Senu Apewokin

Clinical epidemiology of 960 patients with invasive aspergillosis from the PATH Alliance registry

OBJECTIVES The study investigated the epidemiology and outcome of invasive aspergillosis (IA), an important cause of morbidity and mortality in immunocompromised patients. METHODS Cases of proven/probable IA from the Prospective Antifungal Therapy Alliance (PATH Alliance(®)) registry - a prospective surveillance network comprising 25 centers in the United States and Canada that collected data on invasive fungal infections from 2004 to 2008 - were analyzed with respect to clinical outcome. RESULTS Nine hundred and sixty patients with IA were enrolled, the most frequent underlying disease being hematologic malignancy (n=464 [48.3%]). Two hundred and eighty patients (29.2%) received solid organ transplant; 268 patients (27.9%) underwent hematopoietic stem cell transplantation. Identified isolates included Aspergillus fumigatus (72.6%), Aspergillus flavus (9.9%), Aspergillus niger (8.7%) and Aspergillus terreus (4.3%). The lung was most frequently affected. Following diagnosis, 47% patients received monotherapy - voriconazole (70%), an amphotericin B formulation (13.8%), or an echinocandin (10.5%) - while 279 patients (29%) received combination therapy. Twelve-week overall survival was 64.4%. CONCLUSIONS In this series of patients with IA, the lung was the predominant focus of infection, A. fumigatus was the major species isolated, and overall survival appeared slightly improved compared with previous reports.

Renal insufficiency retains adverse prognostic implications despite renal function improvement following Total Therapy for newly diagnosed multiple myeloma

Renal insufficiency (RI) is a frequent complication of multiple myeloma (MM) with negative consequences for patient survival. The improved clinical outcome with successive Total Therapy (TT) protocols was limited to patients without RI. We therefore performed a retrospective analysis of overall survival, progression-free survival and time to progression (TTP) of patients enrolled in TT2 and TT3 in relationship to RI present at baseline and pre-transplant. Glomerular filtration rate was graded in four renal classes (RCs), RC1–RC4 (RC1 ⩾90 ml/min/1.73 m2, RC2 60–89 ml/min/1.73 m2, RC3 30–59 ml/min/1.73 m2 and RC4 <30 ml/min/1.73 m2). RC1–3 had comparable clinical outcomes while RC4 was deleterious, even after improvement to better RC after transplant. Among the 85% of patients with gene expression profiling defined low-risk MM, Cox regression modeling of baseline and pre-transplant features, which also took into consideration RC improvement and MM complete response (CR), identified the presence of metaphase cytogenetic abnormalities and baseline RC4 as independent variables linked to inferior TTP post-transplant, while MM CR reduced the risk of progression and TTP by more than 60%. Failure to improve clinical outcomes despite RI improvement suggested MM-related causes. Although distinguishing RC4 from RC<4, 46 gene probes bore no apparent relationship to MM biology or survival.

Genome-wide scan identifies variant in 2q12.3 associated with risk for multiple myeloma

To the editor: Common inherited genetic variants associated with disease risk may uncover important biological mechanisms behind neoplastic development. Here, we report a novel susceptibility locus associated with multiple myeloma (MM) risk and an additional promising locus, and we replicate 6

Risk factors, preemptive therapy, and antiperistaltic agents for Clostridium difficile infection in cancer patients

Clostridium difficile infection (CDI) is a serious complication of chemotherapy including high‐dose regimens with autologous stem cell transplantation (ASCT). Antiperistaltic agents are contraindicated in CDI and preemptive CDI therapy is not recommended. We assessed the incidence, risk factors, and outcomes of CDI in patients with newly diagnosed multiple myeloma (MM) receiving similar antineoplastic therapy and supportive care including antiperistaltic agents and preemptive CDI antibiotics for significant diarrhea.

Strongyloides hyperinfection diagnosed by bronchoalveolar lavage in an immunocompromized host.

has rarely been reported and seems to be associated with the disseminative form of the infection in immunosuppressed patients. Two cases of parotid cryptococcosis have been recently published 5,6 and, to the best of our knowledge, this is the third English-language case report of a clinical manifestation of C. neoformans infection in the parotid gland. FNAC was performed to confirm the initial suspicion of parotid gland tumour, but it rather identified the presence of C. neoformans. The diagnosis of cryptococcosis by FNAC has been reported in several organs, including the lung, thyroid, spleen, lymph nodes and pancreas. Cytologically, C. neoformans presents a spherical shape and measures approximately 5–15 lm, occasionally exhibiting narrow-base budding. The strong pink-to-red colour of the thick mucinous capsule of C. neoformans after mucicarmin staining also contributes to the diagnosis of cryptococcosis. The great offer of food and shelter and the ecological unbalance caused by the lack of natural predators contribute to the unrestrained multiplication of pigeons in urban areas. This report of parotid cryptococcosis in an immunocompetent individual demonstrates the importance of FNAC in the diagnosis of lesions in major salivary glands and warns about the risk of the uncontrolled increase of the bird population in urban centres.

