JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
Subarachnoid hemorrhage-negative terson syndrome after balloon-assisted coil embolization in a patient with underlying antiphospholipid antibody syndrome.
Retin Cases Brief Rep
PUBLISHED: 11-06-2014
Show Abstract
Hide Abstract
To report subarachnoid hemorrhage-negative Terson syndrome after coil embolization of an unruptured intracranial aneurysm in a patient with underlying antiphospholipid syndrome.
Related JoVE Video
How we manage JAK inhibition in allogeneic transplantation for myelofibrosis.
Eur. J. Haematol.
PUBLISHED: 09-22-2014
Show Abstract
Hide Abstract
Hematopoietic stem cell transplantation (HCT) is currently the only curative treatment for myelofibrosis (MF), but this option is complicated by high incidences of associated morbidity and mortality. Ruxolitinib, a Janus activated kinase (JAK) 1/2 inhibitor, has proven to be beneficial in reduction of splenomegaly, improvement of constitutional symptoms, and possibly in overall survival. However, use of JAK inhibitors in the peri-transplant period has been complicated by unpredictable response, return of MF symptoms or cytokine storm reaction upon discontinuation, and lack of long term response data. This review considers the current limited available data on JAK inhibitor use prior to HCT, including common side effects and possible impact of severe adverse events on discontinuation of the drug. We provide our experience and recommendations regarding use of JAK inhibition in patients undergoing HCT. Additional studies are needed to determine the optimal schedule of JAK inhibitors in the transplant protocols and their impact on engraftment, graft versus host disease, and survival. This article is protected by copyright. All rights reserved.
Related JoVE Video
Nonpermissive HLA-DPB1 mismatch increases mortality after myeloablative unrelated allogeneic hematopoietic cell transplantation.
Blood
PUBLISHED: 08-26-2014
Show Abstract
Hide Abstract
We examined current outcomes of unrelated donor allogeneic hematopoietic cell transplantation (HCT) to determine the clinical implications of donor-recipient HLA matching. Adult and pediatric patients who had first undergone myeloablative-unrelated bone marrow or peripheral blood HCT for acute myelogenous leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, and myelodysplastic syndrome between 1999 and 2011 were included. All had high-resolution typing for HLA-A, -B, -C, and -DRB1. Of the total (n = 8003), cases were 8/8 (n = 5449), 7/8 (n = 2071), or 6/8 (n = 483) matched. HLA mismatch (6-7/8) conferred significantly increased risk for grades II to IV and III to IV acute graft vs host disease (GVHD), chronic GVHD, transplant-related mortality (TRM), and overall mortality compared with HLA-matched cases (8/8). Type (allele/antigen) and locus (HLA-A, -B, -C, and -DRB1) of mismatch were not associated with overall mortality. Among 8/8 matched cases, HLA-DPB1 and -DQB1 mismatch resulted in increased acute GVHD, and HLA-DPB1 mismatch had decreased relapse. Nonpermissive HLA-DPB1 allele mismatch was associated with higher TRM compared with permissive HLA-DPB1 mismatch or HLA-DPB1 match and increased overall mortality compared with permissive HLA-DPB1 mismatch in 8/8 (and 10/10) matched cases. Full matching at HLA-A, -B, -C, and -DRB1 is required for optimal unrelated donor HCT survival, and avoidance of nonpermissive HLA-DPB1 mismatches in otherwise HLA-matched pairs is indicated.
Related JoVE Video
Hospital acquired urinary tract infection by multidrug-resistant Brevundimonas vesicularis.
Indian J Pathol Microbiol
PUBLISHED: 08-15-2014
Show Abstract
Hide Abstract
Infections caused by Brevundimonas vesicularis, a nonfermenting Gram-negative bacterium, are very rare. Here, we report the first case of multidrug-resistant hospital acquired urinary tract infection by B. vesicularis. Patient was successfully treated with antimicrobial therapy with piperacillin-tazobactam and amikacin.
Related JoVE Video
Wedgeless 'V' shaped distal femoral osteotomy with internal fixation for genu valgum in adolescents and young adults.
Acta Orthop Belg
PUBLISHED: 08-06-2014
Show Abstract
Hide Abstract
The treatment of angular malalignment includes restoration of normal mechanical axis alignment and joint orientation.The supracondylar wedgeless distal femoral 'V' osteotomy, as a treatment modality, is sparsely explored in the literature. This study was conducted at a tertiary level teaching referral hospital from October 2010 to September 2012. Forty six lower limbs (in 30 patients) were operated with a wedgeless 'V' osteotomy that was fixed with a buttress 'L' plate. The pre-operative deformity, post-operative correction and knee range of movement were noted. Mobilisation was started at 3 weeks after surgery and full weight-bearing was allowed at 3 months. The knee score by Bostman et al. was used for functional outcome. The mean age of the patients in our study was 16.9 years (range: 15 years to 23 years). The patients were followed up for a mean period of 19.8 months (range, 15 months to 29 months). The mean radiological tibiofemoral angle was 22.2 degrees (range, 16 degrees to 29 degrees) before surgery, that improved to a mean postoperative value of 5.1 degrees (range, 0 degrees to 10 degrees) (p < 0.001). The mean preoperative lateral distal femoral angle was 79.23 degrees that improved to a mean value of 89.13 degrees after surgery (p < 0.001). The mean mechanical axis deviation was 19.56 mm before surgery that improved to a mean postoperative value of 3.7 mm (p < 0.001). All patients reached a correction of the deformity and 44 cases out of a total of 46 had an excellent functional outcome, 2 patients had a good functional outcome. None had an unsatisfactory outcome. Two cases had a deep wound infection that subsided after implant removal. None of the cases had other complications. The distal femoral 'V' shaped osteotomy is a simple procedure for the correction of genu valgum in individuals nearing skeletal maturity and is easy to perform. It has the advantage of being wedgeless as it does not cause limb length discrepancy. Internal fixation helps in early rehabilitation after surgery.
Related JoVE Video
Cutaneous Mycobacterium fortuitum Infection: Successfully Treated with Amikacin and Ofloxacin Combination.
Indian J Dermatol
PUBLISHED: 07-30-2014
Show Abstract
Hide Abstract
Cutaneous infections caused by atypical mycobacteria are uncommon and the diagnosis can be missed unless there is strong clinical suspicion supported by laboratory confirmation. We report a case of chronic discharging sinus caused by Mycobacterium fortuitum in a young healthy immunocompetent individual. The patient recovered completely following amikacin and ofloxacin therapy.
Related JoVE Video
Controversies and dilemmas in allogeneic transplantation for myelofibrosis.
Best Pract Res Clin Haematol
PUBLISHED: 07-19-2014
Show Abstract
Hide Abstract
JAK1/2 inhibitors have broadened the therapeutic options in myelofibrosis. Though not curative, they result in a meaningful clinical benefit with relatively fewer side effects. In contrast, allogeneic hematopoietic cell transplantation (HCT) is a potentially curative option, but is associated with significant morbidity and mortality. Hence, an important question is the optimal timing of HCT in the era of JAK inhibitors. Timing of HCT is a crucial decision, and need to be individualized based on the personal preferences and goals of therapy; in addition to patient, disease, and transplant related factors. Risk stratification by the currently established prognostic scoring systems need to be further refined by incorporation of prognostically significant mutations to guide the treatment choices better. Data on use of JAK inhibitors prior to HCT have just started to emerge. We discuss some of the current controversies and dilemmas in transplantation for myelofibrosis based on a few real life scenarios.
Related JoVE Video
MPD-RC 101 prospective study of reduced-intensity allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis.
Blood
PUBLISHED: 06-24-2014
Show Abstract
Hide Abstract
From 2007 to 2011, 66 patients with primary myelofibrosis or myelofibrosis (MF) preceded by essential thrombocythemia or polycythemia vera were enrolled into a prospective phase 2 clinical trial of reduced-intensity allogeneic hematopoietic stem cell transplantation (AHSCT), Myeloproliferative Disorder Research Consortium 101 trial. The study included patients with sibling donors (n = 32) receiving fludarabine/melphalan (FluMel) as a preparative regimen and patients with unrelated donors (n = 34) receiving conditioning with FluMel plus anti-thymocyte globulin (ATG). Patient characteristics in the 2 cohorts were similar. Engraftment occurred in 97% of siblings and 76% of unrelated transplants, whereas secondary graft failure occurred in 3% and 12%, respectively. With a median follow-up of 25 months for patients alive, the overall survival (OS) was 75% in the sibling group (median not reached) and 32% in the unrelated group (median OS: 6 months, 95% confidence interval [CI]: 3, 25) (hazard ratio 3.9, 95% CI: 1.8,8.9) (P < .001). Nonrelapse mortality was 22% in sibling and 59% in unrelated AHSCT. Survival correlated with type of donor, but not with the degree of histocompatibility match, age, or JAK2(V617F) status. In patients with MF with sibling donors, AHSCT is an effective therapy, whereas AHSCT from unrelated donors with FluMel/ATG conditioning led to a high rate of graft failure and limited survival. This trial was registered at www.clinicaltrials.gov as #NCT00572897.
