Clinical Management Of Patients Research Articles

Italian Society of Pediatric Cardiology (SICP) position paper on the prevention, diagnosis, treatment and follow-up of cardiotoxicity in pediatric patients with cancer

The survival of pediatric cancer patients has significantly increased thanks to the improvement of oncological treatments. Therefore, it is of utmost importance to manage short- and long-term cardiovascular complications. In pediatric cardio-oncology, there are no recognized guidelines as in adults. Several recommendations and many indications have been derived from the data obtained in the adult cancer population, resulting in greater discrepancies in the clinical management of patients. The aim of this position paper of the Italian Society of Pediatric Cardiology (SICP) is to collect the main evidence regarding the diagnosis, prevention, treatment and follow-up of cardiotoxicity in children, to provide useful indications for clinical practice, and to promote a network between pediatric centers.

Huoxue Jiedu Huayu recipe inhibits macrophage-secreted vascular endothelial growth factor-a on angiogenesis and alleviates renal fibrosis in the contralateral kidneys of unilateral ureteral obstruction rats.

Male Wistar rats were randomly divided into 4 groups: the sham group, UUO group (180 d of left ureter ligation), UUO plus eplerenone (EPL) group, and UUO plus HJHR group. After 180 d of oral drug administration, blood and contralateral kidneys were collected for analysis. Angiogenesis- and fibrosis-related indexes were detected. HJHR and EPL improved structural damage and renal interstitial fibrosis in the contralateral kidney and reduced the protein expression levels of α-smooth muscle actin (α-SMA), vimentin and collagen I. Moreover, these treatments could reduce the expression of vascular endothelial growth factor-A (VEGFA) by inhibiting the infiltration of macrophages. Furthermore, HJHR and EPL significantly reduced the expression of CD34 and CD105 by downregulating VEGFA production, which inhibited angiogenesis. Finally, the coexpressions of CD34, CD105 and α-SMA were decreased in the HJHR and EPL groups, indicating that endothelial-to-mesenchymal transition was inhibited. These findings confirm that HJHR alleviates contralateral renal fibrosis by inhibiting VEGFA-induced angiogenesis, encourage the use of HJHR against renal interstitial fibrosis and provide a theoretical basis for the clinical management of patients with CKD.

Update on recent advances in amyotrophic lateral sclerosis.

In the last few years, our understanding of disease molecular mechanisms underpinning ALS has advanced greatly, allowing the first steps in translating into clinical practice novel research findings, including gene therapy approaches. Similarly, the recent advent of assistive technologies has greatly improved the possibility of a more personalized approach to supportive and symptomatic care, in the context of an increasingly complex multidisciplinary line of actions, which remains the cornerstone of ALS management. Against this rapidly growing background, here we provide an comprehensive update on the most recent studies that have contributed towards our understanding of ALS pathogenesis, the latest results from clinical trials as well as the future directions for improving the clinical management of ALS patients.

A Systematic Literature Review on Inflammatory Markers in the Saliva of Patients with Multiple Sclerosis: A Cause or a Consequence of Periodontal Diseases

Background and Objectives: Multiple sclerosis (MS) is a chronic neurodegenerative disease often linked with systemic conditions such as periodontal diseases (PDs). This systematic review aims to explore the association between inflammatory markers in saliva and PDs in MS patients, assessing the use of saliva as a non-invasive tool to monitor disease progression. Materials and Methods: 82 publications were examined after a thorough search of scholarly databases to determine whether inflammatory markers were present in MS patients and whether they were associated with periodontal disease (PD). Quality and bias were assessed using the Newcastle–Ottawa Scale, resulting in eight articles that were thoroughly analyzed. Results: The results point to a strong correlation between MS and periodontal disorders, which may point to the same pathophysiological mechanism. It does, however, underscore the necessity of additional study to determine a definitive causal association. Conclusions: The findings indicate a strong association between MS and PDs, likely mediated by systemic inflammatory responses detectable in saliva. The review highlights the importance of oral health in managing MS and supports the utility of saliva as a practical, non-invasive medium for monitoring systemic inflammation. Further research is necessary to confirm the causal relationships and to consider integrating salivary diagnostics into routine clinical management for MS patients.

