Fibroblast growth factor receptors in cancer: genetic alterations,diagnostics, therapeutic targets and mechanisms of resistance

Fibroblast growth factor receptors (FGFRs) are aberrantly activated through single-nucleotide variants, gene fusions and copy number amplifications in 5–10% of all human cancers, although this frequency increases to 10–30% in urothelial carcinoma and intrahepatic cholangiocarcinoma. We begin this review by highlighting the diversity of FGFR genomic alterations identified in human cancers and the current challenges associated with the development of clinical-grade molecular diagnostic tests to accurately detect these alterations in the tissue and blood of patients. The past decade has seen significant advancements in the development of FGFR-targeted therapies, which include selective, non-selective and covalent small-molecule inhibitors, as well as monoclonal antibodies against the receptors. We describe the expanding landscape of anti-FGFR therapies that are being assessed in early phase and randomised controlled clinical trials, such as erdafitinib and pemigatinib, which are approved by the Food and Drug Administration for the treatment of FGFR3-mutated urothelial carcinoma and FGFR2-fusion cholangiocarcinoma, respectively. However, despite initial sensitivity to FGFR inhibition, acquired drug resistance leading to cancer progression develops in most patients. This phenomenon underscores the need to clearly delineate tumour-intrinsic and tumour-extrinsic mechanisms of resistance to facilitate the development of second-generation FGFR inhibitors and novel treatment strategies beyond progression on targeted therapy.Subject terms: Cancer, Cancer     

Religious Allergic Contact Dermatitis

Henna, derived from a combination of natural leaves and coloring additives, is a common decorative dye traditionally used in many Islamic religious celebrations. Para‐phenylenediamine (PPD), a major component of black henna tattoo, is a strong sensitizer and common allergen. We report a case of severe connubial allergic contact dermatitis after black henna heterotransfer in a girl.     

Emergency department patient payer status after implementation of the Affordable Care Act: A nationwide analysis using NHAMCS data

ObjectiveTo evaluate changes in insurance status among emergency department (ED) patients presenting in the two years immediately before and after full implementation of the Affordable Care Act (ACA).MethodsWe evaluated National Hospital Ambulatory Medical Care Survey (NHAMCS) Emergency Department public use data for 2012–2015, categorizing patients as having any insurance (private; Medicare; Medicaid; workers' compensation) or no insurance. We compared the pre- and post-ACA frequency of insurance coverage—overall and within the older (≥65), working-age (18–64) and pediatric (<18) subpopulations—using unadjusted odds ratios with 95% confidence intervals. We also conducted a difference-in-differences analysis comparing the change in insurance coverage among working-age patients with that observed for older Medicare-eligible patients, while controlling for sex, race and underlying temporal trends.ResultsOverall, the proportion of ED patients with any insurance did not significantly change from 2012 to 2013 to 2014–2015 (74.2% vs 77.7%) but the proportion of working-age adult patients with at least one form of insurance increased significantly, from 66.0% to 71.8% (OR 1.31, CI: 1.13–1.52). The difference-in-differences analysis confirmed the change in insurance coverage among working-age adults was greater than that seen in the reference population of Medicare-eligible adults (AOR 1.70, CI: 1.29–2.23). The increase was almost entirely attributable to increased Medicaid coverage.ConclusionIn the first two years following full implementation of the ACA, there was a significant increase in the proportion of working-age adult ED patients who had at least one form of health insurance. The increase appeared primarily associated with expansion of Medicaid.     

