Outcomes, controversies and gastric volume after laparoscopic sleeve gastrectomy in the treatment of obesity

AbstractBackgroundLaparoscopic sleeve gastrectomy is a surgical procedure for the treatment of morbid obesity. However, there are still controversies regarding its efficiency in terms of weight reduction and incidence of complications. In this prospective study, the experience is presented of a referral centre for the treatment of morbid obesity with laparoscopic sleeve gastrectomy.Material and methodsA prospective study on 73 patients subjected to laparoscopic sleeve gastrectomy from February 2009 to September 2013. Patients were followed-up for a period of 12 months, evaluating the development of complications, reduction of gastric volume, and the weight loss associated with the surgery, as well as their impact on the improvement of comorbidities present at beginning of the study.ResultsThere was a statistically a significantly reduction between the preoperative body mass index (BMI) and the BMI at 12 months after laparoscopic sleeve gastrectomy (p<0.001), despite there being an increase in the gastric volume during follow-up, measured at one month and 12 months after surgery (p<0.001). Five patients (6.85%) had complications, with none of them serious and with no deaths in the whole series.ConclusionsLaparoscopic sleeve gastrectomy is a safe and effective technique for the treatment of morbid obesity. Its use is associated with a significant reduction in the presence of comorbidities associated with obesity. Multicentre studies with a longer period of monitoring are required to confirm the efficacy and safety of this surgical technique

Photodynamic Therapy for the Treatment of Complex Anal Fistula

Background and objectives: To validate and analyze the results of intralesional photodynamic therapy in the treatment of complex anal fistula. Study design/materials and methods: This prospective multicentric observational study enrolled patients treated for complex anal fistula who underwent intralesional photodynamic therapy (i-PDT). The included patients were treated from January 2016 to December 2018 with a minimum follow-up of 1 year to evaluate recurrence, continence and postoperative morbidity. Intralesional 5-aminolevulinic acid (ALA) gel (2%) was injected directly into the fistula. The internal and external orifices were closed. After an incubation period of 2 hours, the fistula was irradiated using an optical fiber connected to a red laser (Multidiode 630 PDT) operating at 1 W/cm for 3 minutes (180 J). Results: In total, 49 patients were included (61.2% male). The mean age was 48 years, and the mean duration of fistula was 13 months. Of the fistulas included, 75.5% were medium transphincteric, and 24.5% were high transphincteric. The median fistula length was 4 ± 1,14 cm (range: 3-5). A total of 41 patients (83.7%) had a previous history of fistula surgery. Preoperatively, some degree of anal incontinence was found in 5 patients (10.2%). No center reported any other procedure-related complications intraoperatively. Phototoxicity was found in one patient. In the first 48 hours after the procedure, fever was reported in 2 patients (4%). At the end of follow-up, total healing was observed in 32/49 patients (65.3%). No patient reported new incontinence postoperatively. Conclusion: i-PDT could be considered a good choice in patients with complex anal fistulas to avoid surgery and its complications. Lasers Surg. Med. © 2019 Wiley Periodicals, Inc

Controlled manipulation of enzyme specificity through immobilization-induced flexibility constraints

