Emerging Evidence and Treatment Perspectives from Randomized Clinical Trials in Systemic Sclerosis: Focus on Interstitial Lung Disease

Systemic sclerosis (SSc) is a complex rare autoimmune disease with heterogeneous clinical manifestations. Currently, interstitial lung disease (ILD) and cardiac involvement (including pulmonary arterial hypertension) are recognized as the leading causes of SSc-associated mortality. New molecular targets have been discovered and phase II and phase III clinical trials published in the last 5 years on SSc-ILD will be discussed in this review. Details on the study design; the drug tested and its dose; the inclusion and exclusion criteria of the study; the concomitant immunosuppression; the outcomes and the duration of the study were reviewed. The two most common drugs used for the treatment of SSc-ILD are cyclophosphamide and mycophenolate mofetil, both supported by randomized controlled trials. Additional drugs, such as nintedanib and tocilizumab, have been approved to slow pulmonary function decline in SSc-ILD. In this review, we discuss the therapeutic alternatives for SSc management, offering the option to customize the design of future studies to stratify SSc patients and provide a patient-specific treatment according to the new emerging pathogenic features of SSc-ILD

Autologous Haematopoietic Stem Cell Transplantation and Systemic Sclerosis: Focus on Interstitial Lung Disease

Autologous hematopoietic stem cells transplantation (AHSCT) has been employed as treatment for severe systemic sclerosis (SSc) with high risk of organ failure. In the last 25 years overall survival and treatment-related mortality have improved, in accordance with a better patient selection and mobilization and conditioning protocols. This review analyzes the evidence from the last 5 years for AHSCT-treated SSc patients, considering in particular the outcomes related to interstitial lung disease. There are increasing data supporting the use of AHSCT in selected patients with rapidly progressive SSc. However, some unmet needs remain, such as an accurate patient selection, pre-transplantation analysis to identify subclinical conditions precluding the transplantation, and the alternatives for post-transplant ILD recurrence

The COVID-19 Assessment for Survival at Admission (CASA) Index: A 12 Months Observational Study

Objective: Coronavirus disease 2019 (COVID-19) is a disease with a high rate of progression to critical illness. However, the stratification of patients at risk of mortality is not well defined. In this study, we aimed to define a mortality risk index to allocate patients to the appropriate intensity of care. Methods: This is a 12 months observational longitudinal study designed to develop and validate a pragmatic mortality risk score to stratify COVID-19 patients aged ≥18 years and admitted to hospital between March 2020 and March 2021. Main outcome was in-hospital mortality. Results: 244 patients were included in the study (mortality rate 29.9%). The Covid-19 Assessment for Survival at Admission (CASA) index included seven variables readily available at admission: respiratory rate, troponin, albumin, CKD-EPI, white blood cell count, D-dimer, Pa02/Fi02. The CASA index showed high discrimination for mortality with an AUC of 0.91 (sensitivity 98.6%; specificity 69%) and a better performance compared to SOFA (AUC = 0.76), age (AUC = 0.76) and 4C mortality (AUC = 0.82). The cut-off identified (11.994) for CASA index showed a negative predictive value of 99.16% and a positive predictive value of 57.58%. Conclusions: A quick and readily available index has been identified to help clinicians stratify COVID-19 patients according to the appropriate intensity of care and minimize hospital admission to patients at high risk of mortality

Effects of spreading olive mill wastewater on soil properties and crops, a review

The disposal of olive mill wastewaters (OMWs) is a major problem that affects soil and groundwater. Different papers have discussed the effects of OMW discharge on soil characteristics, plant production and phytotoxicity. In this work, a holistic approach is proposed and the main research studies regarding the effects of OMWs on crops and soils are reviewed. Generally, direct application of OMWs exerts a temporary positive effect on soil physical properties. However, in clay soils, the accumulation of salts from these wastewaters could lead to the disintegration of the soil structure. Deterioration of soil structure would decrease the soil hydraulic conductivity, which is a key parameter for determining the volume of OMW that can be spread on a soil. Organic matter (OM) makes up approximately 65% of the OMW dry weight. Among the soil chemical characteristics, the soil pH remains almost constant following OMW applications. Polyphenols are the most limiting factor for spreading OMWs on soils because of their antimicrobial and phytotoxic effects. Nevertheless, these polyphenols are rapidly degraded depending on environmental conditions. Due to the highly variable chemical composition of the OMWs, these effluents provide variable macronutrient inputs (especially potassium and phosphorus), which potentially reduce necessary fertilizer inputs. Regarding soil microflora, the OMWs exert the following two contrasting actions: stimulating microflora development by temporarily enriching soil carbon and inhibiting certain microorganisms and phytopathogenic agents by adding antimicrobial substances to the soil. For many crops, spreading OMWs benefits crop yield. However, the application of OMWs may also damage germination. Thus, the application of OMWs should adequately precede sowing. The beneficial effects of OMWs on crop yields indicate that these wastewaters may become very important sources of OM and nutrients in agriculture soils and positively impact soil fertility. However, to improve their effectiveness, some use restrictions based on soil characteristics were outlined

Effects of olive mill wastewater physico-chemical treatments on polyphenol abatement and Italian ryegrass (Lolium multiflorum Lam.) germinability

Direct spreading on agricultural lands may represent an environmentally friendly disposal method and a possible use of water and nutrients from olive mill wastewaters (OMWs). However, the agronomic use of OMWs is limited, among others by polyphenols, which exert phytotoxic effects. Activated charcoal (AC) has been recognized as a very effective agent for polyphenol abatement, as it enables an irreversible process of phenol adsorption. Addition of calcium hydroxide (Ca(OH)2) has also been described as a cheap and effective method in polyphenols abatement. However, the effects of Ca(OH)2 addition to OMW on seed germination are unclear. In this paper, the effects of AC and/or Ca(OH)2 on OMW polyphenols abatement, and Lolium multiflorum seed germination have been investigated. The highest polyphenols removal, approximately 95%, was observed when 80 g L 121 of AC was added to OMWs (the maximum dose in this investigation). The addition of Ca(OH)2 not only improved the effectiveness of the AC treatment but also resulted in a significant rise in Lolium seed germination at the highest AC doses (60 and 80 g L 121). Considering the high salinity (7300 \u3bcS cm 121) of these wastewaters, low quantities of Ca(OH)2 may also exert a protective effect on soil structure counteracting the sodium-induced dispersion through the binding action of calcium cation on clays and organic matter

Carbon dioxide emissions from horizontal sub-surface constructed wetlands in the Mediterranean Basin

Constructed wetlands (CWs) are widely used natural-like systems for wastewater treatment where organic matter is removed through carbon dioxide (CO2) emissions. Several studies have been conducted regarding emissions and the sequestration of CO2 in CWs in the Northern Hemisphere; however, to the best of our knowledge, no studies have been performed in the Mediterranean Basin. This work quantified daily and cumulative CO2 emissions from a full-scale CW horizontal subsurface flow (HSSF) bed during semiarid Mediterranean spring climate conditions. The average daily CO2-C that was released in the atmosphere during the first 50 days ranged from approximately 17.5% to 32.6% of the C that was removed from wastewater. Considering both the Phragmites australis aerial part dry matter production (0.83 kg m−2) and the average CO2-C emissions, after 50 days of vegetative regrowth, the HSSF bed was demonstrated to act as a CO2 sink. The cumulative CO2 efflux was 452.15 ± 50.40 CO2 g m−2 and 276.02 ± 12.07 CO2 g m−2 for vegetated and unvegetated sites, respectively