Can microalgae grown in wastewater reduce the use of inorganic fertilizers?

Alternatives to conventional inorganic fertilizers are needed to cope with the growing global population and contamination due to the production and use of those inorganic compounds. The recovery of nutrients from wastewater and organic wastes is a promising option to provide fertilization in a circular economy approach. In this context, microalgae-based systems are an alternative to conventional wastewater treatment systems, reducing the treatment costs and improving the sustainability of the process, while producing nutrient-rich microalgal biomass. The aim of the present study is to evaluate the use of microalgal biomass produced during domestic wastewater treatment in high rate algal ponds as a biofertilizer in basil crops (Ocimum basilicum L.). Wastewater was successfully treated, with removal efficiencies in the secondary treatment of 69, 91 and 81% in terms of chemical oxygen demand (COD), total inorganic nitrogen (TIN) and phosphates (PO43-P), respectively. The microalgal biomass, composed mainly by Scenedesmus, presented the following composition: 12% of dry weight and nutrients concentration of 7.6% nitrogen (N), 1.6% phosphorus (P) and 0.9% potassium (K). The study compared the performance of 3 different fertilizers: 1) microalgae fertilizer (MF), 2) inorganic fertilizer (IF) as positive control and 3) the combination of both microalgae and inorganic fertilizer (MF + IF). Comparable plant growth (i.e., number of leaves, shoot fresh and dry weight and leaf fresh weight) was observed among treatments, except for leaf dry weight, which was significantly higher in the IF + MF and MF treatments (28 and 27%, respectively) in comparison with the control. However, the microalgae treatment provided the lowest chlorophyll, N and K leaf content. In conclusion, this study suggests that combining microalgae grown in wastewater with an inorganic fertilizer is a promising nutrients source for basil crops, enhancing the circular bioeconomy.

Intraoperative radiotherapy for extremity soft-tissue sarcomas: can long-term local control be achieved?

BACKGROUND: Intraoperative electron-beam radiation therapy (IOERT) during limb-sparing surgery has the advantage of delivering a single high boost dose to sarcoma residues and surgical bed area near to radiosensitive structures with limited toxicity. Retrospective studies have suggested that IOERT may improve local control compared to standard radiotherapy and we aimed to demonstrate this theory. Therefore, we performed an observational prospective study to determine (1) if it is possible to achieve high local control by adding IOERT to external-beam radiation therapy (EBRT) in extremity soft-tissue sarcomas (STS), (2) if it is possible to improve long-term survival rates, and (3) if toxicity could be reduced with IOERT MATERIALS AND METHODS: From 1995-2003, 39 patients with extremity STS were treated with IOERT and postoperative radiotherapy. The median follow-up time was 13.2 years (0.7-19). Complications, locoregional control and survival rates were collected. RESULTS: Actuarial local control was attained in 32 of 39 patients (82%). Control was achieved in 88% of patients with primary disease and in 50% of those with recurrent tumors (p = 0.01). Local control was shown in 93% of patients with negative margins and in 50% of those with positive margins (p = 0.002). Limb-sparing was achieved in 32 patients (82%). The overall survival rate was 64%. 13% of patients had grade ≥3 acute toxicity, and 12% developed grade ≥3 chronic toxicity. CONCLUSION: IOERT used as a boost to EBRT provides high local control and limb-sparing rates in patients with STS of the extremities, with less toxicity than EBRT alone.

Enhancing sustainability through microalgae cultivation in urban wastewater for biostimulant production and nutrient recovery.

Microalgae can produce biostimulants in form of phytohormones, which are compounds that, even if applied in low concentrations, can have stimulant effects on plants growth and can enhance their quality and their resistance to stress. Considering that microalgal biomass can grow recovering nutrients from wastewater, this circular approach allows to use residues for the production of high added value compounds (such as phytohormones) at low cost. The interest on biostimulants production from microalgae have recently raised. Scientists are focused on the direct application of these cellular extracts on plants, while the number of studies on the identification of bioactive molecules, such as phytohormones, is very scarce. Two cyanobacteria strains (Synechocystis sp. (SY) and Phormidium sp. (PH)) and a chlorophyte (Scenedesmus sp. (SC)) were cultured in laboratory-scale PBRs with a working volume of 2.5 L in secondary urban wastewater varying N:P ratio in the cultures to obtain the highest productivity. The variation of N:P ratio affects microalgae growth, and SY and PH presented higher productivities (73 and 48 mg L-1 d, respectively) under higher N:P ratio (> 22:1). Microalgal biomass was freeze-dried and phytohormones content was measured with ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The three microalgae showed similar phytohormones profiles, being the auxin (indole-3-acetic acid, IAA) the most abundant (72 ng g-1DW in SY). Proteins were major macronutrient for all strains, reaching 48 %DW in PH culture. To optimize the biostimulants production, a balance between the production of such compounds, biomass productivity and nutrients removal should be taken into consideration. In this sense, SC was the most promising strain, showing the highest N and P removal rates (73 % and 59 %, respectively) while producing phytohormones.

