Objective Antibiotic (AB) usage strongly affects microbial intestinal metabolism and thereby impacts human health. Understanding this process and the underlying mechanisms remains a major research ...goal. Accordingly, we conducted the first comparative omic investigation of gut microbial communities in faecal samples taken at multiple time points from an individual subjected to β-lactam therapy. Methods The total (16S rDNA) and active (16S rRNA) microbiota, metagenome, metatranscriptome (mRNAs), metametabolome (high-performance liquid chromatography coupled to electrospray ionisation and quadrupole time-of-flight mass spectrometry) and metaproteome (ultra high performing liquid chromatography coupled to an Orbitrap MS2 instrument UPLC-LTQ Orbitrap-MS/MS) of a patient undergoing AB therapy for 14 days were evaluated. Results Apparently oscillatory population dynamics were observed, with an early reduction in Gram-negative organisms (day 6) and an overall collapse in diversity and possible further colonisation by ‘presumptive’ naturally resistant bacteria (day 11), followed by the re-growth of Gram-positive species (day 14). During this process, the maximum imbalance in the active microbial fraction occurred later (day 14) than the greatest change in the total microbial fraction, which reached a minimum biodiversity and richness on day 11; additionally, major metabolic changes occurred at day 6. Gut bacteria respond to ABs early by activating systems to avoid the antimicrobial effects of the drugs, while ‘presumptively’ attenuating their overall energetic metabolic status and the capacity to transport and metabolise bile acid, cholesterol, hormones and vitamins; host–microbial interactions significantly improved after treatment cessation. Conclusions This proof-of-concept study provides an extensive description of gut microbiota responses to follow-up β-lactam therapy. The results demonstrate that ABs targeting specific pathogenic infections and diseases may alter gut microbial ecology and interactions with host metabolism at a much higher level than previously assumed.
Local ablative therapies (LAT) have shown positive but heterogenous outcomes in the treatment of colorectal liver metastases (CRLM). The aim of this systematic review is to evaluate LAT and compare ...them with surgical resection.
In accordance with PRISMA guidelines, Medline, EMBASE, Cochrane and Web of Science databases were searched for reports published before January 2019. We included papers assessing radiofrequency ablation (RFA), microwave ablation (MWA), cryoablation (CA) and electroporation (IRE) treating resectable CRLM with curative intention. We evaluated LAT related complications and oncological outcomes as tumour progression (LTP), disease-free survival (DFS) and overall survival (OS).
The literature search yielded 6767 records; 20 papers (860 patients) were included. No included studies related mortality with LAT. Median adverse events percentage was 7%: (8% RFA;7% MWA). Median 3y-DFS was 32% (24% RFA; 60% MWA); 5y-DFS was 27%: (18% RFA; 38.5% MWA). Median 3y-OS was 59% (60% RFA; 70% MWA; 34% CA), 5y-OS was 44.5% (43% RFA; 55% MWA; 20% CA).
Surgical resection showed decreased LTP, improved DFS and OS than those reported with LAT, with RFA accounting for reduced 1y-DFS (RR 0.83, 95%CI 0.71–0.98), 3y-DFS (RR 0.5, 95%CI 0.33–0.76), 5y-DFS (RR 0.53, 95%CI 0.28–0.98) and 5y-OS (RR 0.76, 95%CI 0.58–0.98) in comparison with surgical resection.
Low quality evidence suggests that both RFA and MWA seem superior to CA. MWA presents similar adverse events when compared to RFA with a possible increase in DFS and OS. Surgical resection still seems to provide superior DFS and OS in comparison with LAT.
Various parameters have been considered for predicting survival in pancreatic ductal adenocarcinoma. Information about western population is missing. The aim of this study is to assess the ...association between Glucose transporter type 1 (GLUT-1) expression and prognosis for patients with PDAC submitted for surgical resection in a European cohort.
Retrospective analysis of PDAC specimens after pancreatoduodenectomy assessing GLUT-1 expression according to intensity (weak vs strong) and extension (low if < 80% cells were stained, high if > 80%) was performed. Statistical analysis was performed using the exact Fisher test, Student t test or the Mann-Whitney U test. Survival was analysed using the Kaplan-Meier method and compared with the Log-rank test. The differences were considered significant at a two-sided p value of < 0.05. All statistical analyses were performed using SPSS® 23.0 for Windows (SPSS Inc., Chicago, IL, USA).
Our study consisted of 39 patients of which 58.9% presented with weak and 41.1% with strong intensity. The median extension was 90%: 28.2% cases presented with a low extension and 71.8% with a high extension. No significant differences related to intensity were found. The high-extension group showed a higher percentage of T3 PDAC (92.9% vs 63.6%, p = 0.042) and LNR20 (35.7% vs 0%, p = 0.037) as well as shorter disease-free survival (17.58 vs 54.46 months; p = 0.048).
Our findings suggest that GLUT-1 could be related to higher aggressivity in PDAC and could be used as a prognostic marker, identifying patients with a worse response to current therapies who could benefit from more aggressive treatments.
OBJECTIVE:To compare the rates of R0 resection in pancreatoduodenectomy (PD) for pancreatic and periampullary malignant tumors by means of standard (ST-PD) versus artery-first approach (AFA-PD).
