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Background: The contemporary management and resectability of locally advanced lung cancer are undergoing significant changes as new data emerge regarding immunotherapy and targeted treatments. The objective of this document is to review the literature and present consensus among a group of multidisciplinary experts to guide the determination of resectability and management of locally advanced non-small cell lung cancer (NSCLC) in the context of contemporary evidence., Methods: The Society of Thoracic Surgeon Workforce on Thoracic Surgery assembled a multidisciplinary expert panel composed of thoracic surgeons and medical and radiation oncologists with established expertise in the management of lung cancer. A focused literature review was performed, and expert consensus statements were developed using a modified Delphi process to address 3 major themes: (1) assessing resectability and multidisciplinary management of locally advanced lung cancer, (2) neoadjuvant (including perioperative) therapy, and (3) adjuvant therapy., Results: A consensus was reached on 19 recommendations. These consensus statements reflect updated insights on resectability and multidisciplinary management of locally advanced lung cancer based on the latest literature and current clinical experience, mainly focusing on the appropriateness of surgical therapy and emerging data regarding neoadjuvant and adjuvant therapies., Conclusions: Despite the complex decision-making process in managing locally advanced lung cancer, this expert panel agreed on several key recommendations. This document provides guidance for thoracic surgeons and other medical professionals in the optimal management of locally advanced lung cancer based on the most updated evidence and literature., Competing Interests: Disclosures Samuel S. Kim reports a relationship with Intuitive Surgical Inc that includes: funding grants and speaking and lecture fees. David T. Cooke reports a relationship with Bristol-Myers Squibb Co that includes: speaking and lecture fees. Biniam Kidane reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and speaking and lecture fees; with Merck & Co Inc that includes: consulting or advisory and speaking and lecture fees; with Roche that includes: consulting or advisory and speaking and lecture fees; with Medtronic that includes: consulting or advisory and speaking and lecture fees; and with Olympus Corporation that includes: consulting or advisory and speaking and lecture fees. Samuel S. Kim reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Luis Tapia Vargas reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory. Jyoti Patel reports a relationship with AbbVie Inc that includes: consulting or advisory; with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory; with Bristol-Myers Squibb Co that includes: consulting or advisory; with Gilead Sciences Inc that includes: consulting or advisory; with Guardant Health Inc that includes: consulting or advisory; with Sanofi that includes: consulting or advisory; with Tempus that includes: consulting or advisory; with AnHeart Therapeutics that includes: consulting or advisory; with Blueprint Genetics that includes: consulting or advisory; and with Black Diamond Therapeutics that includes: consulting or advisory. Joel Neal reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory; with Genetec Inc that includes: consulting or advisory; with Exelixis Inc that includes: consulting or advisory; with Takeda Pharmaceutical Company Ltd that includes: consulting or advisory; with Eli Lilly and Company that includes: consulting or advisory; with Amgen Inc that includes: consulting or advisory; with Sanofi that includes: consulting or advisory; and with Bristol-Myers Squibb Co that includes: consulting or advisory. Joseph Shrager reports a relationship with AstraZeneca Pharmaceuticals LP that includes: consulting or advisory and with Becton Dickinson and Company that includes: consulting or advisory. The other authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: The study aims to address the global burden of dental caries, a highly prevalent disease affecting billions of individuals, including both children and adults. Recognizing the significant health challenges posed by untreated dental caries, particularly in low- and middle-income countries, our goal is to improve early-stage detection. Though effective, traditional diagnostic methods, such as bitewing radiography, have limitations in detecting early lesions. By leveraging Artificial Intelligence (AI), we aim to enhance the accuracy and efficiency of caries detection, offering a transformative approach to dental diagnostics., Materials and Methods: This study proposes a novel deep learning-based approach for dental caries detection using the latest models, i.e., YOLOv7, YOLOv8, and YOLOv9. Trained on a dataset of over 3,200 images, the models address the shortcomings of existing detection methods and provide an automated solution to improve diagnostic accuracy., Results: The YOLOv7 model achieved a mean Average Precision (mAP) at 0.5 Intersection over Union (IoU) of 0.721, while YOLOv9 attained a mAP@50 IoU of 0.832. Notably, YOLOv8 outperformed both, with a mAP@0.5 of 0.982. This demonstrates robust detection capabilities across multiple categories, including caries," "Deep Caries," and "Exclusion.", Conclusions: This high level of accuracy and efficiency highlights the potential of integrating AI-driven systems into clinical workflows, improving diagnostic capabilities, reducing healthcare costs, and contributing to better patient outcomes, especially in resource-constrained environments., Clinical Relevance: Integrating these latest YOLO advanced AI models into dental diagnostics could transform the landscape of caries detection. Enhancing early-stage diagnosis accuracy can lead to more precise and cost-effective treatment strategies, with significant implications for improving patient outcomes, particularly in low-resource settings where traditional diagnostic capabilities are often limited., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Conflict of Interests: The authors declare that they have no known financial and non-financial conflicts or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Broad-based molecular testing with next-generation sequencing (NGS) is now the standard of care in advanced non-small cell lung cancer (NSCLC). Two approaches to molecular testing are (1) reflexive testing at pathologic NSCLC confirmation, often using an in-house molecular panel, and (2) send-out testing to private vendors, ordered by a clinician. This study explored the outcomes with reflex versus send-out testing., Methods: A retrospective chart review was conducted of patients diagnosed with de novo stage IV NSCLC in 2019 and 2020 at three hospitals in the same system, one academic hospital (Northwestern Memorial Hospital, or NMH) utilizing reflex, in-house NGS, and two community-based hospitals (Central DuPage Hospital, or CDH, and Delnor, or D) sending out tissue samples for testing. The outcomes assessed were the time from biopsy to results, biopsy to treatment, the incidence of first-line targetable mutations and the use of first-line targeted therapies, and overall survival., Results: In total, 191 patients met the inclusion criteria, 85 at NMH, 106 at CDH + D, and in total, 131 in 2019 and 60 in 2020. The time to results was significantly shorter with reflexive NGS when compared with send-out testing; the time to treatment was also shorter but not statistically significant. At CDH + D, the time to results was significantly shorter with a limited panel than with comprehensive testing, but the time to treatment was similar. NGS testing rates were 95% at NMH and 84.5% at CDH + D ( p = 0.009), with 31.0% at NMH receiving 1L targeted therapies versus 20.8% at CDH + D ( p = 0.08). In 2019, the median time from biopsy to treatment was 35 days at NMH and 38 days at CDH and Delnor; in 2020, time to treatment was 26 days and 37 days, respectively. Overall survival trended longer in 2020 relative to 2019 independent of site., Conclusion: Reflexive NGS testing is associated with a shorter time to actionable results and higher rates of first-line targetable mutations than send-out testing. In practices with send-out testing, limited panels had slightly faster turnaround times but no difference in time to treatment. If resources allow, reflexive NGS should be considered in healthcare systems for patients with NSCLC.

