Safety and efficacy of vismodegib in patients aged ≥65 years with advanced basal cell carcinoma.

Because many patients with unresectable basal cell carcinoma (BCC) are aged ≥65 years, this study explores the efficacy and safety of vismodegib in these patients with locally advanced (la) or metastatic (m) basal cell carcinoma (BCC) in the ERIVANCE BCC trial and the expanded access study (EAS).We compared patients aged ≥65 years to patients aged <65 years taking vismodegib 150 mg/day, using descriptive statistics for response and safety. Patients aged ≥65 years (laBCC/mBCC) were enrolled in ERIVANCE BCC (33/14) and EAS (27/26). Investigator-assessed best overall response rate in patients ≥65 and <65 years was 46.7%/35.7% and 72.7%/52.6% (laBCC/mBCC), respectively, in ERIVANCE BCC and 45.8%/33.3% and 46.9%/28.6%, respectively, in EAS. These differences were not clinically meaningful. Safety was similar in both groups, although those aged ≥65 years had a higher percentage of grade 3-5 adverse events than those aged <65 years. Vismodegib demonstrated similar clinical activity and adverse events regardless of age

Guinea pig fetus does not change its presentation during second half of gestation

Objectives: The aims of this paper are: 1. To investigate spontaneous changes in fetal presentation during the second half of gestation in guinea pig fetus, 2. to observe provoked changes of fetal presentation, by passive positioning fetus into an upside-down position and “sitting” position. Eight fetuses from singleton pregnancies were included. Experimental design: Ultrasound examinations (Toshiba Nemio SSA-550A apparatus) were started on the 26th day of gestation (GD). Each fetus was examined 2-3 times in each 5-day interval until the end of gestation. First the spontaneous orientation of fetus was determined by tracking along the longitudinal and transversal axes of the fetus with the ultrasound probe. Then the fetus was brought into a head-down position relative to gravity for 5 minutes. The examination was repeated with the fetus in the head-up position. Results: In the period from the 26th – 30th GD in 7 of 21 observations spontaneous changes of presentation were observed. From the 31st GD all 133 observations were negative regarding spontaneous changes of presentation and situs. The chi-squared test showed that difference in spontaneous changes of presentation and situs before versus after 30th day of gestation had a statistical significance (χ² = 25.16 p 0.05). Fetuses were brought into a head-down and head-up 154 times. In none of these attempts did a fetus change presentation during the five minutes of observation. Conclusion: Guinea pig fetuses do not spontaneously or at provocation change presentation after 30th GD

Non-invasive treatment of multiple enamel hypoplasia: A case report

Objective. Enamel hypoplasia is a quantitative disorder of enamel deposition during the secretory phase and is characterised by a deficiency of the enamel, while hypomineralization is a qualitative disorder caused by incomplete mineralization and maturation of the enamel, followed by the porosity of the solid dental tissues and the opalescent tooth colour. Clinically, hypoplasia is a risk for caries, tooth sensitivity, erosion, and affects the aesthetic appearance of a patient with a psychological connotation. The aim of the paper is to present the case report, the possibility of preventive measures and restorative treatments with minimally invasive requirements in these patients. Methods. At the Faculty of Medical Sciences, University of Kragujevac, in March 2018, a thirteen-year-old boy was diagnosed with isolated hypoplastic enamel defects on teeth 24, 25, 26, 33 and 34. Results. Enamel hypoplasia was diagnosed by anamnesis, clinical and radiological examination. Preventive measures and conservative interventions were used to prevent progressive abrasion and early tooth loss due to caries and its complications. Conclusion. Early diagnosis, timely preventive methods and minimally invasive restorative treatment can correct anomalies and prevent possible complications.Publishe

Evaluation of pre-analytical factors affecting plasma DNA analysis.

