Antimicrobial Stewardship Program Prompts Increased and Earlier Infectious Diseases Consultation

A recent analysis demonstrated that infectious diseases (ID) specialty intervention was associated with decreased mortality and hospital readmission. These benefits were greatest if involvement occurred within two days of hospital admission. Antimicrobial stewardship programs should augment the services of an ID specialist team and promote formal consultation. Implementation of an antimicrobial stewardship program at the Providence Veterans Affairs Medical Center was associated with an increased number of consults (increase of 72.2%) and decreased time to consult (3.5 days sooner), which might also dramatically improve patient outcomes, including mortality and readmission rates

Ischemia–reperfusion impairs blood–brain barrier function and alters tight junction protein expression in the ovine fetus

The blood–brain barrier is a restrictive interface between the brain parenchyma and the intravascular compartment. Tight junctions contribute to the integrity of the blood–brain barrier. Hypoxic–ischemic damage to the blood–brain barrier could be an important component of fetal brain injury. We hypothesized that increases in blood–brain barrier permeability after ischemia depend upon the duration of reperfusion and that decreases in tight junction proteins are associated with the ischemia-related impairment in blood–brain barrier function in the fetus. Blood–brain barrier function was quantified with the blood-to-brain transfer constant (Ki) and tight junction proteins by Western immunoblot in fetal sheep at 127 days of gestation without ischemia, and 4, 24, or 48 h after ischemia. The largest increase in Ki (P \u3c 0.05) was 4 h after ischemia. Occludin and claudin-5 expressions decreased at 4 h, but returned toward control levels 24 and 48 h after ischemia. Zonula occludens-1 and -2 decreased after ischemia. Inverse correlations between Ki and tight junction proteins suggest that the decreases in tight junction proteins contribute to impaired blood–brain barrier function after ischemia. We conclude that impaired blood–brain barrier function is an important component of hypoxic–ischemic brain injury in the fetus, and that increases in quantitatively measured barrier permeability (Ki) change as a function of the duration of reperfusion after ischemia. The largest increase in permeability occurs 4 h after ischemia and blood–brain barrier function improves early after injury because the blood–brain barrier is less permeable 24 and 48 than 4 h after ischemia. Changes in the tight junction molecular composition are associated with increases in blood–brain barrier permeability after ischemia

Balloon kyphoplasty in the treatment of metastatic disease of the spine: a 2-year prospective evaluation

There is currently little data on the longer term efficacy and safety of balloon kyphoplasty (BKP) in patients with metastatic vertebral compression fractures (VCFs). To prospectively assess the long-term efficacy and safety of BKP in treating thoracic and lumbar spinal metastatic fractures that result in pain or instability. Sixty-five patients (37 men, mean age: 66 years) underwent 99 BKP procedures. Patient-related outcomes of pain visual analogue scale (VAS) and Oswestry Disability Index were assessed pre- and post-operatively and after 3, 6, 12 and 24 months. Correction of vertebral height and kyphotic deformity were assessed by radiographic measurements. Mean pain VAS and Oswestry Disability Index significantly improved from pre- to post-treatment (P < 0.0001), this improvement being sustained up to 24-month follow up. A gain in height restoration and a reduction of the post-operative kyphotic angle were seen post-operatively and at 3 months although these radiographic outcomes returned to pre-operative levels at 12 months. BKP was associated with a rate of cement leakage and incidence vertebral fracture of 12 and 8%, respectively. No symptomatic cement leaks or serious adverse events were seen during the 24 months of follow up. BKP is a minimally invasive procedure that provides immediate and long-term pain relief and improvement in functional ability in selected patients with metastatic VCFs. The procedure appears to have good long-term safety

Nanovesicles from Malassezia sympodialis and Host Exosomes Induce Cytokine Responses – Novel Mechanisms for Host-Microbe Interactions in Atopic Eczema

BACKGROUND: Intercellular communication can occur via the release of membrane vesicles. Exosomes are nanovesicles released from the endosomal compartment of cells. Depending on their cell of origin and their cargo they can exert different immunoregulatory functions. Recently, fungi were found to produce extracellular vesicles that can influence host-microbe interactions. The yeast Malassezia sympodialis which belongs to our normal cutaneous microbial flora elicits specific IgE- and T-cell reactivity in approximately 50% of adult patients with atopic eczema (AE). Whether exosomes or other vesicles contribute to the inflammation has not yet been investigated. OBJECTIVE: To investigate if M. sympodialis can release nanovesicles and whether they or endogenous exosomes can activate PBMC from AE patients sensitized to M. sympodialis. METHODS: Extracellular nanovesicles isolated from M. sympodialis, co-cultures of M. sympodialis and dendritic cells, and from plasma of patients with AE and healthy controls (HC) were characterised using flow cytometry, sucrose gradient centrifugation, Western blot and electron microscopy. Their ability to stimulate IL-4 and TNF-alpha responses in autologous CD14, CD34 depleted PBMC was determined using ELISPOT and ELISA, respectively. RESULTS: We show for the first time that M. sympodialis releases extracellular vesicles carrying allergen. These vesicles can induce IL-4 and TNF-α responses with a significantly higher IL-4 production in patients compared to HC. Exosomes from dendritic cell and M. sympodialis co-cultures induced IL-4 and TNF-α responses in autologous CD14, CD34 depleted PBMC of AE patients and HC while plasma exosomes induced TNF-α but not IL-4 in undepleted PBMC. CONCLUSIONS: Extracellular vesicles from M. sympodialis, dendritic cells and plasma can contribute to cytokine responses in CD14, CD34 depleted and undepleted PBMC of AE patients and HC. These novel observations have implications for understanding host-microbe interactions in the pathogenesis of AE