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International audience; We have previously shown that ultrasonography can detect hyperechogenic crystal deposits in the kidney medulla of patients with gout. In this cross-sectional study we investigated the frequency and clinical correlates of hyperechogenic kidney medulla in 502 consecutive primary consultants for gout (ACR/EULAR criteria) at the Vien Gut medical center in Ho Chi Minh City, Vietnam. None of these patients received urate-lowering drugs. Kidney medulla echogenicity on B-mode ultrasonography was compared to that of the kidney cortex. Overall, 36% patients showed a hyperechoic pattern of Malpighi pyramids. On univariate analysis, the pattern was significantly associated with age, estimated gout duration, steroid-dependency, clinical tophi, urate arthropathy, double contour thickness at the scanned joints, coronary heart disease, arterial hypertension, hyperuricemia, proteinuria, leukocyturia, and decreased estimated glomerular filtration rate. On multivariable analysis, the hyperechoic pattern was associated with estimated disease duration, clinical tophi, urate arthropathy, double contour thickness and decreased estimated glomerular filtration rate. No hyperechoic pattern was observed in 515 consecutive consultants without gout. Thus, hyperechoic kidney medulla was frequently demonstrated in Vietnamese patients with tophaceous gout and associated with features of tubulointerstitial nephritis. This finding revives the hypothesis of microcrystalline nephropathy of gout, predominantly seen in untreated gouty patients, which could be an important target for urate-lowering therapy.

To evaluate extent of interstitial lung disease (ILD) and esophageal involvement using high-resolution computed tomography (HRCT) in early diffuse systemic sclerosis (dSSc)-patients after autologous hematopoietic stem cell transplantation (aHSCT).Overall chest HRCT, lung function and skin score changes were evaluated in 33 consecutive dSSc-patients before and after aHSCT during yearly routine follow-up visits between January 2000 and September 2016. Two independent radiologists blindly assessed the ILD extent using semi-quantitative Goh and Wells method, the widest esophageal diameter (WED) and the esophageal volume (EV) on HRCT. Patients were retrospectively classified as radiological responders or non-responders based on achieved stability or a decrease of 5% or more of HRCT-ILD at 24 months post-aHSCT.Using a linear mixed model, the regression of the extent of ILD and of ground glass opacities were significant at 12 months (ILD p= 0.001; ground glass opacities p= 0.0001) and at 24 months (ILD p= 0.007; ground glass opacities p= 0.0008) after aHSCT, with 18 patients classified as radiological responders (probability of response 0.78, 95% CI (0.58; 0.90), meanwhile the WED and the EV increased significantly at 12 months (WED p= 0.03; EV p= 0.34) and at 24 months (WED p= 0.002; EV p= 0.007). Kaplan-Meier analyses showed a trend towards better 5-year survival rates (100% vs 60%; HR 0.23 95%CI 0.03-1.62, p= 0.11) among radiological responders vs non-responders at 24 months follow-up.Real-world data analysis confirmed significant improvement in extent of HRCT SSc-ILD 24 months after aHSCT, although esophageal dilatation worsened requiring specific attention.

Objective To evaluate the predictive value of angle of progression (AoP) of the fetal head for a failed vacuum delivery. Methods This was a prospective observational study that included women with a singleton pregnancy of ≥ 37 weeks' gestation, in cephalic presentation requiring vacuum extraction. Transperineal ultrasound was performed immediately before vacuum extraction, although AoP was measured on stored images after delivery. Vacuum extraction was defined as failed when the duration of extraction exceeded 20 min or the vacuum cup detached more than three times. We compared the demographic and ultrasound data of failed vacuum deliveries with those that were successful. The predictive value of AoP for failure of vacuum delivery was calculated. Results AoP was measured in 235 women. Vacuum extractions failed in 30 (12.8%) women (29/184 nulliparous and 1/51 parous) and resulted in 28 vaginal deliveries by forceps and two Cesarean deliveries. Median AoP was significantly lower in the vacuum failure group compared with those with successful vacuum delivery (136.6° (interquartile range (IQR), 129.8–144.1°) vs 145.9° (IQR, 135.0–158.4°); P

