Multiple myeloma presenting with high-output heart failure and improving with anti-angiogenesis therapy: two case reports and a review of the literature

<p>Abstract</p> <p>Introduction</p> <p>Common manifestations of multiple myeloma include osteolytic lesions, cytopenias, hypercalcemia, and renal insufficiency. Patients may also exhibit heart failure which is often associated with either past therapy or cardiac amyloidosis. A less recognized mechanism is high-output heart failure. Diuretic therapy in this setting has little efficacy in treating the congested state. Furthermore, effective pharmacotherapy has not been established. We report two patients with multiple myeloma and high-output heart failure who failed diuretic therapy. The patients were given dexamethasone in conjunction with lenalidomide and thalidomide, respectively. Shortly thereafter, each patient demonstrated a significant improvement in symptoms. This is the first report of successful treatment of multiple myeloma-induced high-output failure via the utilization of these agents.</p> <p>Case presentation</p> <p>Two patients with multiple myeloma were evaluated for volume overload. The first was a 50-year-old man with refractory disease. Magnetic resonance imaging demonstrated diffuse marrow replacement throughout the pelvis. Cardiac catheterization conveyed elevated filling pressures and a cardiac output of 15 liters/minute. He quickly decompensated and required mechanical ventilation. The second patient was a 61-year-old man recently diagnosed with multiple myeloma and volume overload. Skeletal survey demonstrated numerous lytic lesions throughout the pelvis. His cardiac catheterization also conveyed elevated filling pressures and a cardiac output of 10 liters/minute. Neither patient responded to diuretic therapy and they were subsequently started on dexamethasone plus lenalidomide and thalidomide, respectively. The first patient's brisk diuresis allowed for extubation within 48 hours after the first dose. He had a net negative fluid balance of 15 liters over 10 days. The second patient also quickly diuresed and on repeat cardiac catheterization, his cardiac output had normalized to 4.7 liters/minute.</p> <p>Conclusion</p> <p>Multiple myeloma can cause high-output failure. The mechanism is likely extensive bony involvement causing innumerable intramedullary arteriovenous fistulas. Diuretic therapy is not effective in treating this condition. Lenalidomide and thalidomide, both of which inhibit angiogenesis, seem to be viable treatment options. Based on the rapid and effective results seen in these two patients, a potential novel mechanism of 'pharmacologic fistula ligation' with these agents may be the most effective way to treat this presentation.</p

High spatial resolution myocardial perfusion cardiac magnetic resonance for the detection of coronary artery disease

To evaluate the feasibility and diagnostic performance of high spatial resolution myocardial perfusion cardiac magnetic resonance (perfusion-CMR). Methods and results Fifty-four patients underwent adenosine stress perfusion-CMR. An in-plane spatial resolution of 1.4 x 1.4 mm(2) was achieved by using 5x k-space and time sensitivity encoding (k-t SENSE). Perfusion was visually graded for 16 left ventricular and two right ventricular (RV) segments on a scale from 0 = normal to 3 = abnormal, yielding a perfusion score of 0-54. Diagnostic accuracy of the perfusion score to detect coronary artery stenosis of >50% on quantitative coronary angiography was determined. Sources and extent of image artefacts were documented. Two studies (4%) were non-diagnostic because of k-t SENSE-related and breathing artefacts. Endocardial dark rim artefacts if present were small (average width 1.6 mm). Analysis by receiver-operating characteristics yielded an area under the curve for detection of coronary stenosis of 0.85 [95% confidence interval (CI) 0.75-0.95] for all patients and 0.82 (95% CI 0.65-0.94) and 0.87 (95% CI 0.75-0.99) for patients with single and multi-vessel disease, respectively. Seventy-four of 102 (72%) RV segments could be analysed. Conclusion High spatial resolution perfusion-CMR is feasible in a clinical population, yields high accuracy to detect single and multi-vessel coronary artery disease, minimizes artefacts and may permit the assessment of RV perfusion

Vitamin D supplementation and breast cancer prevention : a systematic review and meta-analysis of randomized clinical trials

In recent years, the scientific evidence linking vitamin D status or supplementation to breast cancer has grown notably. To investigate the role of vitamin D supplementation on breast cancer incidence, we conducted a systematic review and meta-analysis of randomized controlled trials comparing vitamin D with placebo or no treatment. We used OVID to search MEDLINE (R), EMBASE and CENTRAL until April 2012. We screened the reference lists of included studies and used the “Related Article” feature in PubMed to identify additional articles. No language restrictions were applied. Two reviewers independently extracted data on methodological quality, participants, intervention, comparison and outcomes. Risk Ratios and 95% Confident Intervals for breast cancer were pooled using a random-effects model. Heterogeneity was assessed using the I2 test. In sensitivity analysis, we assessed the impact of vitamin D dosage and mode of administration on treatment effects. Only two randomized controlled trials fulfilled the pre-set inclusion criteria. The pooled analysis included 5372 postmenopausal women. Overall, Risk Ratios and 95% Confident Intervals were 1.11 and 0.74–1.68. We found no evidence of heterogeneity. Neither vitamin D dosage nor mode of administration significantly affected breast cancer risk. However, treatment efficacy was somewhat greater when vitamin D was administered at the highest dosage and in combination with calcium (Risk Ratio 0.58, 95% Confident Interval 0.23–1.47 and Risk Ratio 0.93, 95% Confident Interval 0.54–1.60, respectively). In conclusions, vitamin D use seems not to be associated with a reduced risk of breast cancer development in postmenopausal women. However, the available evidence is still limited and inadequate to draw firm conclusions. Study protocol code: FARM8L2B5L

