Enfermedad diverticular de colon no complicada sintomática: revisión sistemática del diagnóstico y tratamiento

Symptomatic uncomplicated diverticular colon disease (SUDCD) is a highly prevalent disease in our setting, which significantly affects the quality of life of patients. Recent changes in understanding the natural history of this disease and technological and pharmacological advances have increased the available options for both diagnosis and treatment. However, consensus regarding the use of these options is scarce and sometimes lacks scientific evidence. The objective of this systematic review is to clarify the existing scientific evidence and analyse the use of the different diagnostic and therapeutic options for SUDCD, comparing their advantages and disadvantages, to finally suggest a diagnostic-therapeutic algorithm for this pathology and, at the same time, propose new research questions.     

Is pre-operative anaemia a risk marker for in-hospital mortality and morbidity after valve replacement?

AIMS: To assess the level of pre-operative haemoglobin (HB) as a risk marker for morbidity and mortality in the early post-operative period of patients who underwent elective valve replacement. METHODS AND RESULTS: Between January 1998 and March 2004, clinical and outcomes data were collected for the 201 patients who had elective valve replacement. For each gender, the criterion to choose the best cut-off point was that which achieved the maximum likelihood after several General Additive Model models performed in a Bootstrap procedure. The best cut-off point obtained for pre-operative HB was 12 g/dL. Overall peri-operative mortality (deaths occurring during hospital period or within 30 days) was 9.5%. After adjusting well-known independent pre-operative risk factors for operative mortality, pre-operative HB <12 g/dL was identified as an independent predictor for in-hospital mortality (OR, 3.23; 95% CI, 1.09-9.55; P = 0.03). Also adjusting for EuroScore, pre-operative HB remained significant (OR, 3.64; 95% CI, 1.32-10.06; P = 0.01). The same model was applied to post-operative morbidity, and pre-operative HB <12 g/dL was identified as an independent predictor with and without EuroScore (OR, 4.67; 95% CI, 2.03-10.71; P < 0.001), (OR, 5.18; 95% CI, 2.18-12.3; P < 0.001), respectively. CONCLUSION: In patients undergoing elective valve replacement pre-operative HB <12 g/dL is a risk marker of in-hospital mortality and serious adverse outcomes.     

l‐Methionine anti‐biofilm activity against Pseudomonas aeruginosa is enhanced by the cystic fibrosis transmembrane conductance regulator potentiator,ivacaftor

Background

Biofilms may contribute to refractory chronic rhinosinusitis (CRS), as they lead to antibiotic resistance and failure of effective clinical treatment. l ‐Methionine is an amino acid with reported biofilm‐inhibiting properties. Ivacaftor is a cystic fibrosis transmembrane conductance regulator (CFTR) potentiator with mild antimicrobial activity via inhibition of bacterial DNA gyrase and topoisomerase IV. The objective of this study was to evaluate whether co‐treatment with ivacaftor and l ‐methionine can reduce the formation of Pseudomonas aeruginosa biofilms.

Methods

P aeruginosa (PAO‐1 strain) biofilms were studied in the presence of l ‐methionine and/or ivacaftor. For static biofilm assays, PAO‐1 was cultured in a 48‐well plate for 72 hours with stepwise combinations of these agents. Relative biofilm inhibitions were measured according to optical density of crystal violet stain at 590 nm. Live/dead assays (BacTiter‐Glo? assay, Promega) were imaged with laser scanning confocal microscopy. An agar diffusion test was used to confirm antibacterial effects of the drugs.

Results

l ‐Methionine (0.5 μM) significantly reduced PAO‐1 biofilm mass (32.4 ± 18.0%; n = 4; p < 0.001) compared with controls. Low doses of ivacaftor alone (4, 8, and 12 μg/mL) had no effect on biofilm formation. When combined with ivacaftor (4 μg/mL), a synergistic anti‐biofilm effect was noted at 0.05 μM and 0.5 μM of l ‐methionine (two‐way analysis of variane, p = 0.0415) compared with corresponding concentrations of l ‐methionine alone.

