Colorectal polypectomy during insertion and withdrawal or only during withdrawal? A randomized controlled trial.

BACKGROUND AND STUDY AIMS: Removal of colorectal polyps is routinely performed during withdrawal of the endoscope. However, polyps detected during insertion of the colonoscope may be missed at withdrawal. We aimed to evaluate whether polypectomy during both insertion and withdrawal increases polyp detection and removal rates compared with polypectomy at withdrawal only, and to assess the duration of both approaches. PATIENTS AND METHODS: Patients were included into the study when the first polyp was detected, and randomized into two groups; in group A, polyps ≤ 10 mm in diameter were removed during insertion and withdrawal of the colonoscope, while in group B, these polyps were removed at withdrawal only. Main outcome measures were duration of colonoscopy, number of polyps detected during insertion but not recovered during withdrawal, technical ease, patient discomfort, and complications. RESULTS: 150 patients were randomized to group A and 151 to group B. Mean (± standard deviation [SD]) duration of colonoscopy did not differ between the groups (30.8 ± 15.6 min [A] vs. 28.5 ± 13.8 min [B], P = 0.176). In group A 387 polyps (mean 2.58 per colonoscopy) were detected and removed compared with 389 polyps detected (mean 2.58 per colonoscopy) in group B of which 376 were removed (13 polyps were missed, mean size [SD] 3.2 [1.3] mm; 7.3 % of patients). Patient tolerance was similar in the two groups. CONCLUSIONS: Removal of polyps ≤ 10 mm during withdrawal only is associated with a considerable polyp miss rate. We therefore recommend that these polyps are removed during both insertion and withdrawal.

Single nucleotide polymorphisms, apoptosis, and the development of severe late adverse effects after radiotherapy.

PURPOSE: Evidence has accumulated in recent years suggestive of a genetic basis for a susceptibility to the development of radiation injury after cancer radiotherapy. The purpose of this study was to assess whether patients with severe radiation-induced sequelae (RIS; i.e., National Cancer Institute/CTCv3.0 grade, > or =3) display both a low capacity of radiation-induced CD8 lymphocyte apoptosis (RILA) in vitro and possess certain single nucleotide polymorphisms (SNP) located in candidate genes associated with the response of cells to radiation. EXPERIMENTAL DESIGN: DNA was isolated from blood samples obtained from patients (n = 399) included in the Swiss prospective study evaluating the predictive effect of in vitro RILA and RIS. SNPs in the ATM, SOD2, XRCC1, XRCC3, TGFB1, and RAD21 genes were screened in patients who experienced severe RIS (group A, n = 16) and control subjects who did not manifest any evidence of RIS (group B, n = 18). RESULTS: Overall, 13 and 21 patients were found to possess a total of <4 and > or =4 SNPs in the candidate genes. The median (range) RILA in group A was 9.4% (5.3-16.5) and 94% (95% confidence interval, 70-100) of the patients (15 of 16) had > or =4 SNPs. In group B, median (range) RILA was 25.7% (20.2-43.2) and 33% (95% confidence interval, 13-59) of patients (6 of 18) had > or =4 SNPs (P < 0.001). CONCLUSIONS: The results of this study suggest that patients with severe RIS possess 4 or more SNPs in candidate genes and low radiation-induced CD8 lymphocyte apoptosis in vitro.

Natural gene-expression variation in Down syndrome modulates the outcome of gene-dosage imbalance.

Down syndrome (DS) is characterized by extensive phenotypic variability, with most traits occurring in only a fraction of affected individuals. Substantial gene-expression variation is present among unaffected individuals, and this variation has a strong genetic component. Since DS is caused by genomic-dosage imbalance, we hypothesize that gene-expression variation of human chromosome 21 (HSA21) genes in individuals with DS has an impact on the phenotypic variability among affected individuals. We studied gene-expression variation in 14 lymphoblastoid and 17 fibroblast cell lines from individuals with DS and an equal number of controls. Gene expression was assayed using quantitative real-time polymerase chain reaction on 100 and 106 HSA21 genes and 23 and 26 non-HSA21 genes in lymphoblastoid and fibroblast cell lines, respectively. Surprisingly, only 39% and 62% of HSA21 genes in lymphoblastoid and fibroblast cells, respectively, showed a statistically significant difference between DS and normal samples, although the average up-regulation of HSA21 genes was close to the expected 1.5-fold in both cell types. Gene-expression variation in DS and normal samples was evaluated using the Kolmogorov-Smirnov test. According to the degree of overlap in expression levels, we classified all genes into 3 groups: (A) nonoverlapping, (B) partially overlapping, and (C) extensively overlapping expression distributions between normal and DS samples. We hypothesize that, in each cell type, group A genes are the most dosage sensitive and are most likely involved in the constant DS traits, group B genes might be involved in variable DS traits, and group C genes are not dosage sensitive and are least likely to participate in DS pathological phenotypes. This study provides the first extensive data set on HSA21 gene-expression variation in DS and underscores its role in modulating the outcome of gene-dosage imbalance.

