcome in PTCL. Of the 36 patients enrolled, 16 were histologically diagnosed with PTCL not otherwise specified and 20 were diagnosed with angioimmunoblastic T cell lymphoma. All patients received curative-intent anthracycline-containing chemotherapy regimens. Post-PET images were visually evaluated by local nuclear medicine physicians. The median observation period for the surviving patients was 44 months. Positive and negative post-PET results were obtained in 31 % (11/36) and 69 % (25/36) of patients, respectively. The 3-year progression-free survival rates in the positive and negative post-PET result groups were 18 % and 62 %, respectively (P?
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Prognostic index for relapsed acute leukemia after allogeneic stem cell transplant.
Leuk. Lymphoma
PUBLISHED: 02-22-2014
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We retrospectively studied patients who relapsed after allogeneic stem cell transplantation (SCT) to identify factors influencing outcomes. Of the 296 patients (196 with AML and 100 with ALL), 102 (34%) experienced relapse at a median of 222 days (range: 30-2,748) after SCT. Multivariable analysis showed that high disease risk (hazard risk [HR]: 1.95; 95% confidence interval [CI]: 1.17-3.24; p = 0.010), unrelated donor (HR: 1.76; 95% CI: 1.10-2.80; p = 0.018), and interval of < 180 days from SCT to relapse (HR: 2.10; 95% CI: 1.26-3.51; p = 0.004) were independent factors of 2-year post-relapse survival (PRS). These factors were used as a prognostic index for PRS. The 2-year PRS in patients of score 0, score 1, score 2, and score 3 was 38%, 19%, 3%, and 0%, respectively (p < 0.001). Our new prognostic index may be helpful for selecting the treatment for relapsed patients after SCT.
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Human herpesvirus-6 encephalopathy after hematopoietic stem cell transplantation and class I human leukocyte antigen.
Clin Transplant
PUBLISHED: 02-21-2014
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Human herpesvirus-6 (HHV-6) encephalopathy is a serious complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Although reactivation of HHV-6 is often observed after allo-HSCT, encephalopathy only affects a few patients with HHV-6 reactivation. Human leukocyte antigen (HLA) class I is expressed by most somatic cells, and a relationship between some class I alleles and neurological diseases has been reported. The HHV-6 load at two, three, and four weeks after allo-HSCT was examined. HHV-6 encephalopathy was diagnosed from symptoms, results of cerebrospinal fluid examination, and magnetic resonance imaging findings. The relation between HHV-6 reactivation or encephalopathy and the HLA class I status of the recipients was investigated. In 130 patients, 147 allo-HSCT transplantation procedures were carried out. HHV-6 reactivation and encephalopathy occurred in 56 and nine procedures, respectively. HLA mismatch (p = 0.008) and unrelated donor (p = 0.001) were associated with HHV-6 reactivation, but not with HHV-6 encephalopathy. HHV-6 encephalopathy was more frequent in patients with HLA-B*40:06 (p = 0.027). In addition, HLA-A*26:01 and HLA-B*40:06 were found to be associated with each other (p = 0.089), while HLA-B*40:06 and HLA-C*08:01 showed a significant association (p < 0.001). The HLA class I alleles of recipients may be associated with the occurrence of HHV-6 encephalopathy after allo-HSCT.
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Human leukocyte antigen-DR expression on flow cytometry and tumor-associated macrophages in diffuse large B-cell lymphoma treated by rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone therapy: retrospective cohort study.
Leuk. Lymphoma
PUBLISHED: 02-18-2014
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Loss of human leukocyte antigen (HLA)-DR expression may be related to a poor prognosis of diffuse large B-cell lymphoma (DLBCL), and tumor-associated macrophages (TAMs) may influence tumor progression. We retrospectively reviewed 36 patients with newly diagnosed DLBCL who received R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) therapy at Kanagawa Cancer Center in Japan from 2004 to 2010. HLA-DR expression by lymphoma cells was evaluated using flow cytometry, and TAMs in lymphoma tissue were detected by immunohistochemistry for CD68 as a marker of macrophages and CD163 as a marker of M2 TAMs. Three-year overall survival was, respectively, 100% versus 69.6% in the HLA-DR "bright" and "not bright" groups (p = 0.012). Patients from the HLA-DR "not bright" group with strong CD163 expression had a much worse prognosis than other patients. The HLA-DR status shown by flow cytometry can be used to predict the prognosis of patients with DLBCL receiving R-CHOP therapy and prognostic accuracy can be increased by also assessing TAMs.
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Predictive value of risk assessment scores in patients with hematologic malignancies undergoing reduced-intensity conditioning allogeneic stem cell transplantation.
Am. J. Hematol.
PUBLISHED: 02-15-2014
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Reduced-intensity conditioning allogeneic stem cell transplantation (RIC allo-SCT) is associated with less toxicity and is used for older patients. We retrospectively studied the predictive value of two risk assessment scores, which were the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) and the pre-transplantation assessment of mortality (PAM) score, for assessing the outcome of RIC allo-SCT. Seventy-eight patients underwent transplantation between 2005 and 2013 at a single institution. RIC was performed with fludarabine and melphalan with/without total body irradiation. The 3-year overall survival of patients with an HCT-CI >3 was significantly worse than that of patients with an HCT-CI 0-3 (31.6% vs. 59.6%, P?=?0.020). Also, the 3-year overall survival of patients with a PAM score >24 was significantly worse than that of those with a PAM score ?24 (29.2% vs. 61.4%, P?=?0.005). The present findings suggest that changing the cut-off values of these risk assessment scores can improve prediction of outcomes in patients receiving RIC allo-SCT with this conditioning regimen and we need validation by large-scale study with other regimens.
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European Treatment and Outcome Study score does not predict imatinib treatment response and outcome in chronic myeloid leukemia patients.
Cancer Sci.
PUBLISHED: 01-23-2014
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The Sokal and Hasford scores were developed in the chemotherapy and interferon era and are widely used as prognostic indicators in patients with chronic myeloid leukemia (CML). Recently, a new European Treatment and Outcome Study (EUTOS) scoring system was developed. We performed a multicenter retrospective study to validate the effectiveness of each of the three scoring systems. The study cohort included 145 patients diagnosed with CML in chronic phase who were treated with imatinib. In the EUTOS low- and high-risk groups, the cumulative incidence of complete cytogenetic response (CCyR) at 18 months was 86.9% and 87.5% (P = 0.797) and the 5-year overall survival rate was 92.6% and 93.3% (P = 0.871), respectively. The cumulative incidence of CCyR at 12 months, 5-year event-free survival and 5-year progression-free survival were not predicted using the EUTOS scoring system. However, there were significant differences in both the Sokal score and Hasford score risk groups. In our retrospective validation study, the EUTOS score did not predict the prognosis of patients with CML in chronic phase treated with imatinib.
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Validation of the European Group for Blood and Marrow Transplantation (EBMT) risk score in patients receiving allogeneic hematopoietic stem cell transplantation at a single center in Japan.
Clin Transplant
PUBLISHED: 01-15-2014
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We validated the European Group for Blood and Marrow Transplantation (EBMT) risk score in 273 consecutive adult patients receiving allogeneic hematopoietic stem cell transplantation between 2000 and 2010 at our center. The patients were divided into four groups according to the EBMT risk score: low risk (LR, score 0-2), intermediate risk-1 (IR-1, score 3), intermediate risk-2 (IR-2, score 4), and high risk (HR, score 5-7). The five-yr overall survival of the LR (n = 65), IR-1 (n = 67), IR-2 (n = 70), and HR (n = 71) groups was 72%, 57%, 41%, and 25%, respectively (p < 0.001). The five-yr transplant-related mortality rates were 16%, 30%, 25%, and 36%, respectively (p = 0.07). The five-yr cumulative incidence of relapse was 20%, 18%, 37%, and 41%, respectively (p < 0.001). In the subgroup analysis, the prognostic value of the EBMT risk score was confirmed in patients undergoing myeloablative conditioning (MAC), but not in those undergoing reduced-intensity conditioning (RIC). The results suggest that the EBMT risk score is a useful tool to predict transplant outcome for patients undergoing MAC, but not for those undergoing RIC and may be beneficial for stratifying patients in clinical studies.
