Diagnosis Of Primary Disease Research Articles

Neoadjuvant chemotherapy followed by liver resection for patients with metastatic colorectal cancer.

147 Background: Colorectal cancer is one of the leading causes of cancer related deaths with liver being most common site of CRC metastasis. More than 50% of the CRC patients will develop metastatic liver lesion that eventually leads to death in about 70% of them. In this retrospective review we reviewed the outcome of pts who received neoadjuvant chemotherapy followed by resection of liver lesion for metastatic colorectal cancer. Methods: 304 pts who had preoperative chemotherapy were identified from 1045 metastatic colorectal cancer patients who had liver metastasectomy at Mayo Clinic between 1997 and 2018. A retrospective review was conducted by using data from electronic medical records. Statistical analyses utilized Kaplan-Meier method, Log-rank test, and Cox proportional hazards models. Results: There were 113 (37%) female and 191 (63%) male pts. Median age at primary disease diagnosis was 56.5 yrs. Two hundred forty-nine pts presented with stage IV metastatic colorectal cancer. Primary tumor locations were: 53 right-sided, 117 left-sided and 133 rectum. 152 (50%) pts had extrahepatic metastases. Two pts were found to be MSI-H, 113 MSS, 189 unknown. BRAF mutation was found in 6 patients. RAS mutation was present in 84 patients, with 124 unknown. Pts received chemotherapy for median of 2.82 months. Single agent fluoropyrimidine was administered in 38 (12%) pts and rest receiving chemotherapy doublet or triplet with fluropyrimidine plus oxaliplatin being most common regimen. The median overall survival from primary diagnosis for the entire group was 74.5 months. Median overall survival from liver metastasectomy was 60.0 months. In univariate analysis, metachronous disease, age < 60 yrs, and an absence of extrahepatic lesions led to statistically significant improvement of overall survival from primary diagnosis. Metachronous and extrahepatic lesions remained statistically significant in multivariate analysis. Conclusions: Neoadjuvant chemotherapy followed by liver metastasectomy is beneficial for highly-selected metastatic colorectal cancer pts. Compared to a historical control of 30-36 months, our patient population had a median overall survival of about 5 years from resection.

FDG PET Hybrid Imaging.

Molecular imaging with positron emission tomography (PET) using tumour-seeking radiopharmaceuticals has gained wide acceptance in oncology with many clinical applications. The hybrid imaging modality PET/CT (computed tomography) allows assessing molecular as well as morphologic information at the same time. Therefore, PET/CT represents an efficient tool for whole-body staging and re-staging within one imaging modality. In oncology, the glucose analogue 18-F-fluorodeoxyglucose (FDG) is the most widely used PET/CT radiopharmaceutical in clinical routine. FDG PET and FDG PET/CT have been used for staging and re-staging of tumour patients in numerous studies. This chapter will discuss the use and the main indications of FDG PET/CT in oncology with special emphasis on lung cancer, lymphoma, head and neck cancer, melanoma and breast cancer (among other tumour entities). A review of the current literature is given with respect to primary diagnosis, staging and diagnosis of recurrent disease. Besides its integral role in diagnosis, staging and re-staging of disease in oncology, there is increasing evidence that FDG PET/CT can be used for therapy response assessment (possibly influencing therapeutic management and treatment planning) by evaluating tumour control, which will also be discussed in this chapter.

Flow Cytometry for the Diagnosis of Primary Immunodeficiency Diseases: A Single Center Experience

PurposeWhile there is an urgent need for diagnosis and therapeutic intervention in patients with primary immunodeficiency diseases (PIDs), current genetic tests have drawbacks. We retrospectively reviewed the usefulness of flow cytometry (FCM) as a quick tool for immunophenotyping and functional assays in patients suspected to have PIDs at a single tertiary care institute.MethodsBetween January 2001 and June 2018, patients suspected of having PIDs were subjected to FCM tests, including lymphocyte subset analysis, detection of surface- or intracellular-target proteins, and functional analysis of immune cells, at Samsung Medical Center, Seoul, Korea. The genetic diagnosis was performed using Sanger or diagnostic exome sequencing.ResultsOf 60 patients diagnosed with definite or probable PID according to the European Society of Immune Deficiencies criteria, 24 patients were provided with useful information about immunological dysfunction after initial FCM testing. In 10 patients, the PID diagnosis was based on abnormal findings in FCM testing without genetic tests. The FCM findings provided strong evidence for the diagnosis of severe combined immunodeficiency (n = 6), X-linked chronic granulomatous diseases (CGD) (n = 6), leukocyte adhesion deficiency type 1 (n = 3), X-linked agammaglobulinemia (n = 11), autoimmune lymphoproliferative syndrome-FASLG (n = 1), and familial hemophagocytic lymphohistiocytosis type 2 (n = 1), and probable evidence for autosomal recessive-CGD (n = 2), autosomal dominant-hyper-immunoglobulin E (IgE)-syndrome (n = 1), and STAT1 gain-of-function mutation (n = 1). In PIDs derived from PIK3CD (n = 2), LRBA (n = 2), and CTLA4 mutations (n = 3), the FCM test provided useful evidence of immune abnormalities and a tool for treatment monitoring.ConclusionsThe initial application of FCM, particularly with known protein targets on immune cells, would facilitate the timely diagnosis of PIDs and thus would support clinical decisions and improve the clinical outcome.