Proteomics of methylene blue photo-treated plasma before and after removal of the dye by an absorbent filter.

Methylene blue (MB) and light are used for virus inactivation of plasma for transfusion. However, the presence of MB has been the subject of concern, and efforts have been made to efficiently remove the dye after photo-treatment. For this study, plasma was collected by apheresis from 10 donors (group A), then treated using the MacoPharma THERAFLEX procedure (MB; 1 microM, and light exposure; 180 J/cm(2)) (group B), and finally filtered in order to remove the dye (group C). Proteins were analyzed by two-dimensional electrophoresis, and peptides showing modifications were characterized by mass spectrometry. Clottable and antigenic fibrinogen levels, as well as fibrin polymerization time were measured. Analyses of the gels focused on a region corresponding to pI between 4.5 and 6.5, and M(r) from 7000 to 58 000. In this area, 387 +/- 47 spots matched, and four of these spots presented significant modifications. They corresponded to changes of the gamma-chain of fibrinogen, of transthyretin, and of apolipoprotein A-I, respectively. A decrease of clottable fibrinogen and a prolongation of fibrin polymerization time were observed in groups B and C. Removal of MB by filtration was not responsible for additional protein alterations. The effect of over-treatment of plasma by very high concentrations of MB (50 microM) in association with prolonged light exposure (3 h) was also analyzed, and showed complex alterations of most of the plasma proteins, including fibrinogen gamma-chain, transthyretin, and apolipoprotein A-I. Our data indicates that MB treatment at high concentration and prolonged illumination severely injure plasma proteins. By contrast, at the MB concentration used to inactivate viruses, damages are apparently very restricted.

Telementoring during endovascular treatment of abdominal aortic aneurysms: a prospective study.

PURPOSE: To explore the use of telementoring for distant teaching and training in endovascular aortic aneurysm repair (EVAR). METHODS: According to a prospectively designed study protocol, 48 patients underwent EVAR: the first 12 patients (group A) were treated at a secondary care center by an experienced interventionist, who was training the local team; a further 12 patients (group B) were operated by the local team at their secondary center with telementoring by the experienced operator from an adjacent suite; and the last 24 patients (group C) were operated by the local team with remote telementoring support from the experienced interventionist at a tertiary care center. Telementoring was performed using 3 video sources; images were transmitted using 4 ISDN lines. EVAR was performed using intravascular ultrasound and simultaneous fluoroscopy to obtain road mapping of the abdominal aorta and its branches, as well as for identifying the origins of the renal arteries, assessing the aortic neck, and monitoring the attachment of the stent-graft proximally and distally. RESULTS: Average duration of telementoring was 2.1 hours during the first 12 patients (group B) and 1.2 hours for the remaining 24 patients (group C). There was no difference in procedural duration (127+/-59 minutes in group A, 120+/-4 minutes in group B, and 119+/-39 minutes in group C; p=0.94) or the mean time spent in the ICU (26+/-15 hours in group A, 22+/-2 hours in group B, and 22+/-11 hours for group C; p=0.95). The length of hospital stay (11+/-4 days in group A, 9+/-4 days in group B, and 7+/-1 days in group C; p=0.002) was significantly different only for group C versus A (p=0.002). Only 1 (8.3%) patient (in group A: EVAR performed by the experienced operator) required conversion to open surgery because of iliac artery rupture. This was the only conversion (and the only death) in the entire study group (1/12 in group A versus 0/36 in groups B + C, p=0.31). CONCLUSIONS: Telementoring for EVAR is feasible and shows promising results. It may serve as a model for development of similar projects for teaching other invasive procedures in cardiovascular medicine.

