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Introduction/BackgroundRe-irradiation of local recurrences of gynaecological cancer pose a difficult challenge to Oncologist. For their biological and physical characteristics particle therapy (PT) could be an interesting treatment.MethodologyThe aim of the study was to evaluate the feasibility and early clinical outcome in patients (pts) with gynaecological pelvic sidewall recurrence (PSWr). Between May 2014 to December 2018, 10 patients (median age 56) with PSWr within or at the edge of the previously irradiated field were treated using PT. They had recurrence of: cervical (5), endometrial (3), uterine (1) and ovarian (1) cancer. Previous radiotherapy prescription dose ranged from 46 to 59.4 Gy and 5 patients underwent brachytherapy (range: 7–28 Gy).Two patients, with marginal lymph node recurrence, were irradiated with protons with up to a total dose of 25 GyRBE and 51 GyRBE, respectively. The remaining women underwent carbon-ion radiotherapy (median total dose 50.4 GyRBE; range: 36–57) administered in a median number of 12 fractions. Six patients with PSWr received surgical spacer placement by open surgery to keep intestinal tracts apart from the tumour as the distance between tumour and nearest intestinal tracts was not sufficient. No pts received concurrent chemotherapy. Preliminary local control (LC) and toxicity profile (according to CTCAE V4.03 scale) were evaluated.ResultsAll patients completed the planned treatment and no acute toxicities G>2 were observed. For the evaluable patients, 1 case of intermediate G≥3 toxicity was reported in women received sequential Bevacizumab (BV). For pts with a follow-up ≥3 months, median LC was 7 months (range: 3–14), median MFS was 4.5 months (range: 3–14,5) and median OS was 7 months (range: 3–14,5). 1 pt experienced local progression and 4 pts died for systemic progression. Data are still ongoing.ConclusionFor pts with PSWr a PT approach seems to be feasible and our results showed a promising short-term outcome and limited radiation-related side effects. Longer follow-up and large patient accrual are required.DisclosureNothing to disclose.

Knowledge translation can be understood as the ability to translate concepts between different contexts by stakeholders who have different skills, aims, and even feelings in their relation to such concepts. Knowledge translation tools allow for the effective transfer of existing knowledge as well as the emergence of new knowledge of value to some or all of the stakeholders involved in the process. Knowledge translation is particularly challenging in healthcare and medicine, where different practitioners (e.g. physicians, biologists, engineers, researchers) and professionals need methodologies and tools to communicate and share knowledge among them and with patients in an effective manner. To better understand this phenomenon, we conducted a Structured Literature Review (SLR). The concepts knowledge, translation and either healthcare or medicine were used as search terms in the title, abstract or keywords on Scopus, which highlighted more than 2,000 contributions in the medical literature and only 22 in Business and Management. Our review of these documents revealed a need in the healthcare sector for better managerial and organisational practices to cope with the various challenges related to the sharing of knowledge among stakeholders. At the same time, the business and management communities appear to have made significant progress in addressing the same issues. We therefore decided to concentrate our analysis on the works published by the business and management community as a mean to highlight future research directions for the healthcare management sector. Thus, our research identifies areas of relevance which are currently underdeveloped, provides insights on both theoretical and empirical developments and offers a critique of the approaches, research frameworks and methods used, as well as emerging trends in these domains. Despite a lack of an agreed definition of the term Knowledge Translation, our findings highlight a growing interest in the topic, with most of the contributions published after 2015. Scholars have approached the term from a variety of perspectives depending on the nature of the stakeholders of relevance to their studies. Whilst there does not seem to be a predominant framework, the literature reveals several tools and techniques that are effective in enhancing Knowledge Translation in different contexts. New research opportunities in this domain emerge in terms of underinvestigated areas within the healthcare sector.

The main goal of this article is to understand the potential learning applications based on AI technologies for health higher education students. We employed a Systematic Literature Review, contributing to explore to what extent AI technologies are currently influencing the Health learning processes in higher education and the skills developed during the learning path. The intent is to contribute to a more profound understanding of learning contexts, methodologies, technologies, and pedagogical processes with the application of AI technologies. The literature emphasizes that AI can be used to potentiate the learning process and the learning outcomes, especially in laboratory classes, and such contexts are still largely unstudied. To fulfil this gap, some practical applications based on AI technologies applied to health higher education studies were identified, highlighting AI's innovations and possible opportunities for health higher education.

Organizations are challenged by the need to transform Dynamic Knowledge, embedded in each worker, into Static Knowledge, rooted in factual documental information. However, innovation and knowledge creation seem to be facilitated by the personal knowledge and life experiences of people, which appear to be dynamic. The tensions between Dynamic and Static Knowledge in facilitating the transfer and sharing of knowledge arise as compelling research as well as practical topic for organizations. Our paper aims to investigate such tensions by employing a case study. We decided to deepen such dynamics in the healthcare field, given its importance for business and society. In more detail, we analyzed one Emergency Room (ER) department through a series of interviews. Our findings highlight the importance of the right balance between Static and Dynamic Knowledge. On the one hand, the healthcare organization recognized the need to incorporate knowledge into practical and tangible instruments. On the other hand, the flows of Dynamic Knowledge must be fostered through a culture of knowledge translation and sharing, and the development of soft skills.

