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BACKGROUND Granulomatosis with polyangiitis (GPA) is a rare autoimmune disease that involves small-to-medium-sized vessels and forms necrotizing vasculitis with granulomatous inflammation. The formation of a large vessel lesion in GPA patients has been scarcely reported, and it can cause confusion in the diagnosis. CASE SUMMARY A 27-year-old man presented with mild left-sided pleuritic chest pain that started one year prior. An imaging study revealed up to 2.5 cm-sized two irregular nodular consolidation nodule in the left lower lobe. Both nodules showed central necrosis. Also, there was a periaortic mass occluding the branching porting of the subclavian artery. He had positive anti-neutrophil cytoplasmic antibodies (ANCAs), but myeloperoxidase-ANCAs and proteinase 3-ANCAs were negative. The patient also developed symptoms of subclavian vein syndrome during the follow-up. Wedge resection of the lung revealed necrotizing vasculitis, destructive parenchymal abscess and surrounding granuloma, and therefore diagnosed of GPA. The patient started on methotrexate and steroid therapy with a relief of symptomatic. CONCLUSION Here, we present an unusual manifestation of GPA with periaortitis and consequent subclavian steal syndrome, which has never been previously described. This case alerts us that we should include GPA in the differential diagnosis of large vessel vasculitis as well as subclavian steal syndrome.

Introduction. Granulomatosis with polyangiitis (GPA), formerly known as Wegener?s granulomatosis, is characterized by necrotizing granulomatous inflammation in various tissues, including blood vessels, but primarily in the respiratory tract and kidneys. Clinical manifestations can be diverse, including inflammation of the eye and adnexa. Optic neuritis is a very rare ophthalmological manifestation of GPA, not previously described in a teenager. Case report. We presented a case of a 16-year-old girl with a rare extrapulmonary manifestation of GPA. The girl had a previous history of GPA and complained of a sudden blurred vision in the left eye. She was promptly referred to an ophthalmologist who noted a decreased visual acuity of 20/400 in the left eye. Colour vision was impaired in the spectrum of red colour. Clinical examination revealed normal anterior segment findings. On ophthalmoscopy, the left optic nerve oedema was noted. Urgent computed tomography of the left orbit showed a soft tissue mass around the optic nerve in the apex of the orbit. Magnetic resonance imaging confirmed the diagnosis of optic perineuritis. After pulse doses of methylprednisolone, the girl achieved complete resolution of vision in the left eye. Conclusion. If untreated, inflammation of the optic nerve can lead to a permanent loss of vision. Prompt diagnostic and adequate treatment of patients with GPA is needed in order to prevent vision-threatening complications and control the systemic disease.

Raynaud’s phenomenon (RP) is an episodic digital vasospastic condition that is prevalent among 5% of the population. The symptoms range from reversible pallor to ischemia and gangrene. RP can be primary or secondary. We discuss a case of severe RP secondary to granulomatosis with polyangiitis (GPA) that presented with ischemia and gangrene. Studies show that approximately

Objectives Previous studies have shown that adipokines may serve as potential biomarkers reflecting disease activity in various autoimmune diseases. Here, we investigated the relationship between four adipokines and clinical/laboratory findings in patients with microscopic polyangiitis (MPA) and granulomatosis with polyangiitis (GPA). Methods Sera from 63 patients with MPA and GPA who were registered in a prospective cohort were used to detect serum levels of adiponectin, chemerin, resistin, and vaspin using commercial enzyme-linked immunosorbent assay kits. Associations between adipokines and clinical and laboratory data was assessed using Pearson’s correlation analysis. Results The median age was 65.0 years, 24 patients were male, and 42 patients were diagnosed with MPA. The median levels of adiponectin, chemerin, resistin, and vaspin in patient sera were 13.9 ng/mL, 9.2 ng/mL, 23.7 ng/mL, and 0.1 ng/mL, respectively. A significant correlation between chemerin level and five-factor score (FFS) was found (r = 0.320, p = 0.011), and resistin was correlated with both Birmingham vasculitis activity score and FFS (r = 0.256, p = 0.043 and r = 0.320, p = 0.011). Regarding laboratory data, adiponectin level was associated with creatinine, and chemerin level was associated with creatinine, albumin, and erythrocyte sedimentation rate (ESR). On the other hand, resistin was found to be associated with white blood cell count, creatinine, ESR, and C-reactive protein. Age did not have a significant impact on the levels of adipokines. Conclusions The expression of adipokines in the sera of patients with MPA and GPA differs depending on clinical and laboratory features, and serum resistin may be suggested as a potential biomarker reflecting disease activity.

Granulomatosis with polyangiitis (GPA) is a rare cause of prostatitis. Our case illustrates a case of granulomatous prostatitis secondary to unrecognised GPA requiring multiple surgical interventions. The patient presented with lower urinary tract symptoms. They underwent two endoscopic prostatic resections for recurrent urinary obstruction due to granulomatous prostatitis before a diagnosis of GPA was made. The rarity of this pathology, challenges in making a diagnosis and the systemic nature of this disease are emphasised.

The pulmonary vasculitides include a wide spectrum of disorders that have in common inflammation and destruction of pulmonary blood vessels. Granulomatosis with polyangiitis (GPA), formerly known as Wegener granulomatosis, is the most common of the antineutrophil cytoplasmic antibody–associated smal

