Tailored Treatment Strategies Research Articles

Abstract B005: Exploring breast cancer heterogeneity in the context of metastatic tumour microenvironments and therapy resistance

Abstract Breast tumors comprise several sub-populations of cells, so-called “clones”, with specific cellular and molecular characteristics. Some cancer clones can be more ‘aggressive’ than others in particular tumor microenvironments (TMEs), contributing to metastatic progression and drug resistance. Understanding the specific genes/pathways deregulated in these aggressive cancer cells is essential for developing new tailored treatment strategies. To accomplish this, we optimized the use of a lentiviral-based barcoding technique (Berthelet, J., et.al., Sci Adv 2021, Serrano, A., et.al., Nat Rev Cancer 2022) where cancer cells from cell lines and patient-derived xenografts are tagged with optical barcodes and transplanted into the mammary fat pads of immunodeficient mice. Upon resection of tumors and collection of metastatic organs at the experimental endpoint, we analyzed clonal fate and fitness using flow cytometry and imaging. The subsequent molecular characterization of individual clones was determined by bulk and single-cell RNA sequencing. We also leverage the use of these barcoded models to investigate the mechanisms of innate and acquired resistance to Sacituzumab Govitecan (SG), a drug recently approved for the treatment of patients with advanced breast cancer. Our studies revealed unique gene signatures and pathways associated with preferential organ tropism (in the lungs, liver and brain TMEs) and SG resistance. This comprehensive analysis, currently validated using autopsy samples and patient databases, will support the design of new predictive markers and targeted therapies for metastatic breast cancer. Citation Format: Sreeja Reddy Gadipally, Jean Berthelet, Samuel C. Lee, Dharmesh D. Bhuva, Michael Roach, Farrah El-Saafin, Caroline Bell, Yunjian Wu, David Baloyan, Christphe Ginestier, Charafe Jauffret Emmanuelle, Melissa Davis, Robin L. Anderson, Luciano Martelotto, Belinda Yeo, Delphine Merino. Exploring breast cancer heterogeneity in the context of metastatic tumour microenvironments and therapy resistance [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B005.

The impact of preoperative treatment on mismatch repair protein and HER2 expression in colorectal cancer: an analysis of paired samples.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality, highlighting the necessity for multifaceted treatment strategies, including preoperative treatment (PT), which can enhance surgical outcomes and provide prognostic insights. This study aims to clarify the impact of PT-induced changes in mismatch repair (MMR) and human epidermal growth factor receptor 2 (HER2) expression, potentially informing tailored treatment strategies and improving clinical outcomes for CRC patients. This retrospective study analyzed 120 paired samples from CRC patients who underwent preoperative treatment, comparing pre- and post-treatment specimens. A control group of 60 untreated surgical specimens was also included. Immunohistochemistry assessed MMR proteins (MSH6, MSH2, MLH1, PMS2) and HER2 expression. MSI status was determined in samples with low MMR expression. Compared to pre-treatment samples, post-treatment samples exhibited lower levels of MSH6, MSH2, and total MMR expression, along with higher levels of HER2 expression. However, when compared to the untreated control group, there were no significant differences in the expression of MSH6, total MMR, and HER2. All samples that exhibited weak MMR expression and those that shifted to deficient mismatch repair (dMMR) status following treatment had stable microsatellite status. No clear clinicopathological characteristics or prognostic factors were found to be associated with changes in MMR and HER2 expression, except for the use of fluorouracil or capecitabine, which was related to changes in total MMR scores. ypTNM stage and TRG scores were identified as independent factors affecting disease progression in our study. PT is associated with a reduction in MMR expression, notably for the MSH2 protein, while it does not appear to influence HER2 expression.

The development of a C5.0 machine learning model in a limited data set to predict early mortality in patients with ARDS undergoing an initial session of prone positioning.

