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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.

Case report - Introduction The differential diagnosis of paediatric uveitis is extensive. Classification starts by determining infectious versus non-infectious causes, anatomic location and associated intra-ocular and extra-ocular features. A relatively common referral to Paediatric Rheumatology from our Ophthalmology colleagues is of a child with a diagnosis of uveitis. This case highlights the importance and benefits of multidisciplinary team working across our regional network when caring for children with complex and rare conditions. Case report - Case description An 8-year-old-girl was referred by her local ophthalmology team to the paediatric rheumatology clinic with a diagnosis of pars-planitis. She had presented to them with blurred-vision and eye-“floaters”. On review, the girl reported that she had a 4-month-history of headaches and blurred-vision, associated with dizziness. She denied any eye-pain. Corresponding to the onset of her symptoms, she had suffered with Chickenpox. Her mother felt that she had "not been right since then". She noted that she was generally quieter and more fatigued than normal. Over the course of the 4 months, she was noted to have become clumsier and was bumping into things on a regular basis. She reported increasing visual difficulties in her right eye and initially attended for an optician review. The optician was concerned and referred for urgent ophthalmology opinion. She was diagnosed with bilateral pars-planitis, commenced on oral prednisolone and referred for paediatric rheumatology and tertiary ophthalmology assessment. The headaches improved following commencement on steroids. Positive findings on systems review included occasional oral ulcers, 1—2 times-per-month. They started about 1-month prior to the onset of her chickenpox and continued for the following 3—4 months. She denied any history of genital-ulcers or skin-rash. She had new-onset muscle soreness and tiredness after activity. She also described non-specific abdominal pain since having chickenpox, but no associated change in bowel habit. Examination revealed normal skin, hair, nail and joint examination. She had a soft systolic murmur (echocardiogram normal). She had RUQ tenderness on abdominal palpation (abdominal-USS – spleen upper limit of normal. Nil else). Relevant blood and stool samples were sent as part of a uveitis work-up panel. The paediatric ophthalmologist found right-intermediate uveitis with vitreitis and peripheral retinal changes in keeping with a peripheral exudative detachment. Similar changes were seen in the peripheral retina of the left eye. The impression was of bilateral pan-uveitis with retinal involvement. A subsequent oral fluorescein angiogram showed a widespread retinal vasculitis with some occlusive changes in the right-eye, and a tuft of retinal vascular leakage at the 5-o'clock position in the left eye. Case report - Discussion The differential diagnosis for paediatric retinal vasculitis is broad. It includes collagen vascular disorders, Behçet's disease, Eales’ disease, post viral or post vaccination, acquired toxoplasmosis, multiple sclerosis, systemic immunosuppression and Henoch-Schönlein purpura. The ANA, ENAs, dsDNA, ANCA, ACE, Toxoplasma and Lyme serology were all negative for this little girl. Her inflammatory markers were also normal. She was not on any regular medications prior to her illness and had not had any recent vaccinations. She had no significant past medical or family history of note. However, the onset of her symptoms did correspond to her having chickenpox. She was subsequently found to be positive for HLA B51. In view of the ophthalmology findings and positive HLA B51, the little girl was admitted for an urgent MRI/MRI to exclude neuro- Behçets. This was reported as normal. She was treated with a three-day pulse of IV methylprednisolone and discharged on oral prednisolone 10mg OD (weight 33.4kg). At present Bechet’s retinal vasculitis remains high in the list of differentials for this little girl; however, currently she does not strictly meet the diagnostic criteria for Bechet’s disease. She has been commenced on a steroid sparing agent, azathioprine. Her follow-up plan is to be reviewed in the joint paediatric rheumatology and ophthalmology clinic in 1 months’ time. Case report - Key learning points Retinal vasculitis may occur secondary to a systemic disease or an infectious agent, or as an isolated retinal aetiology. Given that the differentials are vast, a detailed history and examination are important to identify signs and symptoms of systemic disease. Appropriate investigations should be chosen to help narrow the differentials and ensure pathology that could lead to significant morbidity and mortality is not missed. With a case such as this, close collaboration between the paediatric ophthalmologist and rheumatologist is paramount to ensure the best outcome for the patient. With regards to treatment, small case series have described a refractory nature of retinal vasculitis in paediatric patients. One study report that almost 80% of patients with paediatric idiopathic uveitis show manifestations of retinal vasculitis, which is associated with a lower probability of inflammation control resulting in a worse visual prognosis. Points for discussion

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%.