Funding Acknowledgements Type of funding sources: None. Background. The differentiation between vagally and non-vagally mediated atrial fibrillation (AF) could be useful to decide adding ganglionated plexi ablation (GPA) to pulmonary vein isolation (PVI) in patients with vagally mediated AF onset. The role of the autonomic nervous system in triggering paroxysmal AF can be analyzed through heart rate variability (HRV) parameters. The low frequency/high frequency ratio (LF/HF) is used as an index of sympatho-vagal interaction. Based on clinical criteria, values of LF/HF Purpose Identify patients with paroxysmal AF who may benefit from GPA in addition to PVI, based on analysis of HRV parameters Material and methods From our database of unselected Holter recordings containing paroxysmal AF episodes, 199 analyzable AF onsets were labelled. We analyzed HRV frequential parameters by segments every 300 RR intervals to identify adrenergic and vagal onsets of AF episodes. We categorized AF onsets, depending of their respective values of LF/HF. We also checked the relationship of these parameters to heart rate (HR). We followed the evolution of the mean normalized values of LF/HF from the beginning of the recordings to the AF onsets (see figure). Results We found a progressive increase of LF/HF in normalized units (mean [95% confidence interval]) from 2.44 [2.12-2.76] to 3.12 [2.85-3.39] in the adrenergic group (n = 113) and a progressive decrease of LF/HF from 1.51 [1.28-1.75] to 1.02 [0.95-1.09] in the vagal group (n = 86). Differences between adrenergic and vagal AF were highly significant using Mann-Whitney test (p Conclusions Our data show potential added value of frequential HRV analysis to guide additional ganglionated plexi ablation to PVI. This remains to be demonstrated in a prospective study. The ratio LF/HF should be considered to optimize the decision-making process for the ablation procedure. Abstract Figure. Frequential HRV parameters before AF

Background and Aims ANCA-associated vasculitis (AAV) is the most common cause of rapidly progressive glomerulonephritis globally and the most common finding in renal biopsies for those above 75 years of age. Patients with AAV have had an improved outcome after the introduction of immunosuppressive therapy. However, there is still an increased risk of end stage renal failure, complications to therapy, comorbidities and death. The European Vasculitis Society (EUVAS) has run several prospective randomized clinical trials (RCT) since late -90’ies as an attempt to improve the outcome for patients with a broad spectrum of AAV. The aim of the current study was to analyze results from a 10-year follow-up of patients who have participated in EUVAS’s randomized clinical trials to report on patient outcomes using current standard of care immunosuppressive treatment. Method Data on patient outcomes were collected from questionnaires to the principal investigators of the original RCTS (74 centers from 17 countries in Europe): MEPEX, NORAM, CYCAZAREM, CYCLOPS, IMPROVE, RITUXVAS and MYCYC. All patients were well characterized at inclusion in the trials respectively, as was the type and duration of induction therapy. Long-term follow-up data regarding cumulative duration and type of immunosuppressive therapy, end stage renal failure (ESRF), renal transplantation, patient survival and comorbidities as cardiovascular events, infections were recorded. Efforts have been made to control and validate the collected data. Results The current dataset comprises 858 patients, of whom 708 were eligible to include in this study. We received questionnaires regarding patient outcomes from 70% of the cohort. The median age was 60 years at time of the diagnosis of AAV; 487 patients had GPA (57%) and 371 MPA (43%). The median follow-up time was 8.0 years (IQR: 2.9-13.6). During the observation period, there were 305 deaths: 78 patients died within the first year of follow up, 69 during the following 5 years, and another 158 patients after 5 years. The main causes of death were infections (25%), cardiovascular disease (14%) and malignancies (13%), followed by pulmonary diseases, vasculitis, others, kidney disease and gastrointestinal disease. Vasculitis were a major contributor to the causes of death in 18% of the patients. Median survival time for the whole cohort was 17.8 years (95%CI: 15.6 – 20.1). Survival rate at 5 and 10 years was 81.6% and 66.5% respectively. Advanced age, low estimated glomerular filtration rate and male sex were negative prognostic factors for patient survival in the Cox model. When we categorized the deaths according to their initial CKD stage, the highest number of deaths was found in the group of patients with low eGFR i.e. an initial CKD stage V (40%). The initial CKD stage, as shown in the Kaplan-Meier curve, was found to have an important impact on the patient survival (LR: 144.4 p In our cohort, 159 patients (18.5%) reached ESRF, of whom 110 patients died (69%); the main cause of death in this group was infection. Conclusion In a series of over 800 patients with AAV, ten-year mortality was predominantly associated with impaired renal function at onset, older age and male gender, rather than subtype of disease. The main strength of this study is that we have a well-defined cohort of patients with AAV, all with well-defined induction treatments and a long period of follow-up with the possibility to analyze possible prognostic factors regarding outcomes. Further analyses are ongoing regarding comparative statistics, cumulative incidence of malignancies, renal transplantation and comorbidities. The data supports efforts to diagnose these patients at an earlier stage, when they have a higher eGFR and to tailor therapy for the individual patient. Although newer treatment modalities are available, there is still a considerable morbidity and mortality in the long-term.

Background/Aims Anti-neutrophil cytoplasmic antibody (ANCAs) associated vasculitis (AAV) encompasses: Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA). The 1999 international consensus for ANCA testing recommended the use of indirect immunofluorescence (IIF) to screen for ANCAs, with immunoassays for proteinase-3 (PR3)-ANCAs and myeloperoxidase (MPO)-ANCAs in positive samples. In 2017 this consensus was revised, recommending the implementation of a strict gating strategy for ANCA requests, followed by high-quality immunoassays as the primary screening method, to reduce the volume of tests requested, reducing the false-positive rates, thereby improving the diagnostic performance of ANCA testing. Testing at the Royal Wolverhampton Trust is based on the 1999 consensus. Tests perform poorly when not carried out in the correct setting due to low pre-test probability; we aimed to implement a gating strategy to filter inappropriate ANCA test requests to improve the diagnostic performance of ANCA testing at our centre. We assessed the use of IIF and antigen specific assays in the diagnosis of AAV. Methods We reviewed the records of patients that had ANCA tests requested in June 2019. A gating strategy in the form of an indication selection ‘pop-up box’ directing clinicians to select an appropriate clinical indication for the request was implemented. We re-audited ANCA requests made post-intervention Feburary 2020. ANCA requests were assessed against clinical indications in the 1999 consensus for appropriateness; we assessed the diagnostic performance by the proportion of ANCA tests correctly identifying AAV and calculating the sensitivity and specificity of IIF and immunoassays for MPO/PR3-ANCAs in detecting AAV. Results Post-intervention, 105 fewer ANCA requests were made (298v403). Due to insufficient information, 345 patients pre-gating and 252 patients post-gating-strategy were used for analysis. The proportion of appropriate requests made was greater post-intervention, 215/252 (85.3%) vs 119/345(34.5%). Pre-intervention AAV was identified in 13 (3.8%) patients; AAV was identified in 21 (8.3%) patients following the gating-strategy introduction. IIF was found to have sensitivity of 91.7% pre and 76.2% post-intervention; specificity was 53.0% pre and 58.9% post-intervention. MPO/PR3 immunoassay testing was found to have a sensitivity of 91.7% pre and 57.1% post-intervention; specificity was 97.4% pre and 97.9% post-intervention. Conclusion The introduction of a gating-strategy for ANCA testing at our centre effectively reduced the overall number of ANCA requests by 26.1% over a 1-month period and significantly increased requests with an appropriate recorded indication. The proportion of tests correctly identifying AAV diagnosis increased following the introduction of the gating strategy indicating an improvement in diagnostic performance of ANCA testing. These results indicate antigen specific testing is more specific for a diagnosis of AAV and sensitivity of IIF was reduced following introduction of the gating strategy suggesting IIF is of no additional benefit when an effective gating strategy is employed. Disclosure N. Cleaton: None. N. Barkham: None. T. Adizie: None.

