Syngas biomethanation: In a transfer limited process, is CO inhibition an issue?

Syngas biomethanation is a promising technology in the process chain converting wastes to methane. However, gas-liquid mass transfer is a limiting factor of the biomethanation process. To reach high methane productivity, increasing the pressure is an interesting strategy to improve mass transfer. However, the CO content in the syngas raises concerns about a potential inhibition of the microorganisms. Therefore, the aim of the research was to assess the ability to work at high CO partial pressures. In this regard, a pressurized continuous stirred column with a working volume of 10L was implemented and a consortium adapted for syngas-biomethanation for 22 months was submitted to 100% CO and increasing pressure. No inhibition phenomenon was observed for logarithmic PCO as high as 1.8 bar (inlet pressure 5.0 bar), which was the first time that such a high CO partial pressure was tested in continuous mode. Mass transfer limitations allowed for the carboxydotrophic microorganisms to consume CO faster than it was transferred, allowing for the dissolved CO concentration to remain under inhibitory concentrations. These results question the habitual consensus that CO inhibition is a limiting factor of syngas biomethanation.

Syngas biomethanation: Study of process performances at high syngas flow rate in pressurized stirred column.

Syngas biomethanation is a promising technology for waste to energy conversion. However, it had not yet been tested at high syngas flow rates. The aim of this study was to assess the possibility for syngas biomethanation to reach high methane productivity at higher syngas inflow rate. A pressurized stirred column was implemented. The syngas inflow rate was gradually increased, and two different increase strategies were compared. The highest methane productivity achieved yet with syngas-biomethanation was obtained, with 23.2 LCH4/L/d, with high conversion efficiencies of 89% for H2 and 82% for CO. The mass transfer performances of the process were investigated, and the existence of a biological enhancement factor was observed. Considering an enhancement factor in bioprocesses is a pioneering concept that could change the way we design bioreactor to improve mass transfer. The high methane productivity obtained in this study paves the way for the process industrialization.

"Biomethanation of syngas by enriched mixed anaerobic consortium in pressurized agitated column".

In a circular economy approach, heterogeneous wastes can be upgraded to energy in the form of syngas via pyrogasification, and then to methane via biomethanation. Working at high pressure is a promising approach to intensify the process and to reduce gas-liquid transfer limitations. However, raising the pressure could lead to reaching the CO inhibition threshold of the microorganisms involved in syngas-biomethanation. To investigate the impact on pressure on the process, a 10L continuous stirred tank reactor working at 4 bars and 55 °C was implemented. Syngas (40% CO, 40% H2, 20% CO2) biomethanation was performed successfully and methane productivity as high as 6.8 mmolCH4/Lreactor/h with almost full conversion of CO (97%) and H2 (98%) was achieved. CO inhibition was investigated and carboxydotrophs appeared less resistant to high CO exposition than methanogens.

Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes

Background: The goal of treatment for patients with synchronous liver metastases (SLM) from rectal cancer is to achieve a complete resection of both tumor locations. For patients with symptomatic locally advanced rectal cancer with resectable SLM at diagnosis, our usual strategy has been the rectum first approach (RF). However, since 2014, we advocate for the interval approach (IS) that involves the administration of chemo-radiotherapy followed by the resection of the SLM in the interval of time between rectal cancer radiation and rectal surgery. Methods: From 2010 to 2016, 16 patients were treated according to this new strategy and 19 were treated according RF strategy. Data were collected prospectively and analyzed with an intention-to-treat perspective. Complete resection rate, duration of the treatment and morbi-mortality were the main outcomes. Results: The complete resection rate in the IS was higher (100%, n = 16) compared to the RF (74%, n = 14, p = 0.049) and the duration of the strategy was shorter (6 vs. 9 months, respectively, p = 0.006). The incidence of severe complications after liver surgery was 14% (n = 2) in the RF and 0% in the IS (p = 1.000), and after rectal surgery was 24% (n = 4) and 12% (n = 2), respectively (p = 1.000). Conclusion: The IS is a feasible and safe strategy that procures higher level of complete resection rate in a shorter period of time compared to RF strategy

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Recurrent attacks of acute hepatic porphyria: major role of the chronic inflammatory response in the liver.

