Explore the vast range of titles available.

Fluvial sediment analysis and water quality assessment are useful to identify anthropic and natural sources of pollution in rivers. Currently, there is a lack of information about water quality in the Pixquiac basin (Veracruz state, Mexico), and this scarcity of data prevents authorities to take adequate measures to protect water resources. The basin is a crucial territory for Xalapa, the capital city of Veracruz state, as it gets 39% of its drinkable water from it. This research analyzed 10 physicochemical parameters and 12 metal concentrations in various rivers and sources during two seasons. Dissolved metals presented average concentrations (µg/L): Al (456.25) > Fe (199.4) > Mn (16.86) > Ba (13.8) > Zn (7.6) > Cu (1.03) > Pb (0.27) > As (0.12) > Ni (0.118) (Cd, Cr and Hg undetectable). Metals in sediment recorded average concentrations (ppm): Fe (38575) > Al (38425) > Mn (460) > Ba (206.2) > Zn (65.1) > Cr (29.8) > Ni (20.9) > Cu (16.4) > Pb (4.8) > As (2.1) (Cd and Hg undetectable). During the rainy season, Water Quality Index (WAWQI) classified stations P17 and P18’s water as “unsuitable for drinking” with values of 110.4 and 117.6. Enrichment factor (EF) recorded a “moderate enrichment” of Pb in sediment in P24. Pollution was mainly explained by wastewater discharges in rivers but also because of erosion and rainfall events. Statistical analysis presented strong relationships between trace and major metals which could explain a common natural origin for metals in water and sediment: rock lixiviation.

The present work aims to elucidate the possibility of injecting ozone into surface waters combined with urban wastewaters in order to improve the water quality of the High Atoyac Sub-basin (HAS) in Central Mexico. For this purpose, twenty physicochemical parameters, eight heavy metals, seven organic compounds, and one biological indicator were assessed in water from different sites of the studied area (the Alseseca River, the Atoyac River and the Valsequillo Reservoir). Results demonstrated that O3 injection led to the decrease of the aromatic fraction of organic molecules since the Spectral Absorption Coefficient at 254 nanometers (SAC254) reduction was found to be 31.7% in the Valsequillo Reservoir water samples. Maximum Chemical Oxygen Demand (COD) removal was observed to be 60.2% from the Alseseca River with a 0.26 mg O3/mg initial COD dose. Among all the phthalates studied in the present work, Di(2-ethylhexyl) phthalate (DEHP) exhibited the highest concentration (5.8 μg/L in the Atoyac River). Treatment with O3 was not effective in eliminating fecal coliforms (FC) in waters that host high organic matter (OM) loads as opposed to waters with low OM. After the injection of 4.7 mg O3/mg COD in the VO3-AT water sample, a 90% removal of Iron (Fe) and Aluminum (Al) was registered; while Manganese (Mn), Nickel (Ni), Zinc (Zn), and Cooper (Cu) showed a 73%, 67%, 81%, and 80% removal, respectively; Chromium (Cr) registered the highest removal (~100%). The present work demonstrated that while finding a suitable O3 dose to improve the quality of water in the HAS, the 5-days Biochemical Oxygen Demand (BOD5)/COD ratio (i.e., biodegradability) is more important than the overall OM removal percentage proving that O3 injection is a feasible process for the treatment of eutrophic waters from HAS.

