Improved Survival In Patients Research Articles

Aneurysm Sac Shrinkage at 1 Year after Fenestrated-Branched Endovascular Aortic Repair of Complex Aortic Aneurysms Offers Mid-Term Survival Advantage

To investigate the impact of 1-year changes in aneurysm sac diameter on patient survival after fenestrated-branched endovascular aortic repair (FB-EVAR) of complex abdominal (CAAA) or thoracoabdominal aortic aneurysms (TAAA). We reviewed the clinical data of patients enrolled in a prospective non-randomized study investigating FB-EVAR (2013-2022). Patients with sequential follow up computed tomography (CT) scans at baseline and 6 to 18 months after FB-EVAR were included in the analysis. Aneurysm sac diameter change was defined as the difference in maximum aortic diameter (MAD) from baseline measurements obtained in centerline of flow. Patients were classified as those with sac shrinkage (≥5mm) or failure to regress (<5mm or expansion) according to sac diameter change. Primary endpoint was all-cause mortality. Secondary endpoints were aortic-related mortality (ARM), aortic aneurysm rupture (AAR) and aorta-related secondary intervention. There were 549 patients treated by FB-EVAR. Of these, 463 patients (71% male, mean 74±8 years-old) with sequential CT imaging were investigated. Aneurysm extent was TAAA in 328 (71%) patients and CAAA in 135 (29%). Sac shrinkage occurred in 270 (58%) patients and failure to regress in 193 (42%) patients, including 19 (4%) patients with sac expansion at 1-year. Patients from both groups had similar cardiovascular risk factors, except for younger age among patients with sac shrinkage (73±8 vs. 75±8 years-old; P<.001). Median follow-up was 38 months (interquartile range, 18-51 months). Five-year survival estimate was 69%±4.1% for sac shrinkage and 46%±6.2% for failure to regress group. Survival estimates adjusted for confounders (age, chronic pulmonary obstructive disease, chronic kidney disease, congestive heart failure, and aneurysm extent) revealed a higher hazard of late mortality in patients with failure to regress (adjusted hazard ratio, 1.72; 95% confidence interval, 1.18-2.52; P=.005). Five-year cumulative incidences of ARM (1.1% vs. 3.1%, P=.30), AAR (0.6% vs. 2.6%, P=.20) and aorta-related secondary intervention (17±2.8% vs. 19±3.8%) were both comparable between the groups. Aneurysm sac shrinkage at 1 year is frequent after FB-EVAR and is associated with improved patient survival, while sac enlargement affects only a minority of patients. The low incidences of ARM and AAR indicate that failure to regress may serve as a surrogate marker for non-aortic-related death.

Australian rheumatologists' perception of autologous haemopoietic stem cell transplantation for the treatment of systemic sclerosis: a cross-sectional survey.

Autologous haemopoietic stem cell transplantation (AHSCT) is an effective treatment for systemic sclerosis (SSc); however, treatment-related toxicity remains a key issue. To investigate the perceptions of rheumatologists on the use of AHSCT for SSc. Australian rheumatologists were asked for their opinion on the role of AHSCT, the indications for treatment and the barriers to the use of AHSCT for SSc. A secondary analysis assessed what factors influenced the perception of AHSCT. A total of 77.8% rheumatologists agreed or strongly agreed with the statement that AHSCT is an accepted treatment for SSc. While 65.1% agreed or strongly agreed that treatment-associated mortality was a significant barrier to referral for AHSCT, only 15.2% agreed or strongly agreed that this risk was unacceptable. Progressive lung or skin disease, or lack of response to other therapies, were considered the main referral criteria. A total of 92.0% of respondents agreed or strongly agreed that reduction of treatment toxicity would increase their likelihood to refer patients for AHSCT. Rheumatologists who were aware of the correct evidence base were more likely to consider AHSCT an acceptable treatment for SSc (4.21 ± 0.7 vs 3.64 ± 0.9, P = 0.007). Rheumatologists desire improved patient selection criteria and access to treatment. In this national survey of rheumatologists, AHSCT is considered an accepted therapy. However, concern about toxicity remains a potential barrier to patient referral. Access, studies to refine patient selection and development of AHSCT protocols that improve safety were identified as key areas of need.

Machine Learning-Based Integrated Multiomics Characterization of Colorectal Cancer Reveals Distinctive Metabolic Signatures.