Objective Management of poor response and of long-term complications after bariatric surgery (BS) is complex and under-investigated. Indications and types of reoperations vary widely and postoperative complication rates are higher compared to primary BS. Benchmarking uses best performance in a given field as reference point for improvement. Our aim was to define ‘‘best possible’’ outcomes for elective secondary BS. Methods The establishment of benchmarks in secondary BS followed a standardized methodology, based on recommendations of a Delphi consensus panel of experts. This multicenter study analyzed patients undergoing elective secondary BS in 18 high-volume centers on 4 continents from 06/2013 to 05/2019. Twenty-one outcome benchmarks were established in low-risk patients, defined as the 75th percentile of the median outcome values of the centers. Benchmark cases had no: previous laparotomy, diabetes, sleep apnea, cardiopathy, renal insufficiency, inflammatory bowel disease, immunosuppression, history of thromboembolic events, BMI>50kg/m2 or age>65 years. Descriptive statistics, multivariate logistic regression and data visualization were performed using the R software. Results Out of 44’884 elective bariatric procedures performed in the participating centers, 5’328 secondary BS cases were identified. The benchmark cohort included 3143 cases, mainly females (85%), aged 43.8±10 years, 8.4±5.3 years after primary BS, with a body mass index 35.2±7kg/m2. Main indications were insufficient weight loss (43%) and gastro-esophageal reflux disease/dysphagia (25%). 90-days postoperatively, 14.57% of benchmark patients presented ≥1 complication, mortality was 0.06% (n = 2). Significantly higher morbidity was observed in non-benchmark cases (OR 1.36) and after conversional or revisional procedures with gastrointestinal suture/stapling (OR 1.7). Benchmark cutoffs at 90-days postoperatively were ≤5.8% re-intervention and ≤8.8% re-operation rate. At 2-years (IQR 1-3) 15.6% of benchmark patients required a reoperation. Conclusion Secondary BS is safe, although postoperative morbidity exceeds the established benchmarks for primary BS. The excess morbidity is due to an increased risk of gastrointestinal leakage and higher need for intensive care. The considerable rate of tertiary BS warrants expertise and future research to optimize the management of non-success after BS.

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 B cells have a central role in the pathogenesis of several renal pathologies. Rituximab, a monoclonal antibody directed against the CD20 receptor expressed on the surface of B cells is an interesting alternative to conventional treatments of kidney pathologies. Method We conducted a descriptive retrospective study of the use of rituximab in nephrology patients. Results We collected 25 patients including 12 women and 13 men. The mean age was 33,5 [16-55] years. The rituximab was indicated for an extramembranous glomerulopathy in 6 patients, a focal segmental glomerulosclerosis in 4 patients, a minimal change disease in 4 patients, a lupus nephritis in 5 patients, and a granulomatosis with polyangiitis in 2 patients. Four kidney transplant patient received rituximab for the treatment of antibody mediated rejection in 3 cases and large cell lymphoma in 1 case. The average time between the diagnosis of the renal disease and starting treatment with rituximab was of 76 +/- 46,5 months. And it was of 16 [ 0,7 ; 59,8] months after transplantation in kidney transplant recipients. Side effects have been observed in 11 cases (44%). A favorable response has been obtained in 10 cases (40 %), within an average of 2,27 months, with at least one relapse in 4 cases. The follow-up time was 36,33 +/- 31,67 months. Conclusion Rituximab has been shown to be helpful in several cases of kidney disease. It may reduce the need for maintenance immunosuppression and help in some cases that are refractory to other therapies.

Background and Aims Delayed graft function (DGF), defined as the need for dialysis within one week post-transplantation, is associated with poorer kidney graft survival. We aimed to identify risk factors for DGF throughout 3 decades and evaluate their effect on graft survival. Method Retrospective study including 3081 kidney transplants performed at our transplantation unit between January 1st, 1989 and December 31st, 2018, split in 3 decades (1: 1989-1998; 2: 1999-2008; 3: 2009-2018). Data regarding donor and recipient demographics, time on dialysis, immunization, cold ischemia time, hemodynamic parameters and immunosuppression were collected from our prospectively maintained data base. Results Main donor, recipient and perioperative characteristics are summarized in table 1. There were clear differences in these characteristics between the decades, standing out more adverse features from both recipients and donors. Overall incidence rate of DGF was 16% (n=493): 14% in decade 1; 19.3% in decade 2 and 15% in decade 3. On univariate analysis, most studied variables included in table 1 were statistically significant as predictors of DGF. However, on multivariate analysis, we found that in the first decade the predominant risk factors for DGF were pre-transplant dialysis time and cold-ischemia time, whilst in the following decades donor characteristics, as well as recipient’s weight became more relevant (table 2). Conclusion The observed shift from donor-unrelated variables in the first decade into donor-related variables in the second and third decades as the main determinants of DGF highlights the impact of expanding donor’s acceptance criteria. Nevertheless, the increase in expanded criteria donors did not translate into poorer overall results, probable contributors being shorter cold-ischemia times and stronger immunosuppression.

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.