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P&nbsp

International audience; A 62-year-old man, who was a heavy drinker, presented with deep asthenia, isolated fever, inflammatory syndrome (CRP 120 mg/l) and cytopenias (Hb 6.5 g/dl, platelet count 100 G/l). A whole-body CT scan found dysmorphic hepatomegaly and splenomegaly. Endoscopy revealed bleeding gastrointestinal angiodysplasia and non-bleeding oesophageal varices. After coagulation for angiodysplasia and blood transfusions, the Hb level remained around 8.5 g/dl. To investigate blood malignancy, a bone marrow biopsy revealed small-vessel vasculitis (Fig. 1A, 2), fibrinoid necrosis affecting the small vessel walls (Fig. 1A, 3), multinucleated giant cells (Fig. 1A, 1) constituting microgranulomas (Fig. 1A, 4) and...

INTRODUCTION Survival prediction in brain metastases (BMs) remains challenging. Current prognostic models have been created and validated almost completely with data from patients receiving radiotherapy only, leaving uncertainty about surgical patients. Therefore, the aim of this study was to build and validate a model predicting 6-month survival after BM resection using different machine learning (ML) algorithms. METHODS An institutional database of 1062 patients who underwent resection for BM was split into a 80:20 training and testing set. Seven different ML algorithms were trained and assessed for performance. Moreover, an ensemble model was created incorporating random forest, adaptive boosting, gradient boosting, and logistic regression algorithms. Five-fold cross validation was used for hyperparameter tuning. Model performance was assessed using area under the receiver-operating curve (AUC) and calibration and was compared against the diagnosis-specific graded prognostic assessment (ds-GPA); the most established prognostic model in BMs. RESULTS The ensemble model showed superior performance with an AUC of 0.81 in the hold-out test set, a calibration slope of 1.14, and a calibration intercept of -0.08, outperforming the ds-GPA (AUC 0.68). Patients were stratified into high-, medium- and low-risk groups for death at 6 months; these strata strongly predicted both 6-months and longitudinal overall survival (p < 0.001). CONCLUSIONS We developed and internally validated an ensemble ML model that accurately predicts 6-month survival after neurosurgical resection for BM, outperforms the most established model in the literature, and allows for meaningful risk stratification. Future efforts should focus on external validation of our model.

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 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?

Eosinophilic Granulomatosis with Polyangiitis (EGPA, Churg-Strauss syndrome) is a rare anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) characterised by respiratory manifestations and systemic organ involvement [1]. Particularly, cardiac manifestations occur in 40–60% of patients, representing the leading cause of mortality [2]. Recent reports suggest that venous thromboembolic events might also represent a consistent burden of disease [3, 4], as already known for the other AAVs [5–7], possibly due to eosinophil-mediated vascular inflammation [5]. Nevertheless, the occurrence of arterial and venous thrombotic events (AVTE) has never been systematically explored in EGPA. Footnotes This manuscript has recently been accepted for publication in the European Respiratory Journal . It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article. Conflict of interest: Alessandra Bettiol Conflict of interest: Renato Alberto Sinico Conflict of interest: Franco Schiavon Conflict of interest: Sara Monti Conflict of interest: Enrica Paola Bozzolo Conflict of interest: Franco Franceschini Conflict of interest: Marcello Govoni Conflict of interest: Claudio Lunardi Conflict of interest: Giuseppe Guida Conflict of interest: Giuseppe Lopalco Conflict of interest: Giuseppe Paolazzi Conflict of interest: Angelo Vacca Conflict of interest: Gina Gregorini Conflict of interest: Pietro Leccese Conflict of interest: Matteo Piga Conflict of interest: Fabrizio Conti Conflict of interest: Paolo Fraticelli Conflict of interest: Luca Quartuccio Conflict of interest: Federico Alberici Conflict of interest: Carlo Salvarani Conflict of interest: Silvano Bettio Conflict of interest: Simone Negrini Conflict of interest: Carlo Selmi Conflict of interest: Savino Sciascia Conflict of interest: Gabriella Moroni Conflict of interest: Loredana Colla Conflict of interest: Carlo Manno Conflict of interest: Maria Letizia Urban Conflict of interest: Alfredo Vannacci Conflict of interest: Maria Rosa Pozzi Conflict of interest: Paolo Fabbrini Conflict of interest: Stefano Polti Conflict of interest: Mara Felicetti Conflict of interest: Maria Rita Marchi Conflict of interest: Roberto Padoan Conflict of interest: Paolo Delvino Conflict of interest: Roberto Caporali Conflict of interest: Carlomaurizio Montecucco Conflict of interest: Lorenzo Dagna Conflict of interest: Adriana Cariddi Conflict of interest: Paola Toniati Conflict of interest: Dr. Tamanini reports other from Glaxo Smith Kline, outside the submitted work. Conflict of interest: Federica Furini Conflict of interest: Alessandra Bortoluzzi Conflict of interest: Elisa Tinazzi Conflict of interest: Lorenzo Delfino Conflict of interest: Iuliana Badiu Conflict of interest: Giovanni Rolla Conflict of interest: Vincenzo Venerito Conflict of interest: Florenzo Iannone Conflict of interest: Alvise Berti Conflict of interest: Roberto Bortolotti Conflict of interest: Vito Racanelli Conflict of interest: Guido Jeannin Conflict of interest: Angela Padula Conflict of interest: Alberto Cauli Conflict of interest: Roberta Priori Conflict of interest: Armando Gabrielli Conflict of interest: Milena Bond Conflict of interest: Martina Tedesco Conflict of interest: Giulia Pazzola Conflict of interest: Paola Tomietto Conflict of interest: Marco Pellecchio Conflict of interest: Chiara Marvisi Conflict of interest: Federica Maritati Conflict of interest: Alessandra Palmisano Conflict of interest: Christian Dejaco Conflict of interest: Johann Willeit Conflict of interest: Stefan Kiechl Conflict of interest: Iacopo Olivotto Conflict of interest: Peter Willeit Conflict of interest: Domenico Prisco Conflict of interest: Augusto Vaglio Conflict of interest: Giacomo Emmi

