Academic literature on the topic '665.7.038.5 (043.5)'

Room-temperature single-crystal X-ray structure determinations are recorded for a number of adducts of hydrated lanthanoid(III) trichlorides with 2,2′-bipyridine (‘bpy’) and 1,10-phenanthroline (‘phen’), crystallized from water, methanol or ethanol solutions, containing mononuclear arrays with 1 : 2 Ln/bpy or phen stoichiometry. LaCl3/phen/H2O(1 : 3 : 9), [(phen)2La(OH2)5]Cl3.phen.4H2O, although of overall 1 : 3 LaCl3/phen stoichiometry, has a lattice phen; it is orthorhombic, Pnna, a 19·947(7), b 16·457(5), c 12·213(2) Å, Z = 4; conventional R on |F| was 0·030 for No 2567 ‘observed’ (I >3σ(I)) diffractometer reflections. LaCl3/phen/H2O/MeOH (1 : 2 : 6 : 1), [(phen)2La(OH2)5]Cl3.H2O.MeOH, is triclinic, P 1, a 19·060(3), b 9·252(3), c 8·994(3) Å, α 69·33(3), β 86·81(2), γ 89·66(2)°, Z = 2, R 0·037 for No 5452. LaCl3/bpy/H2O (1 : 2 : 6), [(bpy)2La(OH2)4Cl]Cl2.2H2O, is monoclinic, P 21/c, a 19·389(3), b 9·071(1), c 16·873(2) Å, β 114·10(1)°, Z = 4, R 0·029 for No 4699. All three of these complexes have a nine-coordinate [(N,N′-bidentate)2La(unidentate)5] coordination environment with quasi-2 symmetry; that of the remaining compounds following is eight-coordinate [(N,N′-bidentate)2Ln(unidentate)4]. LuCl3/phen/H2O (1 : 2 : 6), [(phen)2Lu(OH2)4]Cl3.2H2O, is monoclinic, C 2/c, a 11·045(7), b 17·660(6), c 14·474(9) Å, β 92·82(5)°, Z = 4, R 0·042 for No 1695, the Lu lying on a crystallographic 2 -axis. Crystals of LnCl3/phen/H2O(1 : 2 : 4), [(phen)2Ln(OH2)3Cl]Cl2.H2O (Ln = Dy, Er, Y), are triclinic, P 1, a≈ 12·6, b ≈ 10·5, c ≈ 10·4 Å, α ≈ 93·3, β ≈ 109·3, γ ≈ 96·8°, Z = 2, R 0·030, 0·040, 0·052 for No 4221, 5100, 2690 respectively. PrCl3/bpy/H2O/EtOH (1 : 2 : 1 : 0·5), [(bpy)2Pr(OH2)Cl3].½EtOH, is triclinic, P 1, a 13·331(3), b 10·734(2), c 9·758(2) Å, α 63·67(2), β 78·99(2), γ 71·24(2)°, Z = 2, R 0·033 for No 4596, while [(bpy)2Pr(OH2)2Cl2]Cl is monoclinic, C 2/c, a 15·921(15), b 11·314(8), c 14·114(8) Å, β 116·70(6)°, Z = 4, R 0·041 for No 2269. ErCl3/bpy/H2O(1 : 2 : 2 (also)), [(bpy)2Er(OH2)2Cl2]Cl, is cubic, I 23, a 26·032(4) Å, Z = 24, R 0·066 for No 1644. Crystals of LnCl3/phen/H2O/MeOH (1 : 2 : 1 : 1), [(phen)2Ln(OH2)Cl3].MeOH (Ln = La, Pr, Nd, Eu), are monoclinic, P 21/a, a ≈ 13·2, b ≈ 10·7, c ≈ 18·5 Å, β ≈ 102·1°, Z = 4, R 0·054, 0·032, 0·040, 0·054 for No 2872, 4792, 3179, 2847 respectively. LnCl3/bpy/H2O/EtOH (1 : 2 : 1 : 1), [(bpy)2Ln(OH2)Cl3].EtOH (Ln = Nd, Eu), are triclinic, P 1, a ≈ 11·3, b ≈ 10·9, c ≈ 10·4 Å, α ≈ 75·5, β ≈ 89·8, γ ≈ 78·0°, Z = 2, R 0·044, 0·056 for No 4979, 3596 respectively. LaCl3/bpy/EtOH (1 : 2 : 0·5) is binuclear [(bpy)2Cl2La(µ-Cl)2LaCl2(bpy)2].EtOH, monoclinic, P 21/c, a 9·6878(2), b 17·5696(3), c 16·1341(2) Å, β 123·10(1)°, Z = 2, R 0·033 for No 4256. A totally unsolvated array is found for YbCl3/bpy (1 : 2), [(bpy)2YbCl3], monoclinic, P 21/c, a 15·065(8), b 8·598(4), c 16·92(1) Å, β 112·46(5)°, Z = 4, R 0·032 for No 3548, in which, alone, the metal atom is seven-coordinate.

