The Prognostic Role of Circulating Tumor Cells (CTCs) in Lung Cancer

Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include “liquid biopsies” through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting

Acute Liver Failure Due To Amoxicillin and Amoxicillin/Clavulanate

The aim of our study is to report upon the presentation of two patients with life-threatening acute liver failure (ALF) due to amoxicillin and amoxicillin/clavulanate. A 59-year-old, Caucasian male presented with ALF 34 days after receiving amoxicillin/clavulanate. Despite aggressive supportive care, he died on hospital day 10. A 42-year-old, Caucasian female presented with ALF 21 days after receiving amoxicillin. She underwent successful liver transplantation on hospital day 19. In both cases, all competing causes of ALF had been excluded, liver pathology was consistent with drug-induced hepatitis, and cases were deemed “definite/highly probable” using causality assessment. Amongst 14 prior ALF/death cases due to amoxicillin/clavulanate, the mean age (62 years), male predominance (57%), and mean delay from drug cessation to presentation (17 days) is similar to what has been reported in patients with self-limited cholestatic hepatitis. Acute liver failure is a rare manifestation of amoxicillin and amoxicillin/clavulanate hepatotoxicity with no obvious clinical features at presentation portending a poor prognosis. Early transfer of patients with severe drug-induced hepatotoxicity (i.e., encephalopathy or coagulopathy) to a transplant center is recommended due to their poor likelihood of recovery.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44436/1/10620_2005_Article_2938.pd

Identification of novel risk loci, causal insights, and heritable risk for Parkinson's disease: a meta-analysis of genome-wide association studies

Background Genome-wide association studies (GWAS) in Parkinson's disease have increased the scope of biological knowledge about the disease over the past decade. We aimed to use the largest aggregate of GWAS data to identify novel risk loci and gain further insight into the causes of Parkinson's disease. Methods We did a meta-analysis of 17 datasets from Parkinson's disease GWAS available from European ancestry samples to nominate novel loci for disease risk. These datasets incorporated all available data. We then used these data to estimate heritable risk and develop predictive models of this heritability. We also used large gene expression and methylation resources to examine possible functional consequences as well as tissue, cell type, and biological pathway enrichments for the identified risk factors. Additionally, we examined shared genetic risk between Parkinson's disease and other phenotypes of interest via genetic correlations followed by Mendelian randomisation. Findings Between Oct 1, 2017, and Aug 9, 2018, we analysed 7·8 million single nucleotide polymorphisms in 37 688 cases, 18 618 UK Biobank proxy-cases (ie, individuals who do not have Parkinson's disease but have a first degree relative that does), and 1·4 million controls. We identified 90 independent genome-wide significant risk signals across 78 genomic regions, including 38 novel independent risk signals in 37 loci. These 90 variants explained 16–36% of the heritable risk of Parkinson's disease depending on prevalence. Integrating methylation and expression data within a Mendelian randomisation framework identified putatively associated genes at 70 risk signals underlying GWAS loci for follow-up functional studies. Tissue-specific expression enrichment analyses suggested Parkinson's disease loci were heavily brain-enriched, with specific neuronal cell types being implicated from single cell data. We found significant genetic correlations with brain volumes (false discovery rate-adjusted p=0·0035 for intracranial volume, p=0·024 for putamen volume), smoking status (p=0·024), and educational attainment (p=0·038). Mendelian randomisation between cognitive performance and Parkinson's disease risk showed a robust association (p=8·00 × 10−7). Interpretation These data provide the most comprehensive survey of genetic risk within Parkinson's disease to date, to the best of our knowledge, by revealing many additional Parkinson's disease risk loci, providing a biological context for these risk factors, and showing that a considerable genetic component of this disease remains unidentified. These associations derived from European ancestry datasets will need to be followed-up with more diverse data. Funding The National Institute on Aging at the National Institutes of Health (USA), The Michael J Fox Foundation, and The Parkinson's Foundation (see appendix for full list of funding sources)

Investigation of Factors Involved in Metastatic Prostate Cancer

Metastatic prostate cancer remains a significant issue for both Urologists who treat the condition and patients afflicted with the disease. Whilst localized disease is able to be effectively treated via several modalities, metastatic disease remains incurable and produces significant morbidity during its inevitable progression to castrate resistance and ultimately death. Whilst many candidate pathways have been identified as playing a role in this stage of the disease, many questions remain unanswered. Recently the Kallikrein related protease family of serine proteases (of which Prostate Specific Antigen or PSA is the best known member) have been implicated as playing a role in the development of osteoblastic bone metastases in prostate cancer. Another group of pathways collectively known as the Wnt Pathways have also recently been implicated in the development, progression and metastatic phases of prostate cancer. These candidates were therefore selected for further investigation using in vivo and in vitro models of prostate cancer and metastasis as well as clinical specimens. Through this process PITX2, a Wnt pathway associated developmental gene was identified as a novel candidate highly expressed in the metastatic phase of prostate cancer compared to benign or localized disease (~13000 fold increase in expression from normal prostate at mRNA level with this pattern being maintained at the protein level on immunohistochemical staining of clinical tissue samples). It was also found to be responsible for enhancing cellular motility and homing of prostate cancer cells toward bone cells and potentially in the development of castrate resistant disease in in vitro experimental models. This previously unidentified factor appears to play a role as a master integrator of several previously implicated growth factor and chemokine pathways in promoting the metastatic phase of prostate cancer. PITX2 may therefore provide a novel biomarker and therapeutic target for metastatic prostate cancer and as such may prove to be a significant new discovery in the ongoing battle against this significant male cancer

Editorial comment

The authors present a robust single-surgeon series of RARP performed using an EP approach. The study focuses on complications, and the authors are to be applauded for using the rigorous Martin-Donat criteria to collect, analyze, and present their data.1,2 In highly experienced hands, it appears that this technique results in morbidity that compares favorably with the much more common TP approach. Specifically, the overall rate of any complication was 8.45%, with lymphoceles, bladder neck contracture, anastomotic leaks, and transfusions all well under 2%..

Prostate cancer organoids: a potential new tool for testing drug sensitivity [Editorial]

Recent technical advances have enabled for the first time, reliable in vitro culture of prostate cancer samples as prostate cancer organoids. This breakthrough provides the significant possibility of high throughput drug screening covering the spectrum of prostate cancer phenotypes seen clinically. These advances will enable precision medicine to become a reality, allowing patient samples to be screened for effective therapeutics ex vivo, with tailoring of treatments specific to that individual. This will hopefully lead to enhanced clinical outcomes, avoid morbidity due to ineffective therapies and improve the quality of life in men with advanced prostate cancer

Sulla poesia in dialetto di Manlio Malabotta

Profilo della poesia in dialetto triestino del grande collezionista d’arte Manlio Malabotta che pubblicò quasi tutte le sue raccolte presso Vanni Scheiwiller