Treatment Decisions For Patients Research Articles

Integrative analysis of anoikis-related prognostic signature to evaluate the immune landscape and predict therapeutic response in stomach adenocarcinoma

Stomach adenocarcinoma (STAD) is the most prevalent gastrointestinal malignancy and seriously threatens the life of the global population. Anoikis, a process of programmed cell death that occurs when cells detach from the extracellular matrix, is closely associated with tumor invasion and metastasis. In this study, we used the TCGA-STAD database to identify the expression patterns and prognostic relevance of anoikis-related genes (ARGs) in STAD. Functional enrichment analysis was used to explore the potential pathway. LASSO and Cox regression were used to construct anoikis-related prognostic signature. The anoikis risk score (ARS) incorporated 7 genes and stratified patients into highand low-risk subgroups by median value splitting. In addition, external validation was performed based on GSE66229, GSE15459, and GSE84437 cohorts. Nomograms were created based on risk characteristics in combination with clinical variants and the performance of the model was validated with time-dependent AUC, calibration curves, and decision curve analysis (DCA). The prognostic signature indicated that the low-risk subgroup had better outcomes and significant correlations with tumor microenvironment, immune landscape, immunotherapy response, and drug sensitivity. In addition, single-cell analysis displayed the cell types, the subcellular localization of prognostic genes, and the cellular interaction to reveal the potential molecular communication mechanism of anoikis resistance. Finally, in vitro experiments confirmed the critical role of CRABP2 in STAD. The results indicated that CRABP2 knockdown inhibited gastric cancer cell proliferation, migration and invasion, and promoted apoptosis. In summary, ARS can serve as a biomarker for predicting survival outcomes in STAD patients, providing new tools for personalized treatment decisions for STAD patients.

Stage III substaging and outcomes in patients with bladder cancer undergoing radical cystectomy.

To examine the association between substaging and outcomes following radical cystectomy (RC) in patients with stage III bladder cancer. We conducted a retrospective observational study using nationwide data from Japan, including 708 patients with stage III bladder cancer who underwent RC. Substaging was based on the American Joint Committee on Cancer's 8th edition. pT3-4aN0 and pTanyN1 were newly defined as stage IIIA, while pTanyN2-3 were defined as stage IIIB. Baseline covariates were balanced using inverse probability of treatment weighting. We analyzed disease-free survival (DFS) and overall survival (OS) across these substages and among the sub-groups: pT3-4aN0, pTanyN1, and pTanyN2-3. We found evidence that stage IIIB bladder cancer had inferior outcomes than stage IIIA (DFS, hazard ratio, 1.61 [95% confidence interval, 1.28-2.02]; OS, 1.61 [1.25-2.09]). Furthermore, there was evidence of the difference in outcomes between pT3-4aN0 versus pTanyN2-3 (DFS, 1.73 [1.35-2.23]; OS, 1.63 [1.23-2.15]), while no evidence of the difference between pT3-4aN0 and pTanyN1 was observed (DFS, 1.27 [0.96-1.67]; OS, 1.09 [0.78-1.53]). We did not find evidence of heterogeneity in the effects of the substaging on OS by the use of perioperative chemotherapy. This prognostic study supports the current stage III substaging of patients with bladder cancer who underwent RC. Importantly, there was no difference in OS between pT3-4N0 and pTanyN1 in patients with stage IIIA bladder cancer. These findings may help guide treatment decisions for patients with stage III operable bladder cancer.

Longitudinal ctDNA measurements for treatment response monitoring in patients with metastatic colorectal cancer undergoing systemic therapy: The ORCA trial.