Conclusion

Ivacaftor enhanced the anti‐biofilm activity of l ‐methionine against the PAO‐1 strain of P aeruginosa. Further studies evaluating the efficacy of ivacaftor/l ‐methionine combinations for P aeruginosa sinusitis are planned.

     

Genetic and chromosomal alterations in Kenyan Wilms Tumor

Wilms tumor (WT) is the most common childhood kidney cancer worldwide and poses a cancer health disparity to black children of sub‐Saharan African ancestry. Although overall survival from WT at 5 years exceeds 90% in developed countries, this pediatric cancer is alarmingly lethal in sub‐Saharan Africa and specifically in Kenya (36% survival at 2 years). Although multiple barriers to adequate WT therapy contribute to this dismal outcome, we hypothesized that a uniquely aggressive and treatment‐resistant biology compromises survival further. To explore the biologic composition of Kenyan WT (KWT), we completed a next generation sequencing analysis targeting 10 WT‐associated genes and evaluated whole‐genome copy number variation. The study cohort was comprised of 44 KWT patients and their specimens. Fourteen children are confirmed dead at 2 years and 11 remain lost to follow‐up despite multiple tracing attempts. TP53 was mutated most commonly in 11 KWT specimens (25%), CTNNB1 in 10 (23%), MYCN in 8 (18%), AMER1 in 5 (11%), WT1 and TOP2A in 4 (9%), and IGF2 in 3 (7%). Loss of heterozygosity (LOH) at 17p, which covers TP53, was detected in 18% of specimens examined. Copy number gain at 1q, a poor prognostic indicator of WT biology in developed countries, was detected in 32% of KWT analyzed, and 89% of these children are deceased. Similarly, LOH at 11q was detected in 32% of KWT, and 80% of these patients are deceased. From this genomic analysis, KWT biology appears uniquely aggressive and treatment‐resistant. © 2015 The Authors. Genes, Chromosomes & Cancer Published by Wiley Periodicals, Inc.     

Exploring the fuzzy border between senolytics and senomorphics with chemoinformatics and systems pharmacology

Biogerontology - Senescent cells accumulate within tissues during aging and secrete an array of pro-inflammatory molecules known as senescent-associated secretory phenotype (SASP), which contribute...     

Modelling the health benefits and economic implications of implanting dual-chamber vs. single-chamber ventricular pacemakers in the UK.

AIMS: To estimate the consequences of managing bradycardia due to sinoatrial node disease or atrioventricular block with dual-chamber vs. single-chamber ventricular pacemakers. METHODS AND RESULTS: A discrete-event simulation was conducted to predict outcomes over 5 years. Patients could develop post-operative complications, clinically relevant pacemaker syndrome leading to replacement of single-chamber with dual-chamber, atrial fibrillation (AF; which if chronic might require anticoagulants) or stroke. Survival, quality-adjusted life years (QALYs), complications, and associated direct medical costs were estimated (2003 British Pounds pounds sterling). Identical patients were simulated after receiving a single-chamber device or a more expensive dual-chamber pacemaker. Probabilities of conditions were obtained from clinical trials. Benefits were discounted at 1.5% and costs at 6%. Post-operative complications increased from 6.4% with single-chamber to 7.7% with dual-chamber but AF decreased (22 vs. 18%) as did clinically relevant pacemaker symptoms (16.8 vs. 0%). Approximately 4300 pounds sterling were accrued per patient over 5 years. Additional health benefits with dual-chamber are achieved at a mean net cost of 43 pounds sterling per patient, leading to 0.09 QALY with a cost-effectiveness ratio of 477 pounds sterling/QALY. CONCLUSION: Implanting the costlier device increases the cost of the initial operation; however, this is expected to be offset by a reduction in costs associated with re-operations and AF.