Background Allopurinol (ALLO) exposes to mild (M) and severe (S) cutaneous adverse reactions (CARs). SCARS have been associated with HLA*B58 01 with various strength of across ethnicities. Little is known about ALLO tolerance in Vietnam (VN). Objectives The aim of this ongoing prospective study was to investigate risk factors, including HLA*B-58 01, for MCARs and SCARs in the predominant Kinh ethnicity of VN Methods All included patients were Kinh Vietnamese. SCARs were recruited at Ho Chi Minh City hospitals, MCARs from the same departments and from the Vien Gut clinic at HCMC (specialised in gout care), and tolerant gouty patients (no skin reaction after at least 3 months from the last increment in ALLO dose) at the Vien Gut clinic. Clinical data were prospectively collected and HLA*B-58 01 typing used the PG5801 DNA detection kit (Pharmigene-Taiwan). Fisher exact test for categorical variables and Kruskal/Wilkonson test for quantitative variables were used for statistics. Results 10 patients experienced a non-fatal SCAR. Toxic necrotic epidermolysis, Stevens-Johnson syndrome and mixed syndrome were diagnosed in 1, 8 and 1 patients respectively. 54 patients stopped ALLO because of MCAR.112 ALLO tolerant patients were recruited. Table 1 shows the main features of interest in the 3 groups. The Odds ratio of HLA*B-58 01 positive patients to develop SCARs was calculated at 171.2 (95% CI: 20; 7889) Conclusions HLA*B-58 01 was significantly associated with SCARs to ALLO in the VN Kinh population. Other known factors but not high ALLO dose were also associated. The only association with MCARs was lack of ALLO titration. Acknowledgements ART Viggo Disclosure of Interest None declared

Background Renal medulla crystal deposits have been demonstrated by pathology in severe gout but little studied by ultrasound (US) scan. Objectives To assess the frequency of hyperechoic renal medulla (HERM) in gouty patients and factors associated with their development. Methods Renal US scan using a Ecube 9 echograph (Alpinion S. Korea), was performed in gout patients (ACR/EULAR criteria) consecutively seen at the Vien Gut general clinic, Ho Chi Minh City, Vietnam, and receiving no ULT at presentation. Age and sex of patients, gout features, associated diseases, serum (S) uric acid (UA), eGFR (MDRD), urinary lab stick parameters, urine UA/creatinine ratio, and fractional clearance of urate (FCU) were recorded. Patients with HERM were counted and compared with those who had no medullary deposits by the Wilcoxon rank sum test for continuous varables and the Fischer exact test for categorical variables. Multivariable logistic model was used to assess relation between variables at inclusion in the study and presence of medulla deposits. Results 503 consecutive patients (500 males) were included. They had a median age of 46 years, median BMI of 25 kg/m2, median gout duration of 4 years. 280 (56%) had clinical tophi, 154 (31%) urate arthropathy, 28;56%) urolithiasis, 112 (22%) hypertension, 58 (11.5%) type 2 diabetes, 5 (1%) coronary heart disease. Their median eGFR was 78 ml/min, SUA 423 micromol/L, FCU 0.063, urine UA/creatinine ratio 0.253, urinary pH 6. Diffuse and bilateral HERM on the B mode with frequent twinkling artefacts on the Doppler mode was identified in 181 (36%) of the 503 patients. Univariate analysis showed that HERM associated with higher age, longer duration of gout, clinical tophi, urate arthropathy (p Conclusions In our gout population, HERM was observed in 36% of patients,correlated with decreased renal function, and clearly associated with severe gout, but not with features of uric acic lithiasis. Disclosure of Interest T. Bardin Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, K. M. Tran: None declared, Q. D. Nguyen: None declared, N. H. Le : None declared, P. Richette Consultant for: Grunnenthal, Ipsen Menarini, Astrazeneca, NovartisSobi, P. Le Van: None declared, J.-M. Correas: None declared, M. Resche-Rigon: None declared

