Combination of granulocyte-monocyte apheresis and ustekinumab: Multicentre and retrospective study.

OBJECTIVE: Granulocyte-monocyte apheresis (GMA) has shown to be safe and effective in ulcerative colitis (UC), also in combination with biologics, mainly with anti-TNF. The aim of this study was to evaluate the efficacy and safety of combining GMA after primary non-response (PNR) or loss of response (LOR) to ustekinumab (UST) in patients with UC. PATIENTS AND METHODS: A retrospective study was performed in 12 IBD Units, including all patients with refractory UC or unclassified IBD (IBD-U) who received combined GMA plus UST. The number and frequency of GMA sessions, filtered blood volume and time of each session were registered. Efficacy was assessed 1 and 6 months after finishing GMA by partial Mayo score, C-reactive protein (CRP) and fecal calprotectin (FC). Descriptive statistics and non-parametric tests were used in the statistical analysis. RESULTS: Seventeen patients were included (15 UC, 2 IBD-U; median age 47 years [IQR, 35-61]; 59% male; 53% E3). Most patients (89%) had prior exposure to anti-TNF agents and 53% to vedolizumab; 65% were also receiving steroids at baseline. Median partial Mayo score at baseline was 6 (IQR, 5-7) and it significantly decreased after 1 and 6 months (p=0.042 and 0.007, respectively). Baseline FC significantly decreased after 6 months (p=0.028) while no differences were found in CRP. During follow-up, 18% patients started a new biologic therapy and 12% required surgery; 64% of patients under steroids were able to discontinue them. Adverse events were reported in one patient. CONCLUSION: GMA can recapture the response to UST in selected cases of UC after PNR or LOR to this drug.

Removal of nitrate and pesticides from groundwater by nano zero-valent iron injection pulses under biostimulation and bioaugmentation scenarios in continuous-flow packed soil columns.

This study evaluates the NO3- removal from groundwater through Heterotrophic Denitrification (HDN) (promoted by the addition of acetate and/or an inoculum rich in denitrifiers) and Abiotic Chemical Nitrate Reduction (ACNR) (promoted by pulse injection of zerovalent iron nanoparticles (nZVI)). HDN and ACNR were applied, separately or combined, in packed soil column experiments to complement the scarce research on pulse-injected nZVI in continuous-flow systems mimicking a Well-based Denitrification Barrier. Together with NO3-, the removal of two common pesticides (dieldrin and lindane) was evaluated. Results showed that total NO3- removal (>97%) could be achieved by either bioestimulation with acetate (converting NO3- to N2(g) via HDN) or by injecting nZVI (removing NO3- via ACNR). In the presence of nZVI, NO3- was partially converted to N2(g) and to a lower extent NO2-, with unreacted NO3- being likely adsorbed onto Fe-(oxy)hydroxides. Combination of both HDN and ACNR resulted in even a higher NO3- removal (>99%). Interestingly, nZVI did not seem to pose any toxic effect on denitrifiers. These results showed that both processes can be alterned or combined to take advantage of the benefits of each individual process while overcoming their disadvantages if applied alone. With regard to the target pesticides, the removal was high for dieldrin (>93%) and moderate for lindane (38%), and it was not due to biodegradation but to adsorption onto soil. When nZVI was applied, the removal increased (generally >91%) due to chemical degradation by nZVI and/or adsorption onto formed Fe-(oxy)hydroxides.

Removal of nitrate from groundwater by nano-scale zero-valent iron injection pulses in continuous-flow packed soil columns.

Injection of zero-valent iron nanoparticles (nZVI) into aquifers has gained increasing attention of researchers for in-situ treatment of NO3--contaminated groundwater. nZVI has proved efficient in chemically reducing NO3- and, according to recent research efforts, in supporting biological denitrification under favoured conditions. Given the scarce research on nZVI pulsed injection in continuous-flow systems, the objective of this study was to evaluate the effect of nZVI pulses on the removal of NO3- from groundwater in packed soil columns and, more particularly, to elucidate whether or not biotic NO3- removal processes were promoted by nZVI. Three identical columns were filled with aquifer soil samples and fed with the same nitrate polluted groundwater but operated under different conditions: (A) with application of nZVI pulses and biocide spiked in groundwater, (B) without application of nZVI pulses and (C) with application of nZVI pulses. Results showed that the application of nZVI (at 30 mg/L and 78 mg/L doses) resulted in an immediate and sharp removal of NO3- (88-94%), accompanied by an increase in pH (from 7.0 to 9.0-10.0), a drop in redox potential (Eh) (from +420 mV to <100 mV) and a release of Fe(II) and Total Organic Carbon (TOC) in the effluent (to 200 mg/L and 150-200 mg/L, respectively). The released TOC came from the organic polymer used as stabilizer of the nZVI particles. Comparison against the sterilized control column revealed that, under the experimental conditions, no biological denitrification developed and that the removal of NO3- was due to chemical reduction by nZVI. The main by-product of the NO3- removal was NH4+, which at the prevailing pH was partially converted to NH3, which dissipated from the aqueous solution resulting in a net removal of total dissolved N. A mass balance of Fe permitted to quantify the percentage of injected nZVI trapped in the column (>98%) and the NO3- retention capacity of the nZVI particles (13.2-85.5 mg NO3-/g nZVI).

Risk of groundwater contamination widely underestimated because of fast flow into aquifers.

Groundwater pollution threatens human and ecosystem health in many regions around the globe. Fast flow to the groundwater through focused recharge is known to transmit short-lived pollutants into carbonate aquifers, endangering the quality of groundwaters where one quarter of the world's population lives. However, the large-scale impact of such focused recharge on groundwater quality remains poorly understood. Here, we apply a continental-scale model to quantify the risk of groundwater contamination by degradable pollutants through focused recharge in the carbonate rock regions of Europe, North Africa, and the Middle East. We show that focused recharge is the primary reason for widespread rapid transport of contaminants to the groundwater. Where it occurs, the concentration of pollutants in groundwater recharge that have not yet degraded increases from <1% to around 20 to 50% of their concentrations during infiltration. Assuming realistic application rates, our simulations show that degradable pollutants like glyphosate can exceed their permissible concentrations by 3 to 19 times when reaching the groundwater. Our results are supported by independent estimates of young water fractions at 78 carbonate rock springs over Europe and a dataset of observed glyphosate concentrations in the groundwater. They imply that in times of continuing and increasing industrial and agricultural productivity, focused recharge may result in an underestimated and widespread risk to usable groundwater volumes.

Proposed methodology to delineate bodies of groundwater according to the European water framework directive. Application in a pilot Mediterranean river basin (Málaga, Spain).

The term "body of groundwater" represents a new administrative tool established by the water framework directive (WFD) in order to manage European groundwaters. Its practical application raises some difficulties due to unclear definitions and the large heterogeneity of European aquifers. In this work, a methodology is proposed to carry out the delineation of bodies of groundwater according to the requirements of the WFD. This methodology faces up to some of the major difficulties that can arise during the delineation, such as the identification of bodies of groundwater in multilayered aquifers, boundaries between superposed groundwater bodies, and delimitation in low permeability materials or in dismembered aquifers. In order to show its practical application, the proposed methodology is applied in a pilot Mediterranean river basin located in southern Spain. Results show that previous knowledge of the hydrogeological conditions is necessary to enable a correct delineation of groundwater bodies. Finally, alternative procedures are proposed for low permeability and small aquifers in order to reduce the number of groundwater bodies identified and simplify their overall management.