...BACKGROUND:Standardized histological examination of PD specimens has shown that most pancreatic resections thought to be R0 resections are R1. “Artery-first approach” is a surgical technique characterized by meticulous dissection of arterial planes and clearing of retropancreatic tissue in an attempt to achieve a higher rate of R0. To date, studies comparing AFA-PD versus ST-PD are retrospective cohort or case-control studies.
METHODS:A multicenter, randomized, controlled trial was conducted in 10 University Hospitals (NCT02803814, ClinicalTrials.gov). Eligible patients were those who presented with pancreatic head adenocarcinoma and periampullary tumors (ampulloma, distal cholangiocarcinoma, duodenal adenocarcinoma). Assignment to each group (ST-PD or AFA-PD) was randomized by blocks and stratified by centers. The primary end-point was the rate of tumor-free resection margins (R0); secondary end-points were postoperative complications and mortality.
RESULTS:One hundred seventy-nine patients were assessed for eligibility and 176 randomized. After exclusions, the final analysis included 75 ST-PD and 78 AFA-PD. R0 resection rates were 77.3% (95% CI68.4–87.4) with ST-PD and 67.9% (95% CI58.3–79.1) with AFA-PD, P=0.194. There were no significant differences in postoperative complication rates, overall 73.3% versus 67.9%, and perioperative mortality 4% versus 6.4%.
CONCLUSIONS:Despite theoretical oncological advantages associated with AFA-PD and evidence coming from low-level studies, this multicenter, randomized, controlled trial has found no difference neither in R0 resection rates nor in postoperative complications in patients undergoing ST-PD versus AFA-PD for pancreatic head adenocarcinoma and other periampullary tumors.
The main antioxidants present in plant extracts-quercetin, β-carotene, gallic acid, ascorbic acid, hydroxybenzoic acid, caffeic acid, catechin and scopoletin-are able to synthesize silver ...nanoparticles when reacting with a Ag NO
solution. The UV-visible absorption spectrum recorded with most of the antioxidants shows the characteristic surface plasmon resonance band of silver nanoparticles. Nanoparticles synthesised with ascorbic, hydroxybenzoic, caffeic, and gallic acids and scopoletin are spherical. Nanoparticles synthesised with quercetin are grouped together to form micellar structures. Nanoparticles synthesised by β-carotene, were triangular and polyhedral forms with truncated corners. Pentagonal nanoparticles were synthesized with catechin. We used Fourier-transform infrared spectroscopy to check that the biomolecules coat the synthesised silver nanoparticles. X-ray powder diffractograms showed the presence of silver, AgO, Ag
O, Ag
O
and Ag
O
. Rod-like structures were obtained with quercetin and gallic acid and cookie-like structures in the nanoparticles obtained with scopoletin, as a consequence of their reactivity with cyanide. This analysis explained the role played by the various agents responsible for the bio-reduction triggered by nanoparticle synthesis in their shape, size and activity. This will facilitate targeted synthesis and the application of biotechnological techniques to optimise the green synthesis of nanoparticles.
Diffuse large B-cell lymphoma patients have a 5% overall risk of central nervous system events (relapse or progression), which account for high morbidity and frequently fatal outcomes,
and shortened ...overall survival of <6 months.
Early diagnosis of central nervous system events is critical for successful treatment and improved prognosis. Identification of patients at risk of central nervous system disease is critical to accurately identify candidates for central nervous system prophylaxis vs.
This report by the Spanish Lymphoma Group (GELTAMO) aims to provide useful guidelines and recommendations for the prevention, diagnosis, and treatment of central nervous system diffuse large B-cell lymphoma patients with, or at risk of, leptomeningeal and/or brain parenchyma lymphoma relapse. A panel of lymphoma experts working on behalf of GELTAMO reviewed all data published on these topics available in PubMed up to May 2016. Recommendations were classified according to the Grading of Recommendations Assessment Development and Evaluation (GRADE) approach.
A practical algorithm based on the proposed recommendations was then developed (Figure 1). Initial discussions among experts were held in May 2014, and final consensus was reached in June 2016. The final manuscript was reviewed by all authors and the Scientific Committee of GELTAMO.
OBJECTIVE:To provide evidence-based recommendations for the management of exocrine pancreatic insufficiency (EPI) after pancreatic surgery.
BACKGROUND:EPI is a common complication after pancreatic ...surgery but there is certain confusion about its frequency, optimal methods of diagnosis, and when and how to treat these patients.
METHODS:Eighteen multidisciplinary reviewers performed a systematic review on 10 predefined questions following the GRADE methodology. Six external expert referees reviewed the retrieved information. Members from Spanish Association of Pancreatology were invited to suggest modifications and voted for the quantification of agreement.
RESULTS:These guidelines analyze the definition of EPI after pancreatic surgery, (one question), its frequency after specific techniques and underlying disease (four questions), its clinical consequences (one question), diagnosis (one question), when and how to treat postsurgical EPI (two questions) and its impact on the quality of life (one question). Eleven statements answering those 10 questions were providedone (9.1%) was rated as a strong recommendation according to GRADE, three (27.3%) as moderate and seven (63.6%) as weak. All statements had strong agreement.
CONCLUSIONS:EPI is a frequent but under-recognized complication of pancreatic surgery. These guidelines provide evidence-based recommendations for the definition, diagnosis, and management of EPI after pancreatic surgery.
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