Citations

Lenalidomide is approved for red blood cell (RBC) transfusion-dependent anemia due to low or intermediate-1 (int-1) risk myelodysplastic syndromes (MDSs) associated with a chromosome 5q deletion with or without additional cytogenetic abnormalities. We report results of a multicenter, phase 2 trial evaluating lenalidomide therapy for transfusion-dependent patients with low- or int-1–risk MDS without deletion 5q. Eligible patients had 50 000/mm3 or more platelets and required 2 U or more RBCs within the previous 8 weeks; 214 patients received 10 mg oral lenalidomide daily or 10 mg on days 1 to 21 of a 28-day cycle. The most common grade 3/4 adverse events were neutropenia (30%) and thrombocytopenia (25%). Using an intention-to-treat analysis, 56 (26%) patients achieved transfusion independence (TI) after a median of 4.8 weeks of treatment with a median duration of TI of 41.0 weeks. In patients who achieved TI, the median rise in hemoglobin was 32 g/L (3.2 g/dL; range, 10-98 g/L [1.0-9.8 g/dL]) from baseline. A 50% or greater reduction in transfusion requirement occurred in 37 additional patients, yielding a 43% overall rate of hematologic improvement (TI response +‖≥ 50% reduction in transfusion requirement). Lenalidomide has clinically meaningful activity in transfusion-dependent patients with low- or int-1–risk MDS who lack the deletion 5q karyotypic abnormality. This study is registered at www.clinicaltrials.gov as no. NCT00064974.

Abstract Using ABQ diagnosis, the sensitivity to detect VF of densitometric versus radiographic assessment in 755 postmenopausal women was 71-81% and specificity was 97%. Misdiagnosis was influenced by image quality and was more common for mild deformities. Introduction: Using densitometric vertebral fracture assessment (VFA), prevalent fractures are identified when vertebral height appears reduced by ≥20%. However, this approach does not discriminate between osteoporotic vertebral fracture (VF) and nonosteoporotic deformity, which increases the false-positive rate. Algorithm-based qualitative diagnosis (ABQ) focuses on vertebral endplate fracture to exclude these deformities but has not been applied in VFA. We wished to determine whether densitometric image quality is adequate for ABQ assessment. Our aims were to (1) calculate agreement between VFA and radiography using ABQ to identify prevalent VF and (2) identify the primary reasons for any discordant diagnosis. Methods: Radiographic and densitometric spine images for postmenopausal women at low risk (LR; n = 459) and high risk (HR; n = 298) of VF were assessed using ABQ. Agreement between imaging modalities for VF diagnosis was assessed by κ statistics using ABQ radiographic readings as the gold standard. Results: The prevalence of VF was 11-29% (radiography) and 9-26% (VFA) in the LR and HR groups, respectively. Agreement between imaging modalities was good or very good (κ = 0.62-0.81 in the LR and HR populations). The sensitivity to detect women with VF by VFA was 71% and 84% in the LR and HR populations, respectively, and specificity was 97%. Fifty-two (77%) and 60 (61%) of vertebrae misclassified by VFA in the LR and HR populations were mild fractures and 37 (54%) and 62 (63%) were wedge fractures. One third of fractures missed by VFA were related to poor or unreadable image quality (n = 27 and 28 vertebrae in the LR and HR populations, respectively). Conclusions: There was good agreement between VFA and radiography using ABQ to identify prevalent VF in women at LR or HR of osteoporotic VF. Vertebrae misclassified by VFA were primarily mild fractures or deformities, and two thirds of all fractures missed by VFA were related to poor or unreadable image quality.

A unique case of combined intrauterine vascular insufficiency and complete brachial plexus palsy is described in a newborn delivered by cesarean section. Intrauterine vascular insufficiency resulted in a right below elbow amputation at 3 weeks of age. Amputation length was preserved after a pedicled thoracoabdominal flap. Function of the C5, C6, and C7 nerve roots returned to normal by 3 months of age.

OBJECTIVE—Triglyceride-rich lipoproteins, primarily chylomicrons, can contribute to plasma free fatty acid (FFA) concentrations via spillover of fatty acids during intravascular hydrolysis into the venous effluent of some tissues. The present study was undertaken to determine whether spillover occurs in the splanchnic bed of humans. RESEARCH DESIGN AND METHODS—Arterial and hepatic venous blood was sampled in postabsorptive (n = 6; study A) and postprandial (n = 5; study B) obese humans during infusion of carbon-labeled (14C or 13C) oleate and 3H triolein, the latter incorporated into a lipid emulsion as a surrogate for chylomicrons. Spillover was determined by measuring production of 3H oleate. RESULTS—Splanchnic spillover was higher than nonsplanchnic systemic spillover in both study A (60 ± 7 vs. 24 ± 6%; P < 0.01) and study B (54 ± 3 vs. 16 ± 5%; P < 0.005). Because portal vein sampling is not feasible in humans, assumptions regarding actual spillover in nonhepatic splanchnic tissues were required for the spillover calculation. A mathematical model was developed and demonstrated that nonhepatic splanchnic spillover rates in study A and study B of 69 and 80%, respectively, provided the best fit with the data. There was preferential splanchnic uptake of triglyceride fatty acids compared with FFAs in study B (fractional extraction 61 ± 3 vs. 33 ± 2%; P < 0.005). CONCLUSIONS—These data confirm previous studies indicating that the transport of FFAs and triglyceride fatty acids are partitioned in tissues and indicate that splanchnic spillover from triglyceride-rich lipoproteins may be a significant source of both portal venous and systemic FFAs.

Patients with monoclonal gammopathy of undetermined significance (MGUS) are at continuous risk of progression. Each year, 1% progress, usually to active multiple myeloma (MM).1 Such patients must be monitored for life. Asymptomatic smoldering multiple myeloma (SMM) has an even greater risk of progression to MM. Recently reported strategies improve our ability to estimate the risk of MM in these patients.