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Background Therapeutic aims in IBDs are to induce remission through rapidly effective treatment. Conventional therapeutic methods including immunosuppression have been available for more than half a century with biological therapies the treatment of choice in patients who fail immunosuppressive drugs. There has been little attempt to longitudinally examine the differences in biopsychological factors and their associations with treatment modalities in IBD patients. Methods 50 IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets and monthly stool and blood samples for inflammatory biomarkers were collected for analysis of association. Microbiome analysis was performed using V4 16SrRNA for identification of microbial phylogenetic relationships. Patients were grouped on whether or not they were in remission and on biological agents. Results At the baseline there were similar ecological indices between the two treatment options in both disease classes; (Shannon, p = 0.380; Pielou’s, p = 0.246; Chao1, p = 0.934). At family level, the CD group showed significant differences (Wilcoxon, p ≤ 0.05) between the treatment received (biologics vs non-biologic) in the abundance of Barnesiellaceae, Bifidobacteriaceae, unclassified Clostridia, and Clostridiaceae (Figure 1A). Results showed similar ecological index values in samples from the two treatment options. Samples in UC groups on biological and non-biologic treatment modes were found to have significantly different microbial communities based on Bray-Curtis dissimilarity (PERMANOVA, p = 0.0031). Microbial family composition in UC group and on two treatment modalities showed a total of 12 families that were significantly different (Wilcoxon, p ≤ 0.05): Acidaminococcaceae, unclassified Bacteroidales, Barnesiellaceae, Christensenellaceae, Clostridiales vadinBB60 group, Coriobacteriaceae, Defluvitaleaceae, Eggerthelaceaem Fusobacteriaceae, Muribaculaceae, Prevotellaceae, and Streptococcaceae (Figure1B). Results identified significant differences in microbial diversity (Shannon index, p = 0.041), and evenness (Pielou’s evenness, p = 0.045) between the two treatment modes. No differences were identified in richness (Chao1) in UC participants. Conclusion Conclusion: Baseline biological indices were mostly similarly distributed between the two treatment options in remissive IBD patients, however biological therapy significantly influenced longitudinal trends of some microbiome dynamics, especially in UC. This suggests an underlying interrelationship between mode of treatment and biopsychological trajectories which might overshadow response to the treatment, requiring further assessment.

Glioblastoma (GBM) is refractory to current T cell-based immunotherapies such as checkpoint blockade. GBM is characterized by extensive infiltration of immunosuppressive macrophages that contribute to the treatment resistance. Here we develop a dual-targeting strategy to synergistically activate tumor-associated macrophages (Mφs), which efficiently overcomes GBM resistance to therapeutic blockade of the PD1 and CTLA4 checkpoints. Consistent with a pro-tumor role of IL-6 in alternative Mφ polarization, we here show that targeting IL-6 by genetic ablation or pharmacological inhibition moderately improves T-cell infiltration into GBM and enhances mouse survival; however, IL-6 inhibition does not synergize PD-1 and CTLA-4 checkpoint blockade. Interestingly, anti-IL-6 therapy reduces CD40 expression in GBM-associated Mφs. We identify a Stat3/HIF-1α-mediated axis, through which IL-6 executes an anti-tumor role to induce CD40 expression in Mφs. Combination of IL-6 inhibition with CD40 stimulation reverses Mφ-mediated tumor immunosuppression, sensitizes tumors to checkpoint blockade, and extends animal survival in two syngeneic GBM models. Notably, this antibody cocktail-based combination immunotherapy with checkpoint blockade almost doubles animal survival in the genetically engineered mouse GBM model and induces complete tumor regression in the GL261 model. Thus, antibody cocktail-based immunotherapy that combines checkpoint blockade with dual-targeting of IL-6 and CD40 may offer exciting therapeutic opportunities for GBM.

Background Advanced HIV infection is associated with an inflammatory arthritis, however few reports have described this disorder in children. This study aimed to describe the clinical features of HIV arthropathy in a case series of children in South Africa and compare these with features of JIA. Methods Retrospective data were collected from HIV-infected children with HIV arthropathy enrolled in a Paediatric Rheumatology clinic in Cape Town, South Africa. Data from a recently described, published cohort of children with JIA enrolled in the same clinic were included for comparison. Ethical approval was granted by the Human Research Ethics Committee of the University of Cape Town, with a waiver for consent. Results Eleven cases of HIV arthropathy were identified. Cases predominantly affected boys (8/11), and the median age of onset was 10.3 years (IQR 6.9–11.6). Most cases presented in the setting of advanced immunosuppression, with a median absolute CD4+ count of 389 cells/uL (IQR 322–449) and median CD4+ proportion of 19.5% (IQR 14.8–25.0) at presentation. The clinical presentation was variable, with both oligoarthritis (6/11) and polyarthritis (5/11) being prevalent. All cases exhibited large joint involvement, which was usually asymmetrical. In addition, four children had asymmetrical small joint involvement. Associated features included enthesitis (4/11) and dactylitis (1/11). The most consistent laboratory feature was elevated acute phase reactants, and typical ultrasonographic findings were joint effusions and synovial hypertrophy. JIA and HIV arthropathy presented at a similar age, with median age at HIV arthritis onset of 10.3 years (IQR 6.9–11.6) versus 9.25 years (IQR 4.5–12.3) at arthritis onset in the JIA subgroup. HIV arthropathy cases were predominantly male (M/F ratio 3.0), whereas JIA cases had an equal sex distribution (M/F ratio 0.9). Oligo-articular disease was more frequently described in children with HIV arthropathy (55%), compared to those with JIA (38%). Conclusion In this series, most cases of HIV arthropathy exhibited asymmetrical large joint oligoarthritis or polyarthritis, and presented in older boys with advanced immunosuppression. HIV arthropathy appears to present at a similar age to JIA, with a comparable pattern of joint involvement to oligo-articular and poly-articular JIA subtypes.

Background A two-dose hepatitis B (HBV) vaccine with an immunostimulatory adjuvant (HBV-ISS, Heplisav-B), was FDA approved in 2017 for adults 18 years and older. In randomized controlled trials (RCTs), HBV-ISS demonstrated a seroprotection rate (SPR) of 90–95% versus 65–80% for Engerix-B (HBV-Eng). No RCTs, however, included people with HIV (PWH), and the SPR and its predictors in this population are unknown. Methods This retrospective cohort study enrolled PWH ages 18 years and older without current HBV seroprotection at an HIV clinic at a tertiary care center. HBV seroprotection was defined as an anti-HBV surface antibody level >= 10 mIU/mL. Patients without follow-up titers after immunization were excluded. The primary outcome was the SPR, the proportion of patients with HBV seroprotection at any point following the first HBV-ISS vaccination. Results Among the 51 PWH included, 50 received 2 doses of HBV-ISS (1 patient who received 1 dose developed seroprotection) (Table 1). Median time to antibody titer measurement was 11 weeks (IQR 7–19 weeks). Median age was 59 years, 90% were men, and 96% had VL < 200. There were no pregnant or breastfeeding patients. The SPR was 82% (42/51) in the cohort, and 86% (38/44) when patients with significant non-HIV immunosuppression (decompensated cirrhosis, solid organ transplantation, active chemotherapy) were excluded. There were no significant differences in SPR based on age, sex, BMI, diabetes mellitus, chronic kidney disease, history of remote anti-HBV surface or core antibody positivity, or prior HBV vaccination (Table 2). Lower current and nadir CD4+ counts were associated with progressively lower SPRs (P for trend < 0.0001 for both) (Figure 1). Table 1. Baseline Demographics and Characteristics Table 2. Seroprotection Rate (SPR) by Variables of Interest Figure 1. Seroprotection Rate (SPR) by Current and Nadir CD4+ Count Conclusion The SPR from HBV-ISS in PWH appears comparable to the immunocompetent patients included in RCTs, especially when patients with significant non-HIV immunosuppression are excluded. The SPR demonstrated in this single-arm, retrospective study was higher than that of HBV-Eng in immunocompetent patients, and consideration should be given to establishing HBV-ISS as first-line HBV vaccination in PWH. Finally, SPR is significantly reduced in those with lower current and nadir CD4+ counts. Further research on the effectiveness of a repeat vaccination series or higher dosing in these subgroups is needed. Disclosures Jennifer Cocohoba, PharmD, AAHIVP, BCPS, Viiv (Grant/Research Support)

Background and Aims The outcome of Plasma cell-rich acute rejection (PCAR) in kidney transplant is reported to be poor. However, PCAR which can be associated with any type of rejection, may not be considered as independent morphological prognostic feature. Different treatment modalities were prescribed with variable responses. We report here four cases of PCAR and describe their presentations, type of rejection, associated conditions and treatment outcome. Method Out of 1920 kidney transplant recipients under follow up in our centre from 1996 till 2019, four patients were reported to have PCAR according to 2007 Banff classification. They were re-evaluated based on 2015 Banff classification. The treatment protocol was tailored according to the type of rejection and associated conditions. Results The four patients, aged 28, 44, 46 and 54 years, had live unrelated renal transplant done somewhere abroad with no data about donor HLA typing. Two of them were females. One had high PRA and she was positive for HBsAg. One patient received induction immunosuppression with basiliximab. They all received prednisolone, mycophenolate and cyclosporine as the maintenance immunosuppression and had immediate graft function. Rejection happened between 23 to 180 months post-transplant. Two patients had acute T-cell mediated Banff 1A rejections with features consistent with early membranous nephropathy. One had acute T-cell mediated rejection Banff 1B and the fourth had borderline T-cell mediated rejection with morphological changes suggestive of chronic active antibody mediated rejection (AMR). Plasma cells constituted 10 to 30% of the interstitial infiltration. All patients received solumedrol pulse. Both patients with features of membranous nephropathy received rituximab and one of them had additionally IVIG. The patient with AMR received plasma exchange and IVIG. However, she did not receive rituximab as she was positive for HBsAg. All patients responded well to treatment and the mean improvement in eGFR was 12.8%, 24.9%, 40.3% and 39.1% at 1-, 3-, 6- and 12-months post treatment. Repeat kidney biopsy at 3 to 12 weeks post treatment showed resolution of plasma cell infiltration in all patients. Conclusion Outcome of PCAR management was favourable among our patients irrespective of the type of rejection and associated conditions.

Background and Aims Emphysematous pyelonephritis (EPN) is an uncommon, acute and severe form of necrotizing infection of the renal parenchyma, collecting system and/or perinephric tissues and is characterized by accumulation of gas within these structures. Patients may present with fever, loin pain, vomiting and shock. Risk factors for EPN include diabetes mellitus (DM), renal stone, obstructive uropathy and immunosuppression. In this report, we describe the clinical, laboratory and imaging characteristics of patients with EPN in Bangladesh. Method This systematic review included all previously published English literature containing information regarding EPN in/or from Bangladesh. Literature search was conducted via “PubMed” using the key words “Bangladesh” and “emphysematous pyelonephritis”. We also searched through Bangladesh Journals Online (BanglaJOL) for articles published in local journals. The search engine “Google” was also used to identify articles. All literature searches were conducted up to 10th January 2021. Unpublished but well-documented EPN cases (28 cases) were added. Cases mentioned elsewhere with inadequate information and possible repetition were excluded. Results Seventeen papers were identified from published literature including 10 case reports, two original research articles, one image and four conference abstracts and one research paper was identified from other source. From them, two case reports were excluded because EPN occurred in non-Bangladeshi nationals; one image and four conference abstracts were also excluded because of inadequate information for cases. Finally, a total of 10 papers (total 92 cases) were eligible for analysis, to which 28 unpublished but well documented cases were added. Among the total 120 cases, females were 92 (76.7%). Age of the patients ranged between 20 and 77 years. DM was the commonest risk factor (118, 98.3%); 16 (13.3%) patients had chronic kidney disease and nine (7.5%) had renal stones. Patients presented with fever (112, 93.3%), loin pain/renal angle tenderness (96, 80%), dysuria (76, 63.3%), altered sensorium (21, 17.5%), anorexia (93, 77.5%), vomiting (101, 84.2%), dehydration (77, 64.2%) and shock (18, 15%). Patients had neutrophil leukocytosis (total white cell counts 11,700–54,200/cmm of blood) and 22 (18.3%) patients had thrombocytopaenia. All patients had high erythrocyte sedimentation rate (36–117 mm/1st h) and C-reactive protein (24–199 mg/L). Overall glycaemic status was poor [random blood glucose during admission was 6.8–35.5 mmol/L and glycated haemoglobin (HbA1c) was 6.2–16.1%]. Fifty six (46.7%) patients were complicated by acute kidney injury (AKI) and 32 (26.7%) patients had hyponatraemia. Diagnosis of EPN was confirmed by computed tomography scan. One patient had EPN in ectopic right kidney, two patients had EPN along with emphysematous cystitis and two patients were complicated with psoas abscess. According to Huang and Tseng classification, five (4.2%) patients had class 4 EPN, 35 (29.2%) patients had class 3, 66 (55%) patients had class 2 and 14 (11.7%) patients had class 1 EPN. Escherichia coli was the most common (67, 55.8%) organism identified on urine culture and 17 (14.2%) patients were complicated by bacteraemia. All patients were treated with resuscitative measures, intravenous antibiotics and other supportive measures. Forty one (34.2%) patients required surgery/interventions [nephrectomy in 19 (15.8%), percutaneous drainage in two (1.7%), open drainage in 20 (16.7%)]. Duration of hospital stay was 6–37 days. Nine (7.5%) patients died in hospital. Conclusion EPN occurred predominantly among female diabetic patients. Clinical presentation included fever, loin pain, dysuria, vomiting, altered sensorium and shock. Class 2 EPN was common. Almost half of all EPN cases developed AKI. One-third EPN cases required surgical interventions including nephrectomy. In-hospital mortality was 7.5%.