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The rate of reduction in the maximum standardized uptake value from the initial to the post-R-CHOP therapy in positron emission tomography scan predicts disease progression in diffuse large B cell lymphoma patients.
Med. Oncol.
PUBLISHED: 01-15-2014
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[18F]fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) is useful for primary staging and evaluation of treatment outcome in diffuse large B cell lymphoma (DLBCL) patients. The reduction in the maximum standardized uptake value (?SUVmax) from the initial to the interim 18F-FDG PET scan has been reported to predict survival in DLBCL patients. We retrospectively evaluated ?SUVmax obtained by PET or PET-computed tomography before and after initial therapy in 31 newly diagnosed DLBCL patients who were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) therapy. Receiver observation characteristic curve analysis was used to evaluate the optimal cutoff value for the ?SUVmax for disease progression. The 3-year progression-free survival rate of patients with ?SUVmax?83 and <83% was found to be 91 and 25%, respectively (P<0.001). The 4-year overall survival rate of patients with ?SUVmax?83 and <83% was found to be 100 and 83%, respectively (P=0.046). The ?SUVmax observed before and after R-CHOP therapy could be useful in the prediction of disease progression and survival in newly diagnosed DLBCL patients.
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Adalimumab for the Treatment of Japanese Patients with Intestinal Behçet's Disease.
Clin. Gastroenterol. Hepatol.
PUBLISHED: 01-10-2014
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& Aims: Behçet's disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet's disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor ?, in patients with intestinal Behçet's disease who were refractory to corticosteroid and/or immunomodulator therapies.
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Biweekly THP-COP therapy for newly diagnosed peripheral T-cell lymphoma patients.
Hematol Oncol
PUBLISHED: 01-04-2014
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Pirarubicin tetrahydropyranyl adriamycin (THP-ADR) is an analogue of doxorubicin. This agent exhibits activity against some doxorubicin-resistant cell lines. We performed a phase II study of biweekly THP-COP [50?mg/m(2) pirarubicin, 750?mg/m(2) cyclophosphamide, 1.4?mg/m(2) vincristine (2.0?mg maximum) on day 1, and 100?mg/body predonisolone on days 1-5] in patients with peripheral T-cell lymphoma (PTCL). Seventeen patients with newly diagnosed PTCL were enrolled. Histological diagnoses were of PTCL, not otherwise specified (n?=?5), or angioimmunoblastic T-cell lymphoma (n?=?12). All diagnostic specimens including those of the historical control group were centrally reviewed by hematological pathologists. All patients received six cycles of biweekly THP-COP. The patient group included 13 male and 4 female patients, with a median age of 62?years. The median follow-up time in surviving patients was 30?months. Overall response rate was 94% with 15 cases of complete remission (88%). The 3-year progression-free survival and overall survival rates were 57% and 75%, respectively. The most frequent adverse events associated with biweekly THP-COP were leukocytopenia (100%), neutropenia (100%), and lymphopenia (100%), followed by alopecia (92%) and anaemia (88%). All of these occurred only transiently, and the patients subsequently recovered. Biweekly THP-COP is a safe and promising therapy for patients with newly diagnosed PTCL. This study is registered in a public database (UMIN000010485). Copyright © 2014 John Wiley & Sons, Ltd.
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Chemotherapy with carboplatin and paclitaxel after failure of primary chemotherapy for advanced thymic carcinoma. A report of three cases and review of the literature.
Tumori
PUBLISHED: 12-12-2013
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For patients with inoperable thymic carcinoma, multidrug chemotherapy containing cisplatin and an anthracycline is often used as first-line chemotherapy. A commonly applied regimen is cisplatin + doxorubicin + vincristine + cyclophosphamide (ADOC). There are relatively few reports on the use of carboplatin and paclitaxel as first-line chemotherapy for thymic carcinoma. In addition, little is known about its efficacy as second-line chemotherapy in patients with advanced thymic carcinoma. We here report on three patients with thymic carcinoma who were treated with carboplatin and paclitaxel as second-line chemotherapy after failure of ADOC. According to the Response Evaluation Criteria in Solid Tumors version 1.1, one patient achieved a partial response and two patients achieved stable disease. The median progression-free survival was 6.7 months and the median overall survival exceeded 3 years. Toxicities were well tolerated. Chemotherapy with carboplatin and paclitaxel appears to be effective as second-line chemotherapy for some persons with thymic carcinoma who fail ADOC.
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Mycobacterium shinjukuense Lung Disease that was Successfully Treated with Antituberculous Drugs.
Intern. Med.
PUBLISHED: 12-03-2013
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An 80-year-old woman was referred to our hospital due to a persistent productive cough. Acid-fast staining and a commercial Mycobacterium tuberculosis identification kit with TRC (TRC kit) were positive. However, a false-positive result on the TRC kit was suspected because Mycobacterium tuberculosis was not detected in the sputum culture. Finally, Mycobacterium shinjukuense was detected in an analysis of the rpoB and hsp65 gene sequences. As the diagnostic criteria proposed by the American Thoracic Society were met, a diagnosis of Mycobacterium shinjukuense lung disease was made. Following treatment with isoniazid, rifampicin and ethambutol with drug susceptibility, the patients acid-fast culture became negative, and the areas of opacity improved.
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Ultrasonography predicts achievement of Boolean remission after DAS28-based clinical remission of rheumatoid arthritis.
Mod Rheumatol
PUBLISHED: 12-02-2013
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Objectives. To determine whether ultrasonography (US) predicts Boolean remission in rheumatoid arthritis (RA) patients who had achieved disease activity score in 28 joints (DAS28)-based remission criteria. Methods. Thirty-one RA patients in DAS28-based clinical remission were recruited. US semiquantitatively determined Gray scale (GS) and power Doppler (PD) signal scores in the bilateral wrists and all metacarpophalangeals and proximal interphalangeals. Total GS score and total PD score were calculated as the sum of individual scores for each joint. Results. Among 22 RA patients, who maintained DAS28 remission for 2 years, 16 met Boolean remission criteria at the end of study. Both total GS and total PD scores at baseline were significantly lower in Boolean remission group than non-remission group. There was no significant difference in other baseline parameters, including duration of disease, duration of remission, mTSS, and disease activity composite parameters between the two groups. Among the factors for Boolean remission criteria at 2 years, patient global assessment score was associated with total GS score at the entry, while swollen joint count was related to total PD score. Conclusions. Null or low grade of GS and PD findings in US are associated with achieving Boolean remission. Thus, US is essential for assessment and prediction of "deeper remission" of RA.
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The transcription factor IRF8 counteracts BCR-ABL to rescue dendritic cell development in chronic myelogenous leukemia.
Cancer Res.