Purpose: Preclinical studies demonstrated that dual inhibition of epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF) pathways delay the emergence of resistance to EGFR tyrosine kinase inhibitors (TKIs), and in trials with first-generation EGFR TKIs, the combination of EGFR VEGF pathway inhibitors prolonged progression-free survival (PFS)., Methods: The RAMOSE trial (ClinicalTrials.gov identifier: NCT03909334, HCRN LUN-18-335) is a randomized, open-label multicenter phase II study comparing osimertinib with ramucirumab (arm A) to osimertinib (arm B) for initial treatment of metastatic EGFR -mutant non-small cell lung cancer (NSCLC) with 2:1 random assignment. The primary end point is PFS for evaluable patients; secondary end points include objective response rates (ORRs), disease control rate (DCR), overall survival, and safety. The stratification criteria were EGFR mutation type and the presence of CNS metastasis., Results: At data cutoff on August 29, 2023, 160 patients consented, 147 patients received treatment, and 139 patients were evaluable with at least one scan. In this preplanned interim analysis, the median follow-up was 16.6 months. Among the evaluable patients, 57 PFS events occurred. The median PFS was 24.8 (A) versus 15.6 (B) months (hazard ratio, 0.55 [95% CI, 0.32 to 0.93]; log-rank P = .023), 12-month PFS rate was 76.7% (A) versus 61.9% (B; P = .026). No significant difference was observed in the ORRs and DCRs between arms. Any-grade (G) adverse events (AEs) occurred in 100% (A) and 98% (B) of patients, with no G5 treatment-related AE (TRAE), one G4 TRAE (hyponatremia, A), and 53% (A) versus 41% (B) G3 TRAEs. AE-related discontinuation occurred in 13 patients (9.7% in A and 8.7% in B). The safety profile was in line with known safety of each drug., Conclusion: Ramucirumab plus osimertinib significantly prolonged PFS compared with osimertinib alone in patients with TKI-naïve EGFR -mutant NSCLC. The combination is safe and well tolerated.

Introduction: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort., Methods: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15-180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone., Results: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02)., Conclusions: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy., (© 2024. The Author(s).)

Background: Stereotactic body radiotherapy (SBRT) is safe and effective for treatment of extracranial metastatic disease, but its safety when combined with immune checkpoint inhibitors (ICI) has not yet been comprehensively reported. Here we report adverse events (AEs) associated with combined SBRT and ICI using prospectively-collected data on patients in three trials investigating multi-site SBRT combined with ICI., Methods: Patients were included from three prospective trials of ICI (pembrolizumab; nivolumab/urelumab or nivolumab/cabiralizumab; nivolumab/ipilimumab) with SBRT to 1-4 sites. AEs were recorded prospectively using the CTCAE v4.0. Survival was analyzed using Kaplan-Meier method with a 90-day landmark. Association of patient characteristics with cumulative incidence of AEs was assessed using Fine-Gray regression., Results: 213 patients were included, with a median follow-up of 10 months. Over the follow-up period, 50 % and 27 % of patients experienced at least one grade ≥ 2 or grade ≥ 3 AE, respectively. Cumulative incidences of grade ≥ 2 and grade ≥ 3 AEs at 6 months were 47 % and 23 %, respectively. Three grade 5 AEs rated "possibly" related to treatment occurred outside the 90-day dose-limiting toxicity window. Landmarked survival analysis of patients with or without grade ≥ 3 AEs showed no significant difference in progression-free or overall survival. Dual-agent ICI was significantly associated with grade ≥ 3 AE., Conclusion: This analysis features the largest prospectively evaluated cohort of patients treated with combination ablative SBRT and ICI to date and provides context for future trial design. We conclude that multi-site SBRT and ICI can be safely co-administered when SBRT is delivered with prioritization of normal tissue constraints., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Connor Lynch: none to declare. Mark C. Korpics: none to declare. Rohan R. Katipally: none to declare. Christine M. Bestvina: Institutional funding from AstraZeneca and Bristol Myers Squibb; consulting fees from AstraZeneca, Bristol Myers Squibb, CVS, Daiichi Sankyo, Genentech, Jazz, Johnson and Johnson, Novartis, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Tempus; participates in the Data Safety Monitoring and/or Advisory Board of AstraZeneca, Bristol Myers Squibb, CVS, Daiichi Sankyo, Genentech, Jazz, Johnson and Johnson, Novartis, Pfizer, Regeneron, Sanofi, Seattle Genetics, Takeda, Tempus. Sean P. Pitroda: Speaker’s Bureau for AACR and Immunorad conferences; co-founder of PersonaDx; co-inventor of patent related to metastatic disease and prognostication via University of Chicago IP office. Jyoti D. Patel: Consulting and Advisory Board for Abbvie, AstraZeneca, Takeda Science Foundation, Genentech, Anheart Therapeutics; travel, accommodations, or expenses from Tempus. Jason J. Luke: DSMB: Abbvie, Agenus, Evaxion, Immutep, Shionogi; Scientific Advisory Board: (no stock) 7 Hills, Affivant, BioCytics, Bright Peak, Exo, Fstar, Inzen, RefleXion, Xilio (stock) Actym, Alphamab Oncology, Arch Oncology, Duke Street Bio, Elipscience, Kanaph, NeoTx, Onc.AI, OncoNano, physIQ, Pyxis, Saros, STipe, Tempest; Consultancy with compensation: Abbvie, Agenus, Alnylam, AstraZeneca, Askgene, Atomwise, Bayer, Bristol-Myers Squibb, Castle, Checkmate, Codiak, Crown, Cugene, Curadev, Day One, Eisai, EMD Serono, Endeavor, Flame, G1 Therapeutics, Genentech, Gilead, Glenmark, HotSpot, Kadmon, Ko Bio Labs, Krystal, KSQ, Janssen, Ikena, Inzen, Immatics, Immunocore, Incyte, Instil, IO Biotech, LegoChem, Macrogenics, Merck, Mersana, Nektar, Novartis, Partner, Pfizer, Pioneering Medicines, PsiOxus, Regeneron, Replimmune, Ribon, Roivant, Servier, STINGthera, Storm, Sumoitomo, Synlogic, Synthekine, Teva; Research Support: (all to institution) AbbVie, Astellas, Astrazeneca, Bristol-Myers Squibb, Corvus, Day One, EMD Serono, Fstar, Genmab, Hot Spot, Ikena, Immatics, Imugene, Incyte, Janux, Kadmon, KAHR, Macrogenics, Merck, Moderna, Nektar, Next Cure, Novartis, Numab, Palleon, Pfizer, Replimmune, Rubius, Servier, Scholar Rock, Synlogic, Takeda, Trishula, Tizona, Tscan, Werewolf, Xencor; Patents: US-11638728 (Microbiome Biomarkers for Anti-PD-1/PD-L1 Responsiveness: Diagnostic, Prognostic and Therapeutic Uses Thereof). Steven J. Chmura: Institutional funding from Bristol Myers Squibb; Family member employed by Astellas Pharmaceuticals. Aditya Juloori: Institutional funding from AstraZeneca; Consulting fees from Isoray, General Electric, and Aqualung., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objective: To establish and evaluate a multimodal, opioid-minimizing pathway for gender-affirming vaginoplasty (GAVa) and vulvoplasty (GAVu) in treating postoperative pain., Methods: A standardized pain pathway including opioids, non-opioid analgesics, and patient counseling was implemented at a single academic institution with a center for transgender care. Postoperative pain levels, analgesia methods, and opioid use for 84 GAVa and 64 GAVu patients were prospectively gathered during inpatient postoperative days 2-4 and outpatient follow-up at 2 weeks. Pertinent patient, operative, and medication administration data were extracted from patient charts and outpatient pain was measured with the Brief Pain Inventory short form (BPI-sf)., Results: On average, GAVa patients used 89.3 MME and GAVu patients used 41.8 MME during inpatient stay. MME decreased daily for both groups. There was no difference in MME between open and robotic GAVa. Forty-nine percent of GAVa patients and 54% of GAVu patients used ketorolac with decreasing daily inpatient use. Postoperative pain levels were similar between GAVa and GAVu patients. Fifty percent of respondents denied postoperative pain in the 24 hours preceding the survey. Forty-four percent of GAVa and of GAVu patients did not use any opioid medications in the outpatient setting, while 81% of GAVa and 83% of GAVu patients used fewer than 20 of 30 prescribed opioid tablets. Ibuprofen and acetaminophen were rated the most effective outpatient analgesics among GAVa and GAVu patients, respectively., Conclusion: The multimodal pathway demonstrated effective postoperative pain control for GAVa and GAVu patients while minimizing opioid use and has changed institutional prescribing practice., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: There are no conflicts of interest.