Background and Aims Kidney transplantation (KTx) in pediatric ages is successful, leading to optimal patients and graft survival with indication, in adolescent age, to transition toward an adult transplant facility. To date, the transition process of adolescents and young adults with KTx is not well defined. Transfer to a different medical facility marks a vulnerable phase in the adolescents’ lives with an increased risk for non-adherence and allograft failure. Some studies report unexpected loss rates in kidney grafts as high as 24%–42% within 3 years after transfer. In addition, some studies show that the age ranging from 18 to 26 years is the age in which graft losses are most concentrated, an age that coincides with the transition. Several makers have been shown to influence non-adherence rate in kidney transplanted patients during transition: a bad doctor-patient relationship, the absence of specialized centers capable to face these particular needs and care requests, the lack of psychological support, and a low availability of specialized nurses. Moreover, many patients are lost to follow-up as the result of breakdowns in the transition and transfer to adult medical care. Method In this study we enrolled patients transited from the pediatric transplant Centre to the adult transplant nephrological facility between 2017 and 2020. Data of KTx, baseline renal disease, post-transplant medications and post-transplant complications were recorded. Follow-up of renal function were performed and analyzed during the transition process and forward during the adult follow-up. Results Data of 19 patients (pts) were analysed. Six were male (31.6%) and 13 female (68.4%). The cause of renal dysfunction was malformations in 10 patients (52.6%), glomerulonephritis (GN) in 5 pts (26.3%) and genetic syndromes in 4 pts (21.1%). They received the kidney transplantation at a median age of 12 years [IQR 10-18]. Median age at transition resulted 31 years [interquartile range (IQR) 30-33]. Seven pts (36.8%) had a history of post-transplant lymphoproliferative disease (PTLD). All patients were receiving steroids, 11 pts (57.9%) cyclosporine A and 8 pts (42.2%) tacrolimus; only 9 pts (47.4%) were receiving mycophenolate or azathioprine. The median follow-up at the adult Transplant Centre was 1 year [IQR 1-2]. After transition, five patients experienced complications: 2 pts developed PTLD de novo, 2 pts had a recurrence of native GN after reduction of immunosuppression for PTLD and pregnancies (one pt underwent re-tx), 1 pt experienced an acute cellular rejection after transition to another Centre and is developing ESRD. The median eGFR slightly decreased from baseline at transition to the last follow-up (80 ml/min/1.73 m2 at baseline [55-112]; 74 ml/min/1.73m2 at last follow-up [35-98]) but this was not significant (p=0.127). Conclusion Our results confirm that the transition from pediatric to adult transplant Centre is not a simple process. Several factors linked to the patient and to the kidney have to be considered in the development of post-transplant complications: the age of transplantation with long term immunosuppression; infections typical of pediatric ages that may develop in adulthood, such as EBV, that force to modulate immunosuppression exposing the patient to increased risk of rejection or recurrence of native disease; the exposure to different immunological stimuli and physiological events such as pregnancies in female patients. These patients may develop complications linked to non-adherence and low compliance to immunosuppressive medications, but also complications typical of adult age, like arterial hypertension, obesity, diabetes, and dyslipidemias. Therefore, defining effective practices for recipient transition and transfer from pediatric to adult medical care are essential to optimize the KTx patients follow-up and outcome.

Background and Aims Number of older patients with end stage kidney disease has been increasing, therefore there are increased number of older kidney transplant recipients. Potent immunosuppression (IS) used in patients after kidney transplantation (KTx) lowered the incidence of acute kidney rejection but increased the risk of post-transplant infection and sepsis as the most common non-cardiac cause of death. Older adults are at high risk of infections due to functional impairment and multiple comorbidities leading to poor outcome after KTx. Nowadays, no change in IS or prophylactic therapy is recommended based on the age of an adult KTx recipient. Female gender may be risk factor for infection after KTx due immunomodulatory effect of sex hormones such as estradiol. Methods The aim of our analysis was to find whether there are sex differences in the incidence of single and repeat infection and whether there is increased incidence of single and recurrent infectious complications in older kidney transplant recipients. Results Our analysis consisted of 100 patients after KTx (66 males, 34 females), average age 47,5 ± 12,6 years, treated with anti-thymocyte globulin as an induction IS. Male gender was a protective factor for the incidence of following infections in the 1st month after KTx: infection in general (P = 0.0054), recurrent infection (P = 0.0239), bacterial (P = 0.0125) and mycotic infection (P = 0.0103), recurrent bacterial infection (P = 0.0258). From the 1st to 6th month after KTx, female gender was identified as a risk factor for the incidence of infection in general (P = 0.0218), bacterial (P = 0.0186) and mycotic infection (P = 0.0318), repeat infection (P = 0.0216), recurrent bacterial infection (P = 0.0368). From 6th to 12th month after KTx, female gender was found as a risk factor for the incidence of bacterial infection (P = 0.0144), single infection (P = 0.0355), recurrent infection (P = 0.0007), single bacterial infection (P = 0.0309). Age > 60 years was not found as a risk factor for the incidence of single, repeat infection regarding its etiology. In our analysis we did not found correlation between gender and the incidence of single or recurrent infection of any etiology, we did not find significant differences in the severity of infections reflected by need for hospitalization, intensive care unit or use of vasopressors neither in gender, nor in older patients. In our study we did not confirm gender or age as a risk factor for the acute kidney rejection. Conclusion In our analysis, we found significant sex differences in the incidence of bacterial, viral, mycotic, single and repeat infection in different time intervals after kidney transplantation, while we did not confirmed age > 60 years is a risk factor for the infectious complications after KTx.

Background and Aims The efficacy and safety of intravenous ferric carboxymaltose (FeCarb) has been demonstrated both in patients with chronic kidney disease and dialysis, but its effects have not been evaluated in kidney transplant (KT) recipients. Method Retrospective study (2016-2018) of KT recipients who received FeCarb during the first 30 days after kidney transplantation (KT). Early efficacy was analyzed by evaluating the first determination of ferrokinetics and hemoglobin levels after administration and late efficacy with the determination >90 days post-administration. Safety parameters were also analyzed. Results Out of 283 KT performed, 77 recipients received one dose of FeCarb (52 received a 500mg dose and 25 a 1000mg dose) after a median of 6 days after the KT (IQR 3.5-9 days). 24 patients required transfusion after administration, 7 of them in the setting of concomitant event and 17 for non-response to FeCarb. Among the non-responders (n=17) there was a higher percentage of women, the initial hemoglobin was lower and they received a higher dose of FeCarb (Table). Responders (n=53) improved early and late ferrokinetic and anemia parameters (Figure). In the multivariate analysis adjusted by gender, controlled infection at the time of FeCarb administration, dose of FeCarb administered, immunosuppression, and previous treatment with erythropoietin, hemoglobin levels below 8 g/dL were associated with increased risk of transfusion after FeCarb administration (HR 11.30 [3.03-42.2]). Tolerability was excellent, with no immediate adverse reactions after FeCarb administration. 17 responders had a controlled infection at the time of FeCarb administration (median days under antibiotic treatment: 3, IQR 1-5). The infection did not worsen the response to FeCarb and no clinical impairment after FeCarb administration was observed. Conclusion: FeCarb administration in early post-transplant anemia is effective in patients with hemoglobin higher than 8g/dl and is not associated with increased risk of infection deterioration.

Glioblastoma is associated with severe and multifaceted immunosuppression affecting all immune organs. Immunosuppression in GBM is a critical barrier to the success of immunotherapies and patient survival. We demonstrated that immunosuppression in the GL261-model of experimental GBM presents with significant thymic and spleen atrophy, MHCII downregulation, presence of potent immunosuppressive factors in serum, and sequestration of T-cells in the bone marrow. Parabiosis studies determined that soluble factors mediate immunosuppression by inhibiting T-cell proliferation, thymic involution, and loss of peripheral T-cells. In contrast, bone marrow T-cell sequestration was not mediated through soluble factors. While the immunosuppression in GBM is severe, a causative link between each facet of immunosuppression and overall survival is lacking. We used two strategies to block T-cell sequestration into the bone marrow and evaluated the extent survival was impacted in experimental GBM. First, we evaluated the extent a novel and off-the-shelf combination immunotherapy that uses extended 1/2-life IL-2 and anti-PD-1 reverses bone marrow T-cell sequestration. Sham treatment or anti-PD1 monotherapy did not alter T-cell sequestration in the bone marrow and animals had no enhanced survival. Extended 1/2-life IL-2 monotherapy and combination strategy both prevented T-cell sequestration into the bone marrow. However, only combined therapy, which also prevented MHC class II downregulation, improved survival. Second, we determined that glioma-bearing adrenalectomized mice do not present with bone marrow T-cell sequestration. However, sera of glioma-bearing adrenalectomized mice is as immunosuppressive as glioma-bearing controls. Blocking bone marrow T-cell sequestration in the presences of serum immunosuppression led to no survival benefit in glioma-bearing adrenalectomized mice compared to controls. In short, bone marrow T-cell sequestration alone does not correspond with overall survival in experimental glioma. Importantly, a concerted effort to reverse MHC class II downregulation and define inhibitory circulating factors may have the highest impact in immunotherapeutic efficacy and improving patient survival.

Case report - Introduction Granulomatosis with Polyangiitis (GPA) is a rare small- to medium-vessel vasculitis associated with anti-neutrophil cytoplasmic autoantibody (ANCA). Its multi-systemic features include pulmonary, ear, nose, and throat (ENT), renal, and neurological manifestations. Its incidence is estimated to be 10.2 cases per million population. It is challenging to diagnose when its symptoms are treated in isolation from one another. This case highlights the difficulty in diagnosing GPA in a patient with respiratory symptoms during the Coronavirus Disease 2019 (COVID-19) pandemic and describes the challenges of managing it in the context of a subsequent COVID-19 infection as the mainstay of treatment remains immunosuppression. Case report - Case description A 78-year-old female non-smoker with a history of leg ulcers developed a 3-month history of cough and haemoptysis and was treated in primary care for suspected sinus and chest infections. She then presented to Accident and Emergency twice for the same symptoms and was discharged after having her antibiotics changed. 2 weeks later, she presented for the third time with cough, ongoing haemoptysis, conjunctivitis in the right eye, pain over the right side of her head, and discharge from her right ear. She was admitted as she was pyrexical, tachycardic and her CRP was 60. COVID-19 swabs were negative. ENT team recommended IV ceftriaxone and metronidazole for suspected orbital cellulitis. Blood cultures remained negative. CT sinuses with contrast showed right sided thrombosis of transverse sinus and bilateral mastoid effusion of the middle ear. Following neurology review, she was anticoagulated with dalteparin. A day later, she was transferred to the Respiratory ward and dropped her Haemoglobin level to 70. Her chest radiograph showed diffuse alveolar haemorrhage and CT images showed widespread bilateral peri-hilar consolidation. A rheumatology opinion was sought and vasculitic screen showed ANCA 268, and PR3 >177. Her urinary protein/creatinine ratio was elevated at 90. Rheumatology team confirmed multi-systemic GPA and recommended starting oral Prednisolone 60 mg daily. After the renal team was consulted, she was moved to a side-room and started on IV Methylprednisolone (pulsed with three doses), along with cyclophosphamide and rituximab. Dalteparin was discontinued. 2 days later, she desaturated, and became pyrexical. Repeat COVID-19 swabs were positive. Three Consultants agreed that Plasma Exchange and Non-Invasive Ventilation (NIV) would be inappropriate. A Do Not Attempt Resuscitation form was signed, and prognosis was discussed with the patient and her 78-year-old husband who requested to visit. Patient deteriorated and unfortunately died 6 days later. Case report - Discussion This case is interesting because it highlights the diagnostic challenge of GPA. Retrospectively, it may be noted that doctors persisted in treating suspected infection although the patient continued to deteriorate. However, a diagnosis should be re-considered if the patient does not respond to treatment and it is important to consider vasculitis as a cause of haemoptysis. Anticoagulation was started since the benefits were considered to outweigh the risks as her haemoptysis was of small volume. The patient soon developed pulmonary haemorrhage, so the risks of anticoagulation should not be underestimated in vasculitis. The Rheumatology team’s cautious approach to immunosuppression was in stark contrast to the renal team’s aggressive approach. The Renal team believed that concerns about protecting the patient from COVID-19 when she was negative from this infection should not take precedence over appropriate immunosuppression from a potentially fatal vasculitis. The patient was admitted at the start of the COVID-19 pandemic and was negative for COVID-19 on admission. She was nursed in a bay on the Respiratory ward where she later became COVID-19 positive. This raises questions about whether the earlier test was a false negative result or whether her infection was hospital-acquired. Infection control guidelines were changing rapidly at the start of the COVID-19 pandemic. The decision to avoid plasma exchange was based on the findings of the PEXIVAS trial. NIV was avoided as it required a full-face mask to minimize particle dispersion but would pose an asphyxiation risk as patient was coughing up blood. Finally, the team learnt to be flexible in these extraordinary circumstances when dealing with the end-of-life decisions of the COVID-19 positive patient. Although her husband was a vulnerable person because of his age, he was given the opportunity to visit while wearing Personal Protective Equipment and agreed to self-isolate for two weeks. Case report - Key learning points This case helped me appreciate the complexity of deciding to immunosuppress an already severely ill patient in the context of the COVID-19 pandemic. I recognised that the patient had a poor prognosis with or without immunosuppression and our role as healthcare professionals was to give her the best chance of recovery. The conference will allow me to interact with other colleagues and discuss what they would do in this situation as our Rheumatology and Renal teams had different approaches. After further reading on false negative results, we found that Johns Hopkins researchers found that testing people for SARS-CoV2 too early in the course of infection is likely to result in a false negative test even though they may eventually test positive for the virus. I have also learnt about the PEXIVAS trial which found that the addition of plasma exchange to standard therapy does not reduce the risk for all-cause mortality among patients with severe ANCA-associated vasculitis. Moreover, a reduced-dose regimen of glucocorticoids is non-inferior to a standard-dose protocol, while reducing the risk for serious infections. Diffuse alveolar haemorrhage (DAH) is not treatable with arterial embolization or bronchoscopic methods due to the diffuse nature of the bleeding. Extracorporeal membrane oxygenation (ECMO) has been used to support patients with DAH but the use of ECMO is controversial due to the need for anticoagulation. The conference will help me deepen my understanding of epidemic rheumatology which will be useful for my clinical practice going forward, especially if there is a second wave of the COVID-19 pandemic. I am keen to use this event to engage with other clinicians on immunosuppression in the context of infection so that I may confidently manage similarly complex cases in the future.

