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Targeted therapies have changed the treatment landscape of non-small-cell lung cancer and led to improved patient survival across all stages of lung cancer. Newer advances in common and novel oncogenic drivers continue to occur at vigorous speed, making it challenging to stay up to date with the rapidly evolving field. In this article, we review the emerging perspectives in the treatment of actionable targets in lung cancer. We focus on the development of newer KRAS-directed therapies, particularly on non-G12C mutations, pan-RAS inhibitors, and RAS-GTP inhibitors. We also describe the current standard of care for EGFR- and ALK-altered NSCLC and dive into the novel treatments expected to be in the clinic soon. A similar approach is taken toward MET, HER2, RET, ROS1, and FGFR alterations as emerging targets in non-small-cell lung cancer. Finally, we conclude this review with the current body of evidence for targeting TROP-2 as a novel target, potentially of importance in post-targeted therapy scenarios.

Proteasome inhibitors (PIs) are an integral component of multiple myeloma therapies. Peripheral neuropathy (PN) is a well-knownconsequence of PIs, most frequently reported with earlier generations such as bortezomib (BTZ). There is a paucity of data highlighting the risk of developing PN with the new-generation PIs carfilzomib (CFZ) and ixazomib (IZB). This study evaluated reports of PN encountered with all three PIs using the Food and Drug Administration Adverse Event (AE) Reporting System (FAERS). Signal disproportionality analysis was reported using the reporting odds ratio (ROR) with 95% confidence interval (CI). PN was reported in a total of 2.1%, 5.0%, and 10.9% of AEs with CFZ, IZB, and BTZ, respectively. The ROR (95% CI) for PN secondary to BTZ, CFZ, and IZB was 34.10 (32.76-35.49), 6.37 (5.50-7.37), and 14.97 (13.63-16.44), respectively. Compared to BTZ, CFZ and IZB have lower rates of reported PN, with RORs of 0.19 (0.16-0.22) and 0.48 (0.43-0.54), respectively.

Bangladesh is facing a growing cancer burden with rising incidence and mortality rates. Limited healthcare infrastructure, high costs, and a shortage of trained professionals contribute to inadequate cancer care, especially in rural areas. Although the country has implemented the “Multisectoral Action Plan for Prevention and Control of Non-communicable Diseases” to improve cancer care, significant gaps remain in access to diagnostic tools, specialized treatment, and affordable cancer drugs. Community-based screening programs for breast and cervical cancer have been introduced, but have limited coverage. Efforts to establish comprehensive cancer centers in each division and integrate advanced technologies, like AI, are underway to enhance early diagnosis, treatment, and surveillance. There is a need for improved healthcare governance, sustainable financing, and collaboration among various sectors to manage and reduce the cancer burden in Bangladesh effectively. Establishing a National cancer registry, expanding access to specialized care, and enhancing research capabilities are crucial steps for improving cancer care management.

BackgroundIn May 2024, the FDA approved tarlatamab, a Delta-like ligand (DLL3)/CD3-targeted bispecific T-cell engager, for patients with extensive-stage small cell lung cancer (SCLC) with disease progression following platinum-based chemotherapy and at least one other prior line of therapy. We aim to examine the cellular immune cell profile changes seen in patients receiving this therapy in standard-of-care (SOC) practice.MethodsPatients who received tarlatamab at Mayo Clinic Rochester consented to research blood. Immune phenotyping was performed on whole blood by flow cytometry and analyzed by Kaluza. Data analysis was performed with Excel and PRISM.ResultsThirteen patients with a median age 64 years (range 41-80) who were treated and evaluable for clinical response were included, 53% were women. All had a history of tobacco use.Nine (69%) patients had progressive disease (PD) after a median of 2 cycles, whereas 4 patients had partial response (PR) or stable disease (SD) after at least 2 cycles and remain on therapy (no-PD). Compared to the no-PD group, those whose disease PD early had higher levels of exhausted CD8 T cells at baseline (PD1+TIGIT+CD57+, PD vs no-PD, cells/µL: 17.4±5.6, 7.6±2.6, p=0.006). Interestingly, a CD8 TIGIT+PD1negCD57neg population was also identified which was higher at baseline (PD vs no-PD, cells/µL: 21.5±16.9, 12.2±5.33, p=0.039) and decreased significantly for the PD group from baseline to day 7 (21.5±16.9 to 9.30±10, p=0.039; figure 1A). This population was found to have a different functional profile than the exhausted phenotype in other solid tumors and its role in small cell lung cancer has not been defined. At day 7, compared to the no-PD group, the PD group also had a high level of B-cells (PD vs no-PD, cells/µL: 10.3±15, 4.07±1.83, p=0.027), classical monocytes (PD vs no-PD, cells/µL: 365±279, 226±121, p=0.035), and immunosuppressive monocytes (CD14+HLA-DRneg monocytes, cells/µL: 119±93, 33±42, p=0.05). In addition, the no-PD group had a statistically significant decrease from baseline to day 7 in intermediate monocytes (32.5±7.9 to 17±2.6, p=0.049; figure 1B).ConclusionsIn this study investigating the SOC outcomes of tarlatamab, early PD was associated with higher presence of exhausted CD8 T cells, B cells, and immunosuppressive monocytes. Analysis of additional patients will be shared at SITC meeting.Abstract 844 Figure 1ACD8 T cell phenotype associated with clinical response[Image Omitted. See PDF.]Abstract 844 Figure 1BMonocyte phenotype associated with clinical response[Image Omitted. See PDF.]

