Financial Analysis of Preoperative Nasal Decolonization With Povidone-Iodine in Closed Pilon Fracture Definitive Fixation.

The purpose of this study is to determine the financial practicality for the use of nasal povidone-iodine (NP-I) in the preoperative holding area in attempt to decrease the rate of infection that is associated with operative fixation of closed pilon fractures. Institutional costs for treating postoperative infection following a closed pilon fracture, along with costs associated with preoperative NP-I use, were obtained. A break-even equation was used to analyze these costs to determine if the use of NP-I would decrease the current infection rate (17%) enough to be financially beneficial for routine use preoperatively. The total cost of treating a postoperative infection was found to be $18,912, with the cost of NP-I being $30 per patient dose. Considering a 17% infection rate and utilizing the break-even equation, NP-I was found to be economically viable if it decreased the current infection rate by 0.0016% (Number Needed to Treat = 63,051.7). This break-even model suggests that the use of NP-I in the preoperative holding area is financially beneficial for decreasing the rate of infection associated with the treatment of closed pilon fractures.

Arthroscopic Removal of Extra-Articular Foreign Bodies From the Shoulder: Inside-Out Technique.

Arthroscopic shoulder surgery can be performed for retrieval of bullets and retained metallic fragments in the glenohumeral and subacromial spaces. Previous case reports and case series have demonstrated the effectiveness of an arthroscopic approach over an open procedure, as it is less invasive, allows for improved inspection and documentation of the joint surfaces and periarticular structures, and potentially leads to a faster recovery. An arthroscopic approach for extracting foreign bodies from both the quadrilateral space and the posterior extra-articular space by first accessing the glenohumeral space has yet to be described. This inside-out technique may afford surgeons the potential for improved visualization and less morbidity compared with a traditional open posterior approach. We report a technique for an arthroscopic inside-out approach for removal of extra-articular foreign bodies retained in either the quadrilateral space or the posterior extra-articular space.

Drug penetration in pediatric brain tumors: Challenges and opportunities.

Larger clinical trial enrollments and a greater understanding of biological heterogeneity have led to improved survival rates for children diagnosed with brain tumors in the last 50 years. However, reducing long-term morbidities and improving survival rates of high-risk tumors remain major challenges. Chemotherapy can reduce tumor burden, but effective drug penetration at the tumor site is limited by barriers in the route of drug administration and within the tumor microenvironment. Bioavailability of drugs is impeded by the blood-brain barrier, plasma protein binding, and structural components by the tumor including the matrix and vasculature contributing to increased interstitial fluid pressure, hypoxia, and acidity. Designing drug delivery systems to circumvent these barriers could lead to improved drug penetration at the tumor site and reduce adverse systemic side effects. In this review, we expand on how systemic and local barriers limit drug penetration and present potential methods to enhance drug penetration in pediatric brain tumors.

Sensitization to Implant Components Is Associated with Joint Replacement Failure: Identification and Revision to Nonallergenic Hardware Improves Outcomes.

BACKGROUND: Over 90% of one million annual US joint replacements are highly successful. Nonetheless, 10% do poorly owing to infection or mechanical issues. Many implant components are sensitizers, and sensitization could also contribute to implant failure. OBJECTIVE: To determine the prevalence of implant sensitization in joint failure patients, their clinical characteristics, and implant revision outcomes. We hypothesized that sensitized patients would improve when revised with nonallergenic materials. METHODS: We prospectively enrolled 105 joint failure patients referred by orthopedic surgeons who had already excluded infection or mechanical causes. Patients provided informed consent, completed a history and physical examination, patch testing to metals and bone cement, and a nickel lymphocyte proliferation test. A study coordinator was able to contact 64% of patients (n = 67) 9 to 12 months later to evaluate outcomes. RESULTS: A total of 59% were sensitized to an implant component: 32% to metal and 37% to bone cement. The nickel lymphocyte proliferation test was 60% sensitive and 96% specific in diagnosing nickel sensitization. Most sensitized subjects reported no or uncertain histories of reactions to a specific material. Implant sensitized patients were younger and reported previous eczema, joint itching, and implant loosening. By 9 to 12 months later, most patients with a revised implant (revised) described significant improvement (16 of 22 revised for sensitization [P = .0003] vs 9 of 13 revised without sensitization [P = .047]) compared with patients without implant revision). All revised patients with sensitization used components to which they were not sensitized. Pain (P = .001), swelling (P = .035), and instability (P = .006) were significantly reduced in the revised sensitized group. CONCLUSIONS: Sensitization to implant components is an important cause of unexplained joint replacement failure. Joint revisions based on sensitization information resulted in significant improvements.