#1465 Enhancing vascular access planning in CKD: validating the 40% KFRE threshold in a French retrospective cohort study

Abstract Background and Aims The optimal timing for dialysis vascular access creation remains a complex clinical decision, balancing the risk of early intervention against the prospect of starting dialysis with a central venous catheter. This study sought to compare the predictive capabilities of the Kidney Failure Risk Equation (KFRE) and estimated Glomerular Filtration Rate (eGFR) in determining the appropriate timing for arteriovenous fistula (AVF) creation in patients with advanced chronic kidney disease (CKD). Method A retrospective cohort of 238 patients referred for ultrasound vascular mapping from April 2013 to June 2023 was analyzed. Data on patient characteristics, laboratory results, and clinical outcomes were collected. The 4-variable and 8-variable KFRE and eGFR were assessed for their ability to predict end-stage kidney disease (ESKD) within a 2-year period. Discrimination was evaluated using receiver operating characteristic (ROC) curves, and calibration was assessed graphically. Net benefit decision curves were utilized to compare the net benefit of the KFRE models at various threshold probabilities. Results The cohort comprised 238 patients with an average age of 65.2 years and a mean eGFR of 13.3 mL/min/m²73. During the median 10.7-month follow-up, 178 patients (74.8%) progressed to ESKD, and 21 (9.2%) died prior to reaching ESKD. At the 1-year mark, the probability of progressing to ESKD was 77.6% (95% CI, 69.9-85.3%) when a 40% threshold for the 4-variable KFRE was applied, compared to 65.8% (95% CI, 58.3-73.3%) with an eGFR threshold of 15 mL/min/m²73. Discrimination analysis demonstrated a superior predictive performance for the 8-variable KFRE at 6 months, with a C-statistic of 0.82 (95% CI: 0.76-0.88). At 1 year, both KFRE models showed strong predictive abilities, with C-statistics of 0.835 (95% CI: 0.78-0.89) for the 4-variable KFRE and 0.82 (95% CI: 0.76-0.875) for the 8-variable KFRE. Sensitivity and specificity analyses underscored the benefits of utilizing the 40% KFRE threshold for predicting ESKD over the eGFR threshold. Conclusion The study demonstrates that both the 4-variable and 8-variable KFRE are valuable tools for predicting the need for vascular access in pre-dialysis patients, outperforming eGFR alone. The 8-variable KFRE, in particular, provides a significant improvement in 6-months ESKD prediction, with potential implications for clinical decision-making and patient management in advanced CKD. These findings advocate for the incorporation of KFRE in the clinical evaluation process for timely and appropriate vascular access planning.

Digital Mammography (DM) vs. Dynamic Contrast Enhancement—Magnetic Resonance Imaging (DCE-MRI) in Microcalcifications Assessment: A Radiological–Pathological Comparison

The aim of this study was to compare the characteristics of breast microcalcification on digital mammography (DM) with the histological and molecular subtypes of breast cancer and to identify the predictive value of DM and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in assessing microcalcifications for radiologic–pathologic correlation. We relied on our prospectively maintained database of suspicious microcalcifications on DM, from which data were retrospectively collected between January 2020 and April 2023. We enrolled 158 patients, all of whom were subjected to biopsy. Additionally, 63 patients underwent breast DCE-MRI. Microcalcifications with a linear branched morphology were correlated with malignancies (p < 0.001), among which an association was highlighted between triple negatives (TNs) and segmental distribution (p < 0.001). Amorphous calcifications were correlated with atypical ductal hyperplasia (ADH) (p = 0.013), coarse heterogeneous (p < 0.001), and fine-pleomorphic (p = 0.008) with atypical lobular hyperplasia (ALH) and fine pleomorphic (p = 0.009) with flat epithelial atypia (FEA). Regarding DCE-MRI, no statistical significance was observed between non-mass lesions and ductal carcinoma in situ (DCIS). Concerning mass lesions, three were identified as DCIS and five as invasive ductal carcinoma (IDC). In conclusion, microcalcifications assessed in DM exhibit promising predictive characteristics concerning breast lesion subtypes, leading to a reduction in diagnostic times and further examination costs, thereby enhancing the clinical management of patients.