Background:B-cell depletion therapy with rituximab is effective in most patients with IgG4-related disease (IgG4-RD) but requires repeated cycles to prevent disease flares leading to prolonged immuno-suppression posing patients at high rik of infectious complications.Objectives:We here aimed to assess B cells after rituximab to predict relapse of IgG4-RD and guide retreatment.Methods:Patients with active IgG4-RD included in this retrospective study fulfilled the ACR/EULAR Classification Criteria. Total CD19+ B cells, plasmablasts, naïve and memory B cells were measured on peripheral blood by flow-cytometry at baseline and six months after rituximab. All patients were treated with two 1gr infusions of rituximab 15 days apart and monitored for 48 months. Disease response was assessed using the IgG4-RD Responder IndexResults:Thirty-three patients were included. Six months after rituximab, disease response was observed in all patients. Complete depletion of CD19+ B cells, plasmablasts, naïve and memory B-cell depletion was achieved in 30%, 55%, 39%, and 42% of cases, respectively. Twenty-three relapses (70%) were observed at a median time of 24 months after rituximab. Relapse rate was significantly higher in patients who failed to achieve complete depletion of CD19+ cells (60% vs 17%, p=0.02), naïve B cells (54% vs 15%, p=0.01), or memory B cells (50% vs 16%, p=0.03) six months after rituximab. The median relapse free survival time was shorter in patients who failed to achieve complete depletion of CD19+ cells (19 vs 38 months, p=0.02), naïve B cells (16 vs 38 months, p=0.01), or memory B cells (19 vs 38 months, p=0.03) six months after rituximab (Figure 1).Conclusion:The degree of B-cell depletion six months after rituximab may predict disease flare and may instruct on the pacing of B-cell depletion therapy in IgG4-RD.REFERENCES:[1] Lanzillotta M, BMJ 2020 Advances in the management of IgG4-related disease.Figure 1.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Systemic lupus erythematosus (SLE) is a multi-organ disease characterised by generalised immune dysfunction. Patients with SLE are more susceptible to infections and higher rates of SLE flares are observed following infectious stimuli (1, 2). Little is known about the qualitative impact of infections on SLE phenotype.Objectives:To assess potential clinical differences between infection-triggered (ITF) and other SLE flares (OF).Methods:A retrospective review of prospectively collected data from >300 patients with SLE was performed. Disease activity was estimated through the SLE disease activity index 2000 (SLEDAI-2K) and the British Isles Lupus Assessment Group (BILAG) 2004 index, damage with the SLE International Collaborating Clinics/American College of Rheumatology Damage index (SDI). DAS-28 was used quantitate arthritis activity. Remission was surrogated by the Lupus Low Disease Activity State (LLDAS) algorithm. Included patient records consisted in couples of consecutive visits showing progression from LLDAS fulfillment to LLDAS loss. Visit couples were divided according to the association vs non-association of recent infections requiring antimicrobial treatment and/or absence from work. Clinical, laboratory and treatment features along with patient history data were compared at inter- and intraindividual level between the two groups. Anti-double stranded DNA antibody titres (ADNA) were recorded in a 0-4 discrete scale. Data are expressed as median (interquartile range), unless otherwise specified.Results:Out of 134 visit couples from 114 patients, 38 were ITF. Viral infections were 11/38. ITF involved one or two BILAG domains in 80% of cases, the most frequent being haematological (61%), mucocutaneous (24%) musculoskeletal 34% and renal (18%) domains. Cardiopulmonary manifestations were numerically less frequent in ITF than OF (0/38 vs 9/96; p=0.060). Although no difference was found in the frequency of musculoskeletal manifestations, ITF were characterised by higher DAS-28 scores [2.6 (2.3-4.1), n=12] than OF [2.0 (1.6-2.7), n=47;p=0.024]. Accordingly, intraindividual comparisons showed higher DAS-28 scores during ITF than during OF (10/11 vs 1/11; p=0.004). Compared to OF, viral IF were associated with lower ADNA titres [0 (0-0) vs 2 (0-3);p=0.046) and a lower frequency of complement consumption (2/11 vs 52/96; p=0.029) along with higher creatinine levels [1.2 (0.8-1.3) vs 0.8 (0.7-0.9)];p=0.016]. No differences were found in flare treatment profiles between ITF and OF.Conclusion:Preliminary data from a monocentric cohort apparently indicate that ITF, especially of viral origin, are associated with distinct clinical and serological phenotypes. This evidence suggests the existence of diverging pathophysiological mechanisms sustaining SLE activity under different conditions, which might benefit for personalized treatments.REFERENCES:[1] Danza A, et al., Lupus. 