Patient Data Research Articles

Sjogren's syndrome due to immune checkpoint inhibitors (ICIs): Insights from a single-institution series and systematic review of the literature.

Careful adverse event assessment and management are important when prescribing immune checkpoint inhibitors (ICIs) to cancer patients. Iatrogenic Sjogren's syndrome is a relatively rare immune-related adverse event (irAEs) that affects the moisture-producing glands. We describe a series of four patients who developed Sjogren's syndrome while being treated with ICIs at a community cancer center in Southern California, USA (1/1/2017-12/31/2023). Patient, drug and disease-related data were collected by retrospective chart review. A systematic search of the PubMed database was performed to identify similar cases in the literature (1/1/2016-12/31//2023). Of 224 cancer patients at our center treated with ICIs, four (1.8%) developed iatrogenic Sjogren's syndrome. All of our patients were male; three received PD-1 inhibitors (nivolumab, pembrolizumab) and one received the PD-L1 inhibitor atezolizumab. The median time to development of Sjogren's syndrome was 24 weeks (range, 8-36 weeks); dry mouth symptoms were more prominent than dry eye symptoms. None of the patients had elevated SS-A, SS-B or antinuclear antibodies. One patient developed multiple tooth cavities and had several extractions, due to severe xerostomia. Management of all patients was primarily symptomatic. Two cases were irreversible; one was reversible and the 4th case is undermined as he is still on ICI therapy. Our systematic review of the literature identified 80 cases in five articles. Incidence of xerostomia was twice of that of xerophthalmia. The male/female ratio was 1.5:1. SS-A, SS-B, or antinuclear antibodies were found in only 9% of patients. Steroids were reported to have had only a limited role in management. The incidence of Sjogren's syndrome due to ICIs in our center was 1.8%. Details of clinical course and management in these patients are presented. Caring for patients with ICI-related Sjogren's syndrome is facilitated by a multidisciplinary effort including oncologists, otolaryngologists, dentists, ophthalmologists and rheumatologists. Expanding the knowledge base pertaining to iatrogenic Sjogren's syndrome in patients on ICIs will be helpful in promoting early detection and treatment, and improving outcomes.

MYBL2 Drives Prostate Cancer Plasticity: Inhibiting its Transcriptional Target CDK2 for RB1-Deficient Neuroendocrine Prostate Cancer.

Phenotypic plasticity is a recognized mechanism driving therapeutic resistance in prostate cancer (PCa) patients. While underlying molecular causations driving phenotypic plasticity have been identified, therapeutic success is yet to be achieved. To identify putative master regulator transcription factors (MR-TF) driving phenotypic plasticity in PCa, this work utilized a multiomic approach using genetically engineered mouse models of prostate cancer combined with patient data to identify MYBL2 as a significantly enriched transcription factor in PCa exhibiting phenotypic plasticity. Genetic inhibition of Mybl2 using independent murine PCa cell lines representing phenotypic plasticity demonstrated Mybl2 loss significantly decreased in vivo growth as well as cell fitness and repressed gene expression signatures involved in pluripotency and stemness. Because MYBL2 is currently not druggable, a MYBL2 gene signature was employed to identify cyclin-dependent kinase-2 (CDK2) as a potential therapeutic target. CDK2 inhibition phenocopied genetic loss of Mybl2 and significantly decreased in vivo tumor growth associated with enrichment of DNA damage. Together, this work demonstrates MYBL2 as an important MR-TF driving phenotypic plasticity in PCa. Further, high MYBL2 activity identifies PCa that would be responsive to CDK2 inhibition.

Effect of time of day on outcomes in elective surgery: asystematic review.

