Outcomes from elective colorectal cancer surgery during the SARS-CoV-2 pandemic

This study aimed to describe the change in surgical practice and the impact of SARS-CoV-2 on mortality after surgical resection of colorectal cancer during the initial phases of the SARS-CoV-2 pandemic

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified

Wastes from industrial processes introduced as chamottes in ceramic membranes

In the present work, chamottes generated as subproducts by different industrial processes have been used to obtain low-cost ceramic membranes

Methylmalonic acidaemia: Examination of genotype and biochemical data in 32 patients belonging to mut, cblA or cblB complementation group

Methylmalonic acidaemia (MMA) is a genetic disorder caused by defects in methylmalonyl-CoA mutase or in any of the different proteins involved in the synthesis of adenosylcobalamin. The aim of this work was to examine the biochemical and clinical phenotype of 32 MMA patients according to their genotype, and to study the mutant mRNA stability by real-time PCR analysis. Using cellular and biochemical methods, we classified our patient cohort as having the MMA forms mut (n = 19), cblA (n = 9) and cblB (n = 4). All the mute and some of the cblB patients had the most severe clinical and biochemical manifestations, displaying non-inducible propionate incorporation in the presence of hydroxocobalamin (OHCbl) in vitro and high plasma odd-numbered long-chain fatty acid (OLCFA) concentrations under dietary therapy. In contrast, mut and cblA patients exhibited a milder phenotype with propionate incorporation enhanced by OHCbl and normal OLCFA levels under dietary therapy. No missense mutations identified in the MUT gene, including mute and mut changes, affected mRNA stability. A new sequence variation (c.562G>C) in the MMAA gene was identified. Most of the cblA patients carried premature termination codons (PTC) in both alleles. Interestingly, the transcripts containing the PTC mutations were insensitive to nonsense-mediated decay (NMD)

Effectiveness of the combination elvitegravir/cobicistat/tenofovir/emtricitabine (EVG/COB/TFV/FTC) plus darunavir among treatment-experienced patients in clinical practice : A multicentre cohort study

Background: The aim of this study was to investigate the effectiveness and tolerability of the combination elvitegravir/cobicistat/tenofovir/emtricitabine plus darunavir (EVG/COB/TFV/FTC + DRV) in treatment-experienced patients from the cohort of the Spanish HIV/AIDS Research Network (CoRIS). Methods: Treatment-experienced patients starting treatment with EVG/COB/TFV/FTC + DRV during the years 2014-2018 and with more than 24 weeks of follow-up were included. TFV could be administered either as tenofovir disoproxil fumarate or tenofovir alafenamide. We evaluated virological response, defined as viral load (VL) < 50 copies/ml and < 200 copies/ml at 24 and 48 weeks after starting this regimen, stratified by baseline VL (< 50 or ≥ 50 copies/ml at the start of the regimen). Results: We included 39 patients (12.8% women). At baseline, 10 (25.6%) patients had VL < 50 copies/ml and 29 (74.4%) had ≥ 50 copies/ml. Among patients with baseline VL < 50 copies/ml, 85.7% and 80.0% had VL < 50 copies/ml at 24 and 48 weeks, respectively, and 100% had VL < 200 copies/ml at 24 and 48 weeks. Among patients with baseline VL ≥ 50 copies/ml, 42.3% and 40.9% had VL < 50 copies/ml and 69.2% and 68.2% had VL < 200 copies/ml at 24 and 48 weeks. During the first 48 weeks, no patients changed their treatment due to toxicity, and 4 patients (all with baseline VL ≥ 50 copies/ml) changed due to virological failure. Conclusions: EVG/COB/TFV/FTC + DRV was well tolerated and effective in treatment-experienced patients with undetectable viral load as a simplification strategy, allowing once-daily, two-pill regimen with three antiretroviral drug classes. Effectiveness was low in patients with detectable viral loads

Mitochondrial apoptosis is induced by Alkoxy phenyl-1-propanone derivatives through PP2A-mediated dephosphorylation of Bad and Foxo3A in CLL

Protein phosphatase 2 A (PP2A) is a tumour suppressor whose strong inhibition underlies the phosphorylation-dependent, anti-apoptotic mechanisms in Chronic Lymphocytic Leukemia (CLL). Inactivation of PP2A is due to the cooperative action of the phosphorylation of Y307 of its catalytic subunit by the aberrant cytosolic pool of the Src Family Kinase Lyn and the interaction with its protein inhibitor SET, which is overexpressed in CLL. In this study, we developed a library of compounds, the most potent being the one named CC11, which restores PP2A activity by disrupting the PP2A/SET complex, thereby triggering the mitochondrial pathway of apoptosis. This process involves the recruitment of the pro-apoptotic BH3-only proteins Bad and Bim to mitochondria, the former upon direct dephosphorylation and the latter being newly expressed upon dephosphorylation and activation of its transcription factor FoxO3a. These findings highlight that PP2A antagonizes the prosurvival pathways controlled by Akt, which phosphorylates and thereby suppresses a variety of pro-apoptotic factors and tumour suppressors including Bad and FoxO3a. Furthermore, the PP2A-mediated pro-apoptotic effect of CC11 is synergistically potentiated by the abrogation of Lyn's activity. Our results show that CC11 represents a promising lead compound for a new therapeutic rationale aimed at abrogating the aberrant oncogenic signals in CLL