The metabolic signature identification of colorectal cancer is critical for its early diagnosis and therapeutic approaches that will significantly block cancer progression and improve patient survival. Here, we combined an untargeted metabolic analysis strategy based on internal extractive electrospray ionization mass spectrometry and the machine learning approach to analyze metabolites in 173 pairs of cancer samples and matched normal tissue samples to build robust metabolic signature models for diagnostic purposes. Screening and independent validation of metabolic signatures from colorectal cancers via machine learning methods (Logistic Regression_L1 for feature selection and eXtreme Gradient Boosting for classification) was performed to generate a panel of seven signatures with good diagnostic performance (the accuracy of 87.74%, sensitivity of 85.82%, and specificity of 89.66%). Moreover, seven signatures were evaluated according to their ability to distinguish between cancer and normal tissues, with the metabolic molecule PC (30:0) showing good diagnostic performance. In addition, genes associated with PC (30:0) were identified by multiomics analysis (combining metabolic data with transcriptomic data analysis) and our results showed that PC (30:0) could promote the proliferation of colorectal cancer cell SW480, revealing the correlation between genetic changes and metabolic dysregulation in cancer. Overall, our results reveal potential determinants affecting metabolite dysregulation, paving the way for a mechanistic understanding of altered tissue metabolites in colorectal cancer and design interventions for manipulating the levels of circulating metabolites.

Validation of the CREST model & Comparison with SCAI Shock Classification for Prediction of Circulatory Death in Resuscitated Out of Hospital Cardiac Arrest.

We validated the CREST model, a 5 variable score for stratifying risk of circulatory etiology death (CED) following out of hospital cardiac arrest (OHCA), and compared its discrimination with the SCAI shock classification. CED occurs in approximately a third of patients admitted after resuscitated OHCA. There is an urgent need for improved stratification of the OHCA patient on arrival to a cardiac arrest centre to improve patient selection for invasive interventions. The CREST model and SCAI shock classification were applied to a dual-centre registry of 723 patients with cardiac etiology OHCA, both with and without ST-elevation myocardial infarction, between May 2012 to December 2020. The primary endpoint was 30-day CED. Of 509 patients included (62.3 years, 75.4% male), 125 patients had CREST=0 (24.5%), 162 were CREST=1 (31.8%), 140 were CREST=2 (27.5%), 75 were CREST=3 (14.7%), 7 were CREST of 4 (1.4%) and no patients were CREST=5. CED was observed in 91 (17.9%) patients at 30 days [STEMI - 51/289 (17.6%); NSTEMI - 40/220 (18.2%)]. For the total population, and both NSTEMI & STEMI subpopulations, increasing CREST score was associated with increasing CED (all p<0.001). CREST score and SCAI classification had similar discrimination for the total population (AUC=0.72/calibration slope=0.95), NSTEMI cohort (AUC=0.75/calibration slope=0.940) and STEMI cohort (AUC=0.69 and calibration slope=0.925). AUC meta-analyses demonstrated no significant differences between the two classifications. The CREST model and SCAI shock classification have similar prediction for the development of CED after OHCA.

Fluorescein-guided surgery in high-grade gliomas: focusing on the eloquent and deep-seated areas