Acute Respiratory Distress Syndrome (ARDS) has a high morbidity and mortality. One therapy that can decrease mortality is ventilation in the prone position (PP). Patients undergoing PP are amongst the sickest, and there is a need for early identification of patients at particularly high risk of death. These patients may benefit from an in-depth review of treatment or consideration of rescue therapies. We report the development of a machine learning model trained to predict early mortality in patients undergoing prone positioning as part of the management of their ARDS. Prospectively collected clinical data were analysed retrospectively from a single tertiary ICU. The records of patients who underwent an initial session of prone positioning whilst receiving invasive mechanical ventilation were identified (n = 131). The decision to perform prone positioning was based on the criteria in the PROSEVA study. A C5.0 classifier algorithm with adaptive boosting was trained on data gathered before, during, and after initial proning. Data was split between training (85% of data) and testing (15% of data). Hyperparameter tuning was achieved through a grid-search using a maximal entropy configuration. Predictions for 7-day mortality after initial proning session were made on the training and testing data. The model demonstrated good performance in predicting 7-day mortality (AUROC: 0.89 training, 0.78 testing). Seven variables were used for prediction. Sensitivity was 0.80 and specificity was 0.67 on the testing data set. Patients predicted to survive had 13.3% mortality, while those predicted to die had 66.67% mortality. Among patients in whom the model predicted patient would survive to day 7 based on their response, mortality at day 7 was 13.3%. Conversely, if the model predicted the patient would not survive to day 7, mortality was 66.67%. This proof-of-concept study shows that with a limited data set, a C5.0 classifier can predict 7-day mortality from a number of variables, including the response to initial proning, and identify a cohort at significantly higher risk of death. This can help identify patients failing conventional therapies who may benefit from a thorough review of their management, including consideration of rescue treatments, such as extracorporeal membrane oxygenation. This study shows the potential of a machine learning model to identify ARDS patients at high risk of early mortality following PP. This information can guide clinicians in tailoring treatment strategies and considering rescue therapies. Further validation in larger cohorts is needed.

Quantitative MODS-Wayne assay for rapid detection of pyrazinamide resistance in Mycobacterium tuberculosis from sputum samples.

PZA susceptibility testing continues to be a challenge, particularly in countries with high TB incidence. In response to this pressing need, we have developed a quantitative MODS-Wayne (MODS-WQ) assay. This approach offers a direct and cost-effective solution representing a significant advancement in TB diagnostics, particularly benefiting resource-limited laboratories, primarily in developing regions. The MODS-WQ assay stands out for its ability to quantify pyrazinoic acid (POA) production, as a reliable indicator of PZA resistance. Unlike traditional qualitative assays, MODS-WQ eliminates the inherent subjectivity in interpretation, providing more accurate and actionable results. Moreover, the MODS-WQ approach accounts for critical factors influencing PZA resistance, including enzymatic efficiency and efflux pump activity. By integrating these factors into the detection process, our methodology offers a comprehensive understanding of PZA resistance levels, enabling tailored treatment strategies for patients.

Abstract A052: Circulating tumor DNA (ctDNA) in plasma and urine of renal cell carcinoma patients with localized disease