BACKGROUND: Acute intermittent porphyria (AIP) is an inherited disorder of haem metabolism characterized by life-threatening acute neurovisceral attacks due to the induction of hepatic δ-aminolevulinic acid synthase 1 (ALAS1) associated with hydroxymethylbilane synthase (HMBS) deficiency. So far, the treatment of choice is hemin which represses ALAS1. The main issue in the medical care of AIP patients is the occurrence of debilitating recurrent attacks. OBJECTIVE: The aim of this study was to determine whether chronic hemin administration contributes to the recurrence of acute attacks. METHODS: A follow-up study was conducted between 1974 and 2015 and included 602 French AIP patients, of whom 46 had recurrent AIP. Moreover, we studied the hepatic transcriptome, serum proteome, liver macrophage polarization and oxidative and inflammatory profiles of Hmbs-/- mice chronically treated by hemin and extended the investigations to five explanted livers from recurrent AIP patients. RESULTS: The introduction of hemin into the pharmacopeia has coincided with a 4.4-fold increase in the prevalence of chronic patients. Moreover, we showed that both in animal model and in human liver, frequent hemin infusions generate a chronic inflammatory hepatic disease which induces HO1 remotely to hemin treatment and maintains a high ALAS1 level responsible for recurrence. CONCLUSION: Altogether, this study has important impacts on AIP care underlying that hemin needs to be restricted to severe neurovisceral crisis and suggests that alternative treatment targeting the liver such as ALAS1 and HO1 inhibitors, and anti-inflammatory therapies should be considered in patients with recurrent AIP.

Treatment strategies for rectal cancer with synchronous liver metastases: surgical and oncological outcomes with propensity-score analysis

Background. The optimal sequence of surgery for rectal cancer (RC) with synchronous liver metastases (SLM) is controversial. Objectives. The primary objective was to explore differences between the rectum first (RF) and the liver first strategy (LF) to achieve the complete resection (CR) of both tumors. Methods. Patients diagnosed of RC with resectable or potentially resectable SLM were included. Data collected prospectively were analyzed with an intention-to-treat perspective, adjusting for between-sample differences (propensity score). The complete resection rate (CRR) was the main outcome variable. Results. During a 5-year period, 23 patients underwent the LF strategy and 24 patients the RF strategy. Median overall survival (OS) was 32 months in the LF group and 41 months in the RF group (p = 0.499), and was 51 and 17 months, respectively, for patients achieving or not achieving CR of both tumors (p < 0.001). CRR’s were 65% in liver first group and 63% in rectum first group, (p = 0.846). No between-strategy differences in morbidity or duration of treatment were observed. Conclusions. This study supports the notion that the achievement of CR of RC and SLM should be the goal of oncological treatment. Both RF and LF strategies are feasible and safe, but no between-strategy differences have been found in the CRR (AU)

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Acquired erythropoietic uroporphyria secondary to myelodysplastic syndrome with chromosome 3 alterations: a case report.

Congenital erythropoietic porphyria is a rare autosomal recessive disease caused by a deficiency of uroporphyrinogen III synthase, owing to mutations in UROS in chromosome 10. Occasionally, patients show a mild, late-onset disease, without germline UROS mutations, associated with haematological malignancies. We report a 65-year-old patient with photosensitivity, overexcretion of porphyrins and thrombocytopenia. Bone marrow analysis gave a diagnosis of myelodysplastic syndrome (MDS) with the presence of a derivative chromosome 3, possibly due to an inversion including 3q21 and 3q26 break points. After allogeneic stem-cell transplantation, complete remission of MDS and uroporphyria was achieved. To our knowledge, this is the first reported case of acquired erythropoietic uroporphyria associated with MDS, with chromosome 3 alterations.

Treatment strategies for rectal cancer with synchronous liver metastases: surgical and oncological outcomes with propensity-score analysis.

BACKGROUND: The optimal sequence of surgery for rectal cancer (RC) with synchronous liver metastases (SLM) is controversial. OBJECTIVES: The primary objective was to explore differences between the rectum first (RF) and the liver first strategy (LF) to achieve the complete resection (CR) of both tumors. METHODS: Patients diagnosed of RC with resectable or potentially resectable SLM were included. Data collected prospectively were analyzed with an intention-to-treat perspective, adjusting for between-sample differences (propensity score). The complete resection rate (CRR) was the main outcome variable. RESULTS: During a 5-year period, 23 patients underwent the LF strategy and 24 patients the RF strategy. Median overall survival (OS) was 32 months in the LF group and 41 months in the RF group (p = 0.499), and was 51 and 17 months, respectively, for patients achieving or not achieving CR of both tumors (p < 0.001). CRR's were 65% in liver first group and 63% in rectum first group, (p = 0.846). No between-strategy differences in morbidity or duration of treatment were observed. CONCLUSIONS: This study supports the notion that the achievement of CR of RC and SLM should be the goal of oncological treatment. Both RF and LF strategies are feasible and safe, but no between-strategy differences have been found in the CRR.

