Background Catheter-related bloodstream infection (CRBSI) is a life-threatening complication of parenteral nutrition. Therefore, optimal management, ideally with catheter salvage, is required to maintain long-term venous access. Objectives We aimed to evaluate successful catheter salvage rates in patients on home parenteral nutrition (HPN). Methods Studies were retrieved from medical databases, conference proceedings, and article reference lists. Data were collected relating to clinical outcomes of 3 treatments: systemic antibiotics, antimicrobial lock therapy (ALT), and catheter exchange. ORs and 95% CIs were calculated from a mixed logistic effects model. Results From 10,036 identified publications, 28 met the inclusion criteria (22 cohort studies, 5 case-control studies, and 1 randomized clinical trial), resulting in a total of 4911 CRBSIs. To achieve successful catheter salvage, the addition of an antimicrobial lock solution was superior to systemic antibiotics alone (OR: 1.75; 95% CI: 1.21, 2.53; P = 0.003). Recurrence of infection was less common in studies that used ALT than in those that used systemic antibiotics alone (OR: 0.26; 95% CI: 0.11, 0.61; P = 0.002). The catheter exchange group was excluded from multilevel regression analysis because only 1 included study applied this treatment. Successful salvage rates were highest for coagulase-negative staphylococci, followed by Gram-negative rods and Staphylococcus aureus . Conclusions The addition of an antimicrobial lock solution seems beneficial for successful catheter salvage in HPN-dependent patients with a CRBSI. Future prospective randomized studies should identify the most effective and pathogen-specific strategy. This review was registered at www.crd.york.ac.uk/PROSPERO as CRD42018102959.
The limitations of current cancer treatments have stimulated the application of nanotechnology to develop more effective and safer cancer therapies. Remarkable progress has been made in the development of nanomedicine to overcome issues associated with conventional cancer treatment, including low drug solubility, insufficient targeting, and drug resistance. The modulation of nanoparticles allows the improvement of drug pharmacokinetics, leading to improved targeting and reduced side effects. In addition, nanoparticles can be conjugated to ligands that specifically target cancer cells. Furthermore, strategies that exploit tumor characteristics to locally trigger drug release have shown to increase targeted drug delivery. However, although some clinical successes have been achieved, most nanomedicines fail to reach the clinic. Factors that hinder clinical translation vary from the complexity of design, incomplete understanding of biological mechanisms, and high demands during the manufacturing process. Clinical translation might be improved by combining knowledge from different disciplines such as cell biology, chemistry, and tumor pathophysiology. An increased understanding on how nanoparticle modifications affect biological systems is pivotal to improve design, eventually aiding development of more effective nanomedicines. This review summarizes the key successes that have been made in nanomedicine, including improved drug delivery and release by polymeric nanoparticles as well as the introduction of strategies that overcome drug resistance. In addition, the application of nanomedicine in immunotherapy is discussed, and several remaining challenges addressed.
dynamic interactions between tumor cells and immune cells promote the initiation, progression, metastasis and therapy-resistance of cancer. With respect to immunotherapy, immune cell populations such as cytotoxic cd8 + T-cells, cd56 + nK cells and myeloid phagocytic cells play decisive roles. from an imaging perspective, the immune system displays unique challenges, which have implications for the design and performance of studies. The immune system comprises highly mobile cells that undergo distinct phases of development and activation. These cells circulate through several compartments during their active life span and accumulate in rather limited numbers in cancer lesion, where their effector phenotype further diversifies. Given these features, accurate evaluation of the tumor microenvironment and its cellular components during anti-cancer immunotherapy is challenging. In-vivo imaging currently offers quantitative and sensitive modalities that exploit long-lived tracers to interrogate, e.g. distinct immune cell populations, metabolic phenotypes, specific targets relevant for therapy or critical for their effector function. This review provides a comprehensive overview of current status for in-vivo imaging tumor-infiltrating immune cell populations, focusing on lymphocytes, nK cells and myeloid phagocytic cells, with emphasis on clinical translation.
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