Related JoVE Video
Incidence, Risk Factors, and Long-Term Outcomes of Sclerotic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-09-2014
Show Abstract
Hide Abstract
Sclerotic chronic graft-versus-host disease (sclGVHD) is associated with significant morbidity and a poor quality of life. We reviewed 502 patients diagnosed with chronic GVHD and analyzed the incidence and risk factors of sclGVHD and long-term outcomes and immunosuppressive therapy (IST) cessation in patients with sclGVHD. With a median onset at 18 months the cumulative incidence of sclGVHD was estimated at 22.6% at 5 years (95% confidence interval, 18.6% to 26.8%). Univariate and multivariate analysis identified 2 risk factors for sclGVHD: non-T cell depletion (hazard ratio [HR] 9.09, P < .001) and peripheral blood stem cell (HR 3.87, P < .001). Overall survival (OS) at 5 years was significantly better in the sclGVHD group (88.1%) compared with the non-sclGVHD group (62.7%; P < .001), as were nonrelapse mortality (7.3% versus 21.5% at 5 years) and relapse rates (9.1% versus 19.3% at 5 years). There was no difference in the rate of IST cessation at 5 years (44.8% versus 49.9%, P = .312), but there was a trend of longer IST duration in the sclGVHD group compared with the non-sclGVHD group (median 71.6 months versus 62.9 months). In conclusion, T cell depletion and graft source affect the risk of sclGVHD. SclGVHD did not adversely affect long-term outcomes or IST duration.
Related JoVE Video
A large cutaneous horn of the glans penis: a rare presentation.
Indian J Surg
PUBLISHED: 06-04-2014
Show Abstract
Hide Abstract
Cutaneous horn (cornu cutaneum) is a relatively uncommon lesion consisting of a projectile, conical, dense, hyperkeratotic nodule which resembles the horn of an animal. Cutaneous horns most frequently occur in sun-exposed parts and are typically found in the face and the scalp, but may also occur on the hands, eyelids, nose, chest, neck, shoulder and penis. Their occurrence on the penis is uncommon. We report a 42-year-old man presenting with penile cutaneous horn. The association with malignancy on the penis makes proper identification of these lesions essential. Standard treatment involves local excision, but the presence of malignancy mandates a partial penectomy.
Related JoVE Video
Outcomes of hematopoietic cell transplantation in adult patients with acquired aplastic anemia using intermediate-dose alemtuzumab-based conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-07-2014
Show Abstract
Hide Abstract
Graft-versus-host disease (GVHD) has no therapeutic benefit after hematopoietic cell transplantation (HCT) for patients with acquired aplastic anemia (AA), and its prevention is highly desirable. We designed a conditioning regimen using an intermediate dose of alemtuzumab (50 to 60 mg) and describe our institutional experience of 41 patients who underwent HCT for AA. The median age at HCT was 37 years (range, 17 to 59). The conditioning regimen was high-dose cyclophosphamide (n = 9) or fludarabine based (n = 32). Additional GVHD prophylaxis was with cyclosporine. With a median follow-up of 3.6 years, overall survival at 3 years was 85%. Survival in patients <40 years and ?40 years was 96% and 67%, respectively (P = .04). Graft failure occurred in 4 (10%) patients; 2 primary and 2 secondary. The cumulative incidences of acute (grades 1 to 2) and chronic GVHD were 27% and 15%, respectively. No patients developed grade 3 to 4 acute GVHD or severe chronic GVHD. The following viral complications were frequent: cytomegalovirus reactivation (79%), herpes simplex (18%), varicella zoster (25%), and BK virus hemorrhagic cystitis (8%). The majority of patients had no significant long-term health issues. This intermediate-dose alemtuzumab-based conditioning regimen results in excellent survival with a favorable impact on GVHD and long-term health outcomes, but close monitoring for viral complications is important.
Related JoVE Video
Fluorodeoxyglucose positron emission tomography with computed tomography detects greater metabolic changes that are not represented by plain radiography for patients with osteonecrosis of the jaw.
J. Oral Maxillofac. Surg.
PUBLISHED: 04-08-2014
Show Abstract
Hide Abstract
Imaging is important to identify subclinical changes and for treatment planning in patients with osteonecrosis of the jaw (ONJ) exposed to antiresorptive therapy. The aim of this study was to compare the findings at radiography with those at fluorodeoxyglucose (FDG) positron emission tomography (PET) with computed tomography (CT) for patients with ONJ related to antiresorptive therapy.
Related JoVE Video
Early lymphocyte recovery at 28 d post-transplant is predictive of reduced risk of relapse in patients with acute myeloid leukemia transplanted with peripheral blood stem cell grafts.
Eur. J. Haematol.
PUBLISHED: 04-04-2014
Show Abstract
Hide Abstract
Allogeneic hematopoietic cell transplantation (HCT) is potentially curative for acute myeloid leukemia (AML). Impact of lymphocyte recovery on post-transplant outcomes has been suggested but reports are conflicting. We evaluated the impact of lymphocyte recovery at 28 d post-HCT in 191 AML patients using peripheral blood stem cells as graft. Patients were divided into those with absolute lymphocyte count (ALC) ? 0.5 × 10(9) /L (n = 111, 58%; high ALC group) and those with ALC < 0.5 × 10(9) /L (n = 80, 42%; low ALC group), at day 28 post-transplant. With a median follow-up of 49 months, overall survival (OS) was significantly improved in the high ALC group (59% at 3 yr) vs. patients with low ALC (40% at 3 yr, P = 0.03). Cumulative incidence of relapse (CIR) was significantly lower in the high ALC group (16% at 3 yr) vs. low ALC group (36% at 3 yr, P = 0.001). Multivariable analysis for CIR demonstrated high ALC group as an independent factor decreasing relapse risk (P = 0.03, HR = 0.49, 95% CI = 0.26-0.92). Multivariable analysis for OS and non-relapse mortality did not demonstrate ALC ? 0.5 × 10(9) /L at 28 d post-transplant to be predictive. We conclude that lymphocyte recovery with ALC ? 0.5 × 10(9) /L at day 28 post-transplant is associated with less relapse in AML patients undergoing allogeneic peripheral blood HCT, but without survival benefit.
Related JoVE Video
Spider genomes provide insight into composition and evolution of venom and silk.
Nat Commun
PUBLISHED: 03-31-2014
Show Abstract
Hide Abstract
Spiders are ecologically important predators with complex venom and extraordinarily tough silk that enables capture of large prey. Here we present the assembled genome of the social velvet spider and a draft assembly of the tarantula genome that represent two major taxonomic groups of spiders. The spider genomes are large with short exons and long introns, reminiscent of mammalian genomes. Phylogenetic analyses place spiders and ticks as sister groups supporting polyphyly of the Acari. Complex sets of venom and silk genes/proteins are identified. We find that venom genes evolved by sequential duplication, and that the toxic effect of venom is most likely activated by proteases present in the venom. The set of silk genes reveals a highly dynamic gene evolution, new types of silk genes and proteins, and a novel use of aciniform silk. These insights create new opportunities for pharmacological applications of venom and biomaterial applications of silk.
Related JoVE Video
Clinical Features of Patients With Philadelphia-Negative Myeloproliferative Neoplasms Complicated by Portal Hypertension.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 03-11-2014
Show Abstract
Hide Abstract
Portal hypertension has been reported to afflict 7% to 18% of patients with Philadelphia-negative MPNs, with complications of variceal bleeding and ascites. The clinical features and outcomes of these patients are unclear.
Related JoVE Video
Prolonged orocecal transit time enhances serum bile acids through bacterial overgrowth, contributing factor to gallstone disease.
J. Clin. Gastroenterol.
PUBLISHED: 03-07-2014
Show Abstract
Hide Abstract
Gallstones (GS) are associated with slow intestinal transit but the effect of altered transit time on physiological changes in gastrointestinal tract among GS patients is poorly understood.
Related JoVE Video
Safety and performance of the Penumbra Liberty stent system in a rabbit aneurysm model.
J Neurointerv Surg
PUBLISHED: 02-21-2014
Show Abstract
Hide Abstract
Endovascular treatment of wide necked and large/giant intracranial aneurysms is challenging. The goal of this study was to evaluate the Liberty stent system in the rabbit elastase aneurysm model for 30, 90, and 180 days.
Related JoVE Video
Aluminum phosphide (celphos) poisoning in children: A 5-year experience in a tertiary care hospital from northern India.
Indian J Crit Care Med
PUBLISHED: 02-20-2014
Show Abstract
Hide Abstract
Aluminum phosphide (ALP) (celphos) is an agricultural pesticide commonly implicated in poisoning. Literature pertaining to the clinical manifestations and treatment outcome of its poisoning among children is limited.
Related JoVE Video
Ipsilateral open anterior hip dislocation and open posterior elbow dislocation in an adult.
Chin. J. Traumatol.
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
Open anterior dislocation of the hip is a very rare injury, especially in adults. It is a hyperabduction, external rotation and extension injury. Its combination with open posterior dislocation of the elbow has not been described in English language-based medical literature. Primary resuscitation, debridement, urgent reduction of dislocation, and adequate antibiotic support resulted in good clinical outcome in our patient. At 18 months follow-up, no signs of avascular necrosis of the femoral head or infection were observed.
Related JoVE Video
Janus kinase inhibitors and allogeneic stem cell transplantation for myelofibrosis.
