End-stage Organ Damage Research Articles

A Novel Preclinical Murine Model of Systemic Lupus Erythematosus-Like Cardiovascular Disease.

Systemic lupus erythematosus (SLE) affects nine women to every man worldwide, and these patients are at greater risk for cardiovascular disease (CVD) morbidity and mortality. Clinical studies have demonstrated that patients with SLE are more likely to develop CVD, including cardiac and vascular dysfunction. Although many preclinical models of SLE are available, including treatment with Toll-like receptor (TLR) 7/8 agonists, a consistent preclinical model of SLE-like CVD with systemic, cardiac, renal, and cerebral endothelial activation and cardiac dysfunction has yet to be described. Here, we hypothesize that acceleration of SLE with the TLR7/8 agonist resiquimod (R848) will promote cardiac and endothelial activation with subsequent end-stage organ damage in the SLE-prone B6.Nba2 mouse model. Female and male SLE-prone B6.Nba2 mice were treated with R848 or acetone, administered topically twice weekly over a four-week period, to accelerate the development of SLE-like pathophysiology. Echocardiography was performed at baseline, 4 weeks, and 16 weeks. At 16 weeks, tissues were harvested, weighed, and analyzed by histology, immunofluorescence, real-time quantitative polymerase chain reaction, and enzyme-linked immunosorbent assays. We found that female R848-treated mice had increased serum anti-Smith and immunoglobulin G complex deposition in the kidney, heart, and brain consistent with SLE-like etiology. Tissue analysis revealed significant enlargement of the spleen in both female and male R848-treated mice, with only cardiac and renal enlargement in females compared to their respective controls. Echocardiographic imaging revealed left ventricular wall thickening by 4 weeks that was followed by a progressive increase in left ventricular internal diameters and subsequent decrease in ejection fraction over the 16-week time course in female mice. We found that circulating levels of soluble vascular adhesion molecule-1 and soluble intracellular adhesion molecule-1 were increased in both female and male R848-treated mice, whereas cardiac and renal fibrosis were significantly increased in only female R848-treated mice. Our data demonstrate that R848 treatment of SLE-prone B6.Nba2 mice is a novel preclinical model to study the sex-dependent pathophysiologic mechanisms of SLE-like CVD.

Abdominal involvement as a primary manifestation of systemic or isolated gastrointestinal vasculitis

Systemic vasculitides can cause a wide variety of gastrointestinal manifestations (GI) ranging from mild and frequently nonspecific abdominal pains to potentially life-threatening bowel perforations. Vascular involvement in systemic vasculitides can affect any GI blood vessel, most commonly mesenteric, hepatic, or splenic arteries. Inflammatory changes affecting different layers of arterial vessel walls can lead to aneurysmatic dilatation or blood vessel occlusion with subsequent organ ischemia leading to mucosal ulcerations, GI bleeding, perforations, or bowel obstruction. While the presence of extraintestinal manifestations may aid in diagnosis, delays in making appropriate diagnoses and rapid initiation of glucocorticoid and immunosuppressive treatment can have detrimental consequences. Awareness of isolated gastrointestinal vasculitis is of particular importance as it frequently remains undiagnosed until end-stage organ damage becomes apparent. Vasculitis mimics such as vascular Ehlers-Danlos syndrome or fibromuscular dysplasia add another lay of complexity in approaching patients with suspected GI vasculitis and should always be carefully considered.

Abstract 2841: Development and validation of a systemic human multiple myeloma model utilizing luciferase expressing MM1.S tumor cells

Abstract Multiple Myeloma (MM) is a complex hematologic malignancy characterized by clonal proliferation of transformed plasma cells leading to overproduction of monoclonal immunoglobulins and subsequently end-stage organ damage. Despite therapeutic advances, MM is an incurable disease with poor prognosis in high-risk patients, and thus relevant preclinical models are necessary to develop novel treatment strategies. We developed a Multiple Myeloma in vivo model by systemic implantation of the luciferase-expressing glucocorticoid sensitive tumor cell line MM1.S (MM1.S-Luc) into immunodeficient NCG mice. First, we generated a MM1.S-Luc monoclonal cell line from a polyclonal pool of stable luciferase-expressing cells by limiting dilution. Single cells from the stable pool were expanded under selective pressure and four MM1.S-Luc monoclonal lines were selected based on in vitro growth properties and bioluminescence intensity. Next, we determined the in vivo tumor growth profile by testing the monoclonal lines at two different cell inoculums, and disease progression was monitored by in vivo serial bioimaging. MM1.S-Luc tumor growth kinetics revealed a long latency and based on our in vivo imaging results, the tumor preferentially localized to the long bones, lungs, and mandible. For validation of the MM1.S-Luc in vivo model, we determined the efficacy and survival benefit in response to various clinically relevant standard of care agents including Dexamethasone, Daratumumab, Cyclophosphamide, Vincristine, Panobinostat, and Bortezomib. The quantification of tumor burden by bioluminescent imaging showed reduced tumor burden and prolonged survival with Panobinostat and Cyclophosphamide. In summary, we have developed a systemic MM1.S-Luc model that recapitulates the disease dissemination and invasiveness of multiple myeloma for evaluating novel therapeutic approaches to treatment. Citation Format: Bincy John, Christopher Currie, Nicole Westrick, Tyler Rowe, Andrew Wong, Elizabeth Rainbolt, Zachary Ward, Chassidy Hall, David Harris. Development and validation of a systemic human multiple myeloma model utilizing luciferase expressing MM1.S tumor cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2841.

