Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma.

Fluorine-18 fluorodeoxyglucose positron emission tomography with computed tomography attenuation correction (PET-CT) in myeloma can detect and enumerate focal lesions by the quantitative characterization of metabolic activity. The aim of this study was to determine the prognostic significance of the suppression of PET-CT activity at a number of time points post therapy initiation: day 7, post induction, post transplant, and at maintenance therapy. As part of the TT4-6 trial series, 596 patients underwent baseline PET-CT and were evaluated serially during their disease course using peak standardized uptake values above background red marrow signal. We demonstrate that the presence of more than 3 focal lesions at presentation identifies a group of patients with an adverse progression-free survival and overall survival. At day 7 of therapy, patients with complete focal lesion signal suppression revert to the same prognosis as those with no lesions at diagnosis. At later time points, the continued suppression of signal remains prognostically important. We conclude that for newly diagnosed patients with focal lesions, treatment until these lesions are suppressed is an important therapeutic goal as the prognosis of these patients is the same as those without lesions at diagnosis. (clinicaltrials.gov identifiers: 00734877, 02128230, 00869232, 00871013).

Linoleic acid metabolites act to increase contractility in isolated rat heart.

Previous in vivo studies in dogs suggest that the 9,10-monoepoxide of linoleic acid (9,10-cis-epoxyoctadecenoic acid [9,10-EOA]) has toxic cardiovascular effects that result in death at higher doses. More recent work with rabbit renal proximal tubule cells suggests that the 12,13-metabolites of linoleic acid are more toxic than the 9,10-isomers. Thus, in the current study, we tested the hypothesis that 12,13-EOA and 12,13-dihydroxyoctadecadienoic acid (12,13-DHOA) have direct adverse effects on the heart. Langendorff-perfused rat hearts were exposed to 30 microM linoleic acid, 30 microM 12,13-EOA, or 30 microM 12,13-DHOA for 60 min followed by a 30-min recovery period. As indicated by peak left intraventricular pressure and/or +dP/dt(max), all three of the agents elicited moderate increases in contractile function that peaked within 10 20 min. The effects of linoleic acid and 12,13-EOA returned to control values during the remainder of the 60-min exposure, whereas the positive inotropic response to 12,13-DHOA was maintained until washout. Sustained arrhythmias and negative inotropic actions were not observed with any of the three compounds. Subsequently, the monoepoxides were infused into conscious rats (35 mg/kg/h) while blood pressure, heart rate, and EKG were monitored for 24 h using biotelemetry techniques. The only effect observed was a slight decline in blood pressure. Thus, current data suggest that linoleic acid and its oxidative metabolites do not have direct cardiotoxic effects during acute exposure.