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Rationale: Meta-analyses of case series of non-arteritic central retinal artery occlusion (CRAO) indicate beneficial effects of intravenous thrombolysis when initiated early after symptom onset. Randomized data are lacking to address this question. Aims: The REperfusion therapy with intravenous alteplase for recovery of VISION in acute central retinal artery occlusion (REVISION) investigates intravenous alteplase within 4.5 h of monocular vision loss due to acute CRAO. Methods: This study is the randomized (1:1), double-blind, placebo-controlled, multicenter adaptive phase III trial. Study outcomes: Primary outcome is functional recovery to normal or mildly impaired vision in the affected eye defined as best-corrected visual acuity of the Logarithm of the Minimum Angle of Resolution of 0.5 or less at 30 days (intention-to-treat analysis). Secondary efficacy outcomes include modified Rankin Score at 90 days and quality of life. Safety outcomes include symptomatic intracranial hemorrhage, major bleeding (International Society on Thrombosis and Haemostasis definition) and mortality. Exploratory analyses of optical coherence tomography/angiography, ultrasound and magnetic resonance imaging (MRI) biomarkers will be conducted. Sample size: Using an adaptive design with interim analysis at 120 patients, up to 422 participants (211 per arm) would be needed for 80% power (one-sided alpha = 0.025) to detect a difference of 15%, assuming functional recovery rates of 10% in the placebo arm and 25% in the alteplase arm. Discussion: By enrolling patients within 4.5 h of CRAO onset, REVISION uses insights from meta-analyses of CRAO case series and randomized thrombolysis trials in acute ischemic stroke. Increased rates of early reperfusion and good neurological outcomes in stroke may translate to CRAO with its similar pathophysiology. Trial registration: ClinicalTrials.gov: NCT04965038; EU Trial Number: 2023-507388-21-00. [ABSTRACT FROM AUTHOR]

Abstract Background Although a device is needed to continuously measure blood glucose levels within an intensive care setting, and several large-scale prospective studies have shown that patients might benefit from intensive insulin, potassium, or glucose therapy during intensive care, no devices are currently available to continuously assess blood glucose levels in critically ill patients. We conceived the study described here to evaluate the clinical use of the Continuous Glucose Monitor (CGM) performed via a central vein, and to determine the impact of phenomena, such as drift and shift, on the agreement between the CGM and a RAPIDLab® 1265 blood gas analyser (BGA). Methods/design In the CONTinuous ASSessment of blood GLUcose (CONTASSGLU) study, up to 130 patients under intensive care will be fitted with the CGM, an ex vivo device that continuously measures blood glucose and lactate levels. Readings from the device taken 8 h after initial placement and calibration will be compared with values measured by a BGA. For this study, we chose the BGA as it is an established standard point-of-care device, instead of the devices used in certified central laboratories. Nevertheless, we will also independently compare the results from the point-of-care BGA with those determined by a central laboratory-based device. Blood samples will be collected from each patient from the same site in which the CGM will measure blood glucose. Consequently, each participant will serve as their own control, and no randomisation is necessary. The 95% limits of agreement and the corresponding confidence intervals will be calculated and compared with a prespecified clinically acceptable relative difference of 20%. Discussion Several attempts have been made to develop a device to continuously measure blood glucose levels within an intensive care setting or to use the devices that were originally designed for diabetes management, as several of these devices are already available. However, none of these devices were successful in intensive care settings. CONTASSGLU may well bridge this gap by confirming the ability of the CGM to continuously measure blood glucose levels in intensive care settings. Trial registration ClinicalTrials.gov NCT01580176

Background: Severe sepsis and septic shock remain a major challenge, even in modern intensive care. In Germany, about 68,000 patients die annually because of septic diseases, characterized by a complex systemic inflammatory response. Causal treatment of the underlying infection is essential for successful management of sepsis, but the course can be positively influenced by supportive and adjuvant measures. The cholinergic anti-inflammatory pathway (CAP) represents a new approach to adjunctive therapy of septic diseases and can be pharmacologically activated by the acetylcholinesterase inhibitor physostigmine (Anticholium®). Promising effects can be found in several in vitro and in vivo models of sepsis, such as a reduction in pro-inflammatory cytokines and improved survival.Methods: Anticholium® per Se is a randomized, double-blind, placebo-controlled, monocentric trial to assess whether the CAP can be transferred from bench to bedside. In this pilot study, 20 patients with perioperative sepsis and septic shock as a result of intra-abdominal infection are enrolled. According to randomization, participants are treated with physostigmine salicylate (verum group) or 0.9% sodium chloride (placebo group) for up to 5 days. The mean Sequential Organ Failure Assessment (SOFA) score during treatment and subsequent intensive care of up to 14 days is used as surrogate outcome (primary endpoint). Secondary outcome measures include 30- and 90-day mortality. An embedded pharmacokinetics and pharmacodynamics study investigates plasma concentrations of physostigmine and its metabolite eseroline. Further analyses will contribute to our understanding of the role of various cytokines in the pathophysiology of human sepsis. A computer-generated list is used for block randomization.Discussion: This randomized, controlled, monocentric trial investigates for the first time the adjunctive use of physostigmine (Anticholium®) in patients with perioperative sepsis and septic shock and may be a pivotal step toward the clinical use in this indication.Trial Registration: EudraCT Number: 2012-001650-26 (entered 14 August 2012), ClinicalTrials.gov identifier: NCT03013322 (registered on 1 Jan 2017). [ABSTRACT FROM AUTHOR]