Recommendations for term and late preterm infants at risk for perinatal bacterial infection.

Since publication of the initial guidelines for the prevention of group B streptococcal disease in 1996, the incidence of perinatal infection has decreased significantly. Intrapartum antibiotic prophylaxis together with appropriate management of neonates at increased risk for early-onset sepsis not only reduces morbidity and mortality, but also decreases the burden of unnecessary or prolonged antibiotic therapy. This article provides healthcare workers in Switzerland with evidence-based and best-practice derived guidelines for the assessment and management of term and late preterm infants (>34 weeks) at increased risk for perinatal bacterial infection. Management of neonates at increased risk for early-onset sepsis depends on clinical presentation and risk factors. Asymptomatic infants with risk factors for early-onset sepsis should be observed closely in an inpatient setting for the first 48 hours of life. Symptomatic neonates must be treated promptly with intravenous antibiotics. As clinical and laboratory signs of neonatal infection are nonspecific, it is mandatory to reevaluate the need for continued antibiotic therapy after 48 hours.

Cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation.

OBJECTIVES: The aims of this study were to assess the 1-year cost-effectiveness of a new combined immunosuppressive and anti-infectious regimen in kidney transplantation to prevent both rejection and infectious complications. METHODS: Patients (pts) transplanted from January 2000 to March 2003 (Group A) and treated with a conventional protocol were compared with pts submitted to a combined regimen including universal cytomegalovirus (CMV) prophylaxis between April 2003 and July 2005 (Group B). Costs were computed from the hospital accounting system for hospital stays, and official tariffs for outpatient visits. Patients with incomplete costs data were excluded from analysis. RESULTS: Fifty-three patients were analyzed in Group A, and 60 in Group B. Baseline characteristics including CMV serostatus were not significantly different between the two groups. Over 12 months after transplantation, acute rejections decreased from 41.5 percent in Group A to 6.7 percent in Group B (p &lt; .001), and CMV infections from 47 percent to 15 percent (p &lt; .001). Overall, readmissions decreased from 68 percent to 55 percent (p = .160), and average hospital days from 28 +/- 19 to 20 +/- 11 days (p &lt; .007). The average number of outpatient visits decreased from 49 +/- 10 to 39 +/- 8 (p &lt; .001). Average 1-year immunosuppressive and CMV prophylaxis costs (per patient) increased from CHF20,402 +/- 7,273 to 27,375 +/- 6,063 (p &lt; .001), graft rejection costs decreased from CHF4,595 +/- 10,182 to 650 +/- 3,167 (p = .005), CMV treatment costs from CHF2,270 +/- 6,161 to 101 +/- 326 (p = .008), and outpatient visits costs from CHF8,466 +/- 1'721 to 6,749 +/- 1,159 (p &lt; .001). Altogether, 1-year treatment costs decreased from CHF39'957 +/- 16,573 to 36,204 +/- 6,901 (p = .115). CONCLUSIONS: The new combined regimen administered in Group B was significantly more effective, and its additional costs were more than offset by savings associated with complications avoidance.

Cyclosporine A, an alternative to the oral lichen planus erosive treatment

We present a double-blind study in two groups afflicted with oral lichen planus erythematous of long evolution and resistant to other treatments. We tested on it a treatment with Cyclosporine A (CyA) which had been successfully used before by many dermatologists. In the group A we used mouthwashes with a 5 ml Cyclosporine A solution to a 10% in olive oil of 0.4 degrees of acidity for five minutes, three times a day for eight weeks. In the control group we used acetonide of triamcinolone 01% in aqueous solution. Patients in group A improved considerably in their symptomatology in a 90% against a 60% in group B. In group A we could appreciate a disappearance of the symptomatology after two weeks of treatment in 60% of patients against 30% in group B. CyA can be an alternative to the conventional treatments in the acute period of lichen planus although it can not be considered as a first option drug because of the high cost of the treatment. For long term, results are not so good and we consider that extensive studies are necessary