PUBLISHED: 11-19-2013
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BCR-ABL tyrosine kinase inhibitors (TKI) have dramatically improved therapy for chronic myelogenous leukemia (CML). However, several problems leading to TKI resistance still impede a complete cure of this disease. IFN regulatory factor-8 (IRF8) is a transcription factor essential for the development and functions of immune cells, including dendritic cells. Irf8(-/-) mice develop a CML-like disease and IRF8 expression is downregulated in patients with CML, suggesting that IRF8 is involved in the pathogenesis of CML. In this study, by using a murine CML model, we show that BCR-ABL strongly inhibits a generation of dendritic cells from an early stage of their differentiation in vivo, concomitant with suppression of Irf8 expression. Forced expression of IRF8 overrode BCR-ABL (both wild-type and T315I-mutated) to rescue dendritic cell development in vitro, indicating that the suppression of Irf8 causes dendritic cell deficiency. Gene expression profiling revealed that IRF8 restored the expression of a significant portion of BCR-ABL-dysregulated genes and predicted that BCR-ABL has immune-stimulatory potential. Indeed, IRF8-rescued BCR-ABL-expressing dendritic cells were capable of inducing CTLs more efficiently than control dendritic cells. Altogether, our findings suggest that IRF8 is an attractive target in next-generation therapies for CML.
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Clinical significance of pre- and 1-year post-transplant serum ferritin among adult transplant recipients.
Leuk. Lymphoma
PUBLISHED: 11-01-2013
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To clarify the significance of post-transplant serum ferritin (SF), we retrospectively assessed pre- and post-transplant SF. Among 256 patients undergoing allogeneic stem cell transplant (SCT) for hematologic malignancies between 2000 and 2011, those who had relapsed within 1 year were excluded, and 110 patients surviving for more than 1 year were included in the analysis. The cut-off value of SF was 1000 ng/mL, and four pre- and post-SF groups were defined: low-low (n = 62), low-high (n = 12), high-low (n = 13) and high-high (n = 23). Outcomes at 5 years for each group were as follows: overall survival (OS) 88.2, 38.1, 92.3 and 76.7%, respectively, p = 0.004, and non-relapse mortality (NRM) 11.3, 53.6, 7.7 and 18.9%, respectively, p = 0.037. Patients receiving larger transfusion volumes or developing chronic graft-versus-host disease (GVHD) demonstrated higher 1-year SF values. In multivariate analysis for OS and NRM, low-high SF remained a significant predictor of OS (hazard ratio [HR] = 3.49, 95% confidence interval [CI]: 1.10-11.0, p = 0.032) and NRM (HR = 2.95, 95%CI: 1.04-8.36, p = 0.041). These results suggest that the elevation of SF at 1 year after SCT, which may reflect transfusion and the development of chronic GVHD, may have an aggravating influence on outcomes after SCT. This study provides a clue to clarifying the clinical significance of SF in a transplant setting.
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Peripheral blood absolute lymphocyte/monocyte ratio as a useful prognostic factor in diffuse large B-cell lymphoma in the rituximab era.
Eur. J. Haematol.
PUBLISHED: 10-21-2013
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The tumor microenvironment, including tumor-infiltrating lymphocytes and myeloid-derived cells, is an important factor in the pathogenesis and clinical behavior of malignant lymphoma. However, the prognostic significance of peripheral lymphocytes and monocytes in lymphoma remains unclear.
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Decreased activities of daily living is a strong risk factor for liver injury by anti-tuberculosis drugs.
Respirology
PUBLISHED: 09-26-2013
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We evaluated the association between activities of daily living and drug-induced liver injury by anti-tuberculosis drugs.
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Standard R-CHOP therapy in follicular lymphoma and diffuse large B-cell lymphoma.
J Clin Exp Hematop
PUBLISHED: 09-03-2013
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The introduction of rituximab (R) has measurably improved the outcome of patients with follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL). To evaluate the outcome of patients with FL and DLBCL under R plus CHOP therapy, we performed a retrospective analysis in Yokohama City University Hematology Group in Japan. Five hundred and twenty-six patients (158, FL ; 368, DLBCL) were scheduled to undergo primary therapy with 6 cycles of full-dose R-CHOP therapy with curative intent. The median observation periods in living patients with FL and DLBCL were 45 months and 43 months, respectively. The complete response, 5-year progression-free survival (PFS), and 5-year overall survival (OS) rates were 86%, 50%, and 92% in the FL group, and 89%, 72%, and 80% in the DLBCL group, respectively. Although PFS was significantly better in the DLBCL group than in the FL group, OS was significantly better in FL patients. We also found that the OS and PFS of grade 3 FL patients were not statistically different from those with grade 1-2. These findings indicate that all grades of FL should be categorized simply as "FL" with regard to R-CHOP therapy. Our results also demonstrate the incurability of FL (grade 1-3B), even with R-CHOP therapy.
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The 3q27 and 18q21 translocations for follicular lymphoma and diffuse large B-cell lymphoma in the rituximab era.
J Clin Exp Hematop
PUBLISHED: 09-03-2013
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The 3q27 and 18q21 chromosomal translocations are major hallmarks in B-cell lymphoma. We aimed to determine the frequencies of these translocations in follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) and to evaluate their prognostic impact in the rituximab era. This study included 98 FL and 93 DLBCL patients whose abnormal karyotypes had been detected using G-banding. Patients uniformly underwent R-CHOP therapy : doxorubicin, cyclophosphamide, vincristine, prednisolone, and rituximab ; survivors were followed up for 29 months (median). The 3q27 and 18q21 translocations were detected in 14 and 77 FL patients and 14 and 22 DLBCL patients, respectively. Overall survival (OS) and progression-free survival (PFS) did not differ significantly between the groups with 3q27, 18q21, concurrent 3q27 and 18q21 translocations, and other chromosomal abnormalities for FL and DLBCL. There were no significant differences in OS and PFS between patients with 3q27 translocation-positive FL and those with 3q27 translocation-positive DLBCL or between the patients with 18q21 translocation-positive FL and those with 18q21 translocation-positive DLBCL. The presence of 3q27 and 18q21 translocations did not correlate with the clinical outcomes of FL or DLBCL patients following R-CHOP treatment.
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Lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant predicts non-relapse mortality in patients with acute leukemia or myelodysplastic syndrome.
Leuk. Lymphoma
PUBLISHED: 08-28-2013
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To clarify the clinical significance of lymphocyte recovery on day 100 after allogeneic hematopoietic stem cell transplant (allo-HSCT), we retrospectively studied 157 patients with hematologic malignancies who underwent allo-HSCT. An absolute lymphocyte count < 500/?L was defined as lymphocytopenia. There was a significant relationship between lymphocytopenia and advanced disease at allo-HSCT or corticosteroid administration within 100 days. Lymphocytopenia on day 100 (hazard ratio [HR]: 2.4; 95% confidence interval [CI]: 1.3-4.5; p = 0.006) and advanced disease at allo-HSCT (HR: 2.2; 95% CI: 1.3-3.9; p = 0.005) were prognostic factors for overall survival by multivariate analysis. Advanced disease was significantly associated with relapse (HR: 2.8; 95% CI: 1.5-5.4; p = 0.002), while lymphocytopenia was an independent predictor of non-relapse mortality (HR: 2.8; 95% CI: 1.1-6.8; p = 0.027). These results suggest that lymphocyte recovery on day 100 may be an important predictor of late complications in patients receiving allo-HSCT for hematologic malignancies.
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Drug-induced liver injury after allogeneic bone marrow transplantation.
Int. J. Hematol.
PUBLISHED: 08-12-2013
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A 23-year-old woman developed acute severe hepatitis and jaundice on day 183 after bone marrow transplantation from HLA-B antigen mismatched-related donor. The administration of prednisolone and cessation of the prescribed drugs resolved the liver injury. Drug lymphocyte stimulation test was positive for acyclovir, and liver biopsy indicated the characteristics of drug-induced liver injury (DILI) rather than graft-versus-host disease. Physicians should keep DILI in mind when considering differential diagnosis for liver complications after allogeneic cell transplantation.
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Recovery of natural killer cells and prognosis after cord blood transplantation.
Leuk. Res.