The timing of elective surgery could affect clinical outcome because of diurnal rhythms of patient physiology as well as surgical team performance. Waiting times for elective surgery are increasing in many countries, leading to increasing interest in undertaking elective surgery in the evening or at night. We aimed to systematically review the literature on the effect of the timing of elective (but not urgent or emergency) surgery on mortality, morbidity and other clinical outcomes. We searched databases for relevant studies combining the terms 'circadian rhythm' and 'anaesthesia/surgery'. Additional relevant articles were found by hand-searching the references. All studies were screened for bias. Included studies examined daytime vs. evening/night-time surgery, morning vs. afternoon surgery, multiple timeslots or used time as a continuous variable. Nineteen retrospective cohort studies, one prospective cohort study and one randomised controlled trial were included (n = 798,914). Evening/night-time elective surgery was associated with a higher risk of mortality when compared with daytime procedures in three studies (n = 611,230), with odds ratios (95%CI) for mortality ranging from 1.35 (1.16-1.56) to 3.98 (1.54-10.30), while no differences were found in three other studies (n = 142,355). No differences were found for morning vs. afternoon surgery (four studies, n = 3277). However, most studies had a low quality of evidence due to their retrospective nature and because not all studies corrected for patient characteristics. Moreover, the studies were heterogeneous in terms of the reported time slots and clinical outcomes. We found that evening/night-time elective surgery is associated with a higher risk of mortality compared with daytime surgery. However, the quality of evidence was graded as low, and thus, future prospective research should publish individual patient data and standardise outcome measures to allow firm conclusions and facilitate interventions.

Corticosteroids for Immune-Related Adverse Events and Checkpoint Inhibitor Efficacy: Analysis of Six Clinical Trials.

Retrospective studies suggest that immunosuppressive treatment of immune-related adverse events (irAEs) impairs survival in patients with melanoma who received immune checkpoint inhibitors. Here, we study this association across tumor types using data from six international phase II/III registrational trials. A post hoc analysis was performed on individual patient data from the anti-programmed cell death-1 (anti-PD-1) + anti-cytotoxic T lymphocyte-associated protein-4 (anti-CTLA-4) treatment arms of six clinical trials (CheckMate-067, -142, -214, -648, -743, and -9LA). Among patients who received systemic immunosuppression for treatment-related adverse events (trAEs), associations of peak and cumulative corticosteroid dose, and use of second-line immunosuppression with overall survival (OS) and progression-free survival (PFS) were assessed using multilevel Cox regression with adjustment for age and sex. Of the 1,959 patients who received anti-PD-1 + anti-CTLA-4 therapy, 834 patients who were treated with immunosuppression for trAEs were included. Eight hundred and thirty-two patients (100%) received corticosteroids and 81 patients (10%) received second-line immunosuppressants. High corticosteroid peak dose was associated with worse PFS: adjusted hazard ratio (HRadj), 1.15 (95% CI, 1.02 to 1.29) for 1 versus 0.5 mg/kg prednisolone and HRadj, 1.43 (95% CI, 1.05 to 1.96) for 2 versus 0.5 mg/kg. Similar effects were observed for OS: HRadj, 1.21 (95% CI, 1.06 to 1.39) and HRadj, 1.66 (95% CI, 1.17 to 2.37) for 1 and 2 versus 0.5 mg/kg, respectively. Cumulative corticosteroid dose was not associated with survival. HRadj of use of second-line immunosuppression was 1.23 (95% CI, 0.90 to 1.68) for PFS and 1.25 (95% CI, 0.88 to 1.77) for OS. Higher corticosteroid peak dose for trAEs is associated with worse survival across tumor types, while cumulative dose is not. Too few patients received second-line immunosuppressants to confirm or reject an association with survival. These data argue for a reconsideration of irAE management approaches, starting with lower corticosteroid dose whenever feasible.

Radiological signs of stone impaction add no value in predicting spontaneous stone passage

Stone size and location are key factors in predicting spontaneous stone passage (SSP), but little attention has been paid to the influence of radiological signs of stone impaction (RSSI). This research aims to determine whether RSSI, alongside stone size, can predict SSP and to evaluate the consistency of ureteral wall thickness (UWT) measurements among observers. In this retrospective study, 160 patients with a single upper or middle ureteral stone on acute non-enhanced computed tomography (NCCT) were analysed. Patient data were collected from medical records. Measurements of RSSI, including UWT, ureteral diameters, and average attenuation above and below the stone, were taken on NCCT by four independent readers blind to the outcomes. The cohort consisted of 70% males with an average age of 51 ± 15. SSP occurred in 61% of patients over 20 weeks. The median stone length was 5.7 mm (IQR: 4.5–7.3) and was significantly shorter in patients who passed their stones at short- (4.6 vs. 7.1, p < 0.001) and long-term (4.8 vs. 7.1, p < 0.001) follow-up. For stone length, the area under the receiver operating characteristic curve (AUC) for predicting SSP was 0.90 (CI 0.84–0.96) and only increased to 0.91 (CI 0.85–0.95) when adding ureteral diameters and UWT. Ureteral attenuation did not predict SSP (AUC < 0.5). Interobserver variability for UWT was moderate, with ± 2.0 mm multi-reader limits of agreement (LOA). The results suggest that RSSI do not enhance the predictive value of stone size for SSP. UWT measurements exhibit moderate reliability with significant interobserver variability.

