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Kidney fibrosis constitutes the shared final pathway of nearly all chronic nephropathies, but biomarkers for the non-invasive assessment of kidney fibrosis are currently not available. To address this, we characterize five candidate biomarkers of kidney fibrosis: Cadherin-11 (CDH11), Sparc-related modular calcium binding protein-2 (SMOC2), Pigment epithelium-derived factor (PEDF), Matrix-Gla protein, and Thrombospondin-2. Gene expression profiles in single-cell and single-nucleus RNA-sequencing (sc/snRNA-seq) datasets from rodent models of fibrosis and human chronic kidney disease (CKD) were explored, and Luminex-based assays for each biomarker were developed. Plasma and urine biomarker levels were measured using independent prospective cohorts of CKD: the Boston Kidney Biopsy Cohort, a cohort of individuals with biopsy-confirmed semiquantitative assessment of kidney fibrosis, and the Seattle Kidney Study, a cohort of patients with common forms of CKD. Ordinal logistic regression and Cox proportional hazards regression models were used to test associations of biomarkers with interstitial fibrosis and tubular atrophy and progression to end-stage kidney disease and death, respectively. Sc/snRNA-seq data confirmed cell-specific expression of biomarker genes in fibroblasts. After multivariable adjustment, higher levels of plasma CDH11, SMOC2, and PEDF and urinary CDH11 and PEDF were significantly associated with increasing severity of interstitial fibrosis and tubular atrophy in the Boston Kidney Biopsy Cohort. In both cohorts, higher levels of plasma and urinary SMOC2 and urinary CDH11 were independently associated with progression to end-stage kidney disease. Higher levels of urinary PEDF associated with end-stage kidney disease in the Seattle Kidney Study, with a similar signal in the Boston Kidney Biopsy Cohort, although the latter narrowly missed statistical significance. Thus, we identified CDH11, SMOC2, and PEDF as promising non-invasive biomarkers of kidney fibrosis.

To study whether replacement of nosocomial ampicillin-resistantRetrospective, matched-cohort study.The study included 20 Dutch and Danish hospitals from 2009 to 2014.Within the study period, 63 patients with VRE bacteremia (36 Dutch and 27 Danish) were identified and subsequently matched to 234 patients with ARE bacteremia (130 Dutch and 104 Danish) for hospital, ward, length of hospital stay prior to bacteremia, and age. For all patients, 30-day mortality after bacteremia onset was assessed.The risk ratio (RR) reflecting the impact of vancomycin resistance on 30-day mortality was estimated using Cox regression with further analytic control for confounding factors.The 30-day mortality rates were 27% and 38% for ARE in the Netherlands and Denmark, respectively, and the 30-day mortality rates were 33% and 48% for VRE in these respective countries. The adjusted RR for 30-day mortality for VRE was 1.54 (95% confidence interval, 1.06-2.25). Although appropriate antibiotic therapy was initiated later for VRE than for ARE bacteremia, further analysis did not reveal mediation of the increased mortality risk.Compared to ARE bacteremia, VRE bacteremia was associated with higher 30-day mortality. One explanation for this association would be increased virulence of VRE, although both phenotypes belong to the same well-characterized core genomic lineage. Alternatively, it may be the result of unmeasured confounding.