PUBLISHED: 08-06-2013
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The relationship between immune reconstitution and the prognosis after cord blood transplantation is unclear. We investigated the influence of natural killer (NK) cell recovery on transplant outcomes. The maximum number of CD56+CD3- cells or CD57+CD16+ cells was determined to assess NK recovery. Although the high CD56+CD3- group and high CD57+CD16+ group showed significantly better overall survival (OS) than the low group on univariate analysis, the high CD57+CD16+ group was associated with better OS on multivariate analysis. These results suggest that CD57+CD16+ cell recovery is more closely related to the outcome after CBT than CD56+CD3- cell recovery.
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[Prognosis of patients with tuberculosis].
Kekkaku
PUBLISHED: 08-01-2013
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The global incidence of tuberculosis peaked around the year 2003 and is currently declining gradually. However, the worldwide incidence of new tuberculosis cases is still estimated to be 8.8 million/year, with 1.5 million deaths occurring per year. Considering that previous studies have determined the risk factors for death due to tuberculosis, we aimed at reviewing the literature to collectively evaluate these risk factors. According our literature review of 12 articles published in English language and 7 articles published in Japanese, the risk factors for death due to tuberculosis are age, human immunodeficiency virus (HIV) co-infection, multi-drug resistant tuberculosis (MDR-TB), malnutrition, low activities of daily living, co-morbidities, unemployment, and drug injection. We developed a scoring system to calculate the Tuberculosis Prognostic Score using 4 risk factors, namely, age, serum albumin level, oxygen requirement, and activities of daily living, after assessing several cohorts in Japan, in which HIV co-infection and MDR-TB are rare and their associations with mortality due to tuberculosis patients are unclear. This scoring system was successfully able to estimate life prognosis of inpatients with newly diagnosed, smear-positive, lung tuberculosis without MDR-TB and/or HIV virus co-infection.
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Small, Moderate, and Large Changes, and the Minimum Clinically Important Difference in the University of California, San Diego Shortness of Breath Questionnaire.
COPD
PUBLISHED: 07-25-2013
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Abstract Minimum clinically important change of 5 points in the University of California, San Diego Shortness of Breath Questionnaire (SOBQ) is established, but cutoff values between a small, a moderate, and a large change are still unknown. We used the data set of National Emphysema Treatment Trial consisting of severe and very severe chronic obstructive pulmonary disease patients, whose mean age was 64 years. Changes from baseline to post-surgical 6-month follow-up were evaluated. The St. Georges Respiratory Questionnaire was used as anchor: |?SGRQ| < 4, meaningless change; 4 ? |?SGRQ| < 8, small change; 8 ? |?SGRQ| < 13, moderate change; 13 ? |?SGRQ|, large change. We decided the final cutoff values for the SOBQ as medians of the three anchor methods. We also decided the range of cutoff values as the range of three values. In a cohort of surgically treated patients (N = 484), we propose value of 5 (range 5-6), 11 (range 9-15), and 16 (range 14-20) for the cutoff values between a meaningless and a small change (minimum clinically important difference), a small and a moderate change, and a moderate and a large change, respectively. In a cohort of medically treated patients, numbers of patients categorized according to ?SOBQ scores were similar to those of the patients categorizes according to the ?SGRQ (N = 480) or ?Forced expiratory volume in 1 second (N = 425). We propose group-level cutoff values and range between a small, a moderate, and a large changes.
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MIB-1 labeling index as a prognostic factor for patients with follicular lymphoma treated with rituximab plus CHOP therapy.
Cancer Sci.
PUBLISHED: 07-03-2013
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The MIB-1 labeling index, which is based on Ki67 immunostaining, is widely used to evaluate the proliferation of tumor cells in lymphoma. However, its clinical significance has not been fully assessed. We retrospectively evaluated the prognostic impact of the MIB-1 labeling index at the time of diagnosis, in 98 patients with follicular lymphoma (FL) grade 1-3b who were treated uniformly with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) therapy. The 5-year progression-free survival (PFS) for an MIB-1 labeling index of ?10% (n = 60) and <10% (n = 38) was 35% and 61%, respectively (P = 0.015). The 5-year overall survival (OS) for an MIB-1 labeling index of ?10% and <10% was 77% and 92%, respectively (P = 0.025). Pathological grading was not correlated with PFS or OS. In multivariate analysis, an MIB-1 labeling index of ?10% was independently associated with poor PFS and OS. In conclusion, an MIB-1 labeling index of 10% is a useful cut-off level for predicting the prognosis of patients with FL.
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Pregnancy outcomes in Japanese patients with SLE: retrospective review of 55 pregnancies at a university hospital.
Clin Rev Allergy Immunol
PUBLISHED: 07-03-2013
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Systemic lupus erythematosus (SLE) is mainly a disease of fertile women and the coexistence of pregnancy is by no means a rare event. How SLE and its treatment affect pregnancy outcomes is still a matter of debate. We performed a retrospective analysis of 41 SLE patients (55 pregnancies) who were followed at our university hospital from January 2000 to December 2009. The mean age of patients was 30.6±4.8 years and mean disease duration was 6.6±5.3 years. After exclusion of artificial abortions, live birth rate was 84%. Significantly, more women with stillbirth pregnancies were complicated with antiphospholipid syndrome (APS) than women with live birth pregnancies (two of eight stillbirth pregnancies (25%) versus one of 42 live birth pregnancies (2%); p=0.014) and hypocomplementemia at conception (four of eight stillbirth pregnancies (50%) versus six of 42 live birth pregnancies (14%); p=0.021). Compared with nonrenal pregnancies, renal pregnancies were younger at SLE disease onset, had a lower positivity of anti-RNP antibody, and were more complicated with pregnancy-induced hypertension. Past maximum dose of prednisolone, the dose of prednisolone at conception, and percentage of past steroid pulse therapy were higher in renal pregnancies. Outcomes of pregnancies were not significantly different both for mothers and for infants between renal and nonrenal pregnancies. We conclude that it is necessary to provide SLE mothers with the proper information before pregnancy. Women with APS or hypocomplementemia should be regarded with particular attention. Optimal management of mothers and infants requires collaborative efforts of rheumatologists and obstetricians.
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Poor performance status is a strong predictor for death in patients with smear-positive pulmonary TB admitted to two Japanese hospitals.
Trans. R. Soc. Trop. Med. Hyg.
PUBLISHED: 06-13-2013
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Estimation of performance status (PS) has been assessed as a tool to determine which patients with newly diagnosed pulmonary TB (PTB) are most at risk of dying. This simple prediction rule has not been validated in patients with PTB with different background characteristics and from different geographic areas.
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Single center study on ethnic and clinical features of Behcets disease in Moscow, Russia.
Clin. Rheumatol.
PUBLISHED: 06-04-2013
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For the purpose of investigating Behcets disease (BD) in Russia, 250 consecutive patients (177 men and 73 women) diagnosed with BD between 1990 and 2010 at the Research Institute of Rheumatology, Russian Academy of Medical Sciences in Moscow were enrolled in this study. The ethnic backgrounds of the patients were reported as follows: 23.2 % (58 cases) from Russia, 12.8 % (32 cases) from Azerbaijan, 14.4 % (36 cases) from Armenia, 8.8 % (22 cases) from Chechnya, and 21.6 % (55 cases) from Dagestan. The remaining 19.2 % (48 cases) were from other regions or of unknown origin. More than half (57.6 %) of the Behcets disease patients originated from Central Asia, specifically Azerbaijan, Armenia, Chechnya, and Dagestan. The mean age at disease onset was 31.5?±?9.38 (13-60)?years old, and the most typical initial manifestations were oral aphthous ulcers. Patients aged 20-39 years old were more commonly affected and displayed a wide clinical spectrum of the disease, with varieties of severe internal organ involvement. The manifestations observed throughout the course of the disease included oral aphthous ulcers (100 %), various cutaneous lesions (88.8 %), genital ulcers (81.2 %), and ocular lesions (54.0 %). Besides these, many organs/systems were implicated in patient cases, namely joint (53.2 %), vascular (25.2 %), neurological (8.0 %), gastrointestinal (25.2 %), and cardiac (5.6 %) systems. Involvements of ocular (p?
