Acute and short-term haemodynamic impact of transcatheter pulmonary valve implantation on left ventricular systolic and diastolic function.

OBJECTIVES: Assess the acute and short-term haemodynamic impact of transcatheter pulmonary valve implantation on left ventricular systolic and diastolic function stratified by pre-transcatheter pulmonary valve implantation physiology. BACKGROUND: Transcatheter pulmonary valve implantation is a widely available option to treat residual or recurrent pulmonary stenosis and pulmonary insufficiency. Transcatheter pulmonary valve implantation acutely increases pulmonary artery size and diastolic pressure in patients with pulmonary insufficiency and acute pulmonary edema has been reported after transcatheter pulmonary valve implantation, possibly related to acute left ventricular volume loading. However, the impact of transcatheter pulmonary valve implantation on left ventricular diastolic function has not been established. METHODS: Patients who underwent transcatheter pulmonary valve implantation from 2010 to 2017 at our centre were grouped by indication for transcatheter pulmonary valve implantation as pulmonary stenosis, pulmonary insufficiency, or mixed disease. Separate analysis was performed on those who underwent transcatheter pulmonary valve implantation for pulmonary stenosis versus pulmonary insufficiency or mixed disease. Intracardiac haemodynamics immediately before and after transcatheter pulmonary valve implantation and echocardiographic assessment of left ventricular systolic and diastolic function at baseline, 1-day post transcatheter pulmonary valve implantation, and 1-year post transcatheter pulmonary valve implantation were compared between groups. RESULTS: In 102 patients who underwent transcatheter pulmonary valve implantation, the indication was pulmonary stenosis in 29 (28%), pulmonary insufficiency in 28 (29%), and mixed disease in 44 (43%). There were no significant differences in left ventricular systolic or diastolic function between groups at baseline, immediately after transcatheter pulmonary valve implantation, or 1-year post implantation. The mean pulmonary artery wedge pressure increased equally across groups. CONCLUSIONS: While patients with pulmonary insufficiency likely have acute left ventricular volume loading following transcatheter pulmonary valve implantation, this does not appear to be haemodynamically significant as transcatheter pulmonary valve implantation was not associated with measurable changes in left ventricular systolic or diastolic function acutely or 1-year post implantation.

Pracinostat plus azacitidine in older patients with newly diagnosed acute myeloid leukemia: results of a phase 2 study.

Pracinostat, a potent oral pan-histone deacetylase inhibitor with modest single-agent activity in acute myeloid leukemia (AML), has shown synergistic antitumor activity when combined with azacitidine. This single-group, multicenter phase 2 study assessed the safety and efficacy of pracinostat combined with azacitidine in patients who were at least 65 years old with newly diagnosed AML and who were ineligible for standard induction chemotherapy. Patients received pracinostat 60 mg/d, 3 d/wk, for 3 consecutive weeks, plus azacitidine 75 mg/m2 daily for 7 days in a 28-day cycle. Primary endpoints were complete remission (CR), CR with incomplete count recovery (CRi), and morphologic leukemia-free state (MLFS) rates of the combination. Secondary endpoints included safety, progression-free survival (PFS), and overall survival (OS) of the regimen. Fifty patients (33 de novo, 12 secondary, and 5 therapy-related AML) were enrolled. Twenty-six patients (52%) achieved the primary endpoint of CR (42%), CRi (4%), and MLFS (6%). Median OS and PFS were 19.1 months (95% confidence interval [CI], 10-26.5 months) and 12.6 months (95% CI, 10-17.7 months), respectively, with a 1-year OS rate of 62%. Forty-three patients (86%) experienced at least 1 grade 3 or worse treatment-emergent adverse event with the combination, with infections (52%), thrombocytopenia (46%), and febrile neutropenia (44%) reported as the most common toxicities. The 30- and 60-day all-cause mortality rates were 2% and 10%, respectively. DNA sequencing revealed somatic mutations at baseline, and clearance rates correlated with response to treatment. Pracinostat plus azacitidine is a well-tolerated and active regimen in the frontline treatment of older patients with AML unfit for intensive therapy. A larger controlled trial is ongoing. This trial was registered at www.clinicaltrials.gov as #NCT01912274.

Effectiveness of cleaning and health education in reducing childhood lead poisoning among children residing near superfund sites in Missouri.