Background and objectives Native kidney biopsies are commonly performed in the diagnosis of acute kidney diseases and CKD. Because of the invasive nature of the procedure, bleeding-related complications are not uncommon. The National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases–sponsored Kidney Precision Medicine Project requires that all participants undergo a kidney biopsy; therefore, the objective of this analysis was to study complication rates of native kidney biopsies performed using automated devices under kidney imaging. Design, setting, participants, & measurements This is a systematic review and meta-analysis of the literature published from January 1983 to March 2018. The initial PubMed search yielded 1139 manuscripts. Using predetermined selection criteria, 87 manuscripts were included in the final analysis. A random effects meta-analysis for proportions was used to obtain combined estimates of complication rates. Freeman–Tukey double-arcsine transformations were used to stabilize variance as complications were rare. Results A total of 118,064 biopsies were included in this study. Patient age ranged from 30 to 79 years, and 45% of patients were women. On the basis of our meta-analysis, pain at the site of biopsy is estimated to occur in 4.3% of biopsied patients, hematomas are estimated to occur in 11%, macroscopic hematuria is estimated to occur in 3.5%, bleeding requiring blood transfusions is estimated to occur in 1.6%, and interventions to stop bleeding are estimated to occur in only 0.3%. Death attributed to native kidney biopsy was a rare event, occurring only in an estimated 0.06% of all biopsies but only 0.03% of outpatient biopsies. Complication rates were higher in hospitalized patients and in those with acute kidney disease. The reported complications varied on the basis of study type and geographic location. Conclusions Although the native kidney biopsy is an invasive diagnostic procedure, the rates of bleeding complications are low. Albeit rare, death can occur postbiopsy. Complications are more frequently seen after kidney biopsies of hospitalized patients with AKI.

Archaea are uniquely adapted to thrive in harsh environments, and one of these adaptations involves the archaeal membrane lipids, which are characterized by their isoprenoid alkyl chains connected via ether linkages to glycerol 1-phosphate. The membrane lipids of the thermophilic and acidophilic euryarchaeota Thermoplasma volcanium are exclusively glycerol dibiphytanyl glycerol tetraethers. The first committed step in the biosynthetic pathway of these archaeal lipids is the formation of the ether linkage between glycerol 1-phosphate and geranylgeranyl diphosphate, and is catalyzed by the enzyme geranylgeranylglyceryl phosphate synthase (GGGPS). The 1.72 Å resolution crystal structure of GGGPS from T. volcanium (TvGGGPS) in complex with glycerol and sulfate is reported here. The crystal structure reveals TvGGGPS to be a dimer, which is consistent with the absence of the aromatic anchor residue in helix α5a that is required for hexamerization in other GGGPS homologs; the hexameric quaternary structure in GGGPS is thought to provide thermostability. A phylogenetic analysis of the Euryarchaeota and a parallel ancestral state reconstruction investigated the relationship between optimal growth temperature and the ancestral sequences. The presence of an aromatic anchor residue is not explained by temperature as an ecological parameter. An examination of the active site of the TvGGGPS dimer revealed that it may be able to accommodate longer isoprenoid substrates, supporting an alternative pathway of isoprenoid membrane-lipid synthesis.

An understanding of the ethical underpinnings of human subjects research that involves some risk to participants without anticipated direct clinical benefit-such as the kidney biopsy procedure as part of the Kidney Precision Medicine Project (KPMP)-requires a critical examination of the risks as well as the diverse set of countervailing potential benefits to participants. This kind of deliberation has been foundational to the development and conduct of the KPMP. Herein, we use illustrative features of this research paradigm to develop a more comprehensive conceptualization of the types of benefits that may be important to research participants, including respecting pluralistic values, supporting the opportunity to act altruistically, and enhancing benefits to a participant's community. This approach may serve as a model to help researchers, ethicists, and regulators to identify opportunities to better respect and support participants in future research that entails some risk to these participants as well as to improve the quality of research for people with kidney disease.