Study of selective immunoglobulin A deficiency among Egyptian patients with food allergy.

IntroductionIgA deficiency is one of the commonest primary antibody deficiencies. Although many affected individuals could be asymptomatic, selected patients suffer from recurrent mucosal infections, allergies, and autoimmune diseases.Aim of the studyTo investigate the prevalence of IgA deficiency among Egyptian patients with food allergy.Material and methodsWe studied 100 patients (62 males, 38 females; mean age, 28.6 years) with multiple food allergies who were recruited on the basis of adequate immunological assessment by history, skin prick test, and confirmed by open challenge test as well as 50 healthy controls. Measurement of levels of IgE and IgA using ELISA technique were performed for all patients and controls.ResultsDeficiency of IgA was detected in 67% of patients with food allergy. Serum IgA levels were significantly lower among patients with food allergy (67.3 µg/ml; range, 56.7-72.0 µg/ml) as compared to healthy control (78.6 µg/ml; range, 72.8-84 µg/ml). Both IgA and IgE levels were not statistically different between patients with food allergy only and those with combined food and aeroallergen. Among food allergic group, serum IgA levels were inversely correlated with serum IgE levels (r = –0.314, p < 0.001).ConclusionsManifestations of atopy, such as food allergy might be a present feature before diagnosis of primary immune deficiency diseases as IgA deficiency.

Screening for primary immunodeficiency diseases by next-generation sequencing in early life.

ObjectiveWe aimed to use next‐generation sequencing (NGS) for the early diagnosis of primary immunodeficiency diseases (PIDs) and define its effects on medical management for an infant cohort in early life.MethodsA single‐centre study was conducted from November 2015 to April 2018. Infants less than 3 months old with infections or abnormal white blood cell counts were enrolled in the study. Gene variants were analysed by NGS, and once a mutation was found in a PID‐associated gene, the immune functions associated with this mutation were detected. The diagnosis rate of PIDs in the cohort was the main outcome. The patients received corresponding management and follow‐up treatments.ResultsAmong 2392 patients who were genetically tested with NGS, 51 infants were diagnosed with PIDs. Seven types of PIDs were detected, and the most common (25/51, 49%) were combined immunodeficiencies with associated or syndromic features. Thirty‐five patients (68.6%) were cured or had improved outcomes after being diagnosed with PID. The NGS cost was US$280 per case.ConclusionsThis study not only highlighted the potential of NGS to rapidly deliver molecular diagnoses of PIDs but also indicated that the prevalence of PIDs is underestimated. With broader use, this approach has the potential to alter clinical strategies.

Yoğun Bakım, Nörolojik Hastalıklar ve Palyatif Bakım için Zamanlama

Introduction: Patients with neurological diseases may require intensive care support as a result of respiratory failure due to various reasons. Some of them benefit from intensive care supportive treatment while others continue to live as caregivers or need rehabilitation programs. It is important for the rational use of intensive care beds that the routing process to the palliative care, rehabilitation centers or discharge ofpatients with prolonged treatment in the intensive care unit should be managed well Materials and Methods: We retrospectively evaluated the data of our patients who were hospitalized with the diagnosis of primary neurological diseases in the intensive care unit and terminated with exitus or referred to home / palliative care between January 2017 and May 2018 with the permission (17073117-050.06 decision no) of XXXXXXXXXXXXXXX scientific studies committee. Patients who transferred to other clinics were excluded from the study. APACHE II/SAPS II scores, hospitalization day, mechanical ventilation time, tracheostomy and percutaneous endoscopic gastrostomy requirement, home ventilator supply and the situation of discharge from intensive care unit of patients were recorded Results: A total of 942 patient files were reviewed retrospectively and 74 (7.8%) of our patients were neurological patients who were died or discharged to directly home\palliative care. Most of the patients in the study had severe dementia (30 patients, 40.5%) and fewer number of patients had ischemic stroke (21 patients, 28.3%). Sixty of the 74 patients (81.1%) died in the intensive care unit. Only 5 patients were transferred to palliative care (6.8%). Conclusion: Increasing transfer from intensive care to palliative care is important for the effective use of intensive care beds. Therefore, it is suggested that intensive care patients should be evaluated periodically to be directed to palliative care

Diagnostic Yield of Next-Generation Sequencing in Patients With Chronic Kidney Disease of Unknown Etiology.

Advances in next-generation sequencing (NGS) techniques, including whole exome sequencing, have facilitated cost-effective sequencing of large regions of the genome, enabling the implementation of NGS in clinical practice. Chronic kidney disease (CKD) is a major contributor to global burden of disease and is associated with an increased risk of morbidity and mortality. CKD can be caused by a wide variety of primary renal disorders. In about one in five CKD patients, no primary renal disease diagnosis can be established. Moreover, recent studies indicate that the clinical diagnosis may be incorrect in a substantial number of patients. Both the absence of a diagnosis or an incorrect diagnosis can have therapeutic implications. Genetic testing might increase the diagnostic accuracy in patients with CKD, especially in patients with unknown etiology. The diagnostic utility of NGS has been shown mainly in pediatric CKD cohorts, while emerging data suggest that genetic testing can also be a valuable diagnostic tool in adults with CKD. In addition to its implications for unexplained CKD, NGS can contribute to the diagnostic process in kidney diseases with an atypical presentation, where it may lead to reclassification of the primary renal disease diagnosis. So far, only a few studies have reported on the diagnostic yield of NGS-based techniques in patients with unexplained CKD. Here, we will discuss the potential diagnostic role of gene panels and whole exome sequencing in pediatric and adult patients with unexplained and atypical CKD.

Diagnosis of primary immunodeficiency diseases in the developing world: the need for education and networking with the developed world.

Even with the evident improvement in knowledge about clinical and molecular aspects and the technology used to diagnose primary immunodeficiency diseases (PIDs), there is still a significant delay in recognition of these diseases in the developing world, specifically in Latin America. In this review, the goal is to outline the challenges that need to overcome for the diagnosis of PIDs and the optimization of resources available based on our experience. We describe the advances achieved in the past decade in Latin America in terms of recognition of PIDs, as well as the need for improvement. We outline the need for continued medical education, the lack of resources for laboratory testing, and how genetic testing through next-generation sequencing (that is becoming a day-to-day tool) can be achieved in the developing world. We aim to gather information about the limitations and challenges for the diagnosis of PIDs in a low-resource environment and the opportunities to benefit from the available advanced tools for diagnosis.

Jakinibs for the Treatment of Immune Dysregulation in Patients With Gain–of–Function Signal Transducer and Activator of Transcription 1 (STAT1) or STAT3 Mutations

To investigate the efficacy of jakinib therapy in patients with gain-of-function (GOF) signal transducer and activator of transcription 1 (STAT1) or signal transducer and activator of transcription 3 (STAT3) mutations.The study included 17 total patients with either a STAT1 GOF (n = 11) or STAT3 GOF (n = 6) mutation who were treated with jakinibs (ruxolitinib or tofacitinib). Patients came from 11 international centers.This was a retrospective study to describe disease-related clinical manifestations and determine indication for treatment, dosage, length of treatment, treatment response, and treatment-associated complications. All subjects underwent thorough pre- and posttreatment clinical and laboratory evaluations and follow-up (follow-up period: 1–34 months).Fourteen patients (82%) responded favorably with clinical improvement to jakinib treatment. Observed clinical improvements included resolution of enteropathy leading to total parenteral nutrition independence, better lung function, improved autoimmune cytopenias, decreased arthritis symptoms, and remission of hemophagocytic lymphohistiocytosis. All patients with STAT1 GOF had resolved chronic mucocutaneous candidiasis with treatment. Most patients tolerated the jakinibs well with minimal or transient adverse effects. An increase in herpes zoster infections (none systemic and all cleared with antiviral agents) was observed in some patients. Four patients died despite treatment with a jakinib. The majority of these patients were critically ill with severe invasive infection or progressive lung disease. One patient died due to posttransplant complications.Jakinibs are both safe and effective in the treatment of patients with STAT1 or STAT3 GOF mutations with clinical manifestations of autoimmunity and/or immune dysregulation.Patients with STAT1 and STAT3 GOF mutations often present in early childhood with severe and/or refractory infections, lymphoproliferation, autoinflammation, and autoimmunity. Jakinibs allow for a targeted therapeutic approach to block the cytokine-induced JAK activation in STAT1 and STAT3 GOF diseases. This is the first study to evaluate the use and clinical impact of jakinibs in STAT1 and STAT3 GOF. The results are overwhelmingly encouraging, with the majority of patients having clinical improvement and reduction or resolution of autoimmune manifestations after treatment with a jakinib. Use of jakinibs late in disease progression or when critically ill was associated with mortality, suggesting early initiation may improve efficacy. This study has significant clinical impact in the treatment of STAT1 and STAT3 GOF and reinforces the notion that early genetic diagnosis of primary immunodeficiency diseases may lead to targeted therapeutic options and improved clinical outcomes.

Flow Cytometry Contributions for the Diagnosis and Immunopathological Characterization of Primary Immunodeficiency Diseases With Immune Dysregulation.

Almost 70 years after establishing the concept of primary immunodeficiency disorders (PIDs), more than 320 monogenic inborn errors of immunity have been identified thanks to the remarkable contribution of high-throughput genetic screening in the last decade. Approximately 40 of these PIDs present with autoimmune or auto-inflammatory symptoms as the primary clinical manifestation instead of infections. These PIDs are now recognized as diseases of immune dysregulation. Loss-of function mutations in genes such as FOXP3, CD25, LRBA, IL-10, IL10RA, and IL10RB, as well as heterozygous gain-of-function mutations in JAK1 and STAT3 have been reported as causative of these disorders. Identifying these syndromes has considerably contributed to expanding our knowledge on the mechanisms of immune regulation and tolerance. Although whole exome and whole genome sequencing have been extremely useful in identifying novel causative genes underlying new phenotypes, these approaches are time-consuming and expensive. Patients with monogenic syndromes associated with autoimmunity require faster diagnostic tools to delineate therapeutic strategies and avoid organ damage. Since these PIDs present with severe life-threatening phenotypes, the need for a precise diagnosis in order to initiate appropriate patient management is necessary. More traditional approaches such as flow cytometry are therefore a valid option. Here, we review the application of flow cytometry and discuss the relevance of this powerful technique in diagnosing patients with PIDs presenting with immune dysregulation. In addition, flow cytometry represents a fast, robust, and sensitive approach that efficiently uncovers new immunopathological mechanisms underlying monogenic PIDs.

Classification of heart sound signals in congenital heart disease based on convolutional neural network

Cardiac auscultation is the basic way for primary diagnosis and screening of congenital heart disease(CHD). A new classification algorithm of CHD based on convolution neural network was proposed for analysis and classification of CHD heart sounds in this work. The algorithm was based on the clinically collected diagnosed CHD heart sound signal. Firstly the heart sound signal preprocessing algorithm was used to extract and organize the Mel Cepstral Coefficient (MFSC) of the heart sound signal in the one-dimensional time domain and turn it into a two-dimensional feature sample. Secondly, 1 000 feature samples were used to train and optimize the convolutional neural network, and the training results with the accuracy of 0.896 and the loss value of 0.25 were obtained by using the Adam optimizer. Finally, 200 samples were tested with convolution neural network, and the results showed that the accuracy was up to 0.895, the sensitivity was 0.910, and the specificity was 0.880. Compared with other algorithms, the proposed algorithm has improved accuracy and specificity. It proves that the proposed method effectively improves the robustness and accuracy of heart sound classification and is expected to be applied to machine-assisted auscultation.

Oxygraphy Versus Enzymology for the Biochemical Diagnosis of Primary Mitochondrial Disease.

Primary mitochondrial disease (PMD) is a large group of genetic disorders directly affecting mitochondrial function. Although next generation sequencing technologies have revolutionized the diagnosis of these disorders, biochemical tests remain essential and functional confirmation of the critical genetic diagnosis. While enzymological testing of the mitochondrial oxidative phosphorylation (OXPHOS) complexes remains the gold standard, oxygraphy could offer several advantages. To this end, we compared the diagnostic performance of both techniques in a cohort of 34 genetically defined PMD patient fibroblast cell lines. We observed that oxygraphy slightly outperformed enzymology for sensitivity (79 ± 17% versus 68 ± 15%, mean and 95% CI), and had a better discriminatory power, identifying 58 ± 17% versus 35 ± 17% as “very likely” for oxygraphy and enzymology, respectively. The techniques did, however, offer synergistic diagnostic prediction, as the sensitivity rose to 88 ± 11% when considered together. Similarly, the techniques offered varying defect specific information, such as the ability of enzymology to identify isolated OXPHOS deficiencies, while oxygraphy pinpointed PDHC mutations and captured POLG mutations that were otherwise missed by enzymology. In summary, oxygraphy provides useful information for the diagnosis of PMD, and should be considered in conjunction with enzymology for the diagnosis of PMD.