There are limited numbers of studies which comprehensively explored the research publications authored by medical students. To descriptively analyze the student-authored research publications originating from Alfaisal University—College of Medicine (Riyadh, Saudi Arabia) over a 6-year period. All student-authored research publications were retrieved from PubMed ® and the College’s publication database. Study inclusion criteria included: (1) at least one medical student author, (2) published and/or accepted in - press PubMed-indexed article from 10 September 2008 to 31 December 2014. Data was transferred to Microsoft Excel Software for descriptive statistical analysis of variable parameters. Seventy-three (n = 73) articles met the study inclusion criteria. They were published by 170 students; the majority were males (79.4 %) and clerkship students (65.9 %). There was a markedly steady increase in number of yearly publications from 1 publication in 2009 to 35 publications by the end of 2014. Fifty (68.5 %), twenty-nine (39.7 %) and thirty-seven (50.7 %) students were first, second and corresponding authors, respectively. The most frequent research areas were clinical science (43.8 %), basic science (23.3 %) and medical education (21.9 %). The most frequent research types were case reports (41.1 %), research articles (32.9 %) and correspondence letters (15.1 %). Fifty-seven (78.1 %) and sixteen (21.9 %) publications took place in local and abroad institutes, respectively. Most publications (71.2 %) had impact factors below 2. The mean ± SD of articles’ impact factors and citations were 3.9 ± 9.9 and 1.9 ± 4.1, respectively. Students demonstrated positive attitudes towards publishing and significantly contributed to the institution’s pool of research publications.

BackgroundThe evidence base for stigma in mental health largely originates from high-income countries.AimsThis study from Pakistan aimed to address the gap in literature on stigma from low- and middle-income countries.MethodThis cross-sectional study surveyed 1470 adults from Karachi, Pakistan. Participants from three groups (healthcare professionals, healthcare students and the general public) completed the adapted Bogardus Social Distance Scale (SDS) as a measure of stigma.ResultsAll three groups reported higher scores of stigma toward mental disorders compared with physical disorders. SDS scores for mental illness in the general public were significantly higher than in healthcare students (mean difference (MD) 6.93, 95% CI 5.45–8.45, P < 0.001) and healthcare professionals (MD 6.93, 95% CI 5.48–8.38, P < 0.001). However, SDS scores between healthcare students and healthcare professionals were not significantly different (MD 0.003, 95% CI −1.14–1.14, P > 0.99). Being female was associated with lower stigma scores and being over the age of 30 years was associated with higher stigma scores.ConclusionsStigma campaigns in Pakistan need to target the general population. However, evidence of negative attitudes toward mental illness in healthcare students and healthcare professionals supports the need for stronger emphasis on psychiatric education within undergraduate and postgraduate training in Pakistan.

Background and aim Antenatal care (ANC) is universally acknowledged as an essential intervention for enhancing the well-being of both mothers and children. The World Health Organization advises a minimum of four ANC visits. The objective of this study is to assess the effectiveness of adequate ANC in mitigating adverse perinatal outcomes. Methods This cross-sectional study was done at the Department of Obstetrics and Gynecology, Delta Medical College & Hospital, Bangladesh, from March 2023 to August 2023. A total of 226 mothers who gave birth at the hospital during this period were enrolled in the study. Results More than 87% of the participants received adequate (≥4 visits) antenatal care from a registered physician. More than 84% of the mothers gave birth via cesarean section. Among the mothers who received inadequate ANC, the proportion of adverse perinatal outcomes was higher (69.0%) than that of those who received adequate ANC (32.0%). A significant association (p<0.05) was noted between inadequate antenatal care and adverse perinatal outcomes. Pregnant women receiving adequate antenatal checkups were 79% less likely to experience adverse perinatal outcomes compared to those receiving inadequate ANC. Conclusion Adequate ANC is a very efficient and economical strategy for mitigating adverse perinatal outcomes.

The local tissue effects of mRNA vaccination remain incompletely understood. We investigated how SARS-CoV-2 mRNA vaccination impacts injection site tissues in the context of different metabolic states and apolipoprotein E (ApoE) status. We administered intramuscular SARS-CoV-2 mRNA vaccination to wild-type and ApoE-deficient mice under regular and high-fat diets, as well as macaques. We performed transcriptomic analysis, ultrastructural examination, functional assessments including grip strength testing, and immunological evaluations to characterize local and systemic responses. Intramuscular vaccination induced localized injury characterized by inflammation, mitochondrial disruption, and reduced grip strength in wild-type animals. Transcriptomic and ultrastructural analyses revealed denervation-associated changes, downregulation of mitochondrial genes, cristae disruption, and activation of immune and apoptotic pathways. ApoE-deficient mice, particularly under Western diet conditions, demonstrated protection from mitochondrial and inflammatory responses despite comparable vaccine expression levels. This protection involved attenuated mitochondrial gene downregulation, preserved mitochondrial DNA integrity, and reduced inflammatory responses. While ApoE deficiency resulted in diminished antibody production, T cell responses remained intact, indicating selective immunomodulation. Cardiac tissue showed minimal transcriptional changes, confirming injection site-specific effects. ApoE deficiency provides protection against vaccine-induced mitochondrial and inflammatory damage at the injection site, with enhanced protective effects under metabolic stress conditions. These findings reveal important interactions between metabolic status, lipid metabolism, and local vaccine responses that may inform vaccination strategies in different patient populations.