It is thought that during immobilization enzymes, as dynamic biomolecules, may become distorted and this may alter their catalytic properties. However, the effects of different immobilization strategies on enzyme rigidity or flexibility and their consequences in specificity and stereochemistry at large scale has not been yet clearly evaluated and understood. This was here investigated by using as model an ester hydrolase, isolated from a bacterium inhabiting a karstic lake, with broad substrate spectrum (72 esters being converted; 61.5 U mg−1 for glyceryl tripropionate) but initially non-enantiospecific. We found that the enzyme (7 nm × 4.4 nm × 4.2 nm) could be efficiently ionic exchanged inside the pores (9.3 nm under dry conditions) of amino-functionalized ordered mesoporous material (NH2-SBA-15), achieving a protein load of 48 mg g−1, and a specific activity of 4.5 ± 0.1 U mg−1. When the enzyme was site-directed immobilized through His interaction with an immobilized cationon the surface of two types of magnetic micro-particles through hexahistidine-tags, protein loads up to 10.2 μg g−1 and specific activities of up to 29.9 ± 0.3 U mg−1, were obtained. We found that ionically exchanged enzyme inside pores of NH2-SBA-15 drastically narrowed the substrate range (17 esters), to an extent much higher than ionically exchanged enzyme on the surface of magnetic micro-particles (up to 61 esters). This is attributed to differences in surface chemistry, particle size, and substrate accessibility to the active site tunnel. Our results also suggested, for the first time, that immobilization of enzymes in pores of similar size may alter the enzyme structures and produce enzyme active centers with different configuration which promote stereochemical conversions in a manner different to those arising from surface immobilization, where the strength of the ionic exchange also has an influence. This was shown by demonstrating that when the enzyme was introduced inside pores with a diameter (under dry conditions) slightly higher than that of the enzyme crystal structure a biocatalyst enantiospecific for ethyl (R)-4-chloro-3-hydroxybutyrate was produced, a feature not found when using wider pores. By contrast, immobilization on the surface of ferromagnetic microparticles produced selective biocatalysts for methyl (S)-(+)-mandelate or methyl (S)-lactate depending on the functionalization. This study illustrates the benefits of extensive analysis of the substrate spectra to better understand the effects of different immobilization strategies on enzyme flexibility/rigidity, as well as substrate specificity and stereochemistry. Our results will help to design tunable materials and interfaces for a controlled manipulation of specificity and to transform non-enantiospecific enzymes into stereo-chemically substrate promiscuous biocatalysts capable of converting multiple chiral molecules.This project received funding from the European Union’s Horizon 2020 research and innovation program Blue Growth: Unlockingthe potential of Seas and Oceans under grant agreement no. 634486 (project acronym INMARE). This research was also supported by the grants PCIN-2014-107 (within ERA NET IB2 grant nr. ERA-IB-14-030 - MetaCat), PCIN-2017-078 (within the ERA-MarineBiotech grant ProBone), BIO2014-54494-R, MAT2016-77496-R, BIO2017-85522-R, and CTQ2016-79138-R from the Spanish Ministry of Economy, Industry and Competitiveness. A.B. acknowledges the support from the Spanish Ministry of Economy, Industry and Competitiveness (MAT2017-88808-R grant), María de Maeztu Units of Excellence Programme (MDM-2016-0618), and the Diputación de Guipúzcoa for current funding in the frame of Gipuzkoa Fellows program. G.D. thanks the German Federal Ministry of Education and Research (BMBF, Grant No. 031A095C) for funding in the frame of the Molecular Interaction Engineering program (Biotechnologie 2020+). The authors gratefully acknowledge financial support provided by the European Regional Development Fund (ERDF). C.C. thanks the Spanish Ministry of Economy, Industry and Competitiveness for a PhD fellowship (Grant BES-2015-073829).Peer ReviewedPostprint (published version

Design and psychometric evaluation of the Quality of Life in patients with Anal Fistula Questionnaire

BACKGROUND: Quality of life is often considered when deciding and evaluating the treatment strategy for patients diagnosed with anal fistula. OBJECTIVE: The purpose of this study was to develop and psychometrically test the Quality of Life in Patients with Anal Fistula Questionnaire. DESIGN: This was an observational cross-sectional study for the development and validation of a psychometric tool. SETTINGS: The study was conducted at a general hospital in the southeast of Spain. PATIENTS: A convenience sample included 54 patients diagnosed with anal fistula. MAIN OUTCOMES MEASURES: The reliability of the tool was assessed through its internal consistency (Cronbach α) and temporal stability (Spearman correlation coefficient (r) between test–retest). The content validity index of the items and the scale was calculated. Correlation analysis and an ordinal regression analysis between the developed tool and the Short Form 12 Health Survey examined its concurrent validity. Principal component analysis and known-group analysis using the Kruskal–Wallis test examined its construct validity. RESULTS: The reliability of the developed questionnaire was very high (α = 0.908; r = 0.861; p < 0.01). Its content validity was excellent (all-item content validity index = 0.79–1.00; scale validity index = 0.92). Evidence of its concurrent validity included strong correlation between the developed tool and Short Form 12 Health Survey (r = 0.734; p < 0.001), and participant scores on the developed tool explained ≈46.2% of the between-subject variation for the participant scores on Short Form 12 Health Survey (Nagelkerke R2 = 0.462). Confirming its construct validity, principal component analysis revealed that 2 factors explained 81.63% of the total variance found. Known-group analysis evidenced the ability of the questionnaire to detect expected differences in patients presenting with different symptomatology. LIMITATIONS: The major limitations of this study were the use of a small sample of Spanish-speaking patients, not including patients in the initial development of the questionnaire, and developing the scoring system using a summation method. CONCLUSIONS: The Quality of Life in Patients with Anal Fistula Questionnaire has proven to be a valid, reliable, and concise tool that could contribute to the evaluation of quality of life among patients with an anal fistula. See Video Abstract at http://links.lww.com/DCR/A368