220 Background: Precise monitoring of treatment response may support and improve treatment decision-making in patients with metastatic colorectal cancer (mCRC). The PLCRC-ORCA study aimed to explore the clinical applicability of personalized ctDNA testing for treatment response monitoring in patients with mCRC. Methods: The prospective, observational ORCA study is a substudy of the Prospective Dutch ColoRectal Cancer cohort (PLCRC). After informed consent, blood samples were collected before initiating first line of treatment (baseline) and subsequently every 8-9 weeks during routine clinical care. ctDNA levels were analyzed using a clinically validated, personalized, tumor-informed 16-plex PCR NGS assay (Signatera™, Natera, Inc). Results: The majority of patients (45/49) had blood samples collected at both baseline and the first on-treatment time point. At baseline, 43/45 (95.6%) patients were ctDNA-positive with a median concentration of 63.5 mean tumor molecules per mL (MTM/mL; range 0.08 to 16,200). In a multivariate linear regression model including metastatic site at baseline and resection status of the primary tumor, ctDNA levels at baseline were lower in patients with metastatic disease limited to the lung (n = 4; p < 0.001) or peritoneum (n = 6; p = 0.002) compared to patients with liver-limited metastases. Moreover, primary tumor resection was independently associated with lower levels of ctDNA at baseline (p = 0.05). At the first measurement on-treatment, 13/45 patients (28.9%) were ctDNA-negative and 32/45 (71.1%) patients were ctDNA-positive with ctDNA levels ranging from 0.04 to 318 MTM/mL. Reduction in ctDNA levels relative to baseline was observed in 42/45 (85.7%) patients while two patients exhibited increased ctDNA levels. One patient had undetectable ctDNA levels at baseline and on treatment. Among the 30 patients with detectable but reduced ctDNA levels on treatment, the median ctDNA levels decreased 55-fold (95% CI: 26–600). Conclusions: The levels of ctDNA in patients with mCRC are influenced by the metastatic site and are lowest among patients with metastases limited to the lung and peritoneum. Our data suggest that clinical applications of ctDNA testing for treatment response monitoring should take the baseline ctDNA levels into account when interpreting ctDNA dynamics. Correlation of ctDNA status with radiological treatment response is underway and will be reported during the conference.

Correlation of plasma LGL1 levels with clinical phenotype and treatment decisions in patients with Gaucher disease: Single site experience

Correlation of plasma LGL1 levels with clinical phenotype and treatment decisions in patients with Gaucher disease: Single site experience

Targeted therapy for older patients with an oncogene driven non-small cell lung cancer: Recommendations from a SIOG expert group.

Lung cancer is mostly a disease of aging with approximately half of newly diagnosed patients being 70years or older. Treatment decisions in this population pose unique challenges because of their heterogeneity with regards to daily functioning, cognition, organ function, comorbidities and polypharmacy, their underrepresentation in clinical trials and the impact of treatment on patient-centered outcomes, particularly in frail patients. The advent of targeted therapies and immunotherapy has revolutionized the management of advanced non-small cell lung cancer (NSCLC). Molecular profiling has allowed for the identification of actionable genomic alterations and targeted therapies have become standard of care for oncogene-driven NSCLC, significantly improving prognosis and quality of life. However, the data on the efficacy and tolerability of these treatments in older patients remain sparse. This review, conducted by the International Society of Geriatric Oncology (SIOG) NSCLC task force, examines the available literature on the use of targeted therapies in patients aged 70years or older with oncogene-driven NSCLC. The task force's expert recommendations aim to guide treatment decisions for older patients with oncogene driven NSCLC.

Systematic literature review (SLR) of prognostic factors (PFs) in locally advanced rectal cancer (LARC) and mismatch repair deficient (dMMR)/microsatellite instability-high (MSI-H) rectal cancer (RC).

303 Background: Innovative immunotherapies arebeing developed to improve clinical outcomes in patients (pts) withdMMR/MSI-H LARC who respond poorly to the current standard of care. A comprehensive overview of PFs in dMMR/MSI-H LARC may provide insight into the natural history of this disease to inform clinical study design and pt risk stratification. Methods: Systematic searches of bibliographic databases (EMBASE, MEDLINE, Cochrane; 2013–2023) and congress websites (2021–2023) were conducted to identify PFs for tumor response and survival outcomes in adult pts with LARC (SLR1) and dMMR/MSI-H RC (SLR2). Given the expected high volume of evidence, SLR1 was limited to large observational studies (≥1000 pts) and clinical trials (≥100 pts); SLR2 had no such limits. Results: 95 of 2307 publications met the inclusion criteria for SLR1. Of the PFs reported in ≥20 studies, older age, more lymph node involvement or fewer nodes assessed, higher T-stage or larger tumor size, higher histologic grade, and more comorbidities were most frequently significantly associated with poorer patient prognosis (Table). 3 of 289 publications met the inclusion criteria for SLR2. Neoadjuvant chemoradiation therapy (CRT) compared to chemotherapy (CT) was associated with statistically significant worse disease-free survival (DFS) and distant metastasis-free survival (DMFS), while T- or N-stage, age, and sex did not significantly impact these outcomes. Low vs middle tumor localization was also associated with worse DMFS. Stage III and IV disease were associated with worse RC-specific survival, while surgical procedure (segmental vs extended) showed no difference in overall survival (OS). The addition of neoadjuvant CRT or adjuvant CRT/CT to surgery alone had no impact on OS but was associated with worse DFS. Conclusions: Evidence regarding PFs in dMMR/MSI-H RC is scarce and may limit its interpretability, highlighting the need for further research that may be informed by the PFs identified from SLR1. The results from these SLRs may be helpful for optimizing patient management and treatment decision making, and to further contextualize RC clinical trials. PFs reported in ≥20 studies with ≥75% of studies reporting significant results in pts with LARC. PF Studies reporting PF (n) Studies reporting significant* impact of PF on prognosis (%) Poorer prognosis group Top 2 most frequently reported outcomes Age 59 81.4 Older OS, DFS Lymph node involvement/assessment 55 78.2 Yes or higher N stage OS, DFS T-stage or tumor size 53 79.2 Higher or larger OS, DFS Histologic grade 37 75.7 Higher OS, pathological complete response (pCR) Comorbidities 23 87.0 More OS, pCR *p-value <0.05 was considered significant as reported in the identified studies.

