Integrating optical and electrical sensing with machine learning for advanced particle characterization.

Particle classification plays a crucial role in various scientific and technological applications, such as differentiating between bacteria and viruses in healthcare applications or identifying and classifying cancer cells. This technique requires accurate and efficient analysis of particle properties. In this study, we investigated the integration of electrical and optical features through a multimodal approach for particle classification. Machine learning classifier algorithms were applied to evaluate the impact of combining these measurements. Our results demonstrate the superiority of the multimodal approach over analyzing electrical or optical features independently. We achieved an average test accuracy of 94.9% by integrating both modalities, compared to 66.4% for electrical features alone and 90.7% for optical features alone. This highlights the complementary nature of electrical and optical information and its potential for enhancing classification performance. By leveraging electrical sensing and optical imaging techniques, our multimodal approach provides deeper insights into particle properties and offers a more comprehensive understanding of complex biological systems.

Clinical and Radiographic Outcomes of Anterior Lumbar Interbody Fusion With Anterior Plate Fixation.

BACKGROUND: Reports on the outcomes following instrumented anterior lumbar interbody fusion (ALIF) with anterior plate fixation are limited. The aim of this study was to assess the clinical and radiographic outcomes of patients undergoing ALIF with anterior plate fixation.  Methods: Medical records and radiographic imaging were reviewed for 100 patients who received ALIF with anterior plate fixation between 2008 to 2021 and completed at least one year of follow-up and postoperative imaging. Prospectively collected patient data included indication for surgery, BMI, age, number and location of levels treated, complications, reoperation rates, fusion rate, and measurements of global lordosis, disc space height, and segmental angulation.  Results: A total of 100 patients were included in this study. The mean length of follow-up was 81.37 months. Changes in preoperative-to-postoperative Oswestry Disability Index (ODI) and Visual Analog Score (VAS) demonstrated improvements of 30.86% and 18.56%, respectively. Major vascular injuries occurred in 3% of the cases. A hardware failure rate of 5% was observed. The reoperation rate was 10%. The radiographic fusion rate derived from computed tomography (CT) and plain film was 95.45% and 88.87%, respectively. Postoperative global lordosis demonstrated a 6.08% increase. Postoperative segmental angulation measurements increased by 57.74%. No statistically significant differences in clinical or radiographic outcomes were observed based on the spine level of fusion or the number of fusions performed.  Conclusions: ALIF with anterior plate fixation achieved an adequate fusion rate with improvements in ODI and VAS scores meeting minimal clinically important difference thresholds. Postoperative disc space heights demonstrated significant improvements compared to preoperative measurements.

Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs.

Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cellular behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular dynamics. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell-ECM mechanotransduction in 3D for regenerative medicine as well as disease modelling.

Vascular aging and cardiovascular disease: pathophysiology and measurement in the coronary arteries.

Age is a key risk factor for cardiovascular disease, including atherosclerosis. However, pathophysiological disease processes in the arteries are not an inevitable feature of aging. Large cohort studies with arterial phenotyping along with clinical and demographic data are essential to better understand factors related to the susceptibility or resilience to age-related vascular pathophysiology in humans. This review explores the mechanisms by which vascular structure and function alters with age, and how these changes relate to cardiovascular pathophysiology and disease. Features of vascular aging in the coronary arteries have historically been difficult to quantify pre-mortem due to their size and location. However, non-invasive imaging modalities including CT Coronary Angiogram are now being used to assess coronary vascular age, and further advances in imaging analysis such as the CT Fat Attenuation Index will help provide further measurement of features associated with coronary vascular aging. Currently, markers of vascular aging are not used as therapeutic targets in routine clinical practice, but non-pharmacological interventions including aerobic exercise and low salt diet, as well as anti-hypertensives have been demonstrated to reduce arterial stiffness. Advances in imaging technology, both in acquisition and advanced analysis, as well as harmonisation of measurements for researchers across the globe will be invaluable in understanding what constitutes healthy vascular aging and in identifying features of vascular aging that are associated with coronary artery disease and its adverse outcomes. Assessing such images in large cohorts can facilitate improved definitions of resilient and susceptible phenotypes to vascular aging in the coronary arteries. This is a critical step in identifying further risk factors and biomarkers within these groups and driving forward the development of novel therapies aimed at slowing or stopping age-related vascular changes in the coronary arteries.

