Genetic of Sporadic Hemophagocytic Lymphohistiocytosis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 82-82
Author(s):  
Coralie Bloch ◽  
Jean-Philippe Jais ◽  
Marine Gil ◽  
Marouane Boubaya ◽  
Felipe Suarez ◽  
...  
Keyword(s):  
Hemophagocytic Lymphohistiocytosis ◽  
Research Funding ◽  
Clinical Symptoms ◽  
Ferritin Level ◽  
Genetic Component ◽  
Trend Test ◽  
Biological Features ◽  
Associated Diseases ◽  
One Year ◽  
The One

Background: Hemophagocytic lymphohistiocytosis (HLH) syndrome is due to an abnormal and sustained activation of T lymphocytes and macrophages releasing pro-inflammatory cytokines in the microenvironment. HLH is characterized by clinical and biological features that includes fever, hepatomegaly, splenomegaly, high ferritin level, pancytopenia and liver biology abnormalities. HLH is commonly divided into genetic/hereditary cases (HLHg) and non genetic/ sporadic (HLHs) with no hints for an inherited causes. However, similarity of both clinical symptoms and biological abnormalities between HLHg and HLHs raised, however, the hypothesis that HLHs could have a genetic component that may be related to HLHg. However contribution of genetic factors in both, pathophysiology and prognosis of sporadic hemophagocytic lymphohistiocytosis (HLHs) remains unknown. To explore the hypothesis of a genetic susceptibility in HLHs, from 2010 to 2017, we constituted a cohort of 205 HLHs patients (adults and children) and analysed genes involved in genetic HLH (HLHg). Methods: Patients fulfillied modified HLH-2004 diagnostic criteria. Data collected included (i) clinical and biological features, (ii) associated diseases (AID), (iii) infectious events, (iv) treatment, and (v) clinical outcome during one year of follow up. HLHg related genes LYST, PRF1, UNC13-D, STX11, STXBP2, RAB27A, SH2D1A, XIAP were NGS sequenced in 172 patients. Selected variants were (i) unknown but met at least two criteria among MAF<0.05, CADD >10, and/or Polyphen HDIV (>0.485) (n=50), (ii) previously related to HLHg (n=2), PRF1 A755G/N252S (MAF <0.05) and PRF1 C272T/A91V (MAF <0.05, CADD >10 and Polyphen HDIV). Two control cohorts were selected, the first one using the variant files from the European subpopulation of the 1000 Genomes (1000G cohort, n=502) phase 3 project and the second one from the local in-house variants data base (in-house cohort, n=5092). Results: Patients presented with neoplasia (n=62), AID (n=46) in which infection was mainly Herpes virus (EBV) (> 80%), or no etiology (idiopathic) (n=64) with a greater infectious diversity. Fifty-two variants met the selection criteria, they were distributed overall in 115 alleles in 84/172 patients. Variants were globally heterozygous. They were recurrent with occurrence in 2 patients for STX11, RAB27A and LYST genes to 10 patients for the N252S and 18 patients for the p.Ala91Val in PRF1. Overall the frequency of individuals exhibiting at least one variant was significantly in excess (48.8%, n=84) in the HLHs versus in in-house (35.9%, n=1826) (p=0.001, CAST test) or versus in 1000G population patients (38.6%, n=194) (p=0.02, CAST test). Importantly, the distribution of patients carrying either 0, 1, 2, 3 or 4 mutated alleles in HLHs cohort was statistically different from the two control populations (Trend test: HLH vs in-house p<0.0001 and HLH vs 1000G p<0.001; SUM test: HLH vs in-house p<0.001 and HLH vs 1000G p=0.001). We observed an excess of patients carrying one or two mutated in the HLHs cohort vs in-house OR (1 allele vs 0 allele) =1.49 [IC 1.05-2.11]; (2 alleles vs 0 allele) =2.52 [IC 1.54-4.00] and vs 1000G OR 1 allele vs 0 allele =1.27 [IC 0.85-1.88]; 2 alleles vs 0 allele =2.76 [IC 1.50-5.05]. Finally, PRF1/RAB27Aa and PRF1/STXBP2 were found to be positively associated with a highier frequency in HLHs group than expected from a random distribution (p<0.01 and p=0.05, respectively). Importantly, severe patients carried a significantly higher number of variants (1, 2 or 3) than the one with a better outcome (p<0.001, Fisher test exact). A multivariate analysis including sex, age, associated diseases, and infectious status as confounding factors, confirm that the number of HLH genes variants is correlated to the severity of the syndrome independently of these others factors OR(S/NS; 1 variant/0 variant)=3.03 [1.45-6.32] (p=0.003) and OR(S/NS; 2 variants/0 variant) =4.55[1.61-12.84] (p=0.004). Conclusion: The results presented in this study strongly support the hypothesis that HLHs has a genetic component when tested with genes of HLH. Overall, this results established clearly a genotype/phenotype correlation between presence of one or more filtered HLH genes variants and severity of the HLH syndrome in patients. Finally, we proposed a di/tri genic model as an expression of genetic component in sporadic HLH. Disclosures Hermine: Novartis: Research Funding; AB science: Consultancy, Equity Ownership, Honoraria, Research Funding; Celgene: Research Funding.

