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Paroxysmal nocturnal hemoglobinuria (PNH) is a rare clonal disorder caused by a somatic mutation of the X-linked phosphatidylinositol glycan class A gene. Allogeneic hematopoietic cell transplantation (HCT) after high-dose conditioning is the only curative treatment; however, it is associated with high treatment-related mortality. Here, we report on allogeneic HCT for PNH after minimal conditioning. Seven adult patients with high-risk PNH underwent peripheral blood HCT from HLA-A-, -B-, -C-, -DRB1-, and -DQB1-matched related (n = 2) and unrelated (n = 5) donors. Conditioning included fludarabine 30 mg/m2/d on days −4 to −2 and 2 Gy of total body irradiation on day 0. After HCT, patients were given immunosuppressive therapy with oral cyclosporine starting on day −3 and mycophenolate mofetil starting on day 0. All 7 patients attained durable engraftment. After 28 days, a median of 77% (range, 53%–96%) T-cell donor chimerism was found in bone marrow and peripheral blood. T-cell chimerism increased to 91% (range, 76%–100%) on day +180 and to 100% in all surviving patients after 12 months. All 7 patients attained complete remissions of their disease. Four patients are alive 13 to 38 months after HCT. Three patients died of treatment-related mortality, 1 because of complications after acute pancreatitis and multiorgan failure, 1 because of infection related to chronic graft-versus-host disease (GVHD), and 1 because of bleeding after liver biopsy for late subacute/chronic GVHD. Allogeneic HCT from related and unrelated donors after minimal conditioning is a new and potentially curative option for patients with advanced PNH. [Copyright &y& Elsevier]

K'gari in South East Queensland, Australia, is the world's largest sand island and a UNESCO World Heritage Area. The island is covered by extensive coastal dune fields that have been divided into seven morphological units (the Awinya, Yankee Jack, Bowarrady, Triangle Cliff, Freshwater, Station Hill, and Cape). Optically-Stimulated Luminescence dating of the dune sequences indicate that the Awinya unit is > 340 ka, and the Yankee Jack and Bowarrady units are ca. 180 ka old. Holocene dune sequences comprise Triangle Cliff (ca. 8.5 ka); Freshwater (ca. 4 ka); Station Hill (ca. 1.5 ka) and Cape (ca. < 0.5 ka). Combining these data with dune ages from the adjacent Cooloola Sand Mass, we demonstrate that for at least the last three glacial cycles the dunes were emplaced during intermediate to high sea-levels. At shorter time intervals (decades to centuries), some dune formation is affected by storminess. Initial formation of the dune field occurred in the mid-Pleistocene, but the most recent widespread stabilisation of dunes occurred late in Marine Isotope Stage 7 (MIS 7: 190–240 ka). The preservation of dunes relates to antecedent topography coupled with the duration and height of individual interglacial high sea-stands. This research confirms K'gari as an outstanding example of geomorphological processes and supports its World Heritage listing. • First chronology of all the major parabolic dune units on K'gari (formerly Fraser Island), the world's largest sand island. • The dune units are emplaced during intermediate to high sea-levels at least as far back Marine Isotope Stage 7. • A major Late Holocene scarp suggests that major cyclones can penetrate SE Queensland on occasions. [ABSTRACT FROM AUTHOR]

Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor–positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials. [ABSTRACT FROM AUTHOR]

Background: Although secondary acute leukemias and myelodysplasia are the known complications of adjuvant chemotherapy for breast cancer, the treatment outcome of these secondary malignancies is presently unclear. We examined the clinical and pathological features as well as the treatment results of a series of patients with acute leukemia/myelodysplasia arising after adjuvant chemotherapy for breast cancer. [ABSTRACT FROM PUBLISHER]

Objectives: We sought to determine whether a multidisciplinary outpatient management program decreases chronic heart failure (CHF) hospital readmissions and mortality over a six-month period.Background: Hospital admission for CHF is an important problem amenable to improved outpatient management.Methods: Two hundred patients hospitalized with CHF at increased risk of hospital readmission were randomized to a multidisciplinary program or usual care. A study cardiologist and a CHF nurse evaluated each patient and made recommendations to the patient's primary physician before randomization. The intervention team consisted of a cardiologist, a CHF nurse, a telephone nurse coordinator and the patient's primary physician. Contact with the patient was on a prespecified schedule. The CHF nurse followed an algorithm to adjust medications. Patients in the nonintervention group were followed as usual. The primary outcome was the composite of the number of CHF hospital admissions and deaths over six months, compared by using a log transformation t test by intention-to-treat analysis.Results: The median age of the study patients was 63.5 years, and 39.5% were women. There were 43 CHF hospital admissions and 7 deaths in the intervention group, as compared with 59 CHF hospital admissions and 13 deaths in the nonintervention group (p = 0.09). The quality-of-life score, percentage of patients on target vasodilator therapy and percentage of patients compliant with diet recommendations were significantly better in the intervention group. Cost per patient, in 1998 U.S. dollars, was similar in both groups.Conclusions: This study demonstrates that a six-month, multidisciplinary approach to CHF management can improve important clinical outcomes at a similar cost in recently hospitalized high-risk patients with CHF. [ABSTRACT FROM AUTHOR]

Costs for management of myocardial ischemia are enormous, yet comparison cost and outcome data for various ischemia treatment strategies from randomized trials are lacking and will require cost and resource utilization data from a large prospective trial. The Asymptomatic Cardiac Ischemia Pilot provided feasibility data for planning such a trial and an opportunity to estimate the long-term costs of different treatment strategies. Economic implications for ischemia management were compared in 558 patients with stable coronary artery disease and myocardial ischemia during both stress testing and daily life. Participants were randomized to 3 different initial treatment strategies and followed for 2 years. Based on cost trends over follow-up, costs for subsequent care were estimated. As expected, due to initial procedural costs, at 3 months, estimated costs for revascularization were approximately 10 times greater than costs for a medical care strategy. Extrapolated costs for anticipated resource consumption for care beyond 2 years, however, were approximately 2 times greater for an initial medical care strategy than for initial revascularization. This was due to increased need for drugs and hospitalizations for both late revascularizations and other ischemia-related events. Estimated costs for anticipated care in the medical strategies reached the anticipated cost of the revascularization strategy within 10 years. Because this cost-equal time period is well within the median life expectancy for such a patient population, these findings could have important public health implications and require testing in a full-scale prognosis trial. We anticipate that over the patients' life expectancy, early revascularization is likely to become either cost-neutral or cost-effective. [ABSTRACT FROM AUTHOR]