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Gastrointestinal manifestations of Behçets disease in Japan: a study of 43 patients.
Rheumatol. Int.
PUBLISHED: 05-22-2013
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We analyzed the clinical gastrointestinal (GI) characteristics of Behçets disease (BD) patients in Japan. We retrospectively reviewed the clinical charts of 412 patients who fulfilled the 1987 Japanese criteria for BD and were treated in two university hospitals from July 1991 to December 2007. Forty-three patients (10.4 %) had BD-related GI lesions, which were shown by imaging examinations. Median age at BD diagnosis and onset of GI episodes were 29.6 and 31.0 years, respectively. The patients suffered from abdominal pain (30/43) and GI bleeding (18/43), while they had lower frequency of eye involvement and higher incidence of arthritis and vascular involvement than BD patients without GI lesions. The lesions were prevalent in the ileum (32/43) followed by cecum (21/43) and esophagus (9/43). The patients were treated with mesalazine and sulfasalazine (41/43), corticosteroids (32/43), immunosuppressants (13/43), and infliximab for 7 patients having refractory lesions, while 10 patients had surgical operation. Two patients died due to non-GI events during the observation. The diagnosis of BD was often difficult because of lack of eye involvement. Surgery is required for some patients in spite of intensive immunosuppressive therapies. Appropriate use of anti-TNF agents may be promising for the GI involvement.
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Concentrated ascites reinfusion therapy for sinusoidal obstructive syndrome after hematopoietic stem cell transplantation.
Artif Organs
PUBLISHED: 05-20-2013
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Sinusoidal obstruction syndrome (SOS) is one of the severe complications of hematopoietic stem cell transplantation (HSCT). Systemic management including respiratory and circulatory support is necessary. In addition, abdominal paracentesis is often needed for pain relief and to reduce the pressure of tense ascites. Concentrated ascites reinfusion therapy (CART) involves the filtration, concentration, and reinfusion of drained ascites, which contributes to reuse of autologous proteins. CART has been reported as supportive therapy for patients with liver cirrhosis and cancer. We retrospectively reviewed the efficacy and safety of CART in three patients (two with acute myelogenous leukemia and one with chronic myeloid leukemia) who developed SOS after allo-HSCT. They all had symptomatic, tense, and diuretic-refractory ascites with right costal pain and marked weight gain. Two patients showed immediate improvement after CART. However, one patient experienced four CARTs with slow recovery. All patients are now alive and are being monitored as outpatients over 2 years with remission. No severe adverse event was observed related to CART, and 25.2-98.0 (median 30.2) grams of albumin was collected and reinfused. CART after paracentesis reduces protein loss in ascites by reinfusion of autologous protein instead of exogenous albumin preparations. Although transient fever is reported as a frequent adverse event, no events like severe bleeding or infection were observed. While its safety has not been fully established in patients with hematological disease after HSCT, CART may be a considerable supportive therapy for SOS with tense ascites.
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Successful treatment of a patient with adult T cell leukemia/lymphoma using anti-CC chemokine receptor 4 monoclonal antibody mogamulizumab followed by allogeneic hematopoietic stem cell transplantation.
Int. J. Hematol.
PUBLISHED: 05-16-2013
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Adult T cell leukemia/lymphoma (ATLL) is an aggressive peripheral T cell neoplasm caused by human T cell lymphotropic/leukemia virus type-1 and has a poor prognosis. A new anti-CC chemokine receptor 4 monoclonal antibody (mogamulizumab) has been shown to be effective for ATLL. Although mogamulizumab is now available in Japan for patients with ATLL, the influence on allogeneic hematopoietic stem cell transplantation (HSCT) remains unclear. Here we report a woman with ATLL resistant to combination chemotherapy, who achieved complete remission following treatment with mogamulizumab and subsequently received allogeneic HSCT. The patient has remained in complete remission with controlled graft-versus-host disease. To our knowledge, this is the first report of an ATLL patient who received mogamulizumab treatment followed by allogeneic HSCT. We suggest that administration of mogamulizumab to chemotherapy-resistant patients with ATLL may improve their disease status before allogeneic HSCT and result in better survival.
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[Comparison of drug-induced hepatitis occurring in elderly and younger patients during anti-tuberculosis treatment with a regimen including pyrazinamide].
Kekkaku
PUBLISHED: 05-16-2013
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In Japan, tuberculosis (TB) patients aged over 80 years are usually treated with a regimen not including pyrazinamide (PZA) because of the risk of drug-induced hepatitis.
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Targeted resequencing implicates the familial Mediterranean fever gene MEFV and the toll-like receptor 4 gene TLR4 in Behçet disease.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 04-30-2013
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Genome-wide association studies (GWAS) are a powerful means of identifying genes with disease-associated common variants, but they are not well-suited to detecting genes with disease-associated rare and low-frequency variants. In the current study of Behçet disease (BD), nonsynonymous variants (NSVs) identified by deep exonic resequencing of 10 genes found by GWAS (IL10, IL23R, CCR1, STAT4, KLRK1, KLRC1, KLRC2, KLRC3, KLRC4, and ERAP1) and 11 genes selected for their role in innate immunity (IL1B, IL1R1, IL1RN, NLRP3, MEFV, TNFRSF1A, PSTPIP1, CASP1, PYCARD, NOD2, and TLR4) were evaluated for BD association. A differential distribution of the rare and low-frequency NSVs of a gene in 2,461 BD cases compared with 2,458 controls indicated their collective association with disease. By stringent criteria requiring at least a single burden test with study-wide significance and a corroborating test with at least nominal significance, rare and low-frequency NSVs in one GWAS-identified gene, IL23R (P = 6.9 × 10(-5)), and one gene involved in innate immunity, TLR4 (P = 8.0 × 10(-4)), were associated with BD. In addition, damaging or rare damaging NOD2 variants were nominally significant across all three burden tests applied (P = 0.0063-0.045). Furthermore, carriage of the familial Mediterranean fever gene (MEFV) mutation Met694Val, which is known to cause recessively inherited familial Mediterranean fever, conferred BD risk in the Turkish population (OR, 2.65; P = 1.8 × 10(-12)). The disease-associated NSVs in MEFV and TLR4 implicate innate immune and bacterial sensing mechanisms in BD pathogenesis.
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Successful treatment of POEMS syndrome with bortezomib and dexamethasone, combined with radiotherapy, and followed by autologous stem cell transplantation.
Int. J. Hematol.
PUBLISHED: 04-17-2013
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POEMS syndrome is a monoclonal plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes. High-dose therapy (HDT) and autologous stem cell transplantation (ASCT) are an effective therapy, but optimal treatment options are still under debate. Bortezomib is an important agent for the treatment of patients with multiple myeloma and has recently been reported as efficacious in the treatment of patients with POEMS syndrome. We present a case of POEMS syndrome in a 33-year-old woman, who was successfully treated with BorDex (bortezomib and dexamethasone) combined with radiotherapy, and followed by ASCT. She was diagnosed with POEMS syndrome with a localized plasmacytoma of bone 5 months after her initial symptoms of heart failure. Her Eastern Cooperative Oncology Group (ECOG) performance status was 4. She was first administered BorDex therapy, which was subsequently combined with radiotherapy. Her general condition including heart failure dramatically improved after four cycles of BorDex therapy and radiation, resulting in partial response. After chemoradiotherapy, HDT and ASCT were performed. After treatment, she was able to walk unassisted and her plasma endothelial growth factor (VEGF) level decreased. She did not experience neurotoxicity induced by bortezomib. Bortezomib was well tolerated and we suggest that BorDex therapy followed by HDT and ASCT may be an effective therapy for POEMS syndrome.