Phenotypes of Patients with Intracerebral Hemorrhage, Complications, and Outcomes.

The objective of this study was to define clinically meaningful phenotypes of intracerebral hemorrhage (ICH) using machine learning. We used patient data from two US medical centers and the Antihypertensive Treatment of Acute Cerebral Hemorrhage-II clinical trial. We used k-prototypes to partition patient admission data. We then used silhouette method calculations and elbow method heuristics to optimize the clusters. Associations between phenotypes, complications (e.g., seizures), and functional outcomes were assessed using the Kruskal-Wallis H-test or χ2 test. There were 916 patients; the mean age was 63.8 ± 14.1 years, and 426 patients were female (46.5%). Three distinct clinical phenotypes emerged: patients with small hematomas, elevated blood pressure, and Glasgow Coma Scale scores > 12 (n = 141, 26.6%); patients with hematoma expansion and elevated international normalized ratio (n = 204, 38.4%); and patients with median hematoma volumes of 24 (interquartile range 8.2-59.5) mL, who were more frequently Black or African American, and who were likely to have intraventricular hemorrhage (n = 186, 35.0%). There were associations between clinical phenotype and seizure (P = 0.024), length of stay (P = 0.001), discharge disposition (P < 0.001), and death or disability (modified Rankin Scale scores 4-6) at 3-months' follow-up (P < 0.001). We reproduced these three clinical phenotypes of ICH in an independent cohort (n = 385) for external validation. Machine learning identified three phenotypes of ICH that are clinically significant, associated with patient complications, and associated with functional outcomes. Cerebellar hematomas are an additional phenotype underrepresented in our data sources.

Neonatal acuity tool-defined staffing ratios in a tertiary Australian neonatal intensive care unit.

There is well-established data linking the adequacy of nurse staffing to patient outcomes. Evidence-based standards for staffing are therefore critical to drive improvements in clinical care. One such evidence-based approach is the use of patient acuity-based tools. The objective of this study is to determine the performance of a neonatal acuity tool in an Australian tertiary neonatal health-care setting, focusing on the classification of patient acuity and nursing:patient staffing ratios compared to current practice. Acuity data were collected in a neonatal intensive care unit (NICU) and special care baby unit (SCBU) over a 10-week period in 2023. Patient data were scored in the 16 domains at two time points (prior to morning and evening nursing shift changeover) for all admitted newborns. For ventilated newborns nursed with a nurse:patient staffing ratio of 1:1, 78% of scores were within the L4-high acuity (score ≥ 26) band, with the remaining scores within the L3-high acuity (18-25) band. For newborns on non-invasive respiratory support in NICU staffed 1:1, the proportion scoring within the L4 acuity band was higher in the nasal high-flow group compared to the nasal continuous positive airway pressure group (P = 0.032), an effect not seen for those nursed 1:2 in NICU or for those on nasal high-flow nursed in SCBU either 1:2 or 1:3. This study of how a neonatal acuity classification system compares with current nurse:patient staffing allocations in an Australian tertiary NICU, suggests refinements in staffing ratios for specific patient groups on respiratory support are possible.

Osteotomy combined with anterior cruciate ligament reconstruction for anterior cruciate ligament injury and biplanar deformity.

It has been confirmed that the increased posterior tibial slope over 12 degrees is a risk factor for anterior cruciate ligament injury, and varus deformity can aggravate the progression of medial osteoarthritis. To evaluate the efficacy of modified high tibial osteotomy (HTO) and anterior cruciate ligament reconstruction (ACLR) in the treatment of anterior cruciate ligament (ACL) injuries with varus deformities and increased posterior tibial slope (PTS) based on clinical and imaging data. The patient data in this retrospective study were collected from 2019 to 2021. A total of 6 patients were diagnosed with ACL injury combined with varus deformities and increased PTS. All patients underwent modified open wedge HTO and ACLR. The degree of correction of varus deformity and the PTS was evaluated by radiography and magnetic resonance imaging. All 6 patients (6 knee joints) were followed up for an average of 20.8 ± 3.7 months. The average age at surgery was 29.5 ± 3.8 years. At the last follow-up, all patients resumed competitive sports. The International Knee Documentation Committee score increased from 50.3 ± 3.1 to 87.0 ± 2.8, the Lysholm score increased from 43.8 ± 4.9 to 86 ± 3.1, and the Tegner activity level increased from 2.2 ± 0.7 to 7.0 ± 0.6. The average movement distance of the tibia anterior translation was 4.8 ± 1.1 mm, medial proximal tibial angle (MPTA) was 88.9 ± 1.3° at the last follow-up, and the PTS was 8.4 ± 1.4°, both of which were significantly higher than those before surgery (P < 0.05). Modified open wedge HTO combined with ACLR can effectively treat patients with ACL ruptures with an associated increased PTS and varus deformity. The short-term effect is significant, but the long-term effect requires further follow-up.