Laparoscopic Ventral Hernia Repair with a Non-Woven Hernia Mesh.

INTRODUCTION: Laparoscopic ventral hernia repair is a commonly performed procedure with a variety of mesh options. A relatively new mesh option is a non-woven polypropylene mesh with a silicone barrier designed for intraabdominal placement. This non-woven randomly oriented polypropylene microfiber hernia mesh may have benefits with potentially better biocompatibility compared with other ventral hernia repair mesh options. MATERIALS AND METHODS: A clinical quality improvement (CQI) program was initiated for ventral hernia patients to better measure and improve outcomes. From March 2013 to September 2015, 62 laparoscopic ventral hernia repairs were performed with this non-woven polypropylene mesh on 61 patients (one patient had two separate hernia repairs). Attempts were made to obtain long-term (> 2 years) follow up. RESULTS: There were 36 females and 25 males. The average age was 58.7 years (range 21-85). The average body mass index (BMI) was 36.2 (range 21.4-62.4). There were 51 (82%) incisional hernias and 11 (18%) primary hernias. There were 29 (47%) recurrent hernias. Mean hernia size was 83.4cm2 (range 1-400) and mean mesh size was 508.5cm2 (range 144-936). The mean operating room (OR) time was 108.2 minutes (range 38-418). The mean length of hospital stay was 2.7 days (range 0-13). There was one intraoperative complication-an injury to an inferior epigastric vessel that had a minor postoperative bleed that was self-limiting and required no treatment. There was one postoperative death due to aspiration on postoperative day #4. There has been one recurrence (1.6%) with long-term follow up. There were two patients (3.2%) with suture site pain postoperatively that resolved with suture site injections of local anesthetic in the clinic. There were no patients that required rehospitalization within 30 days after surgery. There were no mesh-related complications and no incidence of mesh removal was required. CONCLUSION: The results for laparoscopic ventral hernia repair, using a relatively new non-woven randomly oriented polypropylene microfiber mesh, are good with long-term follow up completed in the majority of patients. More experience with this type of mesh could generate evidence for the benefits of this mesh material in laparoscopic ventral hernia repair.

The Value Proposition for Complex Abdominal Wall Reconstruction: How to Make It Work.

BACKGROUND: The challenge for health care in the 21st century is to understand how to measure and improve value in the context of each patient care process for the entire cycle of care. For patients who undergo an abdominal wall reconstruction, there is a great opportunity to improve value because of the high cost and variability in outcomes for this complex operation. METHODS: For almost a decade, our hernia team has been applying the principles of systems and data science to actual patient care. Tools from systems and data science applied to patient care include clinical quality improvement and nonlinear analytical methods such as factor analysis. The most important outcome to measure and improve is the value of care provided for the entire cycle of care. RESULTS: Many measurement and improvement ideas have been applied to the abdominal wall reconstruction process in our hernia program, including the use of a less costly long-term resorbable mesh, multimodal pain management and enhanced recovery process improvement ideas, and surgical technique improvements that have led to decreased wound complications and the elimination of abdominal wall drains. More recently, the data analysis has shown an opportunity to improve outcomes through a robust prehabilitation program, including cognitive therapy to induce neural rewiring before surgery. CONCLUSIONS: Improving value for patients who undergo abdominal wall reconstruction and for all patients in our global health care system should be a unifying goal. Understanding and applying systems and data science tools appropriately are necessary to achieve this goal.

Small Rho GTPases and the Effector VipA Mediate the Invasion of Epithelial Cells by Filamentous Legionella pneumophila.

