421 research outputs found

    Comprehensive meta-analysis of the CHO coding transcriptome

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    Competing in the Clouds: A Strategic Challenge for ITSP Ltd.

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    By 2010, cloud computing had become established as a new model of IT provisioning for service providers. New market players and businesses emerged, threatening the business models of established market players. This teaching case explores the challenges arising through the impact of the new cloud computing technology on an established, multinational IT service provider called ITSP. Should the incumbent vendors adopt cloud computing offerings? And, if so, what form should those offerings take? The teaching case focuses on the strategic dimensions of technological developments, their threats and opportunities. It requires strategic decision making and forecasting under high uncertainty. The critical question is whether cloud computing is a disruptive technology or simply an alternative channel to supply computing resources over the Internet. The case challenges students to assess this new technology and plan ITSP’s responses

    Effect of suture technique on the occurrence of incisional hernia after elective midline abdominal wall closure: study protocol for a randomized controlled trial

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    Background: Based on a recent meta-analysis, a continuous suture technique with a suture to wound length ratio of at least 4: 1, using a slowly absorbable monofilament suture material, is recommended for primary median laparotomy closure. Incisional hernia, which develops in 9 to 20% of patients, remains the major complication of abdominal wall closure. Current clinical data indicate that the incidence of incisional hernias increases by 60% between the first and the third year after median laparotomy, implicating that a follow-up period of 1 year postoperatively is too short with regard to this common complication. Trauma to the abdominal wall can be reduced by improvements in suture technique as well as suture material. Several factors, such as stitch length, suture tension, elasticity, and tensile strength of the suture material are discussed and currently under investigation. A Swedish randomized controlled trial showed a significant reduction in the incisional hernia rate by shortening the stitch length. However, a non-elastic thread was used and follow-up ended after 12 months. Therefore, we designed a multicenter, international, double-blinded, randomized trial to analyze the influence of stitch length, using an elastic, extra-long term absorbable monofilament suture, on the long term clinical outcome of abdominal wall closure. Methods: In total, 468 patients undergoing an elective, median laparotomy will be randomly allocated to either the short stitch or the long stitch suture technique for abdominal wall closure in a 1: 1 ratio. Centers located in Germany and Austria will participate. The primary endpoint measure is the incisional hernia rate 1 year postoperatively, as verified by ultrasound. The frequency of short term and long term complications as well as costs, length of hospital stay and patients' quality of life (EQ-5D-5 L) will be considered as secondary parameters. Following hospital discharge, patients will be examined after 30 days and 1, 3, and 5 years after surgery. Discussion: This study will provide further evidence on whether a short stitch suture technique in combination with an elastic, extra-long term absorbable monofilament suture can prevent incisional hernias in the long term, compared with the long stitch suture technique

    Treatment of Fracture-Related Infection after Pelvic Fracture

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    Background: The management of pelvic fractures is a significant challenge. Surgical site infection can result in the need for revision surgery, cause functional impairment, and lead to a prolonged length of stay and increased treatment costs. Although reports on fracture-related infection (FRI) after pelvic fracture fixation are sparsely reported in the literature, it is a serious complication. This study analysed patients with FRIs after pelvic fracture regarding patient characteristics, treatment strategies, and an evaluation of risk factors for FRI. Methods: In this retrospective single-centre study, FRI was diagnosed based on clinical symptoms of infection and a positive culture of a bacterial infection. Depending on the severity and acuteness of the infection, osseous stabilization was restored either via implant retention (stable implant, no osteolysis), exchange (loose implant or bony defect), or external fixation (recurrence of infection after prior implant retaining revision). Healing of infection was defined as no sign of recurring infection upon clinical, radiological, and laboratory examination in the last follow-up visit. Results: The FRI rate in our patient population was 7.5% (24/316). In 8/24 patients, the FRI occurred within the first three weeks after initial surgery (early) and 16/24 presented with a late onset of symptoms of FRI. A strategy of debridement, antibiotics, and implant retention (DAIR) was successful in 9/24 patients with FRI after pelvic fracture. A total of 10 patients required an exchange of osteo-synthetic implants, whereof three were exchanged to an external fixator. In five patients, we removed the implant because the fracture had already consolidated at the time of revision for infection. A total of 17/24 patients had a poly-microbial infection after a pelvic fracture and 3/24 patients died from post-traumatic multi-organ failure within the first 6 months after trauma. There were no cases of persistent infection within the remaining 21 patients. Conclusions: Although poly-microbial infection is common in FRI after pelvic fracture, the recurrence rate of infection is relatively low. A complex pelvic trauma with significant soft tissue injury is a risk factor for recurrent infection and multiple revisions. A strategy of DAIR can be successful in patients with a stable implant. In cases with recurrent infection or an unstable fracture site, the exchange of implants should be considered

