Parental longevity and survival among patients with multiple myeloma and monoclonal gammopathy of undetermined significance: a population-based study

Parental longevity is associated with an increased life expectancy; results with regard to specific diseases are conflicting. There are limited data focusing on host characteristics and their effect on survival among multiple myeloma (MM) patients and individuals with monoclonal gammopathy of undetermined significance (MGUS). Therefore, our aim was to evaluate the impact of parental longevity on survival of patients with MM and MGUS. A total of 4675 patients with MM, 6812 MGUS patients and 13 398 population-based controls for MM as well as 19 110 controls for MGUS, from 1988 to 2013, were included in the study. Longevity was defined as >90 years of age. Among MM patients, parental longevity was associated with a decreased risk of death [hazard ratio (HR) = 0·92, 95% confidence interval (CI) 0·84–0·99] and the same was true for MGUS patients (HR = 0·87, 95% CI 0·78–0·96). Having one long lived parent significantly decreased the risk of death in both groups, but was not statistically significant when both parents exceeded 90 years of age. In conclusion, parental longevity decreases the risk of death for patients with MM and MGUS which may reflect the importance of the host's genetic and environmental factors in relation to survival.     

Prestroke Mobility and Dementia as Predictors of Stroke Outcomes in Patients Over 65 Years of Age: A Cohort Study From The Swedish Dementia and Stroke Registries

Objectives

To explore the association between prestroke mobility dependency and dementia on functioning and mortality outcomes after stroke in patients>65 years of age.

Perioperative blood transfusion does not decrease survival after surgical treatment of spinal metastases

Purpose

To assess whether perioperative allogenic blood transfusions in patients undergoing surgical treatment for spinal metastases independently influence patient survival.

Methods

A retrospective study including 170 consecutive patients undergoing surgical treatment for spinal metastases in 2009 and 2010 at a tertiary referral center. Variables related to postoperative survival were all included in the same multivariable logistic regression analysis with either 3- or 12-month survival as the dependent variable. The independent variables were: transfusion of allogenic red blood cells, age at surgery, gender, preoperative hemoglobin, revised Tokuhashi score and no. of instrumented levels.

Results

Perioperative allogenic blood transfusion of 1–2 units was associated with increased 12-month survival [p = 0.049, odds ratio 2.619 (confidence interval 1.004–6.831)], but not with 3-month survival. Larger transfusion volumes did not significantly influence survival.

Conclusion

The results of the present study support that perioperative blood transfusion of <5 units does not decrease survival in patients operated for spinal metastases. Transfusion of 1–2 units seems to be associated with increased 12-month survival. Future studies should assess if a liberal transfusion regime can be applied to this group of patients; thereby, prioritizing early postoperative mobilization.     

Painful neuropathies: the emerging role of sodium channelopathies

Pain is a frequent debilitating feature reported in peripheral neuropathies with involvement of small nerve (Aδ and C) fibers. Voltage‐gated sodium channels are responsible for the generation and conduction of action potentials in the peripheral nociceptive neuronal pathway where Na_V1.7, Na_V1.8, and Na_V1.9 sodium channels (encoded by SCN9A, SCN10A, and SCN11A) are preferentially expressed. The human genetic pain conditions inherited erythromelalgia and paroxysmal extreme pain disorder were the first to be linked to gain‐of‐function SCN9A mutations. Recent studies have expanded this spectrum with gain‐of‐function SCN9A mutations in patients with small fiber neuropathy and in a new syndrome of pain, dysautonomia, and small hands and small feet (acromesomelia). In addition, painful neuropathies have been recently linked to SCN10A mutations. Patch‐clamp studies have shown that the effect of SCN9A mutations is dependent upon the cell‐type background. The functional effects of a mutation in dorsal root ganglion (DRG) neurons and sympathetic neuron cells may differ per mutation, reflecting the pattern of expression of autonomic symptoms in patients with painful neuropathies who carry the mutation in question. Peripheral neuropathies may not always be length‐dependent, as demonstrated in patients with initial facial and scalp pain symptoms with SCN9A mutations showing hyperexcitability in both trigeminal ganglion and DRG neurons. There is some evidence suggesting that gain‐of‐function SCN9A mutations can lead to degeneration of peripheral axons. This review will focus on the emerging role of sodium channelopathies in painful peripheral neuropathies, which could serve as a basis for novel therapeutic strategies.     

