Evidence for case-to-case transmission of Creutzfeldt-Jakob disease

Three cases of probable iatrogenic transmission of Creutzfeldt-Jakob disease by neurosurgery are detailed together with a cluster of three cases in Eastern England possibly connected by dental procedures, and the development of Creutzfeldt-Jakob disease in a patient who had been in social contact with a familial case.     

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. Tissues from 40 laboratory-confirmed cases representing these various clinical entities were evaluated by histopathological analysis, special stains, and IHC to characterize the pathological features and investigate the pathogenesis of infection, and to evaluate methods for detection of Exserohilum in formalin-fixed, paraffin-embedded (FFPE) tissues. Fatal cases had necrosuppurative to granulomatous meningitis and vasculitis, with thrombi and abundant angioinvasive fungi, with extensive involvement of the basilar arterial circulation of the brain. IHC was a highly sensitive method for detection of fungus in FFPE tissues, demonstrating both hyphal forms and granular fungal antigens, and PCR identified Exserohilum in FFPE and fresh tissues. Our findings suggest a pathogenesis for meningitis involving fungal penetration into the cerebrospinal fluid at the injection site, with transport through cerebrospinal fluid to the basal cisterns and subsequent invasion of the basilar arteries. Further studies are needed to characterize Exserohilum and investigate the potential effects of underlying host factors and steroid administration on the pathogenesis of infection.CME Accreditation Statement: This activity (“ASIP 2013 AJP CME Program in Pathogenesis”) has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Society for Clinical Pathology (ASCP) and the American Society for Investigative Pathology (ASIP). ASCP is accredited by the ACCME to provide continuing medical education for physicians.The ASCP designates this journal-based CME activity (“ASIP 2013 AJP CME Program in Pathogenesis”) for a maximum of 48 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.CME Disclosures: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose.Epidural and intra-articular steroid injections are commonly administered for treatment of back, neck, and peripheral joint pain, especially in elderly patients. Infections develop in an estimated <1% to 2% of patients who receive spinal injections.^1–3 Introduction of skin flora into the injection site is the most common cause of infection, and Staphylococcus aureus is the most commonly implicated organism.^2,4–6 Fungal infections associated with spinal injections are exceedingly rare and are most frequently attributed to Aspergillus.^7–9 Although individual cases of infection are uncommon, outbreaks of infection associated with contaminated epidural or intra-articular injections are even more unusual. During the past decade, such examples include three outbreaks of Serratia marcescens infection associated with epidural or intra-articular injections,^10–12 an outbreak of Klebsiella pneumoniae and Enterobacter aerogenes bacteremia after sacroiliac (SI) joint steroid injections,¹³ an outbreak of Exophiala dermatitidis infection after epidural and intra-articular steroid injections,¹⁴ and an outbreak of Aspergillus meningitis after spinal anesthesia for caesarean section.⁷ The largest of these outbreaks involved 11 patients.¹⁰In September 2012, the Centers for Disease Control and Prevention (CDC) was alerted to multiple reports of fungal meningitis in patients who had recently received epidural steroid injections. The intensive, multistate, epidemiological and laboratory investigation that ensued identified an unprecedented outbreak of fungal infections associated with epidural, paraspinal, and peripheral joint injections, involving three contaminated lots of preservative-free methylprednisolone acetate (MPA) from a single compounding pharmacy. More than 17,000 vials from three contaminated lots were distributed to medical centers across the United States, and >13,000 people were injected with the potentially contaminated drug before discovery of the source of contamination.¹⁵ Through May 6, 2013, 741 cases and 55 deaths in 20 states have been associated with this outbreak, making it the largest recognized cluster of infections associated with epidural and intra-articular steroid injections. Most cases with a confirmed etiology have been attributed to Exserohilum rostratum. In few cases, other fungal or bacterial species have been identified by molecular studies or culture, either individually or in addition to Exserohilum.^16,17 Herein, we describe the pathological findings from 40 case patients from this outbreak with confirmed Exserohilum infection, correlate these findings with clinical and laboratory data, and use these data to provide insight into the pathogenesis of Exserohilum infections after injection of contaminated MPA.     

Venous renal tumor extension: a prospective US evaluation

To evaluate the ability of ultrasonography (US) to determine venous tumor extension, we studied 120 consecutive patients with renal neoplasms. The incidence of renal vein involvement in this group was 18%; caval tumor extension occurred in 11% of the patients. Real-time US clearly visualized the entire retrohepatic inferior vena cava (IVC) in 96% of the examinations, and the ipsilateral renal vein was well seen on 88% of the scans. Of the caval sonograms that could be evaluated (115/120), intravascular tumor thrombi were detected in all 13 cases (sensitivity and specificity = 100%). Of the assessable sonograms of the renal vein (105/120), tumor invasion was identified by US in 21 of 22 cases (sensitivity = 95.5%, specificity = 100%). Venous tumor involvement was seen with intravascular lesions of different echogenicity, which caused a neoplastic-induced renal or caval vein enlargement in most cases. Our findings show that US is of great value in the preoperative assessment of intravascular tumor extension and provides a useful alternative to inferior venacavography.     

"FEEDING CHARACTERISTICS IN DEMODECTIC MITES OF THE EYELID"

Dernodex folliculorum ingests Oil Red 0 stain which dramatically highlights the alimentary tract, and raises clinical considerations including the question of a viral vector role.     

Ras oncogene directs expression of a differentially sialylated, functionally altered beta1 integrin

Intense investigation has centered on understanding the regulation of integrin cell adhesion receptors. In the present study, we propose that variant N-glycosylation represents an important mechanism for regulation of beta1, but not beta3 or beta5 integrins. We find that expression of oncogenic ras in HD3 colonocytes causes increased alpha2-6 sialylation of beta1 integrins, whereas expression of dominant-negative ras induces decreased alpha2-6 sialylation, relative to cells with wild-type ras. In contrast, neither beta3 nor beta5 integrins are alpha2-6 sialylated, regardless of the state of ras activation. Results from RT-PCR analyses suggest that differential integrin sialylation is due to a ras-dependent alteration in the expression of ST6Gal I, the enzyme that adds alpha2-6-linked sialic acids. Cells that express differentially sialylated beta1 integrins exhibit altered adhesion to collagen I (a beta1 ligand), but not to vitronectin (a beta3 or beta5 ligand). Similarly, the enzymatic removal of cell surface sialic acids from control cells alters binding to collagen, but not to vitronectin. Finally, using a cell-free receptor/ligand-binding assay, we show that purified, desialylated alpha1beta1 integrins have diminished collagen-binding capability, providing strong evidence that sialic acids play a causal role in regulating beta1 integrin function.