Immunostimulatory nucleic acid nanoparticles (NANPs) augment protective osteoblast and osteoclast type I interferon responses to Staphylococcus aureus.

Recalcitrant staphylococcal osteomyelitis may be due, in part, to the ability of Staphylococcus aureus to invade bone cells. However, osteoclasts and osteoblasts are now recognized to shape host responses to bacterial infection and we have recently described their ability to produce IFN-ß following S. aureus infection and limit intracellular bacterial survival/propagation. Here, we have investigated the ability of novel, rationally designed, nucleic acid nanoparticles (NANPs) to induce the production of immune mediators, including IFN-ß, following introduction into bone cells. We demonstrate the successful delivery of representative NANPs into osteoblasts and osteoclasts via endosomal trafficking when complexed with lipid-based carriers. Their delivery was found to differentially induce immune responses according to their composition and architecture via discrete cytosolic pattern recognition receptors. Finally, the utility of this nanoparticle technology was supported by the demonstration that immunostimulatory NANPs augment IFN-ß production by S. aureus infected bone cells and reduce intracellular bacterial burden.

An Outcome Assessment of a Single Institution's Longitudinal Experience with Uveal Melanoma Patients with Liver Metastasis.

There is no FDA-approved treatment for metastatic uveal melanoma (UM) and overall outcomes are generally poor for those who develop liver metastasis. We performed a retrospective single-institution chart review on consecutive series of UM patients with liver metastasis who were treated at Thomas Jefferson University Hospital between 1971-1993 (Cohort 1, n = 80), 1998-2007 (Cohort 2, n = 198), and 2008-2017 (Cohort 3, n = 452). In total, 70% of patients in Cohort 1 received only systemic therapies as their treatment modality for liver metastasis, while 98% of patients in Cohort 2 and Cohort 3 received liver-directed treatment either alone or with systemic therapy. Median Mets-to-Death OS was shortest in Cohort 1 (5.3 months, 95% CI: 4.2-7.0), longer in Cohort 2 (13.6 months, 95% CI: 12.2-16.6) and longest in Cohort 3 (17.8 months, 95% CI: 16.6-19.4). Median Eye Tx-to-Death OS was shortest in Cohort 1 (40.8 months, 95% CI: 37.1-56.9), and similar in Cohort 2 (62.6 months, 95% CI: 54.6-71.5) and Cohort 3 (59.4 months, 95% CI: 56.2-64.7). It is speculated that this could be due to the shift of treatment modalities from DTIC-based chemotherapy to liver-directed therapies. Combination of liver-directed and newly developed systemic treatments may further improve the survival of these patients.

Virtual Reality for Pediatric Needle Procedural Pain: Two Randomized Clinical Trials.

OBJECTIVE: To assess the efficacy and safety of a virtual reality distraction for needle pain in 2 common hospital settings: the emergency department (ED) and outpatient pathology (ie, outpatient laboratory). The control was standard of care (SOC) practice. STUDY DESIGN: In 2 clinical trials, we randomized children aged 4-11 years undergoing venous needle procedures to virtual reality or SOC at 2 tertiary Australian hospitals. In the first study, we enrolled children in the ED requiring intravenous cannulation or venipuncture. In the second, we enrolled children in outpatient pathology requiring venipuncture. In the ED, 64 children were assigned to virtual reality and 59 to SOC. In pathology, 63 children were assigned to virtual reality and 68 to SOC; 2 children withdrew assent in the SOC arm, leaving 66. The primary endpoint was change from baseline pain between virtual reality and SOC on child-rated Faces Pain Scale-Revised. RESULTS: In the ED, there was no change in pain from baseline with SOC, whereas virtual reality produced a significant reduction in pain (between-group difference, -1.78; 95% CI, -3.24 to -0.317; P = .018). In pathology, both groups experienced an increase in pain from baseline, but this was significantly less in the virtual reality group (between-group difference, -1.39; 95% CI, -2.68 to -0.11; P = .034). Across both studies, 10 participants experienced minor adverse events, equally distributed between virtual reality/SOC; none required pharmacotherapy. CONCLUSIONS: In children aged 4-11 years of age undergoing intravenous cannulation or venipuncture, virtual reality was efficacious in decreasing pain and was safe. TRIAL REGISTRATION: Australia and New Zealand Clinical Trial Registry: ACTRN12617000285358p.

Reoperative repair of descending thoracic and thoracoabdominal aneurysms.

