Fusarium species central nervous system infection.

PURPOSE OF REVIEW: Fusarium species are an increasingly important cause of meningitis and invasive disease in immunocompromised patients as well as in otherwise healthy patients as observed in two recent healthcare-associated outbreaks. This review summarizes recently published information on treatment and diagnosis of this infection. RECENT FINDINGS: Incidence of Fusarium species meningitis and invasive fusariosis are increasing. Molecular techniques are improving the speed of diagnosis. New antifungal agents in development show good in vitro activity against some Fusarium species. New technologies, including cerebrospinal fluid (CSF) filtration, may play a role in treatment of central nervous system (CNS) disease. Due to the continued prime importance of the host immune system in recovery, immunomodulatory treatments may play a role in treatment. SUMMARY: The overall incidence of CNS fusariosis is increasing with a continued poor prognosis, but new diagnostic and treatment modalities are in development which may offer improvements.

Neurovascular Complications of Iatrogenic Fusarium solani Meningitis.

A multinational outbreak of nosocomial fusarium meningitis occurred among immunocompetent patients who had undergone surgery with epidural anesthesia in Mexico. The pathogen involved had a high predilection for the brain stem and vertebrobasilar arterial system and was associated with high mortality from vessel injury. Effective treatment options remain limited; in vitro susceptibility testing of the organism suggested that it is resistant to all currently approved antifungal medications in the United States. To highlight the severe complications associated with fusarium infection acquired in this manner, we report data, clinical courses, and outcomes from 13 patients in the outbreak who presented with symptoms after a median delay of 39 days.

Saliva and nasopharyngeal samples have similar sensitivity for detecting SARS-CoV-2.

SOURCE CITATION: Bastos ML, Perlman-Arrow S, Menzies D, Campbell JR. The sensitivity and costs of testing for SARS-CoV-2 infection with saliva versus nasopharyngeal swabs: a systematic review and meta-analysis. Ann Intern Med. 2021;174:501-10. 33428446.

Disseminated Sporotrichosis With Brain Abscesses in an HIV-Infected Patient.

Sporotrichosis is a mycotic infection caused by the Sporothrix schenckii species complex. It typically presents as a localized, mostly cutaneous or lymphocutaneous infection, but has been increasingly presenting as a disseminated infection in immunocompromised individuals, especially in HIV/AIDS patients. We also included a literature review of sporotrichosis in this patient population. The aim of this case report is to raise awareness about atypical presentations of sporotrichosis in an attempt to decrease the time to diagnosis, initiate treatment earlier when infection is suspected, and improve overall survival in vulnerable patient populations.

Specific material effects of wear-particle-induced inflammation and osteolysis at the bone-implant interface: A rat model.

INTRODUCTION: Wear particles produced from prosthetic joints may play critical roles in periprosthetic inflammatory reactions and osteolysis. The objective of this study was to quantify and compare the response to wear debris from different biomaterials at the bone-implant interface in a rat knee model. METHODS: Sixty rats were divided into titanium alloy (Ti-6Al-4V), cobalt chromium (Co-Cr), ceramic (Al2O3), ultrahigh molecular weight polyethylene (UHMWPE), and control (phosphate buffered saline) groups with 12 animals per group. A nonweight-bearing titanium rod was implanted into the right distal femur of each rat followed by intra-articular injections of the biomaterial particles to the surgical knees for up to 16 weeks. Micro-computed tomography scanning was performed monthly and at the time of sacrifice to determine bone densities around the bone-implant interface. Histological evaluations were executed to quantify local inflammatory reactions and osteoclastogenesis. RESULTS: Co-Cr particles resulted in the most severe reductions in bone density. UHMWPE and ceramic particles resulted in a rapid reduction in bone density followed by a recovery. Inflammatory pseudo-membranes were ubiquitously present close to the femoral condyle and pin insertion site. Ceramic particles significantly promoted periprosthetic tissue formation compared with the other groups (p < 0.05). Cathepsin K positive cells were dominantly present at the peri-implant site following challenges of metallic alloy and ceramic particles. CONCLUSION: Different biomaterials in particulate form exert different forms of adverse effects in terms of the amount of osteolysis and inflammatory reactions on bone tissue at the bone-implant interface. It provides information for engineering more appropriate materials for arthroplasty components.

Differentiation of nerve-derived adult pluripotent stem cells into osteoblastic and endothelial cells.