Abstract Introduction: Circulating tumor DNA (ctDNA) is increasingly valuable in cancer care. Early diagnosis of renal cell carcinoma (RCC) significantly improves prognosis. Clear cell RCC (ccRCC), the most prevalent and aggressive subtype, often leads to recurrence in over 20% of localized cases post-nephrectomy. Thus, risk-stratifying tools are crucial for tailored treatment strategies. In this study, we tracked tumor mutations in DNA from plasma (ctDNA) and urine (utDNA) in patients with localized ccRCC to explore their potential as risk-stratifying biomarkers for recurrence. We evaluated ctDNA/utDNA pre-surgery in all RCC patients and conducted longitudinal assessments post-surgery in ccRCC patients. Additionally, for one ccRCC patient with aggressive disease, we analyzed tumor mutations in the plasma of patient- derived xenograft (PDX) replicates. Methodology: RCC patients were recruited from A.C.Camargo Cancer Center. Urine and plasma samples were taken pre-surgery (BL-baseline), and for ccRCC patients, samples were collected at 6-8 weeks and 6, 18 and 30 months post- surgery (M1, M2, M3 and M4, respectively). Patients were monitored for recurrence for up to 6,3 years. We used a customized 28-gene RCC panel and a commercial 409-gene solid tumor panel to identify tumor somatic mutations using Illumina NextSeq 500 and Ion S5 platforms, respectively. Tumor specific mutations were tracked in DNA from patient plasma and urine, and PDX plasma, using the PATS (Personalized amplicon target sequencing) method on Ion S5 Plus platform. Results: Out of 79 RCC patients (58% ccRCC), 57 (72%) had tumor somatic mutations, including 39 (68%) in ccRCC. VHL and PBRM1 were the most frequently mutated genes. Baseline ctDNA/utDNA were analyzed in 51 RCC patients, with 18% (13% plasma, 12% urine) positivity in RCC and 19% (12% plasma, 12% urine) in ccRCC. During ccRCC monitoring, ctDNA/utDNA was positive only in M1 and M3, with 9% (9% plasma, 0% urine) and 18% (12% plasma, 6% urine), respectively. ctDNA-positive baseline plasma was associated to disease progression (p=0.0155) and tumor staging ≥pT3 (p=0.002); these patients also experienced reduced progression-free (p=0.004) and overall (p98%, resembling the patient’s tumor aggressiveness. Conclusions: ccRCC tumors release low levels of tumor DNA in urine and plasma. Pre-surgery plasma positivity for ctDNA appears to indicate a higher risk of recurrence in ccRCC patients. The ctDNA release of PDX tumors replicated that observed in one ccRCC patient with aggressive disease. Citation Format: Ana Carolina Kerekes Miguez, Isabella Tanus Job e Meira, Stephania Martins Bezerra, Adriano de Oliveira Beserra, Walter Henriques da Costa, Tiago Goss dos Santos, Stenio de Cassio Zequi, Giovana Tardin Torrezan, Dirce Maria Carraro. Circulating tumor DNA (ctDNA) in plasma and urine of renal cell carcinoma patients with localized disease [abstract]. In: Proceedings of the AACR Special Conference: Liquid Biopsy: From Discovery to Clinical Implementation; 2024 Nov 13-16; San Diego, CA. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(21_Suppl):Abstract nr A052.

The Diagnosis and Management of Infraoccluded Deciduous Molars: A Systematic Review

The infraocclusion (IO) of primary molars, often seen in retained deciduous teeth, is a common condition that presents significant challenges for pediatric oral health. It occurs when primary molars are positioned below the occlusal plane due to the absence of permanent successors, leading to complications such as misaligned teeth, impaired chewing, and long-term dental health issues. Objectives: This study examines IO prevalence, diagnosis, and treatment approaches. Methods: A systematic review following PRISMA guidelines was conducted, searching PubMed, Web of Science, and Scopus for articles from the last 15 years. Nine articles were included for qualitative analysis. Results: IO was associated with several complications, including root resorption, altered eruption of adjacent teeth, and space loss within the dental arch. Clinical and radiographic evaluations are key to early detection. Severe cases often require invasive treatments, such as tooth extraction and space maintenance, while mild cases could be monitored. Conclusions: IO is prevalent in pediatric dentistry and can lead to significant dental issues if untreated. Early detection and intervention are crucial for preventing complications like tooth misalignment and impacted premolars. Tailored treatment strategies based on severity, along with increased awareness among dental practitioners, are essential to improve long-term outcomes for affected children.

Upadacitinib and Cardiovascular Adverse Events in Rheumatoid Arthritis: A Systematic Review and Meta-Analysis.

Upadacitinib, a Janus kinase (JAK) inhibitor used in rheumatoid arthritis treatment, has prompted safety concerns due to potential cardiovascular adverse events. However, current evidence does not provide a definitive conclusion. We conducted a comprehensive systematic review of the literature up until March 15, 2024, utilizing databases like PubMed/Medline, Embase, and Cochrane CENTRAL. A meta-analysis approach was used to derive pooled odds ratios (OR) along with their 95% confidence intervals (CI) to assess the cardiovascular risk associated with upadacitinib. Publication bias was evaluated using Begg's and Egger's tests. Our meta-analysis included six studies with a total of 4,202 participants. For the 15 mg dosage of Upadacitinib, the pooled OR was 1.20 (95% CI: 0.3-4.3), indicating a nominal, non-significant increase in the risk of cardiovascular adverse events. Analysis of the 30 mg dosage presented a pooled OR of 2.37 (95% CI: 0.6-9.1), pointing to a higher, yet statistically insignificant, potential risk. The absence of publication bias was confirmed through Begg's and Egger's tests. The analysis suggests a potential heightened cardiovascular risk associated with Upadacitinib, more so with the 30 mg dosage. Nevertheless, the lack of statistical significance and the wide confidence intervals necessitate a prudent approach to these findings. Tailored treatment strategies, rigorous monitoring, and further empirical studies are crucial for refining the safety profile of upadacitinib and ensuring optimal patient outcomes.