BackgroundAutoinflammatory diseases (AID) are characterized by severe systemic and organ inflammation as well as high burden of disease for patients and their families. Treatment with the monoclonal antibody canakinumab (CAN), an interleukin-1β inhibitor, has been proven to be safe and effective in clinical trials and real-life.ObjectivesThe present study explores the long-term efficacy and safety of CAN in routine clinical practice conditions in pediatric (age ≥2 years) and adult patients with CAPS (cryopyrin-associated periodic syndromes), FMF (familial Mediterranean fever), TRAPS (tumor necrosis factor receptor-associated periodic syndrome) and HIDS/MKD (hyperimmunoglobulinemia D syndrome/mevalonate kinase deficiency).MethodsRELIANCE is a prospective, non-interventional, observational study based in Germany. Patients with clinically confirmed diagnoses of AID routinely receiving CAN are enrolled. Besides efficacy parameters regarding disease activity and remission, safety parameters were recorded at baseline and assessed at 6-monthly intervals.ResultsHere, we present the interim analysis of patients with AID (N=199) enrolled in the RELIANCE Registry between October 2017 and December 2021. Mean age in this cohort was 24.4 years (2–79 years) and the proportion of female patients was 53% (N=104). At baseline, median duration of prior CAN treatment was 2 years (0–12 years).A total of 123 patients (62%) experienced any AE (N=653) among which nasopharyngitis, increase of inflammatory markers and pyrexia were the most frequent AE with incidence rates per 100 patient years (IR) of 8.3, 6.2, and 6.2, respectively.29 patients (15%) were affected by severe AE (SAE, total number N=90) including 11 patients (6%) with SAE suspected to be drug-related (SADR; total number N=30) with IR from 0.2 to 0.7 (Table 1). Overall, 16 AE comprised upper respiratory tract infections (URI). One death (COVID-19, not related) and one malignancy (skin papilloma, not related) were reported. No vertigo and no hypersensitivity reactions were observed. N=10 (IR 2.36) vaccination reactions were reported (no SAE).Table 1.Overview of the CAN safety data of the RELIANCE study across all study indications (N=199 patients).Type of eventNumber of eventsIR‡AE total653154.43AE non-serious563133.15AE, non-serious, not related31774.97AE, URI163.78AE, non-serious adverse drug reaction24658.18SAE, total9021.28SAE, not related6014.19SADR#, total307.09#Abdominal pain; Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, Haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tachycardia, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (each n=1 event, IR 0.24‡), tonsillectomy (2 events, IR 0.47‡), pyrexia (3 events, IR 0.71‡), not yet coded (hospital admission due to exsiccosis upon gastroenteritis, 1 event, IR 0.35‡)‡IR, incidence rate per 100 patient years; AE, adverse event; URI, upper respiratory tract infection; SAE, severe adverse event, SADR, severe adverse drug reactionIncidence rate = number of events * 36,525 / sum of observation days (=154,442)ConclusionThe interim data from the RELIANCE study, the longest running real-life canakinumab registry, confirm safety of long-term canakinumab treatment across the entire study population. A trend for dose-related increase of SAE/SADR requires continuous close monitoring and awareness in patient groups (children, severe phenotypes, certain genotypes) requiring greater than standard dose treatment regimens.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Jörg Henes Consultant of: Novartis, AbbVie, Sobi, Roche, Janssen, Boehringer-Ingelheim, Grant/research support from: Novartis, Roche, Birgit Kortus-Goetze Consultant of: Novartis, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Prasad Oommen Grant/research support from: Novartis, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ales Janda: None declared, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Catharina Schuetz: None declared, Frank Dressler Consultant of: Abbvie, Mylan, Novartis, Pfizer, Grant/research support from: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Markus Hufnagel Consultant of: Novartis and SOBI, Florian Meier Speakers bureau: Novartis, Michael Fiene: None declared, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

