De la mano de Keynes: "A tract on monetary reform"

En Tract on Monetary Reform, John Maynard Keynes propuso utilizar la base monetaria y el coeficiente de reserva bancaria como variables instrumentales d¿una política monetaria que había sido considerada hasta entonces innecesaria. En este trabajo se intenta desvelar las primeras contribuciones de Keynes al progreso del análisis económico

Polymorphisms in tumor necrosis factor-α increase susceptibility to intra-abdominal Candida infection in high-risk surgical ICU patients*.

OBJECTIVES: To evaluate the influence of genetic polymorphisms on the susceptibility to Candida colonization and intra-abdominal candidiasis, a blood culture-negative life-threatening infection in high-risk surgical ICU patients. DESIGN: Prospective observational cohort study. SETTING: Surgical ICUs from two University hospitals of the Fungal Infection Network of Switzerland. PATIENTS: Eighty-nine patients at high risk for intra-abdominal candidiasis (68 with recurrent gastrointestinal perforation and 21 with acute necrotizing pancreatitis). MEASUREMENTS AND MAIN RESULTS: Eighteen single-nucleotide polymorphisms in 16 genes previously associated with development of fungal infections were analyzed from patient's DNA by using an Illumina Veracode genotyping platform. Candida colonization was defined by recovery of Candida species from at least one nonsterile site by twice weekly monitoring of cultures from oropharynx, stools, urine, skin, and/or respiratory tract. A corrected colonization index greater than or equal to 0.4 defined "heavy" colonization. Intra-abdominal candidiasis was defined by the presence of clinical symptoms and signs of peritonitis or intra-abdominal abscess and isolation of Candida species either in pure or mixed culture from intraoperatively collected abdominal samples. Single-nucleotide polymorphisms in three innate immune genes were associated with development of a Candida corrected colonization index greater than or equal to 0.4 (Toll-like receptor rs4986790, hazard ratio = 3.39; 95% CI, 1.45-7.93; p = 0.005) or occurrence of intra-abdominal candidiasis (tumor necrosis factor-α rs1800629, hazard ratio = 4.31; 95% CI, 1.85-10.1; p= 0.0007; β-defensin 1 rs1800972, hazard ratio = 3.21; 95% CI, 1.36-7.59; p = 0.008). CONCLUSION: We report a strong association between the promoter rs1800629 single-nucleotide polymorphism in tumor necrosis factor-α and an increased susceptibility to intra-abdominal candidiasis in a homogenous prospective cohort of high-risk surgical ICU patients. This finding highlights the relevance of the tumor necrosis factor-α functional polymorphism in immune response to fungal pathogens. Immunogenetic profiling in patients at clinical high risk followed by targeted antifungal interventions may improve the prevention or preemptive management of this life-threatening infection.

Upper and lower respiratory tract viral infections and acute graft rejection in lung transplant recipients.

Background: Lung transplant recipients are frequently exposed to respiratory viruses and are particularly at risk for severe complications. The aim of this study was to assess the association among the presence of a respiratory virus detected by molecular assays in bronchoalveolar lavage (BAL) fluid, respiratory symptoms, and acute rejection in adult lung transplant recipients. Methods: Upper (nasopharyngeal swab) and lower (BAL) respiratory tract specimens from 77 lung transplant recipients enrolled in a cohort study and undergoing bronchoscopy with BAL and transbronchial biopsies were screened using 17 different polymerase chain reaction-based assays. Result: BAL fluid and biopsy specimens from 343 bronchoscopic procedures performed in 77 patients were analyzed. We also compared paired nasopharyngeal and BAL fluid specimens collected in a subgroup of 283 cases. The overall viral positivity rate was 29.3% in the upper respiratory tract specimens and 17.2% in the BAL samples (). We observed a significant association P < .001 between the presence of respiratory symptoms and positive viral detection in the lower respiratory tract (Pp. 012). Conversely, acute rejection was not associated with the presence of viral infection (odds ratio, 0.41; 95% confidence interval, 0.20-0.88). The recovery of lung function was significantly slower when acute rejection and viral infection were both present. Conclusions: A temporal relationship exists between acute respiratory symptoms and positive viral nucleic acid detection in BAL fluid from lung transplant recipients. We provide evidence suggesting that respiratory viruses are not associated with acute graft rejection during the acute phase of infection.

MR features of gastrointestinal stromal tumors.

We report on two patients presenting with gastrointestinal stromal tumors (GIST). The important tumor size and the marked tissular hypersignal seen on T2-weighted magnetic resonance images (MRI) should be considered as magnetic resonance (MR) features strongly indicating diagnosis of GIST.

Radionuclide investigations of the urinary tract in the era of multimodality imaging.