Retrospective analysis of medication-related osteonecrosis of the jaw at a maxillofacial prosthetics clinic

Purpose: Medication-related osteonecrosis of the jaw (MRONJ) poses significant challenges in patient care because of its complex etiology, clinical manifestations, and management. This study aims to provide an overview of patients with MRONJ treated at our clinic over the past 12 years, highlighting incidence, clinical characteristics, and prosthetic treatment outcomes. Materials and Methods: The study included patients with MRONJ who visited our clinic between January 2012 and April 2024. Data on demographic characteristics, lesion location, clinical presentation, primary diseases, prosthetic management and medications were collected from health records. Results: This retrospective analysis of cases of MRONJ over 12 years at a maxillofacial prosthetics clinic reveals a rising prevalence of the condition, particularly in the elderly, with treatments for breast and prostate cancer emerging as prominent risk factors. Distinct medication-specific effects on distribution of lesions suggest variation in pathogenic mechanisms, which require tailored treatment strategies. Management strategies encompass a spectrum of interventions from conservative measures to prosthetic rehabilitation, highlighting the importance of interdisciplinary collaboration and personalized care. Conclusion: The rising incidence of MRONJ, especially among elderly patients, indicates the need for enhanced preventive measures and interdisciplinary care. Breast and prostate cancer treatments are significant risk factors, necessitating tailored monitoring. Effective prosthetic management is crucial for improving oral function and quality of life in MRONJ patients.

From Genomic Exploration to Personalized Treatment: Next-Generation Sequencing in Oncology

Next-generation sequencing (NGS) has revolutionized personalized oncology care by providing exceptional insights into the complex genomic landscape. NGS offers comprehensive cancer profiling, which enables clinicians and researchers to better understand the molecular basis of cancer and to tailor treatment strategies accordingly. Targeted therapies based on genomic alterations identified through NGS have shown promise in improving patient outcomes across various cancer types, circumventing resistance mechanisms and enhancing treatment efficacy. Moreover, NGS facilitates the identification of predictive biomarkers and prognostic indicators, aiding in patient stratification and personalized treatment approaches. By uncovering driver mutations and actionable alterations, NGS empowers clinicians to make informed decisions regarding treatment selection and patient management. However, the full potential of NGS in personalized oncology can only be realized through bioinformatics analyses. Bioinformatics plays a crucial role in processing raw sequencing data, identifying clinically relevant variants, and interpreting complex genomic landscapes. This comprehensive review investigates the diverse NGS techniques, including whole-genome sequencing (WGS), whole-exome sequencing (WES), and single-cell RNA sequencing (sc-RNA-Seq), elucidating their roles in understanding the complex genomic/transcriptomic landscape of cancer. Furthermore, the review explores the integration of NGS data with bioinformatics tools to facilitate personalized oncology approaches, from understanding tumor heterogeneity to identifying driver mutations and predicting therapeutic responses. Challenges and future directions in NGS-based cancer research are also discussed, underscoring the transformative impact of these technologies on cancer diagnosis, management, and treatment strategies.

Effects of Alcohol on EEG Activity: A Systematic Review Focused on Sex-Related Differences in Youth.