"The effect of disc repositioning on regenerative condylar bone remodelling in juvenile patients with temporomandibular joint osteoarthritis: a retrospective cohort study".

A retrospective cohort study was conducted to compare the treatment outcomes between arthroscopic disc repositioning and suturing surgery, and conservative treatment (without disc repositioning) in juvenile patients with anterior disc displacement without reduction (ADDwoR) and temporomandibular joint osteoarthritis (TMJOA). Patients treated with arthroscopic surgery (surgery group) between March 2022 and March 2023, and those treated with conservative therapy (control group) between July 2014 and August 2022 were included. The patients were assessed clinically and with CBCT before and after the treatments (minimum interval of 6months). A total of 38 patients were included in the study, with 19 patients in each of the groups. The postoperative mouth opening and joint pain improved significantly in both groups (P < 0.05), and there was no significant difference between them (P > 0.05). Besides clinical symptom relief, both treatments could promote regenerative condylar remodeling. More importantly, the increase in condylar head height and volume in the surgery group was significantly larger than those in the control group (P < 0.001). The occurrence of regenerative condylar remodeling in the surgery group (96.6%) was significantly higher than that in the control group (68.4%, P < 0.001). However, the occurrence of condylar regeneration was exclusively observed in the surgery group. The arthroscopic surgery has comparable effect to the conservative treatment on improving clinical symptoms, while it has better regenerative condylar remodeling results compared to the conservative treatment. This study demonstrated that arthroscopic surgery was superior to conservative treatment in promoting regenerative condylar remodeling, which is of significance to guide the treatment decision of juvenile patients with ADDwoR and TMJOA.

Frailty and outcomes in adults undergoing systemic anti-cancer treatment: a systematic review and meta-analysis.

It is increasingly recognised that frailty should be assessed and considered in treatment decision-making in patients with cancer. This review and meta-analysis synthesises existing evidence evaluating the association between baseline frailty and Systemic Anti-Cancer Treatment (SACT) outcomes in adults with cancer. Five databases were systematically searched from database inception to January 2023 to identify prognostic factor studies (cohort/case-control design) reporting the associations between validated frailty assessments (pre-treatment) and follow-up outcomes in adults with solid-organ malignancy undergoing SACT. Risk of bias (RoB) was assessed via Quality of Prognosis Studies in Systematic Reviews tool. Where appropriate, associations between frailty and outcomes (survival, toxicity, treatment tolerance, functional decline/quality of life and hospitalisation) were synthesised in meta-analysis and presented as forest plots. 58 studies met inclusion criteria. They were undertaken in a range of tumour sites and mainly in older patients and advanced disease/palliative settings. Most had low/moderate RoB. Nine frailty assessment tools were evaluated. Four outcomes were synthesised in meta-analysis, which demonstrated the prognostic value of two tools: Geriatric-8 (G8; survival, treatment tolerance, hospitalisation) and Vulnerable Elders Survey-13 (VES13; survival, toxicity, treatment tolerance). Overall pooled estimates indicate that frailty conveys an increased risk of mortality (hazard ratio (HR) 1.68, 95% confidence interval 1.41-2.00), toxicity (odds ratio (OR) 1.83, 1.24-2.68), treatment intolerance (OR 1.68, 1.32-2.12) and hospitalisation (OR 1.94, 1.32-2.83). Simple, brief frailty assessments including G8 and VES13 are prognostic for a range of important outcomes in patients undergoing SACT. Risk estimates should be used to support shared decision-making.