Vitamin D and Bone Health; Potential Mechanisms

Osteoporosis is associated with increased morbidity, mortality and significant economic and health costs. Vitamin D is a secosteriod hormone essential for calcium absorption and bone mineralization which is positively associated with bone mineral density [BMD]. It is well-established that prolonged and severe vitamin D deficiency leads to rickets in children and osteomalacia in adults. Sub-optimal vitamin D status has been reported in many populations but it is a particular concern in older people; thus there is clearly a need for effective strategies to optimise bone health. A number of recent studies have suggested that the role of vitamin D in preventing fractures may be via its mediating effects on muscle function (a defect in muscle function is one of the classical signs of rickets) and inflammation. Studies have demonstrated that vitamin D supplementation can improve muscle strength which in turn contributes to a decrease in incidence of falls, one of the largest contributors to fracture incidence. Osteoporosis is often considered to be an inflammatory condition and pro-inflammatory cytokines have been associated with increased bone metabolism. The immunoregulatory mechanisms of vitamin D may thus modulate the effect of these cytokines on bone health and subsequent fracture risk. Vitamin D, therefore, may influence fracture risk via a number of different mechanisms

An extended model for coexistence of superconductivity and paramagnetism in high-Tc superconductors

In the present work, the total magnetization in superconducting state is separated into critical state and paramagnetic components in terms of an H(x)-dependent magnetic flux density. Utilizing this model, we reproduce successfully M-H curves measured by Sandu et al. [Phys. Rev. B 74 (2006) 184511] and Sandu et al. [J. Supercond. Incorp. Novel Magn. 17 (2004) 701] for different forms of Jc. © 2008 Chinese Physical Society

Role of coexistence of superconductivity and paramagnetism in magnetostriction of high-T c superconductors

Total magnetostriction in the superconducting state for high-T c superconductors has been separated into critical state and paramagnetic components in terms of a H (x) dependent magnetic flux density. We show that the paramagnetic part is X (2+X) ?H (x) 2?, where X is paramagnetic susceptibility. We have reproduced successfully ?L/L - H a curves measured by de la Fuente et al. (Phys. C 244:214, 1995), in which they clearly observed coexistence of superconductivity and paramagnetism, employing the concepts presented in this work. © Springer Science+Business Media, LLC 2008

AC losses in coil wound from round wire coated by a superconducting layer

Numerical simulations have been performed in order to predict the behavior of a round wire covered by thin superconducting layer when exposed to AC magnetic field or transporting AC current, as well as for a solenoid coil made from such wire. It was found that the AC loss of a single coated round wire is in good agreement with the predictions based on the existing analytical results for a hollow superconducting cylinder. AC loss in the coil shows two regimes. At low currents it is lower than in the case of the coil made from a full round wire with the same critical current and outer radius. In the range of currents comparable to the critical current the loss superseded the values expected for the reference coil from full wire. These results indicate, that the use of coated round wires instead of full ones does not offer a significant advantage from the point of view of AC loss in a coil winding. © 2011 IEEE.Vedecká Grantová Agentúra MŠVVaŠ SR a SAV: 2/0172/09 European Commission: FU07-CT-2007-00051Manuscript received September 08, 2011; accepted October 24, 2011. Date of publication November 03, 2011; date of current version May 24, 2012. This work was supported in part by the European Commission under the EURATOM contract FU07-CT-2007-00051 and the VEGA agency Grant 2/0172/09 as well as the TUBITAK Grant supporting the stay of Fedai Inanir in Bratislava. F. Gömöry is with the Institute of Electrical Engineering, Slovak Academy of Sciences, 84104 Bratislava, Slovakia (e-mail: [email protected]). F. Inanir is with the Department of Physics, Rize University, 53100, Rize, Turkey. Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TASC.2011.2174579 Fig. 1. Two kinds of superconducting wires used in the calculations. Interior part of CRW is considered as non-conducting and non-magnetic material

Effect of Transport Current on the Pinning Induced Magnetostriction of Type-II Superconductors

We investigated theoretically the influence of the transport current and applied magnetic field on the magnetostriction of type-II superconductors. In order to study the magnetostrictive response of a superconducting slab specimen, three cases of magnetic history of the sample are considered in the present work: (1) the transport current applied after zero-field-cooling, (2) the current and field are applied simultaneously, (3) the current is applied at the remenent critical state. In the proposed model, the exponential critical state model and the Bean model is employed to compute the flux profile within the slab subjected to sufficiently small transport current and applied magnetic field. Simple expressions for the internal stress and the magnetostriction in terms of this magnetic profile are derived. The magnetostriction curves versus the transport current and applied field are presented

Modeling of normal-state like contribution on the pinning induced magnetostriction

To describe the change of the sign of the magnetostriction at the field close to the upper critical field, Bc2, which were observed in some magnetostriction measurements carried out on the type-II superconductors, theoretical magnetostriction curves for the superconducting state were obtained considering the normal-state like contribution. The calculations were performed employing Bean, Kim, Linear, and the exponential critical state models. We have reproduced the magnetostriction curves measured by Nabialek et al. [A. Nabialek, B. Kundys, Yu Bukhantsev, A. Wisniewski, S.M. Kazakov, J. Karpinski, H. Szymczak, Supercond. Sci. Technol. 16 (2003) 707] on MgB2 superconductors and Ikuta et al. [H. Ikuta, Y. Nakayama, N. Hirota, K. Kishio, K. Kitazawa, Appl. Supercond. 1 (1993) 635] on (La1-xSrx)2CuO4 superconductors, in which was observed such sign alternation, employing the exponential model. It is evaluated that inhomogeneity of the magnetic induction across the sample volume owing to the existence of critical current causes the normal-state like contribution to the flux-pinning induced magnetostriction. © 2007 Elsevier B.V. All rights reserved