The potential of wastewater grown microalgae for agricultural purposes: Contaminants of emerging concern, heavy metals and pathogens assessment.

In the coming years, the use of microalgal biomass as agricultural biofertilizers has shown promising results. The use of wastewater as culture medium has resulted in the reduction of production costs, making microalgae-based fertilizers highly attractive for farmers. However, the occurrence of specific pollutants in wastewater, like pathogens, heavy metals and contaminants of emerging concern (CECs), such as pharmaceuticals and personal care products may pose a risk on human health. This study presents an holistic assessment of the production and use of microalgal biomass grown in municipal wastewater as biofertilizer in agriculture. Results showed that pathogens and heavy metals concentrations in the microalgal biomass were below the threshold established by the European regulation for fertilizing products, except for cadmium. Regarding CECs, 25 out of 29 compounds were found in wastewater. However, only three of them (hydrocinnamic acid, caffeine, and bisphenol A) were found in the microalgae biomass used as biofertilizer. Agronomic tests were performed for lettuce growth in greenhouse. Four treatments were studied, comparing the use of microalgae biofertilizer with a conventional mineral fertilizer, and also a combination of both of them. Results suggested that microalgae can help reducing the mineral nitrogen dose, since similar fresh shoot weights were obtained in the plants grown with the different assessed fertilizers. Lettuce samples revealed the presence of cadmium and CECs in all the treatments including both negative and positive controls, which suggests that their presence was not linked to the microalgae biomass. On the whole, this study revealed that wastewater grown microalgae can be used for agricultural purposes reducing mineral N need and guaranteeing health safety of the crops.

Inorganic carbon stimulates the metabolic routes related to the polyhdroxybutyrate production in a Synechocystis sp. strain (cyanobacteria) isolated from wastewater.

Cyanobacteria are capable of transforming CO2 into polyhydroxybutyrate (PHB). In this study, different inorganic carbon concentrations (0-2 gC L-1) were evaluated for a Synechocystis sp. strain isolated from wastewater. Quantitative RT-qPCR was also performed to decipher the links between inorganic carbon and PHB and glycogen metabolism. 2 gC L-1 of bicarbonate stimulated cell growth, nutrients consumption and production of PHB. Using this concentration, a 14%dcw of PHB and an average productivity of 2.45 mgPHB L-1 d-1 were obtained. Gene expression analysis revelated that these conditions caused the overexpression of genes related to glycogen and PHB synthesis. Moreover, a positive correlation between the genes codifying for the glycogen phosphorylase, the acetyl-CoA reductase and the poly(3-hydroxyalkanoate) polymerase was found, meaning that PHB synthesis and glycogen catabolism are strongly related. These results provide an exhaustive evaluation of the effect of carbon on the PHB production and cyanobacterial metabolism.

Radical prostatectomy versus external-beam radiotherapy for localized prostate cancer: long-term effect on biochemical control-in search of the optimal treatment.

BACKGROUND: The optimal management of patients with clinically localized prostate carcinoma remains undefined due in part to the absence of well-designed, randomized trials. METHODS: This retrospective study comprised 505 patients diagnosed with low- or intermediate- risk prostate cancer in 1998-2005 and treated at Hospital Gregorio Marañón (Spain) with radical prostatectomy (RP) or external-beam radiotherapy (EBRT). No adjuvant therapy was administered. Biochemical relapse was defined as a prostate-specific antigen (PSA) level ≥0.4 ng/ml for RP cases and nadir + 2 for EBRT cases. RP was performed in 271 patients (53.6%) and EBRT in 234 patients (46.4%). The median follow-up was 60 months. The analysis end point was to compare the biochemical recurrence-free survival (bRFS) between the two groups. RESULTS: The 5-year bRFS rates for RP and EBRT were 79 ± 2% and 86 ± 2%, respectively (P = 0.48). Multivariate analysis indicated that initial PSA (P = 0.00), perineural invasion in the biopsy specimen (P = 0.00), Gleason score (P = 0.04), EBRT dose (P = 0.02), and positive margins (P = 0.00) were independent predictors of relapse. A decision tree model was constructed with these variables. In the EBRT cohort, a nadir PSA of <0.3 ng/ml was associated with the best 5-year bRFS (96.6 vs. 56.5% if nadir PSA > 1.3 ng/ml). Late biochemical failure (>5 years) was more frequent in the RT group and with low-dose EBRT (≤72 Gy). CONCLUSIONS: The biochemical failure rates were similar between PR and EBRT in low- and intermediate-risk subgroups. Outcome was determined by classic pre-treatment features, perineural invasion, low-dose EBRT (≤72 Gy), and nadir PSA value in the RT cohort.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch. Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients. The 5-year OS rate in patients with limited-stage disease (non-metastatic) is slightly higher than 30%, but less than 5% in patients with extensive-stage disease (metastatic). The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis, planning, and treatment of SCLC. These guidelines emphasise treatment fields, radiation techniques, fractionation, concomitant treatment, and the optimal timing of Ch and radiotherapy. Finally, we discuss the main indications for reirradiation in local recurrence.