Proteomic features of soft tissue tumours in adolescents and young adults.

Adolescents and young adult (AYA) patients with soft tissue tumours including sarcomas are an underserved group with disparities in treatment outcomes. To define the molecular features between AYA and older adult (OA) patients, we analysed the proteomic profiles of a large cohort of soft tissue tumours across 10 histological subtypes (AYA n = 66, OA n = 243), and also analysed publicly available functional genomic data from soft tissue tumour cell lines (AYA n = 5, OA n = 8). Biological hallmarks analysis demonstrates that OA tumours are significantly enriched in MYC targets compared to AYA tumours. By comparing the patient-level proteomic data with functional genomic profiles from sarcoma cell lines, we show that the mRNA splicing pathway is an intrinsic vulnerability in cell lines from OA patients and that components of the spliceosome complex are independent prognostic factors for metastasis free survival in AYA patients. Our study highlights the importance of performing age-specific molecular profiling studies to identify risk stratification tools and targeted agents tailored for the clinical management of AYA patients.

Mining Multimorbidity Trajectories and Co-Medication Effects from Patient Data to Predict Post–Hip Fracture Outcomes

Hip fractures have profound impacts on patients’ conditions and quality of life, even when they receive therapeutic treatments. Many patients face the risk of poor prognosis, physical impairment, and even mortality, especially older patients. Accurate patient outcome estimates after an initial fracture are critical to physicians’ decision-making and patient management. Effective predictions might benefit from analyses of patients’ multimorbidity trajectories and medication usages. If adequately modeled and analyzed, they could help identify patients at higher risk of recurrent fractures or mortality. Most analytics methods overlook the onset, co-occurrence, and temporal sequence of distinct chronic diseases in the trajectory, and they also seldom consider the combined effects of different medications. To support effective predictions, we develop a novel deep learning–based method that uses a cross-attention mechanism to model patient progression by obtaining “contextual information” from multimorbidity trajectories. This method also incorporates a nested self-attention network that captures the combined effects of distinct medications by learning the interactions among medications and how dosages might influence post-fracture outcomes. A real-world patient data set is used to evaluate the proposed method, relative to six benchmark methods. The comparative results indicate that our method consistently outperforms all the benchmarks in precision, recall, F-measures, and area under the curve. The proposed method is generalizable and can be implemented as a decision support system to identify patients at greater risk of recurrent hip fractures or mortality, which should help clinical decision-making and patient management.

Proteomic Blood Profiles Obtained by Totally Blind Biological Clustering in Stable and Exacerbated COPD Patients.

Although Chronic Obstructive Pulmonary Disease (COPD) is highly prevalent, it is often underdiagnosed. One of the main characteristics of this heterogeneous disease is the presence of periods of acute clinical impairment (exacerbations). Obtaining blood biomarkers for either COPD as a chronic entity or its exacerbations (AECOPD) will be particularly useful for the clinical management of patients. However, most of the earlier studies have been characterized by potential biases derived from pre-existing hypotheses in one or more of their analysis steps: some studies have only targeted molecules already suggested by pre-existing knowledge, and others had initially carried out a blind search but later compared the detected biomarkers among well-predefined clinical groups. We hypothesized that a clinically blind cluster analysis on the results of a non-hypothesis-driven wide proteomic search would determine an unbiased grouping of patients, potentially reflecting their endotypes and/or clinical characteristics. To check this hypothesis, we included the plasma samples from 24 clinically stable COPD patients, 10 additional patients with AECOPD, and 10 healthy controls. The samples were analyzed through label-free liquid chromatography/tandem mass spectrometry. Subsequently, the Scikit-learn machine learning module and K-means were used for clustering the individuals based solely on their proteomic profiles. The obtained clusters were confronted with clinical groups only at the end of the entire procedure. Although our clusters were unable to differentiate stable COPD patients from healthy individuals, they segregated those patients with AECOPD from the patients in stable conditions (sensitivity 80%, specificity 79%, and global accuracy, 79.4%). Moreover, the proteins involved in the blind grouping process to identify AECOPD were associated with five biological processes: inflammation, humoral immune response, blood coagulation, modulation of lipid metabolism, and complement system pathways. Even though the present results merit an external validation, our results suggest that the present blinded approach may be useful to segregate AECOPD from stability in both the clinical setting and trials, favoring more personalized medicine and clinical research.

