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Characteristics and Outcomes of Deceased Donor Kidneys Turned Down by A Single Center and Transplanted Elsewhere
No full textBackground: The number of kidney transplants performed in the US remains insufficient for the number of patients awaiting one. To meet these demands and hit nationally set growth targets, it is imperative for transplant centers to review their kidney utilization practice, especially for kidneys that were not accepted. This study analyzed accepted versus turned down kidneys for Henry Ford Hospital to better understand acceptance practices and to evaluate the need for modifying our acceptance criteria. Methods: Retrospective analysis of OPTN data on deceased donor kidneys offered by Gift of Life Michigan to Henry Ford Hospital (HFH) between 8/2/2022 and 7/19/2024. Only kidneys that were ultimately transplanted were included. Kidneys were classified as either “kidney transplanted by center (KTC)” if accepted and transplanted by HFH and “kidney transplanted elsewhere (KTE)” if turned down by HFH and transplanted elsewhere. Kidneys turned down for donor variables or organ quality were included in the analysis. Kidney characteristics and recipient outcomes were compared between the two groups. Outcomes of interest were rate of delayed graft function (DGF), recipient 6-month and 1-year serum creatinine (Se Cr), and 6-month and 1-year graft survival (GS). Results: 312 kidneys were included, with 65 in the KTC group and 247 in the KTE group. Selected analysis results are shown in Figure 1. KTE kidneys came from donors with significantly higher KDPI and terminal creatinine. Other donoror kidney characteristics did not differ significantly between the two groups. Recipients of KTC kidneys had a significantly longer length of hospital stay, but DGF rate, 6-month and 1-year recipient renal function did not differ significantly between the two groups. Rates of 6-month GS were similar, while 1-year GS rates were significantly higher in the KTC group. Conclusions: Despite differences in donor characteristics, renal outcomes did not differ significantly between kidneys we accepted versus those turned down. Findings of comparable outcomes with KTE kidneys can help reframe a center’s understanding of acceptable organ quality metrics and motivate centers to rethink and expand their acceptance criteria. [Formula presented] DISCLOSURES: Z.Y. Lu: None. A. Yoshida: None. A. Patel: None
Probabilistic nested model selection in pharmacokinetic analysis of DCE-MRI data in animal model of cerebral tumor
No full textBest current practice in the analysis of dynamic contrast enhanced (DCE)-MRI is to employ a voxel-by-voxel model selection from a hierarchy of nested models. This nested model selection (NMS) assumes that the observed time-trace of contrast-agent (CA) concentration within a voxel, corresponds to a singular physiologically nested model. However, admixtures of different models may exist within a voxel\u27s CA time-trace. This study introduces an unsupervised feature engineering technique (Kohonen-Self-Organizing-Map (K-SOM)) to estimate the voxel-wise probability of each nested model. Sixty-six immune-compromised-RNU rats were implanted with human U-251 N cancer cells, and DCE-MRI data were acquired from all the rat brains. The time-trace of change in the longitudinal-relaxivity (ΔR(1)) for all animals\u27 brain voxels was calculated. DCE-MRI pharmacokinetic (PK) analysis was performed using NMS to estimate three model regions: Model-1: normal vasculature without leakage, Model-2: tumor tissues with leakage without back-flux to the vasculature, Model-3: tumor vessels with leakage and back-flux. Approximately two hundred thirty thousand (229,314) normalized ΔR(1) profiles of animals\u27 brain voxels along with their NMS results were used to build a K-SOM (topology-size: 8 × 8, with competitive-learning algorithm) and probability map of each model. K-fold nested-cross-validation (NCV, k = 10) was used to evaluate the performance of the K-SOM probabilistic-NMS (PNMS) technique against the NMS technique. The K-SOM PNMS\u27s estimation for the leaky tumor regions were strongly similar (Dice-Similarity-Coefficient, DSC = 0.774 [CI: 0.731-0.823], and 0.866 [CI: 0.828-0.912] for Models 2 and 3, respectively) to their respective NMS regions. The mean-percent-differences (MPDs, NCV, k = 10) for the estimated permeability parameters by the two techniques were: -28%, + 18%, and + 24%, for v(p), K(trans), and v(e), respectively. The KSOM-PNMS technique produced microvasculature parameters and NMS regions less impacted by the arterial-input-function dispersion effect. This study introduces an unsupervised model-averaging technique (K-SOM) to estimate the contribution of different nested-models in PK analysis and provides a faster estimate of permeability parameters
Percutaneous Coronary Intervention In Nstemi Patients With Heart Failure And Leukemia: Insights From The National Readmission Database