Granulomatosis with polyangiitis (GPA) is an autoimmune disease affecting mainly small blood vessels. B-cells are important in the GPA pathogenesis as precursors of autoantibody-producing cells but likely also contribute (auto)antibody-independently. This has been underlined by the effectiveness of B-cell-depletion (with Rituximab) in inducing and maintaining disease remission. Mycophenolate-mofetil (MMF) and azathioprine (AZA) are immunosuppressive therapies frequently used in GPA-patients. Interestingly, MMF-treated GPA-patients are more prone to relapses than AZA-treated patients, while little is known about the influence of these drugs on B-cells. We investigated whether MMF or AZA treatment (or their active compounds) alters the circulating B-cell subset distribution and has differential effects on in vitro B-cell proliferation and cytokine production in GPA-patients that might underlie the different relapse rate. Circulating B-cell subset frequencies were determined in samples from AZA-treated (n = 13), MMF-treated (n = 12), untreated GPA-patients (n = 19) and matched HCs (n = 41). To determine the ex vivo effects of the active compounds of MMF and AZA, MPA and 6-MP respectively, on B-cell proliferation and cytokine production, PBMCs of untreated GPA-patients (n = 29) and matched HCs (n = 30) were cultured for 3-days in the presence of CpG-oligodeoxynucleotides (CpG) with MPA or 6-MP. After restimulation (with phorbol myristate acetate, calcium-ionophore), cytokine-positive B-cell frequencies were measured. Finally, to assess the effect of MMF or AZA treatment on in vitro B-cell proliferation and cytokine production, PBMCs of MMF-treated (n = 18), and AZA-treated patients (n = 28) and HCs (n = 41) were cultured with CpG. The memory B-cell frequency was increased in AZA- compared to MMF-treated patients, while no other subset was different. The active compounds of MMF and AZA showed in vitro that MPA decreased B-cell proliferation in GPA-patients and HCs. B-cell proliferation in MMF- and AZA-treated patients was not different. Finally, the IL-6+ B-cell frequency was decreased by MPA compared to 6-MP. No differences in IL-10+, IL-6+ or TNFα+ B-cell proportions or proliferation were found in MMF- and AZA-treated patients. Our results indicate that MMF could be superior to AZA in inhibiting B-cell cytokine production in GPA-patients. Future studies should assess the effects of these immunosuppressive drugs on other immune cells to elucidate mechanisms underlying the potential differences in relapse rates.

OBJECTIVES: Food insecurity is a public health concern in the US. Collegiate student-athletes may be at increased risk due to the nutritional and physical demands of performance and, limited time for employment and food preparation/intake. The objective of this study was to determine the rate of food insecurity and its characteristics among The National Collegiate Athletic Association (NCAA) student-athletes. METHODS: A cross-sectional analysis of student-athletes attending a public university in rural East Texas in 2018 was conducted. A 26-item questionnaire including sociodemographic characteristics and the six-item U.S. Household Food Security Survey Module (US-HFSSM), adapted to reflect the prior six months while training, was administered electronically to NCAA student-athletes. Each affirmative response to the US-HFSSM was given a score of “1” and summed to create a raw score ranging from 0–6. Participants with a score of 0–1 were considered food secure; those with a score of 2–4 (low food secure) or 5–6 (very low food secure) were considered food insecure. RESULTS: Ninety-one student-athletes (27% response rate) representing 13 sports completed the questionnaire. Participants were 19.81 ± 1.3 years old, mostly female (85.7%), Caucasian (67%), and of normal weight (BMI of 18.5–24.9 kg/m(2); 74.7%). Nearly half (39.6%) reported food insecurity despite receiving wide-ranging assistance via scholarship support (86.1%) and/or the possession of a meal plan (42.9%). Food insecure participants reported limited money (25%) and time (19.4%) as barriers to food intake. Independent-samples t tests were conducted to compare grade point average (GPA) and BMI of food secure and food insecure groups. GPA was lower in the food insecure (M = 3.26, SD = .52) than the food secure group (M = 3.58, SD = .41); (t(63) = 3.06, P = .003) while BMI was higher in the food insecure (M = 24.05, SD = 3.56) than the food secure group (M = 22.85, SD = 2.17); (t(52) = –1.807, P = .077). CONCLUSIONS: Despite the provision of scholarships and meal plans, the prevalence of food insecurity reported among NCAA student-athletes was similar to previous reports among the general collegiate population. Unique solutions that address the increased nutrient demands and time constraints associated with sport participation are warranted. FUNDING SOURCES: N/A.