Biol. Blood Marrow Transplant.
PUBLISHED: 02-03-2014
Show Abstract
Hide Abstract
Myelofibrosis (MF) is a manifestation of several disorders of hematopoiesis, collectively referred to as myeloproliferative neoplasms. Allogeneic hematopoietic stem cell transplantation (ASCT) is the only therapy with proven curative potential. However, most patients with MF are in their 6th or 7th decade of life, and only some of these patients have been considered suitable transplantation candidates. The development of reduced-intensity conditioning regimens with limited toxicity has allowed clinicians to offer ASCT to a growing number of older patients. The availability of Janus Kinase (JAK) 1/2 inhibitors allows clinicians to provide symptom relief and improved quality of life for MF patients. These drugs may also affect the decision regarding, in particular, the timing of ASCT. Future studies need to address the role of JAK1/2 inhibitors in patients who are transplantation candidates and determine their role before and, possibly, after transplantation. The identification of indications for the use of JAK1/2 inhibitors in the context of transplantation may lead to new therapeutic strategies for patients with MF.
Related JoVE Video
Predictors of outcome in adults with BCR-ABL negative acute lymphoblastic leukemia treated with a pediatric-based regimen.
Leuk. Res.
PUBLISHED: 01-22-2014
Show Abstract
Hide Abstract
We retrospectively evaluated the outcome of 156 adults age 17-60 with BCR-ABL negative acute lymphoblastic leukemia treated with a pediatric-inspired protocol. The CR rate was 93%; 5-year overall survival (OS) and disease-free survival were 66% and 70%, respectively. Age <34 years and low presenting WBC were independent predictors of favorable OS (p<0.0001). The 5 year OS of patients age <34 and 34-60 presenting with a low WBC were 85% and 57%, respectively; the 5 year OS for those presenting with a high WBC were 57% and 30%, respectively. Cytogenetics and phenotype were not independent predictors of OS.
Related JoVE Video
Identification of pre-leukaemic haematopoietic stem cells in acute leukaemia.
Nature
PUBLISHED: 01-20-2014
Show Abstract
Hide Abstract
In acute myeloid leukaemia (AML), the cell of origin, nature and biological consequences of initiating lesions, and order of subsequent mutations remain poorly understood, as AML is typically diagnosed without observation of a pre-leukaemic phase. Here, highly purified haematopoietic stem cells (HSCs), progenitor and mature cell fractions from the blood of AML patients were found to contain recurrent DNMT3A mutations (DNMT3A(mut)) at high allele frequency, but without coincident NPM1 mutations (NPM1c) present in AML blasts. DNMT3A(mut)-bearing HSCs showed a multilineage repopulation advantage over non-mutated HSCs in xenografts, establishing their identity as pre-leukaemic HSCs. Pre-leukaemic HSCs were found in remission samples, indicating that they survive chemotherapy. Therefore DNMT3A(mut) arises early in AML evolution, probably in HSCs, leading to a clonally expanded pool of pre-leukaemic HSCs from which AML evolves. Our findings provide a paradigm for the detection and treatment of pre-leukaemic clones before the acquisition of additional genetic lesions engenders greater therapeutic resistance.
Related JoVE Video
Validation of National Institutes of Health global scoring system for chronic graft-versus-host disease (GVHD) according to overall and GVHD-specific survival.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-10-2014
Show Abstract
Hide Abstract
A new severity grading system for graft-versus-host disease (GVHD) was established by the National Institutes of Health (NIH) consensus criteria (NCC). However, its prognostic value still needs to be validated. Four hundred twenty-five consecutive patients who survived beyond 100 days after allogeneic stem cell transplantation were reviewed and reclassified using NCC. GVHD-specific survival (GSS) and cumulative incidence of relapse were compared according to the NIH global score at the onset and peak of chronic GVHD (cGVHD). Of 346 patients with cGVHD diagnosed by the Revised Seattle Criteria, 317 patients were reclassified according to the NCC as classic cGVHD (n = 144) and overlap syndrome (n = 173). The NIH global scores at onset were mild (43.2%), moderate (42.3%), and severe (14.5%), whereas more moderate (55.5%) and severe (31.6%) cGVHD was observed at the peak of cGVHD. With a median follow-up duration of 34 months, the 5-year GSS was significantly worse for the severe group than the moderate/mild groups at onset and at peak: 50.9% ± 7.8% versus 89.7% ± 3.2% versus 93.5% ± 2.4% at onset (P < .001) and 69.1% ± 5.2% versus 93.2% ± 2.1% versus 97.3% ± 2.7% at peak (P < .001). Severe NIH global score at onset and peak were confirmed as a poor prognostic factor for GSS in multivariate analysis. The cumulative incidence of relapse did not differ among the severity groups at onset or peak. In conclusion, the new NIH global scoring system was shown to differentiate a high-risk group of patients (with severe grade cGVHD) in terms of long-term transplant outcomes.
Related JoVE Video
A retrospective observational study of leucoreductive strategies to manage patients with acute myeloid leukaemia presenting with hyperleucocytosis.
Br. J. Haematol.
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
Acute myeloid leukaemia (AML) patients with hyperleucocytosis have higher early mortality, lower complete remission (CR) and overall survival (OS). Whether different pre-induction leucoreduction strategies can improve outcome is unknown. A single centre retrospective cohort study was conducted on AML patients with a white blood cell count (WBC) >100 × 10(9) /l between 1987 and 1997, and on all AML patients between 1998 and 2006, to determine (a) the effect of four different leucoreductive strategies (leukapheresis, hydroxycarbamide, leukapheresis and hydroxycarbamide or no pre-induction leucoreduction) on early (day 28) mortality, CR, and OS; and (b) whether a high presenting WBC remains a negative predictor of OS in patients surviving induction (first 28 d). In the 1998-2006 cohort (n = 702), higher WBC was associated with higher early mortality and lower OS but its effects were greatly diminished in patients who survived the first 28 d (Hazard Ratio 1·094 vs. 1·002). A WBC of 34·1 × 10(9) /l had the highest sensitivity (75·6%) and specificity (67·4%) for early mortality. None of the four leucoreduction strategies differed significantly in early mortality, CR, or OS in patients with WBC>100 × 10(9) /l (n = 166). The number of leucostatic signs was a significant predictor of early mortality (P < 0·0001) and OS (P = 0·0007). The results suggest that AML patients with hyperleucocytosis should be induced, if eligible, without pre-induction leucoreduction.
Related JoVE Video
Management of cytopenias in patients with myelofibrosis treated with ruxolitinib and effect of dose modifications on efficacy outcomes.
Onco Targets Ther
PUBLISHED: 12-17-2013
Show Abstract
Hide Abstract
Ruxolitinib is an oral Janus kinase (JAK) 1/JAK2 inhibitor approved in the US for the treatment of intermediate-or high-risk myelofibrosis (MF). Because thrombopoietin and erythropoietin signal through JAK2, dose-dependent cytopenias are expected with treatment. In the COMFORT-I (COntrolled Myelofibrosis study with ORal JAK inhibitor Treatment I) trial, these cytopenias were effectively managed with dose adjustments. These analyses were conducted to evaluate the relationship between ruxolitinib titrated doses and changes in platelet count and hemoglobin level as well as efficacy measures.
Related JoVE Video
Additional Diagnostic Value of Integrated Analysis of Cardiac CTA and SPECT MPI Using the SMARTVis System in Patients with Suspected Coronary Artery Disease.
J. Nucl. Med.
PUBLISHED: 12-12-2013
Show Abstract
Hide Abstract
CT angiography (CTA) and SPECT myocardial perfusion imaging (MPI) are complementary imaging techniques to assess coronary artery disease (CAD). Spatial integration and combined visualization of SPECT MPI and CTA data may facilitate correlation of myocardial perfusion defects and subtending coronary arteries and thus offer additional diagnostic value over either stand-alone or side-by-side interpretation of the respective datasets from the 2 modalities. In this study, we investigated the additional diagnostic value of a software-based CTA/SPECT MPI image fusion system over conventional side-by-side analysis in patients with suspected CAD.
Related JoVE Video
Spectroscopic correlation and role of Azathioprine in long-term remission in patients of Hashimoto encephalopathy.
Ann Indian Acad Neurol
PUBLISHED: 10-09-2013
Show Abstract
Hide Abstract
Hashimoto encephalopathy remains a Rubiks cube for the present generation of clinical research. Myriad presentations have been noted, and observations recorded in few subgroups of patients have gone on only to be trashed by a second group of patients with a completely different clinical profile. Steroids have been traditionally held to be the treatment for this condition, but long-term side effects associated with it limits its use. Although multiple drugs have been tried, yet there exists no data for their long-term efficacy in maintaining remission. No radiological findings have been consistently associated with this condition. We report the use of azathioprine in maintaining long-term remission in one such patient with Hashimoto encephalopathy and the presence of lactate peak in magnetic resonance spectroscopy of the patient, which showed dramatic regression with institution of immunosuppression.
Related JoVE Video
Chronic meningitis with multiple cranial neuropathies: A rare initial presentation of Wegeners granulomatosis.