Background: A novel combination of vemurafenib (VM), a selectif inhibitor of BRAF V600 mutated protein + oral palbociclib (Palbo) a highly selective reversible oral inhibitor of cyclin-dependent kinases (CDK) 4 and 6, could provide a synergistic antitumor activity in patients with metastatic melanoma harbouring BRAF V600 mutation and CDKN2A loss. VM has been shown to be an inductor of CYP3A4 which is also mainly involved in Palbo metabolism. In this study we investigated the potential pharmacokinetic (PK) drug-drug interactions (DDI) related to the association of VM and Palbo. Methods: metastatic melanoma harbouring BRAF V600 mutation and CDKN2A loss patients were treated with a 14 days on followed by 7 days off dosing schedule of Palbo + continuous bid dosing of VM. Dose levels [DL, Palbo (mg/day)/VM (mg/bid)] ranged from 25/720 to 200/960. For PK analysis, 7 time point samples were collected on D1C1, D21C1, and D7C2, for Palbo and VM assays. Plasma concentrations of Palbo and VM, were measured using ultra high performance liquid chromatography (UHPLC) coupled with tandem mass spectrometry validated methods. Population PK (PPK) was modeled using a non linear mixed effect model program (Monolix version 2018r) by computing the maximum likelihood estimator of the parameters without any approximation of the model (no linearization). The following parameters were calculated absorption constant (Ka); apparent distribution volume (V/F); apparent clearance (CL/F) Results: A total of 18 patients were treated by the combination of Palbo + VM. VM and palbo plasma concentrations were measured in 236 and 275 blood samples respectively. A one-compartment open model with linear elimination adequately described Palbo concentration-time courses. The inter-individual variabilities (ISV) could be well estimated for all stuctural parameters. The PPK parameters obtained for the structural model were: Ka = 0.791 h-1, CL/F=76.0L/h, V1/F=2830 L. Albuminemia had a significant impact on palbo CL. A one-compartment model adequately fitted the VM plasma concentration-time data. The PPK parameters were CL/F=0.133 L/h, V/F=83.6 L and Ka has been fixed at 0.2 h-1. Body weight (BW) was the best size descriptor when VM CL and V terms were normalized to a mean BW of 70 Kg according to an allometric scaling rule. Conclusions: The PPK modeling satisfactorily described the plasma Plabo and VM time-concentration curves in patients. The main covariate effect was related to BW and albuminemia. There is no significant evidence for drug-drug PK interaction between Palbo and VM. PK-PD modeling will be performed. Citation Format: Samuel Huguet, Thierry Lesimple, Arthur Geraud, Mouna Amini-Adle, Caroline Dutriaux, Laetitia Da Meda, Florence Capelle, Zineb Ghrieb, Samia Mourah, Olivier Madar, Didier Bouton, Mathieu Resche-Rigon, Celest Lebbe, Keyvan Rezai. A phase I-II pharmacokinetic drug-drug interaction evaluation of oral palbociclib in combination with vemurafenib in patients suffering metastatic melanoma with BRAF V600 mutated and CDKN2A loss & expression of Rb [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3895.

Objectives: To determine whether a policy based on provisional replacement of catheters every 5 days had an impact on the incidence of arterial catheter-related bloodstream infections in a population of adult surgical intensive care unit patients. Design: Prepost study in which all patients with an arterial catheter who were admitted between 1997 and 2004 were observed. Scheduled replacement of arterial catheters every 5 days during period A (before 2000) was compared to nonscheduled replacement during period B (after 2000). Setting: A 20-bed surgical intensive care unit at a French university hospital. Patients: All intensive care unit patients requiring an arterial catheter. Interventions: Modification to the catheter maintenance policies between period A and period B. Measurements and Main Results: A total of 1,672 consecutive patients were included, and 3,247 arterial catheters were analyzed, yielding an average number of 1.9 (so, 1.7) arterial catheters per patient. The rate of colonization (14.2% before 2000 vs. 16.4% after 2000; p = .10) and the incidence density of arterial catheter colonization (31.32 [95% confidence interval] 27.07-36.25 per 1,000 catheter-days before 2000 vs. 29.79 [95% confidence interval, 26.72-33.21] per 1,000 catheter-days after 2000; p = .11) did not differ significantly between the two periods. However, the rate of arterial catheter-related bloodstream infections (1.4% before 2000 vs. 0.6% after 2000; p = .01) and the arterial catheter-related bloodstream infections incidence density (3.13 [95% confidence interval, 1.97-4.97] before 2000 vs. 1.01 [95% confidence interval, 0.56-1.82] per 1,000 catheter-days after 2000; p < .0001) was significantly higher before 2000. Conclusion: Discontinuation of scheduled replacement of arterial catheters every 5 days did not increase the risk of colonization but decreased the risk of bloodstream infections.