Case report - Introduction Primary Sjögren’s syndrome is a systemic autoimmune disease affecting the exocrine glands, commonly resulting in dryness of mouth and eyes. It can also rarely present with neurological symptoms most commonly peripheral neuropathies. The case highlights a rare case of sensory and motor neuropathy with some features suggestive of Sjögren’s syndrome as an underlying diagnosis. Case report - Case description A 54-year-old Caucasian lady was transferred from a local hospital for specialist neurology care. She described widespread paraesthesia over two months progressing to lower limb weakness worsening over a two-day period. Her symptoms further progressed to involve her arms and new blurred vision. On further questioning she reported previous severe mouth ulcers, possible genital ulcers and painful jaw swelling with long standing history of dry mouth. On thorough neurological examination, the positive findings were mild ptosis of the right eye, paraesthesia on palpation of face, upper limbs had a flaccid tone with reduced power and pseudoathetosis of outstretched arms, reduced proprioception, and absent reflexes. Lower limbs were more affected with worse power and absent proprioception. Schirmer’s test showed normal tear production but saliva production was reduced. MRI brain and spine were reported as pathological enhancement in both optic nerves, no obvious brain parenchymal abnormality, no obvious spinal cord abnormality. Lumbar puncture CSF pro 0.38, white cells 12 (poly 50%, mono 50%), red cells 3700, no organisms on gram stain, opening pressure 21.5 cmH2O. Sural nerve biopsy demonstrated profound loss of sensory axons, severe loss of large myelinated fibres in all fascicles with motor nerve involvement. Muscle biopsy demonstrated chronic neurogenic atrophy. Rheumatology screen showed positive anti Ro 52 antibodies (on an extended myositis screen). EMG demonstrated neurophysiological evidence of widespread marked loss of sensory axons in the upper and lower limbs and partial loss of motor axons in several lower limb territories. USS parotid glands showed some possibly mildly abnormal areas, minor salivary gland biopsy was normal. She received methylprednisolone, IV immunoglobulin and two courses of plasma exchange. Given some improvement following this treatment, further immunosuppression was felt to be appropriate. Initially Mycofenolate mofetil was started and Rituximab is now being considered. Case report - Discussion This case demonstrates a mixed neuropathy picture. Following thorough investigations, many differential diagnoses of mixed neuropathy were considered and excluded (e.g. Guillain Barre, Syphilis, MS, HIV, Hepatitis). Neurological symptoms can develop before the onset of sicca symptoms in Sjögren’s syndrome. With a positive Anti Ro52, xerostomia and clinical improvement with methylprednisolone and plasmaphereses it seems likely there is an underlying autoimmune diagnosis in this case and despite a normal biopsy she would meet the 2016 ACR/EULAR classification criteria for Sjögren’s syndrome. Case report - Key learning points Sjögren’s syndrome should be considered as a potential underlying cause in patients with a sensory ganglionopathy. Neurological symptoms can develop before the onset of sicca symptoms in Sjögren’s syndrome.

Background The European Society of Cardiology (ESC) guidelines for the diagnosis and management of pericardial diseases identify predictive factors of poor prognosis and advise either in favour or against hospitalisation accordingly. Our aim is to evaluate the adequacy of hospitalisation criteria in a cohort of patients presenting to the emergency department (ED) with acute pericarditis. Methods Retrospective analysis of patients admitted in ED with acute pericarditis, from 2009 to 2019. All patients were evaluated by a cardiologist during ED stay who decided if the patient was to be discharged or hospitalized. Hospitalized and discharged patients were compared regarding primary outcome, defined by a composite of: need for pericardiocentesis and/or cardiac surgery, pericarditis recurrence and all-cause death. Clinical decision was then counterpoised with ESC guidelines. Results A total of 192 patients were included in the analysis (aged 46±18.5 years-old, 83.3% male) of which 87 (45.5%) were hospitalized. A total of 25% registered the primary outcome, mainly due to acute pericarditis recurrence, occurring in 21.9%. Predictors of recurrence were: glucocorticoid therapy (OR=11.93, 95% CI 3.13–45.5, p Conclusions Discrepancy between current guidelines and clinical decision did not translate into a different outcome. Funding Acknowledgement Type of funding source: None

Case report - Introduction Primary Sjögren’s syndrome (PSS) is a systemic autoimmune disease that mainly affects exocrine glands. Central nervous system (CNS) involvement in primary SS is extremely rare. In 10–20% of patients diagnosed with PSS, there are lesions in the central nervous system analogous to those presented in multiple sclerosis. We report a case of a 58-year-old female, diagnosed as PSS and multiple sclerosis (MS) (2007), but later, all neurological manifestations turned out to be related to PSS rather MS. This case illustrates how difficult it could be, distinguishing Sjögren’s with CNS involvement from MS, even to an expert clinician. Case report - Case description A 58-year-old lady presented to Rheumatology clinic in 2010 with polyarthralgia, sicca symptoms and Raynaud’s. Immunology tests (positive anti- RO & anti-LA antibodies) and lymph node biopsy were highly suggestive of primary Sjögren’s. She was commenced initially on HCQ and prednisolone. Then Methotrexate was added in because she continued to struggle with inflammatory arthritis. Her Sicca symptoms got gradually worse despite being on Acetylcysteine, Hylo Forte, cyclosporine and Dexamethasone eye drop. Therefore, autologous serum eye drops were tried with good response. Her past medical history included Hypertension and knee OA. She has been under Neurology since 2007 for MS. Her original neurological symptoms were imbalance, dizziness, headaches, and tremor of the right arm which seem to be persistent with no definite relapses. MRI brain and spine were reported as normal with a few non-specific white matter areas, but the lumbar puncture result was positive for unmatched bands in the CSF. Clinical examination revealed action tremor in the right upper limb. She had diminished vibration, pinprick, and cold temperature perception in a stocking distribution. Investigations WBC 2.0, lymphocyte 0.62, DsDNA 1, C3 0.061, C4 0.01. CRP NCS: evidence of sensory and axonal neuropathy predominantly affecting lower limbs. CTCAP 2018 – showed calcification of parotid. No evidence of lymphoproliferative disorder. The latest MRI 2019 showed two new lesions (right corpus &right striatum lesion) which according to Neuro-radiology MDT discussion were not typical of MS and more likely related to underlying CTD. Based on these MRI findings and the recent history of skin vasculitis, the deterioration in her neurological condition was put down to primary Sjögren’s. Therefore, her treatment was escalated to cyclophosphamide during the COVID-19 pandemic with a particularly good outcome. She was then switched to MMF and her condition remained stable. Case report - Discussion Neurological disorders are one of the rare manifestations of primary Sjögren’s. The first reports regarding the involvement of the nervous system in PSS were published in 1980. Distinguishing between multiple sclerosis and CNS-SS is not easy. Not only because of similarities of the MRI findings, but also the course of the disease can be like MS, either chronic or relapsing and remitting. This usually leads to missing or delaying in the diagnosis as shown in this case. However, Peripheral neuropathy is far much common in PSS rather MS which can help in differentiating these two conditions. Distal axonal sensory polyneuropathy is the most usual form of neuropathy in PSS as illustrated in this case. Furthermore, up to 75% of patients with SS and active CNS disease have been shown to have concomitant active peripheral vasculitis affecting the skin, muscles, and nerves. Our patient later developed skin vasculitis and peripheral neuropathy which made us think that all the neurological findings including the lesions on the brain are more likely to be related to PSS rather MS. Cognitive disorders are common manifestations of CNS-SS such as attention disorder and memory deficit. Dementia-related to CNS-SS seems to be reversible after immunosuppressive treatment. A second MDT discussion took place and after considering the risk-benefit ratio, the decision was made to give cyclophosphamide. Patient was given all the information to make an informed decision. Patient asked for more time to think and discuss with her partner, but eventually, she had decided to have cyclophosphamide despite all the risks and uncertainties around the COVID-19 pandemic. Our patient has noticed significant improvement regarding cognition after completing cyclophosphamide treatment and she was pleased with this outcome. Case report - Key learning points 1/ Distinguishing between multiple sclerosis and CNS-SS is difficult 2/ neurophysiological tests should be considered even in asymptomatic patients as they contribute to the detection of early and subtle damage to the nervous system. 3/ Successful outcome being achieved with intensive immunosuppression despite all the uncertainties around the COVID-19 -19 pandemic. 4/ This case highlights the importance of communication and openness in shared decisions, especially while confronting uncertainties such as in COVID-19 pandemic.

Case report - Introduction 15 year old girl with the diagnosis of granulomatosis polyangiitis (GPA) managed with induction regimen of intravenous cyclophosphamide and whilst on maintenance mycophenolate mofetil (MMF) developed multiple cavitating lung lesions with the large cavity abutting pulmonary vein and bilateral segmental pulmonary embolism (PE) posing complex management dilemmas. Case report - Case description 15-year-old girl presented with being unwell for 3 months with malaise, lethargy, joint pains, significant weight loss (10 kg), mouth ulcer and significant hearing loss. Investigations showed anaemia, raised inflammatory markers, and impaired kidney function (estimated glomerular filtration rate eGFR 40). Her ANCA was positive, hearing test showed significant mixed hearing loss and CXR was normal. The renal biopsy confirmed pauci-immune ANCA associated glomerulonephritis with 70% crescents. She was initially managed with intravenous pulse of steroids followed by oral weaning regime, double filtration plasmapheresis and commenced on induction regimen of intravenous cyclophosphamide. She received 6 doses of cyclophosphamide 500 mg/m2 and following good recovery with normalising kidney function; was commenced on maintenance MMF. At this point she developed new onset earache, sore throat, and hoarseness of voice with raised inflammatory markers and worsening symptoms despite antibiotics. This was presumed to a flare of vasculitis and hence was given further pulse of steroids and increased the dose of MMF. The ENT assessment did not reveal any subglottic stenosis. After few weeks, symptoms recurred with cough/hoarseness of voice and associated tiredness. Bloods showed raised inflammatory markers; CXR revealed cavitating lung lesions and a CT chest was arranged. CT chest showed apical sub pleural lung nodule and a large thick-walled cavity measuring 6.6x 4.4 cm abutting the pulmonary vein on the right side and bilateral segmental pulmonary emboli. The child was systemically stable with no respiratory distress and oxygen saturations were 100% in air. Case report - Discussion The management of GPA was further complicated by the pulmonary embolism and cavitating lung lesions abutting pulmonary vein. The management included escalation of immunosuppression with pulse of steroids, further dose of cyclophosphamide and commence Rituximab .The key challenges with the immediate management were risk of bleeding associated with the anticoagulation, treating the pulmonary embolism, risk of diffuse alveolar haemorrhage and managing the patient in a safe setting equipped with all the expertise required. The child was screened for cardiolipin antibodies on multiple occasions and these were negative. An ECHO was done to look for evidence of clot at the end of central line tip, but this was normal. Deep venous thrombosis of legs was ruled out by Doppler scanning. There was no clear source of emboli identified. Although there is emerging evidence for increased incidence of vascular events in GPA adult patients, the data on vascular events in children with GPA is scarce. Merkel and co-workers reported a high occurrence of pulmonary embolism (PE) and deep venous thrombosis (DVT) among GPA patients included in a randomized therapeutic trial (WeCLOT study) 1 .FAURSCHOU et al. reported that GPA was associated with a much lower relative risk of stroke than of pulmonary embolism and deep venous thrombosis; the risk of venous thromboembolic events among GPA patients was increased during early as well as late follow up periods. Currently there are no significant data on the use of antiplatelet and/or anticoagulant therapy in AAV. Following extensive multidisciplinary discussion with respiratory, haematology, cardiology, cardiothoracic surgical and paediatric intensive care teams, and the child was anticoagulated with close monitoring in paediatric high dependency unit and immunosuppression escalated alongside. Case report - Key learning points This case highlights the risk of thromboembolic events in children with GPAProposed mechanisms in the literature for thrombosis in vasculitis at molecular level would probably explain the episode in the absence of source identifiedMultidisciplinary team approach is crucial for management of complex patientsThere were few challenges due to geographical location of the patient and the regional variation of subspecialty cover provided for their local District General HospitalFor discussion- Role of Rituximab early in GPA?