Ann Indian Acad Neurol
PUBLISHED: 10-09-2013
Show Abstract
Hide Abstract
Wegeners granulomatosis (WG) is a systemic necrotizing vasculitis that affects the small blood vessels. It mainly affects the upper and lower respiratory tract and kidneys. Central nervous system (CNS) involvement is rare, and has been reported only in about 8% of cases during the course of illness. Initial presentation with neurologic affection, particularly chronic hypertrophic meningitis is very unusual. We report the case of a 34 year old male who presented with chronic hypertrophic meningitis and multiple cranial nerve involvement as the initial manifestation, without respiratory and renal symptoms. This case highlights the difficulties in diagnosing a rare disease with rarer presentation, and at the same time illustrates that Wegeners granulomatosis should be considered in the differential diagnosis of chronic meningitis.
Related JoVE Video
Limited benefit of pentostatin salvage therapy for steroid-refractory grade III-IV acute graft-versus-host disease.
Clin Transplant
PUBLISHED: 09-23-2013
Show Abstract
Hide Abstract
Corticosteroid-refractory (SR) acute graft-versus-host disease (aGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation. Multiple agents have been evaluated in this setting, but the benefit of pentostatin has not been described well. We report a single-center experience of pentostatin salvage therapy for SR aGVHD. Fifteen patients received pentostatin for SR aGVHD from March 2005 till March 2010 after failure to respond to methylprednisolone ?2 mg/kg/d for at least seven d. All patients had grade III-IV aGVHD prior to pentostatin therapy. Thirteen (87%), 10 (67%), and six (40%) patients had gastrointestinal (GI), skin, and liver involvement of aGVHD, respectively. Pentostatin was given at a median of 33 d after steroid therapy initiation. The dose of pentostatin was 1.4 mg/m(2) daily for three d, repeated every two wk. Eight (53%) patients also received additional therapies. Complete responses were noted in two patients (both in skin). However, one patient relapsed and did not respond to additional salvage treatment. Partial responses were seen in three patients. Fourteen died of GVHD-related causes. This study suggested that pentostatin is of limited benefit in the treatment for SR grade III-IV aGVHD.
Related JoVE Video
Depleted TGF-?1 levels in end stage renal disease patients from North India.
Gene
PUBLISHED: 09-19-2013
Show Abstract
Hide Abstract
End stage renal disease is a clinical state that extends from chronic renal failure and is marked by an irreversible loss of renal function. TGF-?1 mediated renal fibrosis is a common pathology implicated in this form of kidney disease. In this study circulating protein and mRNA levels of TGF-?1 cytokine were investigated among ESRD patients and respective controls from North India. Physician diagnosed 192 ESRD patients, on hemodialysis, and 130 normal controls participated in the present study. TGF-?1 circulating levels were measured by ELISA and its expression was quantified using competitive-PCR. Mean TGF-?1 protein levels were 2.7-fold lower in ESRD patients as compared to normal controls (p<0.001). Additionally, TGF-?1 mRNA transcripts of this cytokine were also significantly lower in the diseased population compared to controls (p<0.001). These results imply that TGF-?1 has not played its anticipated pro-fibrotic role and anti-inflammatory function in the studied population.
Related JoVE Video
Spontaneous hemorrhage of a facial neurofibroma: endovascular embolization before surgical intervention.
J Craniofac Surg
PUBLISHED: 09-17-2013
Show Abstract
Hide Abstract
A 50-year-old man with neurofibromatosis type 1 presented to the emergency department after a spontaneous hemorrhage into a facial plexiform neurofibroma. An emergent selective angiography of the external carotid artery was performed with Onyx embolization of the origin of the internal maxillary artery as well as the superficial temporal artery to minimize arterial bleeding during the subsequent operative hematoma evacuation. This technique was aimed to control blood loss during the surgical procedure and reduce the amount of transfusion product required for resuscitation. This technique provides a viable option to control potentially life-threatening arterial bleeding in emergent settings.
Related JoVE Video
Efficacy, safety and survival with ruxolitinib in patients with myelofibrosis: results of a median 2-year follow-up of COMFORT-I.
Haematologica
PUBLISHED: 09-13-2013
Show Abstract
Hide Abstract
COMFORT-I is a randomized, double-blind, placebo-controlled trial of the Janus kinase 1/Janus kinase 2 inhibitor ruxolitinib in 309 patients with intermediate-2 or high-risk myelofibrosis. This analysis of COMFORT-I describes the long-term efficacy and safety of ruxolitinib (median follow-up, 2 years). Spleen volume was measured by magnetic resonance imaging, and quality of life was evaluated using the EORTC QLQ-C30. Overall survival was determined according to randomized treatment group. At the time of this analysis, 100 of 155 patients randomized to ruxolitinib were still receiving treatment. All patients randomized to placebo crossed over to ruxolitinib or discontinued within 3 months of the primary analysis (median time to crossover, 41 weeks). Mean spleen volume reductions in the ruxolitinib group were 31.6% at week 24 and 34.9% at week 96; improvements in quality of life measures were also maintained. Improved survival was observed for ruxolitinib (n=27 deaths) versus placebo (n=41 deaths) (hazard ratio=0.58; 95% confidence interval: 0.36, 0.95; P=0.03). The incidence of new-onset grade 3 or 4 anemia and thrombocytopenia decreased over time to levels observed in patients receiving placebo. These data indicate that ruxolitinib treatment provides durable reductions in spleen volume and improvements in quality of life and suggest a continued survival advantage for ruxolitinib over placebo.
Related JoVE Video
The benefit of allogeneic transplantation in patients age ?60 years with acute myeloid leukemia is limited to those in first complete remission at the time of transplant.
Biol. Blood Marrow Transplant.
PUBLISHED: 08-27-2013
Show Abstract
Hide Abstract
We evaluated the impact of age and remission status on 242 consecutive patients that underwent allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) in our program between 1999 and 2011. Median age of all patients was 48 years (range 18-71). Based on age and remission status, patients were divided into 4 groups: CR1 age <60 years (n=116); CR2 age <60 years (n=78), CR1 age ?60 years (n=32) and CR2 age ?60 years (n=16). Donors were matched related (n=155, 64%) or matched unrelated (n=87, 36%). Median follow up of survivors was 65 months (range 12-145). In a univariate analysis, 3-year OS of the four groups as defined above was 57%, 43%, 39% and 16% (p=0.003), respectively. In a multivariable analysis, hazard ratios of non-relapse mortality and survival were 2.08 (p=0.06) and 1.52 (p=0.23) in patients ?60 years in CR2 compared to ?60 years in CR1. While a plateau in survival was observed for patients ?60 years in CR1 similar to those <60 years in CR1 and CR2, no long term survivors were seen in patients ?60 years in CR2. Our data suggest disappointing outcome of AML patients ?60 years of age transplanted in CR2. Therefore, if a transplant is indicated, early referral is recommended in patients ?60 years with AML.
Related JoVE Video
Comparison of placebo and best available therapy for the treatment of myelofibrosis in the phase 3 COMFORT studies.
Haematologica
PUBLISHED: 08-02-2013
Show Abstract
Hide Abstract
Prior to Janus kinase inhibitors, available therapies for myelofibrosis were generally supportive and did not improve survival. This analysis compares efficacy outcomes of patients with myelofibrosis in the control arms (placebo [n=154] and best available therapy [n=73]) from the 2 phase 3 COntrolled MyeloFibrosis study with ORal JAK inhibitor Treatment (COMFORT) studies. Spleen volume was assessed by magnetic resonance imaging/computed tomography at baseline and every 12 weeks through week 72; spleen length was assessed by palpation at each study visit. Health-related quality of life and symptoms were assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 Items at baseline and at weeks 4, 8, 12, 16 and 24 in COMFORT-I and weeks 8, 16, 24 and 48 in COMFORT-II. The demographic and baseline characteristics were similar between the control arms of the 2 studies. One patient who received placebo and no patients who received best available therapy had a ?35% reduction in spleen volume from baseline at week 24. At 24 weeks, neither the placebo nor best available therapy arm had clinically meaningful changes in global quality of life or symptom scales. Nonhematologic adverse events were mostly grade 1/2; the most frequently reported in each group were abdominal pain, fatigue, peripheral edema and diarrhea. These data suggest that non-Janus kinase inhibitor therapies provide little improvement in splenomegaly, symptoms or quality of life as compared with placebo. Both COMFORT-I (NCT00952289) and COMFORT-II (NCT00934544) studies have been appropriately registered with clinicaltrials.gov.
Related JoVE Video
Translational profiling of cardiomyocytes identifies an early Jak1/Stat3 injury response required for zebrafish heart regeneration.
Proc. Natl. Acad. Sci. U.S.A.
PUBLISHED: 07-30-2013
Show Abstract
Hide Abstract
Certain lower vertebrates like zebrafish activate proliferation of spared cardiomyocytes after cardiac injury to regenerate lost heart muscle. Here, we used translating ribosome affinity purification to profile translating RNAs in zebrafish cardiomyocytes during heart regeneration. We identified dynamic induction of several Jak1/Stat3 pathway members following trauma, events accompanied by cytokine production. Transgenic Stat3 inhibition in cardiomyocytes restricted injury-induced proliferation and regeneration, but did not reduce cardiogenesis during animal growth. The secreted protein Rln3a was induced in a Stat3-dependent manner by injury, and exogenous Rln3 delivery during Stat3 inhibition stimulated cardiomyocyte proliferation. Our results identify an injury-specific cardiomyocyte program essential for heart regeneration.