2013[2] Joo YB, et al., Scientific Reports. 2021Acknowledgements:NIL.Disclosure of Interests:Giuseppe Alvise Ramirez Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Chiara Calabrese: None declared, Gabriele Domenico Gallina: None declared, Luca Moroni Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Enrica Bozzolo: None declared, Marco Matucci-Cerinic: None declared, Lorenzo Dagna: None declared

Background:Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic autoimmune disease characterised by eosinophilia and small-vessel inflammation. Thromboembolism is a relatively common complication of small-vessel vasculitides, including EGPA. Eosinophils are endowed with a significant thrombogenic potential, possibly due to their ability to cause endothelial damage and activate the coagulation cascade by expressing tissue factor. Modulation of interleukin 5 (IL5) is effective in controlling systemic eosinophilic inflammation. Little is known about the potential impact of anti-IL5 agents on thromboembolism.Objectives:To assess whether treatment with mepolizumab (MPZ, an anti-IL5 monoclonal antibody) affects thromboembolism rates in patients with EGPA.Methods:We retrospectively reviewed the clinical and treatment history of 81 consecutive patients with EGPA. We investigated whether patients had experienced one or more thrombotic events, and gathered details about the timing and type of the first event. We also recorded whether patients did or did not receive MPZ and the timeframe of exposure to the drug. Patients exposed to MPZ were analysed before and during MPZ treatment. Disease activity and chronic damage were assessed with the Birmingham vasculitis activity score (BVAS) version 3 and the Vasculitis Damage Index (VDI), respectively. Data are expressed as median (interquartile range) unless otherwise specified.Results:Of 81 patients with EGPA, 57 were and 24 were not exposed to MPZ. Exposure to MPZ started after 61 (29-150) months from disease onset and was observed for 45 (14-48) months. Eighteen patients experienced 21 thrombotic events. The most frequent were deep vein thrombosis (n=7), followed by myocardial infarction (n=4), endocardial thrombosis (n=4), retinal thrombosis (n=3) and stroke (n=3). Six events (33%) occurred at disease onset, while the remainder occurred after 46 (12-133) months. Thrombotic event incidence rates were 1.1/100 person-years (95%CI=0.1-4.0) in-MPZ and 2.6/100 person-years (95%CI=1.5-4.3) off-MPZ. By excluding pre-exposure observations, patients never exposed to MPZ had a higher rate of thrombotic events (n=9/24) compared to patients receiving MPZ (n=2/57; HR=6.7, 95%CI=1.4-33.3, p=0.018). When pre-exposure records were combined with non-exposures, a similar trend was still observed (HR=4.2, 95%CI= 0.9-20; p=0.062). Compared to patients without thrombosis, patients with thrombosis had higher BVAS scores at EGPA onset [12 (10-14) vs 8 (6-13); p=0.042] and a higher frequency of heart involvement (63% vs 12%; p<0.001). No other associations were found with distinct organ involvement or damage accrual.Conclusion:Treatment with MPZ was associated with a low frequency of thrombotic events, consistent with clinical trials and real-life studies [1-3]. Dampening eosinophilic inflammation through MPZ might contribute to reduce the risk of thrombotic events in patients with EGPA [4], especially at later disease stages. Further studies are needed to validate these findings and obtain insights on potential mechanistic implications of IL5 modulation towards haemostasis.REFERENCES:[1] Wechsler ME, et al., N Engl J Med. 2017.[2] Bettiol A, et al., Arthritis Rheumatol. 2022.[3] Ishii T, et al., Mod Rheumatol. 2023.[4] Bettiol A, et al., Eur Respir J. 2021.Acknowledgements:NIL.Disclosure of Interests:None declared.