PurposeThe vital function of eloquent and deep brain areas necessitates precise treatment for tumors located in these regions. Fluorescein-guided surgery (FGS) has been widely used for high-grade gliomas (HGGs) resection. Nevertheless, the safety and efficacy of utilizing this technique for resecting brain tumors located in eloquent and deep-seated areas remain uncertain. This study aims to assess the safety and extent of resection of HGGs in these challenging tumors with fluorescein and explore its impact on patient survival.MethodsA retrospective analysis was conducted on the clinical and radiological data of 67 consecutive patients with eloquent or deep-seated HGGs who underwent surgery between January 2020 and June 2023. Lacroix functional location grade was used to determine the eloquence of the tumors. The comparison between the fluorescence-guided surgery group (FGS, n = 32) and the conventional white-light microscopic surgery group (non-FGS, n = 35) included assessments of extent of resection (EOR), rates of gross total resection (GTR, 100%) and near-total resection (NTR, 99 to 98%), postoperative Neurologic Assessment in Neuro-Oncology (NANO) scores, overall survival (OS), and progression-free survival (PFS), to evaluate the safety and efficacy of fluorescein-guided technology in tumor resection at these specific locations.ResultsBaseline of demographics, lesion location, and pathology showed no significant difference between the two groups. GTR of the FGS group was higher than the non-FGS group (84.4% vs. 60.0%, OR 3.60, 95% CI 1.18–10.28, p < 0.05). The FGS group also showed higher GTR + NTR (EOR ≥ 98%) than the non-FGS group (93.8% vs. 65.7%, OR 7.83, 95% CI 1.86–36.85, p < 0.01). 87.0% of eloquent tumors (Lacroix grade III) in the FGS group achieved GTR + NTR, compared to 52.2% of control group (OR 6.11, 95% CI 1.50–22.78, p < 0.05). For deep-seated tumors, the rate of GTR + NTR in the two groups were 91.7% and 53.3%, respectively (OR 9.62, 95% CI 1.05–116.50, p < 0.05). No significant difference of the preoperative NANO score of the two groups was found. The postoperative NANO score of the FGS group was significantly lower than the non-FGS group (2.56 ± 1.29 vs. 3.43 ± 1.63, p < 0.05). Median OS of the FGS group was 4.2 months longer than the non-FGS group despite no statistical difference (18.2 months vs. 14.0 months, HR 0.63, 95% CI 0.36–1.11, p = 0.112), while PSF was found significantly longer in FGS patients than those of the non-FGS group (11.2 months vs. 7.7 months, HR 0.59, 95% CI 0.35–0.99, p < 0.05).ConclusionSodium fluorescein-guided surgery for high-grade gliomas in eloquent and deep-seated brain regions enables more extensive resection while preserving neurologic function and improve patient survival.

Chitosan-modified manganese oxide-conjugated methotrexate nanoparticles delivering 5-aminolevulinic acid as a dual-modal T1-T2* MRI contrast agent in U87MG cell detection.

Glioblastoma multiforme is a highly aggressive form of brain cancer, and early diagnosis plays a pivotal role in improving patient survival rates. In this regard, molecular magnetic resonance imaging has emerged as a promising imaging modality due to its exceptional sensitivity to minute tissue changes and the ability to penetrate deep into the brain. This study aimed to assess the efficacy of a novel contrast agent in detecting gliomas during MRI scans. The contrast agent utilized modified chitosan coating on manganese oxide nanoparticles. The modification included adding methotrexate and 5-aminolevulinic acid (MnO2/CS@5-ALA-MTX) to target cells with overexpressed folate receptors and breaking down excess hydrogen peroxide in tumor tissue, resulting in enhanced signal intensity in T1-weighted MR images but diminished signal intensity in T2*-weighted MR images. The nanosystem was characterized and evaluated in MR imaging, safety, and ability to target cells both in vivo and in vitro. MTX-free nanoparticles (MnO2/CS@5-ALA NPs) had no obvious cytotoxicity on cell lines U87MG and NIH3T3 after 24/48 h at a concentration of up to 160 µgr/mL (cell viability more than 80%). In this system, methotrexate enables tumor targeting and the MnO2/5-ALA improves T1-T2*-weighted MRI. In addition, MRI scans of mice with M109 carcinoma indicated significant tumor uptake and NP capacity to improve the positive contrast effect. This developed MnO2/CS@5-ALA-MTX nanoparticle system may exhibit great potential in the accurate diagnosis of folate receptor over-expressing cancers such as glioblastoma.

Strauss criteria for left bundle branch block in cardiac resynchronization therapy: improved response with lower ventricular arrhythmic burden

Abstract Objectives The study sought to evaluate the impact of the stricter Strauss criteria for left bundle branch block (St-LBBB) on cardiac resynchronization therapy (CRT) response, hospitalizations, ventricular arrhythmia (VA) events and mortality. Background Although left bundle branch block (LBBB) is a strong predictor of response to CRT, a significant number of patients remain non-responders. Methods This is a retrospective analysis of prospectively collected data on heart failure (HF) patients with LBBB admitted for CRT implantation. Patients were divided in two groups according to the fulfillment or not of St-LBBB criteria. Results 82 patients with ischemic (ICM) and non-ischemic (NICM) HF [46 (56%) with St-LBBB and 36 (44%) with non-St-LBBB] were included. CRT response was more likely to occur in patients with St-LBBB (p&amp;lt;0.01), with the group of NICM exhibiting the greatest benefit (p&amp;lt;0.01). St-LBBB CRT responders displayed significantly lower rates of HF hospitalization (p&amp;lt;0.0001) compared to non-St-LBBB group. This was mostly evident in patients with NICM (p&amp;lt;0.0001) according to Kaplan-Meier time curves. CRT responders displayed significantly fewer VA events (p&amp;lt;0.001) and lower mortality rates (p&amp;lt;0.0001) than non-responders. Kaplan-Meier estimates demonstrated a significantly lower incidence of VAs in NICM patients with St-LBBB (p:0.049) in comparison to ICM patients with St-LBBB (p:0.25). Lower mortality rates were observed in CRT responders than non-responders (p&amp;lt;0.0001) with the group of NICM with St-LBBB criteria exhibiting the greatest benefit (p:0.0238). Conclusions Patients with NICM and St-LBBB present the greatest benefit with respect to CRT response, HF hospitalizations, VA events, and mortality. St-LBBB criteria may improve patient selection for CRT.