Lung Immune Prognostic Index (LIPI): Prognostic predictor for patients with extensive-stage small-cell lung cancer

Objective: Extensive-stage small-cell lung cancer (ES-SCLC) is an aggressive malignancy with a poor prognosis, for which prognostic factors are being investigated. In this study, we aimed to evaluate the prognostic significance of the Lung Immune Prognostic Index (LIPI) in ES-SCLC patients. Patients and Methods: Our retrospective study evaluated 60 ES-SCLC patients who were followed-up and treated between 2014 and 2022 and whose data could be accessed. Demographic characteristics, treatments and laboratory parameters (lactate dehydrogenase, white blood cell, neutrophil, lymphocyte) were collected from patients’ files and electronic system of our institution. Patients were divided into 3 groups (LIPI 0, LIPI 1 and LIPI 2). Results: The worst survival outcome was in LIPI 2. Median progression-free survival (PFS) was 7.7 months for LIPI 0; 5.6 months for LIPI 1 and 5.4 months for LIPI 2 (p = 0.001). Median overall survival (OS) was 19.7 months, 10.2 months and 7.7 months for LIPI 0, LIPI 1 and LIPI 2, respectively (p = 0.001). In both univariate and multivariate analyses, LIPI was found to be an independent negative prognostic factor (p = 0.001). Conclusion: Lung Immune Prognostic Index is a potentially valuable prognostic marker in ES-SCLC patients. It is thought to be helpful in individualized treatment decisions for ES-SCLC patients. However, further comprehensive multicenter studies are necessary to confirm our results.

Leveraging Guideline-Based Clinical Decision Support Systems with Large Language Models: A Case Study with Breast Cancer.

Multidisciplinary tumor boards (MTBs) have been established in most countries to allow experts collaboratively determine the best treatment decisions for cancer patients. However, MTBs often face challenges such as case overload, which can compromise MTB decision quality. Clinical decision support systems (CDSSs) have been introduced to assist clinicians in this process. Despite their potential, CDSSs are still underutilized in routine practice. The emergence of large language models (LLMs), such as ChatGPT, offers new opportunities to improve the efficiency and usability of traditional clinical decision support systems (CDSSs). OncoDoc2 is a guideline-based CDSS developed using a documentary approach and applied to breast cancer management. This study aims to evaluate the potential of LLMs, used as question-answering (QA) systems, to improve the usability of OncoDoc2 across different prompt engineering techniques (PETs). Data extracted from breast cancer patient summaries (BCPSs), together with questions formulated by OncoDoc2, were used to create prompts for various LLMs, and several PETs were designed and tested. Using a sample of 200 randomized BCPSs, LLMs and PETs were initially compared on their responses to OncoDoc2 questions using classic metrics (accuracy, precision, recall, and F1 score). Best performing LLMs and PETs were further assessed by comparing the therapeutic recommendations generated by OncoDoc2, based on LLM inputs, to those provided by MTB clinicians using OncoDoc2. Finally, the best performing method was validated using a new sample of 30 randomized BCPSs. The combination of Mistral and OpenChat models under the enhanced zero-shot PET showed the best performance as a question-answering system. This approach gets a precision of 60.16%, a recall of 54.18%, an F1 Score of 56.59%, and an accuracy of 75.57% on the validation set of 30 BCPSs. However, this approach yielded poor results as a CDSS, with only 16.67% of the recommendations generated by OncoDoc2 based on LLM inputs matching the gold standard. All the criteria in the OncoDoc2 decision tree are crucial for capturing the uniqueness of each patient. Any deviation from a criterion alters the recommendations generated. Despite a good accuracy rate of 75.57% was achieved, LLMs still face challenges in reliably understanding complex medical contexts and be effective as CDSSs.