Hereditary fibrinogen A -chain amyloidosis: Phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 115: 2998–3007, 2010 Arie J. Stangou, Nicholas R. Banner, Bruce M. Hendry, Mohamed Rela, Bernard Portmann, Julia Wendon, Mark Monaghan, Philip MacCarthy, Muriel Buxton-Thomas, Christopher J. Mathias, Juris J. Liepnieks, John O’Grady, Nigel D. Heaton, and Merrill D. Benson Fibrinogen amyloidosis due to mutations in the fibrinogen -chain gene (AFib) localized on chromosome 4 and composed of six exons belongs to the group of nonneuropathic hereditary renal amyloidoses. It is the most common type of all hereditary renal amyloid diseases in the United States and Europe. Like other forms of amyloidosis, AFib amyloidosis is a protein misfolding disorder. Fibrinogen production is exclusively hepatic. Liver transplantation was therefore considered as a logical mode of treatment, whereas isolated renal transplantation was followed by kidney amyloid recurrence in most patients. Stangou et al. have first revisited the current phenotypic description of AFib amyloidosis and second performed a systematic evaluation for liver and kidney transplantation (LKT) in a series of 22 patients (8 women, 14 men). Three of them had been misdiagnosed as primary systemic AL amyloidosis—a diagnostic error already reported (1). The median age at presentation was 55 years (range 33 to 63 years). Proteinuria was the most common presenting feature (median 24-hour urine protein 7.2 g; range 0 to 11.8 g). At the time of assessment, median GFR was 16 ml/min (range 0 to 52 ml/min). Renal biopsy was performed in 21 of 22 patients and revealed amyloidosis in all patients, with enlarged glomeruli replaced by amyloid with minimal or no extraglomerular involvement—a finding suggestive of this type of amyloidosis (1). Twenty of 22 patients progressed to ESRD. Two patients had liver amyloidosis, complicated in one by end-stage liver disease. Coronary atherosclerotic disease was documented in 15 patients (68%), in half of the patients predating evolution of kidney impairment. Twelve patients had severe systemic vascular disease, involving aorta, splanchnic, or carotid arteries. Two patients underwent carotid endarterectomy. Of interest, the excised material contained amyloid purely consistent of mutant fibrinogen A -chain. Cardiac amyloidosis was not a rare localization. Echocardiography was abnormal in 11 of 21 patients (52%). Three of the four endomyocardial biopsies revealed substantial amyloid deposition. One patient developed dilated amyloid cardiomyopathy in association with coronary disease and myocardial amyloidosis, whereas cardiac amyloidosis usually leads to restrictive cardiomyopathy. In addition, cardiac parasympathetic dysfunction and risk of bradycardia were identified in 12 patients. Seven of them had pacemaker insertion. Autonomic involvement of the gastrointestinal tract was a feature in 15 patients. Only 24% of patients had family history of renal disease. However, 81% had family history of systemic or coronary vascular disease. Family members who had such cardiovascular history were indeed carriers of AFib mutations. Spontaneous splenic rupture occurred in four patients (one during hemodialysis and three during transplantation). The excised spleen contained widespread amyloid. Nine of 14 patients accepted on the waiting list received combined liver and kidney allografts. At a median follow-up of 67 months, six of nine patients are alive and well with normal liver function. Five patients have good renal function. Cardiac amyloidosis has not progressed after LKT. I-labeled serum amyloid P component (SAP) scintigraphy showed regression of systemic visceral amyloid deposits as early as at the first annual follow-up scan after LKT, whereas scintigraphy documented progressive amyloid deposition in two patients who had previously undergone isolated kidney transplant. Serial 99mTcDMSA renal scintigraphy after preemptive LKT in two patients demonstrated stable native renal uptake. Four patients with various liver diseases received, after full information, explanted livers from AFib patients. Only one “domino” recipient had SAP scans and echocardiography for up to 5 years with no evidence of de novo amyloid deposition. The study by Stangou et al. extends the clinical scope of AFib amyloidosis. Stangou et al. encourage evaluation of isolated liver transplant early in the course of amyloid nephropathy to prevent systemic deposition and renal progression to ESRD. Amyloid fibrils in AFib contain exclusively variant fibrinogen. Circulating total fibrinogen consists of a mixture of wild-type/ variant fibrinogen in a ratio of 1:1 to 3:2. Wild-type fibrinogen does not perpetuate amyloid disease. After liver transplant, the variant fibrinogen is eliminated and promptly replaced by Published online ahead of print. Publication date available at www.cjasn.org.

