Citations

Renal impairment is a common complication of multiple myeloma (MM). The estimated glomerular filtration rate (eGFR) using the Modification of Diet in Renal Disease formula is the recommended method for the assessment of renal function in patients with MM with stabilized serum creatinine. In acute renal injury, the RIFLE (risk, injury, failure, loss and end-stage kidney disease) and Acute Renal Injury Network criteria seem to be appropriate to define the severity of renal impairment. Novel criteria based on eGFR measurements are recommended for the definition of the reversibility of renal impairment. Rapid intervention to reverse renal dysfunction is critical for the management of these patients, especially for those with light chain cast nephropathy. Bortezomib with high-dose dexamethasone is considered as the treatment of choice for such patients. There is limited experience with thalidomide in patients with myeloma with renal impairment. Thus, thalidomide can be carefully administered, mainly in the context of well-designed clinical trials, to evaluate if it can improve the rapidity and probability of response that is produced by the combination with bortezomib and high-dose dexamethasone. Lenalidomide is effective in this setting and can reverse renal insufficiency in a significant subset of patients, when it is given at reduced doses, according to renal function. The role of plasma exchange in patients with suspected light chain cast nephropathy and renal impairment is controversial. High-dose melphalan (140 mg/m2) and autologous stem-cell transplantation should be limited to younger patients with chemosensitive disease.

PurposeTo determine whether increased duration of radiation therapy (RT) and overall treatment (RX) time has a detrimental effect in anal cancer.Patients and MethodsData from Radiation Therapy Oncology Group (RTOG) 87-04 and RTOG 98-11 trials were combined to form three treatment groups: RT/fluorouracil (FU)/mitomycin (n = 472), RT/FU/cisplatin (n = 320), and RT/FU (n = 145). Cox proportional hazards models were used with the following variables: RT duration, RT intensity, RX duration, treatment group, age, sex, Karnofsky performance score (KPS), T stage, N stage, and RT dose.ResultsIn the univariate analysis, there was a significant association between RX duration and colostomy failure (CF; hazard ratio [HR] = 1.51; 95% CI, 1.07 to 2.14; P = .02), local failure (HR = 1.52; 95% CI, 1.14 to 2.03; P = .005), locoregional failure (HR = 1.51; 95% CI, 1.15 to 1.98; P = .003), and time to failure (HR = 1.40; 95% CI, 1.10 to 1.79; P = .007). The significance of RX duration was maintained after adjusting for treatment group. In multivariate modeling there was a trend toward an association between RX duration and CF (HR = 1.57; 95% CI, 0.98 to 2.50; P = .06) and a statistically significant association with local failure (HR = 1.96; 95% CI, 1.34 to 2.87; P = .0006). Age, sex, KPS, T stage, N stage, and RT dose, but not RT duration, RT intensity, or RX duration, were found to be statistically significant predictors of OS and colostomy-free survival.ConclusionTotal treatment time, but not duration of radiation therapy, seems to have a detrimental effect on local failure and colostomy rate in anal cancer. Induction chemotherapy may contribute to local failure by increasing total treatment time.

Abstract Aims Heart failure (HF) patients breathe with a rapid shallow pattern during exercise. This study examined the relationship between cardiac size and tachypnoeic breathing in HF patients during exercise. Methods and results Thirty-seven HF patients [age = 55 ± 13 years, ejection fraction (EF) = 27 ± 10%, New York Heart Association (NYHA) class = 2.3 ± 1.2] and 42 controls (CTL) (age = 56 ± 14 years, EF = 63 ± 8%) were recruited. Participants underwent maximal exercise testing, pulmonary function testing, and chest radiography for calculation of total thoracic cavity volume (TTCV), diaphragm, heart, and lung volumes. Heart failure patients were divided into two groups: Group A = cardiac volume < median (n = 18) and Group B = cardiac volume ≥ median of the HF patients (n = 19). There was no difference between groups for TTCV (CTL = 8203 ± 1489 vs. Group A = 8694 ± 1249 vs. Group B = 8195 ± 1823 cm3). Cardiac volume was different between groups for both absolute (CTL = 630 ± 181 vs. Group A = 894 ± 186 vs. Group B = 1401 ± 382 cm3, P< 0.001 for all comparisons) and %TTCV (CTL = 8 ± 2 vs. Group A = 10 ± 1 vs. Group A = 18 ± 5%, P< 0.001 for all comparisons). Similarly, total lung volume as a %TTCV was significantly different among the groups (CTL = 70 ± 4 vs. Group A = 65 ± 5 vs. Group A = 58 ± 7%, P< 0.01 for all comparisons). In HF patients, there was a trend (P = 0.10) towards an independent association between cardiac size and tidal volume (VT) at 75% of VO2 peak whereas this relationship was statistically significant at VO2 peak (P = 0.02) as patients with larger cardiac size had reduced VT. Conclusion This study demonstrates the close relationship between cardiac size and breathing pattern during exercise in HF patients. These results suggest cardiac size may pose a significant constraint on the lungs during exercise and may contribute to tachypnoeic breathing.

Cdc20 is an activator of the anaphase-promoting complex/cyclosome that initiates anaphase onset by ordering the destruction of cyclin B1 and securin in metaphase. To study the physiological significance of Cdc20 in higher eukaryotes, we generated hypomorphic mice that express small amounts of this essential cell cycle regulator. In this study, we show that these mice are healthy and not prone to cancer despite substantial aneuploidy. Cdc20 hypomorphism causes chromatin bridging and chromosome misalignment, revealing a requirement for Cdc20 in efficient sister chromosome separation and chromosome–microtubule attachment. We find that cyclin B1 is newly synthesized during mitosis via cytoplasmic polyadenylation element–binding protein-dependent translation, causing its rapid accumulation between prometaphase and metaphase of Cdc20 hypomorphic cells. Anaphase onset is significantly delayed in Cdc20 hypomorphic cells but not when translation is inhibited during mitosis. These data reveal that Cdc20 is particularly rate limiting for cyclin B1 destruction because of regulated de novo synthesis of this cyclin after prometaphase onset.

SAGE-Journals-Accessible-Video-Player 10.1089/vid.2010.0114.M1 sj-vid-1-vid-10.1089_vid.2010.0114

Objective— To determine whether serum levels of N-terminal (NT) pro–B-type natriuretic peptide (pro-BNP) are higher in patients with poorly compressible arteries (PCA) than in patients with peripheral artery disease (PAD) and control subjects without PCA or PAD. Methods and Results— Medial arterial calcification in the lower extremities results in PCA and may be associated with increased arterial stiffness and hemodynamic/myocardial stress. PCA was defined as having an ankle-brachial index >1.4 or an ankle blood pressure >255 mm Hg, whereas PAD was defined as having an ankle-brachial index ≤0.9. Study participants with PCA (n=100; aged 71±10 years; 70% men) and age- and sex-matched patients with PAD (n=300) were recruited from the noninvasive vascular laboratory. Age- and sex-matched controls (n=300) were identified from a community-based cohort and had no history of PAD. NT pro-BNP levels were approximately 2.5-fold higher in patients with PCA than in patients with PAD and approximately 4-fold higher than in age- and sex-matched controls. In multivariable regression analyses that adjusted for age, sex, smoking, hypertension, history of coronary heart disease/stroke, systolic blood pressure, and serum creatinine, NT pro-BNP levels remained significantly higher in patients with PCA than in patients with PAD and controls ( P <0.001). Conclusion— Patients with medial arterial calcification and PCA have higher serum levels of NT pro-BNP than patients with PAD and controls, which is suggestive of an adverse hemodynamic milieu and increased risk for adverse cardiovascular outcomes.