Current role of radiation therapy for multiple myeloma

BACKGROUND: Radiation therapy (RT) is a treatment modality traditionally used in patients with multiple myeloma (MM), but little is known regarding the role and effectiveness of RT in the era of novel agents, i.e., immunomodulatory drugs and proteasome inhibitors. METHODS: We retrospectively reviewed data from 449 consecutive MM patients seen at our institute in 2010-2012 to assess indications for RT as well as its effectiveness. Pain response was scored similarly to RTOG 0631 and used the Numerical Rating Pain Scale. RESULTS: Among 442 evaluable patients, 149 (34%) patients and 262 sites received RT. The most common indication for RT was palliation of bone pain (n = 109, 42%), followed by prevention/treatment of pathological fractures (n = 73, 28%), spinal cord compression (n = 26, 10%), and involvement of vital organs/extramedullary disease (n = 25, 10%). Of the 55 patients evaluable for pain relief, complete and partial responses were obtained in 76.4 and 7.2%, respectively. Prior RT did not significantly decrease the median number of peripheral blood stem cells collected for autologous transplant, even when prior RT was given to both the spine and pelvis. Inadequacy of stem cell collection for autologous stem cell transplant (ASCT) was not significantly different and it occurred in 9 and 15% of patients receiving no RT and spine/pelvic RT, respectively. None of the three cases of therapy-induced acute myelogenous leukemia/MDS occurred in the RT group. CONCLUSION: Despite the introduction of novel effective agents in the treatment of MM, RT remains a major therapeutic component for the management in 34% of patients, and it effectively provides pain relief while not interfering with successful peripheral blood stem cell collection for ASCT

Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC). A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes

Low-Load High Volume Resistance Exercise Stimulates Muscle Protein Synthesis More Than High-Load Low Volume Resistance Exercise in Young Men

BACKGROUND: We aimed to determine the effect of resistance exercise intensity (%1 repetition maximum-1RM) and volume on muscle protein synthesis, anabolic signaling, and myogenic gene expression. METHODOLOGY/PRINCIPAL FINDINGS: Fifteen men (21+/-1 years; BMI=24.1+/-0.8 kg/m2) performed 4 sets of unilateral leg extension exercise at different exercise loads and/or volumes: 90% of repetition maximum (1RM) until volitional failure (90FAIL), 30% 1RM work-matched to 90%FAIL (30WM), or 30% 1RM performed until volitional failure (30FAIL). Infusion of [ring-13C6] phenylalanine with biopsies was used to measure rates of mixed (MIX), myofibrillar (MYO), and sarcoplasmic (SARC) protein synthesis at rest, and 4 h and 24 h after exercise. Exercise at 30WM induced a significant increase above rest in MIX (121%) and MYO (87%) protein synthesis at 4 h post-exercise and but at 24 h in the MIX only. The increase in the rate of protein synthesis in MIX and MYO at 4 h post-exercise with 90FAIL and 30FAIL was greater than 30WM, with no difference between these conditions; however, MYO remained elevated (199%) above rest at 24 h only in 30FAIL. There was a significant increase in AktSer473 at 24h in all conditions (P=0.023) and mTORSer2448 phosphorylation at 4 h post-exercise (P=0.025). Phosporylation of Erk1/2Tyr202/204, p70S6KThr389, and 4E-BP1Thr37/46 increased significantly (P<0.05) only in the 30FAIL condition at 4 h post-exercise, whereas, 4E-BP1Thr37/46 phosphorylation was greater 24 h after exercise than at rest in both 90FAIL (237%) and 30FAIL (312%) conditions. Pax7 mRNA expression increased at 24 h post-exercise (P=0.02) regardless of condition. The mRNA expression of MyoD and myogenin were consistently elevated in the 30FAIL condition. CONCLUSIONS/SIGNIFICANCE: These results suggest that low-load high volume resistance exercise is more effective in inducing acute muscle anabolism than high-load low volume or work matched resistance exercise modes