Background and Aims The reported incidence of lupus nephritis (LN) is approximately 6.1 cases per million population per year in Scotland based on Scottish Renal Registry biopsy data. Despite immunosuppressive treatment, approximately 10-30% of patients will progress to established renal failure (ERF) within 15 years. In December 2007, our unit moved from a protocol of Cyclophosphamide/ steroid induction with Azathioprine/ Prednisolone maintenance to Mycophenolate/ steroid induction and maintenance. We undertook this study to compare remission rates before and after this change. Method A retrospective electronic patient record analysis was performed for all patients in our centre with a documented native renal biopsy showing a histopathological diagnosis of LN, between 1 July 1993 and 31 December 2017. Repeat biopsies were excluded. Baseline demographics, histopathological class and first and second line induction and maintenance therapies were recorded. Endpoints analysed were; partial and complete response (as defined in KDIGO Clinical Practice Guideline for Glomerulonephritis 2012), time to achieve this response, relapse, progression to ERF and death. Results 120 patients who underwent a biopsy during the 24.5-year period received a diagnosis of lupus nephritis. 82.5% of patients were Caucasian. Median duration of follow-up was 72 months. 15% of patients died and 5% developed ERF within the follow-up period, representing one death per 56 patient years and one incident case of ERF per 168 patient years. There were 40 patients in the pre-December 2007 group and 80 in the post-December 2007 group. Those in the earlier group were younger, with a mean age of 35.4 years versus 44.8 years in the later group (p=0.002). 23% had class V in the earlier group compared to 15% in the later group (p=0.31). Proportions of female patients were 80% and 75% in the early and late groups respectively (p=0.54). Median creatinine was 106µmol/L in the pre-December 2007 group and 89.5 µmol/L in the post-December 2007 group (p=0.96). Patients in the pre- and post- December 2007 groups had comparable rates of complete response, at 72% and 71% respectively. However, those diagnosed before December 2007 were slower to respond, with a median time to achieve complete response of 10.5 months, compared to 6 months in those diagnosed after 1 December 2007 (p=0.007). Conclusion Following a change in our immunosuppressive induction regimen from Cyclophosphamide/ steroids to Mycophenolate/ steroids, our response rates have remained similar, however speed of attaining remission has improved.

Background and Aims Post-transplant lymphoproliferative disorders (PTLD) are a group of heterogeneous lymphoid proliferations in chronic immunosuppressed recipients of solid organ and hematopoietic stem cell transplantation. Due to rarity of this disease, retrospective studies from transplant centers have been the main source to provide knowledge and treatment guidelines, which are still in evolution. This study examined the clinical outcomes and identified the predictors of mortality in adult renal transplant recipients who developed PTLD. Method We have studied the incidence of PTLD in adult renal transplant recipients who were transplanted in our hospital from 1996 to 2019. Data was collected for demographics, transplant and immunosuppression history, EBV and CMV serostatus, diagnosis, treatment and outcomes of PTLD. We performed univariate and multivariate analysis to identify prognostic factors. PTLD was classified according to 2018 WHO lymphoma classification. Results Twenty-four patients (12 males and 12 females) were eligible for the analysis. Mean age at time of the transplant was 43.1 ± 16.9 years, with a time between grafting and PTLD of 66 months (IQR 36-98 months). Mean follow-up time was 87 months (IQR 61-117 months). 25% of patients received a living donor renal transplant. 12,5% of patients received induction therapy with thymoglobulin. Mean age at time of PTLD diagnosis was 48,8 ± 17,9 years. Five cases were from Epstein-Barr virus (EBV) mismatched (D+/R-) transplants and there was seroconversion at time of PTLD diagnosis. 25% of patients had central nervous system involvement. 19 patients have monomorphic PTLD and the most common histological diagnosis was diffuse large B cell lymphoma. We identified that age >30 years at time of the transplant was predictor of mortality (HR 33.01; 95% CI: 3.24-336.14; p=0.003). Surprisingly, presence of B symptoms at time of PTLD diagnosis confer a better prognosis (HR 0,143; 95% CI: 0,035-0,579; p=0.006). All cases were managed with reduction in immunosuppression and converted to everolimus. 8 patients were treated with rituximab and there was no significant difference in the survival of these patients. By the end of follow-up, 7 patients went into remission, 1 returned to chronic dialysis, and 16 patients died (15 of them due to the disease). Mean time between PTLD and death was 3 months (IQR 1-6 months). Conclusion PTLD is an infrequent disease with a poor prognosis in renal transplant patients. Some cases have a close relationship with EBV, but it can also develop in the absence of the classical risk factors. The factor affecting mortality in our population was age >30 years at time of the transplant. Presence of B symptoms at time of PTLD diagnosis seems to confer a better prognosis probably due to early investigation and diagnosis of the disease.

Background and Aims Polyomavirus BK (BKV) viremia has been suggested as a surrogate marker of overimmunosuppression. Due to recent advances in monitoring strategies and pre-emptive therapy, progression to BKV-associated nephropathy (BKVN) has been reduced. Reduction of maintenance immunosuppression during BKVN, however, has been associated with both T-cell mediated rejection (TCMR), antibody-mediated rejection (ABMR), and inferior kidney allograft outcomes. Although the administration of intravenous immunoglobulins (IVIG) failed to treat BKVN, IVIG may have properties to reduce allosensitization. Method We studied 860 kidney transplant recipients (KTRs) predominantly under tacrolimus-based triple-drug maintenance immunosuppression from 2009 to 2018. We identified 130 KTRs (15.1%) with high-level BK viremia >10,000 copies/mL (presumptive BKVN), 180 KTRs (20.9%) with low-level BK viremia Results Very interestingly, KTRs with low-level BK viremia/viruria showed a significantly lower incidence of TCMR compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p5000) between KTRs with low-level BK viremia/viruria, KTRs with no BK viremia/viruria, and KTRs with high-level BK viremia (p>0.05). KTRs with low-level BK viremia/viruria showed superior kidney allograft survival and lower eGFR slope compared to KTRs with no BK viremia/viruria and KTRs with high-level BK viremia (p Conclusion Our results show that low-level BK viremia/viruria is associated with suppression of TCMR and ABMR in the early period posttransplantation, and preservation of kidney allograft function in the long-term. The administration of IVIG didn’t prove beneficial to reduce allosensitization among KTRs with high-level BK viremia.

Background and Aims Nephrotic syndrome in childhood is characterized by proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Although most children respond to glucocorticoid therapy, approximately 10% of patients turn out to be steroid resistant (steroid-resistant nephrotic syndrome [SRNS]). Although several studies in children with SRNS have shown that mutations in genes encoding proteins in the podocyte skeleton may be responsible for the etiology in only one-third of cases, the genetic features related with renal prognosis and response to immunosuppressive agents are not fully recognized. The aim of this study was to investigate the genomic alterations associated with renal prognosis and resistance to immunosuppression in children with SRNS. Method The children with SRNS were enrolled in this study. Custom gene panel was designed for next-generation sequencing analysis of more than 20 target genes (ABCB1, ABCC2, CTLA4, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, FOXP3, GSTP1, IMPDH1, IMPDH2, NOS3, NR3C1, SLCO1B1, SLCO1B3, TPMT, UGT1A9, UGT2B7) and 200 single nucleotide variants (SNVs) which were reported as implicated in renal prognosis of nephrotic syndrome. The target gene panel was enriched for drug metabolism regulating transporters and enzymes. Results A total of 25 children, 16 boys (64%), median age at last visit 17.5 years (13-18 years), median age at diagnosis 7.5 years (2-15), median follow-up 9.58±4.54 years, were included in the study. All patients were diagnosed focal segmental glomerulosclerosis on renal biopsy.

Background and Aims Tunneled central venous catheter (T CVC) use is rising among patients undergoing chronic hemodialysis (HD) and non-tunneled (NT) CVCs are often used for HD initiation in late referral chronic kidney disease (CKD) or acute kidney injury (AKI). Catheter-related bloodstream infections (CRBSI) are a major complication of CVC use. This study examines potential patient- and CVC- related factors associated with CRBSI incidence and its microbiological features. Method In this retrospective single-center study, 413 patients undergoing an extracorporeal treatment (HD or Plasma Exchange) between February 1st 2014 and January 31st 2017 with 561 CVCs were recruited. Clinical data at study entry and CVC type are summarized in table 1. All bloodstream infections (BSI) occurring during the observation period were recorded and classified into CRBSI or non-CRBSI (nCRBSI), and their infecting agents collected. An incidence rate ratio (IRR (95% CI)) was calculated to assess the association between CRBSI incidence rate (IR), expressed as events/1000 catheter-days, and each clinical variable or CVC type. Significant associations at the univariate analyses were investigated with multivariate cox models. Results During a cumulative follow-up time of 66686 catheter-days, 54 (IR: 0.81) CRBSI and 30 (IR: 0.45) nCRBSI events occurred. CRBSI had higher frequency of GRAM+ bacteria compared with nCRBSI (70% vs 33%, p At the univariate analysis, male sex, age Conclusion Patients affected by AKI and use of NT or Femoral CVCs are independently associated with CRBSI risk.

Background and Aims The role of polyomaviruses (PyV) in malignancy is controversial, this can be demonstrated in three ways; Firstly, hit and run mechanism where polyomaviruses contribute to the early phases of oncogenic progression. The second way, where PyV act as a passenger as polyomaviruses neither necessary nor contribute to the oncogenic progression. The third way, where PyV acts as (bystander) as PyV is not related to the malignancy, but PyV could be detected in the anatomically connected sites or neighbouring cells. BKV has been classified as a possible carcinogenic to humans (2b) as there is sufficient evidence that it is carcinogenic to animals, however, BKV carcinogenicity evaluation to humans was inadequate. There are inconsistent data regarding the contribution of BKV to tumors that occur in both animals and humans. Method Retrospective analyses of 492 consecutive renal transplant recipients in a single-center, 2010-2018. Data Source: prospectively managed electronic patient records. Malignancy data in both control and BKV infected groups were assessed. Results A total of 492 cases were studied, were categorized into 2 groups the BKV infected group (n:73) patients and BKV non-infected group (n: 419) patients, then an assessment of different malignancies in both groups. The BKV infected group had 15 cases out of 73 who had malignancy, while the BKV non-infected group had 28 cases out of 419 totally (Table 1). The association between malignancy in BKV was statistically significant (P-value of 0.038). Moreover, the risk factors involved in the development of malignancy in renal transplant recipients were older age, BK virus infection and maintenance immunosuppression agents (Table 2). Lastly, Logistic regression analysis was used to assess predictors of malignancy among renal transplant recipients. For every one-year increase in age among renal transplant recipients, the odds of having a malignancy increase by 4.6% (p=0.003). Meanwhile, there is a 4 times increase in the odds of having malignancy for recipients who are BK virus-positive vs. those who are BK virus negative (p=0.001). Furthermore, there is a 10 times increase in the odds of having malignancy for recipients who are on sirolimus as a maintenance immunosuppressant vs. those who are on TAC/PRED/MMF (p=0.007). Conclusion Our study highlights the statistically significant correlation between BK virus infection and the development of malignancy in renal transplant recipients. However, statistical correlation doesn`t mean causation which makes the potential oncogenic role of BKV is unclear. Also, there is increased reporting of malignancy in patients infected with BKV. Increased vigilance is required for early detection of malignancy in patients infected with BKV not only the patients who are heavily immunosuppressed.

