Despite concerns regarding the environmental impacts of microplastics, knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we utilize an ...optimized enzymatic digestion methodology, previously developed for zooplankton, to explore whether synthetic particles could be isolated from marine turtle ingesta. We report the presence of synthetic particles in every turtle subjected to investigation (n = 102) which included individuals from all seven species of marine turtle, sampled from three ocean basins (Atlantic ATL: n = 30, four species; Mediterranean (MED): n = 56, two species; Pacific (PAC): n = 16, five species). Most particles (n = 811) were fibres (ATL: 77.1% MED: 85.3% PAC: 64.8%) with blue and black being the dominant colours. In lesser quantities were fragments (ATL: 22.9%: MED: 14.7% PAC: 20.2%) and microbeads (4.8%; PAC only; to our knowledge the first isolation of microbeads from marine megavertebrates). Fourier transform infrared spectroscopy (FT‐IR) of a subsample of particles (n = 169) showed a range of synthetic materials such as elastomers (MED: 61.2%; PAC: 3.4%), thermoplastics (ATL: 36.8%: MED: 20.7% PAC: 27.7%) and synthetic regenerated cellulosic fibres (SRCF; ATL: 63.2%: MED: 5.8% PAC: 68.9%). Synthetic particles being isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. These include exposure from polluted seawater and sediments and/or additional trophic transfer from contaminated prey/forage items. We assess the likelihood that microplastic ingestion presents a significant conservation problem at current levels compared to other anthropogenic threats.
Knowledge of the incidence and levels of synthetic particles in large marine vertebrates is lacking. Here, we explore whether synthetic particles could be isolated from marine turtle ingesta and report the presence in every turtle subjected to investigation including individuals from all the seven species of marine turtle, sampled from three ocean basins. Most particles were fibres in lesser quantities were fragments/microbeads and were a range of synthetic materials. Synthetic particles isolated from species occupying different trophic levels suggest the possibility of multiple ingestion pathways. We assess the likelihood this presents a significant conservation problem at current levels.
Background
The effects of hospital volume on in-hospital mortality after esophageal resection are disputed in the literature. We sought to analyze treatment effects in patient subpopulations that ...undergo esophagectomy for cancer based on hospital volume.
Methods
We performed a retrospective analysis of the Nationwide Inpatient Sample from 1998 to 2011. Patients who underwent open or laparoscopic transhiatal and transthoracic esophageal resection were identified using ICD-9 codes. Patients <18 years and those with peritoneal disease were excluded. Multivariate logistic regression analyses were used with mortality as the independent variable to evaluate the effect of low (<6), intermediate (6–19), and high (
≥
20) hospital volume of esophagectomies. These analyses were repeated in different subsets of patients to determine whether hospital volume affected mortality depending on the subpopulation evaluated. Subgroups were created depending on age, race, gender, operative approach, comorbidities, and tumor pathology.
Results
A total of 23,751 patients were included. The overall perioperative mortality rate was 7.7 % (low volume: 11.4 %; intermediate volume: 8.39 %, high volume: 4.01 %), and multivariate analysis revealed that high hospital volume had a protective effect (OR 0.54, 95 % CI 0.45–0.65). On subgroup analyses for low- and intermediate-volume hospitals, mortality was uniformly elevated for the subpopulations when comparing to high-volume hospitals (
p
< 0.05). There was no difference in mortality between low- and medium-volume hospitals and between subgroups.
Conclusion
No lower mortality risk subgroup could be identified in this nationwide collective. This analysis emphasizes that perioperative mortality after esophagectomy for cancer is lower in high-volume hospitals.
Marine turtles utilise terrestrial and marine habitats and several aspects of their life history are tied to environmental features that are altering due to rapid climate change. We overview the ...likely impacts of climate change on the biology of these species, which are likely centred upon the thermal ecology of this taxonomic group. Then, focusing in detail on three decades of research on the loggerhead turtle (Caretta caretta L.), we describe how much progress has been made to date and how future experimental and ecological focus should be directed. Key questions include: what are the current hatchling sex ratios from which to measure future climate-induced changes? What are wild adult sex ratios and how many males are necessary to maintain a fertile and productive population? How will climate change affect turtles in terms of their distribution?
