8q24.21 is a frequently amplified genomic region in colorectal cancer (CRC). This region is often referred to as a ‘gene desert’ due to lack of any important protein-coding genes, highlighting the ...potential role of noncoding RNAs, including long noncoding RNAs (lncRNAs) located around the proto-oncogeneMYC. In this study, we have firstly evaluated the clinical significance of altered expression of lncRNAs mapped to this genomic locus in CRC.
A total of 300 tissues, including 280 CRC and 20 adjacent normal mucosa specimens were evaluated for the expression of 12 lncRNAs using qRT-PCR assays. We analyzed the associations between lncRNA expression and various clinicopathological features, as well as with recurrence free survival (RFS) and overall survival (OS) in two independent cohorts.
The expression of CCAT1, CCAT1-L, CCAT2, PVT1, and CASC19 were elevated in cancer tissues (P=0.039, <0.001, 0.018, <0.001, 0.002, respectively). Among these, high expression of CCAT1 and CCAT2 was significantly associated with poor RFS (P=0.049 and 0.022, respectively) and OS (P=0.028 and 0.015, respectively). These results were validated in an independent patient cohort, in which combined expression of CCAT1 and CCAT2 expression was significantly associated with a poor RFS (HR:2.60, 95% confidence interval CI: 1.04–6.06,P=0.042) and a poor OS (HR:8.38, 95%CI: 2.68–37.0,P<0.001). We established a RFS prediction model which revealed that combined expression of CCAT1, CCAT2, and carcinoembryonic antigen was a significant determinant for efficiently predicting RFS in stage II (P=0.034) and stage III (P=0.001) CRC patients.
Several lncRNAs located in 8q24.21 locus are highly over-expressed in CRC. High expression of CCAT1 and CCAT2 significantly associates with poor RFS and OS. The expression of these two lncRNAs independently, or in combination, serves as important prognostic biomarkers in CRC.
Early liver transplantation (LT) in European centers reportedly improved survival in patients with severe alcoholic hepatitis (AH) not responding to medical therapy. Our aim was to determine if a ...strategy of early LT for severe AH could be applied successfully in the United States. We reviewed 111 patients with severe AH at our center from January 2012 to January 2015. The primary end point was mortality at 6 months or early LT, with a secondary end point of alcohol relapse after LT. Survival was compared between those receiving early LT and matched patients who did not. Using a process similar to the European trial, 94 patients with severe AH not responding to medical therapy were evaluated for early LT. Overall, 9 (9.6%) candidates with favorable psychosocial profiles underwent early LT, comprising 3% of all adult LT during the study period. The 6‐month survival rate was higher among those receiving early LT compared with matched controls (89% vs 11%, p<0.001). Eight recipients are alive at a median of 735 days with 1 alcohol relapse. Early LT for severe AH can achieve excellent clinical outcomes with low impact on the donor pool and low rates of alcohol relapse in highly selected patients in the United States.
In this single‐center experience with the strategy of early liver transplantation for severe alcoholic hepatitis in the United States, clinical outcomes are excellent, with increased six‐month survival, low impact on the donor pool, and low rates of alcohol relapse in highly selected recipients. See the editorial from Lucey and Rice on page 739.
Circulating microRNAs (miRNAs) are attracting major interest as potential non-invasive biomarkers for colorectal cancer (CRC). This study aimed to identify a novel serum miRNA biomarker for the early ...detection and/or evaluating prognosis of CRC patients.
Comprehensive miRNA array analysis was carried out using serum samples from patients with colorectal neoplasia and healthy controls. Next, to verify whether the candidate miRNA possessed a secretory potential, we screened miRNA expression levels in culture medium from 2 CRC cell lines, followed by serum analysis from 12 stage IV CRC, 12 adenoma, and 12 control subjects. Thereafter, we validated expression of candidate miRNAs in 179 primary CRC tissues, as well as serum samples from an independent cohort of 211 CRCs, 56 adenomas, and 57 control subjects.