P-591. Injecting Hope: A Long-Acting Injectable Program to Treat HIV Using Cabotegravir/Rilpivirine at a Ryan-White Funded HIV Clinic

Abstract Background Cabotegravir/rilpivirine (CAB/RPV) was approved as the first long-acting injectable (LAI) antiretroviral (ART) switch regimen. While clinical trials demonstrate CAB/RPV safety and efficacy, access and clinical workflow challenges have hindered implementation in practice. The objective of this study was to describe use of CAB/RPV in a Ryan-White funded clinic. Methods A retrospective chart review was conducted on the first 40 patients, aged &amp;gt; 18 years, referred to the pharmacist CAB/RPV clinic. Referral criteria included HIV-1 RNA &amp;lt; 50 copies/mL and no baseline CAB/RPV resistance. Results The majority of patients were male (90%) and white (85%), with a median age of 48 years (range 20-79), BMI of 28 (range 21-48), and use of 6 non-HIV medications (range 0-25). 73% had prior non-adherence to appointments. A DNA archive genotype was obtained for 8 patients due to lack of data. 4 patients had baseline RPV mutations, 2 were identified post-DNA archive genotyping. 14 patients did not start CAB/RPV (6 opted against, 4 had resistance, 2 had insurance denial, 1 had a high copay, 1 moved). The age of those who opted against LAI was not different from those who switched (p=0.2). Pharmacists devoted significant time to patient evaluation and coordination. 26 patients started CAB/RPV; 50% covered by medical benefit, 46% aged &amp;gt; 50 years. Psychological stress/stigma of daily ART was the main reason for switching. 1 patient travelled 228 miles for injections and 1 was homeless. By month 12, 24 patients (92%), including 1 unhoused patient, maintained control on CAB/RPV. No HBV reactivations occurred. 1 patient discontinued due to soreness. 1 patient (BMI &amp;lt; 30, no baseline resistance) had ongoing viremia of &amp;lt; 200 and was switched back to oral ART; post-CAB/RPV DNA archive genotype revealed no mutations. Conclusion CBV/RPV offers a switch option for patients, even those with unstable housing or history of missed appointments. Older patients on multiple medications still sought LAI CAB/RPV. Our experience shows that DNA archive genotype testing was valuable in guiding treatment decisions for patients lacking prior data and that proper evaluation and coordination identifies appropriate patients for CAB/RPV, resulting in high continuation rates Disclosures All Authors: No reported disclosures

Optimizing care for gastric cancer with overt bleeding: Is systemic therapy a valid option?

Gastric cancer (GC) and gastroesophageal junction cancer (GEJC) represent a significant burden globally, with complications such as overt bleeding (OB) further exacerbating patient outcomes. A recent study by Yao et al evaluated the effectiveness and safety of systematic treatment in GC/GEJC patients presenting with OB. Using propensity score matching, the study balanced the comparison groups to investigate overall survival and treatment-related adverse events. The study's findings emphasize that systematic therapy can be safe and effective and contribute to the ongoing debate about the management of advanced GC/GEJC with OB, highlighting the complexities of treatment decisions in these high-risk patients.

Comprehensive Genome Profiling for Treatment Decisions in Patients with Metastatic Tumors: Real-World Evidence Meta-Analysis and Registry Data Implementation.

Although precision oncology has rapidly been developed in recent years, its real-world impact and challenges in healthcare implementation remain underexplored. Through a meta-analysis of real-world evidence (RWE), we aimed at investigating the applicability and clinical impact of comprehensive cancer genome profiling (CGP) in cancer patients with metastatic solid tumors. We systematically searched Medline, Embase, and Web of Science for RWE studies on CGP and matched therapies in metastatic solid tumors (publication period: 2012-2023). Pooled proportions of actionable genomic alterations, patients treated with matched targeted therapies, treatment, and survival outcomes were calculated. Data from Swedish cancer registries were used as a case-study for nationwide CGP implementation. Out of the 7218 identified studies, 144 were included in our analysis. 59.8% of CGP-tested patients had actionable genomic alterations, with 15.6% (95% Confidence Interval (CI) 13.4-18.2%) of them having received targeted therapy. Objective response was seen in 23.9% (95% CI 20.8-27.3%). Overall, CGP-guided treatment was correlated with prolonged progression-free survival (pooled Hazard Ratio (HR) = 0.63; 95% CI, 0.56-0.70; 18 studies) and overall survival (pooled HR = 0.60; 95% CI, 0.51-0.70; 21 studies) when compared to conventional treatment. Meta-regression time projections analyses showed that these rates will steadily increase by 2030. Pooled analyses of RWE studies indicate that approximately one-fourth of the patients receiving CGP-matched treatment have an objective response. By utilizing meta-regression projections, our nationwide cancer registry case-study offers insights into the potential of precision oncology for patients with metastatic cancer and to inform future healthcare strategies.