Overall survival and treatment modalities in pancreatic adenocarcinoma: a retrospective analysis of a single centre in Western Australia.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a 5-year survival rate of approximately 10.7% in Australia. It is becoming an increasingly common cause of cancer mortality. The therapeutic model for PDAC remains limited, especially for those with metastatic disease on presentation. Methods: We completed a retrospective cohort study including all patients with PDAC presenting between April 2008 and October 2021 to St. John of God Subiaco Hospital in Western Australia. Overall survival (OS) was calculated via Kaplan-Meier method. Results: We identified 251 patients treated for PDAC. Of these, 134 patients (53%) had resectable, borderline resectable or locally advanced (LA) disease at diagnosis and 117 patients (47%) had metastatic disease. The median age of all patients was 66 years (range, 25-87 years). OS in PDAC was 26 months [95% confidence interval (CI): 23-30]. In the non-metastatic group OS was 34 months (95% CI: 30-39). In the metastatic group OS was 19 months (95% CI: 14-22). Treatment modalities varied between patients. Overall 123 patients were treated with chemotherapy alone, 55 patients had chemoradiotherapy, 34 patients had chemotherapy and surgery and 37 had tri-modality treatment including chemotherapy, surgery and radiotherapy. Two patients received cyberknife radiation alone. Conclusions: This retrospective study shows a significant prolonged survival for PDAC patients. Further studies are needed to validate second- and third-line regimens in PDAC.

Two-Year Outcomes of Valve-in-Valve Using New-Generation Transcatheter Devices Compared With Redo-SAVR.

Few studies have compared the clinical outcomes between valve-in-valve transcatheter aortic valve replacement (ViV-TAVR) with new-generation valves and re-operative surgical aortic valve replacement (Redo-SAVR). We compared the clinical outcomes of patients who underwent ViV-TAVR with those of patients who underwent Redo-SAVR at Cedars-Sinai Medical Center between 2015 and 2021. New-generation valves were used for ViV-TAVR. A propensity score-matched (PSM) analysis was performed to adjust for differences in baseline characteristics. The primary end point was all-cause mortality at 30 days and 2 years. In-hospital procedural and clinical outcomes were also compared between the groups. A total of 256 patients (140 who underwent ViV-TAVR and 116 who underwent Redo-SAVR) were eligible for PSM. In the unmatched cohort, patients in the ViV-TAVR group were older and had more co-morbidities than those in the Redo-SAVR group. After PSM, there were no significant differences in all-cause death between the ViV-TAVR and Redo-SAVR groups at 30 days (3.9% vs 2.6%, p = 0.65) or 2 years (6.5% vs 7.8%, p = 0.75). The incidences of stroke and heart failure rehospitalization were similar at 30 days and 2 years. The cumulative complication rates during hospitalization were significantly lower in the ViV-TAVR group than in the Redo-SAVR group (11.7% vs 28.6% p = 0.015). The long-term outcomes of ViV-TAVR using new-generation valves were similar to those of Redo-SAVR, although ViV-TAVR was associated with lower rates of in-hospital complications.

From Risk Assessment to Intervention: A Systematic Review of Thrombosis in Plastic Surgery.

Thromboembolism is a feared complication in plastic surgery and is linked to higher rates of morbidity and mortality. Despite extensive research, there is a lack of consistency between recommendations and clinical protocols to be implemented pre and post-surgery to reduce the incidence of thromboembolism. A systematic literature review was conducted using Pubmed and Scopus databases to determine the risk factors, screening methods, and existing treatment models for thromboembolism prevention. Articles in non-English languages were excluded. Analysis indicated that predominant risk factors include age (>35), elevated body mass index, coagulation disorders, smoking, estrogen therapies, genetic predisposition, vascular endothelium damage, stasis, and use of general anesthesia in patients with a history of cancer. Implementation of a proper prophylactic protocol is dependent on understanding the interplay between the aforementioned risk factors and the utilization of well-defined, evidence-based guidelines, such as the 2005 Caprini Risk Assessment Model and ultrasound surveillance. The literature review revealed that mechanical prophylaxis is the primary prevention method, followed by thromboprophylaxis for patients with higher Caprini scores. Plastic surgeons often underestimate the present risk stratification tools available for the prophylactic intervention of thromboembolism due to the fear of bleeding or hematoma complications postoperatively. In summary, this literature review emphasizes the importance of plastic surgeons selecting protocols that is inclusive of the patient's risk profile to yield a reduced risk of thromboembolism.

