A comprehensive overview of selective and novel fibroblast growth factor receptor inhibitors as a potential anticancer modality.

The arrival of comprehensive genome sequencing has accelerated the understanding of genetically aberrant advanced cancers and target identification for possible cancer treatment. Fibroblast growth factor receptor (FGFR) gene alterations are frequent findings in various rare and advanced cancers refractive to mainstay chemo-therapy or surgical interventions. Several FGFR inhibitors have been developed for addressing these genetically altered FGFR-harboring malignancies, and some have performed well in clinical trials. In contrast, others are still being investigated in different phases of clinical trials. FDA has approved four anticancer agents such as erdafitinib, pemigatinib, infigratinib, and futibatinib, for clinical use in oncogenic FGFR-driven malignancies. These include cholangiocarcinoma, urothelial carcinoma, and myeloid/lymphoid malignancies. Pemigatinib is the only FGFR inhibitor globally approved (USA, EU, and Japan) and available as a targeted therapy for two types of cancer, including FGFR2 fusion or other rearrangements harboring cholangiocarcinoma and relapsed/refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. Myeloid/lymphoid neoplasm is the latest area of application added to the therapeutic armamentarium of FGFR inhibitors. Furthermore, futibatinib is the first-in-class covalent or irreversible pan-FGFR inhibitor that has received FDA approval for locally advanced or metastatic intrahepatic cholangiocarcinoma harboring FGFR2 gene aberrations. This review highlights the current clinical progress concerning the safety and efficacy of all the approved FGFR-TKIs (tyrosine kinase inhibitors) and their ongoing investigations in clinical trials for other oncogenic FGFR-driven malignancies.

Synovial Hemangioma Presenting as Anterior Knee Pain - A Case Series.

Introduction: Synovial hemangioma is a benign soft-tissue tumor of vascular origin. The knee joint is most common joint affected and with highest incidence noted till date. For diagnosis, of such rare presentation radiological investigations such as digital radiograph and magnetic resonance imaging are of utmost importance, and magnetic resonance imaging being considered as investigation of choice. The gold standard treatment being complete excision of the growth. Case 1: A 13-year-old boy presented in out-patient clinic with chief complaint of right sided anterior knee pain since 10 months and patient had history of trauma in past. Magnetic resonance imaging of knee joint showed well circumscribed lesion in infra-patellar area (Hoffa's fat pad), with internal septations present within lesion. Case 2: A 25-year-old female presented to out-patient clinic with chief complaint of left sided anterior knee pain since 2 year, with no history of prior injury. The magnetic resonance imaging of knee joint showed ill-defined lesion around anterior patella-femoral articulation adherent to quadriceps tendon, internal septations present within lesion. For both cases, en bloc excision was performed and good functional outcome was achieved. Conclusion: Knee joint synovial hemangioma is rare presentation to orthopedic outdoors, has slight female predominance with pre-existing history of trauma. In the present study, both cases were of patella-femoral type (anterior and infra-patellar fat pad). For such lesions, en bloc excision is gold standard procedure to prevent recurrence, same procedure was followed in our study, and good functional outcome was achieved.

Mortality profile after 2 years of hip fractures in elderly patients treated with early surgery.

BACKGROUND: In geriatric age group, hip fractures tend to become a major public health hazard. Due to this high occurrence, there is a need to develop standardized, effective, and multidisciplinary management for treatment. These elderly patients have excessive mortality that can extend ahead of the time of recovery. Early surgery after hip fractures has lead to a notable reduction in mortality rates. Still, it is considerably high as compared to other fractures. METHODS: 266 patients of >65 years who were operated within 72 h hours in a tertiary level health care centre for hip fractures were included. They were evaluated with X-rays and grade of Singh's index was noted. Mortality rates and the factors associated with it such as age, sex, co morbidities (using Charlson's co morbidity Index/CCI) were evaluated after 2 year follow up. RESULTS: The overall 2-year mortality reported in our study population was 11.2%. It was broadly lower as compared to most of the other studies. It was 6.3% in females as compared to 18.1% in males. While it was reported to be only 6% in 65-74 years of age, it was 25% in patients who were 85 years and above. 76.6% of the patients had Singh's index of ≤ grade 3 showing osteoporosis. The patients with Low Charlson's score showed only 4.2% mortality while those with high Charlson's score showed 25.5% mortality. CONCLUSION: It was concluded that Mortality among elderly patients after early surgery after osteoporotic hip fractures is quite significant. The factors for improvement in long term survival post-hip fracture may include changing treatment patterns, increasing life expectancy and early surgery. Increase in age, female sex, and high CCI Scores were major risk factors of mortality after hip fractures in a 2-year follow-up period.

Building a specialized lexicon for breast cancer clinical trial subject eligibility analysis.

A natural language processing (NLP) application requires sophisticated lexical resources to support its processing goals. Different solutions, such as dictionary lookup and MetaMap, have been proposed in the healthcare informatics literature to identify disease terms with more than one word (multi-gram disease named entities). Although a lot of work has been done in the identification of protein- and gene-named entities in the biomedical field, not much research has been done on the recognition and resolution of terminologies in the clinical trial subject eligibility analysis. In this study, we develop a specialized lexicon for improving NLP and text mining analysis in the breast cancer domain, and evaluate it by comparing it with the Systematized Nomenclature of Medicine Clinical Terms (SNOMED CT). We use a hybrid methodology, which combines the knowledge of domain experts, terms from multiple online dictionaries, and the mining of text from sample clinical trials. Use of our methodology introduces 4243 unique lexicon items, which increase bigram entity match by 38.6% and trigram entity match by 41%. Our lexicon, which adds a significant number of new terms, is very useful for matching patients to clinical trials automatically based on eligibility matching. Beyond clinical trial matching, the specialized lexicon developed in this study could serve as a foundation for future healthcare text mining applications.

Combined presence of multiple gastrointestinal stromal tumors along with duodenal submucosal somatostatinoma in a patient with neurofibromatosis type 1.

Neurofibromatosis type-1 (NF-1) is an autosomal dominant disorder, with increased risk of developing benign and malignant tumors of the gastrointestinal tract (GIT). However, the synchronous presence of multiple GIT stromal tumors and duodenal submucosal somatostatinoma, like in this 50-year-old female NF-1 patient, is very rare. She presented with hematemesis, malena, along with multiple neurofibromas all over the body. Thorough radiological and peroperative work-up revealed multiple ulcerated submucosal and serosal nodules in the proximal small intestine. Histological work-up revealed diagnosis of a duodenal submucosal somatostatinoma with multifocal serosal gastrointestinal stromal tumors. This case is being reported to highlight the rare coincidence of multiple GIT tumors in an NF-1 patient.