Analysing blood from intraosseous access: a systematic review

Intraosseous (IO) access is used widely as an optional vascular route for critically ill patients. It is still unclear whether the IO access can be used as a source for emergency blood samples. The aim of this study was to systematically review the existing literature on the usability of IO blood samples for analysing the parameters relevant to emergency care. We performed a data search from the Medline and Embase databases, the Cochrane Library and the Clinical trials registry. Animal studies and studies with healthy and ill adults and children were included in the search. The data were collected and reported following the PRISMA guidelines. The PROSPERO database registration number of this review is CRD42017064194. We found 27 studies comparing the blood samples from the IO space with arterial or venous samples, but only three of them followed the recommended guidelines for method comparison studies. The study populations were heterogeneous, and the sample sizes were relatively small (14, 17 and 20 individuals) in the three studies. The results of specific laboratory parameters were scarce and discordant. The evidence on the agreement between IO and arterial and venous samples is still weak. Existing studies with healthy volunteers and animal models provide important insight into the analyses of IO samples, but more evidence, especially from haemodynamically unstable patients, is needed for wider implementation of IO blood sampling in critically ill patients. Correspondence to Milla Jousi, MD, FinnHEMS Research and Development Unit, Lentäjäntie 3, 01530 Vantaa, Finland Tel: +358 50 586 9658; fax: +358 9 8565 7339; e-mail: milla.jousi@hus.fi Received March 29, 2018 Accepted July 31, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Molecular Subtypes of Bladder Cancer

Abstract

Purpose of Review

Recent whole genome characterizations of primary human bladder cancers revealed that they can be grouped into "intrinsic" basal and luminal molecular subtypes. Here, we provide an overview of the subtypes and discuss their biological and clinical properties.

Recent Findings

Basal cancers are characterized by advanced stage and metastatic disease at presentation. They tend to be enriched with squamous and small cell/neuroendocrine features and inactivating mutations and deletions of TP53 and RB1. Basal cancers can be divided into "epithelial" and "mesenchymal" (also known as "claudin low") subsets, and a portion of the latter form a "neuroendocrine/neuronal" subset that is associated with particularly poor survival. Luminal cancers are often enriched with papillary histopathological features and activating mutations in FGFR3, and they can also be divided into additional subsets based on differential stromal cell infiltration, relative genomic instability, and high- versus low-level expression of carcinoma in situ (CIS) gene expression signatures. Importantly, the bladder cancer molecular subtypes display differential sensitivities to neoadjuvant chemotherapy and immune checkpoint blockade, and preliminary data also suggest that they respond differently to radiation with or without hypoxia modulation. Ongoing studies are investigating the relevance of the molecular subtypes to the bladder cancer histopathological variants and to upper tract urothelial cancer.

Summary

The bladder cancer molecular subtypes were associated with different prognoses and responses to conventional and targeted therapies in retrospective studies. If validated in prospective studies, molecular subtyping will be integrated into bladder cancer clinical management.

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Triple-Negative Breast Cancers: Systematic Review of the Literature on Molecular and Clinical Features with a Focus on Treatment with Innovative Drugs

Abstract

Purpose of Review

Triple-negative breast cancer (TNBC) accounts for 15–20% of diagnosed breast tumours, with higher incidence in young and African-American women, and it is frequently associated with BRCA germline mutations. Chemotherapy is the only well-established therapeutic option in both early- and advanced-stages of the disease. TNBC tumours relapse earlier after standard anthracycline- and/or taxane-based chemotherapy treatments, generally within 1–3 years after the diagnosis, and often develop visceral metastases, representing the subtype with a worse prognosis among all breast cancers. In the present review, we will provide an updated overview of the available results of recent clinical trials for this disease and we will describe the implications of the known molecular pathways representing novel targets for development of future therapies for TNBC patients.

Recent Findings

Over the past decade, the advent of gene expression micro-array technology has led to the identification of different actionable targets including various genomic alterations, androgen receptor, PARP, PI3K, VEGF and other proteins of the angiogenic pathway. Thus, novel targeted drugs have been tested in clinical trials reporting promising results in specific TNBC molecular subgroups.

Summary

Although cytotoxic chemotherapy remains the mainstay of treatment for TNBC patients, the identification of novel 'drugable' targets and pathways for developing personalized treatments represents a promising investigational approach in the management of the TNBC subtype.

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Cancers, Vol. 10, Pages 275: The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation

Cancers, Vol. 10, Pages 275: The Impact of p53 Dysfunction in ATR Inhibitor Cytotoxicity and Chemo- and Radiosensitisation

Cancers doi: 10.3390/cancers10080275

Authors: Fiona K. Middleton John R. Pollard Nicola J. Curtin

Rad3-related kinase (ATR) signals replication stress and DNA damage to S and G2 arrest and promotes DNA repair. Mutations in p53, critical for G1 checkpoint control, are common in cancer and predicted to confer vulnerability to ATR inhibitors. Reported data on the impact of p53 status are variable possibly because of the use of unmatched cells and surrogate endpoints of survival. The cytotoxicity of VE-821 alone and its ability to potentiate radiation and gemcitabine cytotoxicity was determined in isogenic and unmatched p53 wild-type (wt) and null/mutant cells, as well as immortalised nonmalignant MCF10 (immortalised non-neoplastic) cells, by colony-forming assay. The effect on cell cycle checkpoints was determined by flow cytometry. The isogenic p53 defective cells were not more sensitive to VE-821 alone. Defective p53 consistently conferred greater chemo- and radiosensitisation, particularly at high dose levels in isogenic cells but not unmatched cells. VE-821 did not sensitise MCF10 cells. We conclude that p53 status is just one factor contributing to chemo- and radiosensitisation by ATR inhibition, the lack of chemo- or radiosensitisation in the noncancerous cells suggests an element of tumour-specificity that warrants further investigation. The greater sensitisation at high-dose irradiation suggests that ATR inhibitors may be most effective with hypofractionated radiotherapy.

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Impact of Recent Studies for the Treatment of Intracerebral Hemorrhage

Abstract

Purpose of Review

The present review will cover most recent and important studies on acute treatment of intracerebral hemorrhage (ICH).

Recent Findings

Overly pessimistic prognostication in ICH may deny meaningful recovery achieved by specialized neurocritical care. Hematoma enlargement represents the most important target of acute ICH care, which is reduced by aggressive blood pressure management (targeting a systolic blood pressure of 140 mmHg) and appropriate hemostatic treatment especially in anticoagulation-associated ICH (INR reversal using prothrombin complex concentrates, eventually idarucizumab, andexanet, or tranexamic acid). Surgical treatment strategies involving fibrinolytics either used for direct hematoma lysis or used for intraventricular clot removal with/without additional lumbar drainage show great promise. Further novel treatment strategies are underway and need validation or evaluation strongly warranting well-designed future ICH research.

Summary

Several randomized and large-sized observational studies have considerably expanded the field and the evidence on how to treat acute ICH patients. Yet, the one breakthrough intervention to improve functional outcome is still missing, though various treatment concepts possibly interacting with one another have been evaluated and such treatment bundle may improve patients' outcome.

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Book Review—Practical cytopathology: a diagnostic approach to fine needle aspiration biopsy, 1st edition

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Book Review—Diagnostic pathology: bone, 2nd edition

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