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Myeloma patients failing to achieve a complete response post autologous stem cell transplantation are heterogeneous, some ultimately achieving deeper responses and prolonged remission, whilst others relapse rapidly with poor outcomes. We evaluated the prognostic impact of the plasma cell proliferative index (PCPI) post-therapy, in 382 patients with myeloma failing to achieve complete response at 100 days post-transplant. Sixty percent (n= 230) of patients had zero clonal or too few clonal plasma cells to accurately assess PCPI (No PCPI). The remaining 40% (n= 152) of patients had PCPI performed with 79% (n= 120) having a low PCPI and 21% (n= 32) having an elevated PCPI. Patients with an elevated PCPI had significantly shorter progression free and overall survival. The median PFS was 8 months for elevated PCPI vs. 19 months for low PCPI vs. 24 months for no PCPI (p< 0.0001). The median OS was 27 months for elevated PCPI vs. 79 months for low PCPI vs. not reached for no PCPI, p< 0.0001). On multivariable analysis post-therapy PCPI was an independent predictor of progression free and overall survival. The PCPI post-therapy is a powerful predictor of survival and risk stratifies myeloma patients failing to achieve complete response early in the disease course.

Background: Waldenström's macroglobulinaemia (WM) is an uncommon lymphoproliferative disorder. Although many options are available, an optimal first-line therapy for WM has not been defined. We postulated that combining bendamustine and rituximab (BR) with a next generation BTK inhibitor would result in deeper responses as measured by complete response (CR) and very good partial response (VGPR) rates, and provide a longer duration of response.

Introduction

Introduction

Introduction:

The plasma cell proliferative index (PCPI), determined by a slide technique or by flow cytometry, detects cells in the S phase of the cell cycle and is a useful prognostic tool in patients with plasma cell disorders such as multiple myeloma and amyloidosis. We conducted a retrospective review analyzing the prognostic effect of PCPI in 306 patients with smoldering multiple myeloma (SMM). Seventy-nine (26%) patients had an elevated PCPI (>0.5). An elevated PCPI predicted an inferior time to progression (median, 3.0 vs 7.1 years for those with a low PCPI; P= .0004). Within 24 months, the progression rate was significantly higher for patients with an elevated PCPI (49% vs. 20%; P< .0001). PCPI is a valuable tool in risk stratifying patients with SMM and identifies patients with earlier progression who may benefit from closer follow-up and consideration of early intervention trials.

We study oxidative coupling of methane (OCM) on alkaline earth metal oxides (AEMOs) doped with either a transition metal (TM) or an alkaline earth metal (AEM) different from that of the host oxide. We assess whether doping can lead to new materials that are better than the pure oxides or deviate from the limitations of the scaling relations. Density functional theory (DFT) calculations show that doped AEMO surfaces follow similar linear scaling relations as observed on pure AEMO; however, doped surfaces bind the adsorbates, hydrogen, and methyl more strongly. Both TM- and AEM-doped AEMOs show that methane activation mostly occurs through a surface-mediated pathway, where at the transition state the methane C–H bond is stretched, and the methyl interacts mostly with the dopant atom and the hydrogen with the lattice oxygen. The stronger hydrogen binding in the doped surfaces leads to a lower methane activation barrier; however, in some cases, the catalyst surface binds the hydrogen too strongly, poisoning the active site and making the catalyst inactive. The doped systems are largely constrained by the scaling relations, but sites closer to the optimum of the volcano plot exist, suggesting room for improvement.

We evaluated the impact of light chain type, lambda (?) or kappa (?), on disease features and outcomes in patients with immunoglobulin light chain (AL) amyloidosis receiving stem cell transplant at the Mayo Clinic between October 2002 and August 2016. Patients with ? AL amyloidosis had higher rates of renal and neurological involvement (? 69% vs ? 57%, P = .02 and ? 16% vs ? 9%, P = .03, respectively). Patients with ? AL amyloidosis had more hepatic involvement (? 7% vs ? 18%, P = .0003). Complete response rate was 43% for both groups and overall response rates were similar (? 85% vs ? 91%, P = .12). Patients with ? light chain amyloidosis had better progression-free and overall survival (PFS: ? 74 months vs ? 101 months, P = .0064 and OS: ? 121 months vs ? not reached, P = .003). Mayo stage 2004 was more predictive of survival in the ? cohort (median OS of 143 months stage I vs 77 months stage II vs 33 months stage III, P < .0001) than in the ? cohort (median OS not reached for stage I and II and 102 months for stage III, P = .044). Conditioning dose predicted survival in the ? cohort only (median OS 149 months for melphalan 200 mg/m2 vs 50 months for melphalan <200 mg/m2, P < .0001; median OS ? not reached for melphalan 200 mg/m2 or <200 mg/m2, P = .38). On multivariate analysis, light chain type remained an independent predictor of survival. Light chain type predicts organ involvement and survival in patients with AL amyloidosis receiving stem cell transplant.