OBJECTIVES: To evaluate the results of reoperation on descending thoracic and thoracoabdominal aneurysms. METHODS: Sixty-nine consecutive patients undergoing reoperative aneurysm repair (20 descending thoracic and 49 thoracoabdominal) were compared to 602 contemporary primary repairs. Propensity matching was used to reduce observable differences in preoperative characteristics. RESULTS: The reoperation group was younger (60.2 vs 65.3 years, P = 0.005) and less were extent I or II (28.6% vs 76%, P < 0.001). In the reoperation group, 82.6% were repaired with clamp-and-sew, 14.5% circulatory arrest and 2.9% partial bypass versus the primary surgery group 62.1%, 8.1% and 29.7%, respectively (P < 0.001). In the reoperation versus primary surgery group, respectively, spinal drainage was used in 73.9% vs 83.7% (P = 0.05), intercostal reimplantation in 11.6% vs 44.2% (P < 0.001), and cold renal perfusion in 36.2% vs 19.8% (P = 0.001). Operative mortality was comparable (8.7% vs 5.3% primary, P = 0.25) but the reoperative extent I subgroup had higher mortality (20% vs 3.1%; P = 0.04). Incidence of major complications was comparable (stroke 0 vs 0.9%, tracheostomy 5.8% vs 8%, renal failure 7.2% vs 5%, spinal cord injury 4.3% vs 2.7%; P > 0.05 for all variables), with the exception of myocardial infarction (2.9% vs 0.5%, P = 0.028). Five-year survival was 57.6% in reoperations and 58% in the primary surgery group (P = 0.878). No differences in the in-hospital and follow-up outcomes were found in the propensity matched comparison. CONCLUSIONS: Reoperative repair of descending thoracic and thoracoabdominal aneurysms can be safely performed with reasonable in-hospital and follow-up outcomes compared to primary aneurysm repair.

Effect of a Computerized Reminder on Splinting of Pediatric Upper Limb Fractures in the Emergency Department.

OBJECTIVE: The primary objective was to assess if a computerized pop-up reminder increased splint application before X-ray in pediatric emergency department patients with deformed upper limb fractures. The secondary objective was to evaluate whether this same reminder improved pharmaceutical analgesia provision in this population. METHODOLOGY: This was a prospective study of 518 pediatric emergency department patients with upper limb fractures after the implementation of a computerized pop-up reminder to give analgesia and apply a splint. The records of those with fractures requiring manipulation were identified and reviewed for data on demographics, clinical characteristics, splint application, and analgesic use. These data were compared with that in a previous retrospective study of 1407 patients in the same population before implementation of the computerized reminder. RESULTS: There were 86 patients with upper limb fractures requiring manipulation identified during the study period. After the computerized intervention, splint application rates improved from 22% to 49% (P = <0.001). There was no significant change to analgesia provision in the first hour after presentation. CONCLUSIONS: A computerized reminder at the point of X-ray ordering significantly improved splint application rates for children with deformed upper limb fractures, though it did not affect pharmaceutical analgesia provision. The computerized pop-up is cheap to implement, easy to use, and potentially transferrable to other institutions and for other uses.

Ascending Aortic Endoballoon Occlusion Feasible Despite Moderately Enlarged Aorta to Facilitate Robotic Mitral Valve Surgery.

OBJECTIVE: Aortic occlusion with an endoballoon is a well-established technique to facilitate robotic and minimally invasive mitral valve surgery. Use of the endoballoon has several relative contraindications including ascending aortic dilatation greater than 38 mm in size. We sought to review our experience using the endoballoon in cases of totally endoscopic mitral valve surgery with aortic diameters greater than 38 mm. METHODS: A retrospective review of our single-site database was conducted to identify patients undergoing totally endoscopic mitral valve surgery by a single surgeon using an endoballoon and who had ascending aortic dilation. We defined aortic dilation as greater than 38 mm. Computed tomography was done preoperatively on all patients to evaluate the aortic anatomy as well as iliofemoral access vessels. Femoral artery cannulation was done in a standardized fashion to advance and position the endoballoon, to occlude the ascending aorta, and to deliver cardioplegia. RESULTS: From October 2011 through June 2015, 196 patients underwent totally endoscopic mitral valve surgery using an endoballoon at our institution. Twenty-two patients (11.2%) had ascending aortic diameters greater than 38 mm (range, 38.1-46.6 mm; mean, 40.5 ± 2.5 mm). In these cases, there were no instances of aortic dissection or other injury due to balloon rupture, balloon migration, device movement leading to loss of occlusion, or inability to complete planned surgery due to occlusion failure. CONCLUSIONS: Our experience suggests that it is possible to successfully use endoaortic balloon occlusion in patients with ascending aortic dilation with proper preoperative imaging and planning.

Busted! Management of paediatric upper limb fractures: not all that it's cracked up to be.

