Leveraging gene expression subgroups to classify DLBCL patients and select for clinical benefit from a novel agent.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, commonly described by cell-of-origin (COO) molecular subtypes. We sought to identify novel patient subgroups through an unsupervised analysis of a large public dataset of gene expression profiles from newly diagnosed de novo DLBCL patients, yielding 2 biologically distinct subgroups characterized by differences in the tumor microenvironment. Pathway analysis and immune deconvolution algorithms identified higher B-cell content and a strong proliferative signal in subgroup A and enriched T-cell, macrophage, and immune/inflammatory signals in subgroup B, reflecting similar biology to published DLBCL stratification research.

Intraventricular granulomatous mass associated with Mycobacterium haemophilum: A rare central nervous system manifestation in a patient with human immunodeficiency virus infection.

We report a rare case of Mycobacterium haemophilum presenting as an intraventricular granulomatous mass with loculated hydrocephalus and seizures in a patient with human immunodeficiency virus. M. haemophilum, a slow-growing mycobacteria, causes localized and disseminated disease among immunocompromised hosts.

Novel poxvirus infection in 2 patients from the United States.

Background: Some human poxvirus infections can be acquired through zoonotic transmission. We report a previously unknown poxvirus infection in 2 patients, 1 of whom was immunocompromised; both patients had known equine contact.

Methods: The patients were interviewed and clinical information was abstracted from the patients' medical files.

Acute muscular sarcocystosis: an international investigation among ill travelers returning from Tioman Island, Malaysia, 2011-2012.

Background: Through 2 international traveler-focused surveillance networks (GeoSentinel and TropNet), we identified and investigated a large outbreak of acute muscular sarcocystosis (AMS), a rarely reported zoonosis caused by a protozoan parasite of the genus Sarcocystis, associated with travel to Tioman Island, Malaysia, during 2011-2012.

Methods: Clinicians reporting patients with suspected AMS to GeoSentinel submitted demographic, clinical, itinerary, and exposure data. We defined a probable case as travel to Tioman Island after 1 March 2011, eosinophilia (>5%), clinical or laboratory-supported myositis, and negative trichinellosis serology.

Cerebral Angiostrongylus cantonensis infection in a captive African pygmy falcon (Polihierax semitorquatus) in southern California.

A 10-month-old, female African pygmy falcon (Polihierax semitorquatus) hatched and housed at the San Diego Zoo developed neurologic signs and died from a cerebral infection with the rat lungworm Angiostrongylus cantonensis. There was an associated mild nonsuppurative meningoencephalitis. This infection was diagnosed on histology and confirmed by detection of species-specific A.

Single-dose replication-defective VSV-based Nipah virus vaccines provide protection from lethal challenge in Syrian hamsters.

Nipah virus (NiV) continues to cause outbreaks of fatal human encephalitis due to spillover from its bat reservoir. We determined that a single dose of replication-defective vesicular stomatitis virus (VSV)-based vaccine vectors expressing either the NiV fusion (F) or attachment (G) glycoproteins protected hamsters from over 1000 times LD50 NiV challenge. This highly effective single-dose protection coupled with an enhanced safety profile makes these candidates ideal for potential use in livestock and humans.

Fatal transplant-associated west nile virus encephalitis and public health investigation-california, 2010.

Background: In December 2010, a case of West Nile virus (WNV) encephalitis occurring in a kidney recipient shortly after organ transplantation was identified.

Methods: A public health investigation was initiated to determine the likely route of transmission, detect potential WNV infections among recipients from the same organ donor, and remove any potentially infected blood products or tissues. Available serum, cerebrospinal fluid, and urine samples from the organ donor and recipients were tested for WNV infection by nucleic acid testing and serology.

Exserohilum infections associated with contaminated steroid injections: a clinicopathologic review of 40 cases.

September 2012 marked the beginning of the largest reported outbreak of infections associated with epidural and intra-articular injections. Contamination of methylprednisolone acetate with the black mold, Exserohilum rostratum, was the primary cause of the outbreak, with >13,000 persons exposed to the potentially contaminated drug, 741 confirmed drug-related infections, and 55 deaths. Fatal meningitis and localized epidural, paraspinal, and peripheral joint infections occurred.

The pox in the North American backyard: Volepox virus pathogenesis in California mice (Peromyscus californicus).

Volepox virus (VPXV) was first isolated in 1985 from a hind foot scab of an otherwise healthy California vole (Microtus californicus). Subsequent surveys in San Mateo County, CA, revealed serological evidence suggesting that VPXV is endemic to this area, and a second viral isolate from a Pinyon mouse (Peromyscus truei) was collected in 1988. Since then, few studies have been conducted regarding the ecology, pathology, and pathogenicity of VPXV, and its prevalence and role as a potential zoonotic agent remain unknown.

Solid organ transplant-associated lymphocytic choriomeningitis, United States, 2011.

Three clusters of organ transplant-associated lymphocytic choriomeningitis virus (LCMV) transmissions have been identified in the United States; 9 of 10 recipients died. In February 2011, we identified a fourth cluster of organ transplant-associated LCMV infections. Diabetic ketoacidosis developed in the organ donor in December 2010; she died with generalized brain edema after a short hospitalization.

Alternatives to retroorbital blood collection in hispid cotton rats (Sigmodon hispidus).