No full textBackground: Cardiac disease is often associated with oncology patients. Our study aims to address the knowledge gap regarding the outcomes of non-ST-elevation myocardial infarction (NSTEMI) patients who have leukemia with concomitant heart failure and are undergoing percutaneous coronary intervention (PCI), providing new insights into this underexplored area. Methods: Between 2016 and 2020, we utilized the National Readmission Database to identify adult patients hospitalized for Non-ST-Elevation Myocardial Infarction (NSTEMI) who have a diagnosis heart failure and leukemia. All statistical analyses were conducted using Stata 18.0 software. Results: From our inclusion criteria, we identified 4,451 hospitalizations, of which 1,286 (28.9%) underwent PCI. The baseline patient characteristics are reported in Table 1. Compared to patients who were not re-vascularized, PCI patients were younger (median age 76 vs 79 years, p\u3c0.05) and had a lower frailty score (median score 4.4 vs 5.6, p\u3c0.05). Mortality was higher in patients who were not re-vascularized (no-PCI) (11.8% vs 5.6%, p\u3c0.05). Gastrointestinal bleeding rates were similar between the two groups (7.1% vs 5.6%, p\u3e0.05). Interestingly, acute kidney injury rates were higher in the non-PCI group (43% vs 37%,p\u3c0.05). Conclusion: The observed higher mortality and complication rates in the non-PCI group, characterized by older age and higher frailty, underscore the impact of patient selection on treatment outcomes. This disparity highlights the complexity of managing NSTEMI patients with comorbid conditions, suggesting a need for more nuanced approaches to treatment planning and further research to optimize strategies for this high-risk population
Proteomic Response Predictor (PRP) For Beta Blocker Survival Benefit In Heart Failure Patients With Reduced Ejection Fraction
No full textBackground: To improve prediction of individual responses to beta-blocker (BB) therapy in Heart failure with reduced ejection fraction (HFrEF) patients, various novel approaches such as proteomics are being used. Aim: Our goal was to derive and validate a proteomic response predictor (PRP) for BB survival benefit in HFrEF patients. Methods: A total of 930 patients with Heart Failure (HF) and low ejection fraction (EF\u3c50%) from the Heart Failure Pharmacogenomic Registry (HFPGR) were studied. Plasma was profiled using SOMAscan v4 (approximately 5k proteins). The cohort was randomly divided into a derivation subset of 623 patients and a validation set in the remaining n=307. The component proteins of PRP were selected using Lasso-penalized Cox regression of all-cause mortality focusing on protein-by-BB interaction, and adjusted for MAGGIC score, BB propensity score, and race. The PRP score was generated using the coefficients from the Cox model results. The PRP was then tested in the validation group as both a continuous variable and a dichotomized variable. Results: Ten proteins (Table 1) were selected for the optimal PRP in the derivation subset. In validation testing, the interaction of BB with PRP on mortality was significant (P=0.000635). To dichotomize the PRP, various cutoffs were compared across deciles within the derivation group. When PRP is dichotomized at the median, the HR associated with BB treatment in the in favorable response PRP group was 0.41 while in the PRP non-responder group and was 1.78 (95%CI = 1.08-2.93) which was statistically significant (Pinteraction=0.016). Conclusions: Using proteomic profiling of plasma, a 10 protein predictor of BB response in HFrEF was created and validated
Response to Appropriate Statistical Methods to Assess Cross-Study Diagnostic 23-Gene Expression Profile Test Performance for Cutaneous Melanocytic Neoplasms
No full textSkin clearance, duration of treatment-free interval, and safety of tapinarof cream 1% once daily: Results from ADORING 3, a 48-week phase 3 open-label extension trial in adults and children down to 2 years of age with atopic dermatitis
No full textBACKGROUND: In 2 pivotal phase 3 trials, tapinarof demonstrated significant efficacy and was well tolerated in patients down to age 2 years with atopic dermatitis.
OBJECTIVE: Assess skin clearance rates, duration of treatment-free intervals, and safety of tapinarof in a phase 3 open-label extension trial.
METHODS: Patients from the ADORING 1 and 2 pivotal phase 3 trials, a 4-week maximal usage pharmacokinetics trial, and tapinarof-naive patients received tapinarof for up to 48 weeks. Treatment was based on Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score. Patients with vIGA-AD≥1 received tapinarof until vIGA-AD=0. Patients achieving vIGA-AD=0 discontinued tapinarof and were monitored for treatment-free interval. Patients with vIGA-AD≥2 were re-treated until vIGA-AD=0.
RESULTS: Seven hundred twenty-eight patients enrolled. Overall, 51.9% achieved vIGA-AD=0, and 81.6% achieved vIGA-AD=0 or 1 at least once. After first achieving complete clearance and discontinuing treatment, the mean first treatment-free interval was 79.8 consecutive days. Tapinarof was well tolerated, with no new safety signals. Most-frequent adverse events were folliculitis (12.1%), nasopharyngitis (6.9%), and upper respiratory tract infection (6.9%).
LIMITATIONS: Open-label; treatment-free interval potentially underestimated.