Most electroencephalographic (EEG) investigations on alcohol have focused on adults, and scarce data is available about the potential of EEG measurements to detect young people at high-risk, as well as, to understand possible sex differences in alcohol impact on the brain. This systematic review aimed to explore sex-related differences in EEG among young people with alcohol misuse, alcohol use disorder (AUD), and offspring of families with AUD. A systematic review of the literature was conducted following PRISMA guidelines. Review protocol was registered in Prospero (ID: CRD42024511471). After article selection process and quality assessment, 25 studies were included in our review. The search included participants between 12 and 30 years old with problematic alcohol consumption, as defined by DSM, AUDIT, or specific alcohol misuse questionnaires. It seems that beta was generally higher in young males with AUD, and they usually exhibited greater interhemispheric connectivity (interHC), whereas young females with AUD tended towards enhanced intraHC. P3 appears to be particularly sensitive to alcohol misuse, with males typically exhibiting a lower amplitude than young females. Other event related potentials (ERPs) such as N415, P640, and the error-related negativity (ERN) lacked sufficient methodological support to draw conclusions regarding sex differences, N340 and P540 suggested avenues for expanding research on memory processing, indicating differences in amplitude between males and females. Considering sex variables in clinical research will enhance our understanding of alterations in brain function and structure with the goal of tailoring treatment strategies for AUD.

A stimulus responsive microneedle-based drug delivery system for cancer therapy.

The intricate nature of the tumor microenvironment (TME) results in the inefficient delivery of anticancer drugs within tumor tissues, significantly compromising the therapeutic effect of cancer treatment. To address this issue, transdermal drug delivery microneedles (MNs) with high mechanical strength have emerged. Such MNs penetrate the skin barrier, enabling efficient drug delivery to tumor tissues. This approach enhances drug bioavailability, while also mitigating concerns such as liver and kidney toxicity associated with intravenous and oral drug administration. Notably, stimulus responsive MNs designed for drug delivery have the capacity to respond to various biological signals and pathological changes. This adaptability enables them to exert therapeutic effects within the TME, exploiting biochemical variations and tailoring treatment strategies to suit tumor characteristics. The present review surveys recent advancements in responsive MN systems. This comprehensive analysis serves as a valuable reference for the prospective application of smart MN drug delivery systems in cancer therapy.

A digital pathology model for predicting radioiodine-avid metastases on initial post-therapeutic 131I scan in patients with papillary thyroid cancer.

Accurate postoperative assessment is critical for optimizing 131I therapy in patients with papillary thyroid cancer (PTC). This study aimed to develop a pathology model utilizing postoperative digital pathology slides to predict lymph node and/or distant metastases on post-therapeutic 131I scan after initial 131I treatment in PTC patients. A retrospective analysis was conducted on 229 PTC patients who underwent total or near-total thyroidectomy and subsequent 131I treatment after levothyroxine (LT4) withdrawal between January 2022 and August 2023. The pathology model was developed through two stages: patch-level prediction and WSI-level prediction. The clinical model was constructed using statistically significant variables identified from univariate and multivariate logistic regression analysis. Of the 229 patients, 19.6% (45/229) exhibited 131I-avid metastatic foci in post-therapeutic 131I scan. Multifactorial analysis identified stimulated thyroglobulin (sTg) as the sole independent risk factor. The AUC of the pathology model in the training and test cohorts were 0.976 (95% CI 0.948-1.000) and 0.805 (95% CI 0.660-0.951), respectively, which were significantly higher than the clinical model (AUC 0.652 and 0.548, Pall < 0.05). This model has the potential to serve as a valuable tool for clinicians in tailoring treatment strategies, thereby optimizing therapeutic outcomes for PTC patients.

A Prospective Study on Laparoscopic Evaluation of Tubal Factors with Polycystic Ovarian Syndrome and Infertility in Bangladeshi Patients