Genetic characterization and diversity of porcine circovirus type 2 in non‐vaccinated South African swine herds

The porcine circovirus type 2 (PCV2) is a swine infectious viral pathogen of great significance in global swine herds. It was recently detected at another Province of South Africa sequel to the first detection of North American‐like strain (PCV2a) at Gauteng about two decades ago, but there is a dearth of information about the genomic features and diversity of the viral strains in circulation within the country and the entire sub‐Saharan Africa region. To date, only one complete genome of the virus from South Africa is available on global data base. This current effort is therefore geared towards the full‐genome characterization of the circulating PCV2 strains in the pigs of Eastern Cape Province. With the use of conventional polymerase chain reaction method, fifteen complete PCV2 genomes were successfully amplified, sequenced and assembled from field samples obtained from non‐vaccinated pigs in the region. Neighbor Joining and Maximum Likelihood phylogenetic analyses of the ORF2 gene and full genomes unanimously showed that most of the assembled genomes (11) belong to genotype PCV2b. Furthermore, three of the characterized sequences formed clade with other reference mutant PCV2b and PCV2b subtype 1C (i.e. PCV2d) strains from the USA, China and South Korea. The last sequence, however, clustered with other reference strains belonging to PCV2 intermediate clade 2 (PCV2‐IM2), recently identified in a global PCV2 strains phylogenetic analysis. This study reports the first complete genome sequences of PCV2b, PCV2d and PCV2‐IM2 in pigs from South Africa, and it gives a possible insight into the genetic characteristics and variability of the viral strains presently in circulation within the country. It further emphasizes the need for more stringent measures in curtailing the introduction and spread of transboundary swine pathogens in the country and entire Southern African region.     

Fecal microbiota transplantation to eradicate vancomycin-resistant enterococci colonization in case of an outbreak

Objective

A rapid and worrying emergence of vancomycin-resistant enterococci (VRE) gut colonization is occurring worldwide and may be responsible for outbreaks, especially in healthcare facilities. While no efficient decolonization strategies are recommended, we assessed fecal microbiota transplantation (FMT) to eradicate VRE colonization.

Recurrent herpes labialis in the pediatric population: Prevalence,therapeutic studies,and associated complications

Recurrent herpes labialis (RHL) is an incredibly common condition, though the medical literature evaluating pediatric aspects is limited. This paper assesses prevalence and therapeutic studies of pediatric RHL as well as disease complications. A comprehensive literature search of English‐language citations based on PubMed queries of selected terms was performed, with exclusion if methodology was not discussed, or if studies had 10 or fewer patients. RHL prevalence in pediatrics has been assessed by measures of point and periodic prevalence, though methodologic limitations may under‐ or over‐estimate the true prevalence of RHL. Studies have been conducted to evaluate therapeutic safety, tolerability, and efficacy of antivirals in the pediatric population. Pediatric RHL point prevalence ranges from 0.72% to 5.2% depending on the population study and the methodologies used. Pediatric RHL carries a significant public health burden and is often implicated in patients with eczema herpeticum, erythema multiforme, reactive infectious mucositis eruptions, and hypersensitivity reactions. There are few studies that evaluate the rates of occurrence of these sequelae associated with pediatric RHL.     

Morbidity Associated With High Gastrocnemius Recession: Retrospective Review of 126 Cases

To evaluate morbidity associated with surgical lengthening of the gastrocnemius, medical records were reviewed retrospectively for 126 patients (mean age, 49.7 years; range, 8-78 years) who had undergone open gastrocnemius recession. Ten patients had isolated recession; 116 had gastrocnemius recession with an additional foot or ankle procedure on the ipsilateral limb. During a mean follow-up period of 19 months (range, 6-50 months), all patients were examined for any postoperative complications associated with the recession. Complications were defined as the presence of postoperative infection, wound dehiscence, nerve problems, decreased muscle strength, scar problems, or calcaneus gait (overlengthening). Uncomplicated outcome was defined as absence of all these complications and return to regular activity, both occurring during a follow-up of at least 6 months. Postsurgical complications developed in 9 (6%) of the 126 patients: 6 (4%) had scar problems, 2 (1.33%) had wound dehiscence, 2 (1.33%) had infection, 3 (2%) had nerve problems, and 1 (0.67%) developed complex regional pain syndrome. No patient complained of either a limp or gait disturbance. Neither persistent decrease in muscle strength nor calcaneus gait was seen. These data suggest that the open gastrocnemius recession procedure has low associated morbidity.