IMPROVING THE KNOWLEDGE, RISK STRATIFICATION AND OUTCOMES IN ADVANCED HEART FAILURE. THE ISMETT HEART FAILURE REGISTRY

Abstract Background Advanced heart failure (AdHF) accounts for approximately 10% of patients in HF clinics worldwide. Clinical management of patients with AdHF remains challenging and most of the available studies focus on chronic but not advanced HF. Registry studies may provide important insights into this specific population. Methods All consecutive patients referred to our centre for AdHF therapies candidacy (left ventricular assist device (LVAD), heart transplant (HTx)) are prospectively studied and enrolled in the registry. On the same day, all patients undergo a comprehensive clinical and instrumental examination, including electrocardiogram, echocardiography, extended laboratory tests and right heart catheterisation. Most patients also undergo a cardiopulmonary exercise test and, in the case of a non–ischaemic aetiology, cardiac magnetic resonance imaging and genetic testing, if not already performed. Echocardiography is also performed to assess advanced echocardiographic measures (biventricular and atrial strain, myocardial work, 3–D chambers assessment). Results Forty–five patients were enrolled from March 1, 2023 to December 22, 2023 (enrolment rate 4.5 patients/month). Mean age was 54 years and 2/3 were male. Median disease duration was 69 (28–165) months. Non–ischemic HF was the most common aetiology with a NYHA IV prevalence of 4% (all others were in NYHA III). 31% of patients had chronic kidney disease and overall liver function was preserved. 67% of patients were treated with sacubitril/valsartan, > 90% were taking beta–blockers (median dose 4.8 mg bisoprolol–equivalent dose) and 84% SGLT2 inhibitors. Both standard and advanced echocardiography showed features of advanced disease. Over a median follow–up of 4 (2 – 6) months 2 (4%) patients died, 5 (11%) underwent urgent HTx and 8 (18%) underwent LVAD implantation. For most variables, there was a trend showing that patients with events were sicker but, currently, the sample size limited the statistical power. Conclusions A systematic comprehensive evaluation of patients with AdHF evaluated for advanced HF therapies could help to reduce the knowledge gap for this high–risk HF population.

Novel tubing connectors reduce ECMO circuit thrombosis.

Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions. A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots. In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (p < 0.0001). In the long-term goat ECMO circuits, the traditional connectors exhibited more thrombi (p < 0.04), and these thrombi were more likely to protrude into the lumen of the tubing (p < 0.001). Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.

Gender-based differences in clinical profile, management and mortality in cardiogenic shock. Prognostic accuracy of CardShock vs IABP Score, the Shock-CAT study

Abstract Funding Acknowledgements None. Background Mortality in cardiogenic shock (CS) remains very high. Gender could influence in aetiology, management, outcomes and risk stratification predictors. Purpose The aim is to analyse differences in clinical profile, management, in-hospital prognosis and mortality risk in CS patients depending on sex and compare the prognostic accuracy of CardShock and IABP scores between sexes in a Mediterranean cohort. Method Shock-CAT study was a multicentre, prospective, observational study conducted between December 2018 and December 2019 in eight public University hospitals in Spain, including CS patients of different aetiologies. Data on clinical presentation, biomarkers, management, including mechanical cardiac/circulatory support (MCS) were analysed comparing women and men. Cardshock and IABP score have been compared to assess 90-days mortality risk between sexes. Results A total of 382 CS patients (p) were included: women 24.9% (n=95 p) and men 75.1% (n=287p). Women were older than men (68.9 vs 64.1 years, P=0.004). CS due to acute coronary syndrome (ACS) was more frequent in men (66.6% vs 43.2%), and myocarditis (1.7 vs 6.3%), stress cardiomyopathy (0.3% vs 8.4%) and severe aortic stenosis (2.4% vs 6.3%) were more prevalent in women, all p&amp;lt;0.001. Cardiac arrest was more prevalent in men than women (38.4% vs 25.3%, p=0.020). MCS was implanted in 35.3% of patients, without gender differences (men 36.6%, women 31.6%, p=0.376). Even though there was a non-significant trend to lower use in women of IABP (31.1% vs 26.5%), Impella (13.5% vs 7.4%) or ECMO (10.4% vs 7.4%). Risk scores were similar between sexes: Cardshock (men:4.32 vs 4.40 women, p=0.674) and IABP score (men: 2.31 vs 2.04 women, p=0.190). There were no differences between men and women in in-hospital mortality (32.4% vs 34.7%, p=0.675) or 6-months mortality (41.5% vs 40%, p=0.989). Receiver-operating characteristic curves demonstrated that IABP shock score had superior prognostic power for predicting 90-days mortality when compared with Cardshock score in men (area under the curve -AUC- 0.72 vs 0.64) respectively, p=0.009, although both scores were similar in women (AUC 0.70 vs 0.72, p=0.635), Figures 1-2. Conclusions Women with CS were older than men and had less ACS and cardiac arrest at admission. There is a non-significant lower use of mechanical assistance devices in women, although in-hospital or 6-months mortality were similar in both sexes. IABP score provided better 90-days mortality risk prediction than CardShock score in men, but both scores were similar in women with cardiogenic shock.Men ROC Curves 90-days MortalityWomen ROC Curves 90-days Mortality