Legionella pneumophila (Lp) exhibits different morphologies with varying degrees of virulence. Despite their detection in environmental sources of outbreaks and in respiratory tract secretions and lung autopsies from patients, the filamentous morphotype of Lp remains poorly studied. We previously demonstrated that filamentous Lp invades lung epithelial cells (LECs) and replicates intracellularly in a Legionella containing vacuole. Filamentous Lp activates ß1integrin and E-cadherin receptors at the surface of LECs leading to the formation of actin-rich cell membrane structures we termed hooks and membrane wraps. These structures entrap segments of an Lp filament on host cell surface and mediate bacterial internalization. Here we investigated the molecular mechanisms responsible for the actin rearrangements needed for the formation and elongation of these membrane wraps and bacterial internalization. We combined genetic and pharmacological approaches to assess the contribution of signaling downstream of ß1integrin and E-cadherin receptors, and Lp Dot/Icm secretion system- translocated effectors toward the invasion process. Our studies demonstrate a multi-stage mechanism of LEC invasion by filamentous Lp. Bacterial attachment to host cells depends on signaling downstream of ß1integrin and E-cadherin activation, leading to Rho GTPases-dependent activation of cellular actin nucleating proteins, Arp2/3 and mDia. This mediates the formation of primordial membrane wraps that entrap the filamentous bacteria on the cell surface. Following this, in a second phase of the invasion process the Dot/Icm translocated effector VipA mediates rapid membrane wrap elongation, leading to the engulfment of the filamentous bacteria by the LECs. Our findings provide the first description of Rho GTPases and a Dot/Icm effector VipA regulating the actin dynamics needed for the invasion of epithelial cells by Lp.

Clinical and laboratory factors contributing to uninterpretable beryllium lymphocyte proliferation tests (BeLPT).

BACKGROUND: The beryllium lymphocyte proliferation test (BeLPT), has become the principal clinical test for detecting beryllium sensitization and chronic beryllium disease. Uninterpretable BeLPT results can occur in a small but significant proportion of tests from poor lymphocyte growth (PG) or over proliferation of lymphocytes (OP). The clinical and laboratory causes of uninterpretable results are not known. METHODS: BeLPT data from the US Department of Energy-supported Former Worker Screening Program were analyzed for a 10-year period. Drivers of uninterpretable BeLPTs were investigated using multivariable models and classification techniques. RESULTS: Three participant attributes were significantly associated with PG, while OP showed no significant associations. Serum lot for the lymphocyte growth medium accounted for 21% of the variation in PG and 16% in OP. CONCLUSION: Serum lots influence the likelihood of having uninterpretable BeLPT. To better understand uninterpretable results and possibly reduce their occurrence, additional laboratory-related factors should be addressed.

Ancestral and more recently acquired syntenic relationships of MADS-box genes uncovered by the Physcomitrella patens pseudochromosomal genome assembly.

KEY MESSAGE: The Physcomitrella pseudochromosomal genome assembly revealed previously invisible synteny enabling realisation of the full potential of shared synteny as a tool for probing evolution of this plant's MADS-box gene family. Assembly of the sequenced genome of Physcomitrella patens into 27 mega-scaffolds (pseudochromosomes) has confirmed the major predictions of our earlier model of expansion of the MADS-box gene family in the Physcomitrella lineage. Additionally, microsynteny has been conserved in the immediate vicinity of some recent duplicates of MADS-box genes. However, comparison of non-syntenic MIKC MADS-box genes and neighbouring genes indicates that chromosomal rearrangements and/or sequence degeneration have destroyed shared synteny over longer distances (macrosynteny) around MADS-box genes despite subsets comprising two or three MIKC genes having remained syntenic. In contrast, half of the type I MADS-box genes have been transposed creating new syntenic relations with MIKC genes. This implies that conservation of ancient ancestral synteny of MIKC genes and of more recently acquired synteny of type I and MIKC genes may be selectively advantageous. Our revised model predicts the birth rate of MIKC genes in Physcomitrella is higher than that of type I genes. However, this difference is attributable to an early tandem duplication and an early segmental duplication of MIKC genes prior to the two polyploidisations that account for most of the expansion of the MADS-box gene family in Physcomitrella. Furthermore, this early segmental duplication spawned two chromosomal lineages: one with a MIKC (C) gene, belonging to the PPM2 clade, in close proximity to one or a pair of MIKC* genes and another with a MIKC (C) gene, belonging to the PpMADS-S clade, characterised by greater separation from syntenic MIKC* genes. Our model has evolutionary implications for the Physcomitrella karyotype.

Cross-Sectional Study of Respiratory Symptoms, Spirometry, and Immunologic Sensitivity in Epoxy Resin Workers.