BackgroundThe cryopyrin-associated periodic fever syndromes (CAPS) are hereditary monogenic autoinflammatory diseases with severe systemic and organ inflammation due to increased production of Interleukin-1β (IL-1β). The subcutaneously administered monoclonal antibody canakinumab (CAN) effectively inhibits IL-1β and results in rapid remission of CAPS symptoms in clinical trials as well as in real-life.ObjectivesThe RELIANCE registry is designed to explore long-term safety and effectiveness of CAN under routine clinical practice conditions in pediatric (≥2 years) and adult patients with CAPS, including Muckle-Wells syndrome (MWS), familial cold autoinflammatory syndrome (FCAS), and neonatal onset multisystem inflammatory disease (NOMID)/chronic infantile neurological cutaneous and articular syndrome (CINCA).MethodsThis prospective, non-interventional, observational study with a 3-year follow-up enrolls patients in Germany with clinically confirmed diagnoses of CAPS routinely receiving CAN. In 6-monthly visits, clinical data, physician assessments and patient-reported outcomes are evaluated starting at baseline.Results98 CAPS patients (52% female; 15 [15%] NOMID/CINCA subtypes) were enrolled by December 2021 (Table 1). At baseline, median age was 20 years and median duration of prior CAN treatment was 6 years. At the 36 months visit, 74% of patients reached disease remission by physicians´ assessment along with increasing rates of absent disease activity (patient’s assessment, median 2.0 at baseline and 0.0 month 36). In addition, patients reported low levels of fatigue (absent to mild/moderate: 87% at baseline and 95% at month 36). At baseline, CAPS impaired social life in 47% of patients (37% at month 36) and 33% (23% at month 36) reported days off from school/work. Lab parameters were within normal limits. Remission and disease control were sustained as evaluated parameters remained stable or even decreased over time.Table 1.Patient and physician assessment of clinical CAPS disease activity and laboratory markers over time.Baseline12 months36 monthsNumber of patients, N987240Number (%) of patients in disease remission (physician assessment)64 (68)48 (70)28 (74)Patient’s assessment of current disease activity; 0–10, median (min; max)2.0 (0; 7)2.0 (0; 7)0.0 (0; 6)Patient’s assessment of current fatigue; 0–10, median (min; max)3.0 (0; 9)2.0 (0; 8)1.0 (0; 8)Number (%) of patients without impairment of social life by the disease34 (53)35 (65.0)17 (63)CRP (mg/dl) | SAA (mg/dl); median0.1 | 0.30.1 | 0.50.1 | 0.3Number (%) of patients with disease-related symptomsprior to inclusion into the study | at baseline12 months36 monthsFever75 (80) | 14 (15)19 (28)4 (11)Fatigue84 (89) | 49 (52)36 (52)17 (46)Conjunctivitis/Uveitis63 (67) | 27 (29)21 (30)7 (19)Headache68 (72) | 30 (32)30 (43)9 (24)Arthralgia/arthritis80 (85) | 32 (34)30 (43)14 (38)Impairment of hearing35 (37) | 23 (25)18 (26)11 (30)Trigger (cold, stress, infections, vaccinations, hormones)71 (76) | 32 (34)21 (30)3 (8)SAENumber of eventsIncidence rate* per 100 patient yearsAll types of SAE | SADR63 | 28#25.98 | 11.55CRP, c-reactive protein; ESR, erythrocyte sedimentation rate; n. a., not annotated; SAA, serum amyloid A; SADR, serious adverse drug reaction; SAE, serious adverse event*Incidence rate = number of events * 36,525 / sum of observation days (=88,558)#Abdominal pain, Alport’s syndrome, appendicitis, arthralgia, blister, cardiovascular disorder, chest pain, circulatory collapse, dehydration, diplopia, dyspnoea, erythema, febrile convulsion, gastroenteritis, glomerulonephritis, haemophilus test positive, myalgia, oedema, pneumonia, premature delivery, skin discoloration, tonsillectomy, tonsillitis bacterial, tonsillitis streptococcal, vision blurred (all N=1 event), pyrexia (3 events)ConclusionThe 36-month interim analysis of the RELIANCE study demonstrates that long-term CAN treatment is safe and effective in patients with CAPS, independent of subtype severity.Disclosure of InterestsJ. B. Kuemmerle-Deschner Consultant of: Novartis, AbbVie, Sobi, Grant/research support from: Novartis, AbbVie, Sobi, Birgit Kortus-Goetze Paid instructor for: Novartis, Prasad Oommen Grant/research support from: Novartis, Ales Janda: None declared, Jürgen Rech Speakers bureau: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD; Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Consultant of: Abbvie, Biogen, BMS, Chugai, GSK, Janssen, Lilly, MSD, Mylan, Novartis, Roche, Sanofi, Sobi, UCB, Grant/research support from: Novartis, Sobi, Catharina Schuetz: None declared, Tilmann Kallinich Consultant of: Sobi, Novartis, Roche, Grant/research support from: Novartis, Frank Weller-Heinemann: None declared, Gerd Horneff Speakers bureau: AbbVie, Bayer, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Grant/research support from: AbbVie, Chugai, Merck Sharp & Dohme, Novartis, Pfizer, Roche, Ivan Foeldvari Consultant of: Novartis, Hexal, Medac, Pfizer, Florian Meier Speakers bureau: Novartis, Michael Borte Grant/research support from: Pfizer, Shire, Tobias Krickau Speakers bureau: Novartis, Consultant of: Novartis, Grant/research support from: Novartis, Julia Weber-Arden Employee of: Novartis, Norbert Blank Consultant of: Novartis, Sobi, Lilly, Pfizer, Abbvie, BMS, MSD, Actelion, UCB, Boehringer-Ingelheim, Roche, Grant/research support from: Novartis, Sobi

The saturated hydrocarbon bisabolane is a diesel fuel substitute that can be derived from sesquiterpene precursors bisabolene or curcumene. These sesquiterpenes are generated from farnesyl diphosphate in reactions catalyzed by eponymous terpenoid cyclases, but they can also be generated by engineered terpenoid cyclases in which cyclization cascades have been reprogrammed by mutagenesis. Here, we describe the X-ray crystal structure determination of F95Q epi-isozizaene synthase (EIZS), in which the new activity of curcumene biosynthesis has been introduced and the native activity of epi-isozizaene biosynthesis has been suppressed. F95Q EIZS generates β- and γ-curcumene regioisomers with greater than 50% yield. Structural analysis of the closed active site conformation, stabilized by the binding of 3 Mg2+ ions, inorganic pyrophosphate, and the benzyltriethylammonium cation, reveals a product-like active site contour that serves as the cyclization template. Remolding the active site contour to resemble curcumene instead of epi-isozizaene is the principal determinant of the reprogrammed cyclization cascade. Intriguingly, an ordered water molecule comprises part of the active site contour. This water molecule may also serve as a final proton acceptor, along with inorganic pyrophosphate, in the generation of curcumene regioisomers; it may also contribute to the formation of sesquiterpene alcohols identified as minor side products. Thus, the substitution of polar side chains for nonpolar side chains in terpenoid cyclase active sites can result in the stabilization of bound water molecules that, in turn, can serve template functions in isoprenoid cyclization reactions.

BackgroundThe delay of the diagnosis of pulmonary hypertension (PH) in patients with systemic sclerosis (SSc) leads to severe impairment of survival.ObjectivesThe objective of this study was to investigate the prognostic impact of right ventricular (RV) function at rest and during exercise on survival in patients with SSc presenting for screening for PH.MethodsData from SSc patients who underwent routinely performed examinations for PH screening including echocardiography and right heart catheterization at rest and during exercise were analyzed. Uni- and multivariable analyses were performed to identify prognostic parameters in SSc and to compare them to known prognostic predictors.ResultsOut of 285 SSc patients screened for PH, 225 patients (81.3% female, mean age 58.1±13.0 years, 68% limited cutaneous SSc, WHO-FC II-III 74%, 24 manifest PH) were included in the analysis. During an observation period of 3.2±2.7 (median 2.6) years 35 patients died. Tricuspid annular plane systolic excursion ≤18 mm (p=0.0004), increase of cardiac index (CI) during exercise ≤ 2 l/min (p=0.0002), RV output reserve >3 mmHg/l/min (p=0.001), peak CI ≤ 5.5l/min (p=0.01), pulmonary arterial compliance >2 ml/mmHg (p=0.0005) and qualitative RV function at rest (p2 were identified as independent prognostic predictors and had >70% sensitivity and specificity to predict development of pulmonary vascular disease (PVD) during follow-up.ConclusionThis study demonstrates that assessment of RV function at rest and during exercise may provide crucial information to identify SSc patients who are at a high risk of an impaired survival and development of PVD.References[1]Brown ZR, et al. Screening for pulmonary arterial hypertension in systemic sclerosis: Now or never!. Eur J Rheumatol. 