650 The Effects of HIV Status on Complications and Outcomes in Patients With Inflammatory Bowel Disease: An Analysis Using the Nationwide Inpatient Sample Database

INTRODUCTION: The effects of HIV status on inflammatory bowel disease (IBD) has been described in the literature but has been limited in cohort size. Here, we examine data from patients with IBD and HIV in the Nationwide Inpatient Sample database over a 7-year period. METHODS: Data between 2008 and 2014 from the Nationwide Inpatient Sample database was extracted. Inclusion criteria for both groups included patients with a primary diagnosis of either Crohn's disease or Ulcerative colitis using International Classification of Diseases, 9th Revision codes. Exclusion criteria included all patients less than 18 years of age. Test group consisted of patients with a primary diagnosis of Crohn's disease or Ulcerative colitis and a concurrent diagnosis of HIV. In hospital mortality and complications including anemia, malabsorption, malnutrition, stenosis, obstruction, fistulas, abscesses, ulcers, perforations, and hemorrhage were compared between the two groups. Univariate and multivariate analyses were used to generate odds ratios. Multivariate analysis included age, gender, race, and calculated Elixhauser scores. Elixhauser Comorbidity scores predicting mortality and readmission were calculated based on weighted scores from 29 different comorbidities. Scores were compared between the two groups using univariate analysis. RESULTS: There were a total of 121835 patients with IBD and no HIV and 475 patients with IBD and HIV for hospitals in the United States between 2008 and 2014. There was no significant difference in hospital mortality between the two groups on univariate analysis (OR 0.5161, P = 0.5092). Of the complications studied, there was a significant difference for obstruction (OR 0.3447, P &lt; 0.0001), ulceration (OR 1.97, p = 0.0063), and hemorrhage (OR 1.75, P = 0.0001) on univariate analysis. For the multivariate analysis, HIV status has a significant effect on anemia (OR 0.291, P = &lt;0.001), malnutrition (OR 0.3, P = &lt;0.001), obstruction (OR 0.411, P = &lt;0.001), and hemorrhage (OR 1.47, P = &lt;0.001). CONCLUSION: HIV status does not seem to have a significant effect on mortality, but appears to be protective against obstruction, anemia, and malnutrition. We suspect the immunocompromised status of HIV patients may lead to fewer bouts of acute inflammation, reducing the rates of complications. It may also be of interest to compare rates of procedures and interventions between the two groups to further explore potential differences.

799 Hospital Length of Stay and Mortality in Patients With Inflammatory Bowel Disease and Atrial Fibrillation

INTRODUCTION: Proinflammatory markers such as interleukin (IL)-6 have been closely associated with various pathological processes, such as oxidative stress, apoptosis, and fibrosis that promote formation of atrial fibrillation (AF). These markers are characteristically elevated in inflammatory bowel disease (IBD). It has been shown that AF has a higher prevalence in IBD. It is important to analyze the effect of comorbid AF and IBD on hospital length of stay and mortality. METHODS: The National Inpatient Sample (NIS) database, representing roughly 20% of all inpatient admissions, was used to identify patients with a primary or secondary diagnosis of Crohn's disease and Ulcerative Colitis from 2012 to 2014. The sample was analyzed to assess for LOS, Charlson comorbidity index (CCI), length of stay (LOS) and inpatient mortality among patients with or without history of AF. The sample was weight to calculate national rates. Categorical variables were analyzed via Chi square test and continuous variables via T-test. Multivariable logistic regression analysis was used to assess the primary outcome of inpatient hospital mortality, with the analysis adjusted for age, sex, race and CCI. RESULTS: A total of 249045 patients from the 2012-2014 NIS database were admitted for IBD; of those 3.9% had history of AF. The average LOS was 4.7 days, rate of and mortality during hospitalization was 0.2%. AF was associated with older patients (mean age 70 vs. 43.5 years, P &lt; 0.001) and higher CCI (3.9 vs. 1.2, P &lt; 0.001) when compared to non AF patients. AF was also associated with increased hospital LOS (5 days vs. 4.4 days, P &lt; 0.05) as well as higher mortality rates (0.9% vs. 0.1%, P &lt; 0.001) when compared to non AF patients. After adjusting for possible confounders including age, sex, race and Charlson comorbidity index, the mortality rate was significantly higher in the AF group (odds ratio 1.8, P &lt; 0.001, 95% CI 1.5-2.4). CONCLUSION: Our study found that hospitalized patients with comorbid IBD and AF had higher mortality rates as well as increased hospital LOS. IBD leads to a chronic inflammatory state promoting systemic inflammation. It has been proposed that this pro-inflammatory state leads to the development of AF in IBD patients. Given the higher incidence of AF in IBD patients compared to the standard population, and the increased mortality and hospital LOS associated with the two conditions, further studies should be done to explore the cause of mortality and any intervention that could improve outcomes.