Background and Aims A relative reduction in proteinuria has been proposed as a surrogate outcome for therapeutic trials in IgA nephropathy. It is currently unknown how long a reduction in proteinuria needs to be maintained in order to mitigate the long-term risk of disease progression. To address this knowledge gap we sought to quantify the association between duration of proteinuria remission and the risk of disease progression in IgA nephropathy. Method In this retrospective multi-ethnic international cohort of adult patients with biopsy-proven IgA nephropathy, we defined proteinuria remission based on three criteria: (i) peak proteinuria on/after biopsy ≥1g/day; (ii) an absolute reduction in proteinuria to Results A total of 1864 patients met criteria for remission, which occurred a median of 8.3 months after biopsy (IQR 3.6-22). They had a median age of 36.8 (IQR 29.4-46.6) years and a median eGFR of 78 (IQR 55-104) mL/min/1.73m2. Median proteinuria was 1.54 (IQR 1.09-2.4) g/day at the time of biopsy and 0.55 (IQR 0.33-0.76) g/day at the time of entering remission. During a median follow-up of 3.9 years, 274 patients (14.7%) experienced the primary outcome. The relationship between duration of proteinuria remission and the primary outcome was non-linear (Figure). Each 3 months in sustained remission up to 51 months was associated with an additional 9% reduction in the risk of disease progression (hazard ratio 0.91, 95% confidence interval 0.89-0.93). In contrast, each additional 3 months in remission beyond 51 months was associated with a smaller non-significant risk reduction (hazard ratio 0.99, 95% confidence interval 0.96-1.03). These finding were robust to multivariable adjustment and were consistent across subgroups based on the MEST histology score, and whether or not the remission occurred while on renin-angiotensin-aldosterone-system blockade or after immunosuppression treatment. Results were similar when relapse was defined as either a 50% or 100% increase in proteinuria from the nadir value after remission to an absolute value of ≥1g/day. Conclusion We observed a strong non-linear dose-response relationship between the duration of proteinuria remission and the risk of disease progression in patients with IgA nephropathy. The ability to quantitate the renal survival benefit related to the duration of remission is an important advance for patients and their physicians. Rather than there being a minimum duration of proteinuria remission in IgA nephropathy, our results demonstrate that even short durations in remission, or small increases in remission duration, are both associated with significant reductions in the risk of disease progression. For future therapeutic trials in IgA nephropathy using proteinuria as a surrogate outcome, our findings illustrate the need to consider the duration of proteinuria reduction, in addition to the magnitude of proteinuria reduction, when evaluating the anticipated treatment effect on long-term clinical endpoints.

Background Autoimmune connective tissue diseases (AI-CTDs: SLE, pSS, IIM) are preceded by asymptomatic ANA positivity. We previously recruited a cohort of new ANA-positive referrals without AI-CTD. 17% met criteria by AI-CTD at 12 months, and this was predicted an IFN Score. This study includes 3 year follow up of that cohort with more detailed analysis of the non-progressor group and predictors. Methods Patients were recruited if they had: (i) ANA; (ii) did not meet criteria for AI-CTD; (iii) symptoms less than 12 months. Diagnostic criteria for AI-CTDs and therapies were assessed at baseline then 12-monthly for 3 years. We categorised progression as:1. Absolute-non-progressors (no clinical criteria at all time points: 0-36 months), 2. Undifferentiated-CTD ( > =1 clinical criterion at baseline and/or at follow up but not meeting criteria), 3. Year-1-progressor (meeting criteria for AI-CTD within 12 months), 4. Late-progressor (meeting criteria for AI-CTD later than 12 months). A 2-score analysis of IFN Status was performed as previously described (Yusof, ARD 2018). Results 3-year follow up was available in 146/150. Proportions in the above categories were: Absolute-non-progressors: 33/146 (23%); Undifferentiated-CTD: 86/146 (59%); Year-1-progressors: 21/146 (14%); Late-progressors: 5/146 (3%). No patient progressed or required immunosuppression after 2 years. 6/86 patients with Undifferentiated-CTD received an immunosuppressant. The present work therefore defines a larger group of 32/146 (22%) with clinically significant disease including 21 Year-1-progressors, 5 late-progressors, and 6 undifferentiated-CTD who needed an immunosuppressant. Clinical features had limited utility in predicting these outcomes. Of 31 patients with no clinical criteria at baseline, 1 progressed to meet criteria within 1 year, 2 progressed at 1-2 years, 3 were prescribed hydroxychloroquine and 1 was prescribed an immunosuppressant. The 108 patients with at least 1 criterion at baseline had the highest risk: 20 progressed to meet criteria within 1 year, 2 progressed at 1-2 years, the others all had U-CTD. 35 were prescribed hydroxychloroquine and 13 were prescribed an immunosuppressant. There was also no association between ENA, C3 or C4 and clinical outcome. The association between Interferon Score B and progression was stronger when comparing Year 1 progressors with absolute non-progressors (p = 0.007). Late progression was not predicted by baseline IFN Scores. However, within U-CTD, patients who required an immunosuppressant had higher expression of IFN Score A (p = 0.011) and IFN Score B (p < 0.001) than those who did not. Conclusion Among ANA-positive referrals, no clinical feature or routine laboratory test could rule out development of clinically significant disease, which included AI-CTD or undifferentiated CTD needing therapy. However, IFN Scores had a unique value in predicting these outcomes. At-risk individuals who ultimately developed clinically significant disease are therefore immunologically but not clinically distinctive. Future work will incorporate biomarkers into clinically applicable risk models to allow earlier exclusion of AI-CTD or trials of preventative treatment. Disclosures S. Ul-Hassan None. K. Dutton None. Z. Wigston None. A. Alase None. M. Md Yusof None. E.M. Vital None.

Background A presentation of acute kidney injury (AKI) in a patient with a longstanding diagnosis of SLE nephritis was challenged following unexpected renal biopsy and immunology resulting in a diagnosis of primary Sjögren's Syndrome (pSS) related fibrillary glomerulonephritis (FGN). Methods A 62 year old Caucasian female presented with AKI and infected leg ulcer. Previously diagnosed with SLE (1996), anti-phospholipid syndrome and non-biopsy proven lupus nephritis (LN), CKD stage G2/3 she was on Hydroxychloroquine and lifelong anticoagulation. Examination revealed bilateral pitting oedema up to knees and a large non healing skin ulcer to left knee. Investigations showed new anaemia (Hb 75g/dl, MCV 94), lymphopaenia, urea- 25 (9.8), Creatinine- 280 (97), urine protein 6.88g/24 hr. USS KUB, ECHO, CXR, virology screen, PET CT were unremarkable. Immunology studies revealed ANA 1:160, anti-Ro, anti-La, but normal DsDNA and C3, C4. In the light of reported sicca symptoms and serology the diagnosis was revised to pSS. Renal biopsy was initially reported as diffuse lupus nephritis (Class IV) with crescents, and focal weak mesangial IgG and C3 but no glomerular deposits. Electron microscopy (EM) demonstrated abundant mesangial and intramembranous deposits with a fibrillary substructure diagnostic of FGN. Immunosuppression with pulsed intravenous (IV) methylprednisolone and IV Cyclophosphamide were given. She developed acute arterial intercostal bleeding at biopsy site and further significant lower gastrointestinal bleeding unamenable to endoscopic therapy or embolisation and the patient died. Results This case highlights the importance of ensuring that serology is interpreted correctly alongside histopathology and urinalysis in the diagnosis of CTD related renal disease. PSS related nephropathy is seen in less than 10% of patients. Tubulointerstitial nephritis (TIN) accounts for 2/3 of patients and glomerulonephritis (GN), typically membranoproliferative GN (MPGN) for most others. FGN in pSS is very rare, with only 3 reported cases to date. Like lupus nephritis, FGN can present with AKI, hypertension and nephrotic range proteinuria. However, renal biopsy proves invaluable in differentiating between the conditions. In FGN characteristically on biopsy disorganised, non-branching fibrils are seen in all glomerular compartments and are negative for congo red stain further differentiating from amyloid FGN. Immunofluorescence microscopy shows uniform staining of the fibrils for immunoglobulins (mostly subclass IgG4). FGN has a poor prognosis with patients developing severe chronic renal failure despite immunosuppression. Conclusion Considering surprising investigation results, it is crucial we rechallenge the validity of longstanding diagnoses as highlighted by our case. In proven pSS with systemic features we recommend screening all patients for renal disease annually including serum electrolytes, urine dipstick, protein creatinine ratio and pH. If abnormalities are identified, renal US and consideration of biopsy is crucial in establishing aetiology as management and prognosis differs between subtypes. Disclosures C. Amoasii None. R. Benson None. J. Harper None. D. Mewar None.

Cestodes are emerging agents of severe opportunistic infections among immunocompromised patients. We describe the first case of human infection, with the recently-proposed genus Versteria causing an invasive, tumor-like hepatic infection with regional and distant extension in a 53-year-old female kidney transplant recipient from Atlantic Canada.

Background Patients with chronic diseases, particularly those requiring immunosuppression, are thought to be at increased risk of poor mental health during the COVID-19 pandemic. However, few studies have assessed the mental health of such patients during the current or past pandemics. We aimed to assess the incidence of depression, anxiety & stress in a cohort of inflammatory bowel disease (IBD) patients early during the COVID-19 pandemic, & explore for association with risk of severe COVID-19 based on British Society of Gastroenterology guidelines, & other factors. Methods A survey including the Patient Health Questionnaire-9, General Anxiety Disorder-7, & Perceived Stress Scale tools for depression, anxiety & stress, respectively, was administered to a cohort of IBD patients from a tertiary centre in London, United Kingdom, in June 2020. Results 274 patients responded to the survey (57% response rate), including 54 low risk, 152 moderate risk, & 68 high risk for severe COVID-19. Moderate-severe depression was observed in 61 (22.5%), moderate-severe anxiety in 49 (18%), while 39 (14%) had both diagnoses (Table). Mean (SD) stress score was 16.2 (7.4). There was no association between degree of severe COVID-19 risk & psychological morbidity. Flare symptoms & fatigue were associated with worse psychological morbidity across all measures, while accessibility of information regarding COVID-19 risk & reducing that risk was protective for depression (OR 0.56 [0.33–0.94], p=0.03), anxiety (OR 0.62 [0.4–0.96], p=0.03), & stress (standardized β-coefficient -0.15 [-0.28--0.03], p=0.02) (Figure). 79 (30%) respondents were interested in receiving psychological support during the pandemic, while 200 (76%) expressed interest beyond the pandemic. Conclusion Depression, anxiety & stress among IBD patients during the pandemic are common, however their frequency is similar to pre-pandemic rates & general population levels reported during the same period. Ensuring easy access to personalized risk information with targeted psychological support may mitigate psychological burden as patients reintegrate into society & deal with future COVID-19 waves or variants.

Background The aim of this study was to determine the disease phenotype, evolution and therapeutic needs of de novo inflammatory bowel disease (IBD) in transplanted patients. Methods A retrospective single center study that included all patients who developed IBD after solid organ transplantation in a tertiary hospital. Data collected included transplant-related variables, IBD phenotype, course of the disease and its treatment. A control group of non-transplanted IBD patients was randomly selected. Results We included 17 post-transplanted IBD patients and 57 non-transplanted IBD patients. Post-trasplanted patients were older at diagnosis, had greater colonic involvement, with an inflammatory behaviour, absence of perianal involvement and extraintestinal manifestations compared to control group (Table 1). The most common immunosuppression regimen was tacrolimus+mycophenolate mofetil (MMF)+prednisone and the most frequent change after diagnosis was the switch of MMF for azathioprine. De novo IBD patients required less biological therapy than the control group (11.8 vs 42.1% p 0.02) and none required surgical intervention compared to 35.1% in the control group (p 0.002). Multivariate analysis carried out on the total population showed that active smoking, perianal disease and extraintestinal manifestations were associated with a greater need for biologics, while the only factor that influenced surgical risk was stricturing and penetrating behaviour of Crohn′s disease. Conclusion De novo IBD after solid organ transplantation has a favorable course, predominating the inflammatory behaviour and requiring less biological therapy and surgical interventions. The absence of extraintestinal manifestations and perianal disease stands out.

Introduction Burn injuries are well known to cause a state of immunosuppression in patients. This can result in wound infections, a common complication in burn injuries, that can lead to sepsis and increased mortality. Human immunodeficiency virus (HIV) is also known to cause immunosuppression in patients. The outcomes of burn patients with pre-existing HIV infections, however, are not yet completely understood. We conducted a systematic review and meta-analysis to compare the outcomes of burn patients with pre-existing HIV against those without this chronic infection. Methods We searched MEDLINE (Pubmed), Google Scholar, Scopus, and Embase for studies that compared outcomes and complications between burn patients with and without HIV. From this search, we screened 445 articles. Through our selection criteria, five articles focusing on HIV patients were selected for systematic review and meta-analysis. Data were analyzed using the Cochrane Review Manager (RevMan) Data Analysis package to produce pooled odds ratios and mean differences from the random effect model. Results Five studies observing a total of 24,419 burn patients, published between 2000 and 2017, were included. Of these, two are prospective studies and three are retrospective chart reviews. The primary outcome of mortality for HIV+ patients compared to HIV- patients had an odds ratio of 2.04 (CI= 0.46–9.14) in the random effects model. Secondary outcomes of sepsis and wound infection odds ratios were 1.47 (CI= 0.44–4.99) and 1.10 (CI= 0.28–4.25), respectively. The length of stay (LOS) between studies showed an overall mean difference of 0.95 (CI=-8.08–9.99). Most studies had a greater proportion of male patients. TBSA between studies ranged from 13.1% and 35%. Conclusions From our results, we concluded that HIV+ had a tendency toward greater mortality (OR=2.04) and sepsis (OR=1.47). However, mortality and sepsis had confidence intervals of [0.46–9.14] and [0.44–4.99], respectively. Therefore, we cannot definitively state that HIV infection is responsible for greater mortality or sepsis in burn patients. Additionally, LOS analysis also showed a wide confidence interval [-8.08–9.99], preventing us from making reliable deductions about this outcome. We believe further research is needed before universal conclusion or recommendations are appropriate.