Background:Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease characterised by significant morbidity. Corticosteroids are the mainstay of treatment but also associate with damage accrual, with evidence suggesting high risk even with short exposures to naïve subjects [1]. Current guidelines suggest a target prednisone dose ≤5mg/day to minimize its detrimental impact [2]. Little is known about the effectiveness of this target in patients with long-standing disease [3].Objectives:To assess whether short-term exposure to high-dose corticosteroids affects damage accrual in patients with SLE flares after diagnosis.Methods:We performed a retrospective analysis of prospectively collected data of 206 patients with SLE followed-up from January 2015 to December 2023. Inclusion criteria were: 1) SLE with a flare after remission from the onset manifestations; 2) availability of ≥2 visits after flare acknowledgement. Patients unable to reduce prednisone dose to ≤5mg/day throughout the follow-up were categorised as high-dose group and compared to the remainder patients (low-dose group). Demographics, SLE clinical history, baseline diseases features, and organ involvement were evaluated. We used Cox regression to estimate the cumulative damage progression rate in the two groups. Organ involvement was assessed with the British Isles Lupus Assessment Group (BILAG) index. Disease activity was also quantitated with the SLE disease activity index 2000 (SLEDAI-2K) along with a 0.0-3.0 physician global assessment scale (PGA). Damage was assessed with the SLE International Collaborating Clinics/American College of Rheumatology Damage index (SDI). Data are expressed as mean ± standard deviation (SD), unless otherwise specified.Results:The study sample consisted in 129 patients (63%) receiving low-dose and 77 (37%) high-dose prednisone. There were no significant differences in terms of sex, age and disease duration between groups. Compared to patients treated with low-dose steroids, patients in the high-dose group had a higher prevalence of skin manifestations, especially of alopecia and cutaneous vasculitis in their history, along with a higher frequency of cardiac involvement and lymphadenopathy (Table 1). The mean disease duration at time of flare was 11±8 years in the high-dose group and 15± 9 years in the low-dose group. Patients in the high-dose group at SLE flares had a higher SLEDAI-2k (7 ± 6 vs 3 ± 2, p<0.001) PGA scores (1.5±0.8 vs 0.5±0.4, p<0.001) compared to the low-dose group. In patients with high-dose prednisone, SLE flares at presentations were characterised by prominent activity in the renal (21% vs 16%, p=0.006), mucocutaneous (31% vs 14%, p=0.003), and constitutional BILAG domain (10% vs 3%, p=0.030) compared to patients in the low-dose group. Over time, patients in the high-dose group had a higher risk of SDI progression compared to patients treated with lower steroid doses (HR=2.55, 95% CI, 1.17 to 5.53; p=0.02; Figure 1. SDI progression occurred early in the treatment course, with an estimated 12% vs 3% 24-month damage accrual incidence in the high- and low-dose group, respectively.Conclusion:Patients with long-standing SLE treated with prednisone doses >5mg/day are characterised by broader disease extent and rapidly accrue damage even with relatively short exposure to corticosteroids, consistent with observations in reacent-onset subjects [1]. Prednisone doses ≤5mg/day significantly minimise, although do not abate damage accrual in patients with longstanding SLE.REFERENCES:[1] Floris A, et al., RMD Open. 2022[2] Fanouriakis A, et al., Ann Rheum Dis. 2023[3] Gerosa M, et al., J Clin Med. 2022Figure 1.Kaplan-Meier survival curves for SDI progressionAcknowledgements:NIL.Disclosure of Interests:None declared.