Cisternal and intraventricular irrigation in subarachnoid and intraventricular haemorrhage

BackgroundSubarachnoid haemorrhage (SAH) and intraventricular haemorrhage (IVH) are associated with poor patient outcomes. Intraventricular fibrinolysis is effective in clearing IVH and improving patient survival and neurological outcome. By similar rationale,...

Target engagement of an anti-MT1-MMP antibody for triple-negative breast cancer PET imaging and beta therapy

PurposeTriple-negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that lacks effective diagnostic and therapeutic options. Membrane type 1 matrix metalloproteinase (MT1-MMP) is an attractive biomarker for improving patient selection. This study aimed to develop a theranostic tool using a highly tumour-selective anti-MT1-MMP antibody (LEM2/15) radiolabelled with 89Zr for PET and 177Lu for therapy in a TNBC murine model. MethodsThe LEM2/15 antibody and IgG isotype control were radiolabelled with 89Zr. PET imaging was performed in a TNBC orthotopic mouse model at 1, 2, 4, and 7 days after administration. Tissue biodistribution and pharmacokinetic parameters were analysed and Patlak linearisation was used to calculate the influx rate of irreversible uptake. The TNBC mice were treated with [177Lu]Lu-DOTA-LEM2/15 (single- or 3-dose regimen) or saline. Efficacy of [177Lu]Lu-DOTA-LEM2/15 was evaluated as tumour growth and DNA damage (γH2AX) in MDA 231-BrM2-831 tumours. ResultsAt 7 days post-injection, PET uptake in tumour xenografts revealed a 1.6-fold and 2.4-fold higher tumour-to-blood ratio for [89Zr]Zr-Df-LEM2/15 in the non-blocked group compared to the blocked and IgG isotype control groups, respectively. Specific uptake of LEM2/15 in TBNC tumours mediated by MT1-MMP-binding was demonstrated by the Patlak linearisation method, providing insights into the potential efficacy of LEM2/15-based treatments. A similar uptake was found for [89Zr]Zr-Df-LEM2/15 and [177Lu]Lu-DOTA-LEM2/15 in tumours 7 days post-injection (6.80 ± 1.31 vs. 5.61 ± 0.66 %ID/g). Tumour doubling time was longer in the [177Lu]Lu-DOTA-LEM2/15 3-dose regimen treated group compared to the control (50 vs. 17 days, respectively). The percentage of cells with γH2AX-foci was higher in tumours treated with [177Lu]Lu-DOTA-LEM2/15 3-dose regimen compared to tumours non-treated or treated with [177Lu]Lu-DOTA-LEM2/15 single-dose (12 % vs. 4–5 %). ConclusionsThe results showed that the 89Zr/177Lu-labelled anti-MT1-MMP mAb (LEM2/15) pair facilitated immune-PET imaging and reduced tumour growth in a preclinical TNBC xenograft model.

Single-cell multiomics profiling reveals heterogeneous transcriptional programs and microenvironment in DSRCTs

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive sarcoma driven by the EWSR1::WT1 chimeric transcription factor. Despite this unique oncogenic driver, DSRCT displays a polyphenotypic differentiation of unknown causality. Using single-cell multi-omics on 12 samples from five patients, we find that DSRCT tumor cells cluster into consistent subpopulations with partially overlapping lineage- and metabolism-related transcriptional programs. Invitro modeling shows that high EWSR1::WT1 DNA-binding activity associates with most lineage-related states, in contrast to glycolytic and profibrotic states. Single-cell chromatin accessibility analysis suggests that EWSR1::WT1 binding site variability may drive distinct lineage-related transcriptional programs, supporting some level of cell-intrinsic plasticity. Spatial transcriptomics reveals that glycolytic and profibrotic states specifically localize within hypoxic niches at the periphery of tumor cell islets, suggesting an additional role of tumor cell-extrinsic microenvironmental cues. We finally identify a single-cell transcriptomics-derived epithelial signature associated with improved patient survival, highlighting the clinical relevance of our findings.