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Absolute monocyte count in follicular lymphoma patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone.
Leuk. Res.
PUBLISHED: 04-09-2013
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Elevated absolute monocyte counts (AMCs) have been reported to indicate poor prognosis for patients with lymphoproliferative disease, including those with follicular lymphoma (FL) receiving various treatments. We evaluated the prognostic impact of AMC in 150 consecutive FL patients who received rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Progression-free survival (PFS) did not differ significantly according to the AMC level. Univariate and multivariate analyses did not indicate a prognostic significance of AMC for PFS. Thus, the AMC is not a prognostic factor for FL patients treated with R-CHOP. However, immunochemotherapy might influence the prognostic impact of AMC.
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Role of hematopoietic stem cell transplantation for relapsed acute promyelocytic leukemia: a retrospective analysis of JALSG-APL97.
Cancer Sci.
PUBLISHED: 04-02-2013
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For patients with relapsed acute promyelocytic leukemia (APL), all-trans retinoic acid-based salvage regimens can achieve second complete remission (CR2), but the optimal post-remission strategy for APL patients after CR2 remains unclear. Hematopoietic stem cell transplantation (HSCT) during CR2 might be effective, but data on the role of HSCT for APL patients after CR2 are limited in Japan. We retrospectively analyzed outcomes for 57 relapsed APL patients who achieved CR2 in the JALSG APL97 study. Of those, six received autologous (auto)-HSCT, 21 received allogeneic (allo)-HSCT, and 30 received various regimens other than HSCT. The 5-year event-free survival (EFS) rate, overall survival (OS) rate and cumulative incidence of relapse (CIR) were 50.7%, 77.4% and 51.0% in the non-HSCT group, 41.7%, 83.3% and 58.3% in the auto-HSCT group and 71.1%, 76.2% and 9.8% in the allo-HSCT group, respectively. Both the EFS rate and CIR were significantly better in the allo-HSCT group than in other groups. Allo-HSCT appears effective in APL patients in CR2, with a low relapse rate beyond a relatively early transplantation-related mortality (19%). Among older patients (age ?40 years), the 5-year OS was significantly better in the non-HSCT group than in the HSCT group (78.0% vs 40.5%; P = 0.04). Further prospective studies with larger patient numbers are required to confirm the impact of HSCT alone and in combination with arsenic trioxide on outcomes for patients with APL in CR2.
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Sensitivity and specificity of the Streptococcus pneumoniae urinary antigen test for unconcentrated urine from adult patients with pneumonia: a meta-analysis.
Respirology
PUBLISHED: 03-28-2013
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Studies on the sensitivity and specificity of the Binax Now Streptococcus pneumonia urinary antigen test (index test) show considerable variance of results. Those written in English provided sufficient original data to evaluate the sensitivity and specificity of the index test using unconcentrated urine to identify S. pneumoniae infection in adults with pneumonia. Reference tests were conducted with at least one culture and/or smear. We estimated sensitivity and two specificities. One was the specificity evaluated using only patients with pneumonia of identified other aetiologies (specificity (other)). The other was the specificity evaluated based on both patients with pneumonia of unknown aetiology and those with pneumonia of other aetiologies (specificity (unknown and other)) using a fixed model for meta-analysis. We found 10 articles involving 2315 patients. The analysis of 10 studies involving 399 patients yielded a pooled sensitivity of 0.75 (95% confidence interval: 0.71-0.79) without heterogeneity or publication bias. The analysis of six studies involving 258 patients yielded a pooled specificity (other) of 0.95 (95% confidence interval: 0.92-0.98) without no heterogeneity or publication bias. We attempted to conduct a meta-analysis with the 10 studies involving 1916 patients to estimate specificity (unknown and other), but it remained unclear due to moderate heterogeneity and possible publication bias. In our meta-analysis, sensitivity of the index test was moderate and specificity (other) was high; however, the specificity (unknown and other) remained unclear.
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[Chronic myeloid leukemia maintained major molecular response with intermittent dosage of imatinib mesylate].
Gan To Kagaku Ryoho
PUBLISHED: 03-20-2013
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A 57-year-old woman was diagnosed as in the chronic myeloid leukemia-chronic phase. Imatinib mesylate(IM)was initiated at 400 mg daily. She achieved complete cytogenetic response at 3 months, and major molecular response at 10 months. IM was reduced to 300 mg daily at 12 months because of grade 1 nausea. IM was reduced to 300 mg for 5 days per week by her demand at 22 months. Major molecular response was maintained with 300 mg of IM for 3 days per week at 77 months. The intermittent IM therapy might be useful for CML patients who cannot tolerate the standard dose of IM.
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R-CHOP therapy alone in limited stage diffuse large B-cell lymphoma.
Br. J. Haematol.
PUBLISHED: 02-25-2013
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Long-term observation has identified a pattern of continuing relapse in limited stage diffuse large B-cell lymphoma (DLBCL) treated by three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) plus involved-field irradiation. We retrospectively analysed 190 untreated patients with limited stage DLBCL treated by R-CHOP alone. All the patients were scheduled to undergo primary therapy with six cycles of full-dose R-CHOP. Cases with a dose reduction of more than 20% were excluded from the study. Additional local irradiation was allowed in patients with partial response (PR). Five patients received additional local irradiation after PR at the end of the R-CHOP therapy. The median observation period was 52 months. Median age at diagnosis was 63 years. The responses to therapy were 180 complete responses, eight PR, and two progression of disease (PD). The 5-year progression-free survival and 5-year overall survival rates were 84% and 90%, respectively, both in plateau. During the observation period, 29 patients experienced PD. The progression sites were the primary sites in 15 patients, outside the primary sites in 10, and undetermined in four patients. These results suggest that the standard strategy of three cycles of R-CHOP followed by involved-field radiotherapy for limited stage DLBCL could be effectively replaced by six cycles of R-CHOP alone.
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Preoperative chemotherapy is effective for stage III resectable non--small-cell lung cancer: metaanalysis of 16 trials.
Clin Lung Cancer
PUBLISHED: 02-20-2013
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The benefit of preoperative chemotherapy for resectable non-small-cell lung cancer is still controversial.
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Successful treatment with third stem cell transplant from an allogeneic donor for a patient with relapsed diffuse large B-cell lymphoma.
Exp Clin Transplant
PUBLISHED: 02-20-2013
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High-dose chemotherapy with autologous stem cell transplant is commonly used for diffuse large B-cell lymphoma that recurs after successful salvage chemotherapy. However, in patients in whom the disease recurs again, the prognosis is poor. A 40-year-old woman who underwent allogeneic stem cell transplant 4 years after autologous stem cell transplant developed recurrent diffuse large B-cell lymphoma 3 years after the initial autologous stem cell transplant. She then underwent reduced-intensity hematopoietic stem cell transplant from a human leukocyte antigen-matched, unrelated donor who was not the previous autologous stem cell transplant donor. She achieved a long survival (328 days after the reduced-intensity hematopoietic stem cell transplant and 1844 days after the first allogeneic transplant). A second allogenic transplant may provide survival benefits in a proportion of patients with malignant lymphoma recurring after allogeneic transplant, although careful consideration is required because of the high risk of treatment-related mortality with second allogenic transplant.