Colonic perianastomotic carcinogenesis in an experimental model

Background To examine the effect of anastomosis on experimental carcinogenesis in the colon of rats. Methods Forty-three 10-week-old male and female Sprague-Dawley rats were operated on by performing an end-to-side ileorectostomy. Group A:16 rats received no treatment. Group B: 27 rats received 18 subcutaneous injections weekly at a dose of 21 mg/kg wt of 1–2 dimethylhydrazine (DMH), from the eighth day after the intervention. Animals were sacrificed between 25–27 weeks. The number of tumours, their localization, size and microscopic characteristics were recorded. A paired chi-squared analysis was performed comparing tumoral induction in the perianastomotic zone with the rest of colon with faeces. Results No tumours appeared in the dimethylhydrazine-free group. The percentage tumoral area was greater in the perianastomotic zone compared to tumours which had developed in the rest of colon with faeces (p = 0.014). Conclusion We found a cocarcinogenic effect due to the creation of an anastomosis, when using an experimental model of colonic carcinogenesis induced by DMH in rats.

Evaluating the impact of summer vacation on the visual acuity of AMD patients treated with ranibizumab.

PurposeTo evaluate the impact of traditional French summer vacation on visual acuity and spectral domain-optical coherence tomography (SD-OCT) of Wet AMD patients being treated with intravitreal Ranibizumab.MethodsThis was a consecutive, comparative, single-centre, prospective analysis. All patients who were being treated with intravitreal injection of 0.5 mg ranibizumab at Cergy Pontoise Hospital, Department of Ophthalmology between July 2013 and September 2014 were included. Patients were divided into two groups: (A) patients who skipped one ranibizumab intravitreal injection during holidays, and (B) patients who received injection during their holidays. Evaluations occurred prior to traditional holiday (baseline) and 2 months later, consisting of BCVA using ETDRS, and a complete ophthalmic examination that included slit-lamp biomicroscopy, fundus examination, fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral domain-optical coherence tomography (SD-OCT). All patients were being treated with PRN anti-VEGF regimen and criteria for reinjection included a visual acuity loss >5 ETDRS letters and/or an increase of central retinal thickness, presence of subretinal fluid, intraretinal fluid, or pigment epithelium detachment. If reinjection criteria were not met, patients were advised to return in 4 weeks.ResultsThe mean visual acuity change was -0.071±0.149 (LogMAR) in group A and +0.003±0.178 in group B (P=0.041). At the second visit (2 months after preholidays visit), 61.8% of patients in group A had SRF and/or intraretinal cysts, and only 27.6% of patients in group B. There was a significant difference in the persistence of fluid between the two groups (P=0.007, χ(2)-test).ConclusionThis cases series demonstrated the detrimental impact of holidays on visual acuity in patients treated with ranibizumab for AMD, which, in spite of their treatment regimen, still leave in vacation. Therefore, it is important to convey the message of treatment adherence to patients, despite their need of holidays.

Generic utilities in chronic obstructive pulmonary disease patients stratified according to different staging systems.

Background To determine generic utilities for Spanish chronic obstructive pulmonary disease (COPD) patients stratified by different classifications: GOLD 2007, GOLD 2013, GesEPOC 2012 and BODEx index. Methods Multicentre, observational, cross-sectional study. Patients were aged ≥40 years, with spirometrically confirmed COPD. Utility values were derived from EQ-5D-3 L. Means, standard deviations (SD), medians and interquartile ranges (IQR) were computed based on the different classifications. Differences in median utilities between groups were assessed by non-parametric tests. Results 346 patients were included, of which 85.5% were male with a mean age of 67.9 (SD = 9.7) years and a mean duration of COPD of 7.6 (SD = 5.8) years; 80.3% were ex-smokers and the mean smoking history was 54.2 (SD = 33.2) pack-years. Median utilities (IQR) by GOLD 2007 were 0.87 (0.22) for moderate; 0.80 (0.26) for severe and 0.67 (0.42) for very-severe patients (p < 0.001 for all comparisons). Median utilities by GOLD 2013 were group A: 1.0 (0.09); group B: 0.87 (0.13); group C: 1.0 (0.16); group D: 0.74 (0.29); comparisons were statistically significant (p < 0.001) except A vs C. Median utilities by GesEPOC phenotypes were 0.84 (0.33) for non exacerbator; 0.80 (0.26) for COPD-asthma overlap; 0.71 (0.62) for exacerbator with emphysema; 0.72 (0.57) for exacerbator with chronic bronchitis (p < 0.001). Comparisons between patients with or without exacerbations and between patients with COPD-asthma overlap and exacerbator with chronic bronchitis were statistically-significant (p < 0.001). Median utilities by BODEx index were: group 02: 0.89 (0.20); group 34: 0.80 (0.27); group 56: 0.67 (0.29); group 79: 0.41 (0.31). All comparisons were significant (p < 0.001) except between groups 34 and 56. Conclusion Irrespective of the classification used utilities were associated to disease severity. Some clinical phenotypes were associated with worse utilities, probably related to a higher frequency of exacerbations. GOLD 2007 guidelines and BODEx index better discriminated patients with a worse health status than GOLD 2013 guidelines, while GOLD 2013 guidelines were better able to identify a smaller group of patients with the best health.