P1152 Single center study of using clinical decision support tool to predict outcomes of vedolizumab therapy in Crohn’s disease patients

Abstract Background There is a need to identify Crohn’s Disease (CD) patients who will be most suitable and obtain most clinical benefit from treatment with vedolizumab (VDZ), an anti-α4β7 integrin inhibitor for the treatment of ulcerative colitis and Crohn’s Disease (CD). Previously, a clinical decision support tool (CDST) has been developed and validated to guide treatment decisions in CD patients treated with VDZ.1 In this study, we analyzed the ability of the CDST to predict clinical outcomes in CD patients. Methods Patients with moderate to severe CD receiving maintenance treatment with VDZ in single center were retrospectively analyzed using the CDST. We divided patient by CDST into low (≤13 points), intermediate (&amp;gt;13 and ≤19 points) and high response probability groups (&amp;gt;19 points) based on the previously developed scoring system. Clinical outcomes assessed included persistence on therapy and CD-related hospitalizations and surgery rates. Results We included 174 patients who were treated with VDZ for at least 6 months in our center. Using the CDST, at baseline, 23 patients (13%) had a low, 81 (47%) had an intermediate, and 70 (40%) had a high probability of treatment response with VDZ. Patients with low probability showed a trend toward reduced persistence on therapy, though this difference did not reach statistical significance (p=0.13). However, when patients were analyzed according to disease location by Montreal classification, a clearer pattern emerged in those with isolated ileal (L1) or colonic (L2) CD. In this subgroup, patients with high probability of treatment response to VDZ demonstrated significantly longer treatment persistence (p=0.038); 91% of these patients remained on therapy after two years compared to 55% in the intermediate group. This trend was not observed in ileocolonic (L3) CD, where persistence rates were similar across groups (83% in high and intermediate groups and 75% in the low probability group; p=0.23). We tried to assess the ability of CDST in prediction of complications of CD and we observed that number of hospitalization days was significantly lower in the high probability group (median: 0; third quartile: 4 days) compared to the intermediate group (median: 17; third quartiles: 9 and 21 days; p&amp;lt;0.001), while surgery rates showed no significant differences across groups (p=0.5). Conclusion The CDST partially identifies CD patients likely to benefit from VDZ. Patients with low CDST scores demonstrate poorer persistence, particularly in the subgroup with L1/L2 localization, and a higher risk of hospitalization, while those with high CDST scores exhibit better treatment persistence. These findings further validate the CDST as a valuable tool for guiding treatment decisions in CD.

P1061 A matching-adjusted indirect comparison (MAIC) of vedolizumab vs risankizumab in patients with moderately-to-severely active Crohn’s disease

Abstract Background Crohn’s disease (CD), a chronic inflammatory bowel disease, requires effective therapies to manage symptoms and prevent complications. Vedolizumab (VDZ; a gut selective anti-α4β7-integrin) and risankizumab (RZB; anti-interleukin-23 p19) are approved for treatment of moderately-to-severely active CD. This matching-adjusted indirect comparison (MAIC) compared the efficacy of VDZ vs RZB using data from 5 phase 3 placebo (PBO)-controlled similarly designed clinical trials (GEMINI 2, VISIBLE 2, ADVANCE, MOTIVATE, FORTIFY).1-4 Methods Individual patient data from VDZ trials (GEMINI 2, VISIBLE 2)1,2 were adjusted for the observed cross-trial differences in patient baseline characteristics to match the aggregated data from RZB trials (ADVANCE, MOTIVATE, FORTIFY) following MAIC guidance from the National Institute for Health Care Excellence (NICE, 2016) using a method-of-moments-based matching approach.3,4 The baseline covariates used in the matching include potential effect modifiers and clinically relevant covariates that improved the balance across trials. Outcomes compared included Crohn’s Disease Activity Index (CDAI) response (decrease of CDAI of ≥ 100 points from baseline) or remission (CDAI ≤ 150). For induction, the CDAI outcomes were commonly available at Week 4, hence we compared between VDZ and the pooled RZB (ADVANCE + MOTIVATE) on the approved dosage anchoring on PBO as the common comparator. For maintenance, CDAI outcomes at Week 52 of VDZ (pooled GEMINI 2 + VISIBLE 2) were compared with each approved RZB maintenance dose (FORTIFY) anchoring PBO as the common comparator. Outcome differences were reported using the effect measure based on the risk differences in PBO-adjusted response rate. Results After matching, baseline characteristics in the induction and maintenance datasets were balanced between VDZ and RZB cohorts (Table). The relative treatment differences were numerically lower with VDZ vs RZB for CDAI response and remission early in induction phase at Week 4 (Figure). At Week 52, the relative treatment effect in CDAI response and remission for VDZ were similar to both RZB doses (Figure). The relative treatment difference in CDAI clinical remission were numerically higher for VDZ than RZB regardless of the dose (180 mg: 2.8% [95% CI -12.3%-18.0%]; 360 mg: 5.4% [-10.1%, 20.9%]). Conclusion Despite the numerically lower CDAI outcomes with VDZ early in induction at Week 4, the CDAI outcomes, especially the clinically more meaningful CDAI remission at Week 52 were comparable between VDZ and both RZB doses. Although direct comparisons are warranted to validate these results, this information may help clinicians make informed treatment decisions for patients with CD.