Comparative analysis of platelet depleted plasma prepared on the Roche 8100 automation line and manually centrifuged platelet poor plasma for routine coagulation assays

Objectives: To evaluate whether the routine coagulation tests can be performed using platelet depleted plasma (PDP, residual platelet count <40000/μL) to achieve maximum efficiency of the automated workflow and compare results of these tests performed with platelet poor plasma (PPP residual platelet count <10,000/μL) prepared manually ‘offline’. Design and Methods: The PDP was obtained first following ‘on line’ centrifugation at 4150 RPM (3000g) for 7 min. The routine coagulation tests, Prothrombin Time (PT), Activated Partial Thromboplastin Clotting Time (aPTT), D-dimer (DD), Antithrombin III (AT3) and Fibrinogen (FBG) were performed. The PPP was obtained from an aliquot of PDP samples with additional ‘manual off line’ centrifugation at 7700 RPM (3314g) for 3 min (total 10 min, online + offline) and the same tests were performed. The statistical analysis was carried out using EP Evaluator v11 to compare results from both methods. Results: The results from both PPP and PDP samples demonstrated strong correlation. For example, PT (R = 0.9989; N = 55, and of Bias −0.12 (−0.67%), aPTT(R = 0.9957; N = 60, Bias 0.26 (0.58%)), AT3(R = 0.9800; N = 49, Bias −2.0 (−2.2%)), FBG (R = 0.9956; N = 57, Bias −1.9 (−0.5%)) and DD (R = 0.9981; N = 38, Bias 0.005 (0.373%)) with insignificant bias. Conclusions: The utilization of the Roche cobas® 8100 automated ‘online’ centrifugation helps achieve optimal workflow efficiency without impacting analytical performance of the PT, aPTT, DD, AT3 and FBG assays. The use of PDP can be superior method to PPP for routine coagulation tests

Role of Cytosolic Calcium-independent Plasmalogen-selective Phospholipase A2 in Hypoxic Injury to Rabbit Proximal Tubules

Although the activation of calcium-independent phospholipase A2 (PLA2) enzymes has been described in the heart, the pathogenetic role of this enzyme(s) in hypoxic cell injury has not been previously examined in any tissue. Therefore, we characterized the time course of activation of calcium-independent PLA2 using both plasmalogen and diacylglycerophospholipid substrates during hypoxia in rabbit proximal tubules and examined whether inhibition of calcium-independent PLA2 activity is associated with a cytoprotective effect. Subjecting rabbit proximal tubules to hypoxia for 5 min resulted in at least a threefold increase in cytosolic calcium-independent PLA2, which was selective for plasmalogen substrates (control 444±69 vs hypoxia 1,675±194 pmol * mg protein- &apos;-min-&apos;, n = 5). In contrast, no changes in PLA2 activity were observed i

Estimation of daily proteinuria in patients with amyloidosis by using the protein-to-creatinine ratio in random urine sample

Measurement of daily proteinuria in patients with amyloidosis is recommended at the time of diagnosis for assessing renal involvement, and for monitoring disease activity. Renal involvement is usually defined by proteinuria &gt;500 mg/day. We evaluated the accuracy of the random urine protein-to-creatinine ratio (Pr/Cr) in predicting 24 hour proteinuria in patient with amyloidosis. We com- pared results of random urine Pr/Cr ratio and concomitant 24-hour urine collections in 44 patients with amyloidosis. We found a strong correlation (Spearman’s ρ=0.874) between the Pr/Cr ratio and the 24 hour urine protein excretion. For predicting renal involvement, the optimal cut-off point of the Pr/Cr ratio was 715 mg/g. The sensitivity and specificity for this point were 91.8% and 95.5%, respectively, and the area under the curve value was 97.4%. We conclude that the random urine Pr/Cr ratio could be useful in the screening of renal involvement in patients with amyloidosis. If validated in a prospective study, the random urine Pr/Cr ratio could replace the 24 hour urine collection for the assessment of daily proteinuria and presence of nephrotic syndrome in patients with amyloidosis