Background: Laparoscopic evaluation plays a crucial role in assessing tubal factors in infertility cases coexisting with polycystic ovarian syndrome (PCOS). PCOS, characterized by hormonal imbalances and ovarian cysts, often leads to irregular ovulation and infertility. Laparoscopy allows for direct visualization of the fallopian tubes, identifying any obstructions or abnormalities that may hinder conception. Understanding the tubal status in PCOS-related infertility helps tailor treatment strategies, optimizing the chances of successful conception for affected couples. Objective: In this study or main goal is to evaluate the tubal factor pathology in case of infertile patients with diagnosed PCOS by laparoscopy. Method: This retrospective study was carried out at tertiary medical hospital from 2022 to 2023 where a total of 100 women who were diagnosed case of infertility with PCOS included in the study. Among these 68 % were primary infertility and 32% were secondary infertility. Results: During the study, in primary infertility 70.59% patient had no history of contraception. Only 8.82% had taken oral pill and 20.59% used barrier method. In secondary infertility had no history of contraception 25% had taken oral pill, 6.25% had taken IUCD and 6.25% used barrier method. Laparoscopic study of fallopian tube showed in primary infertility the tube of the right side was normal looking in 52 (76.47%), peritubal adhesion was present in 12 (17.65%) and hydrosalpinx was present in 4 (5.88%) cases. The tube of the left side was normal looking in 50 (73.53%), peritubal adhesion was present in 10 (14.71%) and hydrosalpinx was present in 8 (11.76%) cases. In secondary infertility the tube of the right side was normal looking in 16 (50.00%), peritubal adhesion was present 8 (25.00%) hydrosalpinx in 6 (18.75%) and the tube was absent in 2 case. In the left side the tube was normal looking in 20 (62.50%), peritubal adhesion was present in 8 (25.00%) and hydrosalpinx in ...

Smart Health Monitoring Approach to Diagnose Attention-Deficit Hyperactivity Disorderbased on Real-Time Activity and Heart Rate Variability using Boosting Models

Introduction: Attention-Deficit Hyperactivity Disorder (ADHD) is a prevalent chronic mental health condition that significantly impacts the psychological and physical wellbeing of millions of adolescents. Early detection and accurate diagnosis are crucial for effective treatment and mitigating the disorder's adverse effects. Despite extensive research efforts, current methods often fall short in simultaneously accounting for daily motor activity and heart rate variability in ADHD detection. Method: Addressing these gaps, this paper introduces a histogram-based gradient-boosting classifier for analyzing real-time activity and heart-rate variability data to automate ADHD diagnosis. By extracting twelve key features from the data and selecting the most significant ones with the extra tree model, we evaluate these features using various classifiers, including histogram-based gradient boosting, light gradient boosting machine, extreme gradient boosting, gradient boosting, and adaptive boosting. Results: The histogram-based gradient-boosting model, validated through ten-fold crossvalidation, outperforms other classifiers with an accuracy of 99.12%, an F1 measure of 99.12%, and a sensitivity of 99.13%. Additionally, it achieves a specificity of 99.1%, an AUC of 0.9995, and a minimal FDR of 0.88%. These results demonstrate that the proposed approach offers a highly effective and precise solution for automated ADHD diagnosis. Conclusion: The implications of these findings suggest that integrating real-time activity and heart-rate variability data into diagnostic processes can significantly enhance the accuracy and efficiency of ADHD assessment, potentially leading to earlier and more reliable diagnoses, improved patient outcomes, and more tailored treatment strategies.

Sex Disparities in Cancer Immunotherapy: A Review

Cancer immunotherapy has revolutionized cancer treatment, particularly through immune checkpoint inhibitors (ICIs) targeting proteins like PD-1, PD-L1, and CTLA-4. While these therapies have shown significant survival benefits across various cancers, sex-based disparities in treatment response and outcomes have emerged. This review explores the mechanisms behind these differences, focusing on genetic, hormonal, and immune system variations between male and female patients. Women tend to exhibit stronger immune responses due to the presence of two X chromosomes and the immunostimulatory effects of estrogen, which enhances immune activity. Conversely, men’s single X chromosome and the immunosuppressive effects of testosterone contribute to a less vigorous immune response. These biological differences manifest in clinical outcomes, with men generally experiencing better overall survival rates from ICIs, while women are more prone to immune-related adverse events (irAEs), including autoimmune toxicities. However, in certain cases, women may demonstrate more robust long-term survival benefits from treatments such as CTLA-4 inhibitors, despite higher toxicity risks. Beyond ICIs, sex disparities also extend to adoptive cell therapies (ACT) and cancer vaccines, where female patients often display stronger immune responses but face increased risks of side effects, necessitating personalized approaches to therapy. The review also discusses emerging research on the tumor microenvironment (TME), gut microbiome, and sex-specific pharmacokinetics and pharmacodynamics as contributing factors to these disparities. Understanding these mechanisms is critical for improving cancer immunotherapy outcomes for both sexes. Future research should focus on investigating the role of sex hormones, the microbiome, and developing biomarkers to better predict responses to immunotherapy. Clinically, the findings highlight the need for tailored treatment strategies that account for sex-specific differences, aiming for more equitable and effective cancer care. Keywords: Cancer immunotherapy, Immune checkpoint inhibitors (ICIs), Sex-based disparities, PD-1 inhibitors, PD-L1 inhibitors, CTLA-4 inhibitors