Rescue liver transplantation for post-hepatectomy liver failure- single center retrospective analysis

IntroductionLiver transplantation (LT) is a well-established method applied for the treatment of various liver diseases, including primary and secondary malignancies, as well as acute liver failure triggered by different mechanisms. In turn, liver failure (PHLF) is the most severe complication observed after liver resection (LR). PHLF is an extremely rare indication for LT. The aim of the present study was to assess the results of LT in patients with PHLF.MethodsRelevant cases were extracted from the prospectively collected database of all LTs performed in our center. All clinical variables, details of the perioperative course of each patient and long-term follow-up data were thoroughly assessed.ResultsBetween January 2000 and August 2023, 2703 LTs were carried out. Among them, six patients underwent LT for PHLF, which accounted for 0.2% of all patients. The median age of the patients was 38 years (range 24–66 years). All patients underwent major liver resection before listing for LT. The 90-day mortality after LT was 66.7% (4 out of 6 patients), and all patients experienced complications in the posttransplant course. One patient required early retransplantation due to primary non-function (PNF). The last two transplanted patients are alive at 7 years and 12 months after LT, respectively.ConclusionsIn an unselected population of patients with PHLF, LT is a very morbid procedure associated with high mortality but should be considered the only life-saving option in this group.

Evaluating the impact of a ward environment with 20 single occupancy rooms and two four-bedded bays on patient and staff experiences and outcomes in an acute NHS Trust: a mixed-methods study protocol

IntroductionTraditionally, wards in acute care hospitals consist predominately of multioccupancy bays with some single rooms. There is an increasing global trend towards a higher proportion of single rooms in hospitals,...

Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma

Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel.

Factors associated with radiographic progression and neurologic decline in patients with isolated traumatic subarachnoid hemorrhage

BackgroundComplicated mild traumatic brain injury (cmTBI) is a common neurosurgical disorder that consumes a significant amount of healthcare resources without a clearly established benefit. Best practices for the management of cmTBI regarding triage, hospital admission, and the necessity for repeat imaging are controversial. Our objective is to describe the rate of radiographic progression and neurologic decline for isolated traumatic subarachnoid hemorrhage (itSAH) patients admitted to the hospital. We hypothesized that only a minority of itSAH patients suffer radiographic progression and that radiographic progression is not necessarily associated with neurologic decline.MethodsDatabase queries and direct patient chart reviews were used to gather patient data. T-tests and Fisher’s exact tests were performed.ResultsA total of 340 patients with cmTBI associated with itSAH were included for analysis. The radiographic progression rate was 5.6%. There was no statistically significant association between age, gender, GCS at presentation, anticoagulation status, and risk of radiographic progression. However, subgroup analysis on anticoagulated patients did show those on warfarin had a statistically significant risk of radiographic progression (p = 0.003). No patient developed neurologic decline, irrespective of whether they developed radiographic progression.ConclusionSecondary triaging, hospital admission, ICU stay, and repeat HCT might not be necessary for awake, GCS 13–15 patients with itSAH without any other significant injuries. In the case of anticoagulant use, but not necessarily antiplatelet use, the medication should be reversed, and admission should be considered.