Socioeconomic status and health disparities drive differences in accelerometer-derived physical activity in fatty liver disease and significant fibrosis

Background and aims The cornerstone of clinical management of patients with nonalcoholic fatty liver disease (NAFLD) are lifestyle changes such as increasing physical activity (PA) aimed at improving cardiometabolic risk. To inform NAFLD prevention and treatment guidelines we aimed to: (i) quantify the role of PA on lowering the risk for NAFLD and fibrosis; (ii) characterize NAFLD and fibrosis association with PA in the context of socioeconomic environment. Methods A sample of 2648 participants from the NHANES 2003–2006 was selected to develop survey weighted multivariable logistic regression models for predicting NAFLD and significant fibrosis, diagnosed non-invasively via fatty liver index (FLI) and fibrosis-4 (FIB-4) index. The PA measures were obtained from a hip-worn accelerometer. Results The predictive model for NAFLD showed AUC of 0.687 and a decrease of 43% in NAFLD risk with moderate vigorous PA (MVPA) (OR = 0.569, p &lt; 0.001). The predictive model for fibrosis had AUC of 0.755 and there was a 48% and a 70% decrease in significant fibrosis risk with MVPA (OR = 0.518, p = 0.022) and total log activity count (TLAC) (OR = 0.296, p = 0.017), respectively. Participants with NAFLD and NAFLD with fibrosis engage in declining PA. Despite having jobs with higher level of PA and participating in more moderate-to-vigorous PA, a larger proportion of Hispanics participants had NAFLD and significant fibrosis. Conclusions These findings demonstrate the role of PA as a protective factor against the presence of NAFLD and significant fibrosis. Protective levels of PA in NAFLD differ by races.

Pre-Operative Measures of Systemic Inflammation Predict Survival After Surgery for Primary Lung Cancer

BackgroundMeasures of systemic inflammation (MSIs) have been developed and shown to help predict prognosis in patients with lung cancer. However, studies investigating the impact of MSIs on outcomes solely in cohorts of patients undergoing curative-intent resection of NSCLC are lacking. In the era of individualized therapies, targeting inflammatory pathways could represent a novel addition to the armamentarium of lung cancer treatment. MethodsA multicentre retrospective review of patients who underwent primary lung cancer resection between 2012 and 2018 was undertaken. MSIs assessed were neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), systemic immune inflammation index (SII), advanced lung cancer inflammation index (ALI), prognostic nutritional index (PNI) and haemoglobin albumin lymphocyte platelet (HALP) score. Cox regression analysis was performed to assess the impact of MSIs on overall survival. ResultsA total of 5029 patients were included in the study. Overall 90-day mortality was 3.7% (n = 185). All MSIs were significantly associated with overall survival on univariable analysis. After multivariable Cox regression analyses, lower ALI (expressed as a continuous variable) (HR 1.000, 95% CI 1.000-1.000, P = .049) and ALI <366.43 (expressed as a dichotomous variable) (HR 1.362, 95% CI 1.137-1.631, P < .001) remained independently associated with reduced overall survival. ConclusionsMSIs have emerged in this study as potentially important factors associated with survival following lung resection for NSCLC with curative intent. In particular, ALI has emerged as independently associated with long-term outcomes. The role of MSIs in the clinical management of patients with primary lung cancer requires further investigation.