    design of the HELP study extension

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    Background Hereditary angioedema (HAE) is characterized by recurrent attacks of subcutaneous or submucosal edema. Attacks are unpredictable, debilitating, and have a significant impact on quality of life. Patients may be prescribed prophylactic therapy to prevent angioedema attacks. Current prophylactic treatments may be difficult to administer (i.e., intravenously), require frequent administrations or are not well tolerated, and breakthrough attacks may still occur frequently. Lanadelumab is a subcutaneously-administered monoclonal antibody inhibitor of plasma kallikrein in clinical development for prophylaxis of hereditary angioedema attacks. A Phase 1b study supported its efficacy in preventing attacks. A Phase 3, randomized, double-blind, placebo- controlled, parallel-arm study has been completed and an open-label extension is currently ongoing. Methods/design The primary objective of the open-label extension is to evaluate the long-term safety of repeated subcutaneous administrations of lanadelumab in patients with type I/II HAE. Secondary objectives include evaluation of efficacy and time to first angioedema attack to determine outer bounds of the dosing interval. The study will also evaluate immunogenicity, pharmacokinetics/pharmacodynamics, quality of life, characteristics of breakthrough attacks, ease of self-administration, and safety/efficacy in patients who switch to lanadelumab from another prophylactic therapy. The open-label extension will enroll patients who completed the double-blind study (“rollover patients”) and those who did not participate in the double-blind study (“non-rollover patients”), which includes patients who may or may not be currently using another prophylactic therapy. Rollover patients will receive a single 300 mg dose of lanadelumab on Day 0 and the second dose after the patient’s first confirmed angioedema attack. Thereafter, lanadelumab will be administered every 2 weeks. Non- rollover patients will receive 300 mg lanadelumab every 2 weeks regardless of the first attack. All patients will receive their last dose on Day 350 (maximum of 26 doses), and will then undergo a 4-week follow-up. Discussion Prevention of attacks can reduce the burden of illness associated with HAE. Prophylactic therapy requires extended, repeated dosing and the results of this study will provide important data on the long-term safety and efficacy of lanadelumab, a monoclonal antibody inhibitor of plasma kallikrein for subcutaneous administration for the treatment of HAE. Trial registration NCT0274159

    BendaEAM versus BEAM as conditioning regimen for ASCT in patients with relapsed lymphoma (BEB): a multicentre, randomised, phase 2 trial.

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    BACKGROUND Replacement of carmustine (BCNU) in the BEAM regimen (BCNU, etoposide, cytarabine, melphalan) with bendamustine (BendaEAM) before autologous stem cell transplantation (ASCT) is feasible in lymphoma. However, randomised trials are lacking. Here, we present the first trial addressing this topic. METHODS This multicentre, randomised, phase 2 study (BEB-trial) conducted at four haematological centres in Austria and Switzerland compares BEAM with BendaEAM in patients with relapsed lymphoma. Both regimens were administered intravenously before ASCT, in BEAM according to the standard protocol (300 mg/m2 BCNU on day -6), in BendaEAM, BCNU was replaced by 200 mg/m2 bendamustine given on days -7 and -6. Eligible patients were aged 18-75 years and had mantle cell lymphoma, diffuse large B-cell lymphoma, or follicular lymphoma in first or second remission or chemosensitive relapse. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine reduces lung toxicity, defined as a decrease of the diffusion capacity of the lung for carbon monoxide by at least 20% at three months after ASCT. Data analyses were performed on an intention-to-treat basis. This study is registered with ClinicalTrials.gov, number NCT02278796, and is complete. FINDINGS Between April 20, 2015, and November 28, 2018, 108 patients were enrolled; of whom 53 were randomly assigned to receive BendaEAM (36 male, 17 female) and 55 to receive BEAM (39 male, 16 female). All patients engrafted rapidly. Lung toxicity did not differ between groups (BendaEAM: n = 8, 19.5%; BEAM: n = 11, 25.6%; risk difference = -6.1%: 95% confidence interval: -23.9% to 11.7%). Acute toxicities of at least grade 3 were comparable in both groups (BendaEAM: 35.8%, BEAM: 30.9%). Overall survival (BendaEAM: 92.5%, BEAM: 89.1%) and complete remission (BendaEAM: 76.7%, BEAM: 74.3%) after 1 year (median follow-up: 369 days) were similar. No difference in quality of life was observed. INTERPRETATION Results were similar for both regimens in terms of survival and response rates. A phase 3 non-inferiority study is required to investigate whether BendaEAM can be considered as an alternative to BEAM. FUNDING Mundipharma

    Anterior Column Reconstruction of Destructive Vertebral Osteomyelitis at the Thoracolumbar Spine with an Expandable Vertebral Body Replacement Implant: A Retrospective, Monocentric Radiological Cohort Analysis of 24 Cases

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    Background: Vertebral osteomyelitis (VO) often necessitates surgical intervention due to bone loss-induced spinal instability. Anterior column reconstruction, utilizing expandable vertebral body replacement (VBR) implants, is a recognized approach to restore stability and prevent neurological compromise. Despite various techniques, clinical evidence regarding the safety and efficacy of these implants in VO remains limited. Methods: A retrospective cohort analysis, spanning 2000 to 2020, was conducted on 24 destructive VO cases at a Level 1 orthopedic trauma center. Diagnosis relied on clinical, radiological, and microbiological criteria. Patient demographics, clinical presentation, surgical interventions, and radiological outcomes were assessed. Results: The study included 24 patients (62.5% male; mean age 65.6 ± 35.0 years), with 58% having healthcare-associated infections (HAVO). The mean radiological follow-up was 137.2 ± 161.7 weeks. Surgical intervention significantly improved the bi-segmental kyphotic endplate angle (BKA) postoperatively (mean −1.4° ± 13.6°). However, a noticeable loss of correction was observed over time. The study reported a mortality rate of 1/24. Conclusions: Anterior column reconstruction using expandable VBR effectively improved local spinal alignment in destructive VO. However, the study underscores the necessity for prolonged follow-up and continuous research to refine surgical techniques and postoperative care. Addressing long-term complications and refining surgical approaches will be pivotal as the field progresses
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