An advanced Artificial Intelligence platform for a personalised treatment of Eating Disorders

IntroductionEating Disorders (EDs) affect individuals globally and are associated with significant physical and mental health challenges. However, access to adequate treatment is often hindered by societal stigma, limited awareness, and resource constraints.MethodsThe project aims to utilize the power of Artificial Intelligence (AI), particularly Machine Learning (ML) and Deep Learning (DL), to improve EDs diagnosis and treatment. The Master Data Plan (MDP) will collect and analyze data from diverse sources, utilize AI algorithms for risk factor identificat io n, treatment planning, and relapse prediction, and provide a patient-facing chatbot for information and support. This platform will integrate patient data, support healthcare professionals, and empower patients, thereby enhancing care accessibility, personalizing treatment plans, and optimizing care pathways. Robust data governance measures will ensure ethical and secure data management.ResultsAnticipated outcomes include enhanced care accessibility and efficiency, personalized treatment plans leading to improved patient outcomes, reduced waiting lists, heightened patient engagement, and increased awareness of EDs with improved resource allocation.DiscussionThis project signifies a pivotal shift towards data-driven, patient-centered ED care in Italy. By integrat ing AI and promoting collaboration, it seeks to redefine mental healthcare standards and foster better well- being among individuals with EDs.

A Proposal for a Process from as Low as Reasonably Achievable to an Ultra-Low-Level Goal in Chest Computed Tomography

Background/Objectives: To define and evaluate a radiation dose optimization process for chest computed tomography (CT) imaging. Methods: Data from unenhanced and enhanced chest CT acquisitions performed between June 2018 and January 2020 in adult patients were included in the study. Images were acquired on a Siemens SOMATOM® Definition Edge CT. Dose values, including Dose.Length Product (DLP) and Volume CT Dose Index (CTDIvol), were collected. Low doses (LDs, 25th percentiles), achievable doses (ADs, 50th percentiles), and diagnostic reference levels (DRLs, 75th percentiles) were calculated before and after parameter modifications. A process was defined and applied to patient data. For unenhanced chest CT, data were differentiated according to three groups: high dose (HD), optimized dose (OD), and ultra-low dose (ULD). Dosimetric changes between protocols were expressed as mean CTDIvol % (CI95%). A Mann and Whitney statistical test was used. The diagnostic quality score (DQS) of a subset of 70 randomly selected CT examinations was evaluated by one radiologist. The DQS was scored according to a three-point Likert scale: (1) poor (definite diagnosis impossible), (2) fair (evaluation of major findings possible), and (3) excellent (exact diagnosis possible). Results: Data were collected from 1929 patients. For unenhanced chest CT protocols, only one process loop was run. A dose comparison between the chest CT protocol before the use of the process and the three groups showed a decrease of −38.3% (9.7%) and −93.4% (24.2%) for OD and ULD, respectively, and an increase of +29.4% (4.7%) for HD. For the enhanced chest CT protocol, two optimization loops were performed, and they resulted in a mean dose reduction of −50.0% (2.6%) compared to the pre-optimization protocol. For all protocols, the DQS was greater than or equal to 2. Conclusions: We proposed a radiation dose optimization process for chest CT that could significantly reduce the dose without compromising diagnosis.

Utilizing radiomics and dosiomics with AI for precision prediction of radiation dermatitis in breast cancer patients

PurposeThis study explores integrating clinical features with radiomic and dosiomic characteristics into AI models to enhance the prediction accuracy of radiation dermatitis (RD) in breast cancer patients undergoing volumetric modulated arc therapy (VMAT).Materials and methodsThis study involved a retrospective analysis of 120 breast cancer patients treated with VMAT at Kaohsiung Veterans General Hospital from 2018 to 2023. Patient data included CT images, radiation doses, Dose-Volume Histogram (DVH) data, and clinical information. Using a Treatment Planning System (TPS), we segmented CT images into Regions of Interest (ROIs) to extract radiomic and dosiomic features, focusing on intensity, shape, texture, and dose distribution characteristics. Features significantly associated with the development of RD were identified using ANOVA and LASSO regression (p-value < 0.05). These features were then employed to train and evaluate Logistic Regression (LR) and Random Forest (RF) models, using tenfold cross-validation to ensure robust assessment of model efficacy.ResultsIn this study, 102 out of 120 VMAT-treated breast cancer patients were included in the detailed analysis. Thirty-two percent of these patients developed Grade 2+ RD. Age and BMI were identified as significant clinical predictors. Through feature selection, we narrowed down the vast pool of radiomic and dosiomic data to 689 features, distributed across 10 feature subsets for model construction. In the LR model, the J subset, comprising DVH, Radiomics, and Dosiomics features, demonstrated the highest predictive performance with an AUC of 0.82. The RF model showed that subset I, which includes clinical, radiomic, and dosiomic features, achieved the best predictive accuracy with an AUC of 0.83. These results emphasize that integrating radiomic and dosiomic features significantly enhances the prediction of Grade 2+ RD.ConclusionIntegrating clinical, radiomic, and dosiomic characteristics into AI models significantly improves the prediction of Grade 2+ RD risk in breast cancer patients post-VMAT. The RF model analysis demonstrates that a comprehensive feature set maximizes predictive efficacy, marking a promising step towards utilizing AI in radiation therapy risk assessment and enhancing patient care outcomes.