Risk Indicators of Sarcoidosis Evolution-Unified Protocol (RISE-UP): protocol for a multi-centre, longitudinal, observational study to identify clinical features that are predictive of sarcoidosis progression

IntroductionSarcoidosis is a pulmonary and systemic granulomatous disease with a wide range of potential outcomes, from spontaneous resolution to end-stage organ damage and death. Currently, clinicians have no easy-to-use risk...

667. Real-world Experience of Cefiderocol with Pseudomonas aeruginosa in the PROVE (Retrospective Cefiderocol Chart Review) Study

Abstract Background Gram-negative (GN) bacterial resistance is an urgent global health problem. Cefiderocol (CFDC) is active against many resistant GN pathogens, including Pseudomonas aeruginosa (PA). PROVE is an ongoing international, retrospective study assessment of CFDC use for Gram-negative infections (GNI). Methods Patients were eligible if they received ≥ 72 hours of CFDC. Patient and pathogen characteristics, hospital course, and antibiotic treatment patterns were described. All-cause mortality (ACM) at 14 and 30 days and clinical cure were examined as outcomes, overall, and by key characteristics such as pathogen susceptibility (determined at the local level), patient demographics, infection site, and severity of illness. Serious adverse drug reactions (SADR) were recorded. Results To date, 123 patients treated with CFDC at 12 sites were included. Sixty-five patients had PA as a pathogen, either alone (N=45) or in combination with another pathogen (N=20) attributed to starting CFDC. The median age was 54 years; 68% were male. The most prevalent comorbidity was diabetes with end stage organ damage (N=15, 23%). CFDC was given in an ICU setting in 54 (82%) patients. Vasopressors and mechanical ventilation were required in 42% and 62%, respectively. Most (91%) PA were carbapenem resistant. The median time from a positive culture to start of CFDC was 6 days. CFDC monotherapy was used in 75%. The most common GN antibiotic class used concurrently with CFDC was aminoglycosides (N=7). Targeted therapy with CFDC against pathogens of known susceptibility with or without prior GN antibiotics accounted for 80% of use. The remainder was used for salvage (15%) or empirically (2%). Susceptibility testing to CFDC, available for 54 cultures (54 patients), showed 94% (51/54) were susceptible. Post-CFDC initiation 14- and 30-day all-cause mortality (ACM) was 9% (95% CI: 3%-19%) and 23% (95% CI: 14%-35%) respectively. Clinical resolution was achieved in 66% (95% CI: 53% -77%). Thirty-day ACM for susceptible pathogens was 25% (13/51). Cefiderocol Use Patterns in Pseudomonas aeruginosa Conclusion Real-world use of CFDC for PA demonstrated that most patients had multiple comorbidities and were severely ill. These data suggest that CFDC is being used appropriately with little empirical use in patients with few treatment options. Disclosures Stephen Marcella, MD, MPH, Shionogi: Shionogi employee|Shionogi, Inc: Employee Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board Sean Nguyen, n/a, Shionogi: Employee Anan Zhou, MPH, Shionogi, Inc: contracting work for Shionogi, Inc.

The Independent Adverse Prognostic Significance of 1q21 Gain/Amplification in Newly Diagnosed Multiple Myeloma Patients