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Upfront autologous stem cell transplantation for untreated high-risk diffuse large B-cell lymphoma in patients up to 60 years of age.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 02-14-2013
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Although rituximab added to CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) is the standard chemotherapy for untreated DLBCL, its therapeutic effect is limited in younger patients with high-intermediate risk or high-risk disease according to the age-adjusted international prognostic index. In fact, the efficacy and safety of HDT plus rituximab followed by ASCT for such patients remain unclear.
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Long-acting beta-agonists reduce mortality of patients with severe and very severe chronic obstructive pulmonary disease: a propensity score matching study.
Respir. Res.
PUBLISHED: 01-31-2013
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Long-acting beta-agonists were one of the first-choice bronchodilator agents for stable chronic obstructive pulmonary disease. But the impact of long-acting beta-agonists on mortality was not well investigated.
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Successful treatment of a pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia.
Int. J. Hematol.
PUBLISHED: 01-15-2013
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The management of acute leukemia during pregnancy is challenging. Delays in treatment for acute leukemia can adversely affect maternal prognosis, but chemotherapy during pregnancy may induce severe adverse effects on the fetus. Here, we report a case of a pregnant woman with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL) who underwent remission induction therapy and successfully delivered a live infant after chemotherapy. The case is a 36-year-old woman diagnosed with Ph(+)ALL in the 27th week of pregnancy. She underwent remission induction therapy including daunorubicin, vincristine, cyclophosphamide, and prednisolone. Imatinib was not used in the induction therapy. She delivered the infant after one course of chemotherapy. The infant and the patient are both alive now, without any major complications.
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Prognostic significance of programmed cell death-1-positive cells in follicular lymphoma patients may alter in the rituximab era.
Eur. J. Haematol.
PUBLISHED: 01-11-2013
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Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ? 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.
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Genome-wide association analysis identifies new susceptibility loci for Behçets disease and epistasis between HLA-B*51 and ERAP1.
Nat. Genet.
PUBLISHED: 01-06-2013
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Individuals with Behçets disease suffer from episodic inflammation often affecting the orogenital mucosa, skin and eyes. To discover new susceptibility loci for Behçets disease, we performed a genome-wide association study (GWAS) of 779,465 SNPs with imputed genotypes in 1,209 Turkish individuals with Behçets disease and 1,278 controls. We identified new associations at CCR1, STAT4 and KLRC4. Additionally, two SNPs in ERAP1, encoding ERAP1 p.Asp575Asn and p.Arg725Gln alterations, recessively conferred disease risk. These findings were replicated in 1,468 independent Turkish and/or 1,352 Japanese samples (combined meta-analysis P < 2 × 10(-9)). We also found evidence for interaction between HLA-B*51 and ERAP1 (P = 9 × 10(-4)). The CCR1 and STAT4 variants were associated with gene expression differences. Three risk loci shared with ankylosing spondylitis and psoriasis (the MHC class I region, ERAP1 and IL23R and the MHC class I-ERAP1 interaction), as well as two loci shared with inflammatory bowel disease (IL23R and IL10) implicate shared pathogenic pathways in the spondyloarthritides and Behçets disease.
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Pathology of asthma.
Front Microbiol
PUBLISHED: 01-01-2013
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Asthma is a serious health and socioeconomic issue all over the world, affecting more than 300 million individuals. The disease is considered as an inflammatory disease in the airway, leading to airway hyperresponsiveness, obstruction, mucus hyper-production and airway wall remodeling. The presence of airway inflammation in asthmatic patients has been found in the nineteenth century. As the information in patients with asthma increase, paradigm change in immunology and molecular biology have resulted in an extensive evaluation of inflammatory cells and mediators involved in the pathophysiology of asthma. Moreover, it is recognized that airway remodeling into detail, characterized by thickening of the airway wall, can be profound consequences on the mechanics of airway narrowing and contribute to the chronic progression of the disease. Epithelial to mesenchymal transition plays an important role in airway remodeling. These epithelial and mesenchymal cells cause persistence of the inflammatory infiltration and induce histological changes in the airway wall, increasing thickness of the basement membrane, collagen deposition and smooth muscle hypertrophy and hyperplasia. Resulting of airway inflammation, airway remodeling leads to the airway wall thickening and induces increased airway smooth muscle mass, which generate asthmatic symptoms. Asthma is classically recognized as the typical Th2 disease, with increased IgE levels and eosinophilic inflammation in the airway. Emerging Th2 cytokines modulates the airway inflammation, which induces airway remodeling. Biological agents, which have specific molecular targets for these Th2 cytokines, are available and clinical trials for asthma are ongoing. However, the relatively simple paradigm has been doubted because of the realization that strategies designed to suppress Th2 function are not effective enough for all patients in the clinical trials. In the future, it is required to understand more details for phenotypes of asthma.
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[A case of IgG4-related disease with deterioration in pulmonary and pituitary involvements during a 10-year clinical course of inflammatory pseudotumor].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 12-23-2011
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A 71-year-old man underwent pleural biopsy due to left pleural effusion and pleural thickening in August, 2001. An inflammatory pseudotumor (IPT) was diagnosed, and therefore systemic oral steroid therapy (prednisolone [PSL] 30 mg/day) was initiated. However, after tapering PSL to 7.5 mg/day, a complication of secondary central diabetes insipidus due to hypophysitis developed in 2008. As his pulmonary condition deteriorated over time and he began to experience exertional dyspnea, he was admitted to our hospital for re-evaluation of the disease in October, 2010. High-resolution CT (HRCT) revealed pulmonary involvements distributed in the interstitium and a high serum IgG4 level (240 mg/dl). Upon re-evaluating the pleural biopsy specimens of the first visit, we found lymphoplasmacytic-type IPT with approximately 10% IgG4-positive plasma cells in the affected areas. After increasing the PSL dose up to 0.6 mg/kg/day, his serum IgG4 levels decreased, his dyspnea improved, and the radiological findings of his pulmonary and pituitary involvements improved. This case was diagnosed as lymphoplasmacytic type IPT which appeared to be highly homologous with IgG4-related disease due to high serum levels of IgG4, pituitary involvements and the observed efficacy of PSL.
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Central nervous system event in patients with diffuse large B-cell lymphoma in the rituximab era.
Cancer Sci.
PUBLISHED: 11-29-2011
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Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate the risk of CNS events in patients with diffuse large B-cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B-cell lymphoma who underwent primary therapy with R-CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15-91 years). We noted 82 CNS events (6.7%) and the cumulative 5-year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2-year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk [RR] 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further.
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Severe obliterative bronchitis associated with Stevens-Johnson syndrome.
Intern. Med.
PUBLISHED: 11-15-2011
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We report a case of Stevens-Johnson syndrome (SJS) in which the patient had been diagnosed with severe obliterative bronchitis. A 29-year-old woman was admitted with a high fever and a widespread vesicular rash. She was diagnosed with SJS and betamethasone administration was started. After one month, her vesicular skin rash improved; however, she developed respiratory failure and was assisted with mechanical ventilation. Computed tomography of the chest demonstrated a hyperlucent lung with narrowing of the peripheral vessels. Bronchoscopy revealed an occlusion of the bronchus when the patient exhaled. The flow-volume curve revealed a severe obstructive pattern. The patient was diagnosed with obliterative bronchitis following SJS. She was treated with a bronchodilator and steroids, but could not breathe adequately without the ventilator. During the following year, her PaCO(2) increased to 100 torr and her heart function also continued to worsen. Despite intensive treatment, she died one year and seven months after the onset of SJS. In SJS and toxic epidermal necrolysis (TEN) patients, chronic pulmonary complications are rare, but there is no effective therapy for obliterative bronchitis following SJS/TEN. Therefore, early awareness of this condition is needed and lung transplantation must be considered at an early stage of this disease.