Aim: To compare the efficacy of virtual reality (VR) glasses and on-screen distraction techniques in managing anxiety and behavior in children receiving dental treatments., Materials and Methods: Forty patients aged 4-8 years requiring restoration were divided into two groups: group I with 20 members using audio-visual distraction aid in the form of VR glasses and group II with 20 participants utilizing on-screen distraction techniques. Each child underwent two appointments one week apart; their anxiety and behavior levels were assessed at each visit using the Facial Image Scale and Frankel's Behavior rating scale., Result: The Wilcoxon signed-rank and Chi-squared test were utilized to assess the correlation between two categorical variables, with VR demonstrating a notable divergence from on-screen distraction., Conclusions: Both on-screen distraction and VR applications decreased anxiety levels and improved behavior. However, VR was substantially more effective in managing these areas., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Journal of Pharmacy and Bioallied Sciences.)

Interest in the importance of gas sensing devices has increased significantly due to their critical function in monitoring the environment and controlling pollution, resulting in an increased market demand. The present review explores perovskite La-Fe-O based gas sensors with a special focus on LaFeO 3 and evaluates their sensitivity to a diverse range of practical target gases that need to be monitored. An analysis has been conducted to assess different routes not only of synthesizing LaFeO 3 material but also of characterization with the targeted use for their gas sensing abilities. Additionally, a comprehensive analysis has been performed to explore the effect of introducing other elements through doping. In view of the LaFeO 3 sensing performance, more common gases like acetone, ethanol, methanol, formaldehyde, NO x , and CO 2 have been targeted. In addition, a discussion on uncommon gases such as CO, SO 2 , TEA, C 2 H 5 , C 6 H 6 , and others is also made to give a complete picture of LaFeO 3 -based gas sensors. The summary and conclusion section of the study addresses the primary obstacles in the synthesis process, the variables that restrict the sensing capabilities of LaFeO 3 , and its commercial fulfillment., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Myofunctional trainer for kids (T4K, Myofunctional Research Co., Australia) is a prefabricated, single-size functional appliance that claims to correct malocclusion at an early age by acting on muscular dysfunctions and repositioning the mandible in a forward direction. Myofunctional therapy through the Trainer System™ was implemented in this case for the treatment of class II malocclusion in mixed dentition. The results showed that an early approach in selected cases, taking into account patient preferences and compliance, is possible and could be considered in treatment planning and relevant future research., How to Cite This Article: Jyoti D, Beni K, Shukla JN, et al. Dentoskeletal Correction by Growth Modification in a Young Child Using Myofunctional Trainer: A Case Report. Int J Clin Pediatr Dent 2024;17(6):728-733., Competing Interests: Source of support: Nil Conflict of interest: None Patient consent statement: The author(s) have obtained written informed consent from the patient’s parents/legal guardians for publication of the case report details and related images.Conflict of interest: None, (Copyright © 2024; The Author(s).)

Competing Interests: Disclosure All authors have nothing to disclose.

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer with driver alterations., Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations., Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Eight new RCTs were identified in the latest search of the literature to date., Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients based on targetable driver alterations.Additional information is available at www.asco.org/living-guidelines.

Purpose: To provide evidence-based recommendations for patients with stage IV non-small cell lung cancer (NSCLC) without driver alterations., Methods: This ASCO living guideline offers continually updated recommendations based on an ongoing systematic review of randomized clinical trials (RCTs), with the latest time frame spanning February to October 2023. An Expert Panel of medical oncology, pulmonary, community oncology, research methodology, and advocacy experts were convened. The literature search included systematic reviews, meta-analyses, and randomized controlled trials. Outcomes of interest include efficacy and safety. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations., Results: This guideline consolidates all previous updates and reflects the body of evidence informing this guideline topic. Ten new RCTs were identified in the latest search of the literature to date., Recommendations: Evidence-based recommendations were updated to address first, second, and subsequent treatment options for patients without driver alterations.Additional information is available at www.asco.org/living-guidelines.

Background: Combination chemotherapy and immunotherapy regimens have significantly improved survival for patients with previously untreated advanced non-small cell lung cancer (NSCLC). Improvements in overall survival (OS) in two separate pembrolizumab trials have demonstrated survival improvements over chemotherapy alone, regardless of PD-L1 status. The optimal chemotherapy backbone for combination with immunotherapy is unknown. We hypothesized nab-paclitaxel may be a well-suited platinum partner to use in combination with checkpoint inhibitor therapy for both adenocarcinoma and squamous histology and conducted a phase I/II trial to assess the efficacy of this regimen in advanced NSCLC., Methods: Adult patients with previously untreated, stage IIIB/IV NSCLC (any histology) with an Eastern Cooperative Oncology Group performance status of 0-1, any PD-L1 expression, and no EGFR mutations or ALK translocations, received carboplatin area under the curve (AUC) 6 day 1, nab-paclitaxel 100 mg/m2 days 1, 8, 15, and pembrolizumab 200 mg day 1 q21 days for 4 cycles followed by maintenance pembrolizumab q3w. Co-primary endpoints were progression-free survival (PFS) and overall response rate (ORR)., Results: Forty-six evaluable patients enrolled, 14 in phase I and 32 in phase II, from June 2015 to July 2018 with a median duration of follow-up of 35.4 months. Median time from enrollment to data lock was 42 months. In the ITT population, the ORR was 35%, median PFS was 5.6 months (95% CI, 4.6-8.2), and median OS was 15.4 months (CI, 12.4-28.1). There were no statistical differences in PFS or OS by PD-L1 status. The 2- and 3-year landmark OS rates were 33% and 24%, respectively., Conclusion: Carboplatin, nab-paclitaxel, and pembrolizumab are a safe and effective regimen for patients with both squamous and nonsquamous NSCLC. Although this study did not meet the prespecified endpoints, the median and landmark OS results are consistent with durable benefit of this regimen as seen in phase III trials for first-line treatment of advanced NSCLC., (© The Author(s) 2023. Published by Oxford University Press.)