Clinical features, management, and outcomes of patients with sterile endophthalmitis associated with intravitreal bevacizumab injection: retrospective case series.

To evaluate clinical features, treatment protocol, outcomes, and complications that developed in this case series of 24 patients who had consecutive sterile endophthalmitis after intravitreal bevacizumab (IVB) injection. In this retrospective case series, IVB was repackaged in individual aliquots from the three batches that were used on the same day. IVB was injected into 26 eyes of 26 patients due to diabetic macular edema, age-related macular degeneration, and branch retinal vein occlusion. All patients had intraocular inflammation. Patients were divided into two groups severe and moderate inflammation according to the intraocular inflammation. The medical records of all patients were reviewed. At each follow-up visit, the complete ophthalmologic examination was performed, including best corrected visual acuity (BCVA), intraocular pressure, biomicroscopy, and posterior fundus examination. Twenty-four of 26 patients were included in the study. Two patients were excluded from this study since they didn't come to follow-up visits. The mean BCVA was 1.00 ± 0.52 Log MAR units before IVB. At the final visit, the BCVA was 1.04 ± 0.47 Log MAR units. These differences were not significant (p = 0.58). Of the 24 eyes, 16 eyes had severe, and 8 eyes had moderate intraocular inflammation. Eleven eyes in the severe inflammation group underwent pars plana vitrectomy due to intense vitreous opacity. Smear, culture results, and polymerase chain reaction results were negative. Sterile endophthalmitis may occur after IVB injection. Differential diagnosis of sterile endophthalmitis from infective endophthalmitis is crucial to adjust the appropriate treatment and prevent long-term complications due to unnecessary treatment.

Germline findings in cancer predisposing genes from a small cohort of chordoma patients

IntroductionChordoma is a rare slow-growing tumor that occurs along the length of the spinal axis and arises from primitive notochordal remnants (Stepanek et al., Am J Med Genet 75:335–336, 1998). Most chordomas are sporadic, but a small percentage of cases are due to hereditary cancer syndromes (HCS) such as tuberous sclerosis 1 and 2 (TSC1/2), or constitutional variants in the gene encoding brachyury T (TBXT) (Pillay et al., Nat Genet 44:1185–1187, 2012; Yang et al., Nat Genet 41:1176–1178, 2009).PurposeThe genetic susceptibility of these tumors is not well understood; there are only a small number of studies that have performed germline genetic testing in this population.MethodsWe performed germline genetic in chordoma patients using genomic DNA extracted by blood or saliva.ConclusionWe report here a chordoma cohort of 24 families with newly found germline genetic mutations in cancer predisposing genes. We discuss implications for genetic counseling, clinical management, and universal germline genetic testing for cancer patients with solid tumors.

Updated European guidelines for clinical management of familial adenomatous polyposis (FAP), MUTYH-associated polyposis (MAP), gastric adenocarcinoma, proximal polyposis of the stomach (GAPPS) and other rare adenomatous polyposis syndromes: a joint EHTG-ESCP revision.

Hereditary adenomatous polyposis syndromes, including familial adenomatous polyposis and other rare adenomatous polyposis syndromes, increase the lifetime risk of colorectal and other cancers. A team of 38 experts convened to update the 2008 European recommendations for the clinical management of patients with adenomatous polyposis syndromes. Additionally, other rare monogenic adenomatous polyposis syndromes were reviewed and added. Eighty-nine clinically relevant questions were answered after a systematic review of the existing literature with grading of the evidence according to Grading of Recommendations, Assessment, Development, and Evaluation methodology. Two levels of consensus were identified: consensus threshold (≥67% of voting guideline committee members voting either 'Strongly agree' or 'Agree' during the Delphi rounds) and high threshold (consensus ≥ 80%). One hundred and forty statements reached a high level of consensus concerning the management of hereditary adenomatous polyposis syndromes. These updated guidelines provide current, comprehensive, and evidence-based practical recommendations for the management of surveillance and treatment of familial adenomatous polyposis patients, encompassing additionally MUTYH-associated polyposis, gastric adenocarcinoma and proximal polyposis of the stomach and other recently identified polyposis syndromes based on pathogenic variants in other genes than APC or MUTYH. Due to the rarity of these diseases, patients should be managed at specialized centres.

