RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

Structural competency in global perspective.

This special issue aims to help fill two critical gaps in the growing literature as well as in practice. First, to bring together scholars and practitioners from around the world who develop, practice, review, and question structural competency with the aim of promoting a dialogue with related approaches, such as Latin American Social Medicine, Collective Health, and others, which have been key in diverse geographical and social settings. Second, to contribute to expanding structural competency beyond clinical medicine to include other health-related areas such as social work, global health, public health practice, epidemiological research, health policy, community organisation and beyond. This conceptual expansion is currently taking place in structural competency, and we hope that this volume will help to raise awareness and reinforce what is already happening. In sum, this collection of articles puts structural competency more rigorously and actively in conversation with different geographic, political, social, and professional contexts worldwide. We hope this conversation sparks further development in scholarly, political and community movements for social and health justice.

Real-World Evidence of EGFR Targeted Therapy in NSCLC- A Brief Report of Decade Long Single Center Experience.

The significance of EGFR targeted therapy in the lung adenocarcinoma is paramount. Several controlled clinical trials have reported considerable survival of EGFR mutation positive patients on receiving the EGFR tyrosine kinase inhibitor (TKI). However, the real-world evidence of benefits of EGFR TKI would be further useful to understand how the designated therapeutic regimen benefits the patients. In this study, we report a decade long real-world evidence of EGFR molecular testing in lung cancer at Tata Memorial Hospital (Mumbai, India). Laboratory and hospital records containing basic demographic details, clinical characteristics, treatment regimen, survival outcome were collected retrospectively. Statistical association and survival analysis were performed using the R programming. The cohort includes 9,053 lung cancer patients tested for EGFR mutations during 2011 to 2019. Baseline T790M and compound mutations were the only mutations observed co-occurring while all other EGFR mutations were mutually exclusive. Furthermore, the baseline T790M were also observed to be associated with TTF1 positivity, smoking and local metastasis. Overall survival of the patients harboring co-occurring compound mutations was significantly lesser than the other EGFR positive patients. Overall, our study suggests that EGFR TKI may provide real-world benefit to the lung cancer patients harboring mutually exclusive EGFR mutations. On the other hand, further systematic study is essential to develop better therapeutic regimen for co-occurring baseline EGFR T790M and other compound mutations.

Comprehensive Development and Implementation of Good Laboratory Practice for NGS Based Targeted Panel on Solid Tumor FFPE Tissues in Diagnostics.

The speed, accuracy, and increasing affordability of next-generation sequencing (NGS) have revolutionized the advent of precision medicine. To date, standardized validation criteria for diagnostic accreditation do not exist due to variability across the multitude of NGS platforms and within NGS processes. In molecular diagnostics, it is necessary to ensure that the primary material of the FFPE sample has good quality and optimum quantity for the analysis, otherwise the laborious and expensive NGS test may result in unreliable information. Therefore, stringent quality control of DNA and RNA before, during, and after library preparation is an essential parameter. Considering the various challenges with the FFPE samples, we aimed to set a benchmark in QC metrics that can be utilized by molecular diagnostic laboratories for successful library preparation and high-quality NGS data output. In total, 144 DNA and 103 RNA samples of various cancer types with a maximum storage of 2 years were processed for 52 gene focus panels. During the making of DNA and RNA libraries, extensive QC check parameters were imposed at different checkpoints. The decision tree approach can be set as a benchmark for FFPE samples and as a guide to establishing a good clinical laboratory practice for targeted NGS panels.

The Association Of HIV With Health Care Spending And Use Among Medicare Beneficiaries.

An increasingly older population of people with HIV raises concerns about how HIV may influence care for Medicare patients. We therefore sought to determine the extent to which HIV influences additional spending on and use of mental health and medical care among Medicare beneficiaries and, importantly, whether treatment with antiretroviral therapy may reduce this additional spending. Using 2016 Medicare claims, we compared risk-adjusted spending and utilization for Medicare beneficiaries with and without HIV, as well as subgroups of people receiving antiretroviral therapy (ART). Compared to beneficiaries without HIV, those with HIV receiving ART incurred 220.6 percent more spending, mostly driven by ART spending, whereas those with HIV not receiving ART incurred 95.4 percent more spending. Among beneficiaries with HIV, those receiving more months of ART had lower spending on treatment for other chronic conditions relative to those receiving fewer months of ART in a dose-response manner. Beneficiaries with HIV not receiving ART incurred the highest spending related to infections, mental health disorders, and other medical conditions compared to beneficiaries in other HIV subgroups receiving ART for various numbers of months. Our findings suggest that ART may be associated with Medicare Parts A and B savings, but ART adherence and the high prices of HIV drugs in Part D need to be addressed.