Recent Insights into Osimertinib Analogues against EGFR Positive Non-small Cell Lung Cancer.

BACKGROUND: Lung cancer is a highly lethal malignancy with a poor prognosis and the leading cause of mortality worldwide. The development of mutations makes lung cancer treatment more challenging and expensive. Successful identification of epidermal growth factor receptor (EGFR) mutations led to the discovery of various third-generation tyrosine kinase inhibitors. Osimertinib is one of the promising and efficacious third-generation EGFR inhibitors and is mainly employed in the treatment of non-small cell lung cancer. Despite the initial effective response, osimertinib causes resistance in most of the patients after around 10 months of therapy, resulting in disease progression. To mitigate the effect of developed resistance, different osimertinib derivatives have been synthesized and evaluated by numerous research groups across the globe. METHODS: Present article illustrates recent research advancements for the utilization of osimertinib and its derivatives in non-small cell lung cancer (NSCLC). Last seven years literature search has been conducted from PubMed, ScienceDirect, and Google Scholar databases, etc. Result: The present review emphasizes the recent advancements of osimertinib analogues that lead to enhanced antitumor potential and safety profile against non-small cell lung cancer. This manuscript also summarizes the different synthetic schemes involved in the synthesis of osimertinib analogues against EGFR reported by different research groups. CONCLUSION: Anticancer mechanistic insights, analytical prospects, drug interactions, pharmacokinetic considerations, and resistance profile of osimertinib are highlighted in the current manuscript.

Potential of nanoemulsions for accelerated wound healing: innovative strategies.

Wounds represent various significant health concerns for patients and also contribute major costs to healthcare systems. Wound healing comprises of overlapped and various coordinated steps such as homeostasis, inflammation, proliferation, and remodeling. In response to the failure of many strategies in delivering intended results including wound closure, fluid loss control, and exhibiting properties such as durability, targeted delivery, accelerated action, along with histocompatibility, numerous nanotechnological advances have been introduced. To understand the magnitude of wound therapy, this systematic and updated review discussing the effectiveness of nanoemulsions has been undertaken. This review portrays mechanisms associated with wound healing, factors for delayed wound healing, and various technologies utilized to treat wounds effectively. While many strategies are available, nanoemulsions have attracted the tremendous attention of scientists globally for the research in wound therapy due to their long-term thermodynamic stability and bioavailability. Nanoemulsions not only aid in tissue repair, but are also considered as an excellent delivery system for various synthetic and natural actives. Nanotechnology provides several pivotal benefits in wound healing, including improved skin permeation, controlled release, and stimulation of fibroblast cell proliferation. The significant role of nanoemulsions in improved wound healing along with their preparation techniques has also been highlighted with special emphasis on mechanistic insights. This article illustrates recent research advancements for the utilization of nanoemulsions in wound treatment. An adequate literature search has been conducted using the keywords 'Nanoemulsions in wound healing', 'Wound therapy and nanoemulsions', 'Herbal actives in wound therapy', 'Natural oils and wounds treatment' etc., from PubMed, Science Direct, and Google Scholar databases. Referred and original publications in the English language accessed till April 2022 has been included, whereas nonEnglish language papers, unpublished data, and nonoriginal papers were excluded from the study.

Melphalan: Recent insights on synthetic, analytical and medicinal aspects.

Cancer is an uncontrolled expansion of atypical cells in the body. These unusual cells are labelled as cancerous or malignant cells. Melphalan, an anticancer drug which is imperatively recognized under the class of alkylating agents. It exhibits broad spectrum antitumor activity, as observed in ovarian cancer, breast cancer, etc. However, it is mainly utilized in the management of multiple myeloma. Several studies across the globe suggest that resistance to melphalan is the major concern that leads to relapsed myeloma. In the present paper, several pivotal approaches to compensate resistance associated with melphalan have been discussed. Numerous chemical and formulation developments concerning melphalan to enhance its salient characteristics and targeted profile have also been portrayed. The rationale of the current article also summarizes the recent analytical methods, structure-activity relationship, pharmacokinetics, interactions, potential adverse effects along with medicinal updates of melphalan. Special attention is also laid on their synthetic developments viz. melphalan derivatives, conjugates and prodrugs along with encouraging insights and research findings.

Prognostic implications of diastolic dysfunction in patients with acute pulmonary embolism.

BACKGROUND: A history of congestive heart failure has been used to determine the prognosis in patients with acute pulmonary embolism. Diastolic dysfunction is responsible for the half of congestive heart failure but has not been understood well. METHODS: A total of 205 patients were reported admitted with acute pulmonary embolism from January 2009 to July 2011. We excluded hemodynamically unstable patients who received thrombolytics or underwent thromboembolectomy. We included hemodynamically stable patients who underwent echocardiogram within 72 hours of diagnosis. We reviewed medical records of 107 patients to investigate whether diastolic dysfunction increases in-hospital mortality or adverse clinical outcomes. RESULTS: Out of 107 patients, 10 patients died during hospitalization with in-hospital mortality rate of 9.3%. Among 84 patients without diastolic dysfunction as assessed by echocardiogram, six patients died with in-hospital mortality rate of 7.1%. Meanwhile, among 23 patients with diastolic dysfunction, four patients died with in-hospital mortality rate of 17.4%. The multivariable adjusted odds ratio was calculated as 2.71, with 95% confidence interval of 0.59 - 12.44. CONCLUSIONS: For hemodynamically stable patients with acute pulmonary embolism, diastolic dysfunction as assessed by echocardiogram could increase in-hospital mortality 2.71 fold, although this was not statistically significant. Further study with a large patient population is needed to determine the statistically significant implications of diastolic dysfunction in patients with acute pulmonary embolism.