Cotton rats (Sigmodon hispidus) are a valuable animal model for many human viral diseases, including polio virus, measles virus, respiratory syncytial virus, and herpes simplex virus. Although cotton rats have been used in research since 1939, few publications address handling and sampling techniques for this species, and the retroorbital sinus remains the recommended blood sampling site. Here we assessed blood sampling methods that are currently used in other species and a novel subzygomatic sampling site for their use in S.

Ruptured mycotic aortic aneurysm in a sooty mangabey (Cercocebus atys).

Mycotic aortic aneurysm is a local, irreversible dilatation of the aorta associated with destruction of the vessel wall by infection and is a grave clinical condition associated with high morbidity and mortality in humans. Rupture of aortic aneurysms can be spontaneous, idiopathic, or due to severe trauma, and the condition has been associated with bacterial and, rarely, fungal infections in humans and animals. Here, we describe a case of ruptured spontaneous aortic aneurysm associated with zygomycetic infection in a 21-y-old female sooty mangabey.

Myocardial injury and bacterial pneumonia contribute to the pathogenesis of fatal influenza B virus infection.

Background: Influenza B virus infection causes rates of hospitalization and influenza-associated pneumonia similar to seasonal influenza A virus infection and accounts for a substantial percentage of all influenza-related hospitalizations and deaths among those aged <18 years; however, the pathogenesis of fatal influenza B virus infection is poorly described.

Methods: Tissue samples obtained at autopsy from 45 case patients with fatal influenza B virus infection were evaluated by light microscopy and immunohistochemical assays for influenza B virus, various bacterial pathogens, and complement components C4d and C9, to identify the cellular tropism of influenza B virus, characterize concomitant bacterial pneumonia, and describe the spectrum of cardiopulmonary injury.

Results: Viral antigens were localized to ciliated respiratory epithelium and cells of submucosal glands and ducts.

Coxiella burnetii infection of marine mammals in the Pacific Northwest, 1997-2010.

Q fever is a zoonotic disease caused by the bacterium Coxiella burnetii. Humans are commonly exposed via inhalation of aerosolized bacteria derived from the waste products of domesticated sheep and goats, and particularly from products generated during parturition. However, many other species can be infected with C.

Rift Valley fever virus vaccine lacking the NSs and NSm genes is safe, nonteratogenic, and confers protection from viremia, pyrexia, and abortion following challenge in adult and pregnant sheep.

Rift Valley fever virus (RVFV) is a mosquito-borne human and veterinary pathogen causing large outbreaks of severe disease throughout Africa and the Arabian Peninsula. Safe and effective vaccines are critically needed, especially those that can be used in a targeted one-health approach to prevent both livestock and human disease. We report here on the safety, immunogenicity, and efficacy of the ΔNSs-ΔNSm recombinant RVFV (rRVFV) vaccine (which lacks the NSs and NSm virulence factors) in a total of 41 sheep, including 29 timed-pregnant ewes.

Blastomycosis in man after kinkajou bite.

We report transmission of Blastomyces dermatitidis fungal infection from a pet kinkajou to a man. When treating a patient with a recalcitrant infection and a history of an animal bite, early and complete animal necropsy and consideration of nonbacterial etiologies are needed.

Bluetongue virus infection alters the impedance of monolayers of bovine endothelial cells as a result of cell death.

Bluetongue virus (BTV) is the cause of bluetongue, an emerging, arthropod-transmitted disease of ungulates. Bluetongue is characterized by vascular injury with hemorrhage, tissue infarction and widespread edema, lesions that are consistent with those of the so-called viral hemorrhagic fevers. To further investigate the pathogenesis of vascular injury in bluetongue, we utilized an electrical impedance assay and immunofluorescence staining to compare the effects of BTV infection on cultured bovine endothelial cells (bPAEC) with those of inducers of cell death (Triton X-100) and interendothelial gap formation (tissue necrosis factor [TNF]).

Bluetongue virus infection activates bovine monocyte-derived macrophages and pulmonary artery endothelial cells.

Bluetongue virus (BTV) is the cause of bluetongue (BT), an emerging, arthropod-transmitted disease of ungulates. The cellular tropism of BTV in ruminants includes macrophages, dendritic cells and endothelial cells (ECs), and fulminant infection is characterized by lesions consistent with those of so-called viral hemorrhagic fevers. Specifically, BT is characterized by vascular injury with hemorrhage, tissue infarction and widespread edema.

Fatal bluetongue virus infection in an alpaca (Vicugna pacos) in California.

In October 2008, a 15-year-old female alpaca (Vicugna pacos) housed at a breeding farm in northern California died after a brief illness characterized by sudden onset of weakness, recumbency, and respiratory distress. Postmortem examination revealed severe hydrothorax and hydropericardium, marked pulmonary edema, and acute superficial myocardial hemorrhage affecting the left ventricle. Bluetongue virus (BTV) was detected in the spleen by quantitative real-time reverse transcription polymerase chain reaction and confirmed by sequence analysis.

Use of contrast-enhanced computed tomography to assess angiogenesis in deep digital flexor tendonopathy in a horse.

We compared contrast-enhanced computed tomography (CT) and high field magnetic resonance (MR) imaging in a horse with deep digital flexor tendonopathy. Lesions in the distal extremity were documented grossly and histopathologically. In contrast-enhanced CT, the deep digital flexor tendon lesions were markedly contrast enhancing with evidence of angiogenesis in the core and dorsal border lesions.