Background: Metastatic pancreatic cancer has a dismal prognosis, with a mean six-month progression-free survival of approximately 50% and a median survival of about 11 months. Despite intensive research, only slight improvements of clinical outcome could be achieved over the last decades. Hence, new and innovative therapeutic strategies are urgently required. ParvOryx is a drug product containing native parvovirus H-1 (H-1PV). Since H-1PV was shown to exert pronounced anti-neoplastic effects in pre-clinical models of pancreatic cancer, the drug appears to be a promising candidate for treatment of this malignancy.Methods: ParvOryx02 is a non-controlled, single arm, open label, dose-escalating, single center trial. In total seven patients with pancreatic cancer showing at least one hepatic metastasis are to be treated with escalating doses of ParvOryx according to the following schedule: i) 40% of the total dose infused intravenously in equal fractions on four consecutive days, ii) 60% of the total dose injected on a single occasion directly into the hepatic metastasis at varying intervals after intravenous infusions. The main eligibility criteria are: age ≥ 18 years, disease progression despite first-line chemotherapy, and at least one hepatic metastasis. Since it is the second trial within the drug development program, the study primarily explores safety and tolerability after further dose escalation of ParvOryx. The secondary objectives are related to the evaluation of certain aspects of anti-tumor activity and clinical efficacy of the drug.Discussion: This trial strongly contributes to the clinical development program of ParvOryx. The individual hazards for patients included in the current study and the environmental risks are addressed and counteracted adequately. Besides information on safety and tolerability of the treatment after further dose escalation, thorough evaluations of pharmacokinetics and intratumoral spread as well as proof-of-concept (PoC) in pancreatic cancer will be gained in the course of the trial.Trial Registration: ClinicalTrials.gov-ID: NCT02653313 , Registration date: Dec. 4th, 2015. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. Methods/Design: The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. Discussion: The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying hypothesis is that allo-HSCT has the capacity to provide long-term disease control to an extent otherwise not possible in pancreatic cancer, thereby substantially improving survival of affected patients. [ABSTRACT FROM AUTHOR]

Interventionist conservation management of territorial large carnivores has increased in recent years, especially in South Africa. Understanding of spatial ecology is an important component of predator conservation and management. Spatial patterns are influenced by many, often interacting, factors making elucidation of key drivers difficult. We had the opportunity to study a simplified system, a single pride of lions (Panthera leo) after reintroduction onto the 85 km2 Karongwe Game Reserve, from 1999-2005, using radio-telemetry. In 2002 one male was removed from the paired coalition which had been present for the first three years. A second pride and male were in a fenced reserve adjacent of them to the east. This made it possible to separate social and resource factors in both a coalition and single male scenario, and the driving factors these seem to have on spatial ecology. Male ranging behaviour was not affected by coalition size, being driven more by resource rather than social factors. The females responded to the lions on the adjacent reserve by avoiding the area closest to them, therefore females may be more driven by social factors. Home range size and the resource response to water are important factors to consider when reintroducing lions to a small reserve, and it is hoped that these findings lead to other similar studies which will contribute to sound decisions regarding the management of lions on small reserves. [ABSTRACT FROM AUTHOR]

The reproductive biology of a pride of lions (Panthera leo) was studied on the 8500 ha Karongwe Game Reserve from 1999 to 2005. Over this period, the pride consisted of between four and 11 lions with a paired coalition of adult males during the first three years and a single adult male for the next three years. We recorded shorter than normal interbirth intervals, high birth rates of 1.3 cubs/lioness/year, very high cub survival rates, and subadults leaving the pride at young ages. This translated into substantially faster growth rates than are typical in large lion populations in ecologically similar circumstances such as Kruger National Park, but are similar to those of lions in Serengeti National Park. These demographic characteristics were probably induced initially by a lack of intense intraspecific competition and high prey availability, but population stability was maintained through the removal of young subadults by management. Interestingly, variability in conception rates between lionesses resulted in lower growth rates than have been found in other similar reintroduced lion populations. These demographic traits characterize many of the small reintroduced lion populations, and call for appropriate management to avoid the consequences of high predator densities. [ABSTRACT FROM AUTHOR]

The prey selection and predatory behaviour of a single pride of lions (Panthera leo) was studied in the 8500 ha Karongwe Game Reserve from 1999--2005. The study focused on the difference between prey selection in the first three years when a two-male coalition was present with a similar period thereafter when one of the males was removed and subadult males dispersed from the pride. A total of 662 kills were recorded, with blue wildebeest ( Connochaetes taurinus), warthog (Phacochoerus africanus), waterbuck (Kobus ellipsiprymnus), zebra (Equus burchelli) and impala ( Aepyceros melampus) being the most preferred species. Although there was preference for these species, and adult prey were favoured, there was no significant selection for prey size, age or gender. There was a significant difference in the number of kills made when the two-male coalition was present as opposed to the single pride male. The solitary pride male spent significantly more time with the females and shared most of their kills, and during this period dispersing subadult males killed a substantial amount of prey when separated from the pride. Knowledge on predator feeding behaviour is important for managers to assess impact on prey populations in small reserves in order to manage them correctly, thereby preventing depletion of such populations. [ABSTRACT FROM AUTHOR]