Personal care products (PCPs) are products used in cleaning, beautification, grooming, and personal hygiene. The rise in diversity, usage, and availability of PCPs has resulted in their higher accumulation in the environment. Thus, these constitute an emerging category of environmental contaminants due to the potential of its constituents (chemical and non-chemical) to induce various physiological effects even at lower concentrations (ng/L). For analyzing the impact of the PCPs constituents on the non-target organism about 300 article including research articles, review articles and guidelines were studied from 2000 to 2023. This review aims to firstly discuss the fate and accumulation of PCPs in the aquatic environment and organisms; secondly provides overview of environmental risks that are linked to PCPs; thirdly review the trends, current status of regulations and risks associated with PCPs and finally discuss the knowledge gaps and future perspectives for future research. The article discusses important constituents of PCPs such as antimicrobials, cleansing agents and disinfectants, fragrances, insect repellent, moisturizers, plasticizers, preservatives, surfactants, UV filters, and UV stabilizers. Each of them has been found to display certain toxic impact on the aquatic organisms especially the plasticizers and UV filters. These continuously and persistently release biologically active and inactive components which interferes with the physiological system of the non-target organism such as fish, corals, shrimps, bivalves, algae, etc. With a rise in the number of toxicity reports, concerns are being raised over the potential impacts of these contaminant on aquatic organism and humans. The rate of adoption of nanotechnology in PCPs is greater than the evaluation of the safety risk associated with the nano-additives. Hence, this review article presents the current state of knowledge on PCPs in aquatic ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: To describe the characteristics of patients presenting for gender-affirming bilateral simple orchiectomy including interest in and prior education on reproductive options prior to gonad removal., Methods: A retrospective chart review evaluated patients seeking gender-affirming bilateral orchiectomy. Data collected included age, family history, history of fertility preservation education prior to gender-affirming hormone therapy initiation, prior fertility preservation, interest in fertility preservation, and postorchiectomy surgical pathology results where applicable., Results: The cohort included 78 patients. 22% (n = 17) indicated reproductive options were not discussed prior to surgical consultation. 85% (n = 66) were not interested in fertility preservation. Reasons included not having an interest in biological children (74%), not wanting to delay transition (47%), and cost (36%). Patients who were married or in long-term relationships had a higher interest in fertility preservation compared to patients who were not in long-term relationships. 40% of patients with pathology data available had at least some level of spermatogenesis present in their testicular tissue., Conclusion: Fertility preservation counseling prior to surgical referral was lower than expected. This lack of counseling could result in patients not wanting to sperm bank prior to orchiectomy as it could delay their surgical care. Increased adherence to the WPATH guidelines may improve fertility preservation interest. Our data shows a low utilization and interest in sperm preservation for transwomen and nonbinary patients seeking bilateral simple orchiectomy at our institution. Improving counseling regarding fertility preservation options earlier in transition could improve utilization of sperm cryopreservation., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2023. Published by Elsevier Inc.)

Patients with metastatic epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) are widely treated with osimertinib, the preferred first-line treatment option. However, disease progression inevitably occurs, driven by EGFR-dependent or EGFR-independent mechanisms of resistance. Platinum-based chemotherapy is the recommended treatment following progression with osimertinib but responses to platinum-based chemotherapy are transient. Salvage therapies, which are used after progression on platinum-based chemotherapy, have poor clinical outcomes in addition to substantial toxicity. In this podcast, we discuss the current treatment landscape and emerging therapeutic options for patients with metastatic EGFR-mutated NSCLC whose disease has progressed following treatment with osimertinib and platinum-based chemotherapy.Podcast audio available for this article., (© 2023. The Author(s).)

Background: Patients with thoracic malignancies who develop COVID-19 infection have a higher hospitalization rate compared to the general population and to those with other cancer types, but how this outcome differs by race and ethnicity is relatively understudied., Methods: The TERAVOLT database is an international, multi-center repository of cross-sectional and longitudinal data studying the impact of COVID-19 on individuals with thoracic malignancies. Patients from North America with thoracic malignancies and confirmed COVID-19 infection were included for this analysis of racial and ethnic disparities. Patients with missing race data or races and ethnicities with fewer than 50 patients were excluded from analysis. Multivariable analyses for endpoints of hospitalization and death were performed on these 471 patients., Results: Of the 471 patients, 73% were White and 27% were Black. The majority (90%) were non-Hispanic ethnicity, 5% were Hispanic, and 4% were missing ethnicity data. Black patients were more likely to have an Eastern Cooperative Oncology Group (ECOG) Performance Status ≥ 2 (p-value = 0.04). On multivariable analysis, Black patients were more likely than White patients to require hospitalization (Odds Ratio (OR): 1.69, 95% CI: 1.01-2.83, p-value = 0.044). These differences remained across different waves of the pandemic. However, no statistically significant difference in mortality was found between Black and White patients (OR 1.29, 95% CI: 0.69-2.40, p-value = 0.408)., Conclusions: Black patients with thoracic malignancies who acquire COVID-19 infection are at a significantly higher risk of hospitalization compared to White patients, but there is no significant difference in mortality. The underlying drivers of racial disparity among patients with thoracic malignancies and COVID-19 infection require ongoing investigation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Patients with non-small-cell lung cancer (NSCLC) who have never smoked or have tumors with mutations in EGFR generally derive minimal benefit from single-agent PD-1/PD-L1 checkpoint inhibitors. Prior data indicate that adding PD-L1 inhibition to anti-VEGF and cytotoxic chemotherapy may be a promising approach to overcoming immunotherapy resistance in these patients, however prospective validation is needed. This trial in progress (NCT03786692) is evaluating patients with stage IV NSCLC who have never smoked or who have tumors with sensitizing EGFR alterations to determine if a 4-drug combination of atezolizumab, carboplatin, pemetrexed, and bevacizumab can improve outcomes compared to carboplatin, pemetrexed and bevacizumab without atezolizumab., Methods: This is a randomized, phase II, multicenter study evaluating carboplatin, pemetrexed, bevacizumab with and without atezolizumab in 117 patients with stage IV nonsquamous NSCLC. Randomization is 2 to 1 favoring the atezolizumab containing arm. Eligible patients include: 1) those with tumors with sensitizing EGFR alterations in exons 19 or 21 or 2) patients who have never smoked and have wild-type tumors (ie, no EGFR, ALK or ROS1 alterations). Patients are defined as having never smoked if they have smoked less than 100 cigarettes in a lifetime. Patients with EGFR-mutated tumors must have disease progression or intolerance to prior tyrosine kinase inhibitor (TKI) therapy. The primary endpoint is progression-free survival (PFS). Secondary endpoints include overall survival (OS), response rate, duration of response, and time to response., Conclusion: This phase II trial is accruing patients at U.S. sites through the National Comprehensive Cancer Network (NCCN). The trial opened in August 2019 and accrual is expected to be completed in the Fall of 2024., (Copyright © 2023. Published by Elsevier Inc.)