Pre-analytical factors can significantly affect circulating cell-free DNA (cfDNA) analysis. However, there are few robust methods to rapidly assess sample quality and the impact of pre-analytical processing. To address this gap and to evaluate effects of DNA extraction methods and blood collection tubes on cfDNA yield and fragment size, we developed a multiplexed droplet digital PCR (ddPCR) assay with 5 short and 4 long amplicons targeting single copy genomic loci. Using this assay, we compared 7 cfDNA extraction kits and found cfDNA yield and fragment size vary significantly. We also compared 3 blood collection protocols using plasma samples from 23 healthy volunteers (EDTA tubes processed within 1 hour and Cell-free DNA Blood Collection Tubes processed within 24 and 72 hours) and found no significant differences in cfDNA yield, fragment size and background noise between these protocols. In 219 clinical samples, cfDNA fragments were shorter in plasma samples processed immediately after venipuncture compared to archived samples, suggesting contribution of background DNA by lysed peripheral blood cells. In summary, we have described a multiplexed ddPCR assay to assess quality of cfDNA samples prior to downstream molecular analyses and we have evaluated potential sources of pre-analytical variation in cfDNA studies

Network Rewiring in Cancer: Applications to Melanoma Cell Lines and the Cancer Genome Atlas Patients

Genes do not work in isolation, but rather as part of networks that have many feedback and redundancy mechanisms. Studying the properties of genetic networks and how individual genes contribute to overall network functions can provide insight into genetically-mediated disease processes. Most analytical techniques assume a network topology based on normal state networks. However, gene perturbations often lead to the rewiring of relevant networks and impact relationships among other genes. We apply a suite of analysis methodologies to assess the degree of transcriptional network rewiring observed in different sets of melanoma cell lines using whole genome gene expression microarray profiles. We assess evidence for network rewiring in melanoma patient tumor samples using RNA-sequence data available from The Cancer Genome Atlas. We make a distinction between “unsupervised” and “supervised” network-based methods and contrast their use in identifying consistent differences in networks between subsets of cell lines and tumor samples. We find that different genes play more central roles within subsets of genes within a broader network and hence are likely to be better drug targets in a disease state. Ultimately, we argue that our results have important implications for understanding the molecular pathology of melanoma as well as the choice of treatments to combat that pathology

Correction to: Long-term safety and efficacy of vismodegib in patients with advanced basal cell carcinoma: final update of the pivotal ERIVANCE BCC study

Following publication of the original article [1], it was reported that the legend for Fig. 1 was incomplete. The complete figure legend is:https://deepblue.lib.umich.edu/bitstream/2027.42/148648/1/12885_2019_Article_5568.pd

Interim Analysis of Phase 2 Results for Cemiplimab in Patients with Metastatic Basal Cell Carcinoma (mBCC) who Progressed on or are Intolerant to Hedgehog Inhibitors (HHIs)

Abstract not available

Primary Analysis of Phase 2 Results for Cemiplimab in Patients (pts) with Locally Advanced Basal Cell Carcinoma (laBCC) who Progress on or are Intolerant to Hedgehog Inhibitors (HHIs)

Abstract not available

Post-Operative Functional Outcomes in Early Age Onset Rectal Cancer

Background: Impairment of bowel, urogenital and fertility-related function in patients treated for rectal cancer is common. While the rate of rectal cancer in the young (<50 years) is rising, there is little data on functional outcomes in this group. Methods: The REACCT international collaborative database was reviewed and data on eligible patients analysed. Inclusion criteria comprised patients with a histologically confirmed rectal cancer, <50 years of age at time of diagnosis and with documented follow-up including functional outcomes. Results: A total of 1428 (n=1428) patients met the eligibility criteria and were included in the final analysis. Metastatic disease was present at diagnosis in 13%. Of these, 40% received neoadjuvant therapy and 50% adjuvant chemotherapy. The incidence of post-operative major morbidity was 10%. A defunctioning stoma was placed for 621 patients (43%); 534 of these proceeded to elective restoration of bowel continuity. The median follow-up time was 42 months. Of this cohort, a total of 415 (29%) reported persistent impairment of functional outcomes, the most frequent of which was bowel dysfunction (16%), followed by bladder dysfunction (7%), sexual dysfunction (4.5%) and infertility (1%). Conclusion: A substantial proportion of patients with early-onset rectal cancer who undergo surgery report persistent impairment of functional status. Patients should be involved in the discussion regarding their treatment options and potential impact on quality of life. Functional outcomes should be routinely recorded as part of follow up alongside oncological parameters