Neoadjuvant chemotherapy and extrapleural pneumonectomy (EPP) of malignant pleural mesothelioma (MPM) with or without hemithoracic radiotherapy: final results of the randomized multicenter phase II trial SAKK17/04.

Aim: We have previously documented the feasibility of neoadjuvant chemotherapy and EPP in a multicenter trial of MPM (Weder, Ann Oncol 18: 1196, 2007). The objectives of the trimodality trial SAKK17/04 (NCT00334594) were to evaluate the time to loco-regional relapse with or without high dose hemithoracic radiotherapy in a prospective multicenter randomized phase II trial in patients with R0 and R1 resection after neoadjuvant chemotherapy and EPP. Methods: Eligible patients had pathologically confirmed MPM, surgically resectable TNM stage (T1-3 N0-2 M0), PS0-1, ages 18-70 years. Part 1 had a phase II design, and included neoadjuvant chemotherapy with 3 cycles of cisplatin and pemetrexed, followed by restaging and EPP. The primary endpoint of part 1 was complete macroscopic resection (R0-1). Part 2 randomized consenting patients with R0-1 resection into two parallel phase II arms (control arm A and radiotherapy arm B). The primary endpoint for part 2 was loco-regional relapse-free survival (RFS). To detect a 1 year increase with 80% power and 10% alpha, 37 patients were needed for arm B. Secondary endpoints included operability, tolerability of chemotherapy and radiotherapy, survival, and translational research Results: Because accrual of part 2 was slower than planned, the trial was stopped in 2013. Overall, 153 patients entered the trial, of whom 125 underwent surgery and 99 had a complete macroscopic resection (primary endpoint part 1). Of the later patients, 54 could be randomized 1:1 into each arm. Reasons for non-randomization included patient refusal in 24 and ineligibility or protocol deviations in 21. Of the 27 patients randomized to hemithoracic radiotherapy, 25 completed the treatment as planned. For part 1 the median RFS was 8.8 (95%CI: 7.3-10.7) and median OS was 15.0 (95% CI: 12.1-19.3) months. For part 2 the median local RFS for group A was 7.6 (95%CI: 5.5-10.7) and for group B 9.4 (95%CI: 6.5-11.9) months (primary endpoint part 2), while the overall RFS and OS for group A were 5.7 (95%CI: 3.5-8.8) and 16.9 (95%CI: 10.7-23.6) months and for group B 7.6 (95% CI:5.2-10.6) and 14.9 (95%CI: 7.0-17.6) months. Conclusions: This study did not reach the primary endpoint which was defined as one-year increase in loco-regional relapse-free survival and thus does not support the routine use of hemithoracic RT after neoadjuvant chemotherapy and EPP. Disclosure: All authors have declared no conflicts of interest.

High expression levels of macrophage migration inhibitory factor sustain the innate immune responses of neonates.

The vulnerability to infection of newborns is associated with a limited ability to mount efficient immune responses. High concentrations of adenosine and prostaglandins in the fetal and neonatal circulation hamper the antimicrobial responses of newborn immune cells. However, the existence of mechanisms counterbalancing neonatal immunosuppression has not been investigated. Remarkably, circulating levels of macrophage migration inhibitory factor (MIF), a proinflammatory immunoregulatory cytokine expressed constitutively, were 10-fold higher in newborns than in children and adults. Newborn monocytes expressed high levels of MIF and released MIF upon stimulation with Escherichia coli and group B Streptococcus, the leading pathogens of early-onset neonatal sepsis. Inhibition of MIF activity or MIF expression reduced microbial product-induced phosphorylation of p38 and ERK1/2 mitogen-activated protein kinases and secretion of cytokines. Recombinant MIF used at newborn, but not adult, concentrations counterregulated adenosine and prostaglandin E2-mediated inhibition of ