An Integrative Review: Early Mobilization of Patients With External Ventriculostomy Drains in the Neurological Intensive Care Unit.

ABSTRACT: BACKGROUND: Patients in the intensive care unit (ICU) are at a high risk for immobility due to their high acuity and need for invasive devices including external ventriculostomy drains (EVDs). Prolonged patient immobilization is associated with poor outcomes. METHODS: Whittemore and Knafl's 5-stage framework was used to conduct an integrative review to synthesize findings from quantitative research studies on early patient mobilization for patients with EVDs in the neurological ICU. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was used as the reporting guideline. RESULTS: In 12 studies, a total of 412 patients with EVDs in neurological ICUs were actively mobilized with a goal of progressing to ambulation. Mobilization out of bed with a ventriculostomy drain was safe and feasible without significant adverse events. CONCLUSION: There is a need to clarify best practices for early mobilization of patients with EVDs in the neurological ICU and to explore the influence of early mobilization on patients' rates of venous thromboembolism, catheter-associated urinary tract infections, catheter line-associated blood stream infections, ventilator-associated pneumonia, and ventriculostomy-related infections. No studies measured the total time the EVD was clamped during the patient mobilization intervention or the total amount of cerebrospinal fluid drainage on the day of mobilization. Early mobilization of patients with EVDs in the neurological ICU who were permitted out of bed was universally safe and feasible, with minimal adverse events when safety checks were integrated into mobilization protocols.

Intracellular Cryptococcus neoformans disrupts the transcriptome profile of M1- and M2-polarized host macrophages.

Macrophages serve as a first line of defense against infection with the facultative intracellular pathogen, Cryptococcus neoformans (Cn). However, the ability of these innate phagocytic cells to destroy ingested Cn is strongly influenced by polarization state with classically (M1) activated macrophages better able to control cryptococcal infections than alternatively (M2) activated cells. While earlier studies have demonstrated that intracellular Cn minimally affects the expression of M1 and M2 markers, the impact on the broader transcriptome associated with these states remains unclear. To investigate this, an in vitro cell culture model of intracellular infection together with RNA sequencing-based transcriptome profiling was used to measure the impact of Cn infection on gene expression in both polarization states. The gene expression profile of both M1 and M2 cells was extensively altered to become more like naive (M0) macrophages. Gene ontology analysis suggested that this involved changes in the activity of the Janus kinase-signal transducers and activators of transcription (JAK-STAT), p53, and nuclear factor-κB (NF-κB) pathways. Analyses of the principle polarization markers at the protein-level also revealed discrepancies between the RNA- and protein-level responses. In contrast to earlier studies, intracellular Cn was found to increase protein levels of the M1 marker iNos. In addition, common gene expression changes were identified that occurred post-Cn infection, independent of polarization state. This included upregulation of the transcriptional co-regulator Cited1, which was also apparent at the protein level in M1-polarized macrophages. These changes constitute a transcriptional signature of macrophage Cn infection and provide new insights into how Cn impacts gene expression and the phenotype of host phagocytes.

Drawing in 3D: Using 3D printer pens to draw chemical models.

Development of three-dimensional (3D) printing technology has started a new chapter for in-classroom modeling of chemical molecules. The technology provides the opportunity to design and produce various types of personalized models. However, using classical 3D printers is time consuming, and it is hard to involve students in the modeling process during traditional class times. One solution can be using hand-held 3D printers (3D pens) that allow users to instantly draw geometrical structures. Unfortunately, drawing directly in 3D is very difficult, and precise modeling of even small molecules is simply not possible. In this article, a new approach to 3D modeling is described. It is based on 3D templates that enable the drawing of molecular models directly in three dimensions. The modular nature of the templates allows for the creation of a wide variety of structures. The resulting models provide an accurate representation of molecules including correct bond angles and geometry. This approach makes 3D pens a powerful tool for the modeling of chemical structures.

Biologically inspired hierarchical design of nanocomposites based on poly(ethylene oxide) and cellulose nanofibers.

Attempts to create hierarchically structured, uniaxially oriented nanocomposites comprising cellulose nanowhiskers (CNWs), which promise anisotropic mechanical properties, are exceedingly rare. We report here the fabrication of uniaxially-oriented arrays of microfibers based on poly(ethylene oxide) (PEO) and CNWs by electrospinning. Compared with the neat PEO fibers, the incorporation of CNWs within the fibers increased the storage modulus (E') of arrays along the fiber axis of the PEO/CNW nanocomposite fibers. Successful incorporation of the CNWs within each of the as-spun PEO/CNW nanocomposite fibers in the direction parallel to the fiber axis was verified by both scanning and transmission electron microscopy.