Oncological strategies for locally advanced rectal cancer with synchronous liver metastases, interval strategy versus rectum first strategy: a comparison of short-term outcomes.

BACKGROUND: The goal of treatment for patients with synchronous liver metastases (SLM) from rectal cancer is to achieve a complete resection of both tumor locations. For patients with symptomatic locally advanced rectal cancer with resectable SLM at diagnosis, our usual strategy has been the rectum first approach (RF). However, since 2014, we advocate for the interval approach (IS) that involves the administration of chemo-radiotherapy followed by the resection of the SLM in the interval of time between rectal cancer radiation and rectal surgery. METHODS: From 2010 to 2016, 16 patients were treated according to this new strategy and 19 were treated according RF strategy. Data were collected prospectively and analyzed with an intention-to-treat perspective. Complete resection rate, duration of the treatment and morbi-mortality were the main outcomes. RESULTS: The complete resection rate in the IS was higher (100%, n = 16) compared to the RF (74%, n = 14, p = 0.049) and the duration of the strategy was shorter (6 vs. 9 months, respectively, p = 0.006). The incidence of severe complications after liver surgery was 14% (n = 2) in the RF and 0% in the IS (p = 1.000), and after rectal surgery was 24% (n = 4) and 12% (n = 2), respectively (p = 1.000). CONCLUSION: The IS is a feasible and safe strategy that procures higher level of complete resection rate in a shorter period of time compared to RF strategy.

Long-term outcomes of patients with 10 or more colorectal liver metastases.

BACKGROUND: Although the number of colorectal liver metastases (CLM) is decreasingly considered as a contraindication to surgery, patients with 10 CLM or more are often denied liver surgery. This study aimed to evaluate the outcome after liver surgery and to identify prognostic factors of survival in such patients. METHODS: The study population consisted of a multicentre cohort of patients with CLM (N=12 406) operated on, with intention to resect, from January 2005-June 2013 and whose data were prospectively collected in the LiverMetSurvey registry. RESULTS: Overall, the group ⩾10 CLM (N=529, 4.3%) experienced a 5-year overall survival (OS) of 30%. A macroscopically complete (R0/R1) resection (72.8% of patients) was associated with a 3- and 5-year OS of 61% and 39% vs 29% and 5% for R2/no resection patients (P<0.0001). At multivariate analysis, R0/R1 resection emerged as the strongest favourable factor of OS (HR 0.35 (0.26-0.48)). Other independent favourable factors were as follows: maximal tumour size <40 mm (HR 0.67 (0.49-0.92)); age <60 years (HR 0.66 (0.50-0.88)); preoperative MRI (HR 0.65 (0.47-0.89)); and adjuvant chemotherapy (HR 0.73 (0.55-0.98)). The model showed that 5-year OS rates of 30% was possible provided R0/R1 resection associated with at least an additional favourable factor. CONCLUSIONS: Liver resection might provide long-term survival in patients with ⩾10 CLM staged with preoperative MRI, provided R0/R1 resection followed by adjuvant therapy. A validation of these results in another cohort is needed.

Extreme liver surgery as treatment of liver tumors involving the hepatocaval confluence

Objective. Analyze the characteristics, surgical technique, morbidity and survival of patients treated with extreme liver surgery. Materials and methods. We present a series of consecutive patients with malignant liver tumors in hepatocaval confluence treated in a single center with extreme liver surgery (April 2008-March 2015). Data were collected prospectively and analyzed with SPSS 21.0. Results. 12 patients were included. 50 % were male and 50 % were female with a mean age of 59 ± 10 years old. The median of comorbidities was 7 according to the Charlson Age Comorbidity Index. The 75 % of the tumors were metastases, most of them from colorectal cancer. Most of the patients received neoadjuvant chemotherapy and in 58 % preoperative portal embolization was performed. Major hepatectomies were performed (66.7 % extended right hepatectomy, 33.3 % left extended hepatectomy). The 83.3 % of the patients needed vascular reconstruction. Postoperative morbidity was more than grade II in 50 % of the patients according to Dindo-Clavien classification. There was no intraoperative mortality. The postoperative mortality rate at 90 days was 33 % due to hepatic failure and biliary fistula. In December 2015, 33 % of the patients are still alive with a mean survival of 19 months (13-23) with an ECOG Performance Status of 0. Conclusion. Extreme liver surgery carries a high rate of morbidity and mortality that seem to increase with age and with higher tumor volumes, according to the literature. It is a therapeutic option to consider in patients with low comorbidity suffering from malignant neoplasms that involve the hepatocaval confluence, when no other treatment with curative intention can be performed (AU)

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PARAGON II - A single arm multicentre phase II study of neoadjuvant therapy using irinotecan bead in patients with resectable liver metastases from colorectal cancer.