Background/Aims The role of gold changed from first line DMARD to use in cases where other options were limited, either due to contraindication or ineligibility for biologics. In Autumn 2019, IM gold was withdrawn by the manufacturer due to supply issues, without consultation of the Rheumatology community. As such, a group of patients with difficult to manage disease have lost a key DMARD. We aimed to assess the impact of the withdrawal of gold on the management of IA within Northumbria Healthcare Trust. Methods Retrospective case note review. Results We identified 37 patients on gold as of Autumn 2019; 16 for seropositive RA; 4 for PsA; 16 for seronegative RA and 1 for axial spondyloarthritis. 28 were taking gold monotherapy, with 3 receiving regular glucocorticoid in addition. Eight were taking gold in combination with a csDMARD and one in combination with rituximab. Data are currently available for 30 patients regarding the circumstances of gold initiation. Of these, all had received at least one alternative csDMARD which was either inefficacious or intolerable. Reasons for avoiding biologics were not documented in all cases; concerns regarding frequent chest infections were common and documented as a clear contraindication in 5. Follow up has been impacted by COVID-19; only 19 patients have had follow up within the last 6 months, 7 have not been followed up since gold cessation. Fourteen (37.8%) have commenced an alternative DMARD. Six of these have commenced a high cost drug; rituximab (3), adalimumab (2) or tofacitinib (1). Five have commenced hydroxychloroquine (with one subsequently switching to leflunomide),2 methotrexate and 1 minocycline. Seropositive RA and PsA patients are more likely to have commenced an alternative DMARD, 8/16 and 2/4 respectively; compared to 4/16 with seronegative RA. Of 23 patients who have not commenced alternative DMARDs, 17 have been reviewed following gold cessation; 3 were felt to need additional treatment; 1 has been deferred due to COVID-19 and 2 did not meet criteria for biologic treatment when assessed in early 2020 and subsequent follow up has been delayed. Fourteen patients were felt not to need an additional DMARD, although 1 required an increase in methotrexate and 6 continued co-prescribed DMARDs at the usual dose. Conclusion The majority of patients have not required additional treatment although for some patients this may reflect the fact that the COVID-19 pandemic has significantly restricted routine follow up. This unusual case of forced DMARD cessation highlights the fact that drug free remission is possible and the ongoing need for immunosuppression should be reviewed. This also raised the ethical question of weather it is right to cease the production of medication which for some patients may be the only effective treatment option. Disclosure J. Stanway: None. D. Walker: None.

Background/Aims Statins are associated with muscle symptoms, from myalgia with normal CK, to rhabdomyolysis. A sub-group have an autoimmune necrotising myopathy with anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. This can present variably, from mild self-limiting illness to severe myopathy unresponsive to statin withdrawal, requiring long-term immunosuppression. A study from New Zealand estimated the incidence of anti-HMGCR-associated myositis to be 1 in 90,000 statin users, and an incidence of 1 in 500,000 has been estimated in a US population. Anti-HMGCR antibodies were first reported in 2010. As they are new, and testing is not widely available, they may be under-recognised in the routine assessment of patients with myopathies. However, detection is important as prompt immunosuppression may be needed. Methods We compared the 2019 incidence of anti-HMGCR antibodies in Southern England from two different laboratory groups, utilising different testing criteria. The St George’s and Berkshire Surrey Pathology Services (StG/BSPS) laboratories serve a population of 3.25 million and test anti-HMGCR antibodies solely on clinician request. The Southampton laboratory serves a population of 2.33 million and tests anti-HMGCR as part of the immunoblot for all myositis-associated antibodies and where clinical details suggest myositis or ILD. Results In 2019, 14 tests were performed by StG/BSPS and 662 by Southampton, with anti-HMGCR positives of 5 (36%) and 28 (4.2%) respectively. Adjusted to include only the adult population, the incidence of anti-HMGCR antibodies is 1 in 514,000 in the StG/BSPS area versus 1 in 66,000 in the Southampton area. We estimate statins to be used in 308,000 adults in the StG/BSPS and in 220,000 in the Southampton areas, assuming treatment in 12% of adults and age demographics representative of the national population. This suggests an incidence of anti-HMGCR antibodies of approximately 1 in 62,000 statin users in the StG/BSPS area and 1 in 8,000 statin users in the Southampton area, though statin exposure was not confirmed in all positive cases. Preliminary data from 17 anti-HMGCR positive cases shows that 76% had taken statins, for an average duration of 5.84 years (range 0.75-16 years). Median peak CK was 6489 (range 241-27555). 76% required immunosuppression, of which 70% required two or more different treatments. Conclusion The 7.7-fold higher incidence from the Southampton laboratory reflects a proactive approach, selecting far more samples for anti-HMGCR assessment than specifically requested by clinicians. This demonstrates under-awareness of this antibody in routine care. We propose adoption of an algorithm to trigger more widespread testing for anti-HMGCR antibodies, to identify cases amongst those with statin-associated myalgia or myositis, and in others without statin exposure. This will lead to better understanding of the spectrum of clinical disease associated with anti-HMGCR antibodies, as well as early detection and treatment of those who develop a necrotising myopathy. Disclosure V.M.K. Joseph: None. E.C. Rose: None. M. Lloyd: None. C.J. Edwards: None. S.K. Amar: None. T. Forster: None. K.A. Smith: None. R.D. Wheeler: None. P.D.W. Kiely: None.

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?