Predicting the risk of iliofemoral vascular complication in complex transfemoral-TAVR using new generation transcatheter devices.

Objective: Design a predictive risk model for minimizing iliofemoral vascular complications (IVC) in a contemporary era of transfemoral-transcatheter aortic valve replacement (TF-TAVR). Background: IVC remains a common complication of TF-TAVR despite the technological improvement in the new-generation transcatheter systems (NGTS) and enclosed poor outcomes and quality of life. Currently, there is no accepted tool to assess the IVC risk for calcified and tortuous vessels. Methods: We reconstructed CT images of 516 propensity-matched TF-TAVR patients using the NGTS to design a predictive anatomical model for IVC and validated it on a new cohort of 609 patients. Age, sex, peripheral artery disease, valve size, and type were used to balance the matched cohort. Results: IVC occurred in 214 (7.2%) patients. Sheath size (p = 0.02), the sum of angles (SOA) (p < .0001), number of curves (NOC) (p < .0001), minimal lumen diameter (MLD) (p < .001), and sheath-to-femoral artery diameter ratio (SFAR) (p = 0.012) were significant predictors for IVC. An indexed risk score (CSI) consisting of multiplying the SOA and NOC divided by the MLD showed 84.3% sensitivity and 96.8% specificity, when set to >100, in predicting IVC (C-stat 0.936, 95% CI 0.911-0.959, p < 0.001). Adding SFAR > 1.00 in a tree model increased the overall accuracy to 97.7%. In the validation cohort, the model predicted 89.5% of the IVC cases with an overall 89.5% sensitivity, 98.9% specificity, and 94.2% accuracy (C-stat 0.842, 95% CI 0.904-0.980, p < .0001). Conclusion: Our CT-based validated-model is the most accurate and easy-to-use tool assessing IVC risk and should be used for calcified and tortuous vessels in preprocedural planning.

New adverse coronary events in valve-in-valve TAVR and native TAVR-A 2-year matched cohort.

Objective: To assess the incidence of new adverse coronary events (NACE) following transcatheter aortic valve replacement (TAVR) and valve-in-valve TAVR (ViV-TAVR). Background: ViV-TAVR is an accepted treatment for degenerative prostheses among patients with high surgical-risk. TAVR studies have suggested an increased risk of coronary artery obstruction and flow stasis causing thrombus formation. Whether contemporary ViV-TAVR is associated with higher rate of coronary events compared to TAVR is unknown. Methods: We used data from 1,224 TAVR patients between 2016 and 2021. We propensity-matched patients following ViV-TAVR and TAVR by significant predictors to overcome confounders in patients' baseline characteristics and procedural factors. Results: The matched population included 129 patients in each group. In line with prior reports, there was a higher in-hospital coronary artery obstruction rate with ViV-TAVR (3.1 vs. 1.6%; p = 0.23). Despite this, 2-year cumulative NACE rates were similar between groups (4.7 vs. 6.2%, respectively, p = 0.79), with no difference between its components: myocardial infarction (MI) (p = 0.210), unplanned coronary catheterization (p = 0.477), or coronary artery bypass grafting (CABG) (p = 0.998). Moreover, hypoattenuated leaflets thickening (HALT) at 30-day CT was observed in nearly a quarter of the patients with no difference between groups (23.9 vs. 23.1%, HR 1.02, 95% CI 0.50-1.28, p = 0.872). The progression rate of the coronary artery calcium score (CACS), assessed in a third of patients, was similar between groups (p log-rank = 0.468, 95% CI 0.12-1.24). Low coronary artery height was an unfavorable predictor for in-hospital coronary obstruction and 2-year NACE rate (HR 1.20 and HR 1.25, p = 0.001 and p < 0.0001, respectively). Conclusion: At 2-year follow-up, ViV-TAVR was not associated with a higher rate of myocardial infarction, unplanned catheterization, coronary artery bypass grafting, or hypoattenuated leaflet thickening.