OBJECTIVE: The primary objective was to assess use of splinting prior to X-ray in paediatric ED patients with deformed upper limb fractures. Secondary objectives were to evaluate pharmaceutical analgesia use and the impact of demographic, hospital and clinical variables on splint and analgesia provision. METHODS: A retrospective study of 1407 paediatric ED patients who received upper limb X-rays. The records of those with fractures requiring manipulation were identified, and reviewed for data on demographics, mode of arrival, triage category, site of fracture, clinician seniority, pain scoring, splint application and analgesic use. RESULTS: Two hundred and twelve patients had fractures requiring manipulation. Of these, 47 (22%) had a splint applied prior to X-ray and 161 (76%) of patients were prescribed analgesia in the first hour after presentation. A triage category 1 or 2 and arrival by ambulance predicted for splint application. Children with higher recorded pain scores were more likely to receive any analgesia in the first hour (91% with a pain score ≥7 compared with 62% with pain score of ≤6, P < 0.001), and more likely to receive strong analgesia (59% vs 13%, P < 0.001). Those triaged to category 1 or 2 were more likely to receive analgesia in the first hour (P < 0.001). CONCLUSIONS: This study identified significant shortcomings in ED management of children with deformed upper limb fractures. Only a minority were splinted prior to X-ray, and a quarter did not receive any analgesia in the first hour after presentation. Future study should investigate methods to improve ED management of these patients.

Asymptomatic gunshot wound to the heart with retained intracardiac pellet.

A 20-year-old man was transferred to our institution with multiple penetrating thoracoabdominal wounds from a shotgun. Imaging revealed several retained shotgun pellets, 1 of which appeared to be located in the left atrium. He was asymptomatic from a cardiac standpoint and was first taken to the operating room to manage his multiple abdominal injuries. Neither an intraoperative echocardiogram nor a formal postoperative echocardiogram definitively determined pellet location (myocardium versus chamber). Because of concerns for pellet embolus from left atrial positioning, the patient was returned to the operating room. After placing the patient on cardiopulmonary bypass, the pellet was identified within the wall of the left atrium and was successfully removed without complication.

Generation Y in healthcare: the need for new socio-technical consideration for future technology design in healthcare.

While identifying reasons for the failure of information communication technology (ICT) to transform the healthcare system and constructing models of better designed technology with socio-technical integration is relatively straightforward, implementing these solutions into the rapidly changing medical world has proven considerably more difficult. From a technologist's perspective, the promise of technology remains powerful. New technologies, with high level of socio-technical integration have long been considered as one of the most important factors to transform the medical world in order to deliver better and safer care. From the socio-cultural perspective, however, there is an equally powerful force, which has largely been ignored by the greater community: the entry of generation Y into the healthcare system. Generation Y has generated significant changes in many other industries. This powerful socio-cultural change within the healthcare system needs to be more clearly investigated to guide the design and implementation of sociotechnical integrated ICT solutions. This research-in -progress paper presents a methodological approach that both generates an in-depth understanding of generation Y and illuminates criteria that can be used to meaningfully identify the guiding principles for future socio-technical integrated ICT design and implementation. It aims to make a significant contribution to the field of socio-technical approach to ICT design by alluding the audience to this new generation Y phenomenon in healthcare. It provides some preliminary data to support the need to consider generation Y in future ICT design in healthcare.

Ultrastructural examination of spermiogenesis within the testis of the ground skink, Scincella laterale (Squamata, Sauria, Scincidae).

Although the events of spermiogenesis are commonly studied in amniotes, the amount of research available for lizards (Sauria) is lacking. Many studies have described the morphological characteristics of mature spermatozoa in lizards, but few detail the ultrastructural changes that occur during spermiogenesis. The purpose of this study was to gain a better understanding of the subcellular events of spermiogenesis within the temperate ground skink (Scincella laterale). The morphological data presented here represent the first complete ultrastructural study of spermiogenesis within the Scincidae clade. Samples of testes from 20 specimens were prepared using standard techniques for transmission electron microscopy. Many of the ultrastructural changes occurring during spermiogenesis within the ground skink are similar to that of other saurians. However, there were a few unique characteristics that to date have not been described during spermiogenesis in other lizards. For example, during early round spermatid development within the ground skink testis, proacrosomal granules begin to form within the acrosomal vesicle before making contact with the apex of the nucleus. Also, a prominent microtubular manchette develops during spermiogenesis; however, the circular component of the manchete is absent in this species of skink. This developmental difference in manchette formation may lead to the more robust and straight mature spermatozoa that are common within the Scincidae family. These anatomical character differences may be valuable nontraditional sources that along with more traditional sources (i.e., mitochondrial DNA) may help elucidate phylogenetic relationships, which are historically considered controversial at best, among species within Scincidae and Sauria.