Room-temperature single-crystal X-ray structural characterizations of two oxidation products of triphenylstibine of the form XPh3SbOSbPh3X are recorded for X = Cl, NO3. ClPh3SbOSbPh3Cl is monoclinic, P 21/c, Z = 4 f.u., a 9·109(4), b 19·809(8), c 19·30(2) Å, β 109·27(5)°, conventional R on F being 0·038 for No 4431 ‘observe’ (I > 3σ(I)) independent reflections. In this complex, Sb-O-Sb is quasi-linear, 173·1(3)°, in contrast to the previously recorded benzene solvate, in which it is 139·0(3)°; in the nitrate, [(O2NO)Ph3SbOSbPh3(ONO2)], triclinic, P-1, Z = 2 f.u., a 15·609(5), b 13·238(4), c 10·140(2) Å, α 87·11(2), β 88·46(7), γ 72·93(2)°, R 0·036 for No 5275, it is also bent (137·0(2)°). The anionic substituent is opposed to the oxo bridge in the trigonal bipyramidal five-coordinate array about the metal in both complexes. A redetermination of the structure of Ph8Sb4O6 is recorded, presenting a non-disordered model in a triclinic P-1 cell, a 19·98(3), b 11·635(2), c 9·739(2) Å, α 92·28(1), β 98·98(1), γ 99·74(1)°, Z = 2 f.u., R 0·046 for No 3578. A new (‘β’) phase of triphenylstibine, crystallized from hexane/toluene is also recorded: monoclinic, P 21/c, a 15·386(8), b 11·304(5), c 19·078(8) Å, β11·64(4)°, Z = 8, R 0·045 for No 3393.

Background:Ocular involvement in sarcoidosis can be present in up to 80% of patients. If not treated, it can lead to significant visually complications (1-5).Objectives:Our aim was to assess the main a) epidemiology and b) clinical features of ocular sarcoidosis in a wide and unselected series from a single university hospital.Methods:Study of a large cohort (n=384) of all consecutive patients diagnosed with sarcoidosis from January 1, 1999 to December 31, 2019. Finally, 344 patients were included according to the ATS/ERS/WASOG criteria (Eur Respir J. 1999;14:735-7).Results:65 (33 men/32 women) of 344 (18.9%) patients had ocular involvement. Mean age at diagnosis was 45.6±15.9 years. The most frequent extraocular clinical clusters were respiratory (80%), osteoarticular (30.8%) and cutaneous (29.2%) (figure 1). Ocular manifestations and complications are shown in table 1. Uveitis (83.1%), orbital lesions (7.7%) and retinal vasculitis (6.2%) were the most common ocular lesions. Median Best Corrected Visual Acuity (BCVA) at diagnosis and after one year of follow-up was 0.6 [0.3-0.8] and 0.9 [0.30-1], respectively. Retinal vasculitis was associated to the worst BCVA outcome, and panuveitis to more frequent and severe complications.Conclusion:Ocular manifestations, especially uveitis, are frequent in sarcoidosis. A more aggressive and early treatment may be indicated in panuveitis and retinal vasculitis.References:[1]Riancho-Zarrabeitia L, et al. Semin Arthritis Rheum 2015;45:361-8.