Efficacy and Safety of Minimally Invasive Surgery Techniques in The Treatment of Acute Appendicitis: A literature review.

An appendectomy is often used to treat acute appendicitis, which is characterized by inflammation of the vermiform appendix. Techniques in minimally invasive surgery (MIS), such as endoscopic retrograde appendicitis therapy (ERAT), single-incision laparoscopic surgery (SILS), and laparoscopic appendectomy, have become popular substitutes for open surgery. The purpose of this review is to assess the safety and effectiveness of MIS methods for treating acute appendicitis. A comprehensive analysis of English-language literature from 2019 to 2024 was carried out to evaluate the safety and efficacy of MIS procedures for acute appendicitis. Research that satisfied the inclusion requirements was examined for pertinent information on SILS, ERAT, and laparoscopic appendectomy. Compared to open surgery, laparoscopic appendectomy showed shorter hospital stays, less pain after surgery, and quicker recovery rates. Comparable to traditional laparoscopic methods in terms of effectiveness, SILS and TULS provide potential advantages in terms of cosmesis and patient satisfaction. With faster recovery durations and fewer complications, ERAT showed encouraging results; nonetheless, questions about long-term effectiveness and recurrence rates were raised. In order to treat acute appendicitis, MIS procedures provide viable options that may shorten hospital stays, ease postoperative pain, and increase patient satisfaction. More investigation is necessary to improve patient selection criteria and operative approaches in order to maximize the efficacy of MIS in the therapy of appendicitis.

MUltiparametric Score for Ventilation Discontinuation in Intensive Care Patients: A Protocol for an Observational Study.

Mechanical ventilation significantly improves patient survival but is associated with complications, increasing healthcare costs and morbidity. Identifying optimal weaning times is paramount to minimize these risks, yet current methods rely heavily on clinical judgment, lacking specificity. This study introduces a novel multiparametric predictive score, the MUSVIP (MUltiparametric Score for Ventilation discontinuation in Intensive care Patients), aimed at accurately predicting successful extubation. Conducted at Santo Stefano Hospital's ICU, this single-center, observational, prospective cohort study will span over 12 months, enrolling adult patients undergoing invasive mechanical ventilation. The MUSVIP integrates variables measured before and during a spontaneous breathing trial (SBT) to formulate a predictive score. Preliminary analyses suggest an Area Under the Curve (AUC) of 0.815 for the MUSVIP, indicating high predictive capacity. By systematically applying this score, we anticipate identifying patients likely to succeed in weaning earlier, potentially reducing ICU length of stay and associated healthcare costs. This study's findings could significantly influence clinical practices, offering a robust, easy-to-use tool for optimizing weaning processes in ICUs.

Abstract B019: Identification of gene signatures predictive of response to Ad-IFNα/Syn3 in bladder cancer

