Elias Anaissie

Bio: Elias Anaissie is an academic researcher from University of Cincinnati. The author has contributed to research in topics: Multiple myeloma & Transplantation. The author has an hindex of 107, co-authored 372 publications receiving 42808 citations. Previous affiliations of Elias Anaissie include Pennsylvania State University & Celgene.

Antitumor activity of thalidomide in refractory multiple myeloma.

Abstract: Background Patients with myeloma who relapse after high-dose chemotherapy have few therapeutic options. Since increased bone marrow vascularity imparts a poor prognosis in myeloma, we evaluated the efficacy of thalidomide, which has antiangiogenic properties, in patients with refractory disease. Methods Eighty-four previously treated patients with refractory myeloma (76 with a relapse after high-dose chemotherapy) received oral thalidomide as a single agent for a median of 80 days (range, 2 to 465). The starting dose was 200 mg daily, and the dose was increased by 200 mg every two weeks until it reached 800 mg per day. Response was assessed on the basis of a reduction of the myeloma protein in serum or Bence Jones protein in urine that lasted for at least six weeks. Results The serum or urine levels of paraprotein were reduced by at least 90 percent in eight patients (two had a complete remission), at least 75 percent in six patients, at least 50 percent in seven patients, and at least 25 percent in six p...

Treatment of Aspergillosis: Clinical Practice Guidelines of the Infectious Diseases Society of America

Abstract: Aspergillus species have emerged as an important cause of life-threatening infections in immunocompromised patients. This expanding population is composed of patients with prolonged neutropenia, advanced HIV infection, and inherited immunodeficiency and patients who have undergone allogeneic hematopoietic stem cell transplantation (HSCT) and/or lung transplantation. This document constitutes the guidelines of the Infectious Diseases Society of America for treatment of aspergillosis and replaces the practice guidelines for Aspergillus published in 2000 [1]. The objective of these guidelines is to summarize the current evidence for treatment of different forms of aspergillosis. The quality of evidence for treatment is scored according to a standard system used in other Infectious Diseases Society of America guidelines. This document reviews guidelines for management of the 3 major forms of aspergillosis: invasive aspergillosis, chronic (and saprophytic) forms of aspergillosis, and allergic forms of aspergillosis. Given the public health importance of invasive aspergillosis, emphasis is placed on the diagnosis, treatment, and prevention of the different forms of invasive aspergillosis, including invasive pulmonary aspergillosis, sinus aspergillosis, disseminated aspergillosis, and several types of single-organ invasive aspergillosis. There are few randomized trials on the treatment of invasive aspergillosis. The largest randomized controlled trial demonstrates that voriconazole is superior to deoxycholate amphotericin B (D-AMB) as primary treatment for invasive aspergillosis. Voriconazole is recommended for the primary treatment of invasive aspergillosis in most patients (A-I). Although invasive pulmonary aspergillosis accounts for the preponderance of cases treated with voriconazole, voriconazole has been used in enough cases of extrapulmonary and disseminated infection to allow one to infer that voriconazole is effective in these cases. A randomized trial comparing 2 doses of liposomal amphotericin B (L-AMB) showed similar efficacy in both arms, suggesting that liposomal therapy could be considered as alternative primary therapy in some patients (A-I). For salvage therapy, agents include lipid formulations of amphotericin (LFAB; A-II), posaconazole (B-II), itraconazole (B-II), caspofungin (B-II), or micafungin (B-II). Salvage therapy for invasive aspergillosis poses important challenges with significant gaps in knowledge. In patients whose aspergillosis is refractory to voriconazole, a paucity of data exist to guide management. Therapeutic options include a change of class using an amphotericin B (AMB) formulation or an echinocandin, such as caspofungin (B-II); further use of azoles should take into account host factors and pharmacokinetic considerations. Refractory infection may respond to a change to another drug class (B-II) or to a combination of agents (B-II). The role of combination therapy in the treatment of invasive aspergillosis as primary or salvage therapy is uncertain and warrants a prospective, controlled clinical trial. Assessment of patients with refractory aspergillosis may be difficult. In evaluating such patients, the diagnosis of invasive aspergillosis should be established if it was previously uncertain and should be confirmed if it was previously known. The drug dosage should be considered. Management options include a change to intravenous (IV) therapy, therapeutic monitoring of drug levels, change of drug class, and/or combination therapy. Antifungal prophylaxis with posaconazole can be recommended in the subgroup of HSCT recipients with graft-versus-host disease (GVHD) who are at high risk for invasive aspergillosis and in neutropenic patients with acute myelogenous leukemia or myelodysplastic syndrome who are at high risk for invasive aspergillosis (A-I). Management of breakthrough invasive aspergillosis in the context of mould-active azole prophylaxis is not defined by clinical trial data. The approach to such patients should be individualized on the basis of clinical criteria, including host immunosuppression, underlying disease, and site of infection, as well as consideration of antifungal dosing, therapeutic monitoring of drug levels, a switch to IV therapy, and/or a switch to another drug class (B-III). Certain conditions of invasive aspergillosis warrant consideration for surgical resection of the infected focus. These include but are not limited to pulmonary lesions contiguous with the heart or great vessels, invasion of the chest wall, osteomyelitis, pericardial infection, and endocarditis (B-III). Restoration of impaired host defenses is critical for improved outcome of invasive aspergillosis (A-III). Recovery from neutropenia in a persistently neutropenic host or reduction of corticosteroids in a patient receiving high-dose glucocorticosteroids is paramount for improved outcome in invasive aspergillosis. A special consideration is made concerning recommendations for therapy of aspergillosis in uncommon sites, such as osteomyelitis and endocarditis. There are very limited data on these infections, and most involve D-AMB as primary therapy simply because of its long-standing availability. Based on the strength of the randomized study, the panel recommends voriconazole for primary treatment of these very uncommon manifestations of invasive aspergillosis (B-III). Management of the chronic or saprophytic forms of aspergillosis varies depending on the condition. Single pulmonary aspergillomas may be best managed by surgical resection (B-III), whereas chronic cavitary and chronic necrotizing pulmonary aspergillosis require long-term medical therapy (B-III). The management of allergic forms of aspergillosis involves a combination of medical and anti-inflammatory therapy. For example, management of allergic bronchopulmonary aspergillosis (ABPA) involves the administration of itraconazole and corticosteroids (A-I). © 2008 by the Infectious Diseases Society of America. All rights reserved.