Biomarker Development in Cardiology: Reviewing the Past to Inform the Future.

Cardiac biomarkers have become pivotal to the clinical practice of cardiology, but there remains much to discover that could benefit cardiology patients. We review the discovery of key protein biomarkers in the fields of acute coronary syndrome, heart failure, and atherosclerosis, giving an overview of the populations they were studied in and the statistics that were used to validate them. We review statistical approaches that are currently in use to assess new biomarkers and overview a framework for biomarker discovery and evaluation that could be incorporated into clinical trials to evaluate cardiovascular outcomes in the future.

Comparing the effect of distance to treatment facility on reconstruction and breast conservation therapy for early-stage invasive ductal carcinoma between the nation and the mountain region.

BACKGROUND: Our objective is to evaluate the effect of distance to facility on the use of breast conservation therapy and reconstruction for early stage breast cancer. METHODS: Utilizing the National Cancer Database, we identified females, age <65, with Stage I invasive ductal carcinoma from 2004 to 2015. Using logistic regression, we compared radiation, mastectomy, and reconstruction treatment patterns. A subgroup analysis was performed within the mountain region (MR). RESULTS: Nationwide, there are decreasing odds of radiation, increasing odds of mastectomy, and increasing odds of reconstruction. Patients living farther were less likely to receive radiation, more likely to undergo mastectomy, with no effect on reconstruction. Within the MR, patients living farther from their facility were less likely to receive radiation, more likely to undergo mastectomy, however, they were less likely to undergo reconstruction. CONCLUSIONS: Nationwide and within the MR, patients living farther from their facility are less likely to receive radiation and more likely to undergo mastectomy. There is a disparity between the MR and the nation in use of reconstruction for this population.

Design and testing of selective inactivators against an antifungal enzyme target.

Systemic infections from fungal organisms are becoming increasingly difficult to treat as drug resistance continues to emerge. To substantially expand the antifungal drug landscape new compounds must be identified and developed with novel modes of action against previously untested drug targets. Most drugs block the activity of their targets through reversible, noncovalent interactions. However, a significant number of drugs form irreversible, covalent bonds with their selected targets. While more challenging to develop, these irreversible inactivators offer some significant advantages as novel antifungal agents. Vinyl sulfones contain a potentially reactive functional group that could function as a selective enzyme inactivator, and members of this class of compounds are now being developed as inactivators against an antifungal drug target. The enzyme aspartate semialdehyde dehydrogenase (ASADH) catalyzes a key step in an essential microbial pathway and is essential for the survival of every microorganism examined. A series of vinyl sulfones have been designed, guided by molecular modeling and docking studies to enhance their affinity for fungal ASADHs. These newly synthesized compounds have been examined against this target enzyme from the pathogenic fungal organism Candida albicans. Vinyl sulfones containing complementary structural elements inhibit this enzyme with inhibition constants in the low-micromolar range. These inhibitors have also led to the rapid and irreversible inactivation of this enzyme, and show some initial selectivity when compared to the inactivation of a bacterial ASADH. The best inactivators will serve as lead compounds for the development of potent and selective antifungal agents.

Persistent pathology of the patent foramen ovale: a review of the literature.

A patent foramen ovale (PFO) is an interatrial shunt, with a prevalence of 20-34% in the general population. While most people do not have secondary manifestations of a PFO, some reported sequelae include ischaemic stroke, migraine, platypnoea-orthodeoxia syndrome and decompression illness. Furthermore, in some cases, PFO closure should be considered for patients before neurosurgery and for patients with concomitant carcinoid syndrome. Recent trials support PFO closure for ischaemic stroke patients with high risk PFOs and absence of other identified stroke mechanisms. While PFOs can be associated with migraine with auras, with some patients reporting symptomatic improvement after closure, the evidence from randomised controlled trials is less clear in supporting the use of PFO closure for migraine treatment. PFO closure for other indications such as platypnoea-orthodeoxia syndrome, decompression illness and paradoxical embolism are based largely on case series with good clinical outcomes. PFO closure can be performed as a day surgical intervention with high procedural success and low risk of complications.

The efficacy of combined bright light and melatonin therapies on sleep and circadian outcomes: A systematic review.

The aim of this systematic review was to investigate the effects of combined melatonin and bright light therapies on improved sleep and circadian outcomes. We conducted a systematic review that resulted in a total of eight papers meeting criteria. Four papers investigated the effectiveness of combined therapy in inducing a circadian phase shift on healthy participants. Combined therapy outperformed single light and melatonin therapies in phase advancing, but not in delaying, dim light melatonin onset (DLMO). The other four papers investigated the effect of combined therapy on sleep outcomes. Two of them were performed in elderly populations suffering from cognitive decline and two in delayed sleep-wake phase disorder (DSWPD) patients. While combined therapy was more beneficial than single therapy in elderly populations it did not show any benefit in DSWPD patients. The reported adverse effects of melatonin in elderly populations must be carefully considered. Future studies should investigate the separate and combined effect of melatonin and bright light on sleep and circadian outcomes in different target populations.

Undernutrition and Hypoleptinemia Modulate Alloimmunity and CMV-specific Viral Immunity in Transplantation.

BACKGROUND: Immunological mechanisms linking undernutrition to infection and the alloimmune response are poorly understood in transplantation. We aimed to determine how undernutrition and hypoleptinemia impact T-cell allospecific and cytomegalovirus (CMV) viral-specific immunity in a murine model. METHODS: Fed, fasted for 48 h (model of undernutrition), and fasted with leptin injections (leptin rescue), C57BL/6 mice received skin grafts from either C57BL/6 (syngeneic) or BALB/c (allogeneic) mice donors. Allograft rejection and survival were monitored. Fed, fasted, and leptin rescue C57BL/6 mice were inoculated with murine cytomegalovirus (mCMV). Mouse spleens were retrieved for T-cell flow cytometry analysis, mCMV DNA extraction, and quantitative polymerase chain reaction. Serum leptin levels were measured with ELISA. RESULTS: Fasted mice had prolonged rejection-free and graft survival compared with fed mice (P = 0.0002 and P = 0.043). Leptin administration did not alter rejection-free survival or allograft failure. CD8+ central memory T cell and CD8+ effector T cell proportions were significantly lower in fasted mice receiving allogeneic skin transplants compared with fed mice (P = 0.0009 and P = 0.0015). Fasted mice had higher viral loads (P = 0.0028) and impaired mCMV-specific interferon-gamma-producing CD8+ T cells (P = 0.0007), which improved with leptin rescue (P = 0.032). CONCLUSIONS: Undernutrition and its associated hypoleptinemia correlated with impaired allospecific and viral-specific immunities. Leptin administration decreased mCMV viral burden and increased mCMV-specific T-cell immunity, however, it did not increase rejection or worsen graft survival in complete major histocompatibility complex-mismatched skin allografts. Leptin may be a potential adjunctive therapy for CMV viremia in undernourished transplant recipients.

The role of FDG-PET-CT is limited in initial staging of nodal metastasis for thin cutaneous melanoma.

INTRODUCTION: Positron emission tomography computed tomography (PET-CT) is often used to stage nodal metastases in thin cutaneous melanoma, with limited evidence. METHODS: A retrospective review of patients with cutaneous malignant melanoma treated at our institution was performed from 2005 to 2015, identifying those who received a PET-CT prior to lymphadenectomy. Biopsy features, lymph node status, and PET-CT results were collected. We calculated the overall sensitivity, specificity, accuracy, likelihood ratios, and positive predictive value of PET-CT in identifying nodal metastases. Results were stratified by initial biopsy tumor depth. RESULTS: We identified 367 cases; 95 obtained a PET-CT prior to lymphadenectomy. Overall, sensitivity and specificity of PET-CT was 34.6% and 95.4%, respectively. The positive likelihood ratio and negative likelihood ratio were 7.62 and 0.68, respectively. The accuracy was 78.2%. The positive predictive value for T3 and T4 melanomas were 100% and 81.4%, respectively. For thin melanomas, specificity and accuracy was 88.2% and 88.2%, respectively. CONCLUSIONS: PET-CT has low specificity and its use alone is not recommended for initial staging of nodal metastases in thin cutaneous malignant melanoma.