Purpose: Lung Cancer Master Protocol (Lung-MAP), a public-private partnership, established infrastructure for conducting a biomarker-driven master protocol in molecularly targeted therapies. We compared characteristics of patients enrolled in Lung-MAP with those of patients in advanced non-small-cell lung cancer (NSCLC) trials to examine if master protocols improve trial access., Methods: We examined patients enrolled in Lung-MAP (2014-2020) according to sociodemographic characteristics. Proportions for characteristics were compared with those for a set of advanced NSCLC trials (2001-2020) and the US advanced NSCLC population using SEER registry data (2014-2018). Characteristics of patients enrolled in Lung-MAP treatment substudies were examined in subgroup analysis. Two-sided tests of proportions at an alpha of .01 were used for all comparisons., Results: A total of 3,556 patients enrolled in Lung-MAP were compared with 2,215 patients enrolled in other NSCLC studies. Patients enrolled in Lung-MAP were more likely to be 65 years and older (57.2% v 46.3%; P < .0001), from rural areas (17.3% v 14.4%; P = .004), and from socioeconomically deprived neighborhoods (42.2% v 36.7%, P < .0001), but less likely to be female (38.6% v 47.2%; P < .0001), Asian (2.8% v 5.1%; P < .0001), or Hispanic (2.4% v 3.8%; P = .003). Among patients younger than 65 years, Lung-MAP enrolled more patients using Medicaid/no insurance (27.6% v 17.8%; P < .0001). Compared with the US advanced NSCLC population, Lung-MAP under represented patients 65 years and older (57.2% v 69.8%; P < .0001), females (38.6% v 46.0%; P < .0001), and racial or ethnic minorities (14.8% v 21.5%; P < .0001)., Conclusion: Master protocols may improve access to trials using novel therapeutics for older patients and socioeconomically vulnerable patients compared with conventional trials, but specific patient exclusion criteria influenced demographic composition. Further research examining participation barriers for under represented racial or ethnic minorities in precision medicine clinical trials is warranted.

Purpose: Acquired RET fusions have been reported at resistance to treatment with EGFR inhibitors in EGFR-mutant non-small cell lung cancer (NSCLC); however, a multicenter cohort of patients with EGFR-mutant lung cancers treated with osimertinib and selpercatinib for RET fusion-mediated osimertinib resistance has not previously been published., Patients and Methods: Patients who received selpercatinib in combination with osimertinib on a prospective expanded access clinical trial (NCT03906331) and single-patient compassionate use programs across five countries were centrally analyzed. All patients had advanced EGFR-mutant NSCLC with a RET fusion detected from tissue or plasma following osimertinib therapy. Clinicopathologic and outcomes data were collected., Results: Fourteen patients with EGFR-mutant and RET fusion-positive lung cancers who experienced prior progression on osimertinib received osimertinib and selpercatinib. EGFR exon 19 deletions (±T790M, 86%) and non-KIF5B fusions (CCDC6-RET 50%, NCOA4-RET 36%) predominated. Osimertinib 80 mg daily and selpercatinib 80 mg twice daily were the most commonly administered dosages. The response rate, disease control rate, and median treatment duration were 50% [95% confidence interval (CI), 25%-75%, n = 12], 83% (95% CI, 55%-95%), and 7.9 months (range, 0.8-25+), respectively. Resistance was complex, involving EGFR on-target (EGFR C797S), RET on-target (RET G810S), and off-target (EML4-ALK/STRN-ALK, KRAS G12S, BRAF V600E) mechanisms; RET fusion loss; or polyclonal mechanisms., Conclusions: For patients with EGFR-mutant NSCLC with an acquired RET fusion as a mechanism of EGFR inhibitor resistance, the addition of selpercatinib to osimertinib was feasible and safe and offered clinical benefit, supporting the prospective evaluation of this combination. See related commentary by Krebs and Popat, p. 2951., (©2023 American Association for Cancer Research.)

Introduction: The traits of craniofacial skeleton varies with race, ethnicity, and culture. Tetragon cephalometric analysis, first given by J Fastlight, et al . in 2000, consist of simple and efficient method of measuring the maxillomandibular relationship and their relation with cranial base., Aims of the Study: urpose of study is to establish cephalometric norms for tetragon analysis in the Bengali population and differences between Bengali males and females., Materials and Methods: A sample of 100 cephalometric radiographs of class I non-orthodontic subjects aged between 18 and 25 years were traced manually and parameters were statistically analyzed by independent t -test using SPSS software., Results: When compared to Fastlicht's Caucasian norms, the upper and lower jaws of the Bengali people are more prognathic and their incisors are relatively proclined. Both jaws were convergent in Bengali population (horizontal growth pattern). Bengali females had a more protrusive upper jaw, proclined anterior teeth, and vertical growth pattern when compared to Bengali males., Conclusion: Tetragon analysis is an efficient tool to quickly assess the dentoalveolar and jaw relations to formulate treatment goals and to compare treatment outcomes., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Pharmacy and Bioallied Sciences.)

Objectives: Mobocertinib, a novel oral epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, is available for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion (ex20ins) mutations after platinum chemotherapy. We performed an indirect comparison of clinical trial data and real-world data (RWD) to determine the relative efficacy of mobocertinib vs. other treatments for these patients., Materials and Methods: Data on the efficacy of mobocertinib from a phase I/II trial (NCT02716116) were compared to RWD from a retrospective study in 12 German centers using inverse probability of treatment weighting to adjust for age, sex, Eastern Cooperative Oncology Group score, smoking status, presence of brain metastasis, time from advanced diagnosis, and histology. Tumor response assessment was based on RECIST v1.1., Results: The analysis included 114 patients in the mobocertinib group and 43 in the RWD group. The confirmed overall response rate (cORR) according to investigator assessment was 0% for standard treatments and 35.1% (95% confidence interval [CI], 26.4-44.6) for mobocertinib (p < 0.0001). Compared to standard regimens in the weighted population, mobocertinib prolonged overall survival (OS, median [95% CI] = 9.8 [4.3-13.7] vs. 20.2 [14.9-25.3] months; hazard ratio [HR] = 0.42 [0.25-0.69], p = 0.0035), progression-free survival (PFS, median [95% CI] = 2.6 [1.5-5.7] vs. 7.3 [5.6-8.8] months; HR = 0.28 [0.18-0.44], p < 0.0001), and time to treatment discontinuation (median [95% CI] = 2.1 [1.2-3.1] vs. 7.4 [6.4-8.5] months; HR = 0.34 [0.18-0.65], p = 0.0004)., Conclusion: Mobocertinib was associated with an improved cORR and prolonged PFS and OS compared to standard treatments for patients with EGFR ex20ins-positive NSCLC previously treated with platinum-based chemotherapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: PC: research funding from AstraZeneca, Amgen, Merck, Novartis, Roche, and Takeda, speaker’s honoraria from AstraZeneca, Pfizer, Novartis, Roche, Takeda, support for attending meetings from AstraZeneca, Daiichi Sankyo, Eli Lilly, Gilead, Janssen, Novartis, Takeda, and personal fees for participating to advisory boards from Boehringer Ingelheim, Chugai, Pfizer and Roche. TP: employee of Evidera/PPD; ownership of stocks from PPD and Thermo Fisher. JLH: employee of Takeda. HML: employee of Takeda. LH: employee of Takeda. SJ: employee of Takeda. MTa: employee of Evidera/PPD; ownership of stocks from PPD and Thermo Fisher. IP: employee of Evidera/PPD; ownership of stocks from PPD and Thermo Fisher. JL: employee of Takeda. PZ: employee of Takeda. JDP: research funding from BMS, consulting fees from AbbVie, AstraZeneca, Takeda. SHO: research funding from Takeda; speaker’s honoraria from Pfizer, AstraZeneca, Takeda/ARIAD, Roche/Genentech, Daiichi Sankyo, and Janssen/JNJ; ownership of stocks from Turning Point Therapeutics and Elevation Oncology. MT: research funding from AstraZeneca, Bristol-Myers Squibb, Merck, Roche, and Takeda; speaker’s honoraria from AstraZeneca, BeiGene, Bristol-Myers Squibb, Boehringer Ingelheim, Celgene, Chugai, Daiichi Sankyo, GlaxoSmithKline, Janssen Oncology, Eli Lilly, Merck, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda; non-financial support from AstraZeneca, Bristol-Myers Squibb, Janssen Oncology, MSD, Pfizer, Roche, and Takeda. AS: research funding from Bayer, Bristol-Myers Squibb, Chugai, and Incyte; speaker’s honoraria from Aignostics, Amgen, Astra Zeneca, Bayer, BMS, Eli Lilly, Illumina, Incyte, Janssen, MSD, Novartis, Pfizer, Qlucore, Roche, Seagen, Takeda, and Thermo Fisher., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

The effect of Lactiplantibacillus plantarum PGB02 isolated from buttermilk on serum cholesterol profile of normal and hypercholesterolemic mice was evaluated. Further changes in the expression of mice genes were determined. The hypercholesterolemia was induced in experimental mice by feeding high cholesterol and fat diet. Serum cholesterol parameters, physical parameters, cholic acid excretion, and cholesterol metabolism related gene expression analysis was carried out. L. plantarum PGB02 efficiently reduced total cholesterol, triglycerides, and LDL-cholesterol and improved HDL-cholesterol in hypercholesterolaemic mice. Body weight was reduced and fecal cholic acid increased in probiotic treatment groups. Gene expression analysis revealed that L. plantarum PGB02 up-regulated the expression of LDL receptors, CYP7A1, ABCA1, ABCG5, ABCG8, and down-regulated the expression of FXR and NPC1L1 genes. Summarizing the mechanism, L. plantarum PGB02 improved hypercholesterolemia by increasing bile acid synthesis and excretion, reducing exogeneous cholesterol absorption from the intestine, and increased LDL clearance through upregulation of LDL-receptors. The present study has given insight into the mechanism of serum cholesterol reduction by bile salt hydrolase positive L. plantarum PGB02 in mice. L. plantarum PGB02 reduced the serum cholesterol level through increased bile acid synthesis and deconjugation and reduced absorption of cholesterol in the intestine. Isolate PGB02 shown cholesterol removal potential as good as statin., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Measuring tissue parameters from increasingly sophisticated mechanical property models may uncover new contrast mechanisms with clinical utility. Building on previous work on in vivo brain MR elastography (MRE) with a transversely-isotropic with isotropic damping (TI-ID) model, we explore a new transversely-isotropic with anisotropic damping (TI-AD) model that involves six independent parameters describing direction-dependent behavior for both stiffness and damping. The direction of mechanical anisotropy is determined by diffusion tensor imaging and we fit three complex-valued moduli distributions across the full brain volume to minimize differences between measured and modeled displacements. We demonstrate spatially accurate property reconstruction in an idealized shell phantom simulation, as well as an ensemble of 20 realistic, randomly-generated simulated brains. We characterize the simulated precisions of all six parameters across major white matter tracts to be high, suggesting that they can be measured independently with acceptable accuracy from MRE data. Finally, we present in vivo anisotropic damping MRE reconstruction data. We perform t-tests on eight repeated MRE brain exams on a single-subject, and find that the three damping parameters are statistically distinct for most tracts, lobes and the whole brain. We also show that population variations in a 17-subject cohort exceed single-subject measurement repeatability for most tracts, lobes and whole brain, for all six parameters. These results suggest that the TI-AD model offers new information that may support differential diagnosis of brain diseases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Lung cancer is the most frequently diagnosed cancer type and the leading cause of cancer-related deaths worldwide. Non-small cell lung cancer (NSCLC) represents most of the diagnoses of lung cancer. Vascular endothelial growth factor receptor-2 (VEGFR2) is a member of the VEGF family of receptor tyrosine kinase proteins, which are expressed on both endothelial and tumor cells, are one of the key proteins contributing to cancer development, and are involved in drug resistance. We previously showed that Musashi-2 (MSI2) RNA-binding protein is associated with NSCLC progression by regulating several signaling pathways relevant to NSCLC. In this study, we performed Reverse Protein Phase Array (RPPA) analysis of murine lung cancer, which suggests that VEGFR2 protein is strongly positively regulated by MSI2. Next, we validated VEGFR2 protein regulation by MSI2 in several human lung adenocarcinoma cell line models. Additionally, we found that MSI2 affected AKT signaling via negative PTEN mRNA translation regulation. In silico prediction analysis suggested that both VEGFR2 and PTEN mRNAs have predicted binding sites for MSI2. We next performed RNA immunoprecipitation coupled with quantitative PCR, which confirmed that MSI2 directly binds to VEGFR2 and PTEN mRNAs, suggesting a direct regulation mechanism. Finally, MSI2 expression positively correlated with VEGFR2 and VEGF-A protein levels in human lung adenocarcinoma samples. We conclude that the MSI2/VEGFR2 axis contributes to lung adenocarcinoma progression and is worth further investigations and therapeutic targeting.