Glioblastoma multiforme (GBM) is an astrocyte derived brain tumor with very poor prognosis, usually with a less than one year survival rate. Immunotherapy has shown promising therapeutic potentials in research and clinical application, however, GBM associated immunosuppressive microenvironment creates a significant barrier for effective anti-GBM immune responses. The immune checkpoint PD-1/PD-L1 pathways play a critical role in tumor-induced immunosupression to evade immune surveillance. Gene-editing tools targeting PD-1/PD-L1 pathway have gained increased research attention, however the major challenge is how to effectively deliver gene-editing tools without causing adverse effects for clinical translation. We have developed a nanoparticle (NP) delivery system from a low molecular weight PEI lipid shell and a PLGA core that can package PD-L1 gRNA-CRISPR/Cas9 plasmid to transfect human U87 glioma cells overexpressing PD-L1. PD-L1 gRNA-CRISPR/Cas9 plasmid is constructed by inserting single guide targeting PD-L1 sequence into GFP CRISPR/Cas9 plasmid for visualizing transfection efficacy. NP is labelled with Rhodamine 6G to monitor cellular uptake and trafficking. Fluorescence microscopy shows human U87 glioma cells can quickly uptake PD-L1 GFP-CRISPR/Cas9 plasmid-NPs within 2 hours as indicated by the Rhodamine 6G. GFP expression was obtained after 48 hours of transfection and maintained up to 7 days without causing toxicity. Western blot analysis confirmed successful knockdown of PD-L1 in U87 cells. These findings reveal that NPs made by a cationic branched PEI lipid shell and a PLGA core are non-toxic and efficient in delivering CRISPR/Cas9 system to U87 cells. Editing of pathological gene in human glioma cells with PD-L1 GFP-CRISPR/Cas9 plasmid using NPs as a delivery system may provide a novel immunotherapy platform to treat GBM.

Background There has been a global increase in people who are intravenous drug user, diabetic, and elderly (aged greater than 65 years). These characteristics may alter the incidence of new diseases and potentially affect how diseases are diagnosed. As such this study’s purpose was to investigate baseline characteristics of patients with pulmonary blastomycosis. Case studies for Blastomyces have demonstrated positive cultures in 72% to 87% of patients. Therefore data will be analyzed to determine if there is any significant difference in culture results. Methods This study was a retrospective single-center ecological study. Patient charts were identified via ICD code search for blastomycosis. All protected health information was de-identified following data collection. Results 32 patients were identified with either pathology or culture proven blastomycosis. 8 patients (25%) had positive fungal cultures for blastomycosis. The average age of patients with pulmonary blastomycosis was 59.5 years old with 11 elderly patients (34%). There were 11 females (34%); 2 with hepatitis C (6%); 12 with diabetes (38%); 10 with immunosuppression (pancytopenia, chronic steroid usage, organ transplant, cystic fibrosis) (32%); 9 with COPD (32%); 21 with Tobacco abuse (67%); 7 with cancer (22%); 7 with work exposure (working around turned dirt or indoor mold) (22%) and 1 with opiate use (3%). No significant difference was found for culture results. Baseline Characteristics Culture Characteristics Conclusion Our culture results were exceedingly low in part due to some samples not being collected for fungal culturing and having to send-out the samples. The average age was consistent with the endemic region of Tennessee around 59 the previous 10 years.. 2/3 of the patients were tobacco abusers which may have contributed to some impaired ability to clear the fungal spores. Less than half of the patients were elderly, diabetic, immunosuppressed, or intravenous drug users therefore endemic inoculation may still be the main cause. Disclosures All Authors: No reported disclosures

Background Microbiological culture data is a longstanding gold standard in diagnostics. Unfortunately, yield from cultures have been inconsistent and slow, prompting the need for newer tests including the plasma-based next-generation sequencing (NGS) tool. This study aims to describe the use of NGS and the corresponding change in management. Methods A descriptive retrospective study was done on hospitalized adults at CHI-Baylor St. Luke’s in Houston, Texas with NGS tests from Jan 1, 2017 to Dec 31, 2018. Graph 1 - Next Generation Sequencing Test Breakdown Results There were 167 NGS tests performed. Most patients were non-Hispanic (n=129) Caucasian (n=106) males (n=116) with a mean age of 52. Furthermore, 61 were immunocompromised patients [solid organ transplant (n=30), HIV-AIDS (n=14) and rheumatology patients on immunosuppression (n=12)]. During the study, the hospital staff prepared a list of indications for NGS testing including: systemic or deep seated infection where a biopsy or other workup is negative or not possible (n=50), fever of unknown origin (n=26), culture negative endocarditis (n=15), HIV/AIDS with fever (n=10), transplant patient with fever (n=5). There were 60 cases where the indications were not on this list (36%). Results showed that 118/167 (71%) were positive. The most common organisms identified were gram-negative bacteria (54/118; 46%) followed by viruses (49/118; 42%), gram-positive bacteria (48/118; 41%), fungi (16/118; 14%), atypical bacteria (9/118; 8%), mycobacterium (4/118; 3%), and parasites (4/118; 3%). Blood cultures were concurrently obtained in 148/167 (89%) of the cases and returned negative in 137/148 (93%) of cases. In terms of change of management, the largest change was found in glycopeptide use (36 fewer patients after NGS results). Next was on anti-mycobacterial drugs where 27 were added among 8 instances. Only 36 patients were taken off antibiotics, even though 49 patients had negative results. In total, 120 out of 160 cases had antibiotic changes. Table 1 - Demographic and Laboratory Characteristics Graph 2 - Change in Number of Antibiotics (Total: Before and After) Graph 3 - Indications for Testing and Change in Number of Antibiotics Conclusion We observed a large decrease in glycopeptide use after NGS results which suggests physicians’ comfort in withdrawing MRSA coverage. In addition, anti-mycobacterial coverage increased corresponding to early mycobacterial detection with NGS. This study highlights the importance of clinical judgement in the age of rapid diagnostics. Disclosures All Authors: No reported disclosures

Background Therapeutic aims in IBDs are to induce remission through rapidly effective treatment. Conventional therapeutic methods including immunosuppression have been available for more than half a century with biological therapies the treatment of choice in patients who fail immunosuppressive drugs. There has been little attempt to longitudinally examine the differences in biopsychological factors and their associations with treatment modalities in IBD patients. Methods 50 IBD participants (24 UC, 26 CD) in clinical remission were followed for 12 months. Complete longitudinal datasets including demography, disease status (HBI, Mayo score), monthly stool and blood samples for inflammatory biomarkers, monthly validated scores of psychological state, baseline physiological state and autonomic function were collected for analysis of association. Microbiome analysis was performed using V4 16SrRNA for identification of microbial phylogenetic relationships. Patients were grouped on whether or not they were in remission on biological agents. Results CD: There was a larger magnitude of change in linear trends of anxiety (p = 0.007) in CD patients on non-biologic treatment. Quality of life (QOL), health-related quality of life (HRQOL) and faecal calprotectin measures were similar regardless of treatment. Longitudinal quadratic trends of CRP were significantly different between the two (p = 0.039) with the larger magnitude of change in non-biologic groups. CD patients had similar microbial profile when compared between two treatment groups. UC: Similar distributions of longitudinal psychological measures were found in two treatment groups, although results suggested significant linear trend (p = 0.019) in QOL scores but not with HRQOL. Faecal calprotectin had significant longitudinal linear trend (p = 0.016) with significant interaction between biologic therapy and this trend (p = 0.023). CRP had significant quadratic trend (p = 0.005) with strong interaction between biologic therapy and this trend (p = 0.009). Microbial α diversity was significantly different between two groups of treatments (Shannon; p = 0.041, evenness; p = 0.045) with biologic group having more diverse and more even microbial community. Conclusion Baseline biological and psychological factors were mostly similarly distributed between the two treatment options in remissive IBD patients, however biological therapy significantly influenced longitudinal trends of some psychological, inflammatory and microbiome dynamics, especially in UC. This suggests an underlying interrelationship between mode of treatment and biopsychological trajectories which might overshadow response to the treatment, requiring further assessment.

Background Amoebic colitis can mimic inflammatory bowel disease (IBD) in clinical presentation, endoscopic and (to some extent) histological findings. Four patients with amoebic colitis were misdiagnosed with IBD or an IBD flare at University Hospitals of Leicester (UHL), UK in 2018. This prompted a change in practise in our department and we began screening for Entamoeba histolytica in patients with newly-diagnosed IBD, a flare or those being considered for biologics. We analysed cases of possible amoebic colitis after this change by reviewing IBD patients with a positive E. histolytica immunofluorescence antibody test (IFAT). Methods We conducted a retrospective electronic and case note review of patients with IBD and positive amoeba IFAT serology >1:80 from April 2019 through September 2019. We collected information including Crohn’s disease (CD), ulcerative colitis (UC), IBD treatment, histological findings, travel history, stool E. histolytica DNA polymerase chain reaction (PCR) and amoebic serology including IFAT and Cellulose Acetate Precipitin test (CAP). The histology of endoscopic biopsies for 16 of the IFAT positive patients was reviewed specifically for amoebic trophozoites. Results During the study period we identified 26 IFAT positive patients, excluded 3 patients that were felt to be non-IBD; 23 were included in the study. The median age was 37.8 (range 16–86); 43.5% were male. Four had a diagnosis of UC; 19 had CD. 12 were new IBD presentations. Seven patients had a relevant travel history (Jamaica, Thailand, Turkey, Italy, Greece, and Spain). Four did not have a travel history. Travel history was unknown for 12. Three patients were on biologics, one on biologics and thiopurines. Five were on thiopurines, three on thiopurines and steroids. Four were on steroids only, four on 5-ASAs. Three were on no treatment. Two out of 16 patients reviewed had amoebic trophozoites on endoscopic biopsy, unfortunately stool PCR was not sent on these two patients. Stool E. histolytica DNA PCR, was sent for 19 patients and was negative in those cases. All 24 patients were negative for CAP. Conclusion While IFAT is helpful in detecting past exposure it is only 75% sensitive for amoebic colitis. Even if IFAT and CAP are combined it is difficult to differentiate amoebic colitis from IBD. It is not clear if these cases represent past infections, early infections that precipitated an IBD flare, early infections that arose in the setting of immunosuppression, or false positive IFATs. The risk of infection in the immunosuppressed patient is high and the consequences of misdiagnosis are significant therefore a comprehensive screening method is merited; this may encompass IFAT ± CAP, stool E. histolytica DNA PCR, and possibly histological review.

Recent studies demonstrate the potential role of the microbiome in immune-oncology, revealing specific microbial taxa can augment the effects of various therapeutic modalities against tumors. Gut dysbiosis, a disequilibrium in the host’s bacterial ecosystem, can potentially lead to overrepresentation of some bacteria and favor chronic inflammation and immunosuppression. However, the effects of microbial dysbiosis on non-gastrointestinal cancers in particular gliomas are unknown. Here, we explored the effects of glioma and Temozolomide (TMZ) on the fecal microbiome (FM) in mice (n=24) and FM and metabolome in humans (n=40). Aged C57/B6 mice were implanted with Gl261 tumor cells or vehicle and were assigned to one of the following treatment (oral) groups: vehicle, 5mg/kg TMZ or 25mg/kg TMZ beginning 14 days after surgery for 3-weeks following a 5 day on/2 day off treatment. Fecal samples were collected prior to surgery, at treatment initiation and weekly thereafter until sacrifice and sequenced for 16s RNA. Fecal samples were collected from humans with newly diagnosed glioma before resection, chemoradiation, and after chemoradiation (16s RNA, metabolomic, neurotransmitter analysis). In mice, FM beta diversity was significantly altered with glioma (p=0.003) while the alpha diversity remained unchanged. At a genus and family level analysis the relative abundance of Bacteroides (p=0.01) and Bacteroidaceae (p=0.02) was increased. Beta diversity of mice receiving 5mg/kg TMZ changed from baseline (p=0.02). Collectively, this suggests that glioma alters the FM, to what consequence remains to be explored. Alpha (Observed OTUs, p=0.029) and beta diversity (p=0.034) differences in mice correlated with survival (< 25 - >25 days). In humans, norepinephrine and 5-hydroxyindoleacetic acid were significantly lower in glioma patients at diagnosis compared to controls. Our findings demonstrate for the first time the relationship between glioma and the gut-brain axis. Understanding alterations in the FM in glioma patients may allow novel interventions and should be further investigated.

Immunotherapy has failed to improve the overall survival (OS) of adults with GBM in all phase III clinical trials to-date. Somewhat less appreciated is that, de novo GBM is a disease associated with a median age of diagnosis at 64 years old. Because of the strong association between advanced aging and human subjects presenting with GBM, we further investigated our previously described observation of a higher mortality rate in elderly C57BL/6 wild-type (WT) mice with intracranial GL261 as compared to young counterparts after treatment with radiotherapy (RT) and anti-PD-1 (PD1)/IDO1 enzyme inhibitor (IDO1i) (Ladomersky et al., 2018; Clinical Cancer Research). Since immunosuppressive IDO1 expression significantly increases in both the mouse and human brain during advanced aging (Ladomersky et al., 2019; Frontiers in Pharm.), we decided to study how IDO1 and aging interact during immunotherapy of GBM. We found that the pretreatment effects of an IDO1 enzyme inhibitor improve OS in young but not elderly WT mice with intracranial GL261 (n=12–15/group; p< 0.05). Strikingly, in the setting of advanced aging, IDO1-/- mice with GBM show improved OS as compared with WT mice (p< 0.01) independent of treatment with an IDO1 enzyme inhibitor. Similarly stunning, 74–80 week old IDO1-/- mice with GBM treated at 14 days post-ic. with RT and PD1/IDO1i survive significantly longer as compared to elderly WT mice administered the same treatment (n=20–22/group; p< 0.05). These results collectively suggest that, the therapeutic effects of IDO1 enzyme inhibition is less effective in the setting of old age, and provides rationale for the development of new approaches that inhibit IDO1-mediated immunosuppression independent of its association with enzyme activity for eventually improving immunotherapeutic efficacy in human subjects with malignant glioma.