As the number of living pediatric solid organ transplant (SOT) recipients continues to grow, there is an increased likelihood that primary care providers (PCPs) will encounter pediatric SOT recipients in their practices. In addition, as end-stage organ failure is replaced with chronic medical conditions in transplant recipients, there is a need for a comprehensive approach to their management. PCPs can significantly enhance the care of immunosuppressed hosts by advising parents of safety considerations and avoiding adverse drug interactions. Together with subspecialty providers, PCPs are responsible for ensuring that appropriate vaccinations are given and can play an important role in the diagnosis of infections. Through early recognition of rejection and posttransplant complications, PCPs can minimize morbidity. Growth and development can be optimized through frequent assessments and timely referrals. Adherence to immunosuppressive regimens can be greatly improved through reinforcement at every encounter, particularly among adolescents. PCPs can also improve long-term outcomes by easing the transition of pediatric SOT recipients to adult providers. Although guidelines exist for the primary care management of adult SOT recipients, comprehensive guidance is lacking for pediatric providers. In this evidence-based overview, we outline the main issues affecting pediatric SOT recipients and provide guidance for PCPs regarding their management from the first encounter after the transplant to the main challenges that arise in childhood and adolescence. Overall, PCPs can and should use their expertise and serve as an additional layer of support in conjunction with the transplant center for families that are caring for a pediatric SOT recipient.

Background and Aims The recipients who have antibodies againts to donors’ HLA (Anti HLA- DSA) carrie a huge risk for allograf (AG) losing. In current study, it was retrospectively evaluated whether the live donor kidney recipients (LDKRs) under desensitization (DS) were exposed to more AG loss, lower AG survival and more complications. Method In 17 of 269 LDKRs had high anti-HLA DSA were found prior to kidney transplantation (KTX). DS was performed with plasmapheresis (PF) and rituximab (RTX) before KTX. In order to determine the risks of DS, LDKRs who had not PF for any reason, were admitted immediately before and after those with LDKRs under DS were used as controls (n: 31). Immucor™ luminex method was used for detecting the anti HLA DSA. DS was performed to the Rs who had more than 5000 MFI DSA against to at least one donor HLA locus with double check. Non-parametric Fisher’s exact test was used for statistical analysis because of distribution of our patients was heterogeneous. Results In 15 Rs had DSA more than 2 HLA loci (MFI range: 5880-21712), remaining 2 Rs had one HLA locus DSA (9959-7762). Mean PF number was of 7 before TX, while 3 after TX. RTX was used in 9 Rs (53%) before TX. KTX performed when anti DSA MFI below 2000 under triple immunosuppression plus anti-thymocitic globulin (ATG) induction therapy. In 4 Rs (13%) had DSA below 5000 MFI among controls (Cs). More female Rs (88% vs. 19%, p0.05), rate of indication biopsy (24 % vs 16 %, p>0.05), rate of CNI toxicity (5.5% vs. 6.5%, p>0.05) were indifferent. During whole follow-up period, creatinine levels and eGFR were compatible at both groups. Urinary infections were more frequent in Rs under DS (53% vs 6.5%, p Conclusion Although our results belong to a single center and also a small group, desensitization before kidney transplantation for high risk kidney recipients are seem to be useful, effective and successful procedure.

Background and Aims Kidney Transplantation across very high donor specific antibodies (DSA) poses a significant challenge even today . With our current understanding and precise desensitization techniques, we are now able to do kidney transplantation across such high DSA . Here we are reporting ten such cases where baseline DSA were more than 10,000 mean fluroscent intensity (MFI) on Single Antigen Bead (SBA) Luminex. Method: It is a retrospective analiysis of ten kidney transplant patients from January 2017 to March 2019 . Patients with MFI more than 10,000 to class II HLA antigens at baseline with negative CDC and flow cytometry cross match were included in this study. All patients were treated with 1 dose of Rituximab (375mg/M? before plasma exchanges (PLEX) were started . Each session of PLEX was followed by 10 grams of intravenous human immunoglobulin (IVIg). Solid based SBA Luminex for both class I and II antigens was repeated after the third exchange and fifth exchange and seventh exchange depending on the level of MFI . Results Ten patients ( seven males three females ) of age 37± 7 years were included in this study . History of blood transfusion with 5±2 units was present in 7 patients . All females were multiparous ( 3±1children). Mean solid based SBA Luminex for class I HLA antigens was 12000 ± 1500 and for II HLA antigens with MFI 16500 ± 3500 (Chart 1). Mean number of PLEX needed was 5 ± 2 . All patients had solid based SBA MFI was 1500±300 and for class II antigens 2500 ± 1500 before transplantation(Chart 2).There was no incidence of acute antibody mediated rejection . Baseline serum creatinine at discharge was1.35±0.35mg%. There were 3 (30%) biopsy proven cases of acute cellular rejection . There was evidence of BK viremia in 3(30%) patients, CMV infection in 1 (10%) patient, Klebsiella pneumonia in 1(10%) patient and cryptosporium infection in 1 (10%) patient each . There was no mortality and mean serum creatinine at 6 months follow-up was 1.55±1.05mg%. All 3 patients of BK Viremia were treated with modification of immunosupression with substitution of leflunamide for mycophenolate and all are doing well with good graft function with a mean serum creatinine of 1.75±0.55mg% . Other infections were treated accordingly. Conclusion: Transplantation across very high donor specific antibodies is possible with excellent immediate and short term graft function with judicious de-sensitization techniques . There was increase in infection rate but none was life threatening and can be managed with proper care.