Background: Early neurological deterioration (END) is a common occurrence in ischemic stroke and contributes significantly to poor outcomes. Although multiple factors that predict END have already been identified, the role of fibrinogen - a key component of the coagulation pathway, is controversial., Objective: To assess the role of fibrinogen in predicting END and poor hospital outcome in patients with acute ischemic stroke., Design: Single-centre prospective observational study., Methods: 141 patients with acute ischemic stroke were analyzed in this prospective observational study from a single tertiary-care hospital in East India. END was defined as a worsening of ≥2 points on the National Institutes of Health Stroke Scale (NIHSS) within 7 days of admission. A score of 3-5 on the Modified Rankin Scale (mRS), a stroke recurrence event or death during hospital stay was considered poor hospital outcome. We performed univariate analysis using age, sex, body-mass index (BMI), hypertension, diabetes, NIHSS scores, stroke etiology, blood glucose and lipid parameters and plasma fibrinogen to develop a logistic regression model to establish the independent predictors of END and poor outcome., Results: Age (Odds Ratio (OR) 1.034 [95% CI 1.001-1.069], P = .046), NIHSS score at admission (OR 1.152 [95% CI 1.070-1.240], P < .001) and fibrinogen (OR 1.011 [95%CI 1.006-1.015], P < .001) were independent predictors of END in patients with acute ischemic stroke. Factors independently associated with poor outcome were NIHSS score at admission (OR 1.257 [95% CI 1.150-1.357], P < .001), fasting plasma glucose (OR 1.007 [95% CI 1.001-1.013], P = .020), and fibrinogen [OR 1.004 [95% CI 1.000-1.007], P = .038)., Conclusion: The significant role of fibrinogen in determining neurological worsening and subsequent poor outcomes in patients with acute ischemic stroke may help in early prognostication and guided therapeutic interventions., Competing Interests: AS: Conceptualization, Methodology, Supervision, Validation, Visualization, Writing – reviewing and editing. DJ: Data curation, Formal analysis, Investigation, Resources, Software, Validation, Visualization. RP: Data curation, Formal analysis, Investigation, Validation, Writing – reviewing and editing. RK: Investigation, Methodology, Validation, Writing – reviewing and editing. RTG: Conceptualization, Supervision. CBS: Conceptualization, Supervision The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Introduction: To evaluate the effectiveness of a standardized multimodal pain pathway for gender affirming orchiectomy (GAO) in adequately addressing postoperative pain while reducing the prescribing of unnecessary opioids., Materials and Methods: A standardized discharge pain pathway for GAO +/- scrotectomy or testicular implants was implemented between May 2020 and March 2022. A retrospective analysis was performed on all consecutive patients who underwent GAO with a single surgeon. Patients answered five questions on postoperative pain management at their 3 week follow up., Results: A total of 69 patients were included in the study. Mean age was 34.3 years (SD ± 10.5; IQR 26-39) with a mean body mass index (BMI) of 27.1 (SD ± 7.5; IQR 22.3-31). No patients were taking narcotics preoperatively. Mean 4.7 tablets (SD ± 4.5; range 0-30) oxycodone tablets taken by GAO patients without concurrent procedures, with 33 patients (47.8%) taking fewer than 4 tablets. Thirteen patients (18.8%) required no narcotics. Four patients (5.8%) requested an additional narcotic prescription, none of whom underwent a concurrent procedure. There was no significant association between BMI and the number of oxycodone tablets taken. All patients used at least one recommended alternative therapy (acetaminophen, ibuprofen and ice packs) with 41 patients (59.4%) using all three., Conclusion: Most patients achieved adequate postoperative pain control as requests for additional narcotic prescriptions were low. Almost half of patients used < 4 tablets, and all patients employed at least one alternative non-narcotic analgesic. Based on these findings, we plan to decrease the quantity of opioids on discharge.

Background: Serclutamab talirine (Ser-T, formerly ABBV-321) is an antibody-drug conjugate consisting of an antibody (AM-1-ABT-806) directed against activated epidermal growth factor receptor (EGFR) and a pyrrolobenzodiazepine dimer. We investigated Ser-T monotherapy in a phase I, first-in-human, dose-escalation, and dose-expansion study in patients with advanced solid tumors associated with EGFR overexpression., Methods: Eligible patients (≥18 years) had advanced, histologically confirmed solid tumors associated with EGFR overexpression (centralized testing). Patients received Ser-T intravenously once every 4 weeks (Q4W; 5-50 μg/kg) in the dose-escalation phase. Herein, preliminary antitumor activity at the recommended phase II dose (RP2D) is reported only for patients with glioblastoma ( n = 24); additional assessments included all treated patients., Results: Sixty-two patients (median age: 58 years) were enrolled within the dose-escalation ( n = 43) and dose-expansion ( n = 19) phases. One dose-limiting toxicity, grade 3 aspartate aminotransferase and alanine aminotransferase elevation, occurred at 20 μg/kg during dose escalation. The Ser-T RP2D regimen of 50 μg/kg × 1 (loading dose) followed by 25 μg/kg Q4W (maintenance dose) was administered during dose expansion. Fatigue (37%) was the only treatment-emergent adverse event (AE) occurring in >25% of patients. Two patients (3%) reported mild treatment-related ocular AEs (eye pruritus). Responses in patients with glioblastoma included 1 partial response (~33 months), 6 stable disease, and 14 progressive disease (not evaluable: n = 3)., Conclusions: Ser-T monotherapy at doses up to 50 μg/kg initial dose, followed by 25 μg/kg Q4W demonstrated a tolerable safety profile with minimal antitumor activity observed in patients with glioblastoma. The glioblastoma dose-expansion cohort was closed due to a lack of efficacy (NCT03234712)., (© The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology.)

Over 500 clinical trials are investigating combination radiotherapy and immune checkpoint blockade (ICB) as cancer treatments; however, the majority of trials have found no positive interaction. Here we perform a comprehensive molecular analysis of a randomized phase I clinical trial of patients with non-small cell lung cancer (NSCLC) treated with concurrent or sequential ablative radiotherapy and ICB. We show that concurrent treatment is superior to sequential treatment in augmenting local and distant tumor responses and in improving overall survival in a subset of patients with immunologically cold, highly aneuploid tumors, but not in those with less aneuploid tumors. In addition, radiotherapy alone decreases intratumoral cytotoxic T cell and adaptive immune signatures, whereas radiotherapy and ICB upregulates key immune pathways. Our findings challenge the prevailing paradigm that local ablative radiotherapy beneficially stimulates the immune response. We propose the use of tumor aneuploidy as a biomarker and therapeutic target in personalizing treatment approaches for patients with NSCLC treated with radiotherapy and ICB., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Lung cancer remains the second most commonly diagnosed cancer worldwide and the leading cause of cancer-related mortality. The mapping of genomic alterations and their role in lung-cancer progression has been followed by the development of new therapeutic options. Several novel drugs, such as targeted therapy and immunotherapy, have significantly improved outcomes. However, many patients with lung cancer do not benefit from existing therapies or develop progressive disease, leading to increased morbidity and mortality despite initial responses to treatment. Alterations in DNA-damage repair (DDR) genes represent a cancer hallmark that impairs a cell's ability to prevent deleterious mutation accumulation and repair. These alterations have recently emerged as a therapeutic target in breast, ovarian, prostate, and pancreatic cancers. The role of DDR alterations remains largely unknown in lung cancer. Nevertheless, recent research efforts have highlighted a potential role of some DDR alterations as predictive biomarkers of response to treatment. Despite the failure of PARP inhibitors (main class of DDR targeting agents) to improve outcomes in lung cancer patients, there is some evidence suggesting a role of PARP inhibitors and other DDR targeting agents in benefiting a distinct subset of lung cancer patients. In this review, we will discuss the existing literature on DDR alterations and homologous recombination deficiency (HRD) state as predictive biomarkers and therapeutic targets in both non-small cell lung and small cell lung cancer.