Abstract Introduction: Interferon α gene therapy (Ad-IFNα/Syn3) is FDA approved for treatment of BCG-unresponsive non-muscle invasive bladder cancer. Ad-IFNα/Syn3 is a non-replicating adenovirus that when transduced into target tissues, produces IFNa2b protein with anti-tumor activity. In the phase 3 multicenter trial, 45.5% of patients with carcinoma-in-situ and 60% of those with Ta/T1 disease who had a complete response to Ad-IFNα/Syn3 at 3 months remained recurrence free at 12 months. Targeting mechanisms of resistance and identifying predictive biomarkers to improve patient selection and overall response rates is a top priority. Towards this, we treated 29 human bladder cancer cell lines with Ad-IFNα/Syn3 and assessed their responses to therapy. We identified sensitive and resistant cell lines and gene signatures predictive of response. Methods: Human bladder cancer cell lines were grown in MEM supplemented with 10% FBS in 96-well plate. After overnight attachment, these were treated with Ad-IFNα/Syn3 (MOI 1000) and cell titre glow assay was performed 72h post-treatment. Cells were also seeded in 6-well plates. and after 24h cell-free supernatants were collected for ELISA and cells were collected for RNA isolation using RNAqueous Total RNA Isolation kit (Thermo Fisher). RNA quality was assessed using Tapestation. RNAseq analysis was carried out using Ion proton Sequencer. Ingenuity pathway analysis (IPA) and gene set enrichment were performed on the sequencing data for the cell lines. ELISA was used to measure IFNα and IL6 protein levels in cell free supernatants. We also tested organoids developed from bladder cancer patients to test drug efficacy and identify gene signatures. Results: Out of the 29 cell lines, we identified that sensitivity to Ad-IFNα/Syn3 was pronounced in luminal cells (8/13 luminal cell lines). Most basal cells were either resistant (&amp;gt;70% viability) or only moderately sensitive to Ad-IFNα/Syn3 (between 70-40% viability) when compared to control. We selected 7 cell lines for sequencing and ELISA measurements: luminal cell lines BV, UC6, Rt4V6 and UC5, and basal cell lines ScaBER, HT1197, and T24. All cell lines mentioned above could be successfully transduced by the adenoviral vector as measured by increased expression of IFNα protein in the cell-free supernatants. Ad-IFNα/Syn3-sensitive luminal cell lines at baseline had lower IFNα and IFNγ scores when compared to resistant basal cell lines. We identified several cell-death pathways enriched in treated cells that were sensitive to Ad-IFNα/Syn3. IL6 measurements in cell free supernatants revealed increased expression of IL6 after treatment in sensitive cells. However, in resistant cells IL6 expression was either high at baseline (ScaBER) or both undetectable at baseline and after treatment (UC5). Conclusion: Our results suggest that the luminal cell lines are more sensitive to Ad-IFNα/Syn3 and that high baseline expression of IFNα and IFNγ in basal cell lines contributes to resistance. IL6 levels are also predictive of response to Ad-IFNα/Syn3. Citation Format: Morgan E. Pierce, Alexis R. Steinmetz, Aruna Nannapaneni, Tanner S. Miest, David J. McConkey, Sharada Mokkapati, Colin P.N. Dinney. Identification of gene signatures predictive of response to Ad-IFNα/Syn3 in bladder cancer [abstract]. In: Proceedings of the AACR Special Conference on Bladder Cancer: Transforming the Field; 2024 May 17-20; Charlotte, NC. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(10_Suppl):Abstract nr B019.

Folic acid-mediated enhancement of the diagnostic potential of luminescent europium-doped hydroxyapatite nanocrystals for cancer biomaging

Early and accurate cancer diagnosis is crucial for improving patient survival rates. Luminescent nanoparticles have emerged as a promising tool in fluorescence bioimaging for cancer diagnosis. To enhance diagnostic accuracy, ligands promoting endocytosis into cancer cells are commonly incorporated onto nanoparticle surfaces. Folic acid (FA) is one such ligand, known to specifically bind to folate receptors (FR) overexpressed in various cancer cells such as cervical and ovarian carcinoma. Therefore, surface modification of luminescent nanoparticles with FA can enhance both luminescence efficiency and diagnostic accuracy. In this study, luminescent europium-doped hydroxyapatite (EuHAp) nanocrystals were prepared via hydrothermal method and subsequently modified with (3-Aminopropyl)triethoxysilane (APTES) followed by FA to target FR-positive human cervical adenocarcinoma cell line (HeLa) cells. The sequential grafting of APTES and then FA formed a robust covalent linkage between the nanocrystals and FA. Rod-shaped FA-modified EuHAp nanocrystals, approximately 100 nm in size, exhibited emission peaks at 589, 615, and 650 nm upon excitation at 397 nm. Despite a reduction in photoluminescence intensity following FA modification, fluorescence microscopy revealed a remarkable 120-fold increase in intensity compared to unmodified EuHAp, attributed to the enhanced uptake of FA-modified EuHAp. Additionally, confocal microscope observations confirmed the specificity and the internalization of FA-modified EuHAp nanocrystals in HeLa cells. In conclusion, the modification of EuHAp nanocrystals with FA presents a promising strategy to enhance the diagnostic potential of cancer bioimaging probes.

Opportunities and challenges in accurate early diagnosis and treatment of lung cancer/pulmonary nodules

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.

Approaches and considerations in the endoscopic treatment of T1 colorectal cancer.