BACKGROUND CONTEXT: Stem cell-involved tissue engineering has gained dramatic attention as a therapeutic strategy for tissue regeneration including bone repair. However, the currently available possibilities to use embryonic stem cells and induced pluripotent stem cells (iPCs) face potential ethical issues, as well as risks of malignant transformation and immune rejection. Recently identified peripheral nerve-derived adult pluripotent stem cells (NEDAPS) that quickly proliferate after exposure to bone morphogenetic protein-2 (BMP-2) or nerve trauma and exhibit many embryonic stem cell characteristics may provide an attractive source cells for a variety of regenerative therapies. PURPOSE: The study aimed to examine the differentiation potential of the NEDAPS cells into osteoblastic cells and endothelial cells. STUDY DESIGN/SETTING: An in vitro investigation was undertaken to induce mouse NEDAPS cells into the phenotypes of osteoblastic and endothelial cells. METHODS: NEDAPS cells were isolated from low-dose BMP-2-exposed mouse sciatic nerves by collagenase and trypsin extraction. The cells were cultured in a stem cell maintenance medium, and the expression of KLF4, Sox2, c-Myc, and Oct4 before differentiation was confirmed. The cells were then subcultured in a complete osteogenic cell induction medium or endothelial cell growth medium, respectively, at 37°C and 5%CO2 atmosphere. Histologic, morphologic, and molecular assessments were performed 7 days later. RESULTS: The cells propagated in complete osteogenic medium for 7 days showed strong staining for type I collagen and alkaline phosphatase, suggesting the structural and functional properties of the osteoblastic cells. Further, real-time polymerase chain reaction (RT-PCR) revealed a significant expression of the osteoblast markers osteocalcin, osteopontin, and type I collagen. Similarly, the cells in endothelial growth medium were successfully differentiated into cobblestone-shaped endothelial cells expressing vascular endothelial growth factor (VEGF) receptors Flk-1 and Flt-1 demonstrated by RT-PCR. CONCLUSIONS: NEDAPS cells are readily induced to osteoblastic and endothelial cells, suggesting therapeutic potential for bone repair and other regenerative therapies.

Quiescent pluripotent stem cells reside within murine peripheral nerves that can be stimulated to proliferate by recombinant human bone morphogenic protein 2 or by nerve trauma.

BACKGROUND: The clinical use of recombinant human bone morphogenic protein 2 (rhBMP-2, Infuse) has been associated with nerve-related complications including new-onset sciatica, and retrograde ejaculation. PURPOSE: To better understand the interaction of rhBMP-2 and peripheral nerves with the intent of making procedures safer. STUDY DESIGN/SETTING: Using a mouse model to examine the direct effect of diluted rhBMP-2 (Infuse) on murine sciatic nerves. METHODS: Animal studies were approved by the Institutional Animal Care and Use Committee. Balb/c mouse sciatic nerves were surgically exposed and 60 ng (in 10 µL) of rhBMP-2 was applied to the nerve. In separate experiments, the sciatic nerves were subjected to mechanical compression using forceps (and not exposed to rhBMP-2). The third group of mice received direct injection of the same amount of rhBMP-2, or sterile saline as a control, into the hamstring area of the posterior thigh without surgery. Mouse limbs with intact sciatic nerve were collected at 24, 48, or 72 hours after treatment for histology processing. A separate set of identically treated sciatic nerves were retrieved from mice at the same time points and cells were isolated by collagenase and trypsin digestion. The isolated cells were cultured in a stem cell medium containing 20% knockout serum and human leukemia inhibitory factor. Immunohistochemical or immunofluorescent cell stains against KLF4, Sox2, c-Myc, and Oct4 were performed on the mouse tissue sections and cell culture slides. In addition, real-time polymerase chain reaction (PCR) was performed to quantify the mRNA expression profiles of the stem cell marker genes in cultured cells. RESULTS: Profound morphological changes of the mouse sciatic nerves were noted after exposure to rhBMP-2, with a rapid and robust cell proliferation within the nerves followed by migration of these cells into surrounding tissue. Immunohistochemical stain revealed strong nuclear stains of KLF4, Sox2, Oct4, and c-Myc on the overwhelming majority of these proliferating cells in the nerve. Intramuscular injections of rhBMP-2 or willful physical compression of the nerves showed similar cell proliferation effects as the direct application of Infuse to the sciatic nerve. The cells in stem cell culture medium grew steadily without feeder cells and appeared fairly uniform. They were adherent to substrate and were motile. Double fluorescent staining on the cells indicated colocalizationof all pairs of the four stem cell markers in the cell nuclei. Real-time PCR confirmed the strong mRNA expressions of KLF4, Sox2, Oct4, and c-Myc in these isolated cells. CONCLUSION: Exposure to BMP-2 causes a marked proliferation of previously quiescent cells within peripheral nerves. These cells simultaneously express KLF4, Sox2, Oct4, and c-Myc, the transcription factors that confer embryonic pluripotency. Work described in the companion paper reveals some of the differentiation capacity of the cells and their likely clinical significance. In addition, the effects of direct exposure of nerves to rhBMP-2 as described here should clearly illuminate the mechanism of BMP-2-related nerve complications. We would suggest that the use of this agent in proximity to known neural structures should only be done with extreme caution.