[2]Riancho-Zarrabeitia L et al. Clin Exp Rheumatol 2014; 32:275-84.[3]Vegas-Revenga N, et al. Am J Ophthalmol 2019; 200:85-94.[4]Calvo-Río V, et al. Clin Exp Rheumatol 2014; 32 (4 Suppl 84): S54-7. Epub 2014 Jul 8.[5]Cordero-Coma et al. Mediators Inflamm. 2014; 2014:717598.Figure 1.Clinical clusters of associations in ocular sarcoidosis.Table 1.Ocular manifestations and associated complications after 1 year of follow-up of 65 patients with ocular sarcoidosis.Type of ocular affectationN (%)Median BCVA at onset[IQR]Median BCVA after 1 year of follow-up[IQR]CataractN (%)OPN (%)OHTN (%)CMEN (%)ERMN (%)Uveitis, pattern54 (83.1)0.6 [0.3-0.8]0.9 [0.6-1]18 (27.7)11 (16.9)7 (10.8)7 (10.8)8 (12.3)Anterior31 (47.7)0.7 [0.3-0.8]0.8 [0.5-1]13 (41.9)2 (6.5)2 (6.5)2 (6.5)2 (6.5)Panuveitis16 (24.6)0.4 [0.2-0.7]0.9 [0.5-1]5 (31.3)7 (43.8)4 (25)5 (31.3)5 (31.3)Posterior5 (5.2)0.5 [0.1-0.9]0.9 [0.9-1]02 (40)1 (20)00Intermediate2 (3.1)0.50.700001Orbitary lesions5 (7.7)0.5 [0.1-0.6]1 [0.1-1]1 (20)01 (20)00Retinal vasculitis4 (6.2)0.6 [0.5-0.8]1 [0.6-1]00001 (25)Dry eye4 (6.2)10.900000Scleritis10.61.000000Abbreviations: BCVA: Best corrected visual acuity; CME: Cystoid macular edema ERM: Epiretinal membrane; OP: Optic Papillitis; OHT: Ocular hypertension.Disclosure of Interests:Carmen Álvarez-Reguera: None declared, Jorge Javier Gaitán-Valdizán: None declared, Raúl Fernández-Ramón: None declared, Rosalía Demetrio-Pablo: None declared, José Luis Martín-Varillas: None declared, Lara Sanchez-Bilbao: None declared, David Martínez-López: None declared, Iñigo González-Mazón: None declared, Miguel Á. González-Gay Speakers bureau: Abbvie, Pfizer, Roche, Sanofi and MSD., Grant/research support from: Abbvie, MSD, Janssen and Roche., Ricardo Blanco Speakers bureau: Abbvie, Pfizer, Roche, Bristol-Myer, Janssen, Lilly and MSD., Grant/research support from: Abbvie, MSD and Roche.

The title compound, formed by reaction of 4-mercapto-4-methylpentan-2-one with bis(ethane-1,2-diamine)nickel(II) perchlorate, has a centrosymmetrical dinuclear cation. Each singlet ground-state nickel(II) ion is in tetrahedrally twisted square-planar coordination by the primary amine and imine nitrogen atoms and the thiolato sulfur atom of one molecule of 7-amino-2,4-dimethyl-5-azahept-4-ene-2-thiolate (adet¯), and the sulfur atom of another molecule, with the sulfur atoms of two ligands forming a planar Ni2S2 bridging group {[Ni2-µ-(adet)2] (ClO4)2, C16H34C12N4Ni2O8S2, Mr 662·9, monoclinic, P21/c, a 8·267(1), b 9·952(1), c 16·234(2) Å, β 103·010(2)°, R1 0·033 for 2531 reflections}.

Abstract Liver histology is regarded as inadequate for grading the severity of H-GVHD. Thus, liver biopsies (LB) are only performed to rule out other causes of liver injury when the results may lead to a radical therapeutic change. In this study we reviewed the pathologic features in LB from 33 consecutive evaluable patients with at least one LB, confirmed diagnosis of H-GVHD and no other concomitant causes of liver dysfunction. We asked whether the pathologic features in the first LB may predict their clinical outcome. Underlying diseases were AML (9), ALL (8), CML (7), MM (4), MDS (3), NHL (1) and AA (1). H-GVHD developed after BM (15) or PB (11) allo-HSCT, or DLI (7). Twenty-eight donors were related and 5 unrelated, 30 HLA-matched and 3 mismatched. All patients received myeloablative TBI-based (31) or chemotherapy only (2) conditioning regimens, and GVHD prophylaxis with cyclosporine-methotrexate (21) or T-cell depletion (12). The onset was acute in 22 (median day 35, range 5–86) and chronic in 11 (median day 139, range 103–545). The median overall survival (OS) from the onset of liver dysfunction was 6.2 months, with a non-relapse mortality (NRM) of 73.2% at 1 year (CI95=50.2–96.2). The causes of NRM were infection (8), liver failure (3), hemorrhage (3) and others (4). The first LB was performed at a median of 14 days (4–68) from the onset of abnormal liver function tests. The commonest pathologic finding in this series was bile duct damage, but ductopenia was uncommon (4). Neither the presence nor the degree of bile duct damage associated with the clinical outcome. Lobular inflammation (LI) was present in 25 cases (grade 1: 16; grade 2: 6; grade 3: 3). Higher degree of LI in the first LB associated with a reduced NRM (P=.001) and improved OS (P<.001). Patients with LI grades 2/3 had higher median OS than those with grades 0/1 (not-reached vs 4.3 months; P=.012), and were more likely to respond to primary treatment (RPT) with steroids (P=.044), the most important clinical prognostic factor for OS in our series (HR=4.3; P=.001). Presentation of H-GVHD as hepatitis, with markedly increased aminotransferases levels, has been reported, in particular after DLI. In our group, there was no association between DLI-induced H-GVHD and LI, or between LI and aminotrasferases peak or biopsy-time levels. No study to date has shown that LI in the LB associated with clinical outcome in H-GVHD. In liver transplantation however, a histologically documented lobular hepatitic phase has been shown to anticipate ductopenia in chronic rejection, and associate with good response to treatment. In addition to LI, hepatocyte ballooning (HB) was associated with NRM (P=.003) and OS (P=.018) in our series. Patients with HB grades 0/1 had higher median OS than those with grades 2/3 (6.5 months vs 1.3 months; P=.004). HB did not associate with RPT. In multivariate analysis the effects of LI and HB on NRM (HR=5.1, P=.033; and HR=5.5, P=. 018, respectively) and OS (HR=4.0, P=.032; and HR=4.2, P=.037, respectively) remained significant. All other pathologic features examined had no association with patient clinical outcome. Our results suggest that LI and HB in the first diagnostic LB from patients with H-GVHD may predict the probability of RPT, NRM and OS. These results should be considered in the indications of LB and the selection of candidate patients with H-GVHD for new experimental therapies and in the design of future trials. Prospective validation of our findings is under way.

Abstract Idiopathic neutropenia in children is marked by low neutrophil counts (<1500/ul) circulating in the peripheral blood in patients whose disease spontaneously develops unrelated to drugs, cancers, specific antibodies, or known genetic deficiencies. Neutrophils, PBMCs and plasma were purified/obtained from 24 subjects (n=17 acute and n=7 chronic) with idiopathic neutropenia, aged 3 months to 11 yrs. After screening a number of cytokines (IL-2, IL-4 IL-6, IL-8, IL-10, IFN-γ, TNF-α), growth factors (GCSF), cell death factors (Fas, FasL, Granzymes/Perforin), and chemokines (CCL5, XCL1, XCR1), QT-PCR studies of neutropenic subjects’ neutrophils indicated an up-to-14-fold increase in Fas transcripts compared to age-matched healthy control neutrophils. FACS analysis on patient neutrophils demonstrated increased expression of Fas (93%+/− 15%) compared to healthy control neutrophils (41%+/−11%). No increase in Fas surface expression was seen on PBMCs or on CD4+T cells from neutropenia patients compared to healthy controls. Studies of patient plasma showed increased FasL in acute and chronic patients (up to 40-fold higher). Increased IL-6 and IL-10 levels in plasma were another distinctive characteristic of neutropenic patients. Healthy control neutrophils incubated in neutropenic patient plasma for 4 hrs showed greater rates of apoptosis (evaluated by PI/Annexin; up to 38-fold higher) compared to incubation with healthy control plasma. Heat denaturation, IgG exclusion, and size separation studies suggest that the killing factor(s) is a heat-sensitive protein which is not IgG and has a MW between 35 and 100 kD. Blocking with anti-FasL antibodies incubated with patient plasma caused a statistically significant 5-fold to 11-fold decrease in neutrophil apoptosis, approaching the rates of healthy controls, implicating FasL as a major mediator of neutrophil regulation. Thus, the Fas/FasL pathway may play an important role in idiopathic neutropenia. Patient number Chronicity Age FasL (pg/ml) Anti-neutrophil Ab Fold increase in neutrophil death over control plasma Fold increase in apoptosis over control plasma 1 chronic 2 yrs 7±1 positive 6.5±0.7 8.5±0.8 2 chronic 18 mo. 6±1 positive 7.3±0.5 8.1±0.2 3 chronic 23 mo. 5±0.5 wk positive/neg 7.8±0.6 8.5±0.4 4 chronic 1 yr 5±2 positive 6.5±0.5 7.3±0.6 5 chronic 5 yrs 7±1 wk positive 6.1±0.9 2.7±0.2 6 chronic 20 mo. 10±1 negative 11.3±1.4 2.1±0.5 7 chronic 11 mo. 6±1 negative 6.1±0.8 5.7±0.6 8 acute 2 yrs 16±2 N/A 18.7±1.3 22.4±2.9 9 acute 2 yrs 18±3 negative 12.0±2.1 19.1±2.5 10 acute 5 yrs 4±1 negative 2.5±0.5 2.6±0.4 11 acute 11 mo. 3±0.6 N/A 1.5±0.3 2.1±0.2 12 acute 3 yrs 17±1 negative 15.3±1.2 19.2±0.8 13 acute 2 yrs 40±3 negative 22.9±1.4 38.4±2.4 14 acute 2 yrs 21±2 N/A 14.3±1.0 20.5±1.2 15 acute 8 mo. 10±0.9 N/A 9.6±0.8 12.0±1.6 16 acute 17 mo. 19±3 negative 21.3±2.2 26.7±3.5 17 acute 6 yrs 8±1 N/A 6.7±1.3 11.5±2.1 18 acute 3 yrs 9±2 N/A 7.2±2.6 8.8±1.5 19 acute 11 yrs 12±2 negative 14.8±0.9 17.4±1.9 20 acute 5 yrs 6±1 negative 3.4±0.6 5.2±0.7 21 acute 4 mo. 8±2 N/A 6.2±1.0 8.1±2.2 22 acute 3 mo. 27±3 N/A 21.4±3.5 39.4±2.4 23 acute 11 yrs 22±1 negative 17.2±3.0 24.3±2.8 24 acute 2 yrs 18±2 positive 15.8±1.2 25.0±1.7 Representative control N/A 4 yrs 1.3±0.4 N/A 1.2±0.3 0.8±0.4

SUMMARYWe analysed nosocomial MRSA cases between January 2004 and December 2006 in a retrospective case-control study in a 250-bed tertiary-care teaching hospital. During the study period, 265 nosocomial Staphylococcus aureus infections were identified in 231 patients. There was a significant increase in methicillin resistance in isolates (MRSA) from these infections with frequencies for 2004 of 39/88 (44·3%), 2005 (62/80, 77·5%), and 2006 (75/97, 77·3%) (P<0·001). Multivariate analysis showed that associated factors for nosocomial MRSA infection were prolonged hospitalization (OR 3·982, 95% CI 2·235–7·094, P<0·001), mechanical ventilation (OR 3·052, 95% CI 1·666–5·590, P<0·001), surgical operation (OR 2·032, 95% CI 1·102–3·748, P=0·023), and male sex (OR 2·000, 95% CI 1·081–3·699, P=0·027). The determination of associated factors for methicillin resistance in nosocomial S. aureus infections in hospitals will play an important role in efforts to reduce MRSA infection rates.

Room-temperature single-crystal X-ray structure determinations are recorded for a number of adducts of hydrated lanthanoid(III) chlorides with 2,2′-bipyridine, ‘bpy’, crystallized from water/ethanol solutions, which contain mononuclear arrays with 1 : 1 Ln/bpy stoichiometry. Extended isomorphous series have been defined pertinent to the heavy end of the Ln series: crystals of LnCl3/bpy/H2O (1 : 1 : 6) ([(bpy)Ln(OH2)6]Cl3), seemingly inclusive of (at least) the range Ln = Ho(-)Lu and Y, are monoclinic, P 21/n, a ≈ 14·2, b ≈ 7·7, c ≈ 17·4 Å, β ≈ 91°, Z = 4, with an eight-coordinate LnN2O6 array; conventional R values on |F| were 0·043, 0·029, 0·057 for No 2435, 3120, 1846 independent ‘observed’ (I > 3σ(I)) diffractometer reflections (Ln = Ho, Lu, Y). Crystals of LnCl3/bpy/H2O (1 : 1·5 : 8) ([(bpy)Ln(OH2)6]Cl3.½bpy.2H2O), seemingly encompassing (at least) the range Ln = Er(-)Lu and Y, are triclinic, P 1, a ≈ 11·7, b ≈ 11·0, c ≈ 10·1 Å, α ≈ 85·8, β ≈ 74·7, γ ≈ 79·5°, Z = 2, R 0·038, 0·033, 0·048 for No 3897, 4377, 3130, and contain similar [(bpy)Ln(OH2)6]3+ cations as does HoCl3/bpy/H2O (1 : 2 : 7), [(bpy)Ho(OH2)6]Cl3.bpy.H2O, orthorhombic, Pbca, a 18·02(2), b 20·06(2), c 15·051(9) Å, Z = 8, R 0·057 for No 3009. By contrast, only sporadic, diverse and unrelated forms are thus far defined among the lighter Ln: EuCl3/bpy/H2O(1 : 1 : 5) ([(bpy)Eu(OH2)4Cl2]Cl.H2O), triclinic, P 1, a 11·506(7), b 11·098(5), c 6·974(8) Å, α 77·35(7), b 85·1(1), γ 89·54(4)°, Z = 2, R 0·063 for No 4633, also contains a mononuclear [(N,N′-bidentate)Ln(unidentate)6] array. PrCl3/bpy/H2O(1 : 1 : 3)(× 4) is a remarkable compound, being 2[(bpy)Pr(OH2)3Cl3] [(bpy)(H2O)2Cl2Pr(µ-Cl)2PrCl2(OH2)2(bpy)].2H2O, triclinic, P 1, a 13·490(4), b 11·121(2), c 10·162(1) Å, α 96·06(1), β 90·08(2), γ 96·43(2)°, Z = 2 f.u., R 0·045 for No 4127, with a mononuclear species of PrCl3/bpy/H2O (1 : 1 : 3) stoichiometry and a binuclear species of 1 : 1 : 2 stoichiometry. A binuclear ethanol solvated array has been characterized for LaCl3/bpy/EtOH (1 : 1 : 2) [(bpy)(EtOH)2Cl2La(µ-Cl)2LaCl2(HOEt)2(bpy)], with eight-coordinate lanthanum; this complex is triclinic, P 1, a 11·426(8), b 10·673(7), c 10·453(7) Å, α 109·60(5), β 113·10(5), γ 105·80(5)°, Z = 1 dimer, R 0·046 for No 2786.

Abstract Abstract 307 Whole-exome (WES) sequencing revealed tremendous mutational heterogeneity in leukemia. While WES can be applied for discovery, it also has potential as a diagnostic tool that can overcome the shortcomings of current methods. We theorized that, in addition to mutation discovery, systematic application of WES in MDS may reveal distinct mutational patterns allowing for new molecular classification. We performed WES in 116 paired exomes, including MDS (n=57), MDS/MPN (n=36), and sAML (n=23). We also included comparative analysis with pAML (N=202; TCGA), and other publicly available data for a total of 333 exomes; 10 patients were studied serially. Paired DNA (marrow/CD3+ cells) was subjected to WES, sequence-aligned by BW Aligner, and variants detected via GATK pipeline (Broad Institute). We used defined criteria to minimize false-positives: P<.001 tumor/control, alterations ≥10% of total tumor reads, <25% in germline, >5% prevalence, and not found in ex/internal SNP databases. This narrowed the spectrum to 645 mutations (54 genes) for analysis with clinical/phenotypic correlations. Mutations were isolated or grouped by pathway, e.g., PRC2, cohesin complex, plexins and dyneins, etc. In MDS, examples of prevalent mutations include SF3B1 (14%), DNMT3A (11%) and U2AF1/2 (9%). In MDS/MPN: TET2 (36%), SRSF2 (22%) and ASXL1 (19%) and SETBP1 (6%); in sAML: NRAS/RAS (16%), RUNX1 (16%) and cohesin mutations (12%), in contrast to pAML with mutational spectrum dominated by FLT3, DNMT3A, NMP1 or SMC3/1A (cohesin complex). The exome panel did not cover 20% patients, suggesting that their pathogenesis may be related to less recurrent events (613 candidates: 2nd screening phase). When mutational spectrum of sAML vs pAML were compared, mutants of SF3B1 (7 vs 1%, P=.04), BCOR (7 vs 1%, P=.04), CDH11/23 (13 vs. 1%, P=.003), FMN2 (7 vs. 1%, P=.04), PPFIA2 (7% vs 0%, P=.01), SPTAN1 (7% vs 0%, P=.01) and VPS8 (7 vs 0%, P=.017) were more frequent in sAML while DNMT3A and NPM1 were less common. Analysis of MDS/MPN revealed mutations in PRC2 (2 vs 11%, P=.05), SRSF2 (5 vs. 22%, P=.010) and TET2 (3 vs. 33%, P<.001) more frequent than in MDS. Mutations in SF3B1 were more recurrent in low/Int-1 IPSS categories compared to Int-2/high/sAML (21 vs. 3%, P=.01), in which mutations in N/KRAS (0 vs. 14%, P=.01) and TP53 (0 vs. 14%, P=.01) were more frequent. Functional group comparisons revealed that lesions in epigenetic (56 vs 23%, P=.001) and signal transduction genes (36 vs 9%, P=.001) were more prevalent in MDS/MPN compared to MDS in which they accumulated according to risk (high vs low: 36 vs 5%, P=.001 or 52% in pAML). Spliceosomal mutations were overrepresented in MDS/MPN vs MDS (58 vs 37%, P=.031), in sAML vs pAML (23 vs 9%, P=.032), and in low risk vs high risk cases (45 vs 22%, P=.02). Cytoskeleton organization gene mutations were overrepresented in sAML vs pAML (39 vs 13%, P=.001). TSG were more frequent in high-risk vs low-risk MDS (30 vs 5%, P=.003). Moreover, TET2 mutations coincided with SRSF2 and PRC2 mutations (P<.001 and P=.010); DNMT3 mutations with SF3B1 and BCOR (P=.04 and P=.004); SRSF2 with ASXL1 (P=.017); RUNX1 with cohesin and BCOR (P=.003 and P=.04), CBL mutations with PRPF8 and ASXL1 (P=.04 or P=.003); TP53 with PRPF8 (P=.04). After analyzing survival impact of individual mutations, functional groups, cytogenetic category and clinical parameters, we found TP53, ETV6, PRPF8, FMN2, UMODL1, KIT, GATA2, complex karyotype and chr. 5 anomalies had a prognostic impact on OS. However, in multivariate analyses, the first variable to stratify our cohort was, as expected, the diagnosis subtype (HR 2.2, P<.001), but also mutations in PRPF8 (HR 5.4, P=.004). In MDS and grouped MDS/MPN, significant variables included KIT (HR 12, P=.022) and TP53 mutations (HR 3.6, P=.045). Apart from traditional analyses, we also applied a recursive partitioning algorithm to construct an unbiased survival tree encompassing every mutation: e.g., PRPF8, CSMD1, U2AF2, IDH2, PPFIA2, SF3B1 and NRAS showed the highest difference in OS with this method. In sum, mutational spectrum of myeloid neoplasms can be assessed with WES. The pattern of frequency and concurrence in each diagnostic subtype differs substantially, a feature that can be exploited diagnostically. Despite heterogeneity, mutations and their combinations can be found to categorize patients and serve as prognostic markers. Analysis of additional cases is ongoing and will be presented at the meeting. Disclosures: Makishima: Scott Hamilton CARES Initiative: Research Funding. Maciejewski:NIH: Research Funding; Aplastic Anemia&MDS International Foundation: Research Funding.

Pulmonary hypertension on heart failure (HF) limits exercise capacity and survival probably because of associated right ventricular (RV) failure. This study investigated the mechanisms of RV function adaptation to early pulmonary hypertension in experimental HF. Seven weeks of rapid ventricular pacing in six dogs induced a HF characterized by cardiomegaly and decreased left ventricular ejection fraction. Compared with eight control dogs, pulmonary hypertension was borderline, with a mean pulmonary artery pressure increased to only 23 ± 2 (means ± SE) mmHg. However, the pulmonary vascular impedance spectrum was globally shifted to higher pressures, with an increase in 0 Hz impedance (resistance) to 662 ± 69 vs. 455 ± 41 dynes·cm−5·m2 in controls ( P < 0.01) and in characteristic impedance to 183 ± 20 vs. 104 ± 7 dynes·cm−5·m2 in controls ( P < 0.01). There was no change in RV end-systolic elastance (Ees), but arterial elastance (Ea) was increased to 1.8 ± 0.3 vs. 0.9 ± 0.1 mmHg/ml in controls so that RV-arterial coupling defined by the Ees-to-Ea ratio (Ees/Ea) was decreased to 0.8 ± 0.1 vs. 1.5 ± 0.1 in controls ( P < 0.01). Inhaled nitric oxide, 40 ppm or 5 μg·kg−1·min−1 nitroprusside iv, did not affect Ees/Ea. Fifty milligrams (iv) of milrinone increased Ees/Ea to 1.6 ± 0.2 by an isolated increase in Ees. We conclude that overpacing-induced HF is accompanied by a borderline pulmonary hypertension but profound RV-arterial uncoupling explained by the failure of RV systolic function to adapt combined effects of increased pulmonary arterial resistance and elastance.

The purpose of this examination was to explore the effects of stride length (SL) perturbations on walking gait, relative to preferred walking (PW) and running (PR), via lower extremity range of motion (ROM) variability. ROM variability at the hip, knee, and ankle joints, in the sagittal and frontal planes were used in evaluating motor control of gait, where increased gait variability has been previously implicated in fall susceptibly. Nine participants (5 male, 4 female; mean age 23.11±3.55 years, height 1.72±0.18m, mass 72.66±14.37kg) free from previous lower extremity injury were examined. Kinematic data were acquired using a 12-camera system (Vicon MX T40-S; 200Hz). Data filtering and interpolation included a low pass, 4th order, Butterworth filter (15Hz cutoff) and cubic spline. Five gait trials were completed for PW and PR, with subsequent SL manipulations computed as a percentage of leg length (LL). SL perturbations included 60%, 80%, 100%, 120%, and 140% of LL. Kinematic analysis involved one stride (two steps) during each gait trial, assessing ROM at the hip, knee, and ankle from heel contact to toe-off for each limb, in the sagittal and frontal planes. Variability was expressed using coefficient of variation (%). Comparisons were made using 3×7 (joint × stride condition) mixed model ANOVAs, with repeated measures on stride condition (α = 0.05), using SPSS 20.0. Differences in lower extremity ROM variability were detected among stride conditions in the frontal and sagittal planes (F[3.185,76.451] = 3.004, p = .033; F[4.595,110.279] = 2.834, p = .022, respectively). Greater ROM variability was observed at, and in excess of SLs of 100%LL relative to PW in the frontal plane (PW: 9.2±4.2%; 100%LL: 11.8±3.6%, p = .014; 120%LL: 13.5±5.8%, p = .046; 140%LL: 13.8±6.5%, p = .016), and between SLs of 80%LL and 120%LL in the sagittal plane (4.9±3.0%; 7.8±4.7%, p = .046, respectively). From this, PW appeared to occur within SLs of 60%LL to 80%LL, while SLs exceeding 100%LL resulted in increased lower extremity ROM variability. This may have consequences for fall susceptibility at increased stride lengths during walking. PR did not reveal significant variability differences (p>.05) compared to walking conditions in either the sagittal or frontal plane (7.5±5.0%; 12.8±7.7%, respectively), suggesting that running represents a separate, but stable gait pattern. In the sagittal plane, ROM variability was significantly lower at the hip (3.9±1.5%), relative to the ankle (8.4±1.6%, p<.001) and knee joints (7.4±2.6%, p = .001), suggesting that gait control may be more active at the ankle and knee joints. Future investigations should examine kinetic changes in gait when altering stride length.