Background Multiple myeloma (MM) is a hematological malignancy with proliferation of monoclonal plasma cells which has complex genetics and prognostic heterogeneity. It involves a variety of primary genetic abnormalities, including t (4; 14), t (11; 14), t (14,16) and hyperdiploid karyotypes, as well as secondary genetic abnormalities, including chromosome copy number abnormalities (1q21+, 1p-, 13q-, 17p-, etc) and secondary translocations like MYC. As the most common secondary genetic event, 1q21+ occurs in about 30-40% of NDMM patients while the proportion is especially higher in Chinese population, accounting for 59.7% (96/161) by a domestic study in 2022, it is closely related to the situation that MM patients may have long disease duration and late stage when initial diagnosed in China. Despite its frequency, considerable debate remains regarding to the prognostic impact of 1q21+ in NDMM, 1q21 status hasn't been included among the high-risk markers listed by the IMWG R-ISS stage, and neither in Chinese guidelines. If 1q21+ is included as one of the poor prognostic factors, it will greatly increase the proportion of high-risk patients in NDMM patients. So, our center has begun to take 1q21 seriously as a heterogeneity problem for clinical discussion. Methods 248 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2021 of a VRD clinical study, with VRD in combination with ASCT or VRD treatment for 8 cycles, were retrospectively analyzed. 135 cases (54.4%) had 1q21+ by CD38-sorted fluorescence in situ hybridization (FISH), among which 153 patients were compared for the involved genes by CytoScan, focusing on the clinical characteristics, treatment response and prognostic significance by combining FISH and CytoScan technology complementary. Results Among the 248 NDMM patients, 54.4% patients with 1q21+ were more likely to have anemia, hypoalbuminemia, renal insufficiency, high lactate dehydrogenase and high proportion of R-ISS-III stage, and are more likely to be combined with 13q14 deletion, t(4;14), and 1p deletion，and they are all at middle-risk or high-risk groups defined by Prognostic Index score. Multivariate analysis showed that 1q21 gain/amplification was an independent adverse prognostic factor (PFS HR=2.358, 95%CI 1.286-4.324, P=0.006; OS HR=2.598, 95%CI 1.050-6.425, P=0.039). 1q21+ subgroup had an inferior outcome (PFS P=0.0133, OS P=0.0293) (Figure 1a). According to the mSMART3.0 stages, double-hit and triple-hit group had the worst prognosis, with a median PFS of 22 months and a median OS of 32 months. Both PFS and OS were clinically significant (P<0.0001), as shown in Figure 1b. Furthermore 1q21 amplification with more than 4 copy numbers had a shorter PFS than 1q21 gain with 3 copy numbers (24 months vs not reached, P=0.0403), but the OS difference hasn't been not clinically significant (Figure 1c). The positive proportion of 1q21 had no effects on prognosis，while the status of 1q21 in the main clone rather than in the subclone defined by CytoScan when the proportion of abnormal clone populations are differed more than 30%, was an adverse factor affecting the prognosis (PFS P=0.0172, OS P=0.1260). (Figure 1d). ASCT plays an important role in the prognostic survival of 1q21 gain and amplification patients (P<0.05). Outcomes of 1q have been widely discussed in CRD/CTD scheme of Myeloma XI, KRd/KCD scheme of FORTE, VRD/PAD of HOVON65 and so on, our study focusing on the patients with VRD +/- ASCT is also unique, demonstrating that the prognosis of 1q21+ in VRD scheme is also poor, but ASCT can overcome the adverse effects significantly. Conclusions Patients with 1q21+ have clinically significant end-stage organ damage and higher tumor burden, more likely to combine 13q14-, t(4;14), 1p32- and other cytogenetic abnormalities. 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in NDMM patients, of which 4 or more copy numbers and main clone position significantly associated with prognosis results. By combining FISH, CytoScan and other technologies with related abnormalities such as 1q21+，17p-, 1p32-，t (4;14), t(14;16), etc., clinical characteristics, efficacy evaluation, and prognosis can be analyzed more accurately, aiming to identify patients with poor prognosis earlier and enhancing the possibility of moving forward to the treatment strategy based on risk stratification in the future. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

The independent adverse prognostic significance of 1q21 gain/amplification in newly diagnosed multiple myeloma patients.

Objective1q21 gain/amplification (1q21+) is a common abnormal karyotype in multiple myeloma, and its proportion in Chinese patients is much higher. If 1q21+ is included as one of the poor prognostic factors, it will greatly increase the proportion of high-risk patients in newly diagnosed multiple myelome (NDMM) patients. Therefore, the poor prognostic significance of 1q21+ is still controversial. This study mainly analyzed the clinical characteristics, treatment response and prognostic significance of 1q21+ in NDMM patients.Methods248 NDMM patients admitted in The First Affiliated Hospital of Soochow University from September 01, 2018 to August 31, 2021 of a VRD registration study, were retrospectively analyzed. 135 cases (54.4%) had 1q21+ by CD38-sorted fluorescence in situ hybridization (FISH). The clinical characteristics, treatment response and prognosis of the general population and subgroups were analyzed, among which 153 patients were compared for the involved genes by CytoScan.ResultsCompared with negative patients, 1q21+ patients were more likely to have anemia, hypoalbuminemia, renal insufficiency, high lactate dehydrogenase and high proportion of R-ISS-III stage. The patients with 1q21+ involving CKS1B detected by Cytoscan had a higher proportion of complex karyotypes and abnormal CNVs, and all at middle-risk or high-risk groups defined by Prognostic Index. Multivariate analysis showed that 1q21+ was an independent adverse prognostic factor (PFS HR=2.358, 95%CI 1.286-4.324, P=0.006; OS HR=2.598, 95%CI 1.050-6.425, P=0.039). 1q21+ subgroup had an inferior outcome (PFS P=0.0133, OS P=0.0293). Furthermore 1q21 amplification had a shorter PFS than 1q21 gain (24 months vs not reached, P=0.0403), but the OS difference was not clinically significant. The proportion of 1q had no effects on prognosis. In addition, 1q21+ in main clone rather than subclone was an adverse factor affecting the prognosis (PFS P=0.0172, OS P=0.1260). Autologous stem cell transplantation can effectively improve the survival of 1q21+ patients (P<0.05).ConclusionPatients with 1q21+ have clinically significant end-stage organ damage and higher tumor burden, more likely to combine 13q14-, t(4;14), 1p32- and other cytogenetic abnormalities. 1q21+ is an independent high-risk cytogenetic factor for poor prognosis in NDMM patients, of which 4 or more copy numbers and main clone position significantly associated with prognosis results.