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 and Aims There are many barriers to kidney transplant and one of them is presence of donor specific antibodies (DSAs) in the recipients. Presence of strong DSA is considered a relative contraindication for kidney transplantation, however, if DSAs are of weak to moderate then desensitization is attempted in many centres with good success rate. Desensitizing such patients can be an acceptable approach to increase the donor pool and facilitating transplants. This is a retrospective analysis of patients who underwent desensitization at our centre after availability of luminex single antigen (LSA) assay Method Between April 2014 and December 2018, 825 patients underwent kidney transplantation at our centre. Patients who were CDC negative but positive FCXM were further analysed with LSA to know the presence and strength of DSAs. Our protocol for desensitization consisted of plasmapheresis (PP) 1.5 volume by double filtration on alternate day and low dose IV IG 100 mg/kg after each PP. Whenever MFI was Results Out of 825 patients, 15 underwent HLA incompatible transplants, of which, 8 were males. All patients were first transplant and 11/13 had history of some sensitizing events in the form of blood transfusion and/or pregnancy. The mean dialysis duration was 8.6 ±14.6 months. FCXM was positive in all the patients with 5 patients had T cell flow positive, 8 had B cell flow positive and 2 had both T & B cell FCXM positivity. Most patients had weak to moderate positive flow cross match. On further evaluation by LSA, all these patients had DSAs, with 3/15 had MFI 2000, out of which one patient had MFI of 7195 and six patients had multiple DSAs. These patients underwent desensitization with PP and IVIG and the end point of treatment was either MFI < 1000 or FCXM negative. Post- transplant DSAs were done in patients with high MFI or clinically indicated. Two patients had increase in post-transplant DSA titres requiring post-transplant plasmapheresis. The mean follow up was 29±6 months. On follow up, only 1 patient developed borderline cellular rejection one year after transplant, which responded with pulse steroids. Three patients had biopsy for asymptomatic rise in creatinine but it showed patchy ATN with no evidence of rejection.. One patient developed transient CMV viremia, one patient developed lymph node tuberculosis (TB) and two patients had UTI, all of them responded to treatment. There was no graft or patient loss till last follow up. Conclusion This study shows that HLA desensitisation is feasible and successful in if patients are selected carefully and evaluate thoroughly. HLA incompatible transplant can provide a new lease of life to those patients who would otherwise not get a kidney due to lack of paired exchange and deceased donor program

Background and Aims TOMOGRAM, multicenter study founded by DESCARTES ERA/EDTA WG, aims to identify transcriptomic and genomic signatures of operational tolerance (OT) in recently identified cohort of OT kidney transplant recipients. Method RNA sequencing of peripheral blood was evaluated in 15 OT patients recently identified by TOMOGRAM consortium in 8 European countries, 23 stable patients (≥ 15 years on immunosuppression, STA), 14 CABMR patients (≥ 1 year, CR), 14 non-transplant CNI-treated patients and 14 healthy controls (HC). Differential expression was performed using DESEq2 and gene annotation analysis using Enrichr. Besides immunosuppression unadjusted model, robust negative-binomial regression model was created to adjust for immunosuppression intake. The models was trained on homogeneous group of STA patients. Results Using model unadjusted for immunosuppression, no differences in transcriptomic profiles between OT, STA and HC groups were identified. Nine transcripts were upregulated and 2 downregulated in OT compared CR group. The number of deregulated transcripts substantially increased when the model was adjusted for immunosuppression. Gene annotation analysis of top ranked deregulated 1109 transcripts (FC>2, adjusted p value 0.89) were used in PCA analysis (ADGRG3, ATG2A, GDPD5, IL16, MX2, SLA2, PRKD2, SLIRP, GNLY, SRCAP, ARGHAP9, IGHM, CD5). The high probability of OT signature was found in a single STA patient. Conclusion Contrary to previous reports which pointed out towards naïve B cell signatures, unique OT patients exhibit other specific immunosuppression-independent transcriptomic profiles.

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.