Treatment of hepatitis C (HCV)–mixed cryoglobulinemia (MC) may target either the viral trigger (HCV) or the downstream B-cell clonal expansion. Prospective cohort study of 38 HCV-MC patients who received a combination of rituximab (375 mg/m2) once a week for 1 month followed by Peg-interferon-α (Peg-IFN-α; 2a, 180 μg or 2b, 1.5 μg/kg) weekly plus ribavirin (600-1200 mg) daily for 48 weeks were compared with 55 HCV-MC patients treated by Peg-IFN-α/ribavirin with the same modalities. In the whole population of HCV-MC patients (n = 93), a complete clinical response was achieved in 73.1% (68 of 93), cryoglobulin clearance in 52.7% (49 of 93), and a sustained virologic response in 59.1% (55 of 93). Compared with Peg-IFN-α/ribavirin, rituximab plus Peg-IFN-α/ribavirin–treated patients had a shorter time to clinical remission (5.4 ± 4 vs 8.4 ± 4.7 months, P = .004), better renal response rates (80.9% vs 40% of complete response, P = .040), and higher rates of cryoglobulin clearance (68.4% vs 43.6%, P = .001) and clonal VH1-69+ B-cell suppression (P < .01). Treatment was well tolerated with 11% of discontinuation resulting from antiviral therapy and no worsening of HCV RNA under rituximab. Our findings indicate that rituximab combined with Peg-IFN-α/ribavirin is well tolerated and more effective than Peg-IFN-α/ribavirin in HCV-MC.

Objective To examine whether a first or second trimester induced abortion with misoprostol influences the risk of late abortion or preterm delivery in subsequent pregnancies. Study design Case–control study in a teaching hospital from January 2005 to June 2006. The cases had singleton pregnancies delivered at 16–36 weeks of gestation after spontaneous late abortions, preterm labor or preterm premature rupture of membrane, or induction of labor for preterm premature rupture of membrane before 37 weeks. The control group was composed of the two consecutive spontaneous singleton deliveries at ≥37 weeks of gestation after each new case (ratio 2/1). The principal outcome measure was late abortion or preterm delivery. The association between late abortion or preterm delivery and a previous induced abortion with misoprostol was first assessed with the Cochran-Mantel-Haenszel chi-square test. Conditional logistic regression models adapted for clustered data were then further used to quantify the effect size, measured by estimated odds ratios (ORs) with their 95% confidence intervals (95% CI). Results The study included 245 cases and 490 controls. There was no significant difference in mean maternal age, number of pregnancies, parity, smoking, or history of first trimester miscarriage between cases and controls. However, a history of late abortion or previous preterm delivery was significantly more frequent among cases than controls. Forty (16.3%) cases and 56 (11.5%) controls had a history of cervical ripening with misoprostol before vacuum curettage or evacuation, or of medical abortion by misoprostol alone or with mifepristone (OR 1.51, 95% CI: 0.95–2.39; p = 0.08). After adjustment for maternal age and number of pregnancies with a multivariable conditional regression model, the adjusted OR was estimated at 1.33 (95% CI: 0.81–2.17; p = 0.25). Conclusion Despite the need for prudence, these results provide some reassurance that induced abortion with misoprostol during the first or second trimester of pregnancy is safe for subsequent pregnancies.