scholarly journals CARDIOSYNCHRONOUS ELECTROMYOSTIMULATION IN PATIENTS WITH ACUTE HEART FAILURE

2013 ◽  
Vol 12 (6) ◽  
pp. 15-20
Author(s):  
G. G. Ivanov ◽  
M. Yu. Orkvasov ◽  
G. Khalabi
Keyword(s):  
Heart Failure ◽  
Conservative Treatment ◽  
Acute Heart Failure ◽  
Clinical Symptoms ◽  
Impedance Measurement ◽  
Pharmacological Therapy ◽  
Group I ◽  
Group Ii ◽  
One Year ◽  
The One

Aim. To study the effectiveness of the external cardiosynchronous electromyostimulation (ECSEMS) in patients with different variants of acute heart failure (AHF).Material and methods. The study included 62 AHF patients: Group I — those receiving only standard pharmacological therapy; and Group II — those in whom standard pharmacological therapy was ineffective after 12 hours, and who were also administered ECSEMS sessions for the next 7 days. The examination included multi-frequency bio-impedance measurement and dispersion mapping.Results. Clinical symptoms were less severe in Group I. In 64% of the Group II patients, the combination treatment was associated with a positive dynamics of the water balance parameters. The 7-day ECSEMS, as a part of the complex management of AHF patients, significantly reduced the one-month lethality, although did not change the one-year survival.Conclusion. The ECSEMS method could be used in order to increase the effectiveness of the conservative treatment of AHF patients. 

scholarly journals Allogeneic Stem Cell Transplantation Overcomes the Negative Prognostic Impact of TP53 Alterations in Mantle Cell Lymphoma

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4668-4668 ◽  
Author(s):  
Richard J Lin ◽  
Caleb Ho ◽  
Patrick Hilden ◽  
Juliet Barker ◽  
Sergio Giralt ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
P53 Protein ◽  
Prognostic Impact ◽  
Cell Transplant ◽  
Protein Overexpression ◽  
Oncogenic Mutation ◽  
Mantle Cell ◽  
One Year ◽  
The One