527 Characteristics of the gut microbiome in solid organ transplant recipients

Solid organ transplantation is the ultimate life-saving intervention in patients with end stage organ damage. However, despite revolutionary advances in transplant medicine, complications such as allograft rejection, malignancy, and disseminated infection continue be a major challenge. A growing body of evidence suggests a potential influence of microbial dysbiosis on transplant outcomes. We therefore aimed to investigate the gut microbiome of solid organ transplant recipients for comparison with healthy controls to identify possible dysbiosis. Microbial genomic data, both bacterial and fungal, was generated from fecal samples of 20 solid organ transplant recipients and 20 matched healthy controls. Analyses included testing for differences in microbial diversity measures and relatively abundant species between cohorts. The bacterial median Shannon diversity index, a measure for alpha diversity of the gut microbiome, was significantly higher in solid organ transplant samples with a median of 3.125 versus 2.449 for healthy controls (p<0.05). Additionally, principal coordinate analyses, based on Bray-Curtis distance, displayed significant differences in the bacterial and fungal microbiota composition between stool of transplant patients and healthy controls (PCo1 vs. PCo2, p<0.05). Furthermore, several alterations in abundance existed at different taxonomic levels, including a a 15-fold increased abundance of Clostridium perfringens (p<0.0001), a 3-fold increased abundance of Staph epidermidis (p<0.0001), and 2-fold increased abundance of Staph aureus (p<0.001) at the species level in transplant patients. Ultimately, we demonstrated that solid organ transplant recipients have gut microbiome dysbiosis, characterized by an increase in microbial diversity and several alterations in taxa abundance. This is in discordance with current trends in microbiome research that associate lower diversity with worse health outcomes; however, it supports the emerging role of the microbiome as a therapeutic target.

Role and Mechanism of the Renin-Angiotensin-Aldosterone System in the Onset and Development of Cardiorenal Syndrome.

Cardiorenal syndrome (CRS), a clinical syndrome involving multiple pathological mechanisms, exhibits high morbidity and mortality. According to the primary activity of the disease, CRS can be divided into cardiorenal syndrome (type I and type II), renal heart syndrome (type III and type IV), and secondary heart and kidney disease (type V). The renin-angiotensin-aldosterone system (RAAS) is an important humoral regulatory system of the body that exists widely in various tissues and organs. As a compensatory mechanism, the RAAS is typically activated to participate in the regulation of target organ function. RAAS activation plays a key role in the pathogenesis of CRS. The RAAS induces the onset and development of CRS by mediating oxidative stress, uremic toxin overload, and asymmetric dimethylarginine production. Research on the mechanism of RAAS-induced CRS can provide multiple intervention methods that are of great significance for reducing end-stage organ damage and further improving the quality of life of patients with CRS.

Causes and Circumstances of Death: Analysis in 266 Sickle Cell Adult Patients

IntroductionSickle cell disease is a genetic disease with acute and chronic complications. Pediatric mortality has decreased in recent decades with the introduction of systematic antibiotic therapy, preventive management of cerebral vasculopathy and therapeutic education of families. However, in the absence of cohort follow-up at birth, life expectancy, which is a different concept from age at death, cannot be assessed.In this retrospective, monocentric study, we describe causes and circumstances of death, acute chronic complications, long-term treatments and baseline biology of these patients. It seems important to analyze the risks of morbidity and mortality in order to decide on the necessary preventive measures.Material and method:Records of patients deceased between 2000 and 2020, from the national referral center (Henri Mondor Hospital), were retrospectively reviewed. The referral center follows 3500 patients. All deaths reported to the hospital, by families, other hospitals and health professionals were retrieved from computerized records. Deaths published by the INSEE (National Institute of Statistical and Economical study) from 2000 to December 2020 were accessible and compared with our databases to identify all our deceased patients. All patients with a medical record in our center were included for the study. Patients who had never visited our center were excluded.Results:During this period 226 patients including 128 women and 138 men are recorded. Genotypes for these patients were 204(76%) SS, 41 (15%) SC, 14(5%) Sβ°thalassemia and 7 (2%) Sβ+thalassemia. The median age at death was 41 years with an IQR [32-51]. 186 (70%) patients were hospitalized, 129 (70%) of whom were admitted to intensive care. 36 (13%) patients died at home, including 15 with opioid addiction and 5 patients with psychiatric pathology, and 4 patients on dialysis. This information was not available for 44 (16%) patients.The causes of death were vaso-occlusive complications with multivisceral failure in 44 cases, 42 sepsis, among which there were 11 renal failures, 9 of which were dialyzed. 5 patients died of COVID 19. Cerebral hemorrhage and neurological accident occurred in 22 cases, 4 of which were known to have macrovasculopathy. 25 patients died of a direct complication of renal failure, of which 17 were dialysed, 8 pre-dialysed and 3 transplanted. Acute liver failure in 16 cases, 10 precapillary pulmonary hypertension, 14 DHTR, 10 end-stage heart failure were noted. Two road accidents, 2 suicides, 1 dementia are repoted. For 51 cases, there was no information on the cause or circumstance of death. The causes of death according to genotype is on Table 1.Concerning the chronic complications, 94/266 (35%) patients had significant chronic organ damage. Sixteen patients had required renal or liver transplantation in their history. End-stage organ damage was frequent, 42 had end-stage renal failure, 21 had major liver failure, of which five were transplanted and 16 were awaiting transplantation. Twenty-one patients had known heart failure, 10 of which were associated with end-stage renal disease. Ten patients were followed for significant precapillary pulmonary hypertension.Transfusion difficulties due to a history of DHTR were found for 33 patients. Fourteen patients had an opioid addiction. Nine patients were pregnant and nine had received corticosteroids.Discussion:Causes of death have changed and chronic organ failure is the leading cause of death, especially in patients with kidney, liver and heart disease. This study does not calculate life expectancy, but there was an increase in age at death of about 1/4 of the patients who were between 51 and 81 years old.The management of sickle cell disease has progressed in recent years and new therapies are being proposed. Prevention of the development of these complications is one of the new challenges, especially for renal disease, which is associated with premature mortality. DHTR and cerebral hemorrhage, Covid-19 are new entities and DHTR was probably underdiagnosed in previous publications. Pregnancy remains a period at risk, for which surveillance should be reinforced. The analysis is ongoing and correlations are currently being investigated between different parameters to find risk factors for mortality. [Display omitted] DisclosuresHabibi: Novartis: Consultancy, Honoraria; bluebird bio: Consultancy, Honoraria, Research Funding. Audard: Addmedica: Consultancy. Michel: Novartis: Consultancy; Amgen: Consultancy; Rigel: Honoraria; Alexion: Honoraria; UCB: Honoraria; Argenx: Honoraria. Galactéros: Addmedica: Membership on an entity's Board of Directors or advisory committees. Bartolucci: INNOVHEM: Other: Co-founder; Bluebird: Consultancy, Research Funding; F. Hoffmann-La Roche Ltd: Consultancy; GBT: Consultancy; Jazz Pharma: Other: Lecture fees; AGIOS: Consultancy; Hemanext: Consultancy; Emmaus: Consultancy; Fabre Foundation: Research Funding; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Lecture fees, Steering committee, Research Funding; Addmedica: Consultancy, Other: Lecture fees, Research Funding.