Spatiotemporal correlation enhanced real-time 4D-CBCT imaging using convolutional LSTM networks

PurposeTo enhance the accuracy of real-time four-dimensional cone beam CT (4D-CBCT) imaging by incorporating spatiotemporal correlation from the sequential projection image into the single projection-based 4D-CBCT estimation process.MethodsWe first derived 4D deformation vector fields (DVFs) from patient 4D-CT. Principal component analysis (PCA) was then employed to extract distinctive feature labels for each DVF, focusing on the first three PCA coefficients. To simulate a wide range of respiratory motion, we expanded the motion amplitude and used random sampling to generate approximately 900 sets of PCA labels. These labels were used to produce 900 simulated 4D-DVFs, which in turn deformed the 0% phase 4D-CT to obtain 900 CBCT volumes with continuous motion amplitudes. Following this, the forward projection was performed at one angle to get all of the digital reconstructed radiographs (DRRs). These DRRs and the PCA labels were used as the training data set. To capture the spatiotemporal correlation in the projections, we propose to use the convolutional LSTM (ConvLSTM) network for PCA coefficient estimation. For network testing, when several online CBCT projections (with different motion amplitudes that cover the full respiration range) are acquired and sent into the network, the corresponding 4D-PCA coefficients will be obtained and finally lead to a full online 4D-CBCT prediction. A phantom experiment is first performed with the XCAT phantom; then, a pilot clinical evaluation is further conducted.ResultsResults on the XCAT phantom and the patient data show that the proposed approach outperformed other networks in terms of visual inspection and quantitative metrics. For the XCAT phantom experiment, ConvLSTM achieves the highest quantification accuracy with MAPE(Mean Absolute Percentage Error), PSNR (Peak Signal-to-Noise Ratio), and RMSE(Root Mean Squared Error) of 0.0459, 64.6742, and 0.0011, respectively. For the patient pilot clinical experiment, ConvLSTM also achieves the best quantification accuracy with that of 0.0934, 63.7294, and 0.0019, respectively. The quantification evaluation labels that we used are 1) the Mean Absolute Error (MAE), 2) the Normalized Cross Correlation (NCC), 3)the Structural Similarity Index Measurement(SSIM), 4)the Peak Signal-to-Noise Ratio (PSNR), 5)the Root Mean Squared Error(RMSE), and 6) the Absolute Percentage Error (MAPE).ConclusionThe spatiotemporal correlation-based respiration motion modeling supplied a potential solution for accurate real-time 4D-CBCT reconstruction.

Down syndrome and associated atrioventricular septal defects in a nationwide Norwegian cohort: Prevalence, time trends, and outcomes.

The prevalence of Down syndrome (DS) is approximately 1 per 1000 births and is influenced by increasing maternal age over the last few decades. DS is strongly associated with congenital heart defects (CHDs), especially atrioventricular septal defect (AVSD). Our objectives were to investigate the prevalence of live-born infants with DS having a severe CHD in the Norwegian population over the last 20 years and compare outcomes in infants with AVSD with and without DS. Information on all births from January 1, 2000 to December 31, 2019 was obtained from the Medical Birth Registry of Norway. We also obtained data on all infants with severe CHDs in Norway registered in Oslo University Hospital's Clinical Registry for Congenital Heart Defects during 2000-2019 and accessed individual-level patient data from the electronic hospital records of selected cases. Infants with AVSD and DS were compared to infants with AVSD without chromosomal defects. Crude and adjusted odds ratios (ORs) of infant mortality and need for surgery during the first year of life, with associated 95% confidence intervals (CIs), were estimated by logistic regression. A total of 1 177 926 infants were live-born in Norway during the study period. Among these, 1456 (0.1%) had DS. The prevalence of infants with DS having a severe CHDs was relatively stable, with a mean of 17 cases per year. The most common CHD associated with DS was AVSD (44.4%). Infants with AVSD and DS were more likely to have cardiac intervention during their first year of life compared to infants with AVSD without chromosomal defects (adjusted OR [aOR]: 2.52; 95% CI 1.27, 4.98). However, we observed no difference in infant mortality during first year of life between the two groups (aOR: 1.08; 95% CI 0.43, 2.70). The prevalence of live-born infants with severe CHDs and DS has been stable in Norway across 20 years. Infants with AVSD and DS did not have higher risk of mortality during their first year of life compared to infants with AVSD without chromosomal defects, despite a higher risk of operative intervention.

