Aortic aneurysm and aortic graft infection related to Mycobacterium bovis after intravesical Bacille Calmette-Guérin therapy-a case series.

BACKGROUND: So called "mycotic" aortic aneurysms account for only 0.7 to 1.3% of all aortic aneurysms and are commonly caused by Staphylococcus aureus and Salmonella species. Bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is part of the therapy of non-muscle-invasive bladder cancer (NMIBC). CASE PRESENTATION: We report a case series of three patients with a mycobacterial graft infection related to BCG after surgical treatment of a presumed mycotic aortic aneurysm as an extremely rare complication after NMIBC treatment. All three patients developed aortic aneurysm after BCG instillation and subsequent mycobacterial graft infection. CONCLUSION: Diagnosis requires a high degree of suspicion because of its nonspecific symptoms and imaging. The pathogen is not detected by standard microbiological testing. Treatment includes triple antimycobacterial therapy and radical surgical interventions. Graft preservation may be considered if no anastomosis is involved.

Using longitudinal targeted maximum likelihood estimation in complex settings with dynamic interventions.

Longitudinal targeted maximum likelihood estimation (LTMLE) has very rarely been used to estimate dynamic treatment effects in the context of time-dependent confounding affected by prior treatment when faced with long follow-up times, multiple time-varying confounders, and complex associational relationships simultaneously. Reasons for this include the potential computational burden, technical challenges, restricted modeling options for long follow-up times, and limited practical guidance in the literature. However, LTMLE has desirable asymptotic properties, ie, it is doubly robust, and can yield valid inference when used in conjunction with machine learning. It also has the advantage of easy-to-calculate analytic standard errors in contrast to the g-formula, which requires bootstrapping. We use a topical and sophisticated question from HIV treatment research to show that LTMLE can be used successfully in complex realistic settings, and we compare results to competing estimators. Our example illustrates the following practical challenges common to many epidemiological studies: (1) long follow-up time (30 months); (2) gradually declining sample size; (3) limited support for some intervention rules of interest; (4) a high-dimensional set of potential adjustment variables, increasing both the need and the challenge of integrating appropriate machine learning methods; and (5) consideration of collider bias. Our analyses, as well as simulations, shed new light on the application of LTMLE in complex and realistic settings: We show that (1) LTMLE can yield stable and good estimates, even when confronted with small samples and limited modeling options; (2) machine learning utilized with a small set of simple learners (if more complex ones cannot be fitted) can outperform a single, complex model, which is tailored to incorporate prior clinical knowledge; and (3) performance can vary considerably depending on interventions and their support in the data, and therefore critical quality checks should accompany every LTMLE analysis. We provide guidance for the practical application of LTMLE.

Influence of different positioning of a local pain catheter on postoperative pain after paramedian laparotomy-a blinded, randomized trial.

BACKGROUND: Continuous application of local anaesthetics reduces postoperative pain after different approaches for laparotomy. In this randomized, blinded trial, we investigated the effect of continuous application of local anaesthetics after paramedian laparotomy either with subfascial or subcutaneous catheter in addition to a standardized systemic analgesia. MATERIALS AND METHODS: Patients with stage III/IV melanoma and indication for radical iliac lymph node dissection (RILND) were randomized to a continuous application of a local anaesthetic through either a subfascial or subcutaneous catheter. Participants and those assessing the outcomes were blinded. The main outcome criterion was the pain level on the first postoperative morning while exercising measured with a visual analogue scale. Minor criteria were the pain measured by the area-under-curve until the third postoperative day, the patient's satisfaction with analgesic treatment, the analgesic requirement, the overall complications and the day of discharge. RESULTS: Fifty-two patients were evaluated. Pain therapy was sufficient in both groups during the postoperative course while resting and during mobilization. There were no significant differences regarding the main and minor outcome criteria. Doses of additional analgesics did not differ between groups. No adverse events or side effects were observed. CONCLUSION: For patients who undergo paramedian laparotomy, none of the investigated techniques is superior to the other at a median pain level under visual analogue scale (VAS) 30 mm on the first postoperative morning. TRIAL REGISTRATION NUMBER: DRKS00003632 (German Register of Clinical Trials).

Delivery of proteins to mammalian cells via gold nanoparticle mediated laser transfection.

Nanoparticle laser interactions are in widespread use in cell manipulation. In particular, molecular medicine needs techniques for the directed delivery of molecules into mammalian cells. Proteins are the final mediator of most cellular cascades. However, despite several methodical approaches, the efficient delivery of proteins to cells remains challenging. This paper presents a new protein transfection technique via laser scanning of cells previously incubated with gold nanoparticles. The laser-induced plasmonic effects on the gold nanoparticles cause a transient permeabilization of the cellular membrane, allowing proteins to enter the cell. Applying this technique, it was possible to deliver green fluorescent protein into mammalian cells with an efficiency of 43%, maintaining a high level of cell viability. Furthermore, a functional delivery of Caspase 3, an apoptosis mediating protein, was demonstrated and evaluated in several cellular assays. Compared to conventional protein transfection techniques such as microinjection, the methodical approach presented here enables high-throughput transfection of about 10 000 cells per second. Moreover, a well-defined point in time of delivery is guaranteed by gold nanoparticle mediated laser transfection, allowing the detailed temporal analysis of cellular pathways and protein trafficking.

Non-ignorable loss to follow-up: correcting mortality estimates based on additional outcome ascertainment.

Loss to follow-up (LTFU) is a common problem in many epidemiological studies. In antiretroviral treatment (ART) programs for patients with human immunodeficiency virus (HIV), mortality estimates can be biased if the LTFU mechanism is non-ignorable, that is, mortality differs between lost and retained patients. In this setting, routine procedures for handling missing data may lead to biased estimates. To appropriately deal with non-ignorable LTFU, explicit modeling of the missing data mechanism is needed. This can be based on additional outcome ascertainment for a sample of patients LTFU, for example, through linkage to national registries or through survey-based methods. In this paper, we demonstrate how this additional information can be used to construct estimators based on inverse probability weights (IPW) or multiple imputation. We use simulations to contrast the performance of the proposed estimators with methods widely used in HIV cohort research for dealing with missing data. The practical implications of our approach are illustrated using South African ART data, which are partially linkable to South African national vital registration data. Our results demonstrate that while IPWs and proper imputation procedures can be easily constructed from additional outcome ascertainment to obtain valid overall estimates, neglecting non-ignorable LTFU can result in substantial bias. We believe the proposed estimators are readily applicable to a growing number of studies where LTFU is appreciable, but additional outcome data are available through linkage or surveys of patients LTFU.