Characteristics and outcomes of octogenarians with revascularized critical limb ischemia: Impact of altered cardiac function for early mortality

Patients with critical limb ischemia (CLI) present with advanced age and end-stage organ damage, in particular heart failure. The aim of the present study is to describe clinical and biological characteristics in octogenarian patients with CLI compared to their younger counterparts and to determine the peri-procedural risk and early mortality after endovascular procedure.From November 2013 to May 2019, 315 consecutive patients were retrospectively included. Clinical and biological parameters were recorded at baseline before endovascular revascularization. The main outcome was total 1-year mortality.The study included 170 octogenarians and 145 non-octogenarians. The mean age of octogenarian patients was 86.9±4.8 years, almost 20 years higher than that registered in non-octagenarians patients (67.4±8.6 years). Octogenarian patients were mostly women (59.4%), presented with lower body mass index (23.8±4.4kg/m2), lower serum albumin level (31.5±5.4g/L) and lower creatinine clearance (66.1±24.5mL/mn) than younger counterparts. They were more likely to be institutionalized in a nursing home (27.1%). In the peri-procedural period, major bleeding occurred in 40 patients (12.7%), without statistical significance between the two age groups. Peri-procedural mortality occurred in 12 patients (3.8%), of whom 10 patients (83%) were octogenarians. Cumulative mortality rate was 25.4% (80 patients) during the one-year follow-up period: 58 octogenarians died (34.1%) compared to 22 non-octogenarian patients (15.2%), P<0.001. Cardiovascular events were highly prevalent, accounting for 40% of overall mortality. Twenty-five patients (8%) experienced major amputation, without significant difference between the two age groups. In octogenarian population, institutionalized status (P=0.004) and BNP level (P=0.001) were positively correlated with mortality whereas systolic blood pressure (P<0.001), left ventricular ejection fraction (P=0.003), serum albumin (P=0.020), C-Reactive protein (P=0.020) and renin-angiotensin system inhibitors at hospital discharge were negatively correlated with mortality. In multivariate analysis for mortality, only BNP level≥500pg/mL (HR 3.27; 95% CI 1.04-10.97; P=0.04), was correlated with mortality, independently of other confounders.In the present study population, octogenarians represent a rather distinct CLI population, 20 years of age older as compared to non-octogenarians, with prevalent malnutrition and institutionalized status. The present results underline a substantial one-year mortality rate of 34.1% in this elderly population following revascularization procedure with a 6% peri-procedural mortality. Decompensated heart failure is an important contributor for mortality.

Urological management and surgical procedures in migrants from Sub-Saharan Africa with urogenital schistosomiasis

Introduction and objectivesAn increasing number of urogenital schistosomiasis (UGS) is being diagnosed in Europe following the unprecedented migratory flux from Sub-Saharan Africa (SSA). This phenomenon represent a challenge for urologists working in a non-endemic area. The aim of this study is to describe the urological management and the surgical procedures of patients with UGS in a tertiary referral centre. PatientsAll subjects from SAA diagnosed with UGS from January 2011 to November 2018 were enrolled retrospectively. Detailed data of patients with UGS undergoing to urological procedures were collected and analysed. ResultsThirty patients were diagnosed with UGS, among them 12 (42.8%) were submitted to surgery. The most common surgical procedure was trans urethral resection of bladder (TURB) for suspected lesions persisted after praziquantel treatment performed in 7 cases (58%). Other surgical procedure were TURB and concomitant ureteroscopy with laser fragmentation for suspected bladder neoplasm with renal stone, endoscopic lithotripsy and percutaneous nephrolithotomy for bladder and renal stones, laparoscopic nephrectomy for end-stage kidney disease, placement of bilateral nephrostomy for hydroureteronephrosis, explorative testicular surgery for a suspected testicular torsion in one case each. Four patients (33%) were lost at the follow up. ConclusionAn increasing number of migrants from SSA diagnosed with UGS has been observed. Some patients required a surgical intervention for suspected neoplastic lesions or end-stage organ damage. It was particularly difficult to perform a regular follow-up in several patients. Further multicentric studies are needed to reach a proper standard in diagnosis, treatment and follow-up of subjects with UGS.