PURPOSE: Perioperative chemotherapy confers a 3-year progression free survival advantage following resection of colorectal liver metastases (CRLM), but is associated with significant toxicity. Chemoembolisation using drug eluting PVA microspheres loaded with irinotecan (DEBIRI) allows sustained delivery of drug directly to tumour, maximising response whilst minimising systemic exposure. This phase II single arm study examined the safety and feasibility of DEBIRI before resection of CRLM. METHODS: Patients with resectable CRLM received lobar DEBIRI 1 month prior to surgery, with a radiological endpoint of near stasis. The trial had a primary end-point of tumour resectability (R0 resection). Secondary end-points included safety, pathologic tumour response and overall survival. RESULTS: 40 patients received DEBIRI, with a median dose of 103 mg irinotecan (range 64-175 mg). Morbidity was low (2.5%, CTCAE grade 2) with no evidence of systemic chemotoxicity. All patients proceeded to surgery, with 38 undergoing resection (95%, R0 resection rate 74%). 30-day post-operative mortality was 5% (n = 2), with neither death TACE related. 66 lesions were resected, with histologic major or complete pathologic response seen in 77.3% of targeted lesions. At median follow up of 40.6 months, 12 patients (34.3%) had died of recurrent disease with a median overall survival of 50.9 months. Nominal 1, 3 and 5-year OS was 93, 78 & 49% respectively. CONCLUSIONS: Resection after neoadjuvant DEBIRI for CRLM is feasible and safe. Single treatment with DEBIRI resulted in tumour pathologic response and median overall survival comparable to that seen after systemic neoadjuvant chemotherapy. Registered at clinicaltrials.gov (NCT00844233).

Expert opinion on advanced techniques for hemostasis in liver surgery.

BACKGROUND: Reduction of perioperative blood loss and intraoperative transfusion are two major factors associated with improving outcomes in liver surgery. There is currently no consensus as to the best technique to achieve this. METHODS: An international Panel of Experts (EP), made up of hepatobiliary surgeons from well-known high-volume centres was assembled to share their experience with regard to the management of blood loss during liver resection surgery. The process included: a review of the current literature by the panel, a face-to-face meeting and an on-line survey completed by the EP prior to and following the face-to-face meeting, based on predetermined case scenarios. During the meeting the most frequently researched surgical techniques were appraised by the EP in terms of intraoperative blood loss. RESULTS: All EP members agreed that high quality research on the subject was lacking. Following an agreed risk stratification algorithm, the EP concurred with the existing research that a haemostatic device should always be used along with any user preferred surgical instrumentation in both open and laparoscopic liver resection procedures, independently from stratification of bleeding risk. The combined use of Ultrasonic Dissector (UD) and saline-coupled bipolar sealing device (Aquamantys(®)) was the EP preferred technique for both open and laparoscopic surgery. CONCLUSIONS: This EP propose the use of a bipolar sealer and UD for the best resection technique and essential equipment to minimise blood loss during liver surgery, stratified according to transfusion risk, in both open and laparoscopic liver resection.

Late-onset cutaneous porphyria in a patient heterozygous for a uroporphyrinogen III synthase gene mutation.

Deficiency of uroporphyrinogen III synthase (UROS) causes congenital erythropoietic porphyria (CEP). The disease, originating from the inheritance of mutations within the UROS gene, presents a recessive form of transmission. In a few patients, a late-onset CEP-like phenotype without UROS mutations appears to be associated with a myelodysplastic syndrome. We report a 60-year-old man with late-onset signs of cutaneous porphyria and accumulation in urine, plasma and faeces of type I porphyrin isomers characteristic of CEP. Analysis of DNA from peripheral leucocytes, skin and bone marrow aspirate showed that he was a heterozygous carrier of a Cys73Arg (c.217 T>C) mutation within UROS. Sequencing of cDNA from peripheral blood confirmed heterozygosity and expression of the normal allele. Measurement of UROS enzymatic activity in erythrocytes showed values ~70% of normal, indirectly indicating expression of the normal allele. Differently from other cases of late-onset uroporphyria, the patient did not present thrombocytopenia or any evidence of a myelodysplastic syndrome. Five years of clinical follow-up showed persistence of skin signs and increased excretion of porphyrins, independently of lifestyle factors or changes in medication regimes. We hypothesize acquired mosaicism (in the bone marrow) affecting the UROS gene. Thus, unstable cellular clones initiated overproduction of isomer I porphyrins leading to a CEP phenotype. This could be explained either by a clonal expansion of the porphyric (Cys73Arg) allele or by loss of function of the normal allele. Cellular turnover would facilitate release of uroporphyrins into circulation and subsequent skin lesions. This is the first case of a CEP heterozygous carrier presenting clinical manifestations.