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[Two cases of juvenile-onset and adult-onset recurrent respiratory papillomatosis].
Nihon Kokyuki Gakkai Zasshi
PUBLISHED: 11-12-2011
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We recently experienced one each of 2 types of recurrent respiratory papillomatosis (RRP). Case 1 (juvenile-onset type): A 30-year-old woman presenting with bloody sputum and large tumors with cavities on her chest Xray film, was referred to our hospital. She had been diagnosed with laryngeal papillomatosis when she was three years old. According to our bronchoscopical examination biopsy, she was diagnosed with squamous cell carcinoma of the lung in addition to papillomatosis of the trachea and bronchus. Although chemotherapy was performed, she died 2 years after the diagnosis of lung cancer without any distinct treatment efficacy. Case 2 (adult-onset type): A 43 year-old woman presenting with fever and dry cough visited our hospital. Chest CT revealed that there was narrowing of bilateral main bronchi and hilar lymphadenopathy. Bronchoscopic examination revealed diffuse papilloma distributed extensively from the trachea to bilateral main bronchi. However, she recovered spontaneously in 6 months and has remained stable without recurrence. Both cases were diagnosed with RRP based on the separation of HPV in case 1 and pathological findings of koilocytosis in case 2. Case 1 was complicated with squamous cell carcinoma of the lung in the clinical course, presumably due to occurrence of malignant conversion of papillomatosis. Since RRP is a rare but refractory disease, novel effective treatment is necessary.
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Pretransplant serum ferritin has a prognostic influence on allogeneic transplant regardless of disease risk.
Leuk. Lymphoma
PUBLISHED: 10-24-2011
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A multicenter retrospective analysis of the influence of pretransplant serum ferritin (SF) was performed in 261 adult recipients of allogeneic hematopoietic stem cell transplant (allo-HSCT), including 159 patients with acute myeloid leukemia (AML), 66 with acute lymphoid leukemia (ALL) and 36 with myelodysplastic syndrome (MDS). Patients were divided into subgroups according to the pretransplant SF level [< 1000 ng/mL (low) vs. ? 1000 ng/mL (high)] and disease status at transplant. A high SF level was significantly associated with high disease risk (p = 0.041), but pretransplant SF and disease risk were independent significant prognostic factors for overall survival (OS), disease-free survival (DFS) and non-relapse mortality rate (NRM) on multivariate analysis. The high-SF group showed a worse outcome than the low-SF group among both standard-risk patients (OS: 54% vs. 64%, p = 0.043; DFS: 46% vs. 57%, p = 0.031) and high-risk patients (OS: 16% vs. 35%, p = 0.001; DFS: 15% vs. 34%, p = 0.001). In conclusion, a high SF at transplant adversely influences the outcome of allo-HSCT regardless of disease risk in patients with acute leukemia and MDS.
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The impact of the dose of natural killer cells in the graft on severe acute graft-versus-host disease after unrelated bone marrow transplantation.
Leuk. Res.
PUBLISHED: 09-17-2011
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The impact of lymphocyte subpopulations on the outcome of bone marrow transplantation (BMT) remains uncertain. We investigated the relationship between the lymphocyte subpopulations of bone marrow grafts and the outcome of BMT. A total of 121 patients who underwent BMT at Kanagawa Cancer Center between 2000 and 2009 were analyzed. Grade III-IV acute graft-versus-host disease (GVHD) occurred in 35.9% of patients who received unrelated BMT with a CD56 cell dose ?2.80×10(6)/kg versus only 9.7% of patients with a CD56 cell dose >2.80×10(6)/kg (P=0.017). In patients receiving related BMT, the cumulative incidence of grade III-IV acute GVHD did not differ significantly in relation to the CD56 cell dose. On multivariate analysis, older donor age (hazard ratio (HR): 1.09, 95% confidence interval (CI): 1.03-1.15, P=0.004) and a high dose of CD56 cells (>2.80×10(6)/kg) (HR: 0.15, 95%CI: 0.03-0.92, P=0.040) were significant determinants of grade III-IV acute GVHD after unrelated BMT. None of the lymphocyte subpopulations had a significant impact on the outcome of transplantation, including the rate of neutrophil engraftment, relapse, relapse-free mortality, and overall survival. Our findings suggest that a high natural killer cell dose prevents severe acute GVHD after unrelated BMT, while sparing the graft-versus-leukemia effect.
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Therapeutic response of patients with adult Stills disease to biologic agents: multicenter results in Japan.
Mod Rheumatol
PUBLISHED: 09-15-2011
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The efficacy of biologics in treating adult Stills disease (ASD) is suggested, but the information is still lacking and the validation is insufficient. To determine the efficacy of several biologic agents in refractory ASD in Japan, a multicenter survey was performed.
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A New Three-Way Translocation t(4;11;7)(q21;q23;q22) in a Mixed-Phenotype Acute Leukemia.
Case Rep Hematol
PUBLISHED: 07-20-2011
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A 68-year-old man was admitted to our hospital in September 2008 because of a left-sided chest pain. Bone marrow examination showed that 85.5% of leukemic cells were positive for myeloperoxidase (MPO) and were negative for esterase stain. Flow cytometric analysis (FCM) revealed the expression of CD19, CD79a, CD13, CD33, CD34, and HLA-DR on the blasts. Cytogenetic analysis of bone marrow cells using the G-banding technique demonstrated 47, XY, +X, t(4;11;7)(q21;q23;q22) in five of the 20 analyzed cells. The patient was diagnosed as having mixed biphenotypic acute leukemia according to the European Group for Immunologic Classification of Leukemia criteria. Mixed-phenotype acute leukemia is a rare, difficult to diagnose entity. Whether patients with mixed-phenotype acute leukemia should be treated with regimens designed for acute myeloid leukemia, acute lymphoblastic leukemia, or both remains unclear.
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Prognostic impact of extranodal involvement in diffuse large B-cell lymphoma in the rituximab era.
Cancer
PUBLISHED: 07-16-2011
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Extranodal involvement is considered a poor prognostic factor for patients with diffuse large B-cell lymphoma (DLBCL); however, the prognostic impact of specific sites of involvement has not been fully elucidated.
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Clinical characteristics of neuro-Behcets disease in Japan: a multicenter retrospective analysis.
Mod Rheumatol
PUBLISHED: 07-05-2011
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To delineate the clinical characteristics of neuro-Behçets disease (NBD), a multicenter retrospective survey was performed in BD patients who had presented any neurological manifestations between 1988 and 2008. The diagnosis of acute NBD, chronic progressive (CP) NBD, and non-NBD was confirmed by retrospective review of clinical records. Data on a total of 144 patients were collected; 76 with acute NBD, 35 with CP NBD, and 33 with non-NBD. High-intensity lesions on T2-weighted magnetic resonance imaging (MRI) were found in 60.5% of the patients with acute NBD, 54.2% with CP NBD, and 42.4% with non-NBD, whereas brainstem atrophy was observed in 7.5% with acute NBD, 71.4% with CP NBD, and 9.0% with non-NBD. The cerebrospinal fluid (CSF) cell count was prominently elevated in patients with acute NBD, but was normal in about 15% of those with CP NBD. The sensitivity and specificity of the CSF cell count for the diagnosis of acute NBD versus non-NBD were 97.4 and 97.0%, respectively (cut-off 6.2/mm(3)). The sensitivity and specificity of CSF interleukin (IL)-6 for the diagnosis of CP NBD versus the recovery phase of acute NBD were 86.7 and 94.7%, respectively (cut-off 16.55 pg/ml). The results indicate that elevation of the CSF cell count and CSF IL-6 and the presence of brainstem atrophy on MRI are useful for the diagnosis of NBD.
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JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.