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     

Traumatic spinopelvic dissociation managed with bilateral triangular osteosynthesis: Functional and radiological outcomes,health related quality of life and complication rates

BackgroundSpinopelvic dissociation (SPD) is difficult to manage and is associated with high mortality and morbidity, including concomitant orthopaedic polytrauma, spine injuries, pelvic ring disruptions, neurological, soft-tissue, and vascular injuries. The purpose of this study is to evaluate the functional and radiological outcomes; health related quality of life and complication rates of patients with traumatic spinopelvic dissociation underwent bilateral triangular osteosynthesis (TOS).MethodsThe study was approved by the medical school's institutional review board (IRB). Prospective data collection of nineteen consecutive cases of traumatic SPD were included in the study from October 2015 to August 2018. Bilateral TOS was performed to manage all patients with SPD. The clinical outcome for fractures was analyzed with Majeed function assessment. Health Related Quality of Life (HRQoL) was assessed with the EQ-6D questionnaire. The reduction quality was evaluated according to Matta criterion. CT scanning was used to verify the fracture union in patients at 24^th weeks postoperatively.ResultsThere were 12 women and 7 men with an average age of 47.2±8.4 years (range, 17-62 years). The average follow-up time was 25.2±3.7 months (average, 22-45 months). The most common mechanism of injury was falling (57%). According to Majeed functional scoring, the results were excellent in 12 cases, good in 5 cases and fair in 2 cases. The median EQVAS score was 78.9±8.4. 15 patients (78.9%) turned back to their original occupation. Pain and mood disorders mainly influenced patients’ present general health status. According to Matta criterion for fracture reduction, the results were excellent in 14 cases, good in 4 cases and fair in 1 case. Complications were noted as wound healing problems (26%), implant loosening (5%) and iatrogenic nerve injury (5%).ConclusionBilateral TOS demonstrates satisfactory functional and radiological outcomes with low complication rates except infection rate in patients with traumatic spinopelvic dissociation. HRQoL is mainly dominated by pain and mood disorders. 78.9% of the patients turned back to their original occupation. Surgeons should be aware of wound healing problems in case of increased muscle mobilization and degloving injuries.Implant removal is required to improve the lumbopelvic mobility.     

Defining the role of advanced care practitioners in pediatric surgery practice

IntroductionThe role of advanced care practitioners (ACPs) in pediatric surgery is increasingly important and not well described.MethodsElectronic surveys were sent to pediatric surgery division chiefs within the Children's Hospital Association.ResultsWe received 77/163 survey responses (47%). The median number of ACPs per service was 3.0 (range 0–35). ACP number correlated with inpatient census, surgeon number, case volume, trauma centers, intensive care unit status, and fellowship programs but not with presence of residents/hospitalists, hospital setting, or practice type. Nearly all programs incorporated nurse practitioners while almost half utilized physician assistants. Approximately one-third of ACPs were designated for subspecialties (35%) such as trauma and colorectal. Only 9% of centers had surgeon-specific ACPs. ACP responsibilities included both inpatient and outpatient tasks. Nearly all ACPs participated in procedures (89%), mostly bedside (80%). All ACPs worked daytime shifts, with less nights and weekends. Most ACPs billed for services (80%). Satisfaction with ACP coverage was widespread and did not correlate with ACP number. Most respondents felt that ACPs enhance, and not hinder, resident/fellow training (85%).ConclusionACPs are useful adjuncts in pediatric surgery. A better understanding of practice patterns may help optimize utilization to enhance patient care and can be used to advocate for appropriate resources.     

Thrombosis and thromboembolism: Brighton collaboration case definition and guidelines for data collection,analysis, and presentation of immunization safety data

This is a Brighton Collaboration case definition of thrombosis and thromboembolism to be used in the evaluation of adverse events following immunization, and for epidemiologic studies for the assessment of background incidence or hypothesis testing. The case definition was developed by a group of experts convened by the Coalition for Epidemic Preparedness Innovations (CEPI) in the context of active development of SARS-CoV-2 vaccines. The case definition format of the Brighton Collaboration was followed to develop a consensus definition and defined levels of certainty, after an exhaustive review of the literature and expert consultation. The document underwent peer review by the Brighton Collaboration Network and by selected expert reviewers prior to submission.