Manejo urológico y procedimientos quirúrgicos en migrantes del África Subsahariana con esquistosomiasis urogenital

Introduction and objectivesAn increasing number of urogenital schistosomiasis (UGS) is being diagnosed in Europe following the unprecedented migratory flux from Sub-Saharan Africa (SSA). This phenomenon represent a challenge for urologists working in a non-endemic area. The aim of this study is to describe the urological management and the surgical procedures of patients with UGS in a tertiary referral centre. PatientsAll subjects from SAA diagnosed with UGS from January 2011 to November 2018 were enrolled retrospectively. Detailed data of patients with UGS undergoing to urological procedures were collected and analysed. ResultsThirty patients were diagnosed with UGS, among them 12 (42.8%) were submitted to surgery. The most common surgical procedure was trans urethral resection of bladder (TURB) for suspected lesions persisted after praziquantel treatment performed in 7cases (58%). Other surgical procedure were TURB and concomitant ureteroscopy with laser fragmentation for suspected bladder neoplasm with renal stone, endoscopic lithotripsy and percutaneous nephrolithotomy for bladder and renal stones, laparoscopic nephrectomy for end-stage kidney disease, placement of bilateral nephrostomy for hydroureteronephrosis, explorative testicular surgery for a suspected testicular torsion in one case each. Four patients (33%) were lost at the follow up. ConclusionAn increasing number of migrants from SSA diagnosed with UGS has been observed. Some patients required a surgical intervention for suspected neoplastic lesions or end-stage organ damage. It was particularly difficult to perform a regular follow-up in several patients. Further multicentric studies are needed to reach a proper standard in diagnosis, treatment and follow-up of subjects with UGS.

2202-PUB: Do Women with Diabetes in Pregnancy Have Better Medication Adherence to Long-Acting Insulin Compared with Intermediate Insulin?

Objective: To determine whether women with pre-existing and gestational diabetes have better medication adherence and pregnancy outcomes when treated with long acting, compared to intermediate acting, insulin. Methods: We performed a retrospective cohort study of all pregnancies complicated by pregestational and gestational DM from 2007-2017 at a Resident Diabetes in Pregnancy clinic at an academic tertiary care center. Patients were excluded if they did not take long acting or intermediate insulin or took an oral agent in addition, had end stage organ damage, multiple gestation, or fetal anomalies. The primary outcome was maternal medication adherence per physician report. The secondary outcome was a composite neonatal outcome including macrosomia, NICU admission, LGA, shoulder dystocia, individual components of the composite, and glycemic control. Demographic characteristics were compared between groups and logistic regression was used to adjust for potential confounders, including advanced maternal age, weight, race, body mass index, and substance abuse. Results: Of 926 patients seen during the study period, 808 women met study criteria, by diabetes type: type 1 (n=48), type 2 (n=293) and GDM (n=467). Demographic characteristics were similar between those who used long-acting vs. intermediate insulin. Adjusted analysis using logistic regression demonstrated no significant difference in medication adherence between groups. There was also no difference in the neonatal composite outcome, components of the composite, or glycemic control. Results were similar in stratified analysis by diabetes type. Conclusion: Medication adherence was similar between women using long and intermediate acting insulin and there was no change in neonatal outcomes. Our findings call into question the notion that the twice daily dosing of intermediate insulin in pregnancy provides tighter glycemic control, although medication adherence did not suffer. Disclosure S.A. Nazeer: None. C.J. Herrick: None. H.E. Duckham: None. E.B. Carter: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-19-ACE-02 to E.B.C.)

The Association between Chronic Conditions, End-of-Life Health Care Use, and Documentation of Advance Care Planning among Patients with Cancer.

Background: Multiple chronic conditions (MCCs) are associated with increased intensity of end-of-life (EOL) care, but their effect is not well explored in patients with cancer. Objective: We examined EOL health care intensity and advance care planning (ACP) documentation to better understand the association between MCCs and these outcomes. Design: Retrospective cohort study. Setting/Subjects: Patients aged 18+ years at UW Medicine who died during 2010-2017 with poor prognosis cancer, with or without chronic liver disease, chronic pulmonary disease, coronary artery disease, dementia, diabetes with end-stage organ damage, end-stage renal disease, heart failure, or peripheral vascular disease. Measurements: ACP documentation 30+ days before death, in-hospital death, and inpatient or intensive care unit (ICU) admission in the last 30 days. We performed logistic regression for outcomes. Results: Of 15,092 patients with cancer, 10,596 (70%) had 1+ MCCs (range 1-8). Patients with cancer and heart failure had highest odds of hospitalization (odds ratio [OR] 1.67, 95% confidence interval [CI] 1.46-1.91), ICU admission (OR 2.06, 95% CI 1.76-2.41), or in-hospital death (OR 1.62, 95% CI 1.43-1.84) versus patients with cancer and other conditions. Patients with ACP 30+ days before death had lower odds of in-hospital death (OR 0.65, 95% CI 0.60-0.71), hospitalization (OR 0.67, 95% CI 0.61-0.74), or ICU admission (OR 0.71, 95% CI 0.64-0.80). Conclusions: Patients with ACP 30+ days before death had lower odds of high-intensity EOL care. Further research needs to explore how to best use ACP to ensure patients receive care aligned with patient and family goals for care.