Background Aortitis is a heterogeneous rare condition causing aortic inflammation, often due to infectious or autoimmune aetiology. Its presentation, diagnosis and optimal management remain poorly understood, often requiring multidisciplinary input. With the advent of improved imaging techniques, an increasing number of radiology reports are identifying features of vasculitis necessitating clinical investigation. We investigated how cases identified on imaging with features of aortitis reflected clinical diagnosis and treatment. We further examined whether radiological detection of aortitis enables more rapid management decisions to improve outcomes. Methods A search was conducted of all radiology reports from St George’s Hospital between 2008 and 2018 for key words indicating “aortitis”, including ‘hyperintense vessel uptake’ and ‘periaortic inflammation.’ From 15,963 initial results, 80 reports were identified with radiological suspicion of aortitis. Results Of 80 cases, 36/80 were diagnosed with autoimmune or idiopathic inflammatory pathology: 9 retroperitoneal fibrosis, 8 idiopathic, 7 Takayasu’s, 4 giant cell arteritis, 2 inflammatory aneurysms, 2 Behçet's, 2 IgG4 disease, 1 lupus, 1 granulomatosis with polyangiitis. Diagnosis of autoimmune or idiopathic aortitis was based on symptomatology, imaging, serology, vessel biopsy, and treatment response. 14/80 had infective aortitis: 11 had positive microbiology and 3 demonstrated empirical antibiotic response. Table 1 shows demographics. 12/80 had atheromatous disease. 18/80 were not further investigated due to comorbidity, lack of correlation with symptoms, or absence of follow-up. Initial imaging modalities with the highest yield were computed tomography (CTs) with aorta protocols and CTs of thorax/abdomen/pelvis. The most useful radiology report terms included: aortitis, periaortic inflammation, Takayasu’s, and hyperintense vessel uptake. Conclusion Our study is the first retrospective case analysis, to our knowledge, of more than 15,000 radiology reports used as a starting point to evaluate for aortitis, identifying a large dataset with a broad case-mix. It contrasts with current literature identifying cases histologically and post-operatively. We found that radiology can be a useful early alert for possible diagnoses which require further assessment. Consequently, we developed an alerting system within our radiology department based on the search terms and imaging modalities identified. This links to a multidisciplinary meeting including vascular and rheumatology, so highlighted cases are discussed early. Disclosures K. Townsend: None. G. Cattini: None. K. Moss: None. K. Stenson: None. P. Holt: None. R. Morgan: None. N. Sofat: None.

Background The National Congenital Anomaly and Rare Disease Registration Service (NCARDRS) records those people with congenital anomalies and rare diseases across the whole of England. The NCARDRS Rare Rheumatology Project is establishing methodologies to identify and register people with rare rheumatic diseases. Hospital Episode Statistics (HES), comprising data from all admitted-patient NHS care in England, provides a promising source for case ascertainment. We aimed to confirm the reliability of diagnostic ICD codes for rare autoimmune rheumatic diseases within HES. Methods We used NCARDRS’ legal permissions (CAG 10-02(d)/2015) to extract cases who had at least one inpatient or daycase admission recorded in HES during 2003 to 2017 with a primary or additional diagnostic code for Kawasaki disease, Takayasu’s arteritis, Adult-onset Still’s disease, Relapsing polychondritis, Polyarteritis nodosa, Granulomatosis with polyangiitis (GPA), Microscopic polyangiitis (MPA) or Eosinophilic granulomatosis with polyangiitis (EGPA). Using Data Sharing Agreements between NCARDRS and NHS Trusts, we reviewed medical records for all cases admitted to one NHS Trust to confirm diagnoses. For ANCA-associated vasculitis (AAV), up to 20 randomly selected cases admitted to 5 Trusts with a diagnostic code of GPA, MPA and EGPA were reviewed. Results Table 1 shows the positive predictive value (PPV) of each diagnosis at one Trust: Kawasaki disease 100%, Takayasu’s arteritis 91.7%, Adult-onset Still’s disease 42.8%, Relapsing polychondritis 40.0%, and Polyarteritis nodosa 5.0%. For AAV, which had a PPV at the index Trust of 92.0%, the PPV across the 5 Trusts varied from 92.9% to 74.0%. Combining all 5 Trusts PPV for AAV was 85.9%. It was higher in MPA (PPV=98.4%) than in GPA (PPV=83.3%) and EGPA (PPV=77.4). Conclusion This is the first study to validate the coding of rare rheumatic disease diagnoses within HES data. Our results highlight heterogeneity in coding accuracy both between conditions and between NHS Trusts. Further work is needed to develop and validate algorithms for conditions where HES coding alone has poor positive predictive value, and test sensitivity. National rare disease registration will enable robust, cost-effective and reproducible population-based epidemiology of rare rheumatic diseases across England which is needed to inform service provision and aid development of new treatments. Disclosures F.A. Pearce None. M. Rutter None. B. Griffiths None. C. Mukhtyar None. R. Al-Jayoussi None. R.A. Watts None. J. Aston None. M. Bythell None. S. Stevens None. P.C. Lanyon None.