Related JoVE Video
Feasibility study of EUS-NOTES as a novel approach for pancreatic cancer staging and therapy: an international collaborative study.
Hepatogastroenterology
PUBLISHED: 07-24-2013
Show Abstract
Hide Abstract
EUS guided Natural Orifice Transluminal Endoscopic Surgery (NOTES) could be a potentially viable approach for pancreatic surgery. EUS-guided access through the stomach wall may prove to be a safe and effective method for accessing the pancreas. The aim of the study was to assess the EUS-guided diagnostic and therapeutic procedures during NOTES for both anterior and posterior approach of the pancreas.
Related JoVE Video
Prevention of seroma formation after axillary dissection--a comparative randomized clinical trial of three methods.
Breast J
PUBLISHED: 07-19-2013
Show Abstract
Hide Abstract
Seroma is a frequent complication after breast cancer surgery. Closed suction drainage for several days is the standard procedure to reduce seroma formation. The aim of this study was to compare the efficacy of external compression dressing, suture flap fixation, and the conventional method of closed suction drains in the prevention of seroma formation. A total of 161 patients were prospectively randomized in a three groups × two subgroups design into control (n = 48), compression dressing (n = 53) and suturing groups (n = 49), and two subgroups, conventional drain removal (n = 75) and early drain removal (n = 75). All patients underwent ALND as part of MRM or BCT. The primary end point was the incidence of seroma. Suture flap fixation significantly reduced the incidence of seroma (p = 0.003), total drain output (p = 0.005), and duration of drainage (p = 0.001) without increase in wound complications. Compression dressing reduced duration of drainage significantly (p = 0.03), but not the total drain output (p = 0.15) or seromas (p = 0.58). Early drain removal on postoperative day 7 irrespective of drain output does not significantly increase seroma formation (p = 0.34) or wound complications. On multivariate analysis, BMI ? 30 (p = 0.02) and longer duration of drainage (p = 0.04) were identified as independent predictors for seroma formation. Obliteration of the dead space after breast cancer surgery by suture flap fixation is a safe and easy procedure, which significantly reduces postoperative seroma formation and duration of drainage. Compression dressing offers no advantage over normal dressing. Drains can be removed safely on postoperative day 7 irrespective of output without significant increase in complications.
Related JoVE Video
Reduced-intensity hematopoietic cell transplantation for patients with primary myelofibrosis: a cohort analysis from the center for international blood and marrow transplant research.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-28-2013
Show Abstract
Hide Abstract
We evaluated outcomes and associated prognostic factors in 233 patients undergoing allogeneic hematopoietic cell transplantation (HCT) for primary myelofibrosis (MF) using reduced-intensity conditioning (RIC). The median age at RIC HCT was 55 yr. Donors were a matched sibling donor (MSD) in 34% of RIC HCTs, an HLA well-matched unrelated donor (URD) in 45%, and a partially matched/mismatched URD in 21%. Risk stratification according to the Dynamic International Prognostic Scoring System (DIPSS) was 12% low, 49% intermediate-1, 37% intermediate-2, and 1% high. The probability of survival at 5 yr was 47% (95% confidence interval [CI], 40% to 53%). In a multivariate analysis, donor type was the sole independent factor associated with survival. Adjusted probabilities of survival at 5-yr were 56% (95% CI, 44% to 67%) for MSD, 48% (95% CI, 37% to 58%) for well-matched URD, and 34% (95% CI, 21% to 47%) for partially matched/mismatched URD (P = .002). The relative risk (RR) for NRM was 3.92 (P = .006) for well-matched URD and 9.37 (P < .0001) for partially matched/mismatched URD. Trends toward increased NRM (RR, 1.7; P = .07) and inferior survival (RR, 1.37; P = .10) were observed in DIPSS intermediate-2/high-risk patients compared with DIPSS low/intermediate-1 risk patients. Our data indicate that RIC HCT is a potentially curative option for patients with MF, and that donor type is the most important factor influencing survival in these patients.
Related JoVE Video
Providing personalized prognostic information for adult leukemia survivors.
Biol. Blood Marrow Transplant.
PUBLISHED: 06-28-2013
Show Abstract
Hide Abstract
Prediction of subsequent leukemia-free survival (LFS) and chronic graft-versus-host disease (GVHD) in adults with acute leukemia who survived at least 1 year after allogeneic hematopoietic cell transplantation is difficult. We analyzed 3339 patients with acute myeloid leukemia and 1434 patients with acute lymphoblastic leukemia who received myeloablative conditioning and related or unrelated stem cells from 1990 to 2005. Most clinical factors predictive of LFS in 1-year survivors were no longer significant after 2 or more years. For acute myeloid leukemia, only disease status (beyond first complete remission) remained a significant adverse risk factor for LFS 2 or more years after transplantation. For lymphoblastic leukemia, only extensive chronic GVHD remained a significant adverse predictor of LFS in the second and subsequent years. For patients surviving for 1 year without disease relapse or extensive chronic GVHD, the risk of developing extensive chronic GVHD in the next year was 4% if no risk factors were present and higher if noncyclosporine-based GVHD prophylaxis, an HLA-mismatched donor, or peripheral blood stem cells were used. Estimates for subsequent LFS and extensive chronic GVHD can be derived for individual patients or populations using an online calculator (http://www.cibmtr.org/LeukemiaCalculators). This prognostic information is more relevant for survivors than estimates provided before transplantation.
Related JoVE Video
A Comparison of Long-Term Outcomes of Donor Lymphocyte Infusions and Tyrosine Kinase Inhibitors in Patients With Relapsed CML After Allogeneic Hematopoietic Cell Transplantation.
Clin Lymphoma Myeloma Leuk
PUBLISHED: 06-17-2013
Show Abstract
Hide Abstract
Donor lymphocyte infusion (DLI) and tyrosine kinase inhibitors (TKIs) are the 2 standard treatment options in chronic myeloid leukemia (CML) that relapses after hematopoietic cell transplantation (HCT), but reports comparing long-term outcomes of these modalities are rare.
Related JoVE Video
Surgical management of long bone pseudarthrosis with severe limb length discrepancy in osteogenesis imperfecta.
J Pediatr Orthop B
PUBLISHED: 05-15-2013
Show Abstract
Hide Abstract
We report a three-stage approach in managing an 18-year-old boy with osteogenesis imperfecta who had pseudarthrosis of the left femur with 150° anterior angulation and 9.5 cm shortening. Severe long bone deformity and pseudarthrosis in osteogenesis imperfecta are difficult to manage because of the relative shortening of the surrounding soft tissue and bone fragility. Our staged approach included excision of the pseudarthrosis, gradual soft tissue lengthening by external fixator, and a modified Sofield-Millar operation, to achieve union, deformity, and limb length correction without compromising much of the bone length. The patient was able to walk with support within 3 months and independently at 1 year. In this report, the management of the nonunion in osteogenesis imperfecta is discussed, with a focus on its difficulties and the management principles.
Related JoVE Video
Treatment of elderly patients with acute lymphoblastic leukaemia using a paediatric-based protocol.
Br. J. Haematol.
PUBLISHED: 05-14-2013
Show Abstract
Hide Abstract
All newly diagnosed patients aged 60-79 years with acute lymphoblastic leukaemia (ALL) receiving induction chemotherapy with a modified paediatric-based regimen over a 7-year period were retrospectively analysed (n = 51, median age 65 years). The treatment regimen consisted of induction, central nervous system prophylaxis, seven cycles of intensification and 24 cycles of maintenance. BCR-ABL1 negative patients received weekly asparaginase during intensification, while BCR-ABL1+ patients received daily imatinib. Post-remission therapy was given in an outpatient setting. The complete response rate was 75%, with an induction mortality of 20%; 6% of patients had resistant disease. 37% of patients who achieved a complete remission relapsed. The estimated 5-year overall survival was 40% for BCR-ABL1 negative and 47% for BCR-ABL1+ patients (P = not significant); the 5-year disease-free survival was 57% and 39%, respectively (P = NS). The post-induction phase was generally well tolerated, with 81% able to complete the intensification phase and proceed to maintenance. In conclusion, administration of this modified paediatric-based protocol is feasible and active for elderly patients with ALL. Survival is superior to most previously reported series in this age group, but remains worse compared to younger patients. Further improvement of the toxicity profile, particularly during induction, is required to improve outcomes.
Related JoVE Video
Unrelated donor allogeneic transplantation after failure of autologous transplantation for acute myelogenous leukemia: a study from the center for international blood and marrow transplantation research.
Biol. Blood Marrow Transplant.