CONCLUSION: Tapinarof was well tolerated and resulted in high skin clearance rates that were maintained off-therapy and consistent safety in patients down to age 2 years
Advances in gastrointestinal endoscopy: A comprehensive review of innovations in cancer diagnosis and management
No full textThe field of gastroenterology has experienced revolutionary advances over the past years, as flexible endoscopes have become widely accessible. In addition to enabling faster, less invasive, and more affordable treatment, flexible endoscopes have greatly improved the detection and endoscopic screening of malignancies and prevented many cancer-related deaths. The development and clinical application of new diagnostic endoscopic technologies, such as magnification endoscopy, narrow-band imaging, endoscopic ultrasound with biopsy, and more recently, artificial intelligence enhanced technologies, have made the recognition and detection of various neoplasms and sub-epithelial tumors more possible. This review demonstrates the latest advancements in endoscopic procedures, techniques, and devices applied in the diagnosis and management of gastrointestinal cancer
Efficacy of a Brief Cognitive Behavioral Treatment Across Body Image Distress Domains: Secondary Outcomes of the BRIGHT Randomized Clinical Trial
No full textReal-world characteristics and survival outcomes of patients with metastatic ALK fusion-positive solid tumors treated with standard-of-care therapies
No full textBACKGROUND: Anaplastic lymphoma kinase (ALK) fusions can be found in different solid tumors. This study aims to describe the clinical characteristics and investigate survival outcomes of patients with ALK fusion-positive solid tumors (excluding non-small cell lung cancer [NSCLC]) treated with standard-of-care therapies in a real-world setting.
PATIENTS AND METHODS: Data for patients with metastatic solid tumors (excluding NSCLC) who had ≥1 Foundation Medicine comprehensive genomic profiling (CGP) test between January 1, 2011 and September 30, 2023, were obtained from a nationwide (US-based) de-identified multi-tumor clinico-genomic database. Patients with ALK wild-type (ALK-WT) tumors were matched with patients with ALK fusion-positive tumors (4:1 ratio) using pre-specified baseline characteristics. Two models were used to analyze survival outcomes: Model 1 used the CGP report date as the index date; Model 2 used the date of metastatic diagnosis as the index date (including adjustment for immortal time bias).
RESULTS: Overall, 22 and 88 patients were included in the ALK fusion-positive and ALK-WT cohorts, respectively. Co-alterations were rare in the ALK fusion-positive cohort. Median overall survival was consistently lower in patients with ALK fusion-positive tumors compared with patients with ALK-WT tumors, across all analyses (hazard ratios between 1.8 and 2.0).
CONCLUSION: Data from this study suggest that ALK fusions have a negative prognostic effect in metastatic solid tumors and highlight the need for further investigation of ALK inhibitors in the tumor-agnostic setting
Dose-Dense Docetaxel and Radium-223 in Bone-Dominant Metastatic Castration-Resistant Prostate Cancer
No full textBACKGROUND: Disease progression in castration-resistant prostate cancer (CRPC) remains bone-dominant and docetaxel-responsive. Docetaxel and radium-223 would be a logical combination but myelosuppression is dose-limiting. Dose-dense schedules of docetaxel have comparable activity to bolus dosing with mitigated myelosuppression. We hypothesized that dose-dense docetaxel with standard radium-223 would be a feasible, safe and effective combination in bone-dominant metastatic CRPC.
METHODS: Subjects had progressive bone-predominant CRPC. Design was dose escalation plus expansion with 28-day cycles. Docetaxel was given every 2 weeks in a 4-week lead-in, then with Radium-223 every 4 weeks up to 6 cycles. Dose-levels (DL) included 1: docetaxel 40 mg/m(2); 1a: docetaxel 40 mg/m(2) with G-CSF on Day 16, 2a: docetaxel 50 mg/m(2) with G-CSF on Day 16. The maximum tolerated dose (MTD) was defined as the highest (DL) of docetaxel achieved without dose-limiting toxicity (DLT). Markers of safety and efficacy were annotated.
RESULTS: Forty-three subjects were enrolled (NCT03737370). The patient population included 21% black, 9% Asians, 93% had prior intensified hormonal therapy, 67% had bone pain, and 76% had ≥ 4 bone metastases. Seven patients dropped out during the 4-week docetaxel lead in. Neutropenia at DL 1 limited combination therapy. No (DLT) occurred at DL 1a (n = 6) or DL 2a (n = 5). Twenty-two patients were enrolled to an expansion cohort with docetaxel 50 mg/m(2) with G-CSF on Day 16 (DL 2a), the designated MTD. Among 35 patients treated with the combination, there were no febrile neutropenia events. One patient had dose-limiting Grade 3 anemia. PSA50 response was 51.4% and PSA90 was 25.7%. Median progression-free survival was 11.7 months, and median overall survival was 20.1 months.
CONCLUSIONS: A lead-in cycle and a dose-dense schedule of docetaxel with G-CSF enabled the combination with radium-223 in standard dose-intensities with minimal hematological toxicity. The regimen will likely combine logically and safely with hormone-intensification for study in high-risk/high-volume castration-sensitive metastatic disease