Background:Vasculopathy, microvascular endothelial cell dysfunction, platelet activation, and interstitial lung disease (ILD) are hallmarks of systemic sclerosis (SSc). Recently, extramedullary thrombopoiesis, involving the adaptation of megakaryocytes (Mks) to stress conditions, has been described in infectious and inflammatory contexts. Activated Mks and platelets both release extracellular vesicles (EVs) and mitochondria. Little is known about Mks activation in SSc.Objectives:We investigated whether Mks-derived EVs, detectable in the blood and amenable to analysis in vitro and in vivo, can provide insights into the state of Mk activation in SSc.Methods:We examined 35 SSc patients and 25 age- and sex-matched healthy donors (HD). EVs were assessed in platelet-free plasma by flow cytometry, and EVs were purified through sequential ultracentrifugation[1,2]. In vitro experiments involved evaluating mitochondria transfer to microvascular primary lung endothelial cells, while lung histology was assessed post-EVs transfer in NSG mice, known for their receptiveness to human tissues.Results:Mks-derived EVs and platelet-derived EVs, containing or lacking mitochondria, accumulated in the plasma of SSc patients (see Table 1). The concentration of both total Mks-EVs and mitochondria-containing Mks-EVs was significantly higher in SSc patients with ILD (see Figure 1). Encapsulation into EVs seemed to enhance the horizontal transfer of mitochondria to nucleated cells. In vivo experiments demonstrated that the injection of SSc-EVs, but not purified mitochondria, rapidly induced lung fibrosis.Table 1.*: P<0.05 vs healthy donors; #: P<0.05 vs patients with ILDConclusion:The accumulation of plasma Mks-derived EVs may serve as an indicator of lung involvement in SSc patients. Further investigations are needed to understand whether extramedullary Mks indeed contribute to the natural history of the disease.REFERENCES:[1] Manfredi AA; et al. Platelet Phagocytosis via P-selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis. Arthritis Rheumatol. 2022. 10.1002/art.41926.[2] Maugeri N; et al. Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis. Sci Transl Med. 2018; 10. 10.1126/scitranslmed.aao3089.Acknowledgements:This project is funded by the European Union - Next Generation EU - NRRP M6C2 - Investment 2.1 Enhancement and strengthening of biomedical research in the NHS.Disclosure of Interests:None declared.

BackgroundPlatelet extracellular vesicles (Plt-EVs) expressing the damage-associated molecular pattern prototypic signal, high mobility group box 1 (HMGB1), accumulate in the blood of patients with systemic sclerosis (SSc) and per se promote autoimmunity, fibrosis and vascular inflammation [1, 2]. A poorly understood defect in critical players in sprouting angiogenesis, angiopoietins and the angiopoietin receptor, TIE2 is also an hallmark of SSc. Normal neutrophils respond to angiopoietin 1 and other stimuli by undergoing activation and upregulating the Tie2 expression [3].ObjectivesWe reasoned that HMGB1 could be a putative candidate signal supporting neutrophils Tie2 overexpression, as it plays a critical role in neutrophil activation and is present as an EV-associated bioactive molecule in the blood of SSc patients[1, 2].MethodsNeutrophil Tie2 expression was assessed in the blood of 39 patients with SSc and 43 healthy donors (HD) sex- aged matched, by flow cytometry and confirmed by immunogold at electron microscopy. Tie2 expression was determined in freshly purified normal neutrophils stimulated with Plt-EVs from SSc patients or from HD or stimulated with rHMGB1 in vitro. Moreover Plt-EVs purified from the plasma of SSc patients or from HD were injected in the tail vein of NSG mice (that are receptive to human tissues). 18 hours after injection the expression of Tie2 of neutrophils in blood and lung histology were analyzed. Box A and low molecular weight heparin (LMWH) have been used as HMGB1 antagonists in vitro and in vivo.ResultsMost SSc neutrophils express Tie2 (84.7±2.4% vs 8.3±1.1% in HD; p <0.0001) regardless of the extent of systemic inflammation. HMGB1 and Plt-EV expressing HMGB1 purified from the plasma of patients with SSc induced up-regulation of TIE2 in vitro. Tie2 induction was abrogated by Box A and LMWH. Plt-EVs from SSc patients (but not from the plasma of HD) injected in immune-deficient NSG mice dramatically upregulated Tie2 neutrophil expression. Neutrophil Tie2 upregulation abated in the presence of HMGB1 inhibitors, BoxA and LMWH. Immunohistochemitry revealed lung fibrosis associated with massive infiltration by Tie2+ neutrophils. Neutrophil ablation by liposome-encapsulated clodronate prevented SSc Plt-EV-induced lung fibrosis, thus causally linking neutrophil activation, Tie2 neutrophil-expressing pulmonary infiltration and tissue remodelling.ConclusionOur data highlight the role of the platelet HMGB1/neutrophil axis in SSc vascular inflammation and fibrosis.References[1]Manfredi AA; et al. Platelet Phagocytosis via P-selectin Glycoprotein Ligand 1 and Accumulation of Microparticles in Systemic Sclerosis. Arthritis Rheumatol. 