Early Characteristics and Progression of Blunt Traumatic Aortic Injuries at a Single Level I Trauma Center.

OBJECTIVES: The most widely accepted grading system for blunt traumatic aortic injury (BTAI) by the Society of Vascular Surgery (SVS) recommends endovascular repair for grade 2 and greater. Non-operative management in grade 2 injuries has been shown to be reasonable in certain circumstances. The natural history of low-grade injuries (1, 2) when managed non-operatively is not well defined. METHODS: Utilizing our trauma registry, patients from 2013 to 2016 with blunt traumatic injury who underwent initial computed tomography were identified. Aortic pathology was graded and grouped by SVS classification. Clinical courses were reviewed for timing of interventions, repeat imaging, concurrent injuries, and outcomes. Analysis of variance and Chi-square tests of significance were utilized to compare between groups. RESULTS: Out of 10,178 patients, we identified 32 with BTAI (grade: 1 (n = 13), 2 (n = 5), 3 (n = 3), 4 (n = 11)). High-grade injuries (3, 4) resulted only from motor vehicle, motorcycle, and pedestrian mechanisms. Initially, 9 patients (28%) required intervention, 5 (16%) were treated non-operatively, and 18 (56%) underwent repeat imaging. On repeat imaging, injuries that did not resolve remained stable and no injuries were found to progress. Of these patients, 9 (50%) required delayed intervention and 9 (50%) successfully underwent non-operative management. Patients with low-grade injuries were more likely to have successful non-operative management than those with high-grade injuries (72% vs 7%; p < 0.01). CONCLUSIONS: While low-grade injuries generally have good outcomes, some ultimately do require delayed intervention, and short-term imaging is not reliable in identifying these cases.

Vedolizumab for ulcerative colitis: Real world outcomes from a multicenter observational cohort of Australia and Oxford.

BACKGROUND: Vedolizumab (VDZ), a humanised monoclonal antibody that selectively inhibits alpha4-beta7 integrins is approved for use in adult moderate to severe ulcerative colitis (UC) patients. AIM: To assess the efficacy and safety of VDZ in the real-world management of UC in a large multicenter cohort involving two countries and to identify predictors of achieving remission. METHODS: A retrospective review of Australian and Oxford, United Kingdom data for UC patients. Clinical response at 3 mo, endoscopic remission at 6 mo and clinical remission at 3, 6 and 12 mo were assessed. Cox regression models and Kaplan Meier curves were performed to assess the time to remission, time to failure and the covariates influencing them. Safety outcomes were recorded. RESULTS: Three hundred and three UC patients from 14 centres in Australia and United Kingdom, [60% n = 182, anti-TNF naïve] were included. The clinical response was 79% at 3 mo with more Australian patients achieving clinical response compared to Oxford (83% vs 70% P = 0.01). Clinical remission for all patients was 56%, 62% and 60% at 3, 6 and 12 mo respectively. Anti-TNF naive patients were more likely to achieve remission than exposed patients at all the time points (3 mo 66% vs 40% P < 0.001, 6 mo 73% vs 46% P < 0.001, 12 mo 66% vs 51% P = 0.03). More Australian patients achieved endoscopic remission at 6 mo compared to Oxford (69% vs 43% P = 0.01). On multi-variate analysis, anti-TNF naïve patients were 1.8 (95%CI: 1.3-2.3) times more likely to achieve remission than anti-TNF exposed (P < 0.001). 32 patients (11%) had colectomy by 12 mo. CONCLUSION: VDZ was safe and effective with 60% of UC patients achieving clinical remission at 12 mo and prior anti-TNF exposure influenced this outcome.

An age-independent gene signature for monitoring acute rejection in kidney transplantation.

Acute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.