Through microarray analysis, we identified significantly higher levels of miRNA-1290 (miR-1290) in serum from patients with colorectal adenomas and cancers. We verified miR-1290 overexpression in serum of CRC patients in a training cohort. In the validation cohort, serum miR-1290 levels were significantly up-regulated in patients with colorectal adenomas (P < 0.0001) and cancers (P < 0.0001). Serum miR-1290 levels could robustly distinguish adenoma area under the curve (AUC) = 0.718 and CRC patients (AUC = 0.830) from normal subjects. High miR-1290 expression in serum and tissue was significantly associated with tumor aggressiveness and poor prognosis. Moreover, serum miR-1290 levels were an independent prognostic factor hazard ratio (HR) = 4.51; 95% confidence interval (CI) = 1.23–23.69; P = 0.0096 and an independent predictor for tumor recurrence (hazard ratio = 3.92; 95% confidence interval = 1.11–25.14; P = 0.032) in CRC.
Serum miR-1290 is a novel biomarker for early detection, recurrence, and prognosis in CRC.
Although there have been no cases of serotype 2 wild poliovirus for more than 20 years, transmission of serotype 2 vaccine-derived poliovirus (VDPV2) and associated paralytic cases in several ...continents represent a threat to eradication. The withdrawal of the serotype 2 component of oral poliovirus vaccine (OPV2) was implemented in April 2016 to stop VDPV2 emergence and secure eradication of all serotype 2 poliovirus. Globally, children born after this date have limited immunity to prevent transmission. Using a statistical model, we estimated the emergence date and source of VDPV2s detected between May 2016 and November 2019. Outbreak response campaigns with monovalent OPV2 are the only available method to induce immunity to prevent transmission. Yet our analysis shows that using monovalent OPV2 is generating more paralytic VDPV2 outbreaks with the potential for establishing endemic transmission. A novel OPV2, for which two candidates are currently in clinical trials, is urgently required, together with a contingency strategy if this vaccine does not materialize or perform as anticipated.
Brain abscess: An overview Muzumdar, Dattatraya; Jhawar, Sukhdeep; Goel, A
International journal of surgery (London, England),
01/2011, Letnik:
9, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Abstract Intracranial abscess is a formidable entity. Despite the advent of newer antibiotics and surgical strategies, the overall outcome and quality of life issues in brain abscess patients still ...remain a continuous challenge for the neurosurgical community. It is a direct interplay between the virulence of the offending microorganism and the immune response of the host. An analysis of our experience in the 289 cases of surgically treated pyogenic brain abscess is presented along with an overview of intra-cranial abscess of varied etiology and in different locations . The etiology, pathogenesis, radiological advances and treatment modalities of brain abscess are discussed in light of current literature.
Native tricuspid valve endocarditis is quite rare without any predisposing factors and poses a diagnostic challenge because of fewer cardiac symptoms and lesser peripheral manifestations. This is a ...case report of a 25-year-old female who presented with high-grade fever, dry cough, decreased appetite, and weight loss for 1 month with no history of intravenous drug use or evidence of underlying cardiac abnormality and was diagnosed with native tricuspid valve endocarditis.
Summary
Background
Little is known about the role of the microbiome in primary sclerosing cholangitis.
Aim
To explore the mucosa‐associated microbiota in primary sclerosing cholangitis (PSC) patients ...across different locations in the gut, and to compare it with inflammatory bowel disease (IBD)‐only patients and healthy controls.
Methods
Biopsies from the terminal ileum, right colon, and left colon were collected from patients and healthy controls undergoing colonoscopy. Microbiota profiling using bacterial 16S rRNA sequencing was performed on all biopsies.
Results
Forty‐four patients were recruited: 20 with PSC (19 with PSC‐IBD and one with PSC‐only), 15 with IBD‐only and nine healthy controls. The overall microbiome profile was similar throughout different locations in the gut. No differences in the global microbiome profile were found. However, we observed significant PSC‐associated enrichment in Barnesiellaceae at the family level, and in Blautia and an unidentified Barnesiellaceae at the genus level. At the operational taxa unit level, most shifts in PSC were observed in Clostridiales and Bacteroidales orders, with approximately 86% of shifts occurring within the former order.
Conclusions
The overall microbiota profile was similar across multiple locations in the gut from the same individual regardless of disease status. In this study, the mucosa associated‐microbiota of patients with primary sclerosing cholangitis was characterised by enrichment of Blautia and Barnesiellaceae and by major shifts in operational taxa units within Clostridiales order.
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