Abstract PO2-03-08: Uncovering Novel Potential Prognostic Biomarkers in Basal-Like Breast Cancer using Transcriptomic Data of 1,899 Patients

Abstract Introduction: Patients with basal-like breast cancer (BLBC) predominantly represented by triple-negative breast cancer have shown a high recurrence rate and are characterized by poor prognosis. There is an urgent need to undercover reliable prognostic biomarkers that can help in the clinical management of such patients and identify additional therapeutic targets. The objective of this study was to create a comprehensive transcriptomic database on a large scale and leverage it to identify and prioritize cancer-related genes associated with BLBC patients’ outcomes. Methods: We identified breast cancer cohorts from public repositories that contained gene expression data at the transcriptome level, along with clinical follow-up information. BLBC were identified using the PAM50 signature. All samples were standardized using a standard array normalization coupled with scaling to have a mean expression across all genes of 1000 in each sample and incorporated into a unified database. Redundant samples were removed. For each gene, Cox univariate survival analysis was conducted, to account for multiple hypothesis testing, the false discovery rate was computed, and a significant cutoff of 1% was employed to determine the highest statistical significance. Association with RFS and OS was performed. Multivariate analysis was performed for selected genes involving clinical and pathological variables. To uncover higher-level functions related to altered RFS, gene ontology analysis was performed using the enrichGO function in the TNM plotter (http://www.tnmplot.com). Results: The complete integrated database comprises 1,899 samples from 52 breast cancer datasets. Altogether, 2,342 genes were correlated with relapse-free survival (RFS), and 1,149 genes were correlated with overall survival (OS). 619 genes were statistically significant for both RFS and OS. The most significant genes were ANGPTL4 (p=4.25E-08, HR=2.02), NHP2 (p=5.98E-10, HR=1.93), STK3 (p=4.86E-10, HR=1.93), GBE1 (p=2.77E-09, HR=1.86), and PMVK (p=3.65E-09, HR=1.85) for RFS and PINK1 (p=1.64E-05 , HR=3.31), CAMK2N1 (p=1.06E-07 , HR=2.93), CACFD1 (p=4.79E-04 , HR=2.61), SCAP (p=3.29E-04 , HR=2.6), SDC1 (p=2.81E-04 , HR=2.57), for OS. The most significant gene ontology biological processes upregulated in tumors with a worse prognosis include GO:0000184, nuclear-transcribed mRNA catabolic process, nonsense-mediated decay (p=6.64E-18); GO:0045047 , protein targeting to ER (p=6.64E-18); GO:0006614, SRP-dependent cotranslational protein targeting to membrane (p=9.08E-18); GO:0072599, establishment of protein localization to endoplasmic reticulum (p=1.30E-17); and GO:0006613, cotranslational protein targeting to membrane (p=1.90E-17). Conclusions: Our results help to prioritize genes and to neglect those which are most likely to fail in studies aiming to establish new clinically useful biomarkers and therapeutic targets in BLBC. Citation Format: Balazs Gyorffy, Libero Santarpia. Uncovering Novel Potential Prognostic Biomarkers in Basal-Like Breast Cancer using Transcriptomic Data of 1,899 Patients [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-03-08.