Attitude and levels of awareness toward organ donation and transplantation among healthcare providers: A cross-sectional study.

End-stage organ damage is the major cause of death worldwide. The number of donors is low, and one of the challenging phases in organ donation is the availability of organ donors. There are many studies that suggest a strong correlation between knowledge and beliefs toward organ donation. A study conducted among Health-Care Providers in the Intensive Care Units at a Tertiary Center at Riyadh reported that only 57% of the health-care providers in the Intensive Care Unit were willing to donate their organs. The objective of our study was to evaluate the knowledge, attitude, and awareness of organ donation and transplantation among health-care providers at different hospitals around the Kingdom of Saudi Arabia. The data of this cross-sectional descriptive study were collected between February and July 2018 in different hospitals all around the Kingdom of Saudi Arabia. The investigators formulated a questionnaire based on several published studies. Ethical approval was obtained from the Unit of Biomedical Ethics, Research Committee at King Abdul Aziz University. Of the 241 participants, 130 (53.9%) were female. In addition, 110 (45.6%) of them were medical residents. Moreover, 224 (92.9%) participants were aware of the concept of organ donation. The overall level of knowledge is good (55.2%).The study showed 62.2% have participated in the organ donation program for their close relatives only. In conclusion, the level of perception and knowledge about organ donation among health-care providers was inadequate, although they showed positive attitudes toward this issue.

Skin improvement is a surrogate for favourable changes in other organ systems in early diffuse cutaneous systemic sclerosis.

Skin improvement in diffuse cutaneous SSc (dcSSc), measured with modified Rodnan skin score (mRSS), is frequently used as a primary outcome in clinical trials, but it is uncertain whether mRSS changes reflect changes in other organ systems. This aim of this study was to explore if skin changes in early dcSSc over 1 and 2 years are associated with changes in severity of other organ involvement. Canadian Scleroderma Research Group database patients with dcSSc, disease duration of ≤5 years, no evidence of initial end-stage organ damage and/or significant comorbidity who had 1 year (n = 154) and 2 years (n = 128) of follow-up data were included. mRSS changes of 25% and/or ≥5 points were considered significant. Organ involvement was assessed by Medsger Disease Severity Score and Canadian Scleroderma Research Group definitions using bivariate, chi-square, ANOVA, adjusted regression and longitudinal mixed effect model analyses. Improvement in mRSS was found in 41% of patients at 1 year and in 50% at 2 years. Improved patients showed less forced vital capacity decline (P = 0.012) and less frequent new cardiac involvement (P = 0.02) over 1 year, as well as better lung (by both Disease Severity Score, P = 0.006, and Δforced vital capacity%, P = 0.026), peripheral vascular (P = 0.006) and joint/tendon (P = 0.002) involvement over 2 years. mRSS worsening was consistently linked to less favourable lung outcomes at both 1- and 2-year follow-up visits, and more severe gastrointestinal disease at 2 years. Changes in lung function in early dcSSc closely parallel skin changes. mRSS improvement reflects better prognosis for visceral disease and may be a reliable outcome measure in clinical trials.

P30 Extra-ocular manifestations of children with sarcoid-like uveitis

Abstract Background Paediatric sarcoidosis represents a spectrum of disease. Early onset sarcoidosis &amp; Blau syndrome associated with NOD2 mutations are characterized by fever, rash, arthritis &amp; organomegaly. Later onset sarcoidosis has wider organ involvement (lungs, kidneys, lachrymal &amp; extra-ocular glands). Both presentations may lead to long term complications due to end-stage organ damage. Ocular sarcoidosis has a well described uveitis phenotype. We aim to describe a retrospective cohort of children with sarcoid-like uveitis &amp; their systemic manifestations at time of study; compare cohort of patients fulfilling IWOS criteria for ocular sarcoidosis versus who did not; and describe their management in retrospective cohort. Methods We performed a retrospective case review of all children currently followed at GOSH with ocular sarcoidosis phenotype with uveitis (ophthalmologist definition based on IWOS, or diagnosis of idiopathic uveitis with raised ACE level at least once. We collected demographics &amp; all extra-ocular involvement described in sarcoidosis. Results n = 52; 27/52 males. Median age at onset of uveitis 4.20 years (1.41-15.16). 49/52 bilateral uveitis. 27/52 (50%) &lt;8years age at onset &amp; 2/6 NOD 2 + belonged to this group. Median ACE 68 U/L at presentation (0-90U/L). Median maximum ACE 74 (14-420). NOD2 tested in 12 patients: 6+ , 6- . 1/6 positive patient had Blau phenotype. Ethnicity: African 12/52, asian 11/52, caucasian 14/52, unknown 15/52. Uveitis: Anterior 17/52(32.6%), Anterior+Intermediate 1/52, intermediate 5/52(9.6%) , posterior 2/52, panuveitis 25/52(48%), undocumented 2/52. ANA positive (&gt;1:80) in 15/47 (32%). Systemic involvement (n = 52): arthritis 29%, liver 29%, lymphadenopathy 19%, renal 16%, lungs 15.3%, skin 17.3%, spleen 7.7%, glands 1.9%. Patients as per adult IWOS criteria: Definite 12/52, Presumed 6/52, Probable7/52 and Not fulfilling – 27/52. Systemic involvement in patients not fulfilling IWOS criteria (27/52) – renal 14.8%, arthritis 22.2%, hilar or peripheral lymphadenopathy 0 %, skin involvement 7.4%, lung 18.5%, splenomegaly 3.7%. Comparing IWOS fulfilling (25) with the ones who did not (27) – systemic involvement consistently less common in the ones NOT fulfilling but only reaches statistical significance difference for involvement. Lymphadenopathy and skin (p &lt; 0.001 and p &lt; 0.050 respectively). Suggesting that paediatric age group cannot be classified as per the adult IWOS ocular sarcoidosis criteria and needs early systemic screening. Medications used to treat uveitis and/or extra-ocular manifestations: methotrexate alone 25%, methotrexate + adalimumab 21.1%, mycophenolate mofetil 9.61%, only systemic steroids 3.8%. 9 patients- no systemic medications at any time during their disease. Conclusion Most sarcoid-like uveitis patients had at least one systemic involvement. 51.9% patients did not fulfil the IWOS ocular sarcoidosis criteria, still had systemic involvement. Hilar lymphadenopathy criteria cannot be applied to the paediatric population, peripheral more common. ACE not a sensitive biomarker to predict sarcoidosis. 17.3 % had mild phenotype &amp; required no treatment. This study demonstrates the importance of close monitoring for systemic manifestations &amp; highlights good clinical response to steroids, MTX, MMF and anti-TNF. Conflicts of Interest The authors declare no conflicts of interest.