Detecting mutations in the plasma of patients with solid tumors is becoming a valuable method of diagnosing and monitoring cancer. The TERT promoter is mutated at high frequencies in multiple cancer ...types, most commonly at positions -124 and -146 (designated C228T and C250T, respectively). Detection of these mutations has been challenging because of the high GC content of this region (approximately 80%). We describe development of novel probe-based droplet digital PCR assays that specifically detect and quantify these two mutations, along with the less common 242-243 CC>TT mutation, and demonstrate their application using human tumor and plasma samples from melanoma patients. Assay designs and running conditions were optimized using cancer cell line genomic DNAs with the C228T or C250T mutations. The limits of detection were 0.062% and 0.051% mutant allele fraction for the C228T and C250T assays, respectively. Concordance of 100% was observed between droplet digital PCR and sequencing-based orthogonal methods in the detection of TERT mutant DNA in 32 formalin-fixed, paraffin-embedded melanoma tumors. TERTmutant DNA was also identified in 21 of 27 plasma samples (78%) from patients with TERTmutant tumors, with plasma mutant allele fractions ranging from 0.06% to 15.3%. There were no false positives in plasma. These data demonstrate the potential of these assays to specifically detect and quantify TERTmutant DNA in tumors and plasma of cancer patients.
Introduction
Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are commonly performed bariatric procedures in obesity management. Gastroesophageal reflux disease ...(GERD) in this population has reported rates of 23–100%. GERD after LSG has been noted with recent studies demonstrating de novo reflux or symptom exacerbation despite weight loss. Fundoplication is not an option, and medically refractory GERD after LSG is usually treated with conversion to RYGB. GERD post-RYGB is a unique entity, and management poses a clinical and technical challenge. We evaluate safety and effectiveness of magnetic sphincter augmentation after bariatric surgery.
Materials and methods
A retrospective review of a prospectively maintained database was performed identifying patients that underwent LINX placement for refractory GERD after LSG, LRYGB, or duodenal switch across three institutions. Outcomes included complications, length of stay, PPI use, GERD-HRQL scores, and patient overall satisfaction.
Results
From March 2014 through June 2018, 13 identified patients underwent LINX placement after bariatric surgery: 8 LSG, 4 LRYGB, and 1 duodenal switch. The patients were 77% female, with mean age 43 and average BMI 30.1. Average pre-operative DeMeester score was 24.8. Pre-operatively, 5 patients were on daily PPI, 6 on BID PPI, and 1 on PPI + H2 blocker. We noted decreased medication usage post-operatively, with 4 patients taking daily PPI, and 9 off medication completely. A GERD-HRQL score was obtained pre- and post-operatively in 6 patients with average reduction from 25 to 8.5 (
p
value 0.002). Two patients experienced complications requiring endoscopic dilation after LINX placement. 100% of patients reported overall satisfaction post procedure.
Conclusion
LINX placement is a safe, effective treatment option for surgical management of refractory GERD after bariatric surgery. It can relieve symptoms and obviate the requirement of high-dose medical management. Magnetic lower esophageal sphincter augmentation should be another tool in the surgeon’s toolbox for managing reflux after bariatric surgery in select patients.
Background The recent epidemiologic changes of Clostridium difficile -associated diarrhea (CDAD) have resulted in substantial economic burden to U.S. acute care hospitals. Past studies evaluating ...CDAD-attributable costs have been geographically and demographically limited. Here, we describe CDAD-attributable burden in inpatients, overall, and in vulnerable subpopulations from the Premier hospital database, a large, diverse cohort with a wide range of high-risk subgroups. Methods Discharges from the Premier database were retrospectively analyzed to assess length of stay (LOS), total inpatient costs, readmission, and inpatient mortality. Results Patients with CDAD had significantly worse outcomes than matched controls in terms of total LOS, rates of intensive care unit (ICU) admission, and inpatient mortality. After adjustment for risk factors, patients with CDAD had increased odds of inpatient mortality, total and ICU LOS, costs, and odds of 30-, 60- and 90-day all-cause readmission versus non-CDAD patients. CDAD-attributable costs were higher in all studied vulnerable subpopulations, which also had increased odds of 30-, 60- and 90-day all-cause readmission than those without CDAD. Conclusion Given the significant economic impact CDAD has on hospitals, prevention of initial episodes and targeted therapy to prevent recurrences in vulnerable patients are essential to decrease the overall burden to hospitals.