PUBLISHED: 04-21-2013
Show Abstract
Hide Abstract
The survival of patients with relapsed acute myelogenous leukemia (AML) after autologous hematopoietic stem cell transplantation (auto-HCT) is very poor. We studied the outcomes of 302 patients who underwent secondary allogeneic hematopoietic cell transplantation (allo-HCT) from an unrelated donor (URD) using either myeloablative (n = 242) or reduced-intensity conditioning (RIC; n = 60) regimens reported to the Center for International Blood and Marrow Transplantation Research. After a median follow-up of 58 months (range, 2 to 160 months), the probability of treatment-related mortality was 44% (95% confidence interval [CI], 38%-50%) at 1-year. The 5-year incidence of relapse was 32% (95% CI, 27%-38%), and that of overall survival was 22% (95% CI, 18%-27%). Multivariate analysis revealed a significantly better overal survival with RIC regimens (hazard ratio [HR], 0.51; 95% CI, 0.35-0.75; P <.001), with Karnofsky Performance Status score ?90% (HR, 0.62; 95% CI, 0.47-0.82: P = .001) and in cytomegalovirus-negative recipients (HR, 0.64; 95% CI, 0.44-0.94; P = .022). A longer interval (>18 months) from auto-HCT to URD allo-HCT was associated with significantly lower riak of relapse (HR, 0.19; 95% CI, 0.09-0.38; P <.001) and improved leukemia-free survival (HR, 0.53; 95% CI, 0.34-0.84; P = .006). URD allo-HCT after auto-HCT relapse resulted in 20% long-term leukemia-free survival, with the best results seen in patients with a longer interval to secondary URD transplantation, with a Karnofsky Performance Status score ?90%, in complete remission, and using an RIC regimen. Further efforts to reduce treatment-related mortaility and relapse are still needed.
Related JoVE Video
Renal cell carcinoma presenting as isolated deltoid muscle metastasis 12 years after radical nephrectomy detected on 18F-FDG PET/CT.
Clin Nucl Med
PUBLISHED: 04-13-2013
Show Abstract
Hide Abstract
We report a case of renal cell carcinoma detected to have isolated deltoid metastasis on 18F-FDG PET/CT 12 years after radical nephrectomy. Isolate muscle (deltoid) metastasis from renal cell carcinoma has not been reported in the literature.
Related JoVE Video
Evaluation of Integrated Management of Neonatal and Childhood Illness (IMNCI) Algorithm for Diagnosis and Referral in Under-Five Children.
Indian J Pediatr
PUBLISHED: 03-13-2013
Show Abstract
Hide Abstract
A prospective observational study was conducted on 500 children to evaluate the Integrated Management of Neonatal and Childhood Illnesses (IMNCI) algorithm for diagnosis and referral of children aged 0-59 mo. IMNCI algorithm performed well in diagnosis [except sepsis in 0-7 d (p?
Related JoVE Video
Effect of ruxolitinib therapy on myelofibrosis-related symptoms and other patient-reported outcomes in COMFORT-I: a randomized, double-blind, placebo-controlled trial.
J. Clin. Oncol.
PUBLISHED: 02-19-2013
Show Abstract
Hide Abstract
To assess the effects of ruxolitinib on symptom burden and quality of life (QoL) and to evaluate the ability of the modified Myelofibrosis Symptom Assessment Form (MFSAF) v2.0 to measure meaningful changes in myelofibrosis-related symptoms in patients with myelofibrosis.
Related JoVE Video
Up, down, and around: identifying recurrent interactions within and between super-secondary structures in ?-propellers.
Methods Mol. Biol.
PUBLISHED: 02-01-2013
Show Abstract
Hide Abstract
The examination and analysis of super-secondary structures or other specific structural patterns associated with particular functions, sequence motifs, or structural contexts require that the set of structures examined shares the same feature. This seems obvious but in practice this may often present problems such as identifying complete sets of data avoiding false positives. In the case of the ?-propeller structures the symmetry of the propeller creates problems for many structure similarity search programs. Here we present a procedure that will identify propeller structures in PDB and assign them to the different N-propeller types. In addition we outline methods to examine similarities and differences within and between the four stranded up-and-down blades of the ?-propeller.
Related JoVE Video
Treatment outcomes following leukemic transformation in Philadelphia-negative myeloproliferative neoplasms.
Blood
PUBLISHED: 01-29-2013
Show Abstract
Hide Abstract
Leukemic transformation (LT) is a rare but fatal complication of Philadelphia-negative myeloproliferative neoplasms (MPNs) for which optimal treatment strategies are not known. At our center, we have adopted a treatment approach for LT where patients within the transplant age group who have a reasonable fitness level are treated with curative intent and offered induction chemotherapy. Subsequently, those who respond and have a suitable donor are considered for allogeneic hematopoietic cell transplantation (HCT). In this study, we evaluated the clinical outcomes of this treatment approach in 75 patients with LT. The 2-year overall survival (OS) from the time of LT was 15%. A total of 39 patients (52%) were treated with curative intent (induction ± HCT) and had a 2-y OS of 26% compared with 3% in those noncuratively treated (P < .0001). In the curative intent group, 18 individuals (46%) achieved complete remission (CR) or CR with incomplete recovery and 12 (31%) reverted to a chronic MPN phase, with 17 patients undergoing HCT. Survival of patients posttransplant was significantly improved compared with those who responded to induction but were not transplanted (2-y OS of 47% vs 15%; P = .03). Thus, induction chemotherapy followed by HCT has the potential for long-term disease control in select patients with LT preceded by a MPN.
Related JoVE Video
Birth order and transplantation outcome in HLA-identical sibling stem cell transplantation: an analysis on behalf of the Center for International Blood and Marrow Transplantation.
Biol. Blood Marrow Transplant.
PUBLISHED: 01-25-2013
Show Abstract
Hide Abstract
Allogeneic stem cell transplantation (SCT) is the most effective treatment option for many hematologic malignancies, but graft-versus-host disease (GVHD) remains a major cause of treatment failure. Along with well-established risk factors for transplantation outcomes, recent single-center studies have identified a birth order effect in HLA-identical sibling SCT, with lower rates of acute and chronic GVHD and improved overall survival when the donor is younger than the recipient. One hypothesized mechanism for this effect is microchimerism due to fetomaternal and transmaternal sibling cell trafficking during pregnancy as the donor is exposed to recipient antigens in utero. The aim of the present study was to validate previously reported single-center data in a large, multicenter cohort provided by the Center for International Blood and Marrow Transplantation. All adult and pediatric patients (n = 11,365) with a hematologic malignancy who underwent allogeneic SCT with a graft from an HLA-identical sibling donor between 1990 and 2007 were included. When donors were younger than recipients, there was a significantly lower rate of acute GVHD grade II-IV and chronic GVHD in children, as well as a lower rate of chronic GVHD in adolescents. However, the hypothesized overall positive effect of lower relapse and better survival when donors are younger than recipients was not observed. Our data suggest that if otherwise equally matched, a graft from a younger sibling may be superior to a graft from an older sibling for children and adolescents undergoing SCT.
Related JoVE Video
Exacerbation of latent lupus: is the culprit acid-fast bacilli or antitubercular therapy?
Clin. Rheumatol.
PUBLISHED: 01-24-2013
Show Abstract
Hide Abstract
Typical as well as atypical presentations of systemic lupus erythematosus are being increasingly recognized due to improved diagnostic methods. In a tuberculosis-endemic country like India, it was traditionally believed that the occurrence of tuberculosis in lupus was due to the chronic immunosuppression caused by lupus or because of the use of steroids or isoniazid-induced lupus. Increasingly several patients with no recorded predisposition to lupus with a history of treatment for tuberculosis are coming with evidence of systemic lupus erythematosus rather than a drug-limited story. Whether the development of an autoimmune state is a mere conjecture or the presence of acid-fast bacilli in the body for a prolonged duration causes complex antigenic interactions leading to an antigenic response needs to be looked into. We present a report of three such patients and review the pathogenetic interactions that could possibly explain the role of mycobacterial antigens as a putative antigen in the pathogenesis of lupus.
Related JoVE Video
An injury-responsive gata4 program shapes the zebrafish cardiac ventricle.
Curr. Biol.
PUBLISHED: 01-22-2013
Show Abstract
Hide Abstract
A common principle of tissue regeneration is the reactivation of previously employed developmental programs. During zebrafish heart regeneration, cardiomyocytes in the cortical layer of the ventricle induce the transcription factor gene gata4 and proliferate to restore lost muscle. A dynamic cellular mechanism initially creates this cortical muscle in juvenile zebrafish, where a small number of internal cardiomyocytes breach the ventricular wall and expand upon its surface. Here, we find that emergent juvenile cortical cardiomyocytes induce expression of gata4 in a manner similar to during regeneration. Clonal analysis indicates that these cardiomyocytes make biased contributions to build the ventricular wall, whereas gata4(+) cardiomyocytes have little or no proliferation hierarchy during regeneration. Experimental microinjuries or conditions of rapid organismal growth stimulate production of ectopic gata4(+) cortical muscle, implicating biomechanical stress in morphogenesis of this tissue and revealing clonal plasticity. Induced transgenic inhibition defined an essential role for Gata4 activity in morphogenesis of the cortical layer and the preservation of normal cardiac function in growing juveniles, and again in adults during heart regeneration. Our experiments uncover an injury-responsive program that prevents heart failure in juveniles by fortifying the ventricular wall, one that is reiterated in adults to promote regeneration after cardiac damage.
Related JoVE Video
The clinical benefit of ruxolitinib across patient subgroups: analysis of a placebo-controlled, Phase III study in patients with myelofibrosis.
Br. J. Haematol.