Background Systemic lupus erythematosus (SLE) or lupus (Latin for wolf) is a rare multi-system autoimmune disease that has usually presented by the fifth decade, with a seven-fold higher incidence in females, especially of Afro-Caribbean descent. It is a recognised cause of pyrexia of unknown origin (PUO) though infection and malignancy are far commoner causes. Lupus nephritis (LN) can be life-threatening and affects nearly one-third of patients. We highlight a surprising case of late-onset SLE in a 65-year-old Caucasian man that presented with PUO and early LN. Methods Our patient was known to have atrial fibrillation, hypertension and previous obstructing renal calculus and presented to the Emergency Department with two weeks of right flank pain and fevers. He required critical care admission due to haemodynamic instability. CT excluded obstructive uropathy but a complex right renal cyst was present with mild inflammatory stranding. Bloods showed new neutrophilia (8.31-9.50 x 109/L), anaemia (haemoglobin 93 g/L), thrombocytopenia (platelets 90 x 109/L) and acute kidney injury (creatinine 128 μmol/l from 90 μmol/l baseline). CRP persisted above 110 mg/L. Liver function and ferritin were normal. Despite escalation of antibiotics he remained febrile, creatinine peaked at 291 μmol/L with raised urine protein:creatinine ratio (PCR) of 384 mg/mmol. Repeated septic screens and blood-borne virus tests were negative. Further CT showed mild ascites and pleural effusions. Transthoracic echocardiogram revealed a small pericardial effusion only, and pleural aspirate was a transudate, without malignant cells. Results There was clinical improvement after three weeks despite persistent fevers and he was discharged. However, readmission within three days necessitated inotropic support. After stabilisation, he was transferred under Infectious Diseases in a tertiary hospital. Shortly afterwards, the autoimmune screen showed positive anti-nuclear antibody (ANA), with positive Crithidia luciliae IgG double-stranded DNA (dsDNA) and titres >379 IU/mL. Concurrent hypocomplementaemia (C3 0.22 g/L, C4 0.03 g/L) raised the possibility of LN with SLE and renal biopsy demonstrated class 3 LN. Prompt treatment with intravenous glucocorticoids and mycophenylate mofetil (MMF) resulted in an excellent recovery. Almost a year later, he is taking MMF 1g twice daily with prednisolone 10mg daily. His creatinine is stable at 110 μmol/L, urine PCR around 300 mg/mmol and complements have normalised, despite persistent dsDNA titre of 150 IU/mL. He continues driving taxis and reports a good quality of life. Conclusion There was low suspicion of SLE in this case given the absence of typical symptoms and considering his age, gender and ethnicity. A literature review of male patients with SLE suggested tendency for later-onset and a worse prognosis. There appears to be less LN but when present requires prompt immunosuppression as occurred in this case. Currently, the oldest documented male patient with both SLE and biopsy-proven LN at diagnosis was 74 years old. Disclosures M. Chakravorty None. R. Sandler None. A. El-Nayal None.

Background Many rheumatological conditions are treated with steroids. Patients on long-term steroids are known to be at risk of adrenal insufficiency especially when withdrawing them. Sheffield Teaching Hospital (STH) Endocrinologists advised the following protocol for patients reducing steroids to determine hypothalamic pituitary adrenal status and confirm safe onward withdrawal of steroids:- After 1 month on 3mg prednisolone measure 9am serum cortisol and ACTH (after 24 hours off steroid)- If cortisol 150nmol/L and ACTH >10pg/mL) arrange short Synacthen test (SST). If 30-minute cortisol 430nmol/L - stop steroids and monitor for adrenal insufficiency (give hydrocortisone 20mg TDS to cover illness for 3 months after stopping prednisolone). Methods We performed a retrospective review of records of rheumatology patients having morning cortisol level checked July 2017-January 2019 to determine how many tests were abnormal and to what degree the results changed management. Results 160 cortisol tests were performed. 36 were excluded from further analysis. Of the 124 cases reviewed: 80 females and 44 males. Age range 18-87; mean 64 years. Starting dose of prednisolone 5-60mg. Duration of steroid use 6 months to > 10 years; modal duration 13-24 months (49 patients/40%). 59 patients/48% were taking other immunosuppressants. Prednisolone dose at cortisol testing 1-5mg; modal value 3mg (89 patients/72%). 12 patients/10% had a normal morning cortisol. 9 patients/7% fell into the group ‘cortisol 10 years; modal duration 13-24 months in 9 patients/43%. 12 patients/57% were on other forms of immunosuppression. Conclusion Endocrinology guidance changed the management of 3 patients/2% by the introduction of hydrocortisone compared with previous rheumatology standard practice of weaning prednisolone by 1mg per month or similar. No distinctive characteristics were identified in patients with abnormal SST, except for a greater proportion of men (35% of whole group: 62% of abnormal SST group). Given the limited impact of the investigations, and the shortage of Synacthen, a new protocol has been implemented: if morning cortisol Disclosures R. Smith None. M. Akil Honoraria; AbbVie, Actelion, Celgene, Astra Zenica, Lilly and UCB.