The detection of early colorectal cancer (CRC) is increasing through the implementation of screening programs. This increased detection enhances the likelihood of minimally invasive surgery and significantly lowers the risk of recurrence, thereby improving patient survival and reducing mortality rates. T1 CRC, the earliest stage, is treated endoscopically in cases with a low risk of lymph node metastasis (LNM). The advantages of endoscopic treatment compared with surgery include minimal invasiveness and limited tissue disruption, which reduce morbidity and mortality, preserve bowel function to avoid colectomy, accelerate recovery, and improve cost-effectiveness. However, T1 CRC has a risk of LNM. Thus, selection of the appropriate treatment between endoscopic treatment and surgery, while avoiding overtreatment, is challenging considering the potential for complete resection, LNM, and recurrence risk.

KRAS-mutated non-small cell lung cancer: new therapy strategies

Lung cancer remains one of the most dangerous and most common cancers, requiring constant improvement of diagnostic and treatment methods. The genetic heterogeneity of lung cancer forces us to search for new therapeutic targets in an attempt to achieve greater effectiveness for certain groups of patients. The purpose of the study was to update current knowledge about lung adenocarcinoma with a mutation in the KRAS gene, to consider new opportunities for personalized treatment of KRAS-mutated NSCLC and to form an image of a Russian patient who is potentially indicated for targeted therapy. Material and methods. A search of available literature sources published in the Pubmed, Cochrane Library, Elibrary database was carried out, publications covering the period from 2008 to 2023 were included. Results. The article discussed molecular genetic testing, including NGS next generation sequencing, and its role in determining the presence of KRAS gene mutations in patients with lung cancer. the effectiveness of targeted drugs, such as Sotorasib and Adagrasib was also discussed. The mechanism of action is aimed at suppressing the activity of the mutant KRAS G12C protein, which can significantly improve patient survival prognosis. We obtained data on the results of testing 935 patients with non-squamous non-small cell lung cancer from various medical centers in Russia. The KRAS gene mutation was identified in 160 (17.1 %) patients, of whom 96 (10.3 %) had KRAS G12C variant. The KRAS mutation was determined by PCR in 44 patients and by NGS (including on the FoundationOne platform) in 111 patients. Clinical characteristics, such as gender, age, smoking status, PD-L1 expression level, presence of co-mutations (TP53, STK11, KEAP1, were largely similar between patients from real-world clinical practice and patients included in the CodeBreak100 study. Conclusion. The research results confirm the high effectiveness of Sotorasib and Adagrasib for patients with the KRAS G12C mutation and open up new prospects in the treatment of lung cancer. The clinical data obtained from Russian patients demonstrate consistency with the patient profile from registration studies of these drugs. This once again demonstrates the need to expand the range of molecular genetic testing for timely identification of this group of patients and prescribing the most effective treatment for them.

How I do it. Pancreatojejunostomy: surgical tips to mitigate the severity of postoperative pancreatic fistulas after open or minimally invasive pancreatoduodenectomy.

Pancreatoduodenectomy is the most appropriate technique for the treatment of periampullary tumors. In the past, this procedure was associated with high mortality and morbidity, but with improvements in patient selection, anesthesia, and surgical technique, mortality has decreased to less than 5%. However, morbidity remains increased due to various complications such as delayed gastric emptying, bleeding, abdominal collections, and abscesses, most of which are related to the pancreatojejunostomy leak. Clinically relevant postoperative pancreatic fistula is the most dangerous and is related to other complications including mortality. The incidence of postoperative pancreatic fistula ranges from 5-30%. Various techniques have been developed to reduce the severity of pancreatic fistulas, from the use of an isolated jejunal loop for pancreatojejunostomy to binding and invagination anastomoses. Even total pancreatectomy has been considered to avoid pancreatic fistula, but the late effects of this procedure are unacceptable, especially in relatively young patients. Recent studies on the main techniques of pancreatojejunostomy concluded that duct-to-mucosa anastomosis is advisable, but no technique eliminates the risk of pancreatic fistula. The purpose of this study is to highlight technical details and tips that may reduce the severity of pancreatic fistula after pancreatojejunostomy during open or minimally invasive pancreatoduodenectomy.