Type iiiextracapillary glomerulonephritis (PEGN) is a common cause of rapidly progressive glomerulonephritis and it is usually associated with circulating anti-neutrophil cytoplasmic antibodies (ANCAs). Recent evidence points to complement activation as an important factor in the pathogenesis of PEGN.

La glomerulonefritis extracapilar (GNEC) pauciinmune o de tipo iiies una de las causas más comunes de glomerulonefritis rápidamente progresiva y suele estar asociada con la presencia de anticuerpos antineutrófilos citoplasmáticos (ANCA). Están reportándose evidencias sobre la importancia de la activación del complemento en la patogénesis de la GNEC.

Patients on haemodialysis (HD) have a high prevalence of 25-OH-vitamin D (25-OH-D)deficiency. Secondary hyperparathyroidismis a common condition in these patients, which is very important to control. 25-OH-D is involved in regulating calcium homeostasis. As such, appropriate levels of this vitamin could help to control bone mineral metabolism.

In this work, we investigate the role of alkaline metal oxides (AMO) (MgO, CaO, and SrO) in activating the C–H bond in methane. We use Density Functional Theory (DFT) and microkinetic modeling to study the catalytic elementary steps in breaking the C–H bond in methane and creating the methyl radical, a precursor prior to creating C2products. We study the effects of surface geometry on the catalytic activity of AMO by examining terrace and step sites. We observe that the process of activating methane depends strongly on the structure of the AMO. When the AMO surface is doped with an alkali metal, the transition state (TS) structure has a methyl radical-like behavior, where the methyl radical interacts weakly with the AMO surface. In this case, the TS energy scales with the hydrogen binding energy. On pure AMO, the TS interacts with AMO surface oxygen as well as the metal atom on the surface, and consequently the TS energy scales with the binding energy of hydrogen and methyl. We study the activity of AMO using a mean-field microkinetic model. The results indicate that terrace sites have similar catalytic activity, with the exception of MgO(100). Step sites bind hydrogen more strongly, making them more active, and this confirms previously reported experimental results. We map the catalytic activity of AMO using a volcano plot with two descriptors: the methyl and the hydrogen binding energies, with the latter being a more significant descriptor. The microkinetic model results suggest that C–H bond dissociation is not always the rate-limiting step. At weak hydrogen binding, the reaction is limited by C–H bond activation. At strong hydrogen binding, the reaction is limited due to poisoning of the active site. We found an increase in activity of AMO as the basicity increased. Finally, the developed microkinetic model allows screening for improved catalysts using simple calculations of the hydrogen binding energy.

Patients with Stage 5 chronic kidney disease who are on hemodialysis (HD) remain in a chronic inflammatory state, characterized by the accumulation of uremic toxins that induce endothelial damage and cardiovascular disease (CVD). Our aim was to examine microvesicles (MVs), monocyte subpopulations, and angiopoietins (Ang) to identify prognostic markers in HD patients with or without diabetes mellitus (DM). A total of 160 prevalent HD patients from 10 centers across Spain were obtained from the Biobank of the Nephrology Renal Network (Madrid, Spain): 80 patients with DM and 80 patients without DM who were matched for clinical and demographic criteria. MVs from plasma and several monocyte subpopulations (CD142+/CD16+, CD14+/CD162+) were analyzed by flow cytometry, and the plasma concentrations of Ang1 and Ang2 were quantified by ELISA. Data on CVD were gathered over the 5.5 yr after these samples were obtained. MV level, monocyte subpopulations (CD14+/CD162+and CD142+/CD16+), and Ang2-to-Ang1 ratios increased in HD patients with DM compared with non-DM patients. Moreover, MV level above the median (264 MVs/µl) was associated independently with greater mortality. MVs, monocyte subpopulations, and Ang2-to-Ang1 ratio can be used as predictors for CVD. In addition, MV level has a potential predictive value in the prevention of CVD in HD patients. These parameters undergo more extensive changes in patients with DM.

Achieving an adequate dialysis dose is one of the key goals for dialysis treatments. Here we assessed whether patients receiving the current cleared plasma volume (Kt), individualized for body surface area per recommendations, had improved survival and reduced hospitalizations at 2 years of follow-up. Additionally, we assessed whether patients receiving a greater dose gained more benefit. This prospective, observational, multicenter study included 6129 patients in 65 Fresenius Medical Care Spanish facilities. Patients were classified monthly into 1 of 10 risk groups based on the difference between achieved and target Kt. Patient groups with a more negative relationship were significantly older with a higher percentage of diabetes mellitus and catheter access. Treatment dialysis time, effective blood flow, and percentage of on-line hemodiafiltration were significantly higher in groups with a higher dose. The mortality risk profile showed a progressive increase when achieved minus target Kt became more negative but was significantly lower in the group with 1 to 3 L clearance above target Kt and in groups with greater increases above target Kt. Additionally, hospitalization risk appeared significantly reduced in groups receiving 9 L or more above the minimum target. Thus, prescribing an additional 3 L or more above the minimum Kt dose could potentially reduce mortality risk, and 9 L or more reduce hospitalization risk. As such, future prospective studies are required to confirm these dose effect findings.