Unveiling DNA methylation: early diagnosis, risk assessment, and therapy for endometrial cancer.

Endometrial cancer (EC), one of the most common gynecologic malignancies worldwide, poses a significant burden particularly among young women, with poor treatment outcomes and prognosis for advanced and recurrent patients. Epigenetic changes, encompassing DNA methylation, are involved in the occurrence and progression of tumors and hold promise as effective tools for screening, early diagnosis, treatment strategy, efficacy evaluation, and prognosis analysis. This review provides a comprehensive summary of DNA methylation-based early diagnostic biomarkers in EC, with a focus on recent valuable research findings published in the past two years. The discussion is organized according to sample sources, including cervical scraping, vaginal fluid, urine, blood, and tissue. Additionally, we outline the role of DNA methylation in EC risk assessment, such as carcinogenesis risk, feasibility of fertility preservation approaches, and overall prognosis, aiming to provide personalized treatment decisions for patients. Finally, we review researches on DNA methylation in resistance to first-line treatment of EC and the development of new drugs, and envision the future applications of DNA methylation in EC.

Predictive value of technetium-99m sodium pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism

Objectives: We aim to investigate the predictive value of [99mTc] pertechnetate thyroid scintigraphy in determining the permanence of congenital hypothyroidism (CH). Material and Methods: A retrospective analysis of [99mTc] pertechnetate thyroid scans performed for evaluation of CH at the Nuclear Medicine Unit of a hospital in Hong Kong between January 1, 2008, and December 31, 2018, was conducted. Scintigraphic findings and parameters at diagnosis, including thyroid stimulating hormone (TSH), free thyroxine (fT4), gender, and gestational age, were reviewed. The need for lifelong thyroxine replacement therapy was reviewed. Results: The study included 85 subjects, with 74 (87.1%) presenting with eutopic thyroid and 11 (12.9%) showing thyroid dysgenesis. Patients with scintigraphic evidence of thyroid dysgenesis required permanent thyroid hormone replacement therapy. Among the patients with eutopic thyroid, a higher TSH level was associated with the need for lifelong thyroid hormone replacement therapy (cutoff TSH value 18.72 mIU/L, sensitivity 77.3% and specificity 53.8%). Gender, gestational age, and fT4 did not show significant differences between the transient and permanent CH groups in patients with eutopic thyroid. Conclusion: Scintigraphic findings of thyroid dysgenesis indicate a high prevalence of permanent CH. In patients with eutopic thyroid, higher TSH levels predict the requirement for lifelong thyroid hormone replacement therapy. These results provide insights into the prediction of CH and aid in individualized treatment decisions for patients with CH.

Fluid structure Interaction analysis for rupture risk assessment in patients with middle cerebral artery aneurysms

Accurate rupture risk assessment is essential for optimizing treatment decisions in patients with cerebral aneurysms. While computational fluid dynamics (CFD) has provided critical insights into aneurysmal hemodynamics, most analyses focus on blood flow patterns, neglecting the biomechanical properties of the aneurysm wall. To address this limitation, we applied Fluid-Structure Interaction (FSI) analysis, an integrative approach that simulates the dynamic interplay between hemodynamics and wall mechanics, offering a more comprehensive risk assessment. In this study, we used advanced FSI techniques to investigate the rupture risk of middle cerebral artery bifurcation (MCA) aneurysms, analyzing a cohort of 125 patients treated for a MCA aneurysm at Kepler University Hospital, Linz, Austria. Multivariate analysis identified two significant rupture predictors: High Equivalent Stress Area (HESA; p = 0.049), which quantifies stress distribution relative to the aneurysm surface, and Gaussian curvature (GLN; p = 0.031), which captures geometric complexity. We also introduce the HGD index, a novel composite metric combining HESA, GLN, and Maximum Wall Displacement, designed to enhance predictive accuracy. With a threshold of 0.075, the HGD index exhibited excellent diagnostic performance; in internal validation, 24 of 25 ruptured aneurysms surpassed this threshold, yielding a sensitivity of 0.96. In a 5-fold cross validation the reliability of results was confirmed. Our findings demonstrate that the HGD index provides superior rupture risk stratification compared to conventional single-parameter models, offering a more robust tool for the assessment of complex aneurysmal structures. Further multicenter studies are warranted to refine and validate the HGD index, advancing its potential for clinical application and improving patient outcomes.

