Brad W. Butcher

The graft-versus-lymphoma effect: clinical review and future opportunities

Summary:Numerous lines of preclinical and clinical evidence support the existence of a graft-versus-leukemia effect, but less evidence supporting a comparable graft-versus-lymphoma effect exists. We review here current clinical data addressing the graft-versus-lymphoma effect, including comparisons of autologous, syngeneic, and allogeneic transplantation; responses to immunomodulation; and responses to nonmyeloablative stem cell transplantation. Despite several limitations of the data, we believe that there is sufficient evidence suggesting a significant graft-versus-lymphoma effect. In addition, we discuss approaches for clinical management of lymphoma patients, opportunities for mechanistic studies afforded by donor leukocyte infusions and nonmyeloablative transplantation, and suggestions for clinical studies to further define the magnitude and applicability of the graft-versus-lymphoma effect.

Pauci-immune glomerulonephritis in individuals with disease associated with levamisole-adulterated cocaine: a series of 4 cases.

AbstractExposure to levamisole-adulterated cocaine can induce a distinct clinical syndrome characterized by retiform purpura and/or agranulocytosis accompanied by an unusual constellation of serologic abnormalities including antiphospholipid antibodies, lupus anticoagulants, and very high titers of antineutrophil cytoplasmic antibodies. Two recent case reports suggest that levamisole-adulterated cocaine may also lead to renal disease in the form of pauci-immune glomerulonephritis. To explore this possibility, we reviewed cases of pauci-immune glomerulonephritis between 2010 and 2012 at an inner city safety net hospital where the prevalence of levamisole in the cocaine supply is known to be high. We identified 3 female patients and 1 male patient who had biopsy-proven pauci-immune glomerulonephritis, used cocaine, and had serologic abnormalities characteristic of levamisole-induced autoimmunity. Each also had some other form of clinical disease known to be associated with levamisole, either neutropenia or cutaneous manifestations. One patient had diffuse alveolar hemorrhage. Three of the 4 patients were treated with short courses of prednisone and cyclophosphamide, 2 of whom experienced stable long-term improvement in their renal function despite ongoing cocaine use. The remaining 2 patients developed end-stage renal disease and became dialysis-dependent. This report supports emerging concern of more wide spread organ toxicity associated with the use of levamisole-adulterated cocaine.

Impact of proactive rounding by a rapid response team on patient outcomes at an academic medical center.

BACKGROUND The impact of rapid response teams (RRT) on patient outcomes remains uncertain. OBJECTIVE To examine the effect of proactive rounding by an RRT on outcomes of hospitalized adults discharged from intensive care. DESIGN Retrospective, observational study. SETTING Academic medical center. PATIENTS All adult patients discharged alive from the intensive care unit (ICU) at the University of California San Francisco Medical Center between January 2006 and June 2009. INTERVENTION Introduction of proactive rounding by an RRT. MEASUREMENTS Outcomes included the ICU readmission rate, ICU average length of stay (LOS), and in-hospital mortality of patients discharged from the ICU. Data were obtained from administrative billing databases and analyzed using an interrupted time series (ITS) model. RESULTS We analyzed 17 months of preintervention data and 25 months of postintervention data. Introduction of proactive rounding by the RRT did not change the ICU readmission rate (6.7% before vs 7.3% after; P = 0.24), the ICU LOS (5.1 days vs 4.9 days; P = 0.24), or the in-hospital mortality of patients discharged from the ICU (6.0% vs 5.5%; P = 0.24). ITS models testing the impact of proactive rounding on secular trends found no improvement in any of the 3 clinical outcomes relative to their preintervention trends. CONCLUSIONS Proactive rounding by an RRT did not improve patient outcomes, raising further questions about RRT benefits.

Fluid overload in AKI: epiphenomenon or putative effect on mortality?

Purpose of reviewThe incidence of acute kidney injury (AKI) is increasing dramatically, and despite advances in dialytic therapy and critical care, there has been little improvement in associated morbidity and mortality. Recently, several articles have suggested that fluid overload in patients with AKI is associated with an increased risk of death. Recent findingsObservational studies have demonstrated an association between fluid overload and poor outcomes (including death) in patients with AKI; however, whether this association is causal or due to residual confounding is unknown. A recent study testing the impact of fluid overload and diuretics on outcomes in the context of a randomized controlled trial suggests that the beneficial impact of diuretics in those with AKI is mediated by reducing fluid overload. Finally, potential mechanisms by which fluid overload may contribute to death include failure to recognize AKI due to creatinine dilution, direct tissue edema leading to decreased renal perfusion, and an increased risk of other complications such as sepsis. SummaryOn the basis of the current literature, the relative contributions of the direct effects of fluid overload versus the association of fluid overload with other patient characteristics associated with adverse outcome (e.g. sepsis) remain unknown. Additional human studies, including randomized controlled trials, are warranted to further clarify these issues.

Evolving practices in critical care and their influence on acute kidney injury.

Purpose of reviewThis review highlights the principal advances in critical care over the past year, and discusses the impact of these advances on the diagnosis and management of acute kidney injury (AKI). Recent findingsRecent literature has focused on assessment of volume status and fluid management, particularly in the setting of respiratory and cardiac failure. Other critical care topics are reviewed using a system-based approach. SummaryThe incidence of AKI appears to be increasing, and despite advances in the provision of critical care and renal replacement therapies, there has been little improvement in its associated morbidity and mortality. Nonetheless, recent advances in critical care will impact the diagnosis and management of AKI, as well as shape the future research agenda. Continued work in the fields of critical care and nephrology will undoubtedly be centered on improved biomarkers for the detection of AKI, specific therapies to mitigate or reverse AKI, and techniques to prevent the development of AKI in the critically ill population.