HEALTHCARE RESOURCE USE AND COSTS IN PATIENTS WITH IDIOPATHIC PULMONARY FIBROSIS IN THE US MEDICARE POPULATION

SESSION TITLE: Monday Electronic Posters 3 SESSION TYPE: Original Inv Poster Discussion PRESENTED ON: 10/21/2019 02:30 PM - 03:15 PM PURPOSE: Two idiopathic pulmonary fibrosis (IPF) therapies (pirfenidone and nintedanib) that slow disease progression were approved in 2014 in the United States. We examined healthcare utilization (HCU) and costs associated with these antifibrotic therapies in the Medicare patient population. METHODS: A retrospective observational study of Medicare beneficiaries using the 100% Medicare Research Identifiable File was conducted. Patients aged 67+ diagnosed with IPF (≥1 inpatient or outpatient claim with diagnosis [ICD-9-CM: 516.3, 516.30, 516.31; ICD-10-CM: J84.111, J84.112]) during the study period (1/2010-12/2015) on or before initiation of antifibrotic therapy (index date) between (10/15/2014-12/31/2015) were included. The cohort was divided into 2 groups: pirfenidone or nintedanib initiators. HCU except hospitalization and costs were measured as monthly outcomes (per patient per month, PPPM) during the treatment period and weighted by follow-up length. Claims with primary diagnosis of respiratory disease (ICD-9-CM: 460.xx - 519.xx; ICD-10-CM: J00.xx-J99.xx) or a diagnosis of respiratory disease in any field were defined as respiratory-related for inpatient and outpatient services, respectively. Stabilized inverse probability of treatment weighting using the propensity score (PS) adjusted the baseline confounding factors. To estimate the PS, baseline covariates included: age, gender, region, Charlson comorbidity index (excluding COPD), COPD, stroke, newly diagnosed IPF, pneumonia 3 months prior to initiation, quartile of median income of patient residential area and distance from patient residential area to ILD specialty center. RESULTS: The study identified 3546 patients diagnosed with IPF (2082 pirfenidone, 1464 nintedanib) who initiated antifibrotics. All-cause inpatient costs PPPM (mean, SD) were: pirfenidone ($1129, $3992.6), nintedanib ($1494, $5317.7), P=0.026; all-cause outpatient service costs PPPM: pirfenidone ($1042, $1453.6), nintedanib ($1072, $1462.8), P=0.553; respiratory-related inpatient costs PPPM: pirfenidone ($581, $2559.1), nintedanib ($833, $4180.1), P=0.041; all-cause inpatient hospitalizations: pirfenidone 20.0%, nintedanib 22.6%, P=0.066; days of stay in the hospital: pirfenidone 8.1 days, nintedanib 9.4 days, P=0.101; respiratory-related hospitalizations: pirfenidone 11.1%, 12.4% nintedanib, P=0.257; days of stay in hospital: pirfenidone 7.2 days, nintedanib 9.3 days, P=0.043. CONCLUSIONS: Differences were observed in all-cause inpatient costs, respiratory-related inpatient costs, and respiratory-related hospitalization days between antifibrotics. Respiratory-related hospitalizations have been associated with an increased risk of death in IPF. CLINICAL IMPLICATIONS: Patients receiving pirfenidone vs nintedanib may have overall lower all-cause inpatient costs and fewer respiratory-related hospital days. DISCLOSURES: No relevant relationships by Michael Broder, source=Web Response No relevant relationships by Eunice Chang, source=Web Response Employee $100000 Added 03/06/2019 by Mitra Corral, source=Web Response, value=Salary<br No relevant relationships by Sohum Gokhale, source=Web Response Employee relationship with PHAR, LLC Please note: >$100000 Added 03/13/2019 by Sheila Reddy, source=Web Response, value=Salary

NATIONAL INTER-HOSPITAL TRANSFER PRACTICES FOR PATIENTS WITH ACUTE CARDIOVASCULAR CONDITIONS

Little is known about inter-hospital transfer practices for patients with acute cardiovascular conditions in Canada. Although ST-elevation myocardial infarction systems of care are protocolized in most regions, care processes for other conditions often do not exist. Thus, we described patient characteristics and outcomes of transferred patients with acute cardiovascular disease in Canadian hospitals. We reviewed the Canadian Institute for Health Information (CIHI) Discharge Abstract Database for patients age ≥ 18 years hospitalized with a primary admission diagnosis of acute cardiovascular disease (International Classification of Diseases-10 category “I”) between 2013 and 2018 in all Canadian provinces except Québec. We compared patient characteristics and clinical outcomes based on transfer status (transferred vs. non-transferred) and presenting hospital (teaching hospitals vs. large, medium, and small community hospitals). There were 476,753 patients with acute cardiovascular diagnoses, among whom 48,579 (10.1%) were transferred. Large community hospitals most frequently transferred (n=16,038, 33.0%) and teaching hospitals more frequently received (n=28,653, 59.0%) patients (Figure). Transferred patients were more frequently younger (median age 67 [IQR 18] vs. 74 [IQR 21], p < 0.001), male (69.9% vs. 57.9%, p < 0.001), and had fewer cardiovascular comorbidities (Table). The most common primary diagnoses among transferred patients were non-ST-elevation myocardial infarction (44.2%), ST-elevation myocardial infarction (29.0%), and congestive heart failure (9.4%). Using teaching hospitals as a reference, hospital mortality was lowest among patients transferred to large and medium community hospitals (adjusted OR 0.83, 0.75-0.91 and 0.45, 0.39-0.52, respectively), after adjusting for age, sex, comorbidities, and care location. Hospital mortality was higher for patients transferred to small community hospitals (adjusted OR 1.93, CI 1.64-2.28). Approximately 10% of patients presenting with acute cardiovascular conditions are transferred to other hospitals. Patient transfer is associated with lower in-hospital mortality, although there is variability in outcomes depending on diagnosis, comorbidities, hospital of origin, and destination hospital. Further investigation of transfer practices for acute cardiovascular disease is warranted as regionalized care models continue to develop in Canada.View Large Image Figure ViewerDownload Hi-res image Download (PPT)