Donor transmission of malignant melanoma in a lung transplant recipient 32 years after curative resection.

In the current era of organ shortages and long wait times for life-saving transplants, marginal or extended donors are increasingly being considered; one such category of marginal organs is from donors with a previous history of malignancy. Melanoma in particular has been associated with increased risk of developing late recurrence. In this report, we describe a case of fatal donor melanoma transmission to a 64-year-old lung transplant recipient 32 years after surgical excision of the melanoma. Based on this report and review of the available literature, we conclude that a history of donor melanoma, regardless of the stage and time interval from 'curative' surgical resection, should remain a strong relative contraindication to transplantation.

Lung transplant outcomes in white and African American recipients: special focus on acute and chronic rejection.

BACKGROUND: The effects of lung transplant recipient race on post-transplant outcomes have not been adequately evaluated. This cohort study seeks to determine the characteristics of African American lung transplant recipients and the effects of African American race on post-transplant outcomes, particularly acute and chronic rejection, compared with white recipients, at a single center. METHODS: There were 485 first-time lung transplantations (431 white, 47 African American, 5 Hispanic and 2 Asian recipients) performed at the University of Pennsylvania between 1991 and 2006. All white and African American recipients were compared based on pre-transplant diagnoses and post-transplant survival. The cohort from 1998 to 2006 (239 white and 25 African American recipients) was also compared based on acute rejection score (ARS) and development of bronchiolitis obliterans syndrome (BOS). RESULTS: Chronic obstructive pulmonary disease was the most common diagnosis leading to lung transplantation in both groups, but sarcoidosis was a much more common indication in African American recipients (white, 1%; African American, 28%; p < 0.001). Survival was similar in the two groups (white vs African American groups: 1 month, 90.0% vs 87.2%; 1 year, 74.9% vs 74.5%; 5 years, 52.3% vs 50.5%, respectively; p = 0.84). Freedom from BOS at 3 years (white, 60.3%; African American, 62.8%; p = 0.30) and ARS per biopsy (white, 0.83 +/- 0.82; African American, 0.63 +/- 0.77; p = 0.31) were similar in both groups. CONCLUSIONS: White and African American patients seek lung transplantation for different diseases, but post-transplant outcomes were found to be similar. Larger, multi-center studies are needed to confirm these results.

Assessment of kidney function in lung transplant candidates.

BACKGROUND: Glomerular filtration rate (GFR) is the best measure of kidney function; however, 24-hour creatinine clearance (CrCl) is the initial screening test used for lung transplant candidates at most centers. Although creatinine-based formulas that estimate GFR have been derived, none have been validated in patients with severe lung disease. METHODS: We performed a retrospective cohort study of patients evaluated for lung transplantation at Columbia Presbyterian Medical Center and compared the GFR estimated from the Modification of Diet in Renal Disease (MDRD) and other formulas to the CrCl. We then validated these results in a cohort of patients evaluated at the Hospital of the University of Pennsylvania. RESULTS: There were strong and statistically significant direct correlations between estimated GFR and CrCl. An estimated GFR of <95 ml/min by the MDRD was very sensitive at detecting kidney dysfunction by CrCl in the derivation cohort. In the validation cohort, the negative predictive value of this cut-off was 97%. CONCLUSIONS: Established formulas for estimating GFR are highly discriminating for kidney dysfunction in patients being evaluated for lung transplantation and may actually have greater validity than CrCl in some instances.

Renal and vestibular toxicity due to inhaled tobramycin in a lung transplant recipient.

Chronic rejection is the major hurdle to long-term survival after lung transplantation. Endobronchial infection with Pseudomonas aeruginosa is common in patients with chronic rejection and this may further contribute to deterioration of the allograft. Inhaled tobramycin is commonly used to treat P aeruginosa airways infection in patients with cystic fibrosis. The safety of inhaled tobramycin in transplant recipients, however, has not been established. We describe the first report of a lung transplant recipient who developed renal failure and vestibular injury after receiving inhaled tobramycin. We review the literature regarding the safety of inhaled tobramycin and discuss potential mechanisms that may promote systemic toxicity in transplant recipients.