Mitral annulus motion compared with wall motion scoring index in the assessment of left ventricular ejection fraction.

The biplane disc summation method is the recommended echocardiographic procedure to determine left ventricular (LV) ejection fraction (EF). Assessment of mitral annulus motion (MAM) or wall motion scoring index (WMI) has been reported to be less dependent on image quality compared with the recommended method, and proposed as a surrogate to the disc summation method in calculation of LVEF. We aimed to compare MAM and WMI in the echocardiographic assessment of LVEF. In a randomly selected population-based sample of 75-year-old men and women in sinus rhythm (n = 409) MAM, as measured by M-mode, was compared with WMI, calculated as the mean value of wall motion scoring in 9 LV segments. LVEF, as measured by the biplane disc summation method was used as reference. The limits of agreement (mean difference +/- 1.96 SD) between LVEF and corresponding MAM values were -18 to +13 LVEF%, and between LVEF and corresponding WMI values were -12 to +13 LVEF%. The areas under the receiver operating characteristic curves for MAM and WMI to predict a LVEF < 50% were 0.892 and 0.998, respectively (95% confidence interval of the difference 0.062-0.149). The corresponding areas for MAM and WMI to predict a LVEF < 40% were 0.955 and 0.998, respectively (95% confidence interval of the difference 0.017-0.069). In conclusion, the ability of WMI to estimate LVEF was more favorable than MAM in this population-based sample of 75-year-old participants. The findings suggest that the WMI is preferable to MAM in estimating LVEF.     

Follow‐up nerve conduction studies in CIDP after treatment with IGIV‐C: Comparison of patients with and without subsequent relapse

Introduction: Electrodiagnostic studies (EDX) are not performed routinely before treatment suspension in CIDP, and no data exist regarding their value in predicting clinical relapse. Methods: Serial EDX (baseline and after IGIV‐C therapy) were analyzed from subjects in the ICE clinical trial who responded to IGIV‐C treatment and were subsequently re‐randomized to placebo in an extension phase. Comparisons were made between subjects who relapsed and those who did not. Results: A total of 55% (6/11) of the Relapse group had an increase in total number of demyelinating findings (DF) versus 8% (1/13) in the No Relapse group (P = 0.023). In the Relapse group, 100% had ≥1 new DF and 73% (8/11) had ≥4 new DF versus 60% (8/13) and 8% (1/13), respectively, in the No Relapse group. Conclusions: An increased total number of DF or the occurrence of ≥4 new DF may indicate a higher risk of clinical relapse after treatment cessation in IGIV‐C‐responsive patients. Muscle Nerve 52: 498–502, 2015     

Neuropathy‐associated NaV1.7 variant I228M impairs integrity of dorsal root ganglion neuron axons

Small‐fiber neuropathy (SFN) is characterized by injury to small‐diameter peripheral nerve axons and intraepidermal nerve fibers (IENF). Although mechanisms underlying loss of IENF in SFN are poorly understood, available data suggest that it results from axonal degeneration and reduced regenerative capacity. Gain‐of‐function variants in sodium channel Na_V1.7 that increase firing frequency and spontaneous firing of dorsal root ganglion (DRG) neurons have recently been identified in ～30% of patients with idiopathic SFN. In the present study, to determine whether these channel variants can impair axonal integrity, we developed an in vitro assay of DRG neurite length, and examined the effect of 3 SFN‐associated variant Na_V1.7 channels, I228M, M932L/V991L (ML/VL), and I720K, on DRG neurites in vitro. At 3 days after culturing, DRG neurons transfected with I228M channels exhibited ～20% reduced neurite length compared to wild‐type channels; DRG neurons transfected with ML/VL and I720K variants displayed a trend toward reduced neurite length. I228M‐induced reduction in neurite length was ameliorated by the use‐dependent sodium channel blocker carbamazepine and by a blocker of reverse Na‐Ca exchange. These in vitro observations provide evidence supporting a contribution of the I228M variant Na_V1.7 channel to impaired regeneration and/or degeneration of sensory axons in idiopathic SFN, and suggest that enhanced sodium channel activity and reverse Na‐Ca exchange can contribute to a decrease in length of peripheral sensory axons. Ann Neurol 2012