Trends and Predictors for the Uptake of Colon Cancer Screening Using the Fecal Occult Blood Test in Spain from 2011 to 2017.

Background: In Spain, colorectal cancer screening using the fecal occult blood test, targeted towards the 50-69 age bracket, was implemented on different dates. We aim to assess the temporal trend of colorectal cancer (CRC) screening uptake according to the year of screening implementation in each region and to identify predictors for the uptake of CRC screening. Methods: A cross-sectional study with 12,657 participants from the Spanish National Health Surveys 2011 and 2017 was used. Uptake rates were analyzed according to the date that the screening program was implemented. Results: For regions with programs implemented before 2011, the uptake rate increased 3.34-fold from 2011 to 2017 (9.8% vs. 32.7%; p < 0.001). For regions that implemented screening within the 2011-2016 period, the uptake rose from 4.3% to 13.2% (3.07-fold; p < 0.001), and for regions that implemented screening after 2016, the uptake increased from 3.4% to 8.8% (2.59-fold; p < 0.001). For the entire Spanish population, the uptake increased 3.21-fold (6.8% vs. 21.8%; p < 0.001). Positive predictors for uptake were older age, Spanish nationality, middle-to-high educational level, suffering chronic diseases, non-smoking and living in regions where screening programs were implemented earlier. Conclusions: The different periods for the implementation of CRC screening as well as sociodemographic and health inequalities may have limited the improvement in the screening uptake from 2011 to 2017 in Spain.

Reduction from 2011 to 2017 in adherence to breast cancer screening and non-improvement in the uptake of cervical cancer screening among women living in Spain.

OBJECTIVES: To analyze the uptake of breast and cervical cancer screening according to the 2017 Spanish National Health Survey (SNHS), to compare uptake rates with those obtained in the previous SNHS 2011 and to identify predictors for the uptake for these two screening tests. STUDY DESIGN: Cross-sectional study. MAIN OUTCOME MEASURES: Uptake rates of breast cancer and cervical cancer screening were analyzed for women aged 40-69 and aged 25-65 years, respectively. Independent variables included sociodemographic characteristics and factors related to health status and lifestyle. RESULTS: We found that 66.8 % of women aged 40-69 years had undergone mammography in the previous two years. Positive predictors for mammography uptake were age (50-69 years); marital status (married); Spanish nationality; university education; one or more chronic diseases; no alcohol consumption; physical activity; body mass index <30 kg/m2; and not smoking. We observed that 73.0 % of women aged 25-65 years had undergone cervical cytology screening in the previous three years. Positive predictors for uptake were age (25-52 years); marital status (married); Spanish nationality; middle-high educational level; no chronic diseases; no alcohol consumption; physical activity; body mass index <30 kg/m2; and not smoking. There was a significant decrease in the uptake rate for breast cancer screening from the previous SNHS 2011 (OR 0.89; 95 % CI 0.83-0.94). CONCLUSIONS: The adherence rate for mammography in Spain in 2017 was below the recommended 70 % and was significantly lower than in 2011. The figures for cervical cancer screening were over 70 % and stable over time.

Assessment of Safety and Efficacy of Combined Trabectedin and Low-Dose Radiotherapy for Patients With Metastatic Soft-Tissue Sarcomas: A Nonrandomized Phase 1/2 Clinical Trial.