Background Juvenile osteochondritis dissecans (JOCD) is a condition of bone and cartilage lesions. Contributory factors may include ischaemia, trauma, genetic or biomechanical factors such as abnormal joint loading. Children and young people (CYP) with juvenile idiopathic arthritis (JIA) have low physical activity levels, present with joint abnormalities and are exposed to immunosuppression including steroids which may cause reduced bone density. Here we describe JOCD in CYP with JIA in our service. Methods Retrospective reviews of case notes were conducted for current CYP with JIA in our service with known JOCD, detailing: JIA diagnosis Age & BMI at diagnosisSymptom duration pre-diagnosisManagement (including steroids)JOCD diagnosis Age & BMI at diagnosisImagingManagement Results Table 1 summarises the results. Twelve (n = 10 female) CYP in our cohort of 270 had JOCD with 20 lesions diagnosed on magnetic resonance imaging (MRI). Polyarticular (n = 4) and extended oligoarticular (n = 5) were the commonest JIA sub-types with all CYP receiving systemic therapy and 75% (n = 9) requiring more than one biologic. Mean symptom duration before JIA diagnosis was 6 months (range: 1-24 months) with a mean age of 6.5 years (range: 1.5-13 years). Mean time to JOCD diagnosis was 5.5 years (range: 1.5-10.25 years) with a mean age of 12 years (range: 8-17 years) and 7 CYP having a high BMI (>85th percentile for age). The mean number of previous steroid injections per JOCD joint was 4 (range: 0-17) compared with 3 (range: 0-8) in the non-JOCD joint. Talar dome lesions (n = 9) were commonest, followed by femoral condyle (n = 4 medial, n = 3 lateral). Initial management was conservative, with half (n = 10) requiring surgery. P09 Table 1 Conclusion This review identifies that 4% (n = 12/270) of our CYP with JIA have known JOCD, compared with 0.03% (n = 29/100,000) of the general population. Risk factors appear to be polyarticular disease, exposure to ≥ 4 steroid injections per joint, biologic-resistant disease and high BMI with low physical activity. Where CYP with JIA report symptoms which do not fit an inflammatory pattern there should be a low threshold to consider JOCD, with prospective research needed to better understand the relationship between JOCD and JIA. Conflicts of Interest The authors declare no conflicts of interest.

Background Rituximab is a chimeric monoclonal antibody that depletes the B cell population by targeting cells bearing the CD20 surface marker and is used widely in the management of paediatric rheumatological conditions like juvenile systemic lupus erythematosus (JSLE), juvenile dermatomyositis (JDM), mixed connective tissue disease (MCTD) and juvenile idiopathic arthritis (JIA). Pneumocystis jirovecii pneumonia (PCP) is a potentially fatal opportunistic infection associated with congenital and acquired defects in T cell–mediated immunity. Our guideline did not recommend prophylaxis against PCP for patients on rituximab, unlike patients on cyclophosphamide, who are on cotrimoxazole until three months after cessation of the treatment. Cyclophosphamide is an alkylating agent which affects both B and T lymphocytes. Following the death of 16 year-old girl with JSLE due to PCP, the team reviewed the possible contributing factors, undertook a review of literature and discussed this at multi-disciplinary meetings involving the microbiology and immunology teams. This patient was found to have other risk factors for PCP – low CD4 T cells, concomitant use of corticosteroids and hypogammaglobulinaemia (IgG 3.0g/L). Although there is limited evidence that rituximab on its own increases the risk of PCP, there is emerging data that B cells may have a role in the protection against pneumocystis. Following the review, it was concluded that children on rituximab and an additional immunosuppressant (including corticosteroids) should receive prophylactic cotrimoxazole to cover PCP. Methods Retrospective audit carried out by the team to look at adherence to the new guideline regarding the use of cotrimoxazole for PCP prophylaxis in patients who have had rituximab between August 2017 and May 2019. Results P54 Table 1 Total number of patients who had rituximab 10 Number of patients who had other immunosuppressants concomitantly / recently (within previous 3 months) 7 Number of patients on rituximab monotherapy 2 Number of patients who are 6 months post-treatment 1 Number of patients with other risk factors for PCP 1 (hypogammaglobulinaemia) Number of patients who are eligible for prophylaxis, as per the guideline 8 (7 for concomitant immunosuppression and 1 for hypogammaglobulinaemia) Number of patients on cotrimoxazole 7 (87.5%) - one of the patients is on methotrexate, which is advised not to combine with cotrimoxazole We achieved 87.5% compliance in prescribing cotrimoxazole for PCP prophylaxis to all rheumatology patients receiving rituximab alongside another immunosuppressant agent; the one patient who this was not adhered to was due to potential adverse drug pharmacodynamic interaction between cotrimoxazole and methotrexate. Conclusion Although the current evidence points to increased risk of PCP in patients with inherited and iatrogenic defect of T cell function, there is emerging evidence that B cells may have a role too. Hence more work is required to determine the risk of PCP in patients on B cell targeted therapy (BCTT) and the need for prophylaxis. Conflicts of Interest The authors declare no conflicts of interest.

OBJECTIVES: The aim was to examine the clinical course and dietary patterns among patients incorporating autoimmune protocol (AIP) for management of inflammatory bowel disease (IBD). METHODS: An anonymous online survey was sent through electronic newsletters and support groups utilizing AIP. The survey assessed demographics, IBD disease activity, and medication use. Participants were asked about AIP utilization and food group reintroductions. Abdominal pain (AP), stool frequency (SF), and rectal bleeding (RB) were compared at baseline (BL, prior to starting AIP), week 6 (after starting AIP), and present, for both Crohn's disease (CD) and ulcerative colitis (UC). RESULTS: There were 78 respondents. Mean age was 39.4 years, with mean IBD duration 13.2 years. 78% had prior steroid exposure. 35% currently on immunosuppressive agents. 73% perceived achieving clinical remission due to AIP. This was more common among patients not on immunosuppression (76% vs. 24% on immunosuppression, P

We discuss the rare finding of what initially presented as a common subcutaneous scalp nodule. Yet, after surgical excision, the lesion was found to be a poroid hidradenoma (PH). PH is a rare variant of poroid neoplasms. PH, when observed, is commonly associated with the head and neck. However, it is rarely described in literature beyond the dermatopathologic findings. Here, we describe the clinical presentation of a unique case of a scalp PH in the setting of immunosuppression.

Background Patients with deficiencies of terminal components of complement are at hundreds to thousands fold increased risk of severe and fatal Neisseria spp. infections compared with the general population. Eculizumab is a newly approved monoclonal antibody C5 complement inhibitor. It is indicated for the treatment of atypical hemolytic uremic syndrome (atypical HUS), myasthenia gravis, and paroxysmal nocturnal hemoglobinuria. Because of the complement-depleting effect of Eculizumab dosing (Soliris®, Alexion Pharmaceuticals, Munich, Germany), patients are immunosuppressed for specific infectious pathogens (including Neisseria species) against which protection partially relies on normal complement activity. Because Eculizumab treatment is associated with a dramatically increased risk of Neisseria species. infections, recommendations for Neisseria meningitidis vaccination and antibiotic prophylaxis are contained in Eculizumab prescribing information. However, the most appropriate prevention of infections after Eculizumab has yet to be determined. Methods Case report and literature review. Results A previously healthy 7-year-old male was diagnosed with atypical HUS which included renal failure progressing to dialysis, persistent thrombocytopenia, hemolytic anemia, and hemoglobinuria. Stool cultures and a stool multiplex PCR panel did not detect Shiga-like producing E. coli nor E. coli O157/H7. Eculizumab dosing was therefore planned and Infectious Diseases consultation was obtained for appropriate preventions. The FDA Prescribing Information recommends Neisseria meningitidis vaccination before starting Eculizumab or, if immediate Eculizumab is necessary, to use antibiotic prophylaxis until 2 weeks after vaccination. The accepted protective titer after meningococcal vaccination is population based and uses the serum bactericidal assay (SBA). An antibody titer of >1:4 (human compliment) or 1:8 (rabbit complement) is considered protective. However, this “gold standard” assay incorporates the use of exogenous human or rabbit complement. The protective SBA titers in subjects with terminal complement component deficiencies may not be properly assessed using these same SBA titer protective thresholds. Furthermore, serious meningococcal infections have occurred after appropriate vaccination in patients receiving chronic Eculizumab treatments (ie for paroxysmal nocturnal hemoglobinuria). Finally, SBA protective levels after single Neisseria meningitidis vaccination have not been achieved in majorities of patients with renal failure receiving dialysis and or transplant immunosuppression. Conclusions The current Eculizumab prescribing information recommendations for vaccination and antimicrobial prophylaxis may be inadequate to prevent serious Neisseria infections. Repeated Neisseria meningitidis vaccination and extended antibiotic prophylaxis may afford better protection in patients chronically dosed with Eculizumab.

Ependymoma is the third commonest childhood brain tumour. Relapse is frequent, often fatal and current therapeutic strategies are inadequate. Previous ependymoma research describes an immunosuppressive environment with T-cell exhaustion, indicating a lack of response to T-cell directed immunotherapy. Understanding the immune microenvironment is therefore critical. We present a computational analysis of ependymoma, gene expression derived, immune profiles. Using 465 ependymoma samples from gene expression datasets (GSE64415, GSE50385, GSE100240) and two RNA-seq databases from UK ependymomas, we applied bulk tumour deconvolution methods (CIBERSORT and xCell) to infer immune cell populations. Additionally, we measured checkpoint blockade related mRNAs and used immunohistochemistry to investigate cell populations in ependymoma sections. CIBERSORT indicated high proportions of M2-like macrophages and smaller proportions of activated natural killer (NK) cells, T follicular helper cells, CD4+ memory T-cells and B-cells. xCell overlapped with the M2-like macrophage and CD4+ memory T-cell signatures seen in CIBERSORT. On immunohistochemistry, T and B cells were scarce, with small numbers of CD8+, CD4+ and CD20+ cells in the parenchyma but greater numbers in surrounding regions. CD68 was more highly expressed in the parenchyma. Analysis of nine checkpoint ligands and receptors demonstrated only the TIM3/GAL9 combination was reliably detectable. GAL9 is implicated in tumour interactions with T-cells and macrophages elsewhere, possibly contributing to poorer outcomes. Our study supports the presence of myeloid cells being leading contributors to the ependymoma immune microenvironment. Further work will delineate the extent of myeloid contribution to immunosuppression across molecular subtypes. Modulation of tumour immunity may contribute to better clinical outcomes.

BACKGROUND D2C7 immunotoxin (D2C7-IT) is a dual-specific recombinant immunotoxin comprising an EGFR-wt and mutant-specific (EGFRvIII) monoclonal antibody fragment and a genetically engineered form of the pseudomonas exotoxin. When injected directly into the tumor mass by convection enhanced delivery (CED), in addition to direct tumor cell killing, immunotoxins induce secondary immune responses by the activation of CD4+ and CD8+ T-cells. We completed a phase 1 dose escalation study of D2C7-IT injected by CED into recurrent WHO grade III-IV MG and identified the phase 2 dose (6,920 ng/mL). Three patients remain in partial response more than 58, 38, and 32 months after a single D2C7-IT intratumoral infusion. As optimal induction of anti-tumor immune responses by immunotoxins is impeded by potent MG-mediated immunosuppression, we are assessing the toxicity of the combination of D2C7-IT with atezolizumab in patients with recurrent WHO grade IV MG. METHODS Eligibility includes adult patients with recurrence of a solitary supratentorial WHO grade IV MG; ≥4 weeks after chemotherapy, bevacizumab or study drug; adequate organ function; and KPS >70%. Patient receives an intratumoral infusion of D2C7-IT and initiates two weeks later atezolizumab at 1200mg, followed by atezolizumab every 3 weeks for up to 2 years. Two cohorts of 3 patients are initially accrued to assess the toxicity of the combination. Assuming accrual continues after the initial two cohorts of 3 patients, an additional 12 patients will be accrued to the study. RESULT The first enrolled patient experienced a grade 3 DLT (grade III ALT elevation) after the first infusion of atezolizumab, but showed a more extensive immunotherapeutic effect by imaging than observed with patients on the D2C7-IT monotherapy trial. Enrollment is ongoing. CONCLUSION D2C7-IT monotherapy has shown prolonged survival and disease control in some patients. We are now evaluating the combination of D2C7-IT with checkpoint inhibition.