The sudden increase in the number of critically ill patients following a disaster can be overwhelming. The main objective of this study was to assess the real number of available and readily freeable beds (\"bed surge capacity\") and the availability of emergency operating rooms (OR) in a maximum emergency using a theoretical simulation. The proportion of dismissible patients in four areas (Medical Area, Surgical Area, Sub-intensive Care Units, Intensive Care Units) and three emergency OR was assessed at 2 and 24 hours after a simulated maximum emergency. Four scenarios were modeled. Hospitalization and surgical capacities were assessed on weekdays and holidays. The creation of new beds was presumed by the possibility of moving patients to a lower level of care than that provided at the time of detection, of dislocation of patients to a discharge room, with care transferred to lower-intensity hospitals, rehabilitation, or discharge facilities. The Phase 1 table-top simulations were conducted during the weekday morning hours. In particular, the 24-hour table-top simulations of a hypothetical event lasted about 150 minutes compared to those conducted at 2 hours, which were found to be longer (about 195 minutes). Phase 2 was conducted on two public holidays and a quick response time was observed within the first 40 minutes of the start of the test (about 45% of departments). The availability of simulated beds was greater than that indicated in the maximum emergency plans (which was based solely on the census of beds). Patients admitted to Intensive Care and The Sub-Intensive Area may be more difficult to move than those in low-intensity care. The availability of emergency OR was not problematic. Age influenced the possibility of remitting/transferring patients. Simulation in advance of a maximum emergency is helpful in designing an efficient response plan.

Nephrin Is Expressed on the Surface of Insulin Vesicles and Facilitates Glucose-Stimulated Insulin Release Alessia Fornoni 1 , 2 , Jongmin Jeon 1 , Javier Varona Santos 1 , Lorenzo Cobianchi 1 , 3 , Alexandra Jauregui 1 , 2 , Luca Inverardi 1 , Slavena A. Mandic 4 , Christina Bark 4 , Kevin Johnson 1 , George McNamara 1 , Antonello Pileggi 1 , R. Damaris Molano 1 , Jochen Reiser 2 , Karl Tryggvason 5 , Dontscho Kerjaschki 6 , Per-Olof Berggren 1 , 4 , Peter Mundel 2 , 7 and Camillo Ricordi 1 1 Diabetes Research Institute, University of Miami L. Miller School of Medicine, Miami, Florida; 2 Division of Nephrology and Hypertension–Miami Institute of Renal Medicine, University of Miami L. Miller School of Medicine, Miami, Florida; 3 Istituto di Ricovero e Cura a Carattere Scientifico Fondazione Policlinico San Matteo, Università degli Studi di Pavia, Pavia, Italy; 4 The Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden; 5 Cell Matrix Biology, Karolinska Institutet, Stockholm, Sweden; 6 Clinical Institute of Pathology, Medical University, Vienna, Austria; 7 Division of Molecular Medicine, University of Miami L. Miller School of Medicine, Miami, Florida. Corresponding author: Alessia Fornoni, afornoni{at}med.miami.edu . Abstract OBJECTIVE Nephrin, an immunoglobulin-like protein essential for the function of the glomerular podocyte and regulated in diabetic nephropathy, is also expressed in pancreatic β-cells, where its function remains unknown. The aim of this study was to investigate whether diabetes modulates nephrin expression in human pancreatic islets and to explore the role of nephrin in β-cell function. RESEARCH DESIGN AND METHODS Nephrin expression in human pancreas and in MIN6 insulinoma cells was studied by Western blot, PCR, confocal microscopy, subcellular fractionation, and immunogold labeling. Islets from diabetic ( n = 5) and nondiabetic ( n = 7) patients were compared. Stable transfection and siRNA knockdown in MIN-6 cells/human islets were used to study nephrin function in vitro and in vivo after transplantation in diabetic immunodeficient mice. Live imaging of green fluorescent protein (GFP)-nephrin–transfected cells was used to study nephrin endocytosis. RESULTS Nephrin was found at the plasma membrane and on insulin vesicles. Nephrin expression was decreased in islets from diabetic patients when compared with nondiabetic control subjects. Nephrin transfection in MIN-6 cells/pseudoislets resulted in higher glucose-stimulated insulin release in vitro and in vivo after transplantation into immunodeficient diabetic mice. Nephrin gene silencing abolished stimulated insulin release. Confocal imaging of GFP-nephrin–transfected cells revealed nephrin endocytosis upon glucose stimulation. Actin stabilization prevented nephrin trafficking as well as nephrin-positive effect on insulin release. CONCLUSIONS Our data suggest that nephrin is an active component of insulin vesicle machinery that may affect vesicle-actin interaction and mobilization to the plasma membrane. Development of drugs targeting nephrin may represent a novel approach to treat diabetes. Footnotes The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received May 1, 2009. Accepted October 1, 2009. © 2010 American Diabetes Association