Declination of Treatment, Racial and Ethnic Disparity, and Overall Survival in US Patients With Breast Cancer

Declining treatment negatively affects health outcomes among patients with cancer. Limited research has investigated national trends of and factors associated with treatment declination or its association with overall survival (OS) among patients with breast cancer. To examine trends and racial and ethnic disparities in treatment declination and racial and ethnic OS differences stratified by treatment decision in US patients with breast cancer. This retrospective cross-sectional study used data for patients with breast cancer from the 2004 to 2020 National Cancer Database. Four treatment modalities were assessed: chemotherapy, hormone therapy (HT), radiotherapy, and surgery. The chemotherapy cohort included patients with stage I to IV disease. The HT cohort included patients with stage I to IV hormone receptor-positive disease. The radiotherapy and surgery cohorts included patients with stage I to III disease. Data were analyzed from March to November 2023. Race and ethnicity and other sociodemographic and clinicopathologic characteristics. Treatment decision, categorized as received or declined, was modeled using logistic regression. OS was modeled using Cox regression. Models were controlled for year of initial diagnosis, age, sex, health insurance, median household income, facility type, Charlson-Deyo comorbidity score, histology, American Joint Committee on Cancer stage, molecular subtype, and tumor grade. The study included 2 837 446 patients (mean [SD] age, 61.6 [13.4] years; 99.1% female), with 1.7% American Indian, Alaska Native, or other patients; 3.5% Asian or Pacific Islander patients; 11.2% Black patients; 5.6% Hispanic patients; and 78.0% White patients. Of 1 296 488 patients who were offered chemotherapy, 124 721 (9.6%) declined; 99 276 of 1 635 916 patients (6.1%) declined radiotherapy; 94 363 of 1 893 339 patients (5.0%) declined HT; and 15 846 of 2 590 963 patients (0.6%) declined surgery. Compared with White patients, American Indian, Alaska Native, or other patients (adjusted odds ratio [AOR], 1.47; 95% CI, 1.26-1.72), Asian or Pacific Islander patients (AOR, 1.29; 95% CI, 1.15-1.44), and Black patients (AOR, 2.01; 95% CI, 1.89-2.14) were more likely to decline surgery; American Indian, Alaska Native, or other patients (AOR, 1.13; 95% CI, 1.05-1.21) and Asian or Pacific Islander patients (AOR, 1.21; 95% CI, 1.16-1.27) were more likely to decline chemotherapy; and Black patients were more likely to decline radiotherapy (AOR, 1.05; 95% CI, 1.02-1.08). Asian or Pacific Islander patients (AOR, 0.81; 95% CI, 0.77-0.85), Black patients (AOR, 0.86; 95% CI, 0.83-0.89), and Hispanic patients (AOR, 0.66; 95% CI, 0.63-0.69) were less likely to decline HT. Furthermore, Black patients who declined chemotherapy had a higher mortality risk than White patients (adjusted hazard ratio [AHR], 1.07; 95% CI, 1.02-1.13), while there were no OS differences between Black and White patients who declined HT (AHR, 1.05; 95% CI, 0.97-1.13) or radiotherapy (AHR, 0.98; 95% CI, 0.92-1.04). This cross-sectional study highlights racial and ethnic disparities in treatment declination and OS, suggesting the need for equity-focused interventions, such as patient education on treatment benefits and improved patient-clinician communication and shared decision-making, to reduce disparities and improve patient survival.

Advanced antibacterial materials for the prevention of nosocomial infections

Abstract Nosocomial infections, as the most common adverse event in healthcare environments, have become an urgent global challenge. It is of great significance in solving nosocomial infections to improve patient survival rate and reduce the economic burden on patients. Antibacterial materials play a crucial role in the prevention and treatment of nosocomial infections. Since traditional antibacterial materials are not sufficient to satisfy the increasing clinical requirements, advanced antibacterial materials are widely developed in biomedical applications and hospital health fields, aiming at achieving more efficient, longer-lasting and safer antimicrobial effect. This article outlines the construction strategies and mechanisms of advanced antibacterial materials, including bacterial adhesion prevention, release of antibacterial agents, contact-kill materials and multi-strategy-based sterilization. Meanwhile, the latest progress of advanced antibacterial materials in clinical departments and public environments is summarized and explored, including dressings, medical sutures, implants, bone cements, catheters, plastics products, ceramics, and fiber fabrics. Finally, the challenges and future directions for researches, as well as translations of advanced antibacterial materials are discussed, providing comprehensive reference and guidance for the development of medical system and clinical application.