Objectives: To assess the diagnostic accuracy of chest CT in clinically suspected patients with COVID-19 using reverse transcriptase PCR (RT-PCR) as the reference standard and establish the correlation between CT Severity Score (CTSS) and RT-PCR results., Design and Setting: Retrospective cohort study. Single-centre tertiary care hospital-based study., Participants: We enrolled 112 clinically suspected patients with COVID-19 between 1 April 2021 and 31 May 2021. Chest CT and RT-PCR tests were performed for all patients at a time interval of no longer than 7 days between the two tests. Patients with prior chronic respiratory illnesses were excluded. The diagnostic performance of chest CT was evaluated using RT-PCR as the reference standard. The CTSS was calculated for all patients with positive chest CT findings, and it was correlated with results of the RT-PCR assay., Main Outcome Measures: The primary outcome measures were determination of the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of chest CT using RT-PCR as the standard of reference. The correlation between CTSS and RT-PCR was the secondary outcome., Results: 85/112 (76%) patients tested positive on the RT-PCR whereas 91/112 (81%) had chest CT findings typical of SARS-CoV-2 infection. Chest CT had a sensitivity of 90.6% (95% CI 82.3% to 95.8%), a specificity of 48.1% (95% CI 28.7% to 68.0%), a PPV of 84.6% (95% CI 79.2% to 88.8%), an NPV of 61.9% (95% CI 43.0% to 77.8%) and an accuracy of 80.4% (95% CI 71.8% to 87.3%). There was a significant correlation between the CTSS and RT-PCR positivity (p value=0.003)., Conclusion: In our experience, chest CT has a good sensitivity and provides a reliable diagnostic tool for moderate-to-severe COVID-19 cases in resource limited settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Despite a global pandemic that continued to inflict chaos and confusion on the world, resulting in fewer cancer screenings and delayed surgeries, remarkable lung cancer treatment advancements were made in 2021. From immunotherapy in the adjuvant setting to the approval of the first-in-class, highly selective inhibitor of KRAS G12C, these treatment advances have significant clinical impact in patients with lung cancer. LAY SUMMARY: There has been tremendous innovation in the treatment of nonsmall cell lung cancer. The year 2021 was marked by new approaches to adjuvant therapy and the availability of agents to target new subsets of nonsmall cell lung cancer., (© 2022 American Cancer Society.)

Magnetic particle spectroscopy (MPS) in the Brownian relaxation regime, also termed magnetic spectroscopy of Brownian motion (MSB), can detect and quantitate very low, sub-nanomolar concentrations of molecular biomarkers. MPS/MSB uses the harmonics of the magnetization induced by a small, low-frequency oscillating magnetic field to provide quantitative information about the magnetic nanoparticles' (mNPs') microenvironment. A key application uses antibody-coated mNPs to produce biomarker-mediated aggregation that can be detected using MPS/MSB. However, relaxation changes can also be caused by viscosity changes. To address this challenge, we propose a metric that can distinguish between aggregation and viscosity. Viscosity changes scale the MPS/MSB harmonic ratios with a constant multiplier across all applied field frequencies. The change in viscosity is exactly equal to the multiplier with generality, avoiding the need to understand the signal explicitly. This simple scaling relationship is violated when particles aggregate. Instead, a separate multiplier must be used for each frequency. The standard deviation of the multipliers over frequency defines a metric isolating viscosity (zero standard deviation) from aggregation (non-zero standard deviation). It increases monotonically with biomarker concentration. We modeled aggregation and simulated the MPS/MSB signal changes resulting from aggregation and viscosity changes. MPS/MSB signal changes were also measured experimentally using 100 nm iron-oxide mNPs in solutions with different viscosities (modulated by glycerol concentration) and with different levels of aggregation (modulated by concanavalin A linker concentrations). Experimental and simulation results confirmed that viscosity changes produced small changes in the standard deviation and aggregation produced larger values of standard deviation. This work overcomes a key barrier to using MPS/MSB to detect biomarkers in vivo with variable tissue viscosity.

Introduction In polytrauma patients, it is crucial to identify the severity of the injuries to ensure patient safety and survival. Polytrauma leads to hypotension and hypoperfusion, which results in an anaerobic metabolism with acidosis and a decrease in base excess. Thus, blood lactate levels above a certain threshold indicate the existence of global tissue hypoxia, which is a precursor to shock and multiple organ dysfunction syndrome (MODS). The serum lactate and base deficit (BD) levels are used in polytrauma patients as measures of damage severity and resuscitation endpoints and as a way to evaluate therapy efficacy and to predict outcomes. Thus, arterial blood gas analysis is of great value in assessing the status and prognosis of patients with polytrauma. There are few comparative studies on the predictive values of these markers in trauma patients. To determine which measure can more accurately predict the prognosis of polytrauma patients, the present study investigated the predictive values of mortality of these indicators for mortality within 48 hours of admission to the emergency room (ER) in patients with polytrauma. Methods This prospective study was designed for a single tertiary care center in northern India. We included 90 patients with polytrauma who were between the ages of 18 and 70 years, with the exception of pregnant women, who presented to the ER within six hours of injury with an injury severity score (ISS) >16, serum lactate level >2.0 mmol/L, and BD -4.0 mEq/L at the time of admission. If the patient's ISS was >16 at the time of ER presentation, arterial blood samples were drawn to determine the serum lactate and BD level at the time of admission and at 12, 24, and 48 hours intervals after ER admission. The primary outcome was the change in serum lactate and BD level in polytrauma. The secondary outcomes were an association of serum lactate and BD with mortality and the correlation between serum lactate with the BD and ISS with mortality of polytrauma patients. The timing of all outcome assessments was at 48 hours after each patient's ER admission. Results Lactate clearance from 0-12 hours (t = 2.28, p <0.05), 0-24 hours (t = 6.01, p <0.001), and 0-48 hours (t = 7.98, p <0.001) and a correction in BD from 0-24 (t = 2.68, p <0.01 ) and 0-48 hours (t = 5.46, p <0.001) were significantly higher in nonsurvivors as compared with survivors. In survivors and nonsurvivors, mean serum lactate levels (2.46 ± 1.46 versus 4.15 ± 2.99, t = 3.31, p <0.001, 95%Cl) and mean BD (-3.17 ± 2.58 versus -6.5 ± 4.91, t = 3.86, p <0.001, 95%CI) had a statistically significant difference. The serum lactate and BD levels at time of ER admission (r L0, BD0 = -0.765, p <0.01) and 48 hours after ER admission (r L48, BD 48 = -0.652, p <0.001) were highly negatively correlated. Conclusion In polytrauma patients, serum lactate and BD are simple, quick, and independent biochemical predictors of 48-hour mortality, and this single arterial blood test would thereby improve decision-making for resuscitation effectiveness. Prolonged lactate and BD normalization time were associated with higher mortality. Serum lactate and BD are negatively correlated. A higher ISS at admission was associated with a higher incidence of mortality in polytrauma patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Jyoti et al.)