Extreme liver surgery as treatment of liver tumors involving the hepatocaval confluence.

OBJECTIVE: Analyze the characteristics, surgical technique, morbidity and survival of patients treated with extreme liver surgery. MATERIALS AND METHODS: We present a series of consecutive patients with malignant liver tumors in hepatocaval confluence treated in a single center with extreme liver surgery (April 2008-March 2015). Data were collected prospectively and analyzed with SPSS 21.0. RESULTS: 12 patients were included. 50 % were male and 50 % were female with a mean age of 59 ± 10 years old. The median of comorbidities was 7 according to the Charlson Age Comorbidity Index. The 75 % of the tumors were metastases, most of them from colorectal cancer. Most of the patients received neoadjuvant chemotherapy and in 58 % preoperative portal embolization was performed. Major hepatectomies were performed (66.7 % extended right hepatectomy, 33.3 % left extended hepatectomy). The 83.3 % of the patients needed vascular reconstruction. Postoperative morbidity was more than grade II in 50 % of the patients according to Dindo-Clavien classification. There was no intraoperative mortality. The postoperative mortality rate at 90 days was 33 % due to hepatic failure and biliary fistula. In December 2015, 33 % of the patients are still alive with a mean survival of 19 months (13-23) with an ECOG Performance Status of 0. CONCLUSION: Extreme liver surgery carries a high rate of morbidity and mortality that seem to increase with age and with higher tumor volumes, according to the literature. It is a therapeutic option to consider in patients with low comorbidity suffering from malignant neoplasms that involve the hepatocaval confluence, when no other treatment with curative intention can be performed.

Levamisol: un peligroso adulterante de la cocaína muy presente en nuestro medio / No disponible

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The coral reefs optimization algorithm: a novel metaheuristic for efficiently solving optimization problems.

This paper presents a novel bioinspired algorithm to tackle complex optimization problems: the coral reefs optimization (CRO) algorithm. The CRO algorithm artificially simulates a coral reef, where different corals (namely, solutions to the optimization problem considered) grow and reproduce in coral colonies, fighting by choking out other corals for space in the reef. This fight for space, along with the specific characteristics of the corals' reproduction, produces a robust metaheuristic algorithm shown to be powerful for solving hard optimization problems. In this research the CRO algorithm is tested in several continuous and discrete benchmark problems, as well as in practical application scenarios (i.e., optimum mobile network deployment and off-shore wind farm design). The obtained results confirm the excellent performance of the proposed algorithm and open line of research for further application of the algorithm to real-world problems.

Retrospective analysis of pathological response in colorectal cancer liver metastases following treatment with bevacizumab

AIMS: Pathological response has been shown to be a predictor for survival after preoperative chemotherapy and surgical resection of colorectal cancer liver metastases. This retrospective analysis evaluated the effect on pathological response of adding bevacizumab to standard neoadjuvant chemotherapy in patients with metastatic colorectal cancer (mCRC) and liver metastases. METHODS: Patient records from two Spanish centres were retrospectively examined for this analysis. Patients were included if they had stage IV mCRC with liver metastases, were unresectable or marginally resectable tumour before chemotherapy, and had oxaliplatin- or irinotecan-based chemotherapy, with or without bevacizumab, before resection. Tumour response was evaluated using response evaluation criteria in solid tumours (RECIST). Pathological response was assessed by pathologists blinded to treatment. RESULTS: Ninety-five patients were included. Good pathological responses (PR0/PR1) were observed in 37 patients (39 %). The RECIST response rate was 51 %. Only 42 % of patients with a good pathological response had a complete or partial response according to RECIST, while 57 % of those with a poor pathological response had a complete or partial response according to RECIST. RECIST response rates were similar with and without bevacizumab, although 49 % of bevacizumab-treated patients had a good pathological response versus 27 % of those receiving chemotherapy alone (χ (2) P = 0.0302). CONCLUSION: Pathological response may be a better indicator of treatment efficacy than RECIST for patients with mCRC receiving bevacizumab in the neoadjuvant setting. Adding bevacizumab to chemotherapy has the potential to increase pathological response rates. Well-designed prospective clinical studies are required to establish the efficacy and tolerability of this approach (AU)

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