Abstract TP53 alterations detected by chromosome 17p deletion, oncogenic mutation, or p53 protein overexpression portend extremely poor prognosis for patients with mantle cell lymphoma (MCL), despite aggressive upfront therapy including consolidative high-dose therapy autologous stem cell transplant and; more recently, novel agents such as ibrutinib or lenalidomide. We reviewed outcomes of 42 patients with available TP53 status who had received reduced-intensity/non-myeloablative conditioning (RIC/NMA) allogeneic hematopoietic cell transplant (allo-HCT) for MCL at our institution and examined the impact of TP53 alteration and other clinical factors on outcomes. Nineteen patients had TP53 alterations including 17p deletion (n=3), oncogenic mutation (n=7), and strong p53 protein overexpression by immunohistochemistry (n=9). There were no differences in demographic or clinical characteristics among patients with and without TP53 alterations (Table 1). With a median follow-up for survivors of 23 months (range 4-119), the one-year overall survival (OS) and progression-free survival (PFS) is 87% (95% CI 72-94) and 74% (95% CI 57-85), respectively (Figure 1A). The one-year cumulative incidence of relapse and non-relapse mortality is 16% (95% CI 6-29) and 10% (95% CI 3-22), respectively (Figure 1B). The cumulative incidences of grade II-IV acute GVHD is 38% at 180 days (95% CI 24-53), and of any chronic GVHD is 33% at three-year (95% CI 17-49). Importantly, there is no statistically significant difference in OS (p=0.582, Figure 1C), and cumulative incidence of relapse (p=0.715, Figure 1D) among patients with and without TP53 alterations. In univariate and multivariate analyses, we find that only Ki67 >30% is a significant predictor of PFS (HR 4.1, 95% CI 1.1-15.5, p=0.024), and that only Karnofsky Performance Status (KPS) <90 is a significant predictor of OS (HR 4.9, 95% CI 1.4-17, p=0.01). This is the first report that RIC/NMA allo-HCT could overcome the negative prognostic impact of TP53 alterations in MCL with relatively low incidence of transplant-related mortality. While requiring prospective evaluation, our data supports the consideration of RIC/NMA allo-HCT for MCL patients with TP53 alterations. Disclosures Ho: Invivoscribe, Inc.: Honoraria. Hamlin:Portola: Consultancy. Perales:Novartis: Other: Personal fees; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Personal fees and Clinical trial support; Merck: Other: Personal fees; Takeda: Other: Personal fees; Abbvie: Other: Personal fees. Sauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

scholarly journals DETECTION OF AEROLYSIN (aerA) GENE IN AEROMONAS HYDROPHILA STRAINS ISOLATED FROM DISEASED CARP

2014 ◽  
Vol 6 (2) ◽  
Author(s):  
Vladimir Radosavljević ◽  
Miroslav Ćirković ◽  
Dragana Ljubojević ◽  
Nikolina Novakov ◽  
Đorđe Cvetojević ◽  
...  
Keyword(s):  
Clinical Symptoms ◽  
Pcr Amplification ◽  
Sudden Increase ◽  
Extracellular Lipase ◽  
Extracellular Proteases ◽  
Hemolytic Toxin ◽  
One Year ◽  
The One ◽  
Motile Aeromonas Septicaemia ◽  
Common Infection

Bacterial septicemia caused by motile aeromonads is common infection in the intensive fish production. Aeromonas (A.) hydrophila is often present in fish populations. Ubiquitous distribution of these bacteria in the aquatic environment, and the stress caused by intensive breeding are predisposing factors for the occurence of the disease. A. hydrophila is considered a major cause of septicaemia caused by motile aeromonads. Several A. hydrophila extracellular products (ECP) are considered as important factors in pathogenesis, primarily aerolysin (aerA), the extracellular lipase, cytolytic enterotoxin, hemolytic toxin and extracellular proteases. PCR detection of aerolysin (aerA) is considered a reliable method of identifying potentially pathogenic Aeromonas strains. In spring 2012, after a sudden increase in water temperature, disease occured in common carp population in one fish farm in Serbia. Five specimens of the one-year-old carp with clinical symptoms of motile aeromonas septicaemia were used for isolation of the bacteria. Identification of A. hydrophila was done on the basis of morphological, physiological, cultural and biochemical characteristics. PCR amplification of DNA from A. hydrophila isolates revealed presence of aerolysin (aerA) gene in all examined A. hydrophila isolates from carp with motile aeromonas septicaemia.

scholarly journals Post-Transplant Cyclophosphamide Is Associated with Improved Clinical Outcomes in HLA-Mismatched Unrelated Donor Hematopoietic Cell Transplantation

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1814-1814
Author(s):  
Antonio M. Jimenez ◽  
Miguel-Angel Perales ◽  
Sean M Devlin ◽  
Lazaros J. Lekakis ◽  
Craig S. Sauter ◽  
...  
Keyword(s):  
Cell Transplantation ◽  
Graft Versus Host Disease ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Unrelated Donor ◽  
Graft Versus Host ◽  
Post Transplant ◽  
One Year ◽  
The One ◽  
Neutrophil Engraftment

