In this study of bariatric surgery, adolescents and adults showed marked weight loss that was similar in magnitude in the two groups 5 years after surgery. However, adolescents had remission of ...diabetes and hypertension more often than adults.
Human streptococci that belong to Streptococcus dysgalactiae subspecies equisimilis (SDSE) have long been known under the name of β-hemolytic groups C and G streptococci. Extensive taxonomic studies ...during the past years have distinguished most of the veterinary pathogens belonging to Lancefield groups C and G from those of human origin. After being considered nonpathogenic for many years, SDSE is now recognized as an important bacterial pathogen. The clinical spectrum of diseases caused by this species closely resembles Streptococcus pyogenes infections, including the occurrence of poststreptococcal sequelae. In accordance with these observations, many of the virulence factors present in S. pyogenes can also be found in SDSE strains. High nucleotide-sequence identities in virulence genes and the association of these genes with mobile genetic elements support the hypothesis of extensive horizontal gene-transfer events among streptococcal species of the pyogenic group. Recent epidemiological studies have shown increasing numbers of invasive SDSE infections, often among immunocompromised patients, and suggest that this species will probably gain even more clinical importance in the near future. For a better understanding of the changing epidemiology and pathogenicity of SDSE, an increased awareness of these microorganisms as human pathogens and proper identification are mandatory.
Members of the species-rich Fusarium solani species complex (FSSC) are responsible for approximately two-thirds all fusarioses of humans and other animals. In addition, many economically important ...phytopathogenic species are nested within this complex. Due to their increasing clinical relevance and because most of the human pathogenic and plant pathogenic FSSC lack Latin binomials, we have extended the multilocus haplotype nomenclatural system introduced in a previous study (D. C. Chang, G. B. Grant, K. O'Donnell, K. A. Wannemuehler, J. Noble-Wang, C. Y. Rao, L. M. Jacobson, C. S. Crowell, R. S. Sneed, F. M. T. Lewis, J. K. Schaffzin, M. A. Kainer, C. A. Genese, E. C. Alfonso, D. B. Jones, A. Srinivasan, S. K. Fridkin, and B. J. Park, JAMA 296:953-963, 2006) to all 34 species within the medically important FSSC clade 3 to facilitate global epidemiological studies. The typing scheme is based on polymorphisms in portions of the following three genes: the internal transcribed spacer region and domains D1 plus D2 of the nuclear large-subunit rRNA, the translation elongation factor 1 alpha gene (EF-1α), and the second largest subunit of RNA polymerase II gene (RPB2). Of the 251 isolates subjected to multilocus DNA sequence typing, 191 sequence types were differentiated, and these were distributed among three strongly supported clades designated 1, 2, and 3. All of the mycosis-associated isolates were restricted to FSSC clade 3, as previously reported (N. Zhang, K. O'Donnell, D. A. Sutton, F. A Nalim, R. C. Summerbell, A. A. Padhye, and D. M. Geiser, J. Clin. Microbiol. 44:2186-2190, 2006), and these represent at least 20 phylogenetically distinct species. Analyses of the combined DNA sequence data by use of two separate phylogenetic methods yielded the most robust hypothesis of evolutionary relationships and genetic diversity within the FSSC to date. The in vitro activities of 10 antifungals tested against 19 isolates representing 18 species that span the breadth of the FSSC phylogeny show that members of this complex are broadly resistant to these drugs.
A large aggregate collection of clinical isolates of aspergilli (n = 218) from transplant patients with proven or probable invasive aspergillosis was available from the Transplant-Associated ...Infection Surveillance Network, a 6-year prospective surveillance study. To determine the Aspergillus species distribution in this collection, isolates were subjected to comparative sequence analyses by use of the internal transcribed spacer and β-tubulin regions. Aspergillus fumigatus was the predominant species recovered, followed by A. flavus and A. niger. Several newly described species were identified, including A. lentulus and A. calidoustus; both species had high in vitro MICs to multiple antifungal drugs. Aspergillus tubingensis, a member of the A. niger species complex, is described from clinical specimens; all A. tubingensis isolates had low in vitro MICs to antifungal drugs.
We used real-time polymerase chain reaction and culture to demonstrate persistent colonization of soils by Coccidioides immitis, an agent of valley fever, in Washington State linked to recent human ...infections and located outside the endemic range. Whole-genome sequencing confirmed genetic identity between isolates from soil and one of the case-patients.
Successful adoptive chimeric antigen receptor (CAR) T-cell therapies against hematological malignancies require CAR-T expansion and durable persistence following infusion. Balancing increased CAR-T ...potency with safety, including severe cytokine-release syndrome (sCRS) and neurotoxicity, warrants inclusion of safety mechanisms to control in vivo CAR-T activity. Here, we describe a novel CAR-T cell platform that utilizes expression of the toll-like receptor (TLR) adaptor molecule, MyD88, and tumor-necrosis factor family member, CD40 (MC), tethered to the CAR molecule through an intentionally inefficient 2A linker system, providing a constitutive signal that drives CAR-T survival, proliferation, and antitumor activity against CD19
and CD123
hematological cancers. Robust activity of MC-enhanced CAR-T cells was associated with cachexia in animal models that corresponded with high levels of human cytokine production. However, toxicity could be successfully resolved by using the inducible caspase-9 (iC9) safety switch to reduce serum cytokines, by administration of a neutralizing antibody against TNF-α, or by selecting "low" cytokine-producing CD8
T cells, without loss of antitumor activity. Interestingly, high basal activity was essential for in vivo CAR-T expansion. This study shows that co-opting novel signaling elements (i.e., MyD88 and CD40) and development of a unique CAR-T architecture can drive T-cell proliferation in vivo to enhance CAR-T therapies.
Last year, invasive fungal infections were identified in association with injections of contaminated methylprednisolone from a compounding pharmacy. In this report, the epidemiology of the outbreak ...is presented from its identification in September 2012 through mid-2013.
There has been no systematic surveillance in the United States for adverse events that occur after glucocorticoid injections for the treatment of chronic musculoskeletal pain, but infection is a known, although probably rare, risk documented in the medical literature.
1
–
6
Infections that develop after a procedure are usually bacterial
2
,
7
–
10
; fungal infections are extremely rare.
11
–
14
We present data on a multistate outbreak of fungal meningitis and other infections associated with injections of preservative-free methylprednisolone acetate that was purchased from a single compounding pharmacy and describe the public health response to the outbreak.
Methods
Index Patient and Early . . .
PDF