Importance: Active therapeutic combinations, such as trabectedin and radiotherapy, offer potentially higher dimensional response in second-line treatment of advanced soft-tissue sarcomas. Dimensional response can be relevant both for symptom relief and for survival. Objective: To assess the combined use of trabectedin and radiotherapy in treating patients with progressing metastatic soft-tissue sarcomas. Design, Setting, and Participants: Phase 1 of this nonrandomized clinical trial followed the classic 3 + 3 design, with planned radiotherapy at a fixed dose of 30 Gy (3 Gy/d for 10 days) and infusion of trabectedin at 1.3 mg/m2 as the starting dose, 1.5 mg/m2 as dose level +1, and 1.1 mg/m2 as dose level -1. Phase 2 followed the Simon optimal 2-stage design. Allowing for type I and II errors of 10%, treatment success was defined as an overall response rate of 35%. This study was conducted in 9 sarcoma referral centers in Spain, France, and Italy from April 13, 2015, to November 20, 2018. Adult patients with progressing metastatic soft-tissue sarcoma and having undergone at least 1 previous line of systemic therapy were enrolled. In phase 2, patients fitting inclusion criteria and receiving at least 1 cycle of trabectedin and the radiotherapy regimen constituted the per-protocol population; those receiving at least 1 cycle of trabectedin, the safety population. Interventions: Trabectedin was administered every 3 weeks in a 24-hour infusion. Radiotherapy was required to start within 1 hour after completion of the first trabectedin infusion (cycle 1, day 2). Main Outcomes and Measures: The dose-limiting toxic effects of trabectedin (phase 1) and the overall response rate (phase 2) with use of trabectedin plus irradiation in metastatic soft-tissue sarcomas. Results: Eighteen patients (11 of whom were male) were enrolled in phase 1, and 27 other patients (14 of whom were female) were enrolled in phase 2. The median ages of those enrolled in phases 1 and 2 were 42 (range, 23-74) years and 51 (range, 27-73) years, respectively. In phase 1, dose-limiting toxic effects included grade 4 neutropenia lasting more than 5 days in 1 patient at the starting dose level and a grade 4 alanine aminotransferase level increase in 1 of 6 patients at the +1 dose level. In phase 2, among 25 patients with evaluable data, the overall response rate was 72% (95% CI, 53%-91%) for local assessment and 60% (95% CI, 39%-81%) for central assessment. Conclusions and Relevance: The findings of this study suggest that the recommended dose of trabectedin for use in combination with this irradiation regimen is 1.5 mg/m2. The trial met its primary end point, with a high overall response rate that indicates the potential of this combination therapy for achieving substantial tumor shrinkage beyond first-line systemic therapy in patients with metastatic, progressing soft-tissue sarcomas. Trial Registration: ClinicalTrials.gov Identifier: NCT02275286.

Salvage brachytherapy for locally-recurrent prostate cancer after radiation therapy: A comparison of efficacy and toxicity outcomes with high-dose rate and low-dose rate brachytherapy.

BACKGROUND: Brachytherapy (BT) is widely used for salvage therapy in patients with biochemical failure (BF) after radiotherapy for prostate cancer (PCa). Although low-dose-rate (LDR) and high-dose-rate (HDR) BT are both used for salvage therapy, it is not clear whether there are any differences between these two approaches in terms of efficacy or toxicity in this setting. Therefore, we review the institutional experience of the members of the Urological Tumour Working Group (URONCOR) of the Spanish Society of Radiation Oncology (SEOR) to compare these two techniques. METHODS AND MATERIALS: Between 2001 and 2016, 119 patients with biopsy-proven, locally-recurrent PCa underwent salvage BT (LDR, n = 44; HDR, n = 75) after primary radiotherapy. Relapse-free survival (RFS) and cause-specific survival (CSS) after salvage therapy were analyzed. Toxicity was assessed according to the RTOG scale. RESULTS: Median follow-up after salvage BT was 52 months. Overall, the 5-year prostate-specific antigen (PSA) RFS rate was 71% (95% CI, 65.9%-75.9%). No significant between-group differences in RFS were observed (p = 0.063). Five-year CSS for the LDR- and HDR-BT groups were 96.5% and 93%, respectively. Overall, 38 patients (32%) developed biochemical progression (Phoenix definition) after salvage BT: 14 patients (32%) in the LDR group and 24 (32.5%) in the HDR group. On the multivariate analysis, the following variables were significantly associated with progression, time to BF from primary radiotherapy <30 months (p = 0.014); and post-salvage nadir PSA (p = 0.000). There were no significant between-group differences in toxicity. Overall, there were 13 cases of urethral stricture, 22 cases of urinary incontinence, and 13 cases of haematuria. Toxicity ≥grade 3 was observed in 23.5% of patients. CONCLUSIONS: These findings show that both HDR-BT and LDR-BT yield comparable efficacy and toxicity outcomes in patients undergoing salvage treatment for locally-recurrent prostate cancer after primary radiotherapy. Predictors of worse outcomes after salvage BT were post-salvage nadir PSA and time to BF from initial radiotherapy.

Exclusion criteria vs reality: dual BRAF/MEK inhibition and radiotherapy in a patient with melanoma metastatic to the brain and ECOG 3.

BACKGROUND: Prognosis of metastatic melanoma is changing due to advances in immunotherapy and targeted therapy. However, management of patients with brain metastases in day-to-day practice continues to be a challenge. CASE REPORT: We describe a 40-year-old woman diagnosed with symptomatic brain metastases from cutaneous melanoma and Eastern Cooperative Oncology Group 3. She was treated, off label, with BRAF inhibitor (dabrafenib) + MEK inhibitor (trametinib) and radiotherapy. There was significant, long-lasting, response (17 months), no clinically relevant toxicity, and clear improvement in quality of life. CONCLUSIONS: This case is an example of real-life application of advances in targeted therapy.