PUBLISHED: 01-17-2013
Show Abstract
Hide Abstract
Myelofibrosis (MF) patients can present with a wide spectrum of disease characteristics. We analysed the consistency of ruxolitinib efficacy across patient subgroups in the COntrolled MyeloFibrosis Study With ORal JAK Inhibitor Treatment (COMFORT-I,) a double-blind trial, where patients with intermediate-2 or high-risk MF were randomized to twice-daily oral ruxolitinib (n = 155) or placebo (n = 154). Subgroups analysed included MF subtype (primary, post-polycythaemia vera, post-essential thrombocythaemia), age (?65, > 65 years), International Prognostic Scoring System risk group, baseline Eastern Cooperative Oncology Group performance status (0, 1, ?2), JAK2 V617F mutation (positive, negative), baseline haemoglobin level (?100, <100 g/l), baseline platelet count (100-200 × 10(9)/l, >200 × 10(9)/l), baseline palpable spleen size (?10, >10 cm), and baseline quartile of spleen volume and Total Symptom Score (TSS; Q1 = lowest, Q4 = highest). Mean percentage change from baseline to week 24 in spleen volume and TSS were calculated for ruxolitinib and placebo in each subgroup. Overall survival was estimated by Kaplan-Meier method according to original randomization group. In ruxolitinib-treated patients, reductions in spleen volume and TSS and evidence of improved survival relative to placebo across subgroups were consistent with those seen in the COMFORT-I population, confirming that ruxolitinib is an effective therapy for the spectrum of MF patients studied in COMFORT-I.
Related JoVE Video
High-dose cytarabine-based consolidation shows superior results for older AML patients with intermediate risk cytogenetics in first complete remission.
Leuk. Res.
PUBLISHED: 01-05-2013
Show Abstract
Hide Abstract
We evaluated outcomes in two consecutive groups of AML patients age>60 years in CR after 7+3 induction therapy. Group 1 received consolidation with cytarabine 1.5g/m(2) q12h×6+daunorubicin for two cycles, while group 2 received consolidation with 7+3 followed by mitoxantrone+etoposide. For patients with intermediate-risk cytogenetics, group 1 had a significantly superior DFS (p=0.046), and a trend toward better OS (p=0.087). The treatment group remained a significant predictor of DFS on multivariate analysis. The results indicate that a high-dose cytarabine-containing consolidation regimen produces superior outcomes in AML patients age>60 years with intermediate-risk cytogenetics.
Related JoVE Video
Finite element analysis of dental implant as orthodontic anchorage.
J Contemp Dent Pract
PUBLISHED: 12-22-2011
Show Abstract
Hide Abstract
The purpose of this three-dimensional (3D) finite element study was to investigate orthodontic loading simulation on a single endosseous implant and its surrounding osseous structure, to analyze the resultant stresses and to identify the changes in the bone adjacent to the implant following orthodontic loading.
Related JoVE Video
Apical force distribution due to orthodontic forces: a finite element study.
J Contemp Dent Pract
PUBLISHED: 12-22-2011
Show Abstract
Hide Abstract
This finite element study was conducted to calculate the distribution of stresses in the periodontal ligament when various orthodontic forces were applied, with emphasis on the effect on root apex.
Related JoVE Video
Comparison of cosmetic outcome between single-incision laparoscopic cholecystectomy and conventional laparoscopic cholecystectomy: an objective study.
J Laparoendosc Adv Surg Tech A
PUBLISHED: 12-06-2011
Show Abstract
Hide Abstract
Single-incision laparoscopic cholecystectomy (SILC) has been projected to have better cosmetic outcome compared with conventional laparoscopic cholecystectomy (CLC). However, there are scarce data that have objectively compared the patients perception of cosmetic outcome after SILSC and CLC.
Related JoVE Video
Risk factors for acute GVHD and survival after hematopoietic cell transplantation.
Blood
PUBLISHED: 10-18-2011
Show Abstract
Hide Abstract
Risk factors for acute GVHD (AGVHD), overall survival, and transplant-related mortality were evaluated in adults receiving allogeneic hematopoietic cell transplants (1999-2005) from HLA-identical sibling donors (SDs; n = 3191) or unrelated donors (URDs; n = 2370) and reported to the Center for International Blood and Marrow Transplant Research, Minneapolis, MN. To understand the impact of transplant regimen on AGVHD risk, 6 treatment categories were evaluated: (1) myeloablative conditioning (MA) with total body irradiation (TBI) + PBSCs, (2) MA + TBI + BM, (3) MA + nonTBI + PBSCs, (4) MA + nonTBI + BM, (5) reduced intensity conditioning (RIC) + PBSCs, and (6) RIC + BM. The cumulative incidences of grades B-D AGVHD were 39% (95% confidence interval [CI], 37%-41%) in the SD cohort and 59% (95% CI, 57%-61%) in the URD cohort. Patients receiving SD transplants with MA + nonTBI + BM and RIC + PBSCs had significantly lower risks of grades B-D AGVHD than patients in other treatment categories. Those receiving URD transplants with MA + TBI + BM, MA + nonTBI + BM, RIC + BM, or RIC + PBSCs had lower risks of grades B-D AGVHD than those in other treatment categories. The 5-year probabilities of survival were 46% (95% CI, 44%-49%) with SD transplants and 33% (95% CI, 31%-35%) with URD transplants. Conditioning intensity, TBI and graft source have a combined effect on risk of AGVHD that must be considered in deciding on a treatment strategy for individual patients.
Related JoVE Video
Post-laparoscopic wound infection caused by scotochromogenic nontuberculous Mycobacterium.
Jpn. J. Infect. Dis.
PUBLISHED: 09-23-2011
Show Abstract
Hide Abstract
Nontuberculous mycobacteria are known to produce soft-tissue infections following surgical procedures. We report a non-healing surgical wound infection caused by a scotochromogenic nontuberculous mycobacterium, possibly Mycobacterium flavescens, which was earlier thought to be saprophytic. This organism was isolated from the wound discharge at the site of incision following a laparoscopic cholecystectomy; the finding suggests that M. flavescens is a clinically important pathogen in cases of surgical wound infections.
Related JoVE Video
Feasibility of outpatient consolidation chemotherapy in older versus younger patients with acute myeloid leukemia.
Am. J. Hematol.
PUBLISHED: 09-20-2011
Show Abstract
Hide Abstract
Intensive consolidation chemotherapy for acute myeloid leukemia (AML) patients in complete remission is being increasingly administered on an outpatient basis. Although this approach has been found to be safe and feasible in younger patients, its safety in older patients remains unknown. We therefore undertook an evaluation of outpatient-based consolidation chemotherapy in older AML patients, and compared results to younger patients treated at the same institution over the same time period. The overall rate of readmission was ~50%, mostly for infections, with mean admission duration of 2 weeks. The overall mortality rate was 2.2%. Readmission rates and duration of readmission were somewhat higher in older patients, but infection rate, intensive care (ICU) admissions, and mortality rates were comparable to those in the younger patient cohort. However, we also observed that rates of febrile neutropenia, bacteremia, ICU admission, and death were significantly higher during the second consolidation, as compared with the first, in both younger and older patients. We conclude that outpatient-based consolidation therapy can be safely undertaken in a substantial proportion of fit older patients with AML.
Related JoVE Video
Pancreatic cyst fluid analysis--a review.
J Gastrointestin Liver Dis
PUBLISHED: 07-05-2011
Show Abstract
Hide Abstract
An increased number of pancreatic cysts are being diagnosed due to the increased usage of cross-sectional imaging. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of these cystic lesions have led to their better detection and characterization. The aim of this review is to assess the value of cyst fluid analysis for the differential diagnosis of pancreatic cystic lesions, in view of the recent progresses of molecular analysis methods. Pancreatic cysts can be either simple (retention) cysts, pseudocysts and cystic neoplasms, while these are further subdivided into serous cystadenomas, mucinous cystic neoplasms (MCNs) or intraductal papillary mucinous neoplasms (IPMNs). EUS is now being used to investigate cystic pancreatic lesions, particularly by means of EUS guided cyst aspiration and sampling of the cyst wall or septa, as well as mural nodules. Cyst fluid can be further studied after aspiration in order to analyze cytology, viscosity, extracellular mucin, other tumor markers (CEA, CA 19-9,CA 15-3, Ca 72-4, etc.), enzymes (amylase, lipase), as well as DNA analysis of DNA quality/content or mutational analysis to study allelic imbalance/LOH (loss of heterozygosity) and K-ras mutations. After careful review of the published studies, a conclusion was reached that the use of tumor and molecular markers in conjunction with multimodality detection methods such as CT, MR and EUS-FNA allows risk stratification, while being also cost-effective.
Related JoVE Video
Assessment of hand functions in rheumatoid arthritis using SF-SACRAH (short form score for the assessment and quantification of chronic rheumatoid affections of the hands) and its correlation to disease activity.
Rheumatol. Int.