P087 Defining the economic burden of venous thromboembolism after surgery for inflammatory bowel disease: A national inpatient sample study

BACKGROUND: Venous thromboembolism (VTE) may be considered an extra-intestinal manifestations of inflammatory bowel disease (IBD) related to inflammation associated hypercoagulability, and at least 4% of patients requiring surgery for IBD develop a VTE post-operatively. However, the economic burden associated with VTE after surgery for IBD has not been reported. Therefore we aimed to use a large national database to define the rate of post-operative VTE, and VTE-associated healthcare costs. METHODS: A retrospective, cross-sectional analysis was performed using National Inpatient Sample (NIS) dataset from 2010 to 2014. The International Classification of Disease 9th edition (ICD-9) diagnostic and procedure codes were used to identify patients with primary diagnosis of Crohn's disease (CD) or Ulcerative colitis (UC) who underwent major abdominopelvic surgery. VTE included any extremity DVT, pulmonary embolism, portomesenteric venous thrombosis, and cerebral venous sinus thrombosis. The national VTE rate and VTE associated costs were estimated using the sampling weights provided and following explicit instructions given by Healthcare Cost and Utilization Project (HCUP). Univariate and multivariate logistic regression models were used to compare patient characteristics, hospital characteristics and outcomes between VTE and non-VTE groups. The total average direct costs in dollars were then compared between the 2 groups using linear regression accounting for complex survey design, and the resulting difference, in dollars, extrapolated to the national population. P-values &lt;0.05 were considered statistically significant. RESULTS: Any VTE was identified in 1,656 (5.3%) out of a total of 31,242 patients. On univariate analysis, older age, white race, higher Elixhauser comorbidity score, UC diagnosis, hospital transfer prior to surgery, larger bed size and urban teaching hospital were associated with VTE; conversely, elective surgery, laparoscopic approach and colectomy (compared to proctectomy and &gt;1 type of resection) were associated with lower risk of VTE. On multivariate analysis age, Elixhauser score, resection type, transfer status, hospital bed size, location and teaching status of hospital were independently associated with VTE. Proctectomy and &gt;1 type of resection were independent factors associated with increased risk of VTE compared to colectomy alone (OR 1.5, 95% CI 1.3–1.9; OR 1.4, 95% CI 1.2–1.6 respectively; both P &lt; 0.001). In terms of outcomes, patients who developed VTE had an increased length of stay (11.3 vs 7.6 days; P &lt; 0.001) and higher inpatient mortality (5.4% vs 3.7%; OR 1.5, 95% CI 1.2–1.8; P &lt; 0.001) compared to the non-VTE cohort. Direct costs were significantly higher in the VTE group, with an addition cost of $14,939 (95% CI $12,369–$17,510, P &lt; 0.001) per admission. After adjusting for clinically relevant covariates, the cost difference was $10,507 (95% CI $9,649–$11,365, P &lt; 0.001). Nationwide, the additional cost of VTE was estimated to be $17,031,847 annually. CONCLUSION(S): VTE after abdominopelvic surgery for IBD occurs in &gt;5% of patients nationally, and is associated with additional costs of $10,000 per patient, translating into over $17 million dollars in the United States annually. Novel screening and prophylactic regimens are sorely needed to reduce this morbid, costly, and potentially avoidable complication.

SUN-174 EPIDEMIOLOGY AND OUTCOME OF ACUTE KIDNEY INJURY IN INTENSIVE CARE UNIT PATIENTS IN LAOS: A MULTICENTER, PROSPECTIVE, OBSERVATIONAL STUDY

