Distal axon degeneration seen in many peripheral neuropathies is likely to share common molecular mechanisms with Wallerian degeneration. Although several studies in mouse models of peripheral neuropathy showed prevention of axon degeneration in the slow Wallerian degeneration (Wlds) mouse, the role of a recently identified player in Wallerian degeneration, Sarm1, has not been explored extensively. In this study we show that mice lacking the Sarm1 gene are resistant to distal axonal degeneration in a model of chemotherapy induced peripheral neuropathy caused by paclitaxel and a model of high fat diet induced putative metabolic neuropathy. This study extends the role of Sarm1 to axon degeneration seen in peripheral neuropathies and identifies it as a likely target for therapeutic development.

Studies comparing the efficacy and cost of stem cell mobilization with intermediate-dose CY (ID-CY) and G-CSF against plerixafor and G-CSF, specifically in multiple myeloma (MM) patients treated in the novel therapy era, are not available. Eighty-eight consecutive patients undergoing mobilization with ID-CY (3-4 g/m 2 ) and G-CSF (n ¼ 55) were compared with patients receiving plerixafor and G-CSF (n ¼ 33). Compared with plerixafor, ID-CY use was associated with higher median peak peripheral blood CD34 þ cell count (68 vs 160 cells/mL, Po0.001), and CD34 þ cell yield on day 1 of collection (6.9 Â 10 6 vs 11.7 Â 10 6 cells/kg, Po0.001). Total CD34 þ cell yield was significantly higher in the ID-CY patients (median collection 16.6 Â 10 6 vs 11.6 Â 10 6 cells/kg; Po0.001). ID-CY use was associated with significantly more frequent episodes of febrile neutropenia (16.3% vs 0%; P ¼ 0.02), intravenous antibiotic use (16.3% vs 3%; P ¼ 0.03) and hospitalizations (P ¼ 0.02). The average total cost of mobilization in the plerixafor group was significantly higher compared with the ID-CY group ($28 980 vs $22 504.8; P ¼ 0.001). Our data indicate robust stem cell mobilization in MM patients treated with novel agents, with G-CSF and either ID-CY or plerixafor. When compared with plerixafor, ID-CY-containing mobilization was associated with significantly lower average total mobilization costs.

Age is an adverse prognostic factor in patients with heart failure. We aimed to assess the impact of age and noncardiac co-morbidities in the outcome of patients undergoing cardiac resynchronization therapy (CRT), and determine which of these two factors is the most important predictor of survival. The study involved a single-center retrospective assessment of 697 consecutive CRT implants during a 12-year period. Patient co-morbidity profile was assessed using the Charlson Co-morbidity Index (CCI) and the Charlson Age-Co-morbidity Index (CACI). Predictors of survival free from heart transplantation were assessed. CRT-related complications and cause of death analysis were assessed within tertiles of the CACI. During a mean follow-up of 1,813 ± 1,177 days, 347 patients (49.9%) died and 37 (5.3%) underwent heart transplantation. On multivariate Cox regression, female gender (HR = 0.78, 95% confidence interval [CI] 0.62 to 0.99, p = 0.041), estimated glomerular filtration rate (HR per ml/min = 0.99, 95% CI 0.98 to 0.99, p < 0.001), left ventricular ejection fraction (HR per % = 0.99, 95% CI 0.98 to 1.00, p = 0.022), New York Heart Association class (HR = 1.83, 95% CI 1.53 to 2.20, p < 0.001), presence of left bundle branch block (HR = 0.70, 95% CI 0.56 to 0.87, p = 0.001), and CACI tertile (HR = 1.37, 95% CI 1.18 to 1.59, p < 0.001) were independent predictors of all-cause mortality or heart transplantation. Compared with age and the CCI, the CACI was the best discriminator of all-cause mortality. Inappropriate therapies occurred less frequently in higher co-morbidity tertiles. In conclusion, patient co-morbidity profile adjusted to age impacts on mortality after CRT implantation. Use of the CACI may help refine guideline criteria to identify patients more likely to benefit from CRT.

Background:The long-term effect of tricuspid regurgitation (TR) has on and long-term mortality.In the present study, we sought to examine whether patients undergoing an implantable cardiac device procedure (pacemaker-PPM, implantable cardiac defibrillator-ICD or cardiac resynchronisation therapy pacemaker/defibrillator-CRT-D/P) have an increased risk of TR and to determine the effect of this on long-term survival.Methods: A total of 326 patients who underwent device implant and had pre-and post-implant transthoracic echocardiogram were included in the analysis. New heart failure (HF) onset and allcause mortality were the study endpoints over a follow-up period of median 11.8 years.Results: Pre-implant, none/trivial, moderate and severe TR were present in 304 (93.3%), 12 (3.7%) and 10 (3.1%) patients, respectively. TR grade increased post implant in 150 (46%) patients. There was a significant increase in the proportion of patients with RV dysfunction after implantation (89 (27.3%)) compared to pre-implantation (44 (13.5%)), p<0.0001. Moderate or greater TR was an independent predictor of new HF onset [OR:4.50 (95%CI: 2.06-9.81), p=0.0002]. Independent predictors of mortality were post-pacemaker ≥moderate TR [HR: 4.18

Almost a third of patients fulfilling current guidelines criteria have suboptimal responses following cardiac resynchronization therapy (CRT). Circulating biomarkers may help identify these patients. We aimed to assess the predictive role of full blood count (FBC) parameters in prognosis of heart failure (HF) patients undergoing CRT device implantation. We enrolled 612 consecutive CRT patients and FBC was measured within 24 hours prior to implantation. The follow-up period was a median of 1652 days (IQR: 837–2612). The study endpoints were i) composite of all-cause mortality or transplant, and ii) reverse left ventricular (LV) remodeling. On multivariate analysis [hazard ratio (HR), 95% confidence interval (CI)] only red cell count (RCC) (p = 0.004), red cell distribution width (RDW) (p < 0.001), percentage of lymphocytes (p = 0.03) and platelet count (p < 0.001) predicted all-cause mortality. Interestingly, RDW (p = 0.004) and platelet count (p = 0.008) were independent predictors of reverse LV remodeling. This is the first powered single-centre study to demonstrate that RDW and platelet count are independent predictors of long-term all-cause mortality and/or heart transplant in CRT patients. Further studies, on the role of these parameters in enhancing patient selection for CRT implantation should be conducted to confirm our findings.