Melanoma lacks validated blood-based biomarkers for monitoring and predicting treatment efficacy. Cell-free circulating tumour DNA (ctDNA) is a promising biomarker; however, various detection methods ...have been used, and, to date, no large studies have examined the association between serial changes in ctDNA and survival after BRAF, MEK, or BRAF plus MEK inhibitor therapy. We aimed to evaluate whether baseline ctDNA concentrations and kinetics could predict survival outcomes.
In this clinical validation study, we used analytically validated droplet digital PCR assays to measure BRAFV600-mutant ctDNA in pretreatment and on-treatment plasma samples from patients aged 18 years or older enrolled in two clinical trials. COMBI-d (NCT01584648) was a double-blind, randomised phase 3 study of dabrafenib plus trametinib versus dabrafenib plus placebo in previously untreated patients with BRAFV600 mutation-positive unresectable or metastatic melanoma. Patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. COMBI-MB (NCT02039947) was an open-label, non-randomised, phase 2 study evaluating dabrafenib plus trametinib in patients with BRAFV600 mutation-positive metastatic melanoma and brain metastases. Patients in cohort A of COMBI-MB had asymptomatic brain metastases, no previous local brain-directed therapy, and an ECOG performance status of 0 or 1. Biomarker analysis was a prespecified exploratory endpoint in both trials and performed in the intention-to-treat populations in COMBI-d and COMBI-MB. We investigated the association between mutant copy number (baseline or week 4 or zero conversion status) and efficacy endpoints (progression-free survival, overall survival, and best overall response). We used Cox models, Kaplan-Meier plots, and log-rank tests to explore the association of pretreatment ctDNA concentrations with progression-free survival and overall survival. The effect of additional prognostic variables such as lactate dehydrogenase was also investigated in addition to the mutant copy number.
In COMBI-d, pretreatment plasma samples were available from 345 (82%) of 423 patients and on-treatment (week 4) plasma samples were available from 224 (53%) of 423 patients. In cohort A of COMBI-MB, pretreatment and on-treatment samples were available from 38 (50%) of 76 patients with intracranial and extracranial metastatic melanoma. ctDNA was detected in pretreatment samples from 320 (93%) of 345 patients (COMBI-d) and 34 (89%) of 38 patients (COMBI-MB). When assessed as a continuous variable, elevated baseline BRAFV600 mutation-positive ctDNA concentration was associated with worse overall survival outcome (hazard ratio HR 1·13 95% CI 1·09–1·18, p<0·0001 by univariate analysis), independent of treatment group and baseline lactate dehydrogenase concentrations (1·08 1·03–1·13, p=0·0020), in COMBI-d. A ctDNA cutoff point of 64 copies per mL of plasma stratified patients enrolled in COMBI-d as high risk or low risk with respect to survival outcomes (HR 1·74 95% CI 1·37–2·21, p<0·0001 for progression-free survival; 2·23 1·73–2·87, p<0·0001 for overall survival) and was validated in the COMBI-MB cohort (3·20 1·39–7·34, p=0·0047 for progression-free survival; 2·94 1·18–7·32, p=0·016 for overall survival). In COMBI-d, undetectable ctDNA at week 4 was significantly associated with extended progression-free and overall survival, particularly in patients with elevated lactate dehydrogenase concentrations (HR 1·99 95% CI 1·08–3·64, p=0·027 for progression-free survival; 2·38 1·24–4·54, p=0·0089 for overall survival).
Pretreatment and on-treatment BRAFV600-mutant ctDNA measurements could serve as independent, predictive biomarkers of clinical outcome with targeted therapy.
Novartis.
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