MO290CLINICAL DIFFERENCES AND OUTCOMES IN ANCA ASSOCIATED VASCULITIS PATIENTS ACCORDING TO SEROLOGICAL PHENOTYPE – EXPERIENCE FROM CROATIAN REFERRAL CENTER

Background and Aims ANCA associated vasculitis (AAV) are usually classified according to clinical presentation (Chapel-Hill consensus conference). There is however suggestion by some authors that AAVs could be classified according to ANCA specificity. We aimed to compare AAV patients in our cohort according to serological phenotype. Method This study included 106 consecutive AAV patients with renal involvement in the period from 2007-2017. We performed renal biopsy on patients using automatic 16 Gauge needle. Light, immunofluorescent and electronic microscopy were performed. Category variables were analysed with Fisher Exact testom and continuous with Kruskal-Wallis testom. Statistical difference was then analysed posthoc with Chi-square test. Primary outcomes were combined outcome progression to end-stage renal disease, defined as persistent (more than three months) need for renal replacement therapy or permanent reduction of EGFR to <15ml/minute (according to CKD EPI formula) and/or death (ESRDD), death (D) and ESRD alone, and disease relapse. Kaplan Meyer survival analysis and multivariate Cox proportional hazard regression analysis were used to explore difference between phenotypes and finding significant predictors regarding outcomes. Results The study included 106 AAV patients with renal involvement: 66 (61,1%) MPA, 20 (18,5%) GPA, 20 (18,5%) RLV. There were 14 (13%) PR3-ANCA positive patients, 57 (52,8%) MPO ANCA positive, 5 (4,6%) PR3-ANCA+MPO-ANCA and 32 (29,6%) ANCA negative patients. Average SCr was 316,5 μmol/l (IQR 207,0-548,5), 24-hour proteinuria median was 1,7g/24h (IQR 0,8-2,8). Clinicaly PR3 positive AAVs had significantly more ENT (p<0,001) and skin (p=0,001) involvement, and ANCA negatives had significantly less lung involvement (p<0,001), and less expressed constitutional symptom (p=0,031). Interestingly both MPO and PR3 positive AAV patients had approximately equal percentage of lung involvement. Both PR3 (p=0,021) and MPO (p=0,009) positive AAVs had higher BVAS score compared to ANCA negatives, while on average there was no significant difference between MPO, PR3 and double positives. PR3 (p=0,007) and MPO (p=0,003) positive AAVs had higher CRP levels than ANCA negatives, and PR3 AAVs had on average higher CRP than MPO AAVs though not statistically significant. There was strong tendency (p=0,087) to PR3 AAVs having more acute tubular damage than other groups and also strong tendency (p=0,092) of having more crescentic formations than MPO AAVs and ANCA negatives but similar to double positives. Though it was not statistically significant ANCA negatives had higher median of IFTA compared to other groups. PR3 AAVs and double positives required significantly more often treatment with PLEX (p=0,042) and dialysis (p=0,04) compared to MPO positive AAVs and ANCA negatives. We then grouped patients into ANCA positives and ANCA negatives. ANCA negative patients were younger (p=0,02), expressed clinicaly more as RLV (p<0,001). BVAS score was lower in ANCA negative group (p= 0,003). ANCA positive patients presented more often with RPGN (p=0,027) and ANCA negatives with nephrotic syndrome. There was tendency of ANCA positives being treated with PLEX more often (p=0,074). In the primary outcome analysis there were no statistically significant differences between serological phenotypes though for relapse rate (p=0,155) curve dynamics through follow up time seems to show higher relapse rate for PR3 and double positive AAVs after 2 years of follow up. Conclusion Serological classification of AAVs is an interesting way for overcoming the limitations of clinical classification. Apart from differences between MPO, PR3 and double positive AAVs, it appears there are even more significant differences between ANCA positive and negative ones.

Development and Validation of a Simple Risk Score for Diagnosing COVID-19 in the Emergency Room

As the COVID-19 pandemic continues to escalate and place pressure on hospital system resources, a proper screening and risk stratification score is essential. We aimed to develop a risk score to identify patients with increased risk of COVID-19, allowing proper identification and allocation of limited resources. A retrospective study was conducted of 338 patients who were admitted to the hospital from the emergency room and tested for COVID-19 at an acute care hospital in the Metropolitan Washington D.C. area. The dataset was split into development and validation sets with a ratio of 6:4. Demographics, presenting symptoms, sick contact, triage vital signs, initial laboratory and chest X-ray results were analyzed to develop a prediction model for COVID-19 diagnosis. Multivariable logistic regression was performed in a stepwise fashion to develop a prediction model, and a scoring system was created based on the coefficients of the final model. Among 338 patients admitted to the hospital from the emergency room, 136 (40.2%) patients tested positive for COVID-19 and 202 (59.8%) patients tested negative. Nursing facility residence (2 points), sick contact (2 points), constitutional symptom (1 point), respiratory symptom (1 point), gastrointestinal symptom (1 point), obesity (1 point), hypoxia at triage (1 point), and leukocytosis (-1 point) were included in the prediction score. A risk score for COVID-19 diagnosis achieved AUROC of 0.87 (95% CI 0.83-0.92) in the development dataset and 0.83 (95% CI 0.76-0.90) in the validation dataset. A risk prediction score for COVID-19 can be used as a supplemental tool to assist clinical decision to triage, test, and quarantine patients admitted to the hospital from the emergency room.

Development and validation of a simple risk score for diagnosing COVID-19 in the emergency room

As the COVID-19 pandemic continues to escalate and place pressure on hospital system resources, a proper screening and risk stratification score is essential. We aimed to develop a risk score to identify patients with increased risk of COVID-19, allowing proper identification and allocation of limited resources. A retrospective study was conducted of 338 patients who were admitted to the hospital from the emergency room to regular floors and tested for COVID-19 at an acute care hospital in the Metropolitan Washington D.C. area. The dataset was split into development and validation sets with a ratio of 6:4. Demographics, presenting symptoms, sick contact, triage vital signs, initial laboratory and chest X-ray results were analysed to develop a prediction model for COVID-19 diagnosis. Multivariable logistic regression was performed in a stepwise fashion to develop a prediction model, and a scoring system was created based on the coefficients of the final model. Among 338 patients admitted to the hospital from the emergency room, 136 (40.2%) patients tested positive for COVID-19 and 202 (59.8%) patients tested negative. Sick contact with suspected or confirmed COVID-19 case (3 points), nursing facility residence (3 points), constitutional symptom (1 point), respiratory symptom (1 point), gastrointestinal symptom (1 point), obesity (1 point), hypoxia at triage (1 point) and leucocytosis (−1 point) were included in the prediction score. A risk score for COVID-19 diagnosis achieved area under the receiver operating characteristic curve of 0.87 (95% confidence interval (CI) 0.82–0.92) in the development dataset and 0.85 (95% CI 0.78–0.92) in the validation dataset. A risk prediction score for COVID-19 can be used as a supplemental tool to assist clinical decision to triage, test and quarantine patients admitted to the hospital from the emergency room.

Correlations between clinical features and CD4 cell count in HIV patients with tuberculosis

Background: The correlation between tuberculosis and HIV is evident from the higher incidents of tuberculosis estimated 5-8% per year among HIV infected person with lesser CD4cell count. The high seroprevalence with tuberculosis in occurrence among AIDS patients.Methods: 100 HIV positive patients with tuberculosis who were admitted to medicine department and who visited to ARTS center were taken up for study for period of two years from December 2014 to 2016. Type of study is a observational comparative cross sectional study The investigation for HIV and TB were done as per NACO and WHO recommendation ELISA test CD4 cell counts AFB staining chest X-ray FNAC Mountoux test pleural fluid analysis Ascitic fluid analysis CSF fluid analysis USG of thorax CT scan of thorax.Results: It is seen that the maximum number of patients belong to the age group 31-40 years male 40 (40%) and female 4(4%) the common occupation in the study group was driver 36 (36%) the common constitutional symptom was weight loss physical examination reveal underweight (BMI <16-18.5) 54 (54%) among the study extra-pulmonary TB 63 (63%) X-ray chest finding pleural effusion found in 21% of patients CD4 cell counts 200-500 /µl was seen maximum number of patients.Conclusions: The CD4cell counts is important investigation in HIV and TB patients it is main investigation to know prognosis of HIV also important for initiation of ARV drugs.it is evident from this study the decrease the CD4cell counts there is increase the incidence of tuberculosis.

Correlations between clinical features and CD4 cell count in HIV patients with tuberculosis

Background: The correlation between tuberculosis and HIV is evident from the higher incidents of tuberculosis estimated 5-8% per year among HIV infected person with lesser CD4cell count. The high seroprevalence with tuberculosis in occurrence among AIDS patients.Methods: 100 HIV positive patients with tuberculosis who were admitted to medicine department and who visited to ARTS center were taken up for study for period of two years from December 2014 to 2016. Type of study is a observational comparative cross sectional study The investigation for HIV and TB were done as per NACO and WHO recommendation ELISA test CD4 cell counts AFB staining chest X-ray FNAC Mountoux test pleural fluid analysis Ascitic fluid analysis CSF fluid analysis USG of thorax CT scan of thorax.Results: It is seen that the maximum number of patients belong to the age group 31-40 years male 40 (40%) and female 4(4%) the common occupation in the study group was driver 36 (36%) the common constitutional symptom was weight loss physical examination reveal underweight (BMI <16-18.5) 54 (54%) among the study extra-pulmonary TB 63 (63%) X-ray chest finding pleural effusion found in 21% of patients CD4 cell counts 200-500 /µl was seen maximum number of patients.Conclusions: The CD4cell counts is important investigation in HIV and TB patients it is main investigation to know prognosis of HIV also important for initiation of ARV drugs.it is evident from this study the decrease the CD4cell counts there is increase the incidence of tuberculosis.

Phase I/II trial of glasdegib in patients with primary or secondary myelofibrosis.

7061 Background: Glasdegib is a small molecule inhibitor of the Sonic Hedgehog pathway, and data from the single arm, lead-in cohort of a phase 1b/2 trial in myelofibrosis (MF) are shown. Methods: Patients (age ≥18 yrs) with primary/secondary MF previously-treated with ≥1 Janus Kinase inhibitor (JAKi) were enrolled and received glasdegib 100 mg QD orally in 28 day cycles. AEs and laboratory abnormalities were assessed. Key efficacy endpoints were proportion of patients with spleen volume reduction (SVR) ≥35% and ≥50% reduction in total symptom score (TSS) measured by the MPN Symptom Assessment Diary (MPN-SAD) at Week 24. Results: 21 patients were enrolled between Oct '14-Oct '15 in this ongoing study. Mean age was 69.3 yrs (range 58-83). Median duration of treatment was 85 days (22-343). 52% were refractory patients with inadequate response to prior JAKi. Baseline symptoms were mostly mild (1-4), except fatigue (>4). No patients achieved SVR ≥35%, 5 patients had some SVR (maximum 2.3-21.4% reduction from baseline), and no progressive disease prior to Day 71. At week 24, 1 patient had ≥50% reduction in TSS, but 3/21 and 4/21, respectively showed 30% and 20% TSS reduction. Of 14 patients with severe baseline symptoms (1 with ≥5, or ≥2 with ≥3), 1, 1, and 2 achieved 50%, 30%, and 20% TSS reduction, respectively at week 24. TSS, spleen-related, and constitutional symptom scores showed a trend of reduction over 24 weeks with spleen-related symptoms, inactivity, and fatigue showing greatest improvement (52%, 58%, and 36%, respectively). Dysgeusia (N=13), muscle spasms (N=12), alopecia (N=8), decreased appetite (N=7), fatigue (N=7), lipase increase (N=5), and weight decrease (N=5) occurred in ≥20% patients. None, except 1 episode of fatigue, were considered serious AEs. Glasdegib steady state PK was consistent with previous single agent data. Conclusions: Glasdegib has an acceptable toxicity profile in patients with primary/secondary MF previously treated with JAKi. Symptom responder definition for refractory patients may not be the same as for JAKi naïve patients. Patient reported symptom improvement may be a more sensitive indicator of treatment benefit vs SVR. Further study of glasdegib may be warranted. Clinical Trial Information: NCT02226172.

Isolated Mesenteric Tuberculosis

Introduction: Abdominal tuberculosis is common in developing world, and abdominal tuberculosis is most common presentation of extra pulmonary tuberculosis. High index of suspicion is needed in patient from endemic area with chronic abdominal pain and constitutional symptom for diagnosis of abdominal tuberculosis. In abdominal tuberculosis although intestinal, cecal and lymph node involvement are common, isolated mesenteric tuberculosis is rare presentation and very few cases has been reported. Here we are presenting rare case of a young male with isolated mesenteric tuberculosis who presented with abdominal mass.