Influenza A Outbreak in an Ambulatory Stem Cell Transplant Center

Background  In the era of cost-consciousness regarding healthcare , provision of medical services in an outpatient setting has become increasingly attractive. We report an influenza outbreak in an ambulatory stem cell transplant center in 2013 that highlights unique identification and infection control challenges in this setting. Methods  Nasopharyngeal swabs were performed on patients with suspected influenza-like illnesses (ILI), defined by subjective fever or measured temperature of ≥37.7°C (≥100°F) with cough or sore throat during July 25, 2013 through August 7, 2013. In addition, testing was triggered by an elevated C-reactive protein (CRP). Specimens were analyzed by using eSensor Respiratory Viral Panel. Clinical and epidemiologic information was collected in real time, and frequencies were calculated on demographics, baseline clinical parameters, treatment methods, comorbidities, and symptoms of affected persons. Results  Thirty-one patients had influenza A (H3N2) infection during July 25, 2013 through August 7, 2013. Only 7 patients (23%) met the Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists ILI case definition. Twenty-five patients (81%) had received ≥1 transplant, with 13 (42%) having occurred within 1 year before the outbreak. Twenty-five patients (81%) had received B-cell active chemotherapy <60 days before influenza diagnosis, 6 (19%) were neutropenic, and 25 (81%) lymphopenic. Among clinical and laboratory markers analyzed, abnormal CRP was the most sensitive screening tool for influenza. Twelve (39%) patients were hospitalized (median stay, 10 days; range, 2–20). No deaths occurred. Conclusions  Immunocompromised hosts with influenza have atypical presentations. Existing surveillance case definitions might be insufficient to reliably identify influenza outbreaks in such patients.

438Genetic Variants Associated with the Development of Clostridium Difficile Infection during Autologous Stemcell Transplantation

Difficile Infection during Autologous Stemcell Transplantation Senu Apewokin, MD; Elizabeth Coleman, PhD; Carol Enderlin, PhD; Julia Goodwin, PhD; Jeannette Lee, PhD; Stephen Erickson, PhD; Kent Mckelvey, MD, PhD; Vinay Raj, PhD; Naveen Sanath Kumar, MD; Zhou Daohong, PhD; The Myeloma Institute for Research and Therapy/University of Arkansas for Medical Sciences, Little Rock, AR; University of Arkansas for Medical Sciences, Little Rock, AR

459Clinical Characteristics and Outcomes of West Nile Neuroinvasive Disease in Immunocompromised Hosts: A case-Control Study

Disease in Immunocompromised Hosts: A case-Control Study Senu Apewokin, MD; Aasiya Matin, MD; Naveen Sanath Kumar, MD; Shebli Atrash, MD; Bakhous Aziz; Jameel Muzaffar; Vyjayanthi Ganga, MD; Monica Grazziutti, MD; Medicine, University Of Arkansas For Medical Sciences, Little Rock, AR; Myeloma Institute or Research and Therapy, UNIVERSTIY OF ARKANSAS FOR MEDICAL SCIENCES, LITTLE ROCK, AR; The Myeloma Institute for Research and Therapy/University of Arkansas for Medical Sciences, Little Rock, AR; Myeloma, UAMS myeloma institute., little rock, AR; Mirt, 4301 West Markham, little ROCK, AR

Severe mucositis and Clostridium difficile infection in adult autologous stem cell recipients: another question of the chicken or the egg?

We read with much interest the article by Alonso et al. where they studied Clostridium difficile infection (CDI) in 873 autologous stem cell transplant recipients and reported various risk factors associated with development of CDI [1]. In their discussion, theymentioned grade 2mucositis was a risk factor for development of CDI, and 2 possible explanations were offered. Their first explanation was a potential sampling bias because CDI testing was only by indication. In the second explanation, they postulated that mucosal damage resulting from chemotherapy-induced colitis as well as alteration in gut microbiome led to CDI, thereby implying severe mucositis preceded CDI. In our opinion, although this may be the possible pathogenesis, it is important to also consider an alternate hypothesis; which is that acquisition of CDI in such patients leads to the development of higher grades of mucositis and not necessarily the converse. In other words, severe mucositis could be a manifestation of CDI. In data published by Silva et al. [2] where lethal doses of methotrexate were administered to hamster models, they demonstrated that in the absence of CDI-active antibiotic treatment, enterocolitis developed in 85% of the hamsters.