Oral cancer prediction by noninvasive genetic screening

Oral squamous cell carcinomas (OSCCs) develop in genetically altered epithelium in the mucosal lining, also coined as fields, which are mostly not visible but occasionally present as white oral leukoplakia (OL) lesions. We developed a noninvasive genetic assay using next-generation sequencing (NGS) on brushed cells to detect the presence of genetically altered fields, including those that are not macroscopically visible. The assay demonstrated high accuracy in OL patients when brush samples were compared with biopsies as gold standard. In a cohort of Fanconi anemia patients, detection of mutations in prospectively collected oral brushes predicted oral cancer also when visible abnormalities were absent. We further provide insight in the molecular landscape of OL with frequent changes of TP53, FAT1 and NOTCH1. NGS analysis of noninvasively collected samples offers a highly accurate method to detect genetically altered fields in the oral cavity, and predicts development of OSCC in high-risk individuals. Noninvasive genetic screening can be employed to screen high-risk populations for cancer and precancer, map the extension of OL lesions beyond what is visible, map the oral cavity for precancerous changes even when visible abnormalities are absent, test accuracy of promising imaging modalities, monitor interventions and determine genetic progression as well as the natural history of the disease in the human patient.     

Effect of root perforation repair with mineral aggregate-based cements on the retention of customized fiberglass posts

Odontology - The purpose of this study was to investigate whether the root perforation repair with mineral aggregate-based cements affects the retention of customized fiberglass posts to bovine...     

The magnitude and progress of lean body mass,fat-free mass,and skeletal muscle mass loss following bariatric surgery: A systematic review and meta-analysis

Postbariatric loss of muscle tissue could negatively affect long-term health due to its role in various bodily processes, such as metabolism and functional capacity. This meta-analysis aimed to unravel time-dependent changes in the magnitude and progress of lean body mass (LBM), fat-free mass (FFM), and skeletal muscle mass (SMM) loss following bariatric surgery. A systematic literature search was conducted in Pubmed, Embase, and Web of Science. Fifty-nine studies assessed LBM (n = 37), FFM (n = 20), or SMM (n = 3) preoperatively and ≥1 time points postsurgery. Random-effects meta-analyses were performed to determine pooled loss per outcome parameter and follow-up time point. At 12-month postsurgery, pooled LBM loss was ?8.13 kg [95%CI ?9.01; ?7.26]. FFM loss and SMM loss were ?8.23 kg [95%CI ?10.74; ?5.73] and ?3.18 kg [95%CI ?5.64; ?0.71], respectively. About 55% of 12-month LBM loss occurred within 3-month postsurgery, followed by a more gradual decrease up to 12 months. Similar patterns were seen for FFM and SMM. In conclusion, >8 kg of LBM and FFM loss was observed within 1-year postsurgery. LBM, FFM, and SMM were predominantly lost within 3-month postsurgery, highlighting that interventions to mitigate such losses should be implemented perioperatively.     

Exploring the role of artificial intelligence in the study of fetal heart

The International Journal of Cardiovascular Imaging -     

Limited clinical activity of palbociclib and ribociclib monotherapy in advanced cancers with cyclin D-CDK4/6 pathway alterations in the Dutch DRUP and Australian MoST trials

The Dutch Drug Rediscovery Protocol (DRUP) and the Australian Cancer Molecular Screening and Therapeutic (MoST) Program are similar nonrandomized, multidrug, pan-cancer trial platforms that aim to identify signals of clinical activity of molecularly matched targeted therapies or immunotherapies outside their approved indications. Here, we report results for advanced or metastatic cancer patients with tumors harboring cyclin D-CDK4/6 pathway alterations treated with CDK4/6 inhibitors palbociclib or ribociclib. We included adult patients that had therapy-refractory solid malignancies with the following alterations: amplifications of CDK4, CDK6, CCND1, CCND2 or CCND3, or complete loss of CDKN2A or SMARCA4. Within MoST, all patients were treated with palbociclib, whereas in DRUP, palbociclib and ribociclib were assigned to different cohorts (defined by tumor type and alteration). The primary endpoint for this combined analysis was clinical benefit, defined as confirmed objective response or stable disease ≥16 weeks. We treated 139 patients with a broad variety of tumor types; 116 with palbociclib and 23 with ribociclib. In 112 evaluable patients, the objective response rate was 0% and clinical benefit rate at 16 weeks was 15%. Median progression-free survival was 4 months (95% CI: 3-5 months), and median overall survival 5 months (95% CI: 4-6 months). In conclusion, only limited clinical activity of palbociclib and ribociclib monotherapy in patients with pretreated cancers harboring cyclin D-CDK4/6 pathway alterations was observed. Our findings indicate that monotherapy use of palbociclib or ribociclib is not recommended and that merging data of two similar precision oncology trials is feasible.     

The role of endoscopic ultrasound for portal hypertension in liver cirrhosis

Journal of Medical Ultrasonics - Chronic liver disease is still a major problem because disease progression will ultimately lead to liver cirrhosis. Portal hypertension is the hallmark in advanced...     

Use and Applicability of the Gail Model to Calculate Breast Cancer Risk: A Scoping Review

Objective: To perform a scoping review of the applicability of the Gail model in different countries for different ethnicities. Methods: The review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and search strategies based on the PICOS approach. The reviewed articles were included if they were published between 2013 and 2018 in English, Portuguese, or Spanish; were original articles available in full online; and described the use of the Gail model. The PubMed, Embase, and Web of Science data bases were searched. Results: A total of 38 articles eligible for analysis were identified, of which 16 used the Gail model to assess breast cancer risk in women, eight analyzed the applicability of this tool in their population, seven compared the tool and/or modified it according to the specific risk factors of their population, and seven cited the model in determining eligibility for chemoprevention. Conclusion: The Gail model has different applicabilities Greater effectiveness and breast cancer risk are found in developed countries.     

Glycaemic control for patients with severe acute brain injury: Protocol for a systematic review

Background

Hyperglycaemia is common in patients with acute brain injury admitted to an intensive care unit (ICU). Many studies have found associations between development of hyperglycaemia and increased mortality in hospitalised patients. However, the optimal target for blood glucose control is unknown. We want to conduct a systematic review with meta-analysis and trial sequential analysis to explore the beneficial and harmful effects of restrictive versus liberal glucose control on patient outcomes in adults with severe acute brain injury.

Methods

We will systematically search medical databases including CENTRAL, Embase, MEDLINE and trial registries. We will search the following websites for ongoing or unpublished trials: http://www.controlled-trials.com/ , http://www.clinicaltrials.gov/ , www.eudraCT.com , http://centerwatch.com/ , The Cochrane Library's CENTRAL, PubMed, EMBASE, Science Citation Index Expanded and CINAHL. Two authors will independently review and select trials and extract data. We will include randomised trials comparing levels of glucose control in our analyses and observational studies will be included to address potential harms. The primary outcomes are defined as all-cause mortality, functional outcome and health-related quality of life. Secondary outcomes include serious adverse events including hypoglycaemia, length of ICU stay and duration of mechanical ventilation, and explorative outcomes including intracranial pressure and infection. Trial Sequential Analysis will be used to investigate the risk of type I error due to repetitive testing and to further explore imprecision. Quality of trials will be evaluated using the Cochrane Risk of Bias tool, and quality of evidence will be assessed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach.

Discussion

The results of the systematic review will be disseminated through peer-reviewed publication. With the review, we hope to inform future randomised clinical trials and improve clinical practice.