Changes in skin score in early diffuse cutaneous systemic sclerosis are associated with changes in global disease severity.

To determine whether skin score changes are associated with changes in overall disease severity, function and quality of life in early dcSSc patients. A total of 154 and 128 dcSSc patients from the Canadian Scleroderma Research Group database with 1 and 2 year follow-up and a disease duration ⩽5 years without end-stage organ damage and/or significant comorbidity at the initial visit were included. Skin was assessed using the modified Rodnan skin score (mRSS) and disease severity by the summed Medsger disease severity score (DSS) (without skin domain), physician and patient global assessments, function [HAQ disability index (HAQ-DI)] and quality of life [36-item Short Form Health Survey (SF-36) physical component summary (PCS)]. Analyses were repeated in patients with a disease duration ⩽3 years. At 2 years, 64 (50%) patients had improved skin (mRSS decrease of ⩾5 points and/or ⩾25%). Skin improvers had improved summed DSS (P = 0.002); better physician global assessments of disease activity, severity and damage (all P ⩽ 0.003); better HAQ-DI (P = 0.001) and SF-36 PCS (P = 0.005). Changes in the mRSS were positively correlated with changes in summed DSS (P = 0.006) and other disease outcomes. In the 26 (20.3%) patients with worsened skin (mRSS increase of ⩾5 points and/or ⩾25%), the summed DSS and physician global assessments were worse (P = 0.01 and P ⩽ 0.009, respectively). In the subgroup with a disease duration ⩽3 years, similar associations were found. At 1 and 2 years, overall disease improvement parallels skin improvement in early dcSSc. This is important for prognosis and reflects the value of mRSS as an outcome measure in trials with these patients.

MitraClip improves cardiopulmonary exercise test in patients with systolic heart failure and functional mitral regurgitation

AimsThe aim of this study is to evaluate changes in cardiopulmonary exercise test (CPET) after percutaneous mitral valve repair (PMVR) with MitraClip in patients with heart failure with reduced ejection fraction who are potentially candidates for heart transplantation or destination left ventricular assist device.Methods and resultsProspective registry of all consecutive patients with heart failure with reduced ejection fraction and functional mitral regurgitation (MR) underwent elective PMVR between October 2015 and March 2018 in our institution. Patients with preserved or mid‐range left ventricular ejection fraction (>40%), advanced age (>75 years old), or severe co‐morbidities (end‐stage organ damage) were not included. Treadmill exercise testing with respiratory gas exchange analysis was carried out in 11 patients (male, 72.7%; median age, 67 years old) within the month prior to the procedure and at 6 month follow‐up. PMVR was successfully performed in all patients. At 6 month follow‐up, PMVR was associated with an improvement in New York Heart Association functional class (P = 0.021) and a reduction in MR severity (P = 0.013) and N‐terminal pro‐brain natriuretic peptide levels (2805 [1878–5022] vs. 1485 [654–3032] pg/mL; P = 0.012). All patients completed pre‐procedural and post‐procedural CPET, and all the studies showed a respiratory exchange ratio ≥1 and were consistent with sufficient exercise effort. Compared with pre‐procedural CPET, patients showed a significant increase in exercise time (295 [110–335] vs. 405 [261–540] s; P = 0.047), VO2 (9.8 [9.1–13.4] vs. 13.5 [12.1–16.8] mL/kg/min; P = 0.033), ventilatory anaerobic threshold (510 [430–950] vs. 850 [670–1070] mL/kg/min; P = 0.033), peak O2 pulse (7.2 [4.3–8.6] vs. 8.3 [6.2–11.8] mL/beat; P = 0.033), and workload (5 [3–6] vs. 6 [5–8] metabolic equivalents; P = 0.049).ConclusionsPercutaneous mitral valve repair with MitraClip was associated with an enhancement in cardiopulmonary performance in patients with systolic heart failure and secondary MR.