Repair of Mitral Prolapse: Comparison of Thoracoscopic Minimally-invasive and Conventional Approaches

Objectives: Surgical repair remains the best treatment for severe primary mitral regurgitation (MR). Minimally invasive mitral valve surgery is being increasingly performed, but there is a lack of solid evidence comparing thoracoscopic with conventional surgery. Our objective was to compare outcomes of both approaches for repair of leaflet prolapse. Methods: All consecutive patients undergoing surgery for severe MR due to mitral prolapse from 2012 to 2020 were evaluated according to the approach used. Freedom from mortality, reoperation and recurrent severe MR were evaluated by Kaplan-Meier method. Differences in baseline characteristics were adjusted with propensity score-matched analysis (1:1, nearest neighbour). Results: Three hundred patients met inclusion criteria and were divided into thoracoscopic (N = 188) and conventional (sternotomy; N = 112) groups. Unmatched patients in the thoracoscopic group were younger and had lower body mass index, New York Heart Association class and EuroSCORE II preoperatively. After matching, thoracoscopic group presented significantly shorter mechanical ventilation (9 vs 15 h), shorter intensive care unit stay (41 vs 65 h) and higher postoperative haemoglobin levels (11 vs 10.2 mg/dl) despite longer bypass and cross-clamp times (+30 and +17 min). There were no differences in mortality or MR grade at discharge between groups nor differences in survival, repair failures and reinterventions during follow-up. Conclusions: Minimally invasive mitral repair can be performed in the majority of patients with mitral prolapse, without compromising outcomes, repair rate or durability, while providing shorter mechanical ventilation and intensive care unit stay and less blood loss

Androgenic activation, impairment of the monoaminergic system and altered behavior in zebra!sh larvae exposed to environmental concentrations of fenitrothion

Artículo indizadoFenitrothion is an organophosphorus insecticide usually found in aquatic ecosystems at concentrations in the range of low ng/L. In this manuscript we show that 24 h exposure to environmental concentrations of fenitro- thion, from ng/L to low !g/L, altered basal locomotor activity, visual-motor response and acoustic/vibrational es- cape response of zebra!sh larvae. Furthermore, fenitrothion and expression of gap43a, gfap, atp2b1a, and mbp exhibited a signi!cant non-monotonic concentration-response relationship. Once determined that environmen- tal concentrations of fenitrothion were neurotoxic for zebra!sh larvae, a computational analysis identi!ed poten- tial protein targets of this compound. Some of the predictions, including interactions with acetylcholinesterase, monoamine-oxidases and androgen receptor (AR), were experimentally validated. Binding to AR was the most suitable candidate for molecular initiating event, as indicated by both the up-regulation of cyp19a1b and sult2st3 and the non-monotonic relationship found between fenitrothion and the observed responses. Finally, when the integrity of the monoaminergic system was evaluated, altered levels of L-DOPA, DOPAC, HVA and 5-HIAA were found, as well as a signi!cant up-regulation of slc18a2 expression at the lowest concentrations of fenitrothion. These data strongly suggest that concentrations of fenitrothion commonly found in aquatic ecosystems present a signi!cant environmental risk for !sh communities.This work was supported by the Spanish Government with FEDER Funds (CTM2017-83242-R; D.R.) and the net- work of recognized research groups by the Catalan Government (2017 SGR_902)

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

A multi-stage genome-wide association study of bladder cancer identifies multiple susceptibility loci.

We conducted a multi-stage, genome-wide association study of bladder cancer with a primary scan of 591,637 SNPs in 3,532 affected individuals (cases) and 5,120 controls of European descent from five studies followed by a replication strategy, which included 8,382 cases and 48,275 controls from 16 studies. In a combined analysis, we identified three new regions associated with bladder cancer on chromosomes 22q13.1, 19q12 and 2q37.1: rs1014971, (P = 8 × 10⁻¹²) maps to a non-genic region of chromosome 22q13.1, rs8102137 (P = 2 × 10⁻¹¹) on 19q12 maps to CCNE1 and rs11892031 (P = 1 × 10⁻⁷) maps to the UGT1A cluster on 2q37.1. We confirmed four previously identified genome-wide associations on chromosomes 3q28, 4p16.3, 8q24.21 and 8q24.3, validated previous candidate associations for the GSTM1 deletion (P = 4 × 10⁻¹¹) and a tag SNP for NAT2 acetylation status (P = 4 × 10⁻¹¹), and found interactions with smoking in both regions. Our findings on common variants associated with bladder cancer risk should provide new insights into the mechanisms of carcinogenesis

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

Further characterization of the zebrafish model of acrylamide acute neurotoxicity: gait abnormalities and oxidative stress

Occupational, accidental, or suicidal exposure to acrylamide (ACR) may result in a neurotoxic syndrome. Development of animal models of acrylamide neurotoxicity is necessary for increasing our mechanistic understanding of this syndrome and developing more effective therapies. A new model for acute ACR neurotoxicity has been recently developed in adult zebrafish. Whereas the results of the initial characterization were really promising, a further characterization is needed for testing the construct validity of the model. In this study, the presence of gait abnormalities has been investigated by using ZebraGait, software specifically designed to analyze the kinematics of fish swimming in a water tunnel. The results of the kinematic analyses demonstrated that the model exhibits mild-to-moderate gait abnormalities. Moreover, the model exhibited negative scototaxis, a result confirming a phenotype of anxiety comorbid with depression phenotype. Interestingly, depletion of the reduced glutathione levels was found in the brain without a concomitant increase in oxidative stress. Finally, hypolocomotion and positive geotaxis exhibited by this model were fully recovered 5 days after transferring the fish to clean fish-water. All this data support the validity of the ACR acute neurotoxicity model developed in adult zebrafish.We thank Dr. Caio Maximino, from the Universidade Federal do Sul e Sudeste do Pará (Marabá, Brazil), for his comments and suggestions on the DLT. The IRI Lab technical staff members are gratefully thanked for their valuable assistance in the design of the experimental setup for video-recording the fish swimming. This work was supported by the NATO SfP project MD. SFPP 984777 (D.R.) and the Spanish Government (CTM2017-83242-R; D.R. and J.M.P.). M.F. acknowledges financial support from the Beatriu de Pinós programme (Grant No. 2016 BP 00233) provided by the Secretariat of Universities and Research department of the Ministry for Business and Knowledge, Catalonia Government.Peer reviewe

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