2021. 10.1002/art.41926.[2]Maugeri N; et al. Platelet microparticles sustain autophagy-associated activation of neutrophils in systemic sclerosis. Sci Transl Med. 2018; 10. 10.1126/scitranslmed.aao3089.[3]Burnett A et al. Angiopoietin-1 enhances neutrophil chemotaxis in vitro and migration in vivo through interaction with CD18 and release of CCL4. Sci Rep. 2017; 7: 2332. 10.1038/s41598-017-02216-y.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Background:Systemic lupus erythematosus (SLE) is a multi-organ disease characterised by generalised immune dysfunction and dominated by autoimmunity. High-grade systemic inflammation, resembling autoinflammatory (AI) disorders might complicate and overlap with the classical lupus phenotype (1, 2). Patients with these characteristics amid the spectrum of SLE constitute an ill-defined subgroup despite a potentially higher risk of morbidity and mortality.Objectives:To characterise the clinical profile and long-term SLE outcomes of patients with AI features within a monocentric SLE cohort.Methods:By reviewing the clinical characteristics of about 300 patients with SLE we identified a group of subjects with AI features (AIG), meeting the following criteria: 1) fever without infection or with incomplete antibiotic response, lasting more than two weeks and/or resistant to 0.5mg/kg prednisone-equivalent steroid therapy; 2) history of non-infectious fever ≥40°C or 3) of Macrophage Activation Syndrome (MAS); 4) erythrocyte sedimentation rate (ESR) higher than 75mm/h in at least three consecutive visit, 5) C-reactive protein higher than twice the upper level of normality in at least three consecutive visits, excluding infections; 6) ferritinaemia higher than 600 ng/ml despite 0.5mg/kg prednisone-equivalent steroid therapy. We collected demographic, clinical and treatment data from a series of 140 consecutive patients without these criteria, which constituted a Control Group (CG). Damage accrual was measured with the SLE International Collaborating Clinics/American College of Rheumatology Damage Index (SDI).Results:Thirteen subjects met the inclusion criteria for AIG. The main AI manifestations were non infectious and/or steroid resistant fever longer than two weeks (n=8, 62%) followed by persistent ESR (n=7, 54%). MAS, persistent CRP and Ferritin elevation had a prevalence of 31% (n=4) each. Five subjects (39%) had concomitant SLE and AI onset (Table 1). Compared to the CG, SLE patients in the AIG had a significant higher proportion of constitutional symptoms (77% vs 38%, p=0.032), including fever (92% vs 16%, p<0.001), as expected. Gastrointestinal symptoms were also more frequent in the AIG compared to CG (31% vs 2%, p<0.001). A lower antiphospholipid antibody prevalence was found in AIG, especially with regard to anticardiolipin antibodies (0% vs 32%; p=0.015). No other differences were identified in terms of demographics, clinical and treatment features among the two groups. AIG patients with SLE had a higher risk of SDI progression over time compared to CG patients (HR 5.2, 95%C.I. 1.4-19.5 p=0.012; Figure 1).Conclusion:AI features constitute an uncommon, yet clinically significant aspect of the broad spectrum of SLE manifestations. SLE patients with AI manifestations show a distinct clinical profile and accrue damage more rapidly compared to patients without these clinical characteristics. These data highlight a still unmet need in the care of patients with SLE and suggest that unique pathogenic events occur in patients with AI features, which might insufficiently be tackled by current diagnostic and treatment strategies.REFERENCES:[1] Gavand PE, et al., Autoimmun Rev. 2017[2] Mahajan VK, et al., World J Clin Cases. 2023Acknowledgements:NIL.Disclosure of Interests:Giovanni Benanti: None declared, Giuseppe Alvise Ramirez Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Costanza Vitellaro: None declared, Chiara Calabrese: None declared, Serena Nannipieri: None declared, Luca Moroni Astrazeneca (lessons), Astrazeneca, GSK (advisory boards), Astrazeneca (financial support for publication), Enrica Bozzolo: None declared, Marco Matucci-Cerinic: None declared, Lorenzo Dagna: None declared.