Defining a phenotype of severe COPD patients who develop chronic hypercapnia

IntroductionChronic hypercapnia, defined by elevated blood CO2 levels, is a serious complication most prevalent in severe COPD. It negatively impacts quality of life, increases hospitalization rates, and elevates mortality risks. However, not all severe COPD patients develop chronic hypercapnia, and its underlying mechanisms remain unclear. Identifying clinical and pathophysiological predictors of hypercapnia is essential for tailored treatment strategies. This study investigates the relationship between hypercapnia and patient characteristics, lung function, and CT scan features to identify potential therapeutic targets. MethodsThis cross-sectional study included 1,526 COPD patients from three cohorts: a standard care cohort and two research cohorts (NCT04023409; NCT03053973). Data collected included demographic and clinical information, blood gases, lung function (FEV1, FVC, TLC, RV, DLCOc), and high-resolution CT scans (lung volumes, air trapping, emphysema scores, airway wall thickness (Pi10), and diaphragm indices). ResultsHypercapnia prevalence increased with COPD severity. Hypercapnic patients were older, more likely to smoke, and had more comorbidities. They exhibited lower FEV1 and FVC, and higher RV/TLC ratios, with CT scans showing lower emphysema scores and greater Pi10. Multivariate analysis identified lower PaO2, FEV1% predicted, and emphysema scores, along with higher RV/TLC ratios and NT-proBNP levels, as independent predictors of PaCO2, collectively explaining 46.3% of the variance. ConclusionCOPD patients with chronic hypercapnia are characterized by higher smoking rates, lower PaO2 levels, poorer lung function, less emphysema, and increased airway pathology. These findings underscore the multifactorial nature of hypercapnia in COPD, highlighting the need for personalized therapeutic strategies targeting these factors to improve outcomes.

What is the incidence and non-union rate of radiation-associated fractures? – A systematic review of the literature

BackgroundRadiation-associated fractures (RAFs) are a challenging complication in oncologic patients, yet their incidence remains unknown and optimal management lacks consensus. AimThis review aimed to evaluate the incidence of RAFs in the trunk, pelvis, and extremities as well as non-union rates of surgical and non-surgical treatment. Materials and methodsA systematic review of PubMed and Embase databases was conducted. The study was registered on PROSPERO (ID: CRD42024513017). Studies were included if they reported RAFs in oncologic populations, had a sample size of at least five patients, and provided extractable data on RAF incidence or number. The STROBE checklist was utilized for evaluation of study quality. For eligible studies, quantitative analyses were conducted to determine weighted incidence of RAF and fracture non-union. ResultsThirty-five studies comprising 9,980 patients treated with radiation therapy were included. The weighted incidence of RAFs was calculated to be 6.5% across 8,061 patients. The weighted incidence of femoral RAF was 5.2%, while pelvic RAF incidence was 17.1%. Non-union rates after initial treatment varied from 4% to 100%, with an overall weighted incidence of 48%. Treatments included intramedullary nailing, fixation with screws/plate, prosthetic replacement, conservative treatment, and amputation, with varying success rates. ConclusionThis review highlights RAFs as a significant complication of radiation therapy, with a weighted incidence of 6.5% and a non-union rate of 48%. Advanced radiation techniques have reduced RAF occurrences, but non-union remains a challenge, necessitating tailored treatment strategies. Further research is needed to optimize RAF management and improve patient outcomes.