Background Erdheim-Chester disease (ECD) is a rare non-inherited, non-Langerhans form histiocytosis reclassified as a histiocytic neoplasm was first described in 1930 by Jakob Erdheim and William Chester. Only 500 cases were reported. Onset is usually between 50 to 70 years old. Male to female ratio is 3:1. Symptoms include long bone pain, fever, weight loss, exophthalmos, papilledema, headaches, cranial nerve palsies and sensory disturbances. Skeletal Abnormalities includes bilateral and symmetric cortical osteosclerosis of long bones. Cardiovascular involvement includes a ‘coated aorta’ which can involve renal arteries leading to reno-vascular hypertension. Pulmonary and retroperitoneal fibrosis has been reported. Methods We present a 90 year old gentleman with a complicated history of diplopia, proptosis with large retrobulbar orbital masses (confirmed on CT orbits) increasing in size over 2 years. He was symptomatic with bone pain, recurrent falls, dizziness and shortness of breath. He had a background history of pulmonary embolism, atrial fibrillation, hypertension and osteoporosis. On examination, no joint synovitis or lymphadenopathy noted. Chest examination revealed mild inspiratory crackles. Results CRP was recorded at 150mg/L. ANA, ENA, ANCA, anti-DsDNA, RF, anti-MCV antibodies were negative. IgG4 levels were normal. Pulmonary Function tests showed a restrictive Pattern - FEV1/FVC - 64%, FVC - 68%, TLC - 75%, TLCO - 68% predicted. CT Chest reported aortitis and mild undifferentiated pulmonary fibrosis. CT aorta done subsequently reported extensive soft tissue changes of the abdominal and thoracic Aorta which extended to the renal hila causing bilateral hydronephrosis. There was confirmed retroperitoneal Fibrosis and widespread para-aortic lymphadenopathy. He was stented by the urologists for hydronephrosis. Orbital biopsy of his left eye revealed xanthogranulomatous inflammation with widespread foamy histiocytes (CD68 positive). S100 and CD1a were negative. This confirms a clinical correlation of ECD. Further multidisciplinary discussions suggested that he stays on high dose prednisolone of 30mg daily. Localised radiotherapy was successful in debulking his orbital lesions. Chemotherapy was discussed but he does not wish for this. Conclusion Differential diagnoses for ECD include IgG4 disease, Granulomatosis with polyangiitis, Takayasu’s arteritis, Langherhan Cell histiocytosis, or malignancies. Tissue diagnosis describes infiltration of foamy histiocytes, lymphocytes and lipid laden macrophages. It is distinguished by immunohistological characteristics (ECD positive for CD68, negative for CD1a and S-100 protein) in 80 percent of cases. Serum Assay Samples can show high IFN-alpha, IL1, IL-6 and IL-12 titres. First line treatment is pegylated IFN-alpha. Bisphosphonates can alleviate bone pain. Cladribine has helped those with orbital involvement. Anakinra or Inflixamab improves symptoms of mild forms of ECD. Vemurafenib is used for patients with the BRAFV600 proto-oncogene mutation. PET scans are recommended for disease activity assessment. ECD has a variable prognosis but poorer in those with CNS involvement. With treatment, the mortality rate is 26% and 5-year survival is 68%. Disclosures D. Das None. S. Jones None.

Background Auto-immune rheumatic diseases are multisystem conditions with high morbidity and mortality, where co-ordinated multidisciplinary (MDT) care is necessary to ensure effective and timely treatment. An NHS England Commissioning for Quality and Innovation was implemented in 2016 to support development of MDTs to achieve earlier diagnosis and intervention and standardise quality of care and access to high-cost drugs. Methods A regional network for MDTs was established in one centre, led by Rheumatology with input from other specialities. MDT outcomes are recorded in a bespoke database. We analysed MDT outcomes over a two-year period from September 2017 to August 2019 for the following: disease activity assessments, investigations requested, referrals to other specialists, treatment changes and the reasons for these. Results During this period, 2,750 MDT discussions were recorded for 1,270 patients. The most common diagnoses were giant cell arteritis (30%), systemic lupus erythematosus (9%) and granulomatosis with polyangiitis (6%). Disease activity scores were recorded on 2,744 (99.8%) occasions with BVAS (n = 1,658, mean 0.82, range 0-21) and SLEDAI (n = 379, mean 2.04, range 0-20) used most. This underlines that decisions were consistently based on validated outcome measures. Investigations were ordered on 1165 (42%) occasions. Imaging was requested in 1,124 cases, biopsy in 37, functional tests in 221 and other tests in 18. Ultrasound was requested most often (614). Onward referrals were made in 237 (9%), most frequently to respiratory (32) and ENT (32). On 1550 occasions (56%) a treatment change was made: 1049 (38%) had a new change and 501 (18%) had a previously planned change. The most common reasons were good response to therapy (354 [23%]), inefficacy (345 [22%]) or starting additional therapy (214 [14%]). This shows that a significant number of treatment changes were approved by the MDT, both for treatment reduction as well as escalation. A biologic was added on 65 occasions (4% of treatment changes), most commonly in GCA (8 started on tocilizumab), SLE (5) and GPA (5). Biologics were repeated in 121 (8%) and stopped in 25 (2%). Where biologics were added, mean pre-treatment BVAS was 4.7 and post-treatment was 0.6. Mean reduction in BVAS after treatment was 5.2. The equivalent mean scores for SLEDAI were 7 (pre-treatment), 2 (post-treatment) and 7.7 (reduction). On average, the addition of biologics resulted in reductions in disease activity scores, which provides justification for their use. Conclusion Our data suggest that the large number of MDT reviews over this two-year period contributed significantly to management of systemic auto-immune rheumatic diseases by approving investigations, referrals and treatment changes. This facilitated timely intervention and avoidance of overtreatment. The auditable recording of these reviews and disease activity scores ensured decisions were guided by objective assessments and the use of high-cost drugs was standardised and justifiable. Disclosures K. Sandhu None. N. Ahmad None. A. Verdiyeva None. R. Luqmani None.