Background Membranous nephropathy is the chief etiology of nephrotic syndrome in adults. It is clinically featured and presented by investigational tool as very high of protein levels in urine, edema, hypoalbuminemia and elevated serum level. Idiopathic membranous nephropathy is a chronic pathological form of clinical scenarios and its pathophysiological course involves spontaneous remissions or remissions by immunosupressions with frequent relapses. Aim To assess the efficiency of Rituximab as a secondary line immunosuppression in Patients with Idiopathic Membranous Nephropathy (IMN) who failed to respond to Ponticelli regimen and to compare it with Cyclosporine. Methods This study is a retrospective cohort study including 40 Egyptian patients with biopsy proven IMN who failed primary immunosuppression with cyclophosphamide and steroids according to Ponticelli regimen divided into two equal groups, 20 patients each. Cyclosporine Group: received Cyclosporine, given daily for a minimum of 6 months at doses of 3.5 mg/kg orally and Rituximab Group: received Rituximab weekly for 4 weeks at doses of 375 mg/m2 intravenously. Data collected included UPCR, eGFR, serum albumin, serum creatinine, CBC, lipid profile for 6 times: before giving cyclosporine or rituximab (time 0), after 1month, 3, 6,9 and 12 months. Results 17 patients achieved remission (7 CR and 10 PR) in CSA treated group while 13 patients (1 CR and 12 PR) in RTX group, P = 0.077. UPCR was reduced for >50% in patients receiving Cyclosporine compared to 30% in Rituximab treated group: UPCR was decreased from 5.9±3.5 at time 0 to 2.0±2.8 (p = 0.002) & decreased from 7.3±5.2 to 4.6±3.9 (P = 0.031) in Cyclosporine and Rituximab groups respectively. There was improvement of serum albumin in both groups by the end of study more remarkable in cyclosporine group. The eGFR was non significantly reduced by the end of study in RTX group while it showed significant reduction in CSA group. No serious adverse events were reported all through the study period in both groups. Conclusion Rituximab is an efficient, well tolerated secondary immunosuppressant drug in IMN. Its effect is comparable to CSA regarding remission induction. It induces better results than CSA regarding effect on eGFR but worse results regarding proteinuria improvement. Individualization of immunosuppressant use in IMN should be considered.

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.

Background Norovirus is a common cause of gastroenteritis in both immunocompetent and immunocompromised hosts. In transplant recipients, it can lead to prolonged shedding and chronic diarrhea. Treatment with nitazoxanide, oral immunoglobulin, or mammalian target of rapamycin (mTOR) inhibitors have shown varying degrees of benefit in small studies. The commensal gastrointestinal bacterial flora may influence the pathogenesis of norovirus infection. Metronidazole is often used to modulate gastrointestinal flora, and improvement of an HIV patient with suspected Giardia infection subsequently identified to have norovirus suggested a possible use of this drug for other immune-suppressed patients with norovirus infection. Methods Solid-organ or stem cell transplant recipients testing positive for norovirus in stool from July 2014 to March 2019 were identified from the medical record. Patient characteristics, laboratory data, and medications were systematically reviewed to identify factors associated with clinical improvement. Results Thirty-eight patients met inclusion criteria. Almost 75% of the patients were male. Almost 80% of the patients were solid-organ transplant recipients: 40% heart, 24% kidney, and 15% liver. There were 85 positive norovirus tests among the 38 patients. Of these, 14 involved coinfections with another potential pathogen: 11 with adenovirus, 2 with Clostridioides difficile, and 1 with cytomegalovirus. In 25 of the 85 positive norovirus tests, nitazoxanide was given. Clinical improvement was documented in 15 of these episodes (60%), while no improvement was observed in 10 (40%). Eight positive tests were treated with metronidazole alone, with documented improvement observed during 6 (75%) courses. In 9 additional episodes, metronidazole was given within a week of the test result and 2 of these had improvement. When other antibiotics were used concurrently with metronidazole, 78% of episodes (7/9) did not lead to clinical response. Changes in immunosuppression were used for the treatment of 6 episodes, leading to clinical improvement in 5. Conclusion Metronidazole treatment was associated with clinical improvement of norovirus gastroenteritis in transplant recipients at rates similar to those seen with nitazoxanide therapy. Reduction in immunosuppression also led to clinical improvement but in situations where that cannot be done safely, metronidazole may be an alternative to nitazoxanide. In this cohort, metronidazole was only used as a therapy after nitazoxanide, suggesting that a trial of metronidazole as rescue therapy in comparison to a repeat course of nitazoxanide after the initial failure of nitazoxanide is justified.

Background Trimethoprim-sulfamethoxazole (T/S) and levofloxacin are considered first line agents for the treatment of Burkholderia cepacia complex (Bcc). Combination therapy (CT) is frequently utilized despite limited clinical evidence supporting this. The objective of this study is to compare outcomes associated with different regimens for the treatment of Bcc infections. Methods This is a retrospective cohort study in non-cystic fibrosis adult patients with infection caused by Bcc from 2015 to 2019. The primary outcome is the composite of overall treatment failure defined as clinical failure, microbiologic failure, or mortality at 30 days. Secondary outcomes include mortality, clinical failure, microbiological failure, development of resistance, recurrence, and safety. Comparisons were performed using Chi-squared or Fischer’s exact test for categorical variables and Student’s t test or the Mann-Whitney U test for continuous variables, as appropriate. Multivariable logistic regression analysis was used to identify independent risk factors for overall treatment failure. Results Sixty-eight patients were included, 50 (74%) received monotherapy (MT) and 18 (26%) received CT. MT regimens included meropenem (n=19), ceftazidime (n=15), T/S (n=10), and other (n=6). Various combination regimens were utilized. MT recipients were significantly older, more likely to have renal disease, less likely to have an immunosuppression, and had a higher severity of illness. The most common site of infection was respiratory (78%). No difference was found for overall treatment failure between MT and CT (36.0% vs. 38.9%; p=0.947). No differences were found in the secondary outcomes (Table 1). Overall treatment failure did not differ by treatment regimens utilized. On multivariable analysis controlling for age, renal disease, CCI, immunosuppression, ICU admission, SOFA score, and receipt of MT, only SOFA score was associated with treatment failure [OR 1.43 (95% CI 1.15 to 1.77); p=0.001] and not MT [OR 1.22 (95% CI 0.25 to 5.97); p=0.808]. Table 1: Treatment Outcomes – MT versus CT Conclusion There were no differences in outcomes between MT and CT groups for the treatment of Bcc infection. Treatment outcomes appeared to be driven primarily by disease severity. Additional studies are needed to identify the optimal treatment regimens. Disclosures All Authors: No reported disclosures