The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception. The design is a randomized, parallel groups, open-label study. The setting is in an operating room, postoperative recovery area, and surgical ward. There are 200 patients undergoing open inguinal hernia repair (IHR) with tension-free technique (mesh repair). The intervention is a randomization to receive ketorolac (group K) or tramadol (group T) for 3 days after surgery. The measurements are differences in analgesic efficacy (numeric rating scale [NRS]) in the postoperative (up to 5 days) period, chronic pain incidence (1 and 3 months), side effects, and complications. We found no differences in analgesic efficacy (NRS value ≥4 in the first 96 hours: 26% in group K vs 32% in group T, P = .43); the proportion of patients with NRS ≥4 was similar in both groups, and the time trajectories were not significantly different (P for interaction = .24). Side effects were higher (12% vs 6%) in the tramadol group, although not significantly (P = .14), with a case of bleeding in the ketorolac group and higher incidence of constipation in tramadol group. One patient in each group developed chronic pain. Ketorolac or weak opioids are equally effective on acute pain and on persistent postsurgical pain development after IHR, and drug choice should be based on their potential side effects and patient's comorbidities. Further studies are needed to standardize the most rational approach to prevent persistent postsurgical pain after IHR. •Nonsteroidal anti-inflammatory drugs or weak opioids have the same effectiveness in acute pain relief and in persistent postsurgical pain incidence after open inguinal hernia repair.•The choice between them should be driven by their potential side effects.•Early-starting (intraoperative) analgesia targeting different pain pathway as well as maintenance of analgesia (despite low-invasive surgery) after hospital discharge could help in preventing persistent postsurgical pain.•Studies investigating the effect of different nonsteroidal anti-inflammatory drugs and patient's basal inflammatory status are suggested to get to an individualized therapy.

Continuous wound infusion (CWI) may protect from inflammation, hyperalgesia and persistent pain. Current local anesthetics display suboptimal pharmacokinetic profile during CWI; chloroprocaine (CP) has ideal characteristics, but has never been tested for CWI. We performed an animal study to investigate the pharmacokinetic profile and anti-inflammatory effect of CP during CWI. A total of 14 piglets received an infusion catheter after pararectal laparotomy and were randomly allocated to one of three groups: 5 mL/h infusion of saline (group A), CP 1.5% (group B) and CP 0.5% (group C). Blood sampling was performed to assess absorption and systemic inflammation at 0, 3, 6, 12, 24, 48, 72, 96, 102 and 108 hours. The wound and contralateral healthy abdominal wall were sampled for histological analyses. Absorption of CP from the site of infusion, evaluated as the plasmatic concentrations of CP and its metabolite, 4-amino-2-chlorobenzoic acid (CABA), showed a peak during the first 6 hours, but both CP and its metabolite rapidly disappeared after stopping CP infusion. Local inflammation was reduced in groups B and C (CP-treated < 0.001), in a CP dose-dependent fashion. While CP inhibited in a dose-dependent manner pig mononuclear cells (MNCs) in vitro proliferation to a polyclonal activator, no effect on systemic cytokines' concentrations or on ex vivo monocytes' responsiveness was observed, suggesting the lack of systemic effects, in line with the very short half-life of CP in plasma. CP showed a very good profile for use in CWI, with dose-dependent local anti-inflammatory effects, limited absorption and rapid clearance from the bloodstream upon discontinuation. No cytotoxicity or side effects were observed. CP, therefore, may represent an optimal choice for clinical CWI, adaptable to each patient's need, and protective on wound inflammatory response (and hyperalgesia) after surgery.

The pharmacokinetic properties and clinical advantages of the local anesthetic chloroprocaine are well known. Here, we studied the pharmacokinetic profile of a new hydrogel device loaded with chloroprocaine to investigate the potential advantages of this new strategy for postoperative pain (POP) relief. We performed both in vitro and in vivo analyses by considering plasma samples of four piglets receiving slow-release chloroprocaine. To quantify chloroprocaine and its inactive metabolite 4-amino-2-chlorobenzoic acid (ACBA), a HPLC-tandem mass spectrometry (HPLC-MS/MS) analytical method was used. Serial blood samples were collected over 108 hours, according to the exposure time to the device. Chloroprocaine was consistently found to be below the lower limit of quantification, even though a well-defined peak was observed in every chromatogram at an unexpected retention time. Concerning ACBA, we found detectable plasma concentrations between T and T , with a maximum plasma concentration (C ) observed 3 hours after the device application. In the in vitro analyses, the nanogel remained in contact with plasma at 37°C for 90 minutes, 3 hours, 1 day, and 7 days. Chloroprocaine C was identified 1 day following exposure and C after 7 days, respectively. Additionally, ACBA reached the C following 7 days of exposure. A thorough review of the literature indicates that this is the first study analyzing both in vivo and in vitro pharmacokinetic profiles of a chloroprocaine hydrogel device and is considered as a pilot study on the feasibility of including this approach to the management of POP.