Background: The report of the CUSUM across surgical and interventional procedures has spawned a fair confusion in the literature. Aim: To assess the use of the CUSUM and to clarify its utilisation in the perspective of future studies. Nature of the study: Retrospective review. Methods: A systematic literature search of Medline was carried out. From each article, data regarding the design of the study, the specialty, the performance criterion, the unit under control, the methodology and the model of the CUSUM used, the use of a graph, the use of a test and the type of test applied were retrieved. Results: 31 studies were found relevant. The design was mainly retrospective for the analysis of the learning curve. The main performance criteria under control were morbidity, mortality and success of the procedure. A graph was plotted in all studies as a CUSUM plot or as cumulative sums of non-negative values. A test was used in 17 studies. Mislabelling of the plot and the test, and misuse of control limits were the most commonly reported mistakes. Conclusion: The CUSUM tool is not yet properly reported in the surgical literature. Therefore, reporting of the CUSUM should be clarified and standardised before its use widens.

Abstract 845 Background: ATRA combined to anthracycline-based chemotherapy (CT) for induction and consolidation followed by prolonged maintenance is a standard treatment of newly diagnosed APL, but the outcome and prognostic factors in the elderly are less well established than in younger patients (pts). Methods: We performed a joint analysis of elderly pts included in two subsequent trials of the PETHEMA group (LPA96 and LPA99) and and on the French -Belgian-Swiss APL group (APL93 and APL2000). In the PETHEMA trials, pts received induction therapy with ATRA and idarubicin (Ida 12 mg/m2/d, d2,4,6,8), consolidation with 3 anthracycline monochemotherapy courses (2 with Ida and 1 with mitoxantrone, with ATRA and higher idarubicin dose for Sanz's int and high risk pts in LPA99 trial), and 2-year maintenance with intermittent ATRA and continuous low-dose CT (6MP + MTX). In APL 93 and 2000 trials: pts received induction therapy with ATRA and DNR (60mg/m2/d ×3d)+AraC, (200 mg/m2/d×7) followed by consolidation with a similar course and a final DNR (45 mg/m2/d × 3) + AraC (1-2 g/m2/12h × 8) course (omitted in pts >65y) and the same maintenance as in PETHEMA trials. Median follow up was 75 and 42 months in PETHEMA and APL trials, respectively. Results: 1575 consecutive newly diagnosed APL pts were enrolled in the 4 trials, including 1288 (81%), 105 (6.6%), 91 (5.7%) and 91 (5.7%) aged 70, respectively (ie 287 pts (18%) older than 60). CR rates in these age groups were 94.6%, 84.8%, 81.8% and 78.4% (p=0.0002). All failures were due to early death, except one due to resistant leukemia, in a younger adult. The 5-year cumulative incidence of relapse was 16.5%, 19.1% ,11.9% and 13.5% in pts 70, respectively (p= 0.63). The 5-year OS in these age groups was 85.8%, 68.7%, 63.8% and 56.4% (p70 years, respectively (p In pts >60 yrs, by multivariate analysis, early death was associated with increased WBC (p=0.046), and increased creatinine level (p=0.002). Higher CIR was associated with increased WBC (p=0.002) . In patients older than 60 years, age had no significant impact on CR rate and survival. Finally, no significant differences in outcome were seen between French Belgian Swiss and PETHEMA trials. Conclusion: In pts older than 60, classical APL treatment with ATRA combined to anthracycline based CT followed by prolonged maintenance gives no initial leukemic resistance and similar relapse rate as in younger pts, but significantly lower OS due to a higher incidence of early deaths and of deaths in CR compared with younger pts. Higher WBC counts are associated with an increased incidence of both early deaths and deaths in CR. Improvement in prognosis, therefore, requires better supportive care during induction treatment, while reduction of the amount of myelosuppressive drugs during post induction treatment may be required to reduce deaths in CR. Disclosures: Fenaux: CELGENE: Research Funding; AMGEN: Research Funding.