2020;7(Suppl 3):S187-S192.Disclosure of InterestsPanagiota Xanthouli Speakers bureau: MSD and OMT, outside the submitted work, Julia Miazgowski: None declared, Nicola Benjamin Speakers bureau: Actelion pharmaceuticals, Bayer HealthCare and MSD outside the submitted work., Ojan Gordjani: None declared, Benjamin Egenlauf Speakers bureau: Actelion, MSD, Bayer and OMT (less than $10,000 each)., Satenik Harutyunova Speakers bureau: Bayer, MSD, Actelion and GSK, outside the submitted work., Rebekka Seeger: None declared, Alberto Marra Speakers bureau: MSD, Norbert Blank Speakers bureau: MSD, GSK, Actelion and Bayer Vital., Hanns-Martin Lorenz Speakers bureau: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Consultant of: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Ekkehard Grünig Speakers bureau: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Consultant of: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Christina Eichstaedt: None declared

BackgroundIron deficiency is frequent among patients with systemic sclerosis (SSc), particularly among those with pulmonary hypertension (PH). First data indicate prognostic importance of hypochromic erythrocytes (HRC) >2% among patients with PH1. Hence, the aim of this study was to investigate the predictive value of HRC in SSc patients screened for PH.ObjectivesThe objective of this study was to investigate the predictive value of HRC in SSc patients screened for PH.MethodsIn this retrospective, single-center cohort study SSc patients screened for PH were included. Clinical characteristics, laboratory and pulmonary functional parameters associated with the prognosis of SSc were analysed using uni- and multivariable analysis.ResultsA total of 280 SSc patients were screened, 171 were included in the analysis having complete data of iron metabolism (79% female, 61.0±12.9 years of age, 73.2% limited cutaneous SSc, 56 manifest PH and 112 pulmonary fibrosis). The patients were followed for 2.4±1.8 (median 2.4) years. HRC >2% at baseline was significantly associated with worse survival in the uni- (p=0.018) and multivariable analysis (p2% was identified as independent predictor of mortality, for patients with and without pulmonary manifestations of SSc.ConclusionThis study detected for the first time that HRC >2% is an independent prognostic predictor and can possibly be used as a biomarker among SSc-patients. Further studies are needed to confirm these results.References[1]Xanthouli P, Theobald V, Benjamin N, Marra AM, D’Agostino A, Egenlauf B, Shaukat M, Ding C, Cittadini A, Bossone E, Kögler M, Grünig E, Muckenthaler MU, Eichstaedt CA. Prognostic impact of hypochromic erythrocytes in patients with pulmonary arterial hypertension. Respir Res. 2021 Nov 9;22(1):288. doi: 10.1186/s12931-021-01884-9.Disclosure of InterestsPanagiota Xanthouli Speakers bureau: MSD and OMT, outside the submitted work, Ojan Gordjani: None declared, Christina Eichstaedt: None declared, Nicola Benjamin Speakers bureau: Actelion pharmaceuticals, Bayer HealthCare and MSD., Benjamin Egenlauf Speakers bureau: Actelion, MSD, Bayer and OMT outside the submitted work, Satenik Harutyunova Speakers bureau: Bayer, MSD, Actelion and GSK, outside the submitted work., Alberto Marra Speakers bureau: Bayer/MSD outside the submitted work, Vivienne Theobald: None declared, Nicklas Milde: None declared, Christian Nagel Speakers bureau: Actelion, MSD, Boehringer, Novartis, Bayer, and AstraZeneca, Norbert Blank Speakers bureau: MSD, GSK, Actelion and Bayer Vital., Consultant of: MSD, GSK, Actelion and Bayer Vital., Hanns-Martin Lorenz Speakers bureau: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Consultant of: AbbVie, BMS, Pfizer, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, and Lilly (less than $10,000 each) and research support from AbbVie, MSD, BMS, Cellgene, Medac, GSK, Roche, Chugai, Novartis, UCB, Janssen-Cilag, AstraZeneca, Lilly, Baxter, SOBI, Biogen, Actelion, Bayer Vital, Shire, Octapharm, Sanofi, Hexal, Mundipharm, and Thermo Fisher, Ekkehard Grünig Speakers bureau: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House, Consultant of: Actelion, Bayer AG, and MSD; grants from GSK, Novartis, and United Therapeutics; and personal fees from SCOPE, OrPha Swiss GmbH, and Zurich Heart House