Abstract The current standard of care to prevent graft versus host disease (GVHD) after HLA mismatched unrelated donor (URD) allogeneic hematopoietic cell transplantation (HCT) is tacrolimus, methotrexate (MTX) and anti-thymocyte globulin (ATG). Recently, an approach based on administration of post-transplant cyclophosphamide (PT-Cy) demonstrated promise in a prospective trial for HLA mismatched URD HCT. Here, we compared tacrolimus/MTX/ATG (ATG group) treatment, with that of PT-Cy, mycophenolate mofetil, and tacrolimus or sirolimus (PT-Cy group) after HLA mismatched URD HCT, at two academic centers with similar peri-transplant supportive care practices. Subjects that underwent HCT from a URD mismatched at one or more loci among HLA-A, -B, -C, and -DRB1 from 2010-2020 were included. The primary endpoint of our study was one-year GVHD-free, relapse-free survival (GRFS). Of 128 total subjects included (ATG: 46; PT-Cy: 82), the median age was 54.7 (range: 21.0 - 72.0) in the ATG group and 60.3 (21.0 - 75.2) in the PT-Cy group. Notably, 74 subjects (57.8%) belonged to a racial/ethnic minority, while 53 (41.4%) received a bone marrow (BM) graft, and 26 (20.3%) received a highly mismatched (i.e., &lt;6/8 HLA) graft. A higher proportion of PT-Cy subjects received BM (50% vs. 26.1%, P= 0.01) and highly mismatched grafts (30.5% vs. 2.2%, P=0.001). The groups were well matched for key demographic data, including indication for HCT, high-risk disease, and HCT comorbidity index. The rate of primary neutrophil engraftment at day 28 post HCT was similar between the two groups: 91% (83%-99%), in the ATG group, and 90% (84%-97%), in the PT-Cy group. The median day of neutrophil engraftment was +17 in the ATG, and +20 in the PT-Cy groups. Platelet engraftment at day 100 was 84.8% (74.4% - 95.2%) and 86.6% (79.2% - 94%) in the ATG and PT-Cy groups, respectively. Among subjects that survived 3-months post HCT and had donor chimerism testing, full donor chimerism (≥95% donor) was achieved in 24/26 (92.3%) patients in the ATG group, and 61/68 (89.7%) subjects in the PT-Cy group. Overall, the one-year GRFS was 16% (95% confidence interval: 8% - 31%) vs. 54% (44% - 66%, p &lt; 0.001) in the ATG and PT-Cy groups, respectively. The adjusted, multivariate hazard ratio (HR) for GRFS was 0.34 (0.21 - 0.55, p &lt; 0.001), in association with the use of PT-Cy. The one-year overall survival (OS) in the ATG group was 45% (32% - 62%) vs. 75% (66% - 85%, p &lt; 0.001) in the PT-Cy group. There was no difference in 2-year relapse incidence (27%, 14-39% vs. 19%, 10% - 28%, p = 0.2), whereas 1-year non-relapse mortality (NRM) was increased with ATG-based prophylaxis: (38%, 23% - 52% vs. 16%, 9% - 25%, p = &lt;0.001). The use of PT-Cy was associated with improved GRFS for patients treated with BM (HR = 0.27, 0.11 - 0.62; p = 0.002) and G-CSF mobilized, peripheral blood derived (PB) grafts (HR = 0.39, 0.21 - 0.71; p = 0.002). BM grafts were not an independent predictor of GRFS (HR: 1.2, 0.8 - 1.9; p = 0.5) in a multivariate Cox regression model. The use of PT-Cy, compared to ATG, was associated with lower rates of grade 3-4 acute GVHD in the entire cohort (ATG: 22%, 18% - 45% vs. PT-Cy: 15%, 8% - 23%; p = 0.03), and in the sub-cohorts of patients transplanted with PB (ATG: 33%, 17% - 49% vs. PT-Cy: 20%, 9% - 33%) and BM grafts (ATG: 25%, 1% - 50% vs. PT-Cy: 10%, 1% - 19%). Chronic GVHD requiring systemic immune suppression was more frequent in the ATG/PB group (26%, 13% - 42%) than in the ATG/BM (8%, 0% - 24%), the PT-Cy/PB (8%, 2% - 19%), and the PT-Cy/BM (10%, 1% - 19%) groups. Despite greater HLA-mismatching, PT-Cy following mismatched URD HCT resulted in superior GRFS, OS and lower NRM and GVHD rates compared to ATG-based GVHD prophylaxis. These results indicate that PT-Cy is the preferred method to prevent GVHD after mismatched URD HCT and confers a benefit in patients treated with either PB or BM-derived allografts. Combinatorial approaches, using the T-cell co-stimulatory blockading agent abatacept, in addition to tacrolimus/methotrexate, may also prevent GVHD in this population, and can be compared to a PT-Cy-based approach in a prospective clinical trial. Figure 1 Figure 1. Disclosures Jimenez: AbbVie: Research Funding; Takeda: Research Funding. Perales: MorphoSys: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Karyopharm: Honoraria; Merck: Honoraria; Equilium: Honoraria; Miltenyi Biotec: Honoraria, Other; Medigene: Honoraria; Kite/Gilead: Honoraria, Other; Incyte: Honoraria, Other; Cidara: Honoraria; Takeda: Honoraria; Nektar Therapeutics: Honoraria, Other; Servier: Honoraria; Sellas Life Sciences: Honoraria; Omeros: Honoraria; NexImmune: Honoraria; Novartis: Honoraria, Other. Sauter: Precision Biosciences: Consultancy; Genmab: Consultancy; Celgene: Consultancy, Research Funding; Kite/Gilead: Consultancy; Bristol-Myers Squibb: Research Funding; GSK: Consultancy; Gamida Cell: Consultancy; Novartis: Consultancy; Spectrum Pharmaceuticals: Consultancy; Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding. Beitinjaneh: Kite/Gilead: Other: Ad Board Event Attendee. Ponce: CareDx: Consultancy, Honoraria; Ceramedix: Consultancy, Honoraria; Seres Therapeutics: Consultancy, Research Funding; Kadmon pharmaceuticals: Consultancy, Honoraria; Takeda Pharmaceuticals: Research Funding; Generon Pharmaceuticals: Consultancy. OffLabel Disclosure: Off-label use of Cyclophosphamide for Graft-versus-Host Disease prevention will be discussed in the abstract.