Abstract PO2-21-01: Granular Cell Tumors of the Breast: A Case Series

Abstract Objective: Granular cell tumors (GCT) of the breast are rare, Schwann-cell derived tumors that are largely benign in nature, but may present with malignant characteristics in 1-2% of cases. There are few reports highlighting the clinical presentation, cytologic differences, operative management and clinical outcomes of patients with these benign versus malignant GCTs. Here, the authors report the clinical course of 9 patients identified with either benign or malignant GCT of the breast. Methods: The medical records for a total of 9 patients treated for histologically confirmed GCT of the breast between March 2015 and May 2023 at our institution were retrospectively reviewed. Clinical data, imaging findings, immunohistochemical markers, surgical interventions, and clinical follow-up data were collected and analyzed. Results: All patients were female, with a mean age of 46 years (Range: 29-61). 5 (56%) patients presented with left-sided lesions with an average maximum dimension of 1.1 cm (SD: 0.7 cm). All 9 (100%) tumors were positive for S100, 4 (44%) were positive for CD68, and 3 (33%) were positive for Inhibin. 4 (44%) patients underwent local mass excision, 3 (33%) underwent lumpectomy, 1 (11%) underwent lumpectomy with sentinel lymph node biopsy, and 1 (11%) underwent partial mastectomy with sentinel lymph node biopsy. There were no perioperative complications nor complications noted at postoperative follow up visits. 1 patient (11%) had 2 recorded recurrences of GCT after the initial breast mass excision, with each tumor exhibiting different positive immunohistochemical markers. 1 (11%) patient had a previous history of breast cancer at time of GCT diagnosis, and 1 (11%) patient had concurrent breast malignancy with the granular cell tumor being in the lymph node of the same breast. Conclusions: Granular cell tumors of the breast are rare Schwann cell derived tumors that often present near breast scar tissue as spiculated, ill-defined masses with microcalcifications on radiologic imaging, mimicking breast malignancy, leading to overtreatment. This study found that for GCTBs that present in lymph nodes, regardless of low malignant potential seen histologically, there was a higher risk of recurrence, and may require further workup and close follow up after wide local excision. For all other granular cell tumors presenting with normal appearing lymph nodes on imaging, a local mass excision was adequate in management, with low risk of recurrence or malignant potential. Future studies should be performed analyzing long-term follow up for these patients to determine risk of recurrence over longer periods of time, and risk for breast malignancy. Granular Cell Tumor Characteristics Tumor characteristics including laterality, tumor location, maximum dimension in centimeters, and positive immunohistochemistry markers were shown for each patient. Citation Format: Shwetha Kochi, Madeline Karsten, Monika Masanam, Teagan Thorson, Roshanak Derakhshandeh, Patricia Wehner, Lucy De La Cruz, Jennifer Son. Granular Cell Tumors of the Breast: A Case Series [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-21-01.

Clinical characteristics, management and psychological outcomes of patients with diabetes secondary to chronic pancreatitis

Abstract Aims: To determine the clinical characteristics, management, rates of complications and psychological outcomes of patients with diabetes mellitus secondary to chronic pancreatitis (DMsCP) referred to the Belfast Pancreatic Diabetes Clinic.Methods: Clinical and laboratory data were obtained from online health care records (NIECR). Psychological outcomes and a service‐based questionnaire were performed.Results: Baseline characteristics (n=63 patients [male: 41, female: 22]) at initial referral included: mean age 56.2 years (range 19–84); mean duration of chronic pancreatitis 10.7 years (range 1–40); mean duration of diabetes 7.2 years (range 1–40). Previous pancreatic surgery was performed in 19% (12/63) of patients. Initial mean HbA1c was 82mmol/mol (range 41–189); mean HbA1c at six and 12 months follow‐up was 69.9mmol/mol and 70.6mmol/mol, respectively. Rates of microvascular complications included: retinopathy (background and pre‐proliferative) 16%; microalbuminuria 17%; peripheral neuropathy 14%, with no foot ulceration/amputation occurring. Macrovascular disease occurred in 24% of patients. Sixteen (25%) had missed at least one outpatient diabetes appointment over the preceding year. Quality of life (QoL) as measured by the PANQOLI was low with a mean total score of 64.9/103; 59% (16/27) of the service cohort also breached clinical cut‐offs for the presence of both anxiety (GAD‐7) and depression (PHQ‐9).Summary: DMsCP in our cohort was characterised by significant micro‐ and macrovascular complications, sub‐optimal glycaemic control, reduced clinic attendance and impaired QoL as well as a significant component of anxiety and depression. The optimal care for these patients should consist of a collaborative approach that best meets their complex and multifaceted needs. Copyright © 2024 John Wiley &amp; Sons.