PUBLISHED: 06-11-2011
Show Abstract
Hide Abstract
Rheumatoid arthritis activity is generally evaluated by using DAS-28 score. But this does not reflect the extent of functional hand impairment, a decisive parameter for patient wellbeing as well as for work disability. Several questionnaires to quantify the hand involvement in RA have been elaborated, amongst which SACRAH has been popular since 2003. But this requires evaluating 23 questions on a visual analogue scale. The questions were reduced to 12 in modified-SACRAH (M-SACRAH) and to only five questions in short form SACRAH (SF-SACRAH) so as to make it easily applicable in daily clinical practice. A study was planned to compare M-SACRAH (already validated) to SF-SACRAH in Indian population as no Indian data are available on the same. A total of 100 patients of RA were evaluated for disease activity using DAS-28 score and hand functions using M-SACRAH and SF-SACRAH. The M-SACRAH and SF-SACRAH were then compared based on DAS-28 scores; also M-SACRAH was compared to SF-SACRAH using Spearmans correlation coefficient. The mean value of DAS-28 score was 3.15 ± 0.86. The mean value of SF-SACRAH was 8.065 ± 7.44, and mean value of M-SACRAH was 201.7 ± 201.1008. The correlation of DAS-28 score to SF-SACRAH and M-SACRAH was significant in moderate and high disease activity but insignificant in remission and low disease activity state. The correlation between M-SACRAH and SF-SACRAH showed a spearmans coefficient of 0.998 with a P value of <0.001 (significant correlation). Correlation was significant for all disease activity states and for remission. The study suggests that the disease activity of rheumatoid arthritis (as assessed by DAS-28 score) has a poor correlation with hand functions (as assessed by M-SACRAH and SF-SACRAH) especially in low disease activity and remission states. Further, M-SACRAH and SF-SACRAH are significantly correlated. Therefore, it is suggested that RA patients should be assessed by SF-SACRAH (which includes five questions only) in addition to DAS-28 scoring for better evaluation of hand functions, a detrimental factor in day to day performance of RA patients.
Related JoVE Video
tcf21+ epicardial cells adopt non-myocardial fates during zebrafish heart development and regeneration.
Development
PUBLISHED: 06-08-2011
Show Abstract
Hide Abstract
Recent lineage-tracing studies have produced conflicting results about whether the epicardium is a source of cardiac muscle cells during heart development. Here, we examined the developmental potential of epicardial tissue in zebrafish during both embryonic development and injury-induced heart regeneration. We found that upstream sequences of the transcription factor gene tcf21 activated robust, epicardium-specific expression throughout development and regeneration. Cre recombinase-based, genetic fate-mapping of larval or adult tcf21(+) cells revealed contributions to perivascular cells, but not cardiomyocytes, during each form of cardiogenesis. Our findings indicate that natural epicardial fates are limited to non-myocardial cell types in zebrafish.
Related JoVE Video
Classifying cytogenetics in patients with acute myelogenous leukemia in complete remission undergoing allogeneic transplantation: a Center for International Blood and Marrow Transplant Research study.
Biol. Blood Marrow Transplant.
PUBLISHED: 05-26-2011
Show Abstract
Hide Abstract
Cytogenetics play a major role in determining the prognosis of patients with acute myelogenous leukemia (AML). However, existing cytogenetics classifications were developed in chemotherapy-treated patients and might not be optimal for patients undergoing allogeneic hematopoietic cell transplantation (HCT). We studied 821 adult patients reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) who underwent HCT for AML in first or second complete remission between 1999 and 2004. We compared the ability of the 6 existing classifications to stratify patients by overall survival. We then defined a new scheme specifically applicable to patients undergoing HCT using this patient cohort. Under this scheme, inv(16) is favorable, a complex karyotype (4 or more abnormalities) is adverse, and all other classified abnormalities are intermediate in predicting survival after HCT (5-year overall survival, 64%, 18%, and 50%, respectively; P = .0001). This scheme stratifies patients into 3 groups with similar nonrelapse mortality, but significantly different incidences of relapse, overall and leukemia-free survival. It applies to patients regardless of disease status (first or second complete remission), donor type (matched related or unrelated), or conditioning intensity (myeloablative or reduced intensity). This transplantation-specific classification could be adopted for prognostication purposes and to stratify patients with AML and karyotypic abnormalities entering HCT clinical trials.
Related JoVE Video
Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anemia.
Blood
PUBLISHED: 04-25-2011
Show Abstract
Hide Abstract
We evaluated a novel alemtuzumab-based conditioning regimen in HSCT for acquired severe aplastic anemia (SAA). In a multicenter retrospective study, 50 patients received transplants from matched sibling donors (MSD; n = 21) and unrelated donors (UD; n = 29), using fludarabine 30 mg/m² for 4 days, cyclophosphamide 300 mg/m² for 4 days, and alemtuzumab median total dose of 60 mg (range:40-100 mg). Median age was 35 years (range 8-62). Overall survival at 2 years was 95% ± 5% for MSD and 83% for UD HSCT (p 0.34). Cumulative incidence of graft failure was 9.5% for MSD and 14.5% for UD HSCT. Full-donor chimerism (FDC) in unfractionated peripheral blood was 42%; no patient achieved CD3 FDC. Acute GVHD was observed in only 13.5% patients (all grade I-II) and only 2 patients (4%) developed chronic GVHD. A low incidence of viral infections was seen. Factors influencing overall survival were HSCT comorbidity 2-year index (92% with score 0-1 vs 42% with score ? 2, P < .001) and age (92% for age < 50 years vs 71% ? 50 years, P < .001). Our data suggest that the use of an alemtuzumab-based HSCT regimen for SAA results in durable engraftment with a low incidence of chronic GVHD.
Related JoVE Video
Extra capsular extrusion of femoral capital epiphysis - an unusual presentation of sequelae of septic arthritis of hip.
J Pediatr Orthop B
PUBLISHED: 04-19-2011
Show Abstract
Hide Abstract
Presentations of sequelae of septic hip in infants have been classified by various researchers, depending on the presence or absence of femoral capital epiphysis in acetabulum. This case report describes an unusual presentation of sequelae of septic arthritis of hip in which femoral capital epiphysis had extruded outside the capsule of hip joint in a 1 year and 6-months-old boy.
Related JoVE Video
The efficacy of a novel approach to transversus abdominis plane block for postoperative analgesia after colorectal surgery.
Anesth. Analg.
PUBLISHED: 04-05-2011
Show Abstract
Hide Abstract
The analgesic efficacy of transversus abdominis plane (TAP) block has been established for patients undergoing abdominal surgery. We evaluated the efficacy of a novel approach to TAP block for postoperative analgesia after colorectal surgery.
Related JoVE Video
Severe acute hypertension among inpatients admitted from the emergency department.
J Hosp Med
PUBLISHED: 03-22-2011
Show Abstract
Hide Abstract
Hospitalists often treat patients with severe acute hypertension (AH) presenting to the hospital. Little is known about the epidemiology of this syndrome.
Related JoVE Video
A prospective study comparing the outcomes and health-related quality of life in adult patients with myeloid malignancies undergoing allogeneic transplantation using myeloablative or reduced-intensity conditioning.
Biol. Blood Marrow Transplant.
PUBLISHED: 03-21-2011
Show Abstract
Hide Abstract
We compared the outcomes including health-related quality of life (HRQOL) in adult patients undergoing allogeneic transplantation using myeloablative conditioning (MAC) or reduced-intensity conditioning (RIC). This outcome study was a nonrandomized, prospective, observational noninferiority study, and primarily designed to determine whether RIC was as effective as MAC for myeloid malignancies. Comprehensive longitudinal assessment of HRQOL was done at baseline, day 30, day 100, day 180, and day 365 using validated instruments. A total of 115 patients (MAC, 51; RIC, 64) participated in this study. Of these 115 patients, 105 (91%) participated for HRQOL assessments. The main indication for HCT was acute myeloid leukemia (72%). Except age (median 41 vs 59 years, P < .0001), baseline characteristics were similar in patients undergoing MAC and RIC, respectively. Progression-free survival (PFS) at 1 year was 59% (SE = 7%) and 53% (SE = 6%) for the patients undergoing MAC and RIC, respectively (90% confidence interval [CI] -9% to +21%, P = .53). No significant difference in overall survival (OS), cumulative incidents of acute and chronic graft-versus-host disease (aGVHD, cGVHD), nonrelapse mortality (NRM) or relapse was observed in the 2 cohorts. The trajectory of decline and recovery of HRQOL was similar between the 2 cohorts. We conclude that clinical outcomes and HRQOL in patients with myeloid malignancies undergoing RIC are not inferior to MAC at 1 year.
Related JoVE Video
Co-composting of physic nut (Jatropha curcas) deoiled cake with rice straw and different animal dung.
Bioresour. Technol.
PUBLISHED: 03-15-2011
Show Abstract
Hide Abstract
To address the dispensing of this growing volume, a study on utilization of jatropha (Jatropha curcas) deoiled cake through compost production was carried out. The deoiled cake was composted with rice straw, four different animal dung (cow dung, buffalo dung, horse dung and goat dung) and hen droppings in different proportions followed by assessment, and comparison of biochemical characteristics among finished composts. Nutrient content in finished compost was within the desired level whereas metals such as copper, lead and nickel were much below the maximum allowable concentrations. Although a few finished material contained phorbol ester (0.12 mg/g), but it was far below the original level found in the deoiled cake. Such a study indicates that a huge volume of jatropha deoiled cake can be eliminated through composting.
Related JoVE Video

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

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.