This article presents the role of nuclear medicine procedures in investigating renal and parenchymal disease, as well as upper urinary tract abnormalities. More specifically, the use of scintigraphy is described in the exploration of urinary tract dilatation and UTIs, vesicoureteric reflux, renovascular hypertension, and renal transplants. With a low radiation burden and the absence of sedation, these nuclear medicine procedures are easy to perform and can provide clinicians with valuable data on renal perfusion and the function of individual kidneys, as well as on urinary tract dynamics. However, knowledge of limitations and technical pitfalls is essential in understanding the role of scintigraphy among contemporary imaging methods and the unique information it supplies in nephrourology.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Tomoscintigraphy for detecting gastrointestinal and medullary thyroid cancers: first clinical results using radiolabelled monoclonal antibodies against carcinoembryonic antigen.

Transaxial tomoscintigraphy (or single-photon emission computerised tomography) was used to detect secondary deposits of carcinoma in 17 patients who had been injected with iodine-131-labelled monoclonal antibodies against carcinoembryonic antigen. Of 17 tumor sites studied by tomoscintigraphy 16 were detected (sensitivity 94%); five sites had a volume smaller than 10 cm3. Tomoscintigraphy also detected three unknown tumour deposits later confirmed by surgery or radiology. In contrast, when 21 tumour sites in the same patients were studied by rectilinear scintigraphy, only nine tumour sites were detected (sensitivity 43%), of which eight had a volume larger than 50 cm3.

Upper gastrointestinal bleeding in cirrhosis: clinical and endoscopic correlations

The clinical data of 180 episodes of upper gastrointestinal bleeding in 168 patients with cirrhosis of the liver are examined. The source of bleeding had been determined by early endoscopy in all cases. In men under the age of 50 years, and without symptoms of liver failure, bleeding was due to ruptured gastro-oesophageal varices in 84% of cases. Severe liver failure was associated with acute lesions of gastric mucosa in many cases. No presumptive diagnosis of the source of haemorrhage could be based on the examination of other clinical data (presence of ascites, mode of presentation and pattern of bleeding, history of ulcer disease, alcoholism, and previous medication.

Combined written and oral information prior to gastrointestinal endoscopy compared with oral information alone: a randomized trial.

BACKGROUND: Little is known about how to most effectively deliver relevant information to patients scheduled for endoscopy. METHODS: To assess the effects of combined written and oral information, compared with oral information alone on the quality of information before endoscopy and the level of anxiety. We designed a prospective study in two Swiss teaching hospitals which enrolled consecutive patients scheduled for endoscopy over a three-month period. Patients were randomized either to receiving, along with the appointment notice, an explanatory leaflet about the upcoming examination, or to oral information delivered by each patient's doctor. Evaluation of quality of information was rated on scales between 0 (none received) and 5 (excellent). The analysis of outcome variables was performed on the basis of intention to treat-analysis. Multivariate analysis of predictors of information scores was performed by linear regression analysis. RESULTS: Of 718 eligible patients 577 (80%) returned their questionnaire. Patients who received written leaflets (N = 278) rated the quality of information they received higher than those informed verbally (N = 299), for all 8 quality-of-information items. Differences were significant regarding information about the risks of the procedure (3.24 versus 2.26, p < 0.001), how to prepare for the procedure (3.56 versus 3.23, p = 0.036), what to expect after the procedure (2.99 versus 2.59, p < 0.001), and the 8 quality-of-information items (3.35 versus 3.02, p = 0.002). The two groups reported similar levels of anxiety before procedure (p = 0.66), pain during procedure (p = 0.20), tolerability throughout the procedure (p = 0.76), problems after the procedure (p = 0.22), and overall rating of the procedure between poor and excellent (p = 0.82). CONCLUSION: Written information led to more favourable assessments of the quality of information and had no impact on patient anxiety nor on the overall assessment of the endoscopy. Because structured and comprehensive written information is perceived as beneficial by patients, gastroenterologists should clearly explain to their patients the risks, benefits and alternatives of endoscopic procedures. Trial registration: Current Controlled trial number: ISRCTN34382782.

De la mano de Keynes: "A tract on monetary reform"

En Tract on Monetary Reform, John Maynard Keynes propuso utilizar la base monetaria y el coeficiente de reserva bancaria como variables instrumentales d¿una política monetaria que había sido considerada hasta entonces innecesaria. En este trabajo se intenta desvelar las primeras contribuciones de Keynes al progreso del análisis económico

Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib.

Patients diagnosed with advanced gastrointestinal stromal tumours (GISTs) who are resistant or intolerant to both imatinib and second-line sunitinib have a poor prognosis and few therapeutic options. We evaluated the efficacy of nilotinib, a novel tyrosine kinase inhibitor (TKI) in patients pretreated with imatinib and sunitinib. Fifty-two consecutive patients treated with oral nilotinib, 400mg twice daily, within the nilotinib compassionate use programme in 12 European cancer centres, were included in this retrospective analysis. Median age was 59 years (range 24-80), and all patients had WHO performance score better than 3. All patients had failed both imatinib and sunitinib pretreatment, either due to progressing GIST (96%) or intolerance (4%). Five patients (10%; 95% confidence interval (CI) 2-18) responded to nilotinib and 19 patients (37%; 95% CI 24-50) achieved a disease stabilisation. Nilotinib was generally well tolerated, but six patients (12%) discontinued treatment due to intolerance. Median progression-free survival of nilotinib treatment was 12 weeks (95% CI 9-15; range 0-104) and median overall survival was 34 weeks (95% CI 3-65; range 2-135). Nilotinib is active in GIST resistant to both imatinib and sunitinib. These results warrant further investigation of nilotinib in GIST.