OBJECTIVES: An epoxy resin worker developed hypersensitivity pneumonitis requiring lung transplantation and had an abnormal blood lymphocyte proliferation test (LPT) to an epoxy hardener. We assessed the prevalence of symptoms, abnormal spirometry, and abnormal epoxy resin LPT results in epoxy resin workers compared to unexposed workers. METHODS: Participants completed questionnaires and underwent spirometry. We collected blood for epoxy resin LPT and calculated stimulation indices for five epoxy resin products. RESULTS: We compared 38 exposed to 32 unexposed workers. Higher exposed workers were more likely to report cough (OR 10.86, [1.23-infinity], p = 0.030) or wheeze (OR 4.44, [1.00-22.25], p = 0.049) than unexposed workers, even controlling for smoking. Higher exposed workers were more likely to have abnormal FEV1 than unexposed workers (OR 10.51, [0.86-589.9], p = 0.071), although not statistically significant when adjusted for smoking. There were no differences in proportion of abnormal epoxy resin system LPTs between exposed and unexposed workers. CONCLUSIONS: In summary, workers exposed to epoxy resin system chemicals were more likely to report respiratory symptoms and have abnormal FEV1 than unexposed workers. Use of epoxy resin LPT was not helpful as a biomarker of exposure and sensitization.

Identifying the benefits and risks of emerging treatments for idiopathic pulmonary fibrosis: a qualitative study.

OBJECTIVE: Idiopathic pulmonary fibrosis (IPF) is a rare, progressive, and fatal disease, with very few therapeutic options. Given a paucity of qualitative research to the perspective of patients and other stakeholders in IPF, we sought to identify issues associated with the benefits and risks of emerging treatments and other issues relevant to design of a survey for assessing patient preferences for IPF treatments. METHODS: Semi-structured key informant interviews were conducted, predominately via telephone, with a range of stakeholder perspectives identified through partnership with a national advocacy organization using a combination of purposive and snowball sampling. Stakeholders were asked guiding questions related to emerging trends impacting IPF patients, likely benefits and risks of emerging treatments, and the outcomes most relevant to patients. Detailed and de-identified field notes were analyzed using interpretive phenomenological analysis (IPA), and a taxonomy of key themes was developed. RESULTS: A total of 20 interviews (participation rate 63%) were conducted with patients/advocates/caregivers (n = 7), providers/researchers (n = 8), and experts associated with policy/industry (n = 5). All interviewees expressed great hope with regards to emerging treatments. Three super-ordinate themes emerged: impact of emerging therapies (spanning the benefits, risks, and unintended consequences of emerging therapies); documenting the patient experience (spanning measuring patient-reported outcomes and quality of life and understanding the burden of disease); and coping with disease progression (including symptom mitigation, lung transplantation, and end-of-life considerations). CONCLUSIONS: In identifying issues associated with emerging IPF treatments, we demonstrate the value of qualitative research in understanding the views of diverse stakeholders and in providing a basis for future survey research. As such, qualitative methods should play an important role in understanding the benefits and risks of emerging therapies and in promoting patient-centered drug development.

Cochlear implantation in children with keratitis-ichthyosis-deafness (KID) syndrome: outcomes in three cases.

Three children with keratitis-ichthyosis-deafness (KID) syndrome received cochlear implants at the Royal Victorian Eye and Ear Hospital. KID syndrome is a rare genodermatosis associated with mutation of the connexin-26 gene with characteristics affecting skin, hair, vision and hearing. Ichthyotic involvement of the ear canal epithelium and associated non-erosive keratosis obturans complicate hearing assessment and aid fitting. The tendency to eczematous dermatitis and otitis media is an additional problem with cochlear implantation. All cases have required additional medical management, however the outcomes show that the cochlear implant can be effective in these patients.

Basic fibroblast growth factor and its receptors in idiopathic pulmonary fibrosis and lymphangioleiomyomatosis.