ResumenEl signo del halo invertido se caracteriza por una opacidad central de vidrio esmerilado rodeado por una consolidación del espacio aéreo más densa en forma de una media luna o un anillo. El signo del halo invertido se ha informado en asociación con un amplia gama de enfermedades pulmonares, incluidas las infecciones fúngicas pulmonares invasivas, neumonía por pneumocystis, tuberculosis, neumonía adquirida en la comunidad, granulomatosis linfomatoide, granulomatosis de Wegener, neumonía lipoidea y sarcoidosis. También se observa en neoplasmas pulmonares e infarto y después de radioterapia y ablación por radiofrecuencia de neoplasias malignas pulmonares. También es conocido como signo de halo en reversa o signo del atolón.AbstractThe reversed halo sign is characterized by a central ground-glass opacity surrounded by denser air–space consolidation in the shape of a crescent or a ring. The reversed halo sign has been reported in association with a wide range of pulmonary diseases, including invasive pulmonary fungal infections, pneumocystis pneumonia, tuberculosis, community-acquired pneumonia, lymphomatoid granulomatosis,Wegener granulomatosis, lipoid pneumonia and sarcoidosis. It is also seen in pulmonary neoplasms and infarction, and following radiation therapy and radiofrequency ablation of pulmonary malignancies. It is also known as a reverse halo sign or atoll sign.

Introducción: La granulomatosis con poliangeítis (de Wegener) es una enfermedad poco frecuente, sin embargo, el 80 a 90% de los casos tienen manifestaciones otorrinolaringológicas, muchas como único síntoma inicial de la enfermedad. Objetivos: El propósito de este artículo es revisar la literatura disponible actualizada sobre granulomatosis con poliangeítis: manifestaciones clínicas, estándares de enfoque, diagnóstico y tratamiento en otorrinolaringología. Diseño: Revisión narrativa de la literatura. Materiales y métodos: Revisión de la literatura mediante búsqueda selectiva por términos MeSH: Otorhinolaryngologic Diseases, Granulomatosis with polyangiitis, Wegener Granulomatosis, de las bases de datos:MEDLINE, Current Contents, Cochrane, Pubmed y Scielo, entre los años 2000 y 2014. Resultados: Se revisaron 39 artículos según los requerimientos de los objetivos. La evidencia científica actual reconoce la importancia del conocimiento sobre granulomatosis con poliangeítis (de Wegener) en otorrinolaringología, para obtener diagnósticos tempranos y ofrecer manejos oportunos. Conclusiones: El diagnóstico y tratamiento tempranos de la granulomatosis con poliangeítis (de Wegener) son las únicas herramientas para mejorar el pronóstico y calidad de vida de los pacientes con esta enfermedad.Introduction: Granulomatosis with polyangiitis (Wegener’s) is a rare disease,however 80% to 90% of the cases have otolaryngologic manifestations, many as initial symptoms of the disease. Objectives: The purpose of this article is to review the current literature about granulomatosis with polyangiitis: Clinic manifestations, approach standards, diagnosis and treatment in otolaryngology. Design: Narrative review. Materials and methods: Literature review by selective search for MeSH terms: Otorhinolaryngologic Diseases, granulomatosis with polyangiitis, Wegenergranulomatosis, in the databases: MEDLINE, Current Contents, Cochrane, PubMed and SciELO, between 2000 and 2014. Results: 39 articles were reviewed according to the requirements of the objectives. Current scientific evidence recognizes the importance of the knowledge about granulomatosis with polyangiitis (Wegener’s) in otolaryngology, in order to give an early diagnosis and to provide an opportune treatment. Conclusions: Early diagnosis and treatment of granulomatosis with polyangiitis (Wegener’s) are the only tools to change the prognosis as well as quality of life of patients with this disease.

Patient: Female, 67 Final Diagnosis: GPA and GCA Symptoms: Blurry vision • headache • nosebleed • sinus congestion Medication: — Clinical Procedure: — Specialty: Rheumatology Objective: Rare co-existance of disease or pathology Background: Systemic vasculitis can present with a multitude of symptoms involving multiple organ systems. Clinicians should avoid anchoring bias and be cognizant that different types of vasculitides can be present in the same patient and that the diagnosis of one should not preclude the subsequent diagnosis of another. Case Report: A 67-year-old woman was referred for evaluation of episodes of epistaxis and recurrent severe sinusitis. Her physical examination showed nasal congestion and purpuric rash on the lower extremities. CT of the sinuses showed severe mucosal thickening. ANCA serologies were positive with a c-ANCA titer of 1: 5120 and anti-proteinase-3 (anti-PR3) antibodies of 1061 units. Serum creatinine was elevated at 1.32 mg/dL (GFR of 40.62 ml/min). Urine analysis showed proteinuria and hematuria. The patient declined treatment initially, but while awaiting kidney biopsy she developed episodes of headache and blurry vision. She underwent right temporal artery biopsy 4 days later, which confirmed the diagnosis of GCA. The biopsy showed characteristic histopathology findings and she was started on 60 mg of prednisone daily. The kidney biopsy showed pauci-immune crescentic glomerulonephritis (PICGN) consistent with ANCA-associated vasculitis. We identified all the cases of co-presentation of GCA and GPA in the literature and summarized their clinical features in this report. Conclusions: Astute clinicians should be cognizant of overlapping and atypical presentations of vasculitides to avoid delayed diagnosis and errors in management.

Introduction This is an empirical study to better understand commonly used medical school admission measures and disenrollment decisions during undergraduate medical education as well as graduate medical education (GME) probation or termination decisions. Materials and Methods Based on the data of USUHS medical students matriculating between 1998 and 2011 (N = 2,460), we compared medical school graduates and those disenrolled from medical school on MCAT scores, undergraduate BCPM (Biology, Chemistry, Physics, Math) GPA, and undergraduate overall GPA. We also reported more specific reasons for disenrollment decisions. Next, we compared the students who were referred to the student promotion committee (SPC) with other students on these measures. Moving onto GME, we compared trainees who were put on probation or terminated from training with those who were not on MCAT and undergraduate GPA measures. In addition, we examined the association between being referred to the SPC and GME probation or termination. Results There were 2,347 graduates and 113 disenrolled students from medical school (4.8%). For the disenrolled students, 43 (38.7%) students were disenrolled for exclusively (or primarily) non-academic reasons, and 68 (61.3%) were disenrolled for exclusively (or primarily) academic reasons. The t-tests showed statistically significant differences on the MCAT score of the first attempt (t(2,449) = 7.22, P < 0.01, Cohen's d = 0.70), average MCAT score (t(2,449) = 4.22, P < 0.01, Cohen's d = 0.41), and highest MCAT score (t(2,449) = 3.51, P < 0.01, Cohen's d = 0.34). Logistic regression model selection also revealed that the best predictor for disenrollment was the first MCAT score (exp(b) = 0.83, 95% CI = (0.78, 0.88)). No significant differences on these measures were found from the group comparisons on SPC and GME probation or termination. There was no significant association between SPC appearance and GME probation or termination. Conclusions Academic difficulties, especially in the basic sciences, appear to be the most common factor for disenrollment from medical school. These students also had lower MCAT scores, particularly on the first attempt. The MCAT performance indicators and undergraduate GPA were consistently lower, but not statistically significant, for those who appeared before SPC or were put on probation or terminated from training during GME.