Cost-effectiveness analysis of immune-modulating nutritional support for gastrointestinal cancer patients.

BACKGROUND & AIM: Immune-modulating nutritional formula containing arginine, omega-3 fatty acids and nucleotides has been demonstrated to decrease complications and length of stay in surgical patients. This study aims at assessing the impact of immune-modulating formula on hospital costs in gastrointestinal cancer surgical patients in Switzerland. METHOD: Based on a previously published meta-analysis, the relative risks of overall and infectious complications with immune-modulating versus standard nutrition formula were computed. Swiss hospital costs of patients undergoing gastrointestinal cancer surgery were retrieved. A method was developed to compute the patients' severity level, not taking into account the complications from the surgery. Incremental costs of complications were computed for both treatment groups, and sensitivity analyses were carried out. RESULTS: Relative risk of complications with pre-, peri- and post-operative use of immune-modulating formula was 0.69 (95%CI 0.58-0.83), 0.62 (95%CI 0.53-0.73) and 0.73 (95%CI 0.35-0.96) respectively. The estimated average contribution of complications to the cost of stay was CHF 14,949 (euro10,901) per patient (95%CI 10,712-19,186), independently of case's severity. Based on this cost, immune-modulating nutritional support decreased costs of hospital stay by CHF 1638 to CHF 2488 per patient (euro1195-euro1814). Net hospital savings were present for baseline complications rates as low as 5%. CONCLUSION: Immune-modulating nutritional solution is a cost-saving intervention in gastrointestinal cancer patients. The additional cost of immune-modulating formula are more than offset by savings associated with decreased treatment of complications.

Rôle du pathologiste dans la prise en charge des tumeurs stromales gastro-intestinales (GIST) [The role of the pathologist in the management of gastrointestinal stromal tumors (GIST)]

Considerable progress was realized these last years in the understanding of the molecular mechanisms and the treatment of the GIST. Their diagnosis remains based on the morphology and immunohistochemistry. The evaluation of GIST prognosis was till know difficult to establish but a new histopronostic classification currently used allows a better therapeutic approach. The search for KIT and PDGFRA mutations is recommended to adapt a targeted therapy by KIT inhibitors. The pathologist plays a crucial role in the management of the GIST because it is on him that is based the diagnosis, the evaluation of the prognosis and the treatment (surgery and kit inhibitors).

Liver, gastrointestinal and cardiac toxicity in intermediate hepatocellular carcinoma treated with PRECISION TACE with drug-eluting beads: Results from the PRECISION V randomized trial : B-240

Purpose: To evaluate the toxicity focussing on hepatic, gastrointestinal and cardiac parameters following PRECISION TACE with DC Bead? versus conventional transarterial chemoembolization (cTACE) in the treatment of intermediate-stage hepatocellular carcinoma (HCC). Methods and Materials: This prospective, randomized, multicentre study was conducted under best practice trial management and authorized by local institutional review boards. Informed consent was obtained. 212 patients (185 men/27 women; mean: 67 years) were randomized to be treated with DC Beads? or cTACE. The majority of both groups presented in a more advanced stage. Safety was measured by rate of adverse events (South West Oncology Group criteria) and changes in laboratory parameters. Cardiotoxicity was assessed by means of left ventricular ejection fraction (LVEF) in MRI or echocardiography. The results of the two groups were compared using the chi-square test and Student`s t-test. Results: Mean maximum alanine transaminase increase in the DC Bead group was 50% in the cTACE group (p < 0.001) and 59% for aspartate transaminase (p < 0.001). For bilirubin, mean increase was 5.30±15.13 vs. 13.53±73.89 µmol/L. Concerning gastrointestinal disorders, 120 adverse events (AEs) occurred in 57/93 (61.3%) patients in the DC Bead group vs. 114 in 49/108 (45.4%) in cTACE. Concerning hepatobiliary disorders, serious AEs occurred in 8/93 (8.6%) vs. 11/108 (10.2%) patients. LVEF showed an increase in the DC Bead group by +2.7±10.1 percentage points and a small decrease by -1.5±7.6 in the cTACE group, p=0.018. Conclusion: PRECISION TACE is safe, even in more advanced HCC patients. Serious liver and cardiac toxicity were significantly lower in the DC Bead group.

Septic arthritis of the pubic symphysis caused by Streptococcus mitis.

Septic arthritis of the pubic symphisis is distinguished from osteitis pubis by positive cultures. The symptoms, physical examination and laboratory findings of these two conditions are comparable. We present a case of 57-year-old woman with septic arthritis of pubic symphisis caused by Streptococcus mitis, a commensal oral flora that belongs to viridans group streptococci, which normally reside in the oral cavity, the gastrointestinal and the urogenital tract.