Basic fibroblast growth factor (bFGF) is a potent mitogenic factor for smooth muscle cells, myofibroblasts, and fibroblasts, proliferation of which is a hallmark of idiopathic pulmonary fibrosis (IPF) and lymphangioleiomyomatosis (LAM). Mast cells produce bFGF and have been associated with pulmonary fibrosis. We hypothesize that smooth muscle cell/myofibroblast-like cells will be spatially associated with bFGF-containing mast cells and that bFGF receptors will be expressed on the effector cells in IPF and LAM. We performed quantitative immunohistochemistry for bFGF, mast cell tryptase, smooth muscle actin for smooth muscle cell/myofibroblast-like cells, and fibroblast growth factor receptors (Flg, Bek) and measured collagen and elastic fiber in lung sections from IPF (n = 14), LAM (n = 9), and control lung (n = 10). IPF and LAM lung contained more smooth muscle cell/myofibroblast-like cells than did control lung. bFGF-containing mast cells were abundant both in IPF and LAM and were associated with collagen, elastic fibers, and smooth muscle cell/myofibroblast-like cells in IPF. Flg was expressed on epithelial cells, endothelial cells, smooth muscle cell/myofibroblast-like cells, and macrophages in IPF. In LAM, Flg was expressed on epithelial cells adjacent to smooth muscle cell/myofibroblast-like cell aggregates. Bek was expressed dominantly on smooth muscle cell/myofibroblast-like cells in LAM and on smooth muscle cell/myofibroblast-like cells as well as neutrophils in IPF. These data suggest that mast cell-derived bFGF might exert fibrogenic, proliferative effects on smooth muscle cell/myofibroblast-like cells through its receptors.

Speech perception outcomes in older children who use multichannel cochlear implants: older is not always poorer.

Speech perception outcomes for early-deafened children who undergo implantation as teenagers or young adults are generally reported to be poorer than results for young children. It is important to provide appropriate expectations when counseling adolescents and their families to help them make an informed choice regarding cochlear implant surgery. The considerable variation of results in this group makes this process more difficult. This study considered a number of factors in a group of 25 children who underwent implantation in Melbourne between the ages of 8 and 18 years. Each subject completed open-set speech perception testing with Bamford-Kowal-Bench sentences before and after implantation and preoperative language testing with the Peabody Picture Vocabulary Test. Data were collected regarding the type of hearing loss, age at implantation, age at hearing aid fitting, audiometric details, and preoperative and postoperative communication mode. Results were submitted to a stepwise multiple linear regression analysis with postoperative open-set sentence scores as the dependent variables. The analysis suggested that 3 factors have a significant predictive value for speech perception after implantation: preoperative open-set sentence score, duration of profound hearing loss, and equivalent language age. These 3 factors accounted for 66% of the variance in this group. The results of this study suggest that children who have useful speech perception before implantation, and higher age-equivalent scores on language measures, would be expected to do well with a cochlear implant. Consistent with other studies, a shorter duration of profound hearing loss is also advantageous. The mean sentence score for this group, 47%, was not significantly different from the mean result across all children in the Melbourne program.

Beryllium skin patch testing to analyze T cell stimulation and granulomatous inflammation in the lung.

Chronic beryllium disease (CBD) is characterized by granulomatous inflammation and the accumulation of CD4(+) T cells in the lung. Patch testing of CBD patients with beryllium sulfate results in granulomatous inflammation in the skin. We investigated whether the T cell clonal populations present in the lung of CBD patients would also be present in the involved skin of a positive beryllium patch test and thus mirror the granulomatous process in the lung. CBD patients with clonal TCR expansions in bronchoalveolar lavage (BAL) were selected for study. All three CBD patients studied had a positive response to beryllium sulfate application and a negative patch test to normal saline. Immunohistochemistry showed extensive infiltration with CD4(+) T cells and few, if any, CD8(+) T cells both at 3 days and at later times when granulomas were apparent. T cell infiltration early after skin testing appeared to be nonspecific with the TCR repertoire of infiltrating T cells being distinct from that present in BAL. At later times when granulomas were present, T cell clones in skin overlapped with those in BAL in all patients tested. Total TCR matches in skin and BAL were as high as 40% in selected Vbeta T cell subsets. Studies of peripheral blood T cells before and after patch testing provided evidence for mobilization of large numbers of pathogenic beryllium-reactive T cells into the circulating pool. These studies using skin patch testing provide new insight into the dynamics of T cell influx and mobilization during granulomatous inflammation.

Speech perception in children using cochlear implants: prediction of long-term outcomes.

A group of 102 children using the Nucleus multichannel cochlear implant were assessed for open-set speech perception abilities at six-monthly intervals following implant surgery. The group included a wide range of ages, types of hearing loss, ages at onset of hearing loss, experience with implant use and communication modes. Multivariate analysis indicated that a shorter duration of profound hearing loss, later onset of profound hearing loss, exclusively oral/aural communication and greater experience with the implant were associated with better open-set speech perception. Developmental delay was associated with poorer speech perception and the SPEAK signal coding scheme was shown to provide better speech perception performance than previous signal processors. Results indicated that postoperative speech perception outcomes could be predicted with an accuracy that is clinically useful.