Social Support for People with Morbid Obesity in a Bariatric Surgery Programme: A Qualitative Descriptive Study

Background—Morbid obesity (MO) is a chronic metabolic disease affecting physical, psychological and social wellbeing. Bariatric surgery is a reliable method for losing weight in the long term, improving the quality of life, body image and social life of people with MO. Current literature recognises the importance of social support in controlling weight and coping with MO. The objective of this study was to describe and understand experiences related to social support for patients with MO included in a bariatric surgery programme. Methods—A qualitative descriptive study, where data collection included thirty-one interviews with people diagnosed with MO involved in a bariatric surgery programme. Results—Three main themes emerged from the analysis: (1) accepting the problem in order to ask for help, (2) the need for close support and (3) professional support: opposing feelings. Conclusions—A partner, family and friends are the key pillars of social support for those with MO included in a bariatric surgery programme. Healthcare professionals gave formal support; the bariatric surgery team provided information, trust and assurance. Nurses provided healthcare 24 h a day, making them the main formal support for people in the bariatric surgery programme

Evaluation of 12 GWAS-drawn SNPs as biomarkers of rheumatoid arthritis response to TNF inhibitors. A potential SNP association with response to etanercept

Research in rheumatoid arthritis (RA) is increasingly focused on the discovery of biomarkers that could enable personalized treatments. The genetic biomarkers associated with the response to TNF inhibitors (TNFi) are among the most studied. They include 12 SNPs exhibiting promising results in the three largest genome-wide association studies (GWAS). However, they still require further validation. With this aim, we assessed their association with response to TNFi in a replication study, and a meta-analysis summarizing all non-redundant data. The replication involved 755 patients with RA that were treated for the first time with a biologic drug, which was either infliximab (n = 397), etanercept (n = 155) or adalimumab (n = 203). Their DNA samples were successfully genotyped with a single-base extension multiplex method. Lamentably, none of the 12 SNPs was associated with response to the TNFi in the replication study (p > 0.05). However, a drug-stratified exploratory analysis revealed a significant association of the NUBPL rs2378945 SNP with a poor response to etanercept (B = -0.50, 95% CI = -0.82, -0.17, p = 0.003). In addition, the meta-analysis reinforced the previous association of three SNPs: rs2378945, rs12142623, and rs4651370. In contrast, five of the remaining SNPs were less associated than before, and the other four SNPs were no longer associated with the response to treatment. In summary, our results highlight the complexity of the pharmacogenetics of TNFi in RA showing that it could involve a drug-specific component and clarifying the status of the 12 GWAS-drawn SNP

Validation Study Of Genetic Biomarkers Of Response To Tnf Inhibitors In Rheumatoid Arthritis

Genetic biomarkers are sought to personalize treatment of patients with rheumatoid arthritis (RA), given their variable response to TNF inhibitors (TNFi). However, no genetic biomaker is yet sufficiently validated. Here, we report a validation study of 18 previously reported genetic biomarkers, including 11 from GWAS of response to TNFi. The validation was attempted in 581 patients with RA that had not been treated with biologic antirheumatic drugs previously. Their response to TNFi was evaluated at 3, 6 and 12 months in two ways: change in the DAS28 measure of disease activity, and according to the EULAR criteria for response to antirheumatic drugs. Association of these parameters with the genotypes, obtained by PCR amplification followed by single-base extension, was tested with regression analysis. These analyses were adjusted for baseline DAS28, sex, and the specific TNFi. However, none of the proposed biomarkers was validated, as none showed association with response to TNFi in our study, even at the time of assessment and with the outcome that showed the most significant result in previous studies. These negative results are notable because this was the first independent validation study for 12 of the biomarkers, and because they indicate that prudence is needed in the interpretation of the proposed biomarkers of response to TNFi even when they are supported by very low p values. The results also emphasize the requirement of independent replication for validation, and the need to search protocols that could increase reproducibility of the biomarkers of response to TNFi

Lack of validation of genetic variants associated with anti-tumor necrosis factor therapy response in rheumatoid arthritis: a genome-wide association study replication and meta-analysis