Rapid regression of macroprolactinomas by the new dopamine partial agonist terguride

1986 ◽  
Vol 111 (4) ◽  
pp. 460-466 ◽  
Author(s):  
K.-J. Gräf ◽  
D. Köhler ◽  
R. Horowski ◽  
R. Dorow
Keyword(s):  
Clinical Symptoms ◽  
Partial Agonist ◽  
Imaging Techniques ◽  
Tumour Mass ◽  
Residual Tumour ◽  
Good Tolerance ◽  
Magnetic Resonance Imaging Mri ◽  
One Year ◽  
The One

Abstract. Two patients with macroprolactinomas were treated with the partial dopamine agonist, terguride. The prolactin (Prl) levels were lowered very effectively and in both cases the clinical symptoms improved markedly during the first days of treatment. Computerized tomography (CT) and magnetic resonance imaging (MRI) follow-up studies showed distinct tumour shrinkages which were first documented by MRI within 2 weeks of treatment. Tumour residues were, however, still demonstrable by MRI after more than one year respectively 3 months of therapy. In principal, results from both imaging techniques were comparable with the exception of the one year follow-up study of patient 1. In CT no residual tumour mass was visible whereas MRI showed only little reduction when compared to the 30th week scan. Throughout the treatment terguride was well tolerated without any side effects up to a maximal daily dosage of 3 mg given orally. Presumably the partial agonistic features of terguride contributed to the good tolerance of the treatment as compared to that of full dopamine agonists like bromocriptine or lisuride. Thus, these preliminary results indicate that terguride may be a beneficial alternative in the treatment of prolactinomas and other hyperprolactinaemic states.