The lecture presents modern views on risk factors, pathogenesis, and the main morphological criteria for granulomatosis with polyangiitis (Wegener granulomatosis). Clinical manifestations, imaging findings of pulmonary syndrome in the aforementioned systemic vasculitis as well as the main diagnostic criteria and the principles of treatment are highlighted in detail.

New onset of granulomatosis with polyangiitis (GPA) occurring in patients previously diagnosed with rheumatoid arthritis (RA) is very uncommon. In older individuals, this condition is associated with high mortality, especially in those with renal involvement. We describe the first case of GPA in a patient older than 65 years diagnosed with RA without exposure to biologic disease-modifying anti-rheumatic drugs, presenting with pulmonary nodules due to a limited form of anti-neutrophil cytoplasmic antibody-negative GPA.

Background Given the increasing use of stereotactic radiosurgery (SRS) for brain metastases (BM), there is an emerging need for more precise assessment of survival outcomes after SRS, especially in the modern targeted therapy era. Methods Patients with BM and treated by SRS were eligible in this study. Primary endpoint was overall survival (OS). Cox models were used to identify independent prognostic factors. Survival predictive nomogram was developed and evaluated by Concordance-index (C-index), area under the curve (AUC) and calibration curve. Results From January 2016 to December 2019, a total of 356 BM patients were eligible. Median OS was 17.7 months (95%CI 15.5–19.9) and actual OS at 1- and 2-year measured 63.2% and 37.6%, respectively. Nomogram for OS was developed by incorporating four independent prognostic factors: Karnofsky Performance Score, cumulative tumor volume, driver gene mutation status and serum lactate dehydrogenase. The nomogram was validated in a separate cohort demonstrated a well calibration and good discriminative ability (C-index=0.780, AUC=0.784). The prognostic accuracy of the nomogram (0.792) was considerably enhanced compared with classical prognostic indices, i.e., GPA (0.708), RPA (0.587) and SIR (0.536). Kaplan-Meier curves showed significant difference of OS among stratified low-, median- and high-risk groups (P < .001). Conclusion In conclusion, we developed and validated an individualized prognostic nomogram by integrating physiological, volumetric, clinical chemistry and molecular biological surrogates. This nomogram, should be validated by independent external study, has a potential to facilitate more precise risk-stratifications to guide personalized treatment for BM.

OBJECTIVES: Weight loss supplements (WLS) are commonly used among college students. Although these supplements work through different mechanisms, many of them are sympathomimetic that may impact mental wellbeing. College students are inherently at risk of mental distress; therefore, use of these stimulants may exacerbate their response to stress and increase their risk of anxiety and depression. The purpose of the present study was to assess the pattern of use and perception of WLS among college students, and its association with reported mental distress symptoms. METHODS: Data were collected through an online questionnaire targeting US college students through social media platforms. A parallel study took place at an institution of higher education in Lebanon, a Middle Eastern country where college students commonly use WLS. The questionnaire included demographic questions such as gender, age, self-reported height and weight, hours of sleep, frequency of exercise, class, major and GPA. It also included questions on frequency of dieting, weight loss supplement use, perception, and symptoms associated with use. RESULTS: A total of 583 college students completed the survey. Random Forest Analysis produced a model of 0.98% accuracy with AUC = 0.993, which classified weight loss supplements as the most significant factor associated with mood changes in college students followed by academic class, exercise, GPA, gender, sleep, age and major. To confirm the directionality of these associations, a logistic regression analysis suggested that WLS strongly associated with symptoms of mood changes, followed by a low GPA and being a female. Conversely, upperclassmen, good sleep quality, being 23 years or older, and non- science, technology, engineering and mathematics (STEM) majors inversely correlated with mood changes. A principal component analysis suggested a pattern for frequent dieting, weight loss supplement use and heavy exercise among men, and a pattern of frequent dieting, combining WLS, low quality sleep and no exercise among women. CONCLUSIONS: Use of WLS among college students may be worsening their psychological status. In addition, there is a differential pattern of use among men and women that is worth further investigation. FUNDING SOURCES: Experiment.com.

Classification criteria for the ANCA-associated vasculitides (AAV) were developed in the 1980s, prior to the routine use of ANCA testing. The Diagnostic and Classification of the Systemic Vasculitides (DCVAS) study is an international collaborative project to update classification criteria for each type of systemic vasculitis. Provisional classification criteria for granulomatosis with polyangiitis (GPA) have been developed.

Resumen Mujer de 31 anos con cuadro de poliartralgias, poliartritis asimetrica, fiebre, lesiones vasculiticas en piel, asociado a disminucion de agudeza visual en ojo derecho, el cual presentaba compromiso corneal con adelgazamiento periferico severo, queratitis ulcerativa periferica, hipopion de fibrina y sinequias posteriores. Ante el cuadro clinico y paraclinicos con C-ANCA positivos, se realiza el diagnostico de granulomatosis con poliangeitis con compromiso ocular (adelgazamiento corneal, queratitis ulcerativa periferica, uveitis) y sistemico. Se inicia tratamiento con metilprednisolona y ciclofosfamida con poco control, por lo que se inicia rituximab sistemico, evolucionando hacia la mejoria.