Introduction: In this study, our aim was to elucidate the role of four polymorphisms identified in a prior large genome-wide association study (GWAS) in which the investigators analyzed the responses of patients with rheumatoid arthritis (RA) to treatment with tumor necrosis factor inhibitors (TNFi). The authors of that study reported that the four genetic variants were significantly associated. However, none of the associations reached GWAS significance, and two subsequent studies failed to replicate these associations. Methods: The four polymorphisms (rs12081765, rs1532269, rs17301249 and rs7305646) were genotyped in a total of 634 TNFi-treated RA patients of Spanish Caucasian origin. Four outcomes were evaluated: changes in the Disease Activity Score in 28 joints (DAS28) after 6 and 12 months of treatment and classification according to the European League Against Rheumatism (EULAR) response criteria at the same time points. Association with DAS28 changes was assessed by linear regression using an additive genetic model. Contingency tables of genotype and allele frequencies between EULAR responder and nonresponder patients were compared. In addition, we combined our data with those of previously reported studies in a meta-analysis including 2,998 RA patients. Results: None of the four genetic variants showed an association with response to TNFi in any of the four outcomes analyzed in our Spanish patients. In addition, only rs1532269 yielded a suggestive association (P = 0.0033) with the response to TNFi when available data from previous studies were combined in the meta-analysis. Conclusion: Our data suggest that the rs12081765, rs1532269, rs17301249 and rs7305646 genetic variants do not have a role as genetic predictors of TNFi treatment outcomes

Sub-micro- and nano-sized polyethylene terephthalate deconstruction with engineered protein nanopores

The identification or design of biocatalysts to mitigate the accumulation of plastics, including sub-micro- and nano-sized polyethylene terephthalate (nPET), is becoming a global challenge. Here we computationally incorporated two hydrolytic active sites with geometries similar to that of Idionella sakaiensis PET hydrolase, to fragaceatoxin C (FraC), a membrane pore-forming protein. FraCm1/m2 could be assembled into octameric nanopores (7.0 nm high × 1.6–6.0 nm entry), which deconstructed (40 °C, pH 7.0) nPET from GoodFellow, commodities and plastic bottles. FraCm1 and FraCm2 degrade nPET by endo- and exo-type chain scission. While FraCm1 produces bis(2-hydroxyethyl) terephthalate as the main product, FraCm2 yields a high diversity of oligomers and terephthalic acid. Mechanistic and biochemical differences with benchmark PET hydrolases, along with pore and nPET dynamics, suggest that these pore-forming protein catalytic nanoreactors do not deconstruct macro-PET but are promising in nanotechnology for filtering, capturing and breaking down nPET, for example, in wastewater treatment plants. [Figure not available: see fulltext.]. © 2023, The Author(s).This study was conducted under the auspices of the FuturEnzyme Project funded by the European Union’s Horizon 2020 Research and Innovation Programme under the auspices of the FuturEnzyme Project (grant agreement no. 101000327) and the PlasticsFatE project (grant agreement no. 95921), and Horizon Europe Research and Innovation Programme under grant agreement no. GA101060625 (Nymphe project). We also acknowledge financial support under grants PID2020-112758RB-I00 (M.F.), PDC2021-121534-I00 (M.F.), TED2021-130544B-I00 (M.F.), PID2019-106370RB-I00 (V.G.) and PID2019-105838RB-C31 (F.J.P.) from the Ministerio de Ciencia e Innovación, Agencia Estatal de Investigación (AEI) (Digital Object Identifier MCIN/AEI/10.13039/501100011033), Fondo Europeo de Desarrollo Regional (ERDF) A way of making Europe and the European Union NextGenerationEU/PRTR, UCM-Banco Santander Grants PR87/19-22556 and PR108/20-26896 and UnaEuropa (Unano) SF2106 (to A.M.P.). S.G.-L. was supported by a Real Colegio Complutense Postdoctoral Fellowship for Distinguished Junior Scholars. S.R. thanks the Spanish Ministry of Science and Innovation for a PhD fellowship (FPU19/00608). D.H.-M. thanks Complutense University of Madrid and Banco Santander for a PhD fellowship (CT82/20/CT83/20). A.R.-M. thanks the Spanish Ministry of Science and Innovation for a PhD fellowship (PRE2020-091825) and the project PID2019-106370RB-I00. We thank M. J. Vicente for the ESI–MS analysis, performed at the Servicio Interdepartamental de Investigación (SIDI) from the Autonomous University of Madrid, Spain.Supplementary dataPeer reviewe