CURRENT ASPECTS OF DRUG THERAPY OF CHRONIC HEART FAILURE SYNDROME

2020 ◽  
Vol 4 (2) ◽  
pp. 1085-1096
Author(s):  
T.V. Statkevich ◽  
◽  
N.P. Mitkovskaya ◽  
◽  
Keyword(s):  
Quality Of Life ◽  
Heart Failure ◽  
Drug Therapy ◽  
Chronic Heart Failure ◽  
Clinical Symptoms ◽  
Nyha Class ◽  
Treatment And Prevention ◽  
One Year ◽  
The One

Chronic heart failure (CHF) is an important problem for the country, which has both medical and socio-economic aspects. The presence of the syndrome not only significantly increases the risks of an unfavorable course of diseases underlying its etiological basis, but in itself, through the development of decompensation, causes a high frequency of deaths. Despite all the advances in pharmacotherapy, the prognosis of heart failure remains poor. More than 40% of patients die within 4 years after the diagnosis of heart failure, and the one-year mortality rate for patients with severe CHF (NYHA class IV) exceeds 50%. The foregoing determines the need and importance of using all possible drug and non-drug therapy technologies aimed at reducing mortality, increasing the duration and quality of life of patients with CHF, as well as reducing the number and likelihood of decompensation and related hospitalizations, and makes this direction one of the priorities in medicine. The article describes current approaches to the treatment of patients with CHF syndrome from the perspective of evidence-based medicine and taking into account the recommendations of leading international organizations for the treatment and prevention of cardiovascular diseases. The drugs used were analyzed in terms of their influence on clinical symptoms, quality of life of patients, the risk of hospitalization due to decompensation of CHF, and mortality rates. The emphasis is made on the possibilities, mechanism of action and further prospects for the use of a new class of drugs in the treatment of CHF, acting at the level of the renin-angiotensin-aldosterone system and the system of neutral endopeptidases - inhibitors of angiotensin-neprilisin receptors.

Molecular Remission One Year Following Reduced-Intensity Allogeneic Hematopoietic Cell Transplantation for Chronic Lymphocytic Leukemia Predicts Relapse-Free and Overall Survival: A Multi-Institutional Landmark Analysis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4340-4340
Author(s):  
Aaron C. Logan ◽  
Alex F. Herrera ◽  
Christine E. Ryan ◽  
Andrew R. Rezvani ◽  
Katherine A. Kong ◽  
...  
Keyword(s):  
Overall Survival ◽  
High Risk ◽  
Peripheral Blood ◽  
Research Funding ◽  
Hematopoietic Cell Transplantation ◽  
Chronic Gvhd ◽  
Lymphocytic Leukemia ◽  
Increased Risk ◽  
One Year ◽  
The One