A computational method to predict cerebral perfusion flow after endovascular treatment based on invasive pressure and resistance

Background and objectivePredicting post-operative flow is essential for assessing the risk of adverse events in cerebrovascular stenosis patients following endovascular treatment (EVT). This study aimed to evaluate the accuracy of the CFD simulation model in predicting post-operative velocity, flow and pressure distal to a stenosis, based on cerebrovascular microcirculatory resistance. MethodsThe patient-specific models of the extracranial and intracranial arteries were reconstructed. The cerebrovascular microcirculatory resistance was applied to estimate post-operative blood velocity and flow rates. Pearson correlation and Bland-Altman analyses were used to evaluate the correlation and agreement between CFD calculations and transcranial Doppler (TCD) measurements. ResultsThere was a strong correlation between CFD- and TCD-based mean velocities (r=0.7733; P=0.0002), with volume flow measured by both methods also showing robust correlation (r=0.8621; P<0.0001). Additionally, agreement was found between mean velocities determined by CFD simulation and those estimated by TCD (P=0.2446, mean difference −4.2089; limits of agreement -11.5764 to 3.1586). However, agreement between volume flow from CFD simulations and TCD was less consistent (P=0.0387, mean difference -0.3272, limits of agreement -0.9276 to 0.2731). ConclusionsThe computational method used in this study enables the prediction of hemodynamic changes and offers valuable support in tailoring treatment strategies for cerebrovascular stenosis lesions.

Understanding and Managing Caesarean Scar Ectopic Pregnancy: A Retrospective Analysis of Risk Factors, Strategies, and Outcomes

Objective: Caesarean Scar Ectopic Pregnancies (CSEP) pose distinct diagnostic and management challenges. This study investigates the risk factors, treatment options, and outcomes for CSEP cases treated at Prince Sultan Medical Military City, Riyadh. Methods: Over a two-year period, medical records of 28 patients with CSEP were reviewed, collecting data on patient demographics, obstetric history, and treatment outcomes. This analysis aimed to identify influential risk factors and assess the effectiveness of various management strategies. Results: Treatment success was achieved in 85.7% of cases, with Methotrexate (MTX) proving effective in over half of the cases. The findings suggest significant risk factors and best practices for managing this rare condition. Conclusion: Early detection, risk factor awareness, and tailored treatment strategies are key to optimizing outcomes in patients with CSEP.

Radiomics nomogram combined with clinical factors for predicting pathological complete response in resectable esophageal squamous cell carcinoma.

Predicting the efficacy of neoadjuvant immunochemotherapy (NICT) for esophageal squamous cell carcinoma (ESSC) prior to surgery can minimize unnecessary surgical interventions and facilitate personalized treatment strategies. Our goal is to develop and validate an image-based radiomic model using preoperative computed tomography (CT) scans and clinical data to predict pathological complete response (pCR) in resectable ESSC following neoadjuvant immunotherapy. We retrospectively collected data from patients diagnosed with ESCC at the First Affiliated Hospital of Soochow University between January 2018 and May 2023, who received preoperative neoadjuvant immunochemotherapy. Eligible patients were randomly divided into training and validation sets. Radiomic features extracted from preprocessed CT images were used to develop a radiomic model, incorporating Radiomic score (Rad-score) and clinical factors through multivariate logistic regression analysis. The model's performance was assessed for calibration, discrimination, and clinical utility in an independent validation cohort. We enrolled a total of 105 eligible participants who were randomly divided into two groups: a training set (N=74) and a validation set (N=31). After data dimension reduction and feature selection, we identified 11 radiomic features, which collectively formed the Rad-score. Rad-score had an area under the curve (AUC) of 0.83 (95% CI 0.72-0.93) in the training set and 0.78 (95% CI 0.60-0.95) in the validation set. Multivariate analysis revealed that radiological response and Neutrophil-Lymphocyte Ratio (NLR) were independent predictors of pCR, with p-values of 0.0026 and 0.0414, respectively. We developed and validated a nomogram combining Rad-score and clinical features, achieving AUCs of 0.90 (95% CI 0.82-0.98) in the training set and 0.85 (95% CI 0.70-0.99) in the validation set. The Delong test confirmed the nomogram's superiority over pure radiomic and clinical models. Decision curve analysis (DCA) and integrated discrimination improvement (IDI) assessment supported the clinical value and superiority of the combined model. The nomogram, which integrates Rad-score and clinical features, offers a precise and reliable method for predicting pCR status in ESCC patients who have undergone neoadjuvant immunochemotherapy. This tool aids in tailoring treatment strategies to individual patients.