6 Durable response to immunotherapy-based regimens for IMDC favorable risk patients with metastatic clear cell renal cell carcinoma: a pooled analysis of four published randomized control phase 3 trials

Abstract Background An immune checkpoint inhibitor (ICI) backbone of either ICI doublet (ipilimumab-nivolumab [ipi-nivo]) or tyrosine kinase inhibitor (TKI) with ICI (such as axitinib-pembrolizumab [axi-pembro], cabozantinib-nivolumab [cabo-nivo], or lenvatinib-pembrolizumab [len-pembro]) is the current standard of care for previously untreated, metastatic clear cell renal cell carcinoma (mccRCC). The phase 3 trials that evaluated these four regimens were compared to sunitinib, with no direct head-to-head clinical trial data available. With at least 4-year follow up data available, we compared the long-term responders of the IMDC favorable risk patients enrolled in the four phase 3 trials (CheckMate 214, KEYNOTE-426, CheckMate 9ER, and CLEAR). Methods Pseudo individual patient data (IPD) was obtained from the Kaplan-Meier (K-M) curves using the graph digitizer software IPDfromKM R package to extract coordinates of points on the curves and applied the numerical algorithm to reconstruct survival results. The hazard ratios (HRs) of the favorable risk group for both progression-free survival (PFS) and overall survival (OS) comparing the experimental arms to sunitinib were extracted. Responses were measured at 24 (durable response [DR]) and 36 months (extreme durable response [EDR]) and long-term OS as OS ≥48 months. K-M method using the extracted IPD was used to estimate the survival rates at 24-month PFS, 36-month PFS, and 48-month OS. Then, we compared the survival rates at each time point using the generalized linear model for the survival rates at fixed time points obtained from the K-M method. Results Len-pembro was associated with the highest DR (57.2%) and EDR (44.5%), while ipi-nivo had the lowest DR (36.0%), and cabo-nivo had the lowest EDR (18.8%). There was no difference in 48 month-OS among regimens (p=0.11), ranging between 58.3% (cabo-nivo) and 70.6% (len-pembro). Comparing the sunitinib control arms among the four studies, a numerically higher PFS at 24 months (59%) and 36 months (40%) was observed in the CheckMate 214 trial compared to the ICI-TKI trials (25-35% and 15-20%, respectively). The 48-month OS for the sunitinib arms ranged from 55-70%, and no differences were observed among trials (p=0.55). Comparisons of survival rates for the immunotherapy arm on fixed time-points for IMDC favorable risk subset of patients Conclusions ICI-based regimens provided durable responses to a significant number of patients with favorable risk mccRCC. While TKI-ICI were associated with higher DR and EDR, no differences in OS at 48 months were observed compared to ipi-nivo or sunitinib for favorable risk disease. Longer follow-up is necessary to evaluate long-term outcomes given the favorable prognosis of these patients. We acknowledge the limitations and caveats of cross-trial comparisons.

20 Evaluating intermediate endpoints for overall survival in metastatic renal cell carcinoma treated with immune checkpoint inhibitors: an IMDC study