Real-World Assessment of Clinical Outcomes in Patients with Lower-Risk Myelofibrosis Receiving Treatment with Ruxolitinib

Few trial-based assessments of ruxolitinib in patients with lower-risk myelofibrosis (MF) have been conducted, and no studies have made such assessments in a real-world population. We assessed changes in spleen size and constitutional symptoms during ruxolitinib treatment using a retrospective, observational review of anonymized US medical record data of patients diagnosed with IPSS low-risk (n=25) or intermediate-1-risk (n=83) MF. The majority of patients were male (low risk, 60%; intermediate-1 risk, 69%). Most patients (92% and 77%) were still receiving ruxolitinib at the medical record abstraction date (median observation/exposure time, 8 months). The proportion of patients with moderate or severe palpable splenomegaly (≥10 cm) decreased from diagnosis (56%) to best response (12%). Fatigue was reported in 47% of patients and was the most common constitutional symptom. For most symptoms in both risk groups, shifts in the distribution of severity from more to less severe from diagnosis to best response were observed. Both patients with low-risk and intermediate-1-risk MF experienced a substantial decrease in spleen size with ruxolitinib treatment in real-world settings. For most symptoms examined, there were distinct improvements in the distribution of severity during ruxolitinib treatment. These findings suggest that patients with lower-risk MF may benefit clinically from ruxolitinib treatment.

Significant Improvement In Quality Of Life (QoL) In Patients With Chronic Myeloproliferative Neoplasms and Myelofibrosis Treated With JAK-1 and JAK-2 Inhibitor Ruxolitinib. A Single Institution Experience In Mexico

Introduction Myeloproliferative Neoplasms can shorten the life of patients and affect severely their quality of life as a result of constitutional symptoms mediated by cytokines and from massive splenomegaly characteristic of these diseases. The objective measurement of symptoms in Myelofibrosis is essential for the presence of general constitutional symptoms as fatigue and is considered adverse prognostic value for survival. The systematic measurement of symptoms in Myelofibrosis is essential for assessing the outcome of treatment with JAK-2 inhibitors. Material and Methods To assess the impact on quality of life in patients with Myeloproliferative Neoplasms treated with the inhibitor Ruxolitinib, there was applied the questionnaire Myelofibrosis Symptom Assessment Form (Mesa et al. Leukemia Research. 2009: 33; 1199-1203) to 16 patients included in the Compassionate Use of Ruxolitinib Program: 8 men and 8 women were included with a median age of 63 years; 4 patients with primary Myelofibrosis, 3 with Myelofibrosis post Polycitemia vera and 9 with Myelofibrosis post essential Thrombocythemia. The median patient follow-up was 9 months. The patients started with a dose of 20 mg Ruxolitinib orally every 12 hours. Results The questionnaire was administered to all patients at each visit and the results of the ratings of the patients were presented as median of each answer at baseline, 3, 6 and 12 months of follow-up (table 1). By comparing the differences of each parameter measured between the start and at 3, 6 and 12 months were statistically significant for all variables (P <0.001, CI: 95%). The most significant changes were observed when comparing data at baseline and follow-up to the maximum time, however were obvious from the first quarter of observation on fatigue and symptoms dependent splenomegaly in most general symptoms, which actually disappeared completely after 3 months of treatment and not relapsed during the track and in the perception of the quality of life of patients. The variables with lower proportional change recorded were general activity, mood, walking tolerance and everyday work. Discussion and conclusions The treatment of Myeloproliferative Neoplasms with Ruxolitinib represents a major advance in the management of malignant Myeloproliferative and achieved excellent improvement in overall constitutional symptom control, splenomegaly and the general perception of the quality of life of these patients. The objective measurement of symptoms of Myelofibrosis is essential, since the presence of general constitutional symptoms as fatigue is considered adverse prognostic value for survival and systematic measurement of symptoms in Myelofibrosis is essential for assessing the outcome of treatment with inhibitors JAK-2. Disclosures: No relevant conflicts of interest to declare.