In this study, the authors evaluated whether a combination of tailored education, lead dust removal by trained cleaning specialists, and family follow-up visits would be more effective than conventional health educational programs in reducing elevated blood lead levels in children living in or near lead mining hazardous waste sites. The authors randomized children between 6 and 72 mo of age with blood lead levels between 10 and 20 microg/dl into 3 groups: standard care, tailored newsletters, or tailored newsletters and specialized cleaning. The authors obtained questionnaires, blood lead levels, and environmental lead samples during initiation and compared them with the same items obtained at 3, 6, and 9 mo follow-up. They used a linear mixed effect model to evaluate the intervention effect. Blood lead levels decreased overall 1.54 microg/dl (12.1%) during the study. The authors found that tailored newsletters and specialized cleaning produced the greatest decline in blood lead levels, but no statistical differences were found among the methodologies. The small decline observed in blood lead levels reduced levels to below 10 microg/dl for 40% of the children.

Urothelial cell intracytoplasmic inclusions after treatment of promyelocytic leukemia with arsenic trioxide.

Intramitochondrial inclusions containing arsenite that occur within urothelial cells have been previously described in mice exposed to high concentrations of arsenic but not in rats. In epidemiology studies, similar urothelial cell inclusions have also been observed in the urine of humans exposed to high concentrations of arsenic in the drinking water; however, these inclusions were mistakenly identified as micronuclei. To further examine the urothelial cell inclusions that occur in inorganic arsenic-exposed humans, we evaluated two patients with a history of acute promyelocytic leukemia treated for disease relapse with a combination of all-trans retinoic acid and arsenic trioxide. Posttreatment examination of the patients' urine cytology specimens by light and electron microscopy demonstrated cytoplasmic inclusions in exfoliated superficial urothelial cells similar to those seen in mice. The inclusions were present in decreasing quantities at 3 and 7 months after completion of treatment. No comparable inclusions were detected in exfoliated urothelial cells in urine from six individuals not treated with arsenic trioxide. Based on the results of the examination by light and electron microscopy, we have determined that urothelial cell inclusions in the urine of humans previously identified as micronuclei are instead intracytoplasmic inclusions similar to those found in arsenic-treated mice.

Revisiting use of growth factors in myelodysplastic syndromes.

Myelodysplastic syndromes (MDS) represent a heterogeneous group of clonal hematologic neoplasms characterized by morphologic dysplasia, aberrant hematopoiesis and peripheral blood refractory cytopenias. MDS is recognized to be associated with an increased risk of symptomatic anemia, infectious complications and bleeding diathesis, as well as a risk of progression to acute myeloid leukemia, particularly in patients with a high IPSS score. The advent of use of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) and recombinant erythropoietin (EPO) has improved symptoms in MDS patients in addition to some data that suggest there might be an improvement in survival. G-CSF is an effective therapeutic option in MDS patients, and it should be considered for the management of refractory symptomatic cytopenias. G-CSF and EPO in combination can improve outcomes in appropriate MDS patients such as those with lower-risk MDS and refractory anemia with ring sideroblasts (RARS) . This article reviews use of growth factors for lower-risk MDS patients, and examines the data for G-CSF, EPO and thrombopietic growth factors (TPO) that are available or being developed as therapeutic modalities for this challenging disease.

Comparing quality of care between a consumer-directed health plan and a traditional plan: an analysis of HEDIS measures related to management of chronic diseases.

A cross-sectional, retrospective medical and pharmaceutical claims data analysis was conducted to determine if Healthcare Effectiveness Data and Information Set (HEDIS) measures related to care for chronic conditions differed between enrollees in a traditional comprehensive major medical plan (CMM) and a consumer-directed health plan (CDHP). Eleven HEDIS measures for 2006 were compared for CMM and CDHP enrollees in a health plan. Measures included care for persons with diabetes, asthma, depression, cardiovascular disease, and low back pain, and for persons taking persistent medications for specific conditions. In the CMM population, 1,238,949 members were eligible to be included; 131,763 members in the CDHP population were eligible. Statistical significance testing was performed. As measured by HEDIS, CDHP enrollees received higher quality of care than did CMM enrollees in areas related to low back pain, and eye exams and nephropathy screening for persons with diabetes. No significant differences were found between CDHP enrollees and CMM enrollees for measures describing medication management for persons with depression and asthma, annual monitoring for persons taking persistent medications, cholesterol management for persons with cardiovascular disease, or HbA1c testing and low-density lipoprotein screening for persons with diabetes. Enrollees in CDHPs who have chronic conditions received care at levels of quality equal to or better than CMM enrollees. The potential for increased financial responsibility in the CDHP plan did not appear to deter those enrollees from pursuing necessary care. Future research should control for the demographic factors thought to influence both selection into a plan design and quality of care.