Abstract Background In Phase 3 trials, the assessment for primary endpoint of overall survival (OS) necessitates extended follow-up periods, a larger pool of events, and higher associated costs. Hence, we sought to determine whether shorter intermediate (IEs) such as Objective Response (OR), Time to Treatment Failure (TTF) and Time to Next Therapy (TTNT) are associated with OS in patients receiving immune checkpoint (ICI)-based therapy. Methods We included all International mRCC Database Consortium (IMDC) patients who received contemporary first line(1L) ICI from 2013 to 2023. IEs were defined from ICI start until drug cessation or death for TTF, and initiation of next line or death for TTNT, or censored at date of last follow-up. OR included investigators-assessed complete or partial response per RECIST1.1 criteria. First, we assessed the endpoint correlations across all follow-up times of individual patient data using Kendall’s Tau (KT) correlation by a Clayton copula. A KT &amp;gt;0.49 indicates a strong correlation (Wicklin R., 2023). Then we evaluated associations of OS with TTF and TTNT status at the 6-month landmark using Cox regression adjusting for IMDC risk groups, metastatic sites, histology, age, and prior nephrectomy, stratified by ICI type and years of ICI start. The KT correlation was estimated by the R GJRM package (https://www.r-project.org/). All other statistical analyses were done with SAS 9.4 software (SAS Institute, Cary, NC). Results The cohort consisted of 1667 patients with a median follow-up of 15.4 months (IQR: 7.1-28.6). For the 6-month landmark analysis in OS, patients who died or had less than 6 months of follow-up were excluded, affecting 278 for OR, 373 for TTF, and 380 for TTNT. Median age at 1L start was 63 years (IQR: 56-70), with 73% being male and 65% undergoing nephrectomy before starting 1L. A total of 1132 patients received dual ICI, while 535 received an ICI+TKI combination. Over the entire follow-up of individual patient data, the Kendall’s Tau correlation was 0.49 (95%CI: 0.45-0.52) for TTF with OS and 0.67 (95%CI: 0.64-0.69) for TTNT with OS. The Kendall’s Tau correlations between endpoints were also similar in subgroup analyses by IMDC risk group and type of regimen and the strongest in the ICI+TKI subgroup with a Kendall’s Tau correlation of 0.73(0.66-0.78). On the 6-month OS landmark analysis (Table), patients who discontinued their 1L regimen had poor OS (adjusted HR: 2.77 (95%CI: 2.16-3.55)). Additionally, those who transitioned to a 2L therapy within the first 6 months showed worse OS, reflected by an HR of 2.82 (2.22-3.59). Patients who did not have an objective response also had worse OS (adjusted HR: 2.74 (95%CI: 2.15-3.49)). On the other hand, patients with an objective response had an 18-month OS rate (equivalent of 12-month OS post the 6-month landmark) of 91% (95%CI: 88%-93%) vs 74% (95%CI: 70%-78%) for those with no response at 6 months. Table. Landmark analysis of OS from 6 months of post therapy initiation, according to OR, TTF and TTNT event status at 6 months, in whole cohort and by IMDC and treatment groups. Conclusions Our study explored TTF, TTNT and OR as clinical IEs for OS. TTNT demonstrated the strongest association with OS, particularly in the ICI+TKI subgroup, making it a potentially clinically meaningful intermediate endpoint for evaluating treatment efficacy in ICI-based regimens.

New Web-Based Ventilator Monitoring System Consisting of Central and Remote Mobile Applications in Intensive Care Units

A ventilator central monitoring system (VCMS) that can efficiently respond to and treat patients’ respiratory issues in intensive care units (ICUs) is critical. Using Internet of Things (IoT) technology without loss or delay in patient monitoring data, clinical staff can overcome spatial constraints in patient respiratory management by integrated monitoring of multiple ventilators and providing real-time information through remote mobile applications. This study aimed to establish a VCMS and assess its effectiveness in an ICU setting. A VCMS comprises central monitoring and mobile applications, with significant real-time information from multiple patient monitors and ventilator devices stored and managed through the VCMS server, establishing an integrated monitoring environment on a web-based platform. The developed VCMS was analyzed in terms of real-time display and data transmission. Twenty-one respiratory physicians and staff members participated in usability and satisfaction surveys on the developed VCMS. The data transfer capacity derived an error of approximately 10−7, and the difference in data transmission capacity was approximately 1.99×10−7±9.97×10−6 with a 95% confidence interval of −1.16×10−7 to 5.13×10−7 among 18 ventilators and patient monitors. The proposed VCMS could transmit data from various devices without loss of information within the ICU. The medical software validation, consisting of 37 tasks and 9 scenarios, showed a task completion rate of approximately 92%, with a 95% confidence interval of 88.81–90.43. The satisfaction survey consisted of 23 items and showed results of approximately 4.66 points out of 5. These results demonstrated that the VCMS can be readily used by clinical ICU staff, confirming its clinical utility and applicability. The proposed VCMS can help clinical staff quickly respond to the alarm of abnormal events and diagnose and treat based on longitudinal patient data. The mobile applications overcame space constraints, such as isolation to prevent respiratory infection transmission of clinical staff for continuous monitoring of respiratory patients and enabled rapid consultation, ensuring consistent care.