Abstract Introduction: Chronic lymphocytic leukemia (CLL) cells typically carry one or more clonally rearranged immunoglobulin (Ig) genes. The specific sequence of an Ig rearrangement, or clonotype, can serve as a marker of minimal residual disease (MRD) in blood or bone marrow samples. The clonoSEQ assay (Adaptive Biotechnologies Corp) employs a next-generation sequencing (NGS) based MRD quantification method that uses consensus primers to amplify and then sequence the entire repertoire of Ig genes in a clinical sample. Each Ig clonotype, including the one marking a patient's CLL, can then be individually quantified with high precision. We previously demonstrated the utility of this NGS approach for predicting relapse-free survival in a single-institution cohort of CLL patients undergoing reduced-intensity allogeneic hematopoietic cell transplantation (RIC alloHCT). In this landmark analysis, we now assess the prognostic utility of molecular MRD quantification one year following RIC alloHCT in a multi-institution cohort. Methods: We retrospectively evaluated the outcomes and MRD status of patients surviving without relapse to one year after RIC alloHCT for CLL. Patients were assessable for MRD based on availability of a tumor specimen from which to determine the CLL-associated Ig heavy chain (IgH) clonotypes and a cryopreserved peripheral blood mononuclear cell (PBMC) aliquot obtained one year post-HCT. Forty-six patients underwent conditioning with total lymphoid irradiation and anti-thymocyte globulin (TLI/ATG) and 56 were conditioned with fludarabine and busulfan (Flu/Bu) regimens. Clonal IgH rearrangements were identified by NGS-based IgH profiling in CLL-bearing blood or marrow samples obtained prior to HCT and these clonotypes were quantified in the IgH repertoire of PBMC samples from one year (+/- 90 days) post-HCT. Results: One hundred two patients were assessable for outcomes beyond the one year post-HCT landmark. Amongst 97 patients with a diagnostic sample available, the IgH clonotype calibration rate was 90%. Five archived diagnostic samples yielded insufficient DNA to proceed with clonotype identification. 87/102 (85%) patients had paired tumor and one year PBMC samples suitable for MRD quantification. Patients receiving TLI/ATG or Flu/Bu conditioning had similar clinical characteristics. Median relapse-free survival (RFS) from the one year landmark was 4.7 years with TLI/ATG and 6.8 years with Flu/Bu (p=0.08; Figure 1A), and overall survival was not significantly different (Figure 1B). Acute GVHD (grades 2-4) occurred in 15.6% with TLI/ATG and 37.5% with Flu/Bu. Chronic GVHD occurred in 53% and 77%, respectively, with less extensive grade chronic GVHD using TLI/ATG (39%) compared with Flu/Bu (73%). Amongst patients alive and in remission one year after RIC alloHCT, peripheral blood MRD <10-6 was associated with more favorable outcomes, with just 5.3% relapsing within 7 years post transplant, compared with 59% relapse in those with ≥10-6 MRD (HR 11, 95% CI 4.3-28, p<0.0001; Figure 1C). MRD negativity one year post-HCT was also associated with improved long term overall survival (HR 2.6, 95% CI 1.1-6.4, p=0.03; Figure 1D). Conclusions: In this non-randomized retrospective analysis of outcomes after RIC alloHCT for high-risk CLL, use of TLI/ATG or Flu/Bu conditioning regimens were associated with similar RFS, though a trend toward earlier relapse with TLI/ATG is observed. Flu/Bu was associated with substantially higher rates of acute and chronic GVHD and higher rates of death in remission. Irrespective of conditioning regimen used, molecular MRD quantification at one year post-HCT provides strong positive and negative predictive value for subsequent relapse. Identification of MRD positive patients at risk for relapse may permit the implementation of post-HCT immune modulation or maintenance treatment to reduce relapse risk for those in need, but spare MRD negative patients from the potential for additional toxicity. Figure 1. Relapse-free (A) and overall (B) survival in high-risk CLL patients undergoing RIC alloHCT following TLI/ATG or Flu/Bu conditioning. At one year after RIC alloHCT, peripheral blood MRD ≥10-6 strongly predicts increased risk of relapse (p<0.0001) (C) and decreased overall survival (p=0.03) (D). Figure 1. Relapse-free (A) and overall (B) survival in high-risk CLL patients undergoing RIC alloHCT following TLI/ATG or Flu/Bu conditioning. At one year after RIC alloHCT, peripheral blood MRD ≥10-6 strongly predicts increased risk of relapse (p<0.0001) (C) and decreased overall survival (p=0.03) (D). Disclosures Logan: Pharmacyclics: Consultancy; Amgen: Consultancy; Jazz Pharmaceuticals: Consultancy. Herrera:Genentech: Research Funding; Sequenta, Inc.: Research Funding; Pharmacyclics: Research Funding. Rezvani:Pharmacyclics: Research Funding. Kong:Adaptive Biotechnologies Corp: Employment, Equity Ownership. Faham:Adaptive Biotechnologies Corp.: Employment, Other: Stockholder. Miklos:Pharmacyclics: Research Funding.

Resources: Internet Resources for the Independent Medical Evaluator – 2007

2007 ◽  
Vol 12 (4) ◽  
pp. 4-7
Author(s):  
Christopher R. Brigham ◽  
Jenny Walker
Keyword(s):  
Head Trauma ◽  
Clonic Seizure ◽  
Acute Subdural Hematoma ◽  
Orbital Fracture ◽  
Orbital Wall ◽  
First Occurrence ◽  
One Year ◽  
The One ◽  
Neurological Injuries ◽  
Medial Orbital Wall

