The role of exosomes in metastasis and progression of melanoma

The mechanisms of melanoma metastasis have been the subject of extensive research for decades. Improved diagnostic and therapeutic strategies are of increasing importance for the treatment of melanoma due to its high burden of mortality in the advanced stages of the disease. Intercellular communication is a critical event for the progression of cancer. Collective evidence suggests that exosomes, small extracellular membrane vesicles released by the cells, are important facilitators of intercellular communication between the cells and the surrounding environment. Although the emerging field of exosomes is rapidly gaining traction in the scientific community, there is limited knowledge regarding the role of exosomes in melanoma. This review discusses the multifaceted role of melanoma-derived exosomes in promoting the process of metastasis by modulating the invasive and angiogenic capacity of malignant cells. The future implications of exosome research and the therapeutic potential of exosomes are also discussed.     

Stability and change in family psychosocial risk over 6 months in pediatric cancer and its association with medical and psychosocial healthcare utilization

Purpose: Family psychosocial risk in pediatric oncology can be assessed using the Psychosocial Assessment Tool (PAT), a brief parent report screener based on the Pediatric Psychosocial Preventative Health Model (PPPHM; universal, targeted, and clinical). However, little is known about risk over the course of treatment and its association with medical and psychosocial healthcare utilization. Methods: Primary caregivers of children with cancer participated in this prospective multisite investigation, completing the PAT at diagnosis (T1; n = 396) and 6 months later (T2; n = 304). Healthcare utilization data were extracted from electronic health records. Results: The distribution of PPPHM risk levels at T1 and T2 was highly consistent for the samples. Two‐thirds of families remained at the same level of risk, 18% decreased and 16% increased risk level. Risk was not related to sociodemographic or treatment variables. The PAT risk score correlated with psychosocial contacts over the 6‐month period. Conclusions: Although the majority of families reported universal (low) risk on the PAT and were stable in their risk level over 6 months, reassessing risk is helpful in identifying those families who report higher level of risk during treatment than at diagnosis. PAT scores were related to psychosocial services that are provided to most but not all families and could be tailored more specifically to match risk and delivery of evidence‐based care.     

Neonatal weight loss and gain patterns in caesarean section born infants: integrative systematic review

There is evidence that caesarean section delivery can impact on neonatal weight loss and weight gain patterns in the first 5 days of life. We conducted an integrative systematic review to examine the association of mode of delivery on early neonatal weight loss. Pubmed, Cumulative Index to Nursing and Allied Health Literature, Web of Science, Excerpta Medica dataBASE, and Medical Literature Analysis and Retrieval System Online were searched for relevant papers published before June 2019. Reference lists from the relevant papers were then backwards and forwards searched. As neonatal weight loss was reported in different formats, a meta‐analysis could not be carried out. Most studies did not distinguish between elective and emergency caesarean sections or instrumental and nonassisted vaginal deliveries. Seven papers were included. All papers except one found that caesarean section was associated with higher weight loss in the early days of life. Two papers presented data from studies on babies followed up to 1 month. One study found that on day 25, babies born by caesarean section had significantly higher weight gain than those born vaginally, while another found that by day 28, babies born vaginally gained more weight per day (11.9 g/kg/day) than those born by caesarean section (10.9 g/kg/day; p = .02). Overall, infants born by caesarean section lost more weight than those born vaginally, but due to the small number of studies included, more are needed to look at this difference and why it may occur. This discrepancy in weight between the two groups may be corrected over time, but future studies will need larger sample sizes and longer follow‐up periods to examine this.     

Management of recurrent urinary tract infections in adults

Many women will experience one or more urinary tract infection (UTI) during their life. The most unfortunate will have many. Men presenting with infections, and women with recurrent episodes, require further investigation. A diagnosis of a UTI is often based on a typical spectrum of symptoms, with confirmatory urine cultures lagging a few days behind. Unfortunately, symptoms of a UTI may not be typical, and other conditions can manifest similarly. Treatment of UTI with antibiotics is usually required, but there is increasing awareness of the need for antimicrobial stewardship to avoid the misuse and overuse of antibiotics, even as patients are increasingly reluctant to take them. Recurrent UTI can cause significant morbidity and disruption to daily activities yet investigations rarely demonstrate a reversible cause. There are a host of different antibiotic and non-antibiotic interventions that aim to lower the risk of further infections. However, these are not reliably effective, bring side effects of their own and are often proposed to this desperate population of patients on the back of weak evidence of efficacy.     

Intra-arterial administration of cell-based biological agents for ischemic stroke therapy

Introduction: Ischemic stroke is becoming a primary cause of disability and death worldwide. To date, therapeutic options remain limited focusing on mechanical thrombolysis or administration of thrombolytic agents. However, these therapies do not promote neuroprotection and neuro-restoration of the ischemic area of the brain.

Areas covered: This review highlights the option of minimal invasive, intra-arterial, administration of biological agents for stroke therapy. The authors provide an update of all available studies, discuss issues that influence outcomes and describe future perspectives which aim to improve clinical outcomes. New therapeutic options based on cellular and molecular interactions following an ischemic brain event, will be highlighted.

Expert opinion: Intra-arterial administration of biological agents during trans-catheter thrombolysis or thrombectomy could limit neuronal cell death and facilitate regeneration or neurogenesis following ischemic brain injury. Despite the initial progress, further meticulous studies are needed in order to establish the clinical use of stem cell-induced neuroprotection and neuroregeneration.     

Fragmentation of care as a barrier to optimal ESKD management

Caring for patients with end-stage kidney disease (ESKD) in the United States is challenging, due in part to the complex epidemiology of the disease's progression as well as the ways in which care is delivered. As CKD progresses toward ESKD, the number of comorbidities increases and care involves multiple healthcare providers from multiple subspecialties. This occurs in the context of a fragmented US healthcare delivery system that is traditionally siloed by provider specialty, organization, as well as systems of payment and administration. This article describes the role of care fragmentation in the delivery of optimal ESKD care and identifies research gaps in the evidence across the continuum of care. We then consider the impact of care fragmentation on ESKD care from the patient and health system perspectives and explore opportunities for system-level interventions aimed at improving care for patients with ESKD.     

An off-the-shelf plasma-based material to prevent pacemaker pocket infection

Bacterial infection of subcutaneous “pockets” housing cardiovascular implantable electronic devices is a significant clinical complication. In this study, pacemakers encapsulated in a blood plasma-based material (PBM) composited with antibiotics were investigated for use as prophylactics against such infections. PBMs, which are made from pooled allogeneic plasma and platelets, are off-the-shelf biomaterials that can be manufactured in the form of complex 3D shapes, extrudable putties, or injectable pastes. In vitro studies with PBM pastes formulated with rifampicin and minocycline demonstrated antibiotic release over 6 days, activity against Escherichia coli, and reduced cytotoxic effects of the antibiotics on fibroblasts. The materials were also evaluated in vivo in a rabbit model in which pacemaker pockets were inoculated with methicillin-resistant Staphylococcus aureus (S. aureus) strain and examined 1 week later. The pockets containing the pacemaker plus S. aureus were grossly purulent and culture positive, whereas pockets into which PBM with antibiotics were injected around the pacemaker were free of purulence and culture negative (p < 0.001). None of the pockets into which PBM without antibiotics were placed demonstrated purulence, but 60% were culture positive. These results demonstrate the potential of PBMs to deliver antibiotics to diminish the incidence of pocket infections for pacemakers and other implantable devices.