INTRODUCTION Indoleamine 2,3-dioxygenase 1 (IDO; IDO1) is a rate-limiting enzyme that metabolizes the essential amino acid tryptophan into kynurenine. Recent work by our group has revealed that IDO promotes tumor development and suppresses immune cell functions independent of its enzyme activity. Moreover, pharmacologic IDO enzyme inhibitors that currently serve as the only class of drugs available for targeting immunosuppressive IDO activity, fail to improve the survival of patients with GBM. Here, we developed IDO-Proteolysis Targeting Chimeras (IDO-PROTACs). PROTACs bind to a specific protein and recruit an E3 ubiquitin ligase that enhance proteasome-mediated degradation of the target protein. METHODS A library of ≥100 IDO-PROTACs were developed by joining BMS986205 (IDO binder) with a linker group to various E3-ligase ligands. Western blot analysis of PROTAC-induced IDO degradation was tested in vitro among multiple human and mouse GBM cell lines including U87, GBM6, GBM43 and GL261 along a time course ranging between 1–96 hours of treatment and at varying concentrations. The mechanism of IDO protein degradation was investigated using pharmacologic ligands that inhibit or compete with the proteasome-mediated protein degradation pathway. RESULTS Primary screening identified several IDO-PROTACs with IDO protein degradation potential. Secondary screening showed that our lead compound has a DC50 value of ~0.5µM with an ability to degrade IDO in all GBM cells analyzed, and an initial activity within 12 hours of treatment that extended for up to 96 hours. Mutating the CRBN-binding ligand, pretreatment with the ubiquitin proteasome system inhibitors MG132 or MLN4924 or using unmodified parental compound all inhibited IDO protein degradation. CONCLUSIONS This study developed an initial IDO-PROTAC technology that upon further optimization, can neutralize both IDO enzyme and non-enzyme immunosuppressive effects. When combined with other forms of immunotherapy, IDO-PROTACs have the potential to substantially enhance immunotherapeutic efficacy in patients with GBM.

Adult low-grade gliomas generally progress to glioblastoma, a more aggressive CNS tumor with an extremely poor prognosis. Despite intensive efforts, numerous promising glioma therapies have failed to provide survival benefits. These failures reflect many factors, including intertumoral heterogeneity and immunosuppression by the tumor microenvironment (TME). We propose a novel approach to addresses these challenges through integrative deconvolution of bulk gene expression data generated from more than 5000 human gliomas and 7000 normal human brain samples. Inherent variation in the cellular composition and cellular activities of these samples allowed us to identify highly correlated modules of genes that represent specific cell types and cell states. By comparing gene coexpression modules in glioma vs. normal human brain, we have identified cell type-specific gene expression changes in the glioma TME that are highly reproducible. In contrast to single-cell methods, which sample only a fraction of the tumor tissue and fail to capture major nonmalignant cell-types, our results derive from billions of cells and thousands of individuals and are therefore highly robust. We find that a number of genes encoding cell-surface proteins are specifically up-regulated in immune and vascular cells of the glioma TME. Surprisingly, among those genes up-regulated in glioma vasculature are multiple members of the angiotensin pathway, suggesting non-canonical roles for these proteins in the glioma setting. We propose that these proteins may form a specific ‘zip code’ for glioma within the brain’s vasculature that can be targeted directly or by conjugation with existing drugs. More generally, our analytical approach has revealed reproducible gene expression changes in specific cell types of the glioma TME that provide more stable therapeutic targets than those that are expressed by genetically mutable malignant cells. We have also discovered novel, aberrantly coexpressed genes in microglia, oligodendrocytes, and astrocytes which we are testing in state-of-the-art human brain assembloid systems.

Background An antibiotic time out is when a clinician is prompted to reevaluate antibiotic therapy for appropriateness after 48–72 hrs. The purpose of this study is to evaluate the impact of a prescriber-led electronic antibiotic timeout alert. Methods This was a retrospective cohort study conducted at seven hospitals of a health system. The alert prompts prescribers to reevaluate antibiotic therapy after > 72 hours upon opening the electronic chart. Prescribers can then choose to “Continue”, “Renew”, “Discontinue” or “Defer” for each antibiotic. The alert fires for every time the chart is opened, for every prescriber, every time any antibiotic has been active for > 72 hours and no action response (i.e., “Continue”, “Renew”, “Discontinue”) has been selected. This was a 6 month study from November 1, 2018 – April 30, 2019. The primary outcome measure was the percentage of patients having > 1 antibiotic discontinued via the electronic antibiotic timeout alert. Secondary outcomes included frequency of timeout alerts per patient, and percentage of discontinuations per response, by drug, by indication and by patient age. Results A total of 213950 alerts fired for 13263 patients during the study period. 94.2% and 0.4% of responses were “Defer” and “Discontinue”, respectively. The average number of alerts per patient was 16.1. The percentage of patients who had at least one discontinuation was 5.3%. 38.2% of patients had no response other than “Defer”. There were a total of 10306 action responses, 4.8% of which were “Discontinue”. Among action responses, discontinue rates for the indications of “COPD exacerbation”, “Prophylaxis, Surgical/Procedural”, “Prophylaxis, Immunosuppression”, “Osteomyelitis” were 9.6%, 12%, 1.3% and 1%, respectively. Azithromycin and trimethoprim/sulfamethoxazole had discontinuation rates of 9.3% and 0.9%, respectively. Patient age had a significant impact on discontinuation rates with rates of 4.7%, 3.5%, and 10.9% for patients > 18, 2–17 and < 2 years of age (p< 0.001). Conclusion An electronic antibiotic timeout alert implemented at seven hospitals was largely ignored. This alert may be refined by limiting it to antibiotic orders with specific features associated with higher rates of discontinuation. Disclosures All Authors: No reported disclosures

OBJECTIVES: In order to evaluate the therapeutic potential of resolvins to reduce inflammation in CCI-PICS, we recapitulated Glue Grant leukotriene and resolvin lipidomic scores above to quantify lipidomics in severe sepsis/septic shock survivors. METHODS: Ongoing University of Florida (UF) Sepsis Critical Illness Research Center (SCIRC) research studies indicate that Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) occurs as a result of a self-perpetuating cycle of low-grade inflammation. However, specialized pro-resolving mediators (SPMs) – metabolically active lipid byproducts of omega-3 fatty acids – can promote inflammatory deceleration and resolution. Post hoc analysis of the Glue Grant Data developed a mathematical lipidomic expression to better understand genes responsible for production and degradation of resolvins and leukotrienes. Leukotriene Score = (ALOX5 * ALX5AP * LTA4H * LTB4R)/(HPGD + PTGR1 + CYP4F3) Resolvin Score = [(ALOX5 * ALOX15) * (FPR2 + GPR32 + CMKLR1)]/(HPGD + PTGR1) When the targeted genes were scored using a weighted scheme accounting for enzyme and receptor activity, patients with uncomplicated recoveries had higher resolvin scores (P

Background Inflammatory bowel disease (IBD) patient’s knowledge is a key factor for shared treatment decision making. Some studies have already investigated IBD knowledge but never focused on patient’s awareness about the major disease outcomes nor clinical course nor therapeutic aspects. The aim of the present study is to assess disease knowledge in IBD patients using a novel 11 items questionnaire. Methods An 11 items questionnaire was developed. The questionnaire explored different aspects of IBD course and prognosis: pattern of symptoms, disease complications, need for surgery, risk and prevention of colon-rectal cancer (CRC), extra-intestinal manifestations (EIMs), predictors of poor prognosis, benefit/risk of immunosuppressive and biological therapy and IBD in pregnancy. The questionnaire was handed out to consecutive Crohn’s disease (CD) and ulcerative colitis (UC) patients in regular follow-up at a referral centre. Clinical and socio-demographic characteristics were collected in a dedicate database. Descriptive analysis of quantitative variables was presented as mean or median. Fisher test and Student’s t-test were used for categorical and continuous variables. A p < 0.05 was considered statistically significant. Results Three hundred and four patients were enrolled and 290 completed the questionnaire (95%). Of these 53% UC and 47% CD. The mean age was 51 years (range 18–83); 56% were male. Most of the patients were in clinical remission (85%). The mean number of appropriate answer was 4 upon 11. Overall only 26% answered successfully more than half of the items. Looking at the single items, two third of patients were aware of current strategies of CRC prevention, chance of EIMs and woman capability to become pregnant. The questions about immunosuppression and biologic therapy were more correctly answered by those patients who had experienced them (p = 0.000001), whereas those about the risk of surgery were not influenced by the patient’s previous clinical history (UC p = 1; CD p = 0.067). Only about one third of women were aware of the most relevant risk factor of worst pregnancy outcome. Age Conclusion These results suggest that the overall disease knowledge in IBD patients is low and should be improved. Young age, education and biologic exposure are associated with an adequate awareness of disease course. This questionnaire should be validated and correlated to other patient-related measures such as health engagement and health literacy in prospective studies.

Background Ileocolonic resection is the most common surgery in Crohn’s disease (CD). However, stricture formation in the anastomosis is considered to be a frequent cause of significant morbidity in CD and a reason for reoperation. Endoscopic balloon dilatation (EBD) is an established modality for non-surgical treatment of strictures in CD, however, summary data from the Czech Republic are lacking. Methods All EBDs of CD anastomotic strictures performed in the 7 centres from the Czech Republic between January 1, 2013, and May 30, 2019, were included. Demographics, disease characteristics, concomitant medication and procedure outcomes were analysed. Technical success was defined as an ability to pass the endoscope through the site of the stricture following the procedure. Complications included perforation and bleeding with the need for intervention or hospitalisation. Kaplan–Meier and logistic regression analysis were performed. Results In total, 615 procedures performed in 282 patients, 52.1% males, were included. Mean age at the time of the first procedure was 41.9 ± 12.7 years and mean disease duration was 14.5 ± 8.4 years. Single dilatation was performed in 47.9% of patients, 52.1% requested repeated interventions (2–10, median 2). Cumulative probability of redilatation at 6 months, 1 year and 3 years was 20.2% (95% CI 14.8–26.2%), 31.8% (95% CI 26.5–37.2%) and 59.4% (95% CI 55.5–63.0%) respectively. Cumulative probability of a need for reoperation at 6 months, 1 year and 3 years was 4.4% (95% CI 0.5–16.9%), 8.2% (95% CI 2.3–19.3%) and 14.8% (95% CI 7.1–25.2%) respectively. Technical success was reached in 81.1% of procedures and relief of symptoms in 86.7%. The success of the procedure was dependent on the age of the patient (OR 0.98; 95% CI 0.96–0.99), smoking (OR 0.57; 95% CI 0.32–0.98) and concomitant immunosuppression use (OR 1.99; 95% CI 1.31–3.02). Complications occurred in 2.6% of the procedures. Reintervention until 6 months after the procedure was needed in 26.7% of cases, out of which repeated dilatation in 21.3% of cases and early surgery took place in 5.4% of cases. The technical success (OR 0.44; 95% CI 0.29–0.67) and repeated dilatation (OR 1.57; 95% CI 1.09–2.27) were significantly associated with the need for reintervention until 6 months. Conclusion In a large multicentric Czech cohort, the EBD in Crohn’s disease anastomotic strictures was proven to be safe and effective with results comparable to the available international data.

Background Both anal abscesses and fistulas are potential complications in the course of Crohn’s disease. Chronic immunosuppression, loose stools and poor wound healing in this population pose a challenge to the treatment of perianal diseases. The purpose of our hospital research was to determine the dominant bacterial species found in perianal abscesses and fistula discharge, resulting in anal abscess and/or fistula outflow in patients with Crohn’s disease hospitalised in a tertiary IBD centre in Poland. Methods The results of tests of patients admitted and subsequently conservatively treated or treated for anal fistula or abscess in the period from January 1, 2017 to June 30, 2019 were evaluated. Information obtained from medical records included clinical information, results of laboratory tests and results of swab cultures of perianal lesions for culturing and antibiotic sensitivity of microorganisms isolated. Material was collected from patients in accordance with applicable procedures. Results In the analysed period, a total of 306 swabs from perianal lesions from 44 patients with the diagnosis of Crohn’s Disease were collected, of which microbial growth was observed in 38 patients. Escherichia coli (45.5%, p < 0.001) was the most frequently isolated pathogen, Staphylococcus aureus was the second most common pathogen (15.9%, p < 0.001). In vitro sensitivity tests showed that Escherichia coli (ESBL-extended-spectrum-beta-lactamase producing strain with a broader substrate spectrum) was found in 4 samples, Staphylococcus aureus (MRSA- strain resistant to all beta-lactam antibiotics: penicillins with inhibitors, cephalosporins, monobactams, carbapenems except for ceftaroline). The analysis of the results obtained did not show seasonal variability in the number of positive microbiological tests found on cultures of perianal lesions. Conclusion A retrospective analysis of microbiological results of anal abscesses and fistula outflow was performed in patients with Crohn’s Disease with perianal changesi. Escherichia coli was the predominant pathogen isolated. The second most common organism was Staphylococcus, isolated from 9 patients. Staphylococci were not found in samples from other patients with IBD. The evaluation of the obtained results shows that positive results of cultures of swabs from lesions in the anal area were found more often in samples taken from men (25 samples–65.8%) than from women (13 samples–34.2%).