Invasive Fungal Infections among Organ Transplant Recipients: Results of the Transplant‐Associated Infection Surveillance Network (TRANSNET)

Abstract: Methods. The Transplant-Associated Infection Surveillance Network (TRANSNET) is a consortium of 23 US transplant centers, including 15 that contributed to the organ transplant recipient dataset. We prospectively identified IFIs among organ transplant recipients from March, 2001 through March, 2006 at these sites. To explore trends, we calculated the 12-month cumulative incidence among 9 sequential cohorts. Results. During the surveillance period, 1208 IFIs were identified among 1063 organ transplant recipients. The most common IFIs were invasive candidiasis (53%), invasive aspergillosis (19%), cryptococcosis (8%), nonAspergillus molds (8%), endemic fungi (5%), and zygomycosis (2%). Median time to onset of candidiasis, aspergillosis, and cryptococcosis was 103, 184, and 575 days, respectively. Among a cohort of 16,808 patients who underwent transplantation between March 2001 and September 2005 and were followed through March 2006, a total of 729 IFIs were reported among 633 persons. One-year cumulative incidences of the first IFI were 11.6%, 8.6%, 4.7%, 4.0%, 3.4%, and 1.3% for small bowel, lung, liver, heart, pancreas, and kidney transplant recipients, respectively. One-year incidence was highest for invasive candidiasis (1.95%) and aspergillosis (0.65%). Trend analysis showed a slight increase in cumulative incidence from 2002 to 2005. Conclusions. We detected a slight increase in IFIs during the surveillance period. These data provide important insights into the timing and incidence of IFIs among organ transplant recipients, which can help to focus effective prevention and treatment strategies.