Numerous publications reported the incidence of acute kidney injury (AKI) around the world. However, there is still no any reports of incidence and outcomes of this high burden disease from Laos PDR. The objectives of this study were to determine the incidence of AKI in ICU patients; to characterize the differences in a etiology, illness severity and to determine the factors of AKI and the outcome of AKI among ICU patients in Lao PDR. As part of South Eastasia-AKI (SEA-AKI) study, we collected the data by registration in electronic web-based format from 5 ICU centers across Laos PDR. The data were serially collected on the first 28 days of ICU admission. Standard Kidney Disease Improving Global Outcomes (KDIGO) criteria were used to define AKI incidence. We used mortality at hospital discharge time as the clinical outcome. We also explored the impact of age, gender, co-morbidity disease, Acute Physiology and Chronic Health Evaluation II (APACHE II) score and primary diagnosis to the AKI incidence and outcome. This is the first and the largest prospective observational study of AKI epidemiology in Laos. We have enrolled 1,480 patients from January 1st, 2016 to December 31th, 2016. After exclusion of end stage renal disease patients (n=20), we finally had 1,460 patients in our cohorts. AKI occurred in 508 patients (34.8%; KDIGO stage1- 4.04%; stage2- 10.27%; stage3- 20.48%). The hospital mortality for AKI patients was 59% compared with 41% in non AKI group (P < 0.001). In the multivariable adjusted model, we found that age, hypertension, diabetes, and chronic kidney disease, severity score and the primary diagnosis of renal related disease were independent risk factors for AKI incidence. AKI is very common disease in Laos and yielded high hospital mortality rate. AKI incidence varied by age, gender, disease severity, and primary diagnosis. Early diagnosis and intervention to reduce severity of disease, and early ICU admission will alleviate AKI and improve outcomes

89Zr]A2cDb Immuno-PET of Prostate Cancer in a Human Prostate Stem Cell Antigen Knock-in (hPSCA KI) Syngeneic Model.

A great challenge in the diagnosis and treatment of prostate cancer is distinguishing between indolent or local disease and aggressive or metastatic disease. Antibody-based positron emission tomography (immuno-PET) as a cancer-specific imaging modality could improve diagnosis of primary disease, aid the detection of metastases to regional lymph nodes as well as to distant sites (e.g., bone), and monitor response to therapy. In search for a more physiologically relevant disease model, a human prostate stem cell antigen knock-in (hPSCA KI) mouse model was generated. The use of a syngeneic prostate cancer cell line transduced to express human PSCA (RM-9-hPSCA) enabled the evaluation of anti-PSCA immuno-PET in immunocompetent mice and in the context of normal tissue expression of PSCA. Two PSCA-specific humanized antibody fragments, A11 minibody and A2 cys-diabody, were radiolabeled with positron emitters iodine-124 and zirconium-89, respectively ([124I]A11 Mb and [89Zr]A2cDb), and used for immuno-PET in wild-type, hPSCA KI and tumor-bearing mice. The hPSCA KI mice express PSCA at low levels in the normal prostate, bladder and stomach, reproducing the expression pattern seen in humans. [124I]A11 Mb immuno-PET detected increased levels of PSCA expression in the stomach, and because I-124 is non-residualizing, very little activity was seen in organs of clearance (liver, kidney, spleen). However, due to the longer half-life of the 80kDa protein, blood activity (and thus urine activity) at 20h postinjection remains high. The smaller 50kDa [89Zr]A2cDb cleared faster, resulting in lower blood and background activity, despite the use of a residualizing radiometal. Importantly, [89Zr]A2cDb immuno-PET showed antigen-specific targeting of PSCA-expressing tumors and minimal nonspecific uptake in PSCA-negative controls. Tracer biodistribution was not significantly impacted by normal tissue expression of PSCA. [89Zr]A2cDb immuno-PET yielded high tumor-to-blood ratio at early time points. Rapid renal clearance of the 50kDa tracer resulted in an unobstructed view of the pelvic region at 20h postinjection that would allow the detection of cancer in the prostate.

Hospitalization Rates for Respiratory Diseases After L'Aquila Earthquake.

The study aims to investigate the impact of the earthquake on public health, in terms of hospitalizations for respiratory diseases in the Abruzzo region, focusing on the area damaged by the earthquake “Crater”. We collected data of hospitalizations of residents in Abruzzo between 2009 and 2015. Hospital Discharge Records (HDRs) with a primary diagnosis of respiratory disease were included and divided into pneumonia, Chronic Obstructive Pulmonary Disease (COPD), and respiratory insufficiency. Absolute frequencies and standardized hospitalization rates were calculated to perform both a short-term and a medium-long term analysis. A linear regression was performed using standardized hospitalization rates and the time. A total of 108.669 respiratory-related records were collected and the most frequent subgroup was respiratory insufficiency. Standardized Hospitalization Rates (SHRs) for respiratory diseases resulted higher in the non-Crater than Crater area, but the short-term analysis showed a significant increase in hospitalizations for pneumonia and respiratory insufficiency in the Crater area. The medium-long term analysis reported a significant difference on the slope decrease of hospitalizations for acute and chronic respiratory diseases in the Crater versus the non-Crater area. The earthquake may have played a triggering role in the increased detection of respiratory diseases. A temporal relationship between the quake and an increase in admissions was found although it is not yet possible to detect a direct cause-effect relationship.