Background Transplant recipients are more vulnerable to infections including COVID-19, given their co-morbidities and chronic immunosuppression. Most preliminary care series report rapid clinical progression and higher mortality compared to the general population. Methods Retrospective study at Harper University Hospital - Detroit Medical Center. Twenty-five renal transplant recipients (RTR) presenting consecutively with COVID-19 symptoms and positive NP swab PCR for SARS-CoV2 between 03/01/2020 - 05/01/2020 were included. Data on demographics, clinical presentation, laboratory findings, management and outcomes were collected. Results All 25 patients were hospitalized. Patients had a median age of 56, all African American and deceased donor transplant recipients. Most had hypertension (96%), about half (52%) had diabetes, 64% had pulmonary disease including obstructive sleep apnea, COPD and pulmonary hypertension. Most common presenting symptom was dyspnea (64%), followed by fever and cough (56%) and diarrhea (56%). One-half of patients had multifocal opacities on initial chest x-ray (52%). Immunosuppression with tacrolimus and low dose prednisone was continued, while mycophenolate mofetil was held on admission. Following institution guidelines, hydroxychloroquine was given to 32%, while 48% received both hydroxychloroquine and steroids. Prophylactic anticoagulation was given to 80% of patients and therapeutic coagulation to 8%. Oxygen supplementation given to 60% of patients and one patient required intubation. Three patients (12%) required transfer to the intensive care unit, one expired. At follow-up, treatment with mycophenolate was reintroduced based on resolution of symptoms and laboratory parameters. Conclusion COVID-19 infected RTR in this small cohort had lower mortality of 4% (n=1) compared to State-wide mortality of 10%. Despite multiple co-morbidities and chronic immunosuppression, our patient cohort had excellent prognosis and lower mortality compared to other series. Exact reasons for this optimal outcome are explored. Disclosures All Authors: No reported disclosures

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 Immunosuppression during liver transplantation (LT) enables the prevention and treatment of organ rejection, but poses a risk for severe infectious diseases. Antimicrobials are often required for patients after LT. Recently, the genomes of multiple microorganisms have been detected in blood, which is essentially sterile. Immune modulation and antimicrobials affect the blood microbiome. Thus, determining the impact of immunosuppression and antimicrobials on the microbiome may be important to understand immunocompetence, predict clinical adverse events after LT such as acute cellular rejection (ACR), and treat infectious diseases. Methods Fifty-one patients who received LT at Nagoya University Hospital from 2016 to 2018 were enrolled. Plasma samples were retrospectively collected within a week after LT, 4±1 weeks after LT, 8±1 weeks after LT, and within 2 days after a positive blood culture. A total of 111 plasma samples were analyzed using shotgun next-generation sequencing (NGS). Sequence data were imported into the custom-made analysis pipeline PATHDET. Results The relative abundance of Anelloviridae, Nocardiaceae, Microbacteriaceae, and Enterobacteriaceae significantly changed during the postoperative period (figure 1). Microbiome diversity was higher within a week after LT than at 8 weeks after LT. Antimicrobials were significantly associated with the microbiome of LT recipients. In addition, the proportion of Enterobacteriaceae was significantly decreased (figure 2) and the plasma microbiome diversity was significantly higher in patients with ACR than in non-ACR patients. Finally, sequencing reads of bacteria isolated from blood cultures were predominantly identified by NGS in 8 of 16 samples (figure 3), and human herpesvirus 6 was detected as a causative pathogen in one recipient with severe infectious diseases. Change in the relative abundance of each microorganism at the family level of taxonomic hierarchy in plasma samples after liver transplantation Comparison of the plasma microbiome at the family level in patients with and without acute cellular rejection Relative abundance of microorganisms at the species level in plasma from patients with positive blood cultures Conclusion The metagenomic NGS technique has great potential in revealing the plasma microbiome and is useful as a comprehensive diagnostic procedure in clinical settings. Temporal dynamics of specific microorganisms may be used as indirect markers for the determination of immunocompetence and ACR in LT recipients. 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.