Prospective Surveillance for Invasive Fungal Infections in Hematopoietic Stem Cell Transplant Recipients, 2001–2006: Overview of the Transplant-Associated Infection Surveillance Network (TRANSNET) Database

Abstract: Background The incidence and epidemiology of invasive fungal infections (IFIs), a leading cause of death among hematopoeitic stem cell transplant (HSCT) recipients, are derived mainly from single-institution retrospective studies. Methods The Transplant Associated Infections Surveillance Network, a network of 23 US transplant centers, prospectively enrolled HSCT recipients with proven and probable IFIs occurring between March 2001 and March 2006. We collected denominator data on all HSCTs preformed at each site and clinical, diagnostic, and outcome information for each IFI case. To estimate trends in IFI, we calculated the 12-month cumulative incidence among 9 sequential subcohorts. Results We identified 983 IFIs among 875 HSCT recipients. The median age of the patients was 49 years; 60% were male. Invasive aspergillosis (43%), invasive candidiasis (28%), and zygomycosis (8%) were the most common IFIs. Fifty-nine percent and 61% of IFIs were recognized within 60 days of neutropenia and graft-versus-host disease, respectively. Median onset of candidiasis and aspergillosis after HSCT was 61 days and 99 days, respectively. Within a cohort of 16,200 HSCT recipients who received their first transplants between March 2001 and September 2005 and were followed up through March 2006, we identified 718 IFIs in 639 persons. Twelve-month cumulative incidences, based on the first IFI, were 7.7 cases per 100 transplants for matched unrelated allogeneic, 8.1 cases per 100 transplants for mismatched-related allogeneic, 5.8 cases per 100 transplants for matched-related allogeneic, and 1.2 cases per 100 transplants for autologous HSCT. Conclusions In this national prospective surveillance study of IFIs in HSCT recipients, the cumulative incidence was highest for aspergillosis, followed by candidiasis. Understanding the epidemiologic trends and burden of IFIs may lead to improved management strategies and study design.

Harrison's Principles of Internal Medicine

Abstract: The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

KDIGO clinical practice guidelines for acute kidney injury.

Abstract: tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

Biofilms: Survival Mechanisms of Clinically Relevant Microorganisms

Abstract: Though biofilms were first described by Antonie van Leeuwenhoek, the theory describing the biofilm process was not developed until 1978. We now understand that biofilms are universal, occurring in aquatic and industrial water systems as well as a large number of environments and medical devices relevant for public health. Using tools such as the scanning electron microscope and, more recently, the confocal laser scanning microscope, biofilm researchers now understand that biofilms are not unstructured, homogeneous deposits of cells and accumulated slime, but complex communities of surface-associated cells enclosed in a polymer matrix containing open water channels. Further studies have shown that the biofilm phenotype can be described in terms of the genes expressed by biofilm-associated cells. Microorganisms growing in a biofilm are highly resistant to antimicrobial agents by one or more mechanisms. Biofilm-associated microorganisms have been shown to be associated with several human diseases, such as native valve endocarditis and cystic fibrosis, and to colonize a wide variety of medical devices. Though epidemiologic evidence points to biofilms as a source of several infectious diseases, the exact mechanisms by which biofilm-associated microorganisms elicit disease are poorly understood. Detachment of cells or cell aggregates, production of endotoxin, increased resistance to the host immune system, and provision of a niche for the generation of resistant organisms are all biofilm processes which could initiate the disease process. Effective strategies to prevent or control biofilms on medical devices must take into consideration the unique and tenacious nature of biofilms. Current intervention strategies are designed to prevent initial device colonization, minimize microbial cell attachment to the device, penetrate the biofilm matrix and kill the associated cells, or remove the device from the patient. In the future, treatments may be based on inhibition of genes involved in cell attachment and biofilm formation.

Revised Definitions of Invasive Fungal Disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group

Abstract: BACKGROUND: Invasive fungal diseases are important causes of morbidity and mortality. Clarity and uniformity in defining these infections are important factors in improving the quality of clinical studies. A standard set of definitions strengthens the consistency and reproducibility of such studies. METHODS: After the introduction of the original European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group definitions, advances in diagnostic technology and the recognition of areas in need of improvement led to a revision of this document. The revision process started with a meeting of participants in 2003, to decide on the process and to draft the proposal. This was followed by several rounds of consultation until a final draft was approved in 2005. This was made available for 6 months to allow public comment, and then the manuscript was prepared and approved. RESULTS: The revised definitions retain the original classifications of "proven," "probable," and "possible" invasive fungal disease, but the definition of "probable" has been expanded, whereas the scope of the category "possible" has been diminished. The category of proven invasive fungal disease can apply to any patient, regardless of whether the patient is immunocompromised, whereas the probable and possible categories are proposed for immunocompromised patients only. CONCLUSIONS: These revised definitions of invasive fungal disease are intended to advance clinical and epidemiological research and may serve as a useful model for defining other infections in high-risk patients.