Prognostic and Predictive Values of F-18 FDG PET/CT Volumetric Parameters in Small Cell Lung Cancer

Introduction: Volumetric parameters of the 18F-FDG PET/CT can contribute to the treatment decision in high risk patients. In the present study, we aimed to examine the predictive, prognostic, and clinical value of PET/CT by using the two volumetric parameters: metabolic tumor volume (MTV) and total lesion glycolysis (TLG), SUVmax to concurrently evaluate survival data in patients diagnosed with small cell lung cancer (SCLC). Methods: 244 patients with SCLC, who underwent 18F-FDG PET/CT imaging for staging purpose were enrolled. Primary tumor SUVmax, MTV (40-70%) and TLG (40-70%) obtained from PET/CT were documented. Results: All lesions (n=244) showed 18F-FDG uptake, mean SUVmax of 19.74±8.71 [range (min – max) = 3.80 - 58.80]. SUVmax was significantly higher in tumors with diameters &gt; 2 cm compared to those with diameters ≤ 2 cm (p=0.000). The mean survival time was significantly shorter in patients with tumor diameter greater than 2 cm, locoregional LN involvement, distant nodal metastasis, or distant organ metastasis (p=0.019, p

Twelve-Month Outcomes and Optical Coherence Tomography (OCT) Biomarkers After Intravitreal Dexamethasone Implantation in Pseudophakic Eyes with Post-Vitrectomy Cystoid Macular Edema (CME)-Refractory to Medical Therapy.

Background: In this study, we evaluated the incidence of cystoid macular edema (CME) after pars plana vitrectomy (PPV) for different retinal pathologies and assessed the role of optical coherence tomography (OCT) biomarkers in guiding treatment decisions in post-surgical CME patients who were refractory to medical therapy over a follow-up period of 12 months. Methods: Medical records of consecutive pseudophakic patients, who underwent PPV for different retinal pathologies, were retrospectively evaluated in this single-center, uncontrolled study. The incidence of post-PPV CME was assessed. Eyes with post-PPV CME in the first 2 months after surgery, with available clinical and OCT data for 12 months after surgery, were included in the evaluation. The mean best-corrected visual acuity (BCVA; logMAR), mean central macular thickness (CMT; μm) change, and response to different treatments [medical therapy and intravitreal dexamethasone (DEX) implant] were evaluated 1, 3, 6, 9, and 12 months after PPV. The impact of OCT biomarkers on the exposure to DEX implants was assessed. Adverse events, potentially related to the treatment, were investigated as well. Results: Of the 346 pseudophakic patients (352 eyes) who participated in this study, 54 (54 eyes) developed CME within the first 2 months after PPV (incidence of 15.3%). Among them, 48 patients were deemed eligible for the 12-month analysis. Preoperative mean BCVA (1.44 ± 0.99 logMAR) significantly improved to 0.32 ± 0.37 logMAR after 12 months (p < 0.001). The mean baseline CMT of 347 (±123.5) μm significantly decreased to 290 μm (±80.4; p = 0.003) by the end of the follow-up. Twenty-five eyes (52%) required one or more DEX implants for CME, due to being refractory to topical therapy. Significant correlations were found between the mean CMT values at various time points. Additionally, patients who required DEX implants at months 3 and 9 were more likely to present intraretinal fluid (IRF), disorganization of inner retinal layers (DRIL), disorganization of outer retinal layers (DROL), and hyper-reflective foci (HRF) at 1-month OCT. Five patients experienced a slight increase in intraocular pressure (IOP), which was successfully managed with topical medication. Conclusions: Topical therapy alone can be a valuable option for post-PPV CME in approximately 50% of patients. Significant visual recovery and macular thickness reduction at 12 months demonstrated that DEX implants can be a safe and effective second-line treatment for pseudophakic patients with post-PPV CME and who are refractory to medical therapy. Early post-surgical OCT biomarkers may indicate a more severe CME that might benefit from the steroid implant.