Abstract Rating patients with head trauma and multiple neurological injuries can be challenging. The AMA Guides to the Evaluation of Permanent Impairment (AMA Guides), Fifth Edition, Section 13.2, Criteria for Rating Impairment Due to Central Nervous System Disorders, outlines the process to rate impairment due to head trauma. This article summarizes the case of a 57-year-old male security guard who presents with headache, decreased sensation on the left cheek, loss of sense of smell, and problems with memory, among other symptoms. One year ago the patient was assaulted while on the job: his Glasgow Coma Score was 14; he had left periorbital ecchymosis and a 2.5 cm laceration over the left eyelid; a small right temporoparietal acute subdural hematoma; left inferior and medial orbital wall fractures; and, four hours after admission to the hospital, he experienced a generalized tonic-clonic seizure. This patient's impairment must include the following components: single seizure, orbital fracture, infraorbital neuropathy, anosmia, headache, and memory complaints. The article shows how the ratable impairments are combined using the Combining Impairment Ratings section. Because this patient has not experienced any seizures since the first occurrence, according to the AMA Guides he is not experiencing the “episodic neurological impairments” required for disability. Complex cases such as the one presented here highlight the need to use the criteria and estimates that are located in several sections of the AMA Guides.

Catheter-directed foam sclerotherapy treatment of saphenous vein incompetence

VASA ◽  
2012 ◽  
Vol 41 (2) ◽  
pp. 120-124 ◽  
Author(s):  
Asciutto ◽  
Lindblad
Keyword(s):  
Saphenous Vein ◽  
Short Term ◽  
Foam Sclerotherapy ◽  
Results Of Treatment ◽  
Ulcer Healing Rate ◽  
Complete Obliteration ◽  
Ceap Classification ◽  
One Year ◽  
The One

Background: The aim of this study is to report the short-term results of catheter-directed foam sclerotherapy (CDFS) in the treatment of axial saphenous vein incompetence. Patients and methods: Data of all patients undergoing CDFS for symptomatic primary incompetence of the great or small saphenous vein were prospectively collected. Treatment results in terms of occlusion rate and patients’ grade of satisfaction were analysed. All successfully treated patients underwent clinical and duplex follow-up examinations one year postoperatively. Results: Between September 2006 and September 2010, 357 limbs (337 patients) were treated with CDFS at our institution. Based on the CEAP classification, 64 were allocated to clinical class C3 , 128 to class C4, 102 to class C5 and 63 to class C6. Of the 188 patients who completed the one year follow up examination, 67 % had a complete and 14 % a near complete obliteration of the treated vessel. An ulcer-healing rate of 54 % was detected. 92 % of the patients were satisfied with the results of treatment. We registered six cases of thrombophlebitis and two cases of venous thromboembolism, all requiring treatment. Conclusions: The short-term results of CDFS in patients with axial vein incompetence are acceptable in terms of occlusion and complications rates.

Regional household poverty and mobility analysis – a transition probability approach

2020 ◽  
Vol 63 (3) ◽  
pp. 286-302
Author(s):  
Damian Mowczan ◽  
Keyword(s):  
Transition Probability ◽  
General Level ◽  
Transition Matrices ◽  
Equivalent Unit ◽  
Central Statistical ◽  
Per Capita ◽  
Probability Matrices ◽  
General Mobility ◽  
One Year ◽  
The One

The main objective of this paper was to estimate and analyse transition-probability matrices for all 16 of Poland’s NUTS-2 level regions (voivodeship level). The analysis is conducted in terms of the transitions among six expenditure classes (per capita and per equivalent unit), focusing on poverty classes. The period of analysis was two years: 2015 and 2016. The basic aim was to identify both those regions in which the probability of staying in poverty was the highest and the general level of mobility among expenditure classes. The study uses a two-year panel sub-sample of unidentified unit data from the Central Statistical Office (CSO), specifically the data concerning household budget surveys. To account for differences in household size and demographic structure, the study used expenditures per capita and expenditures per equivalent unit simultaneously. To estimate the elements of the transition matrices, a classic maximum-likelihood estimator was used. The analysis used Shorrocks’ and Bartholomew’s mobility indices to assess the general mobility level and the Gini index to assess the inequality level. The results show that the one-year probability of staying in the same poverty class varies among regions and is lower for expenditures per equivalent units. The highest probabilities were identified in Podkarpackie (expenditures per capita) and Opolskie (expenditures per equivalent unit), and the lowest probabilities in Kujawsko-Pomorskie (expenditures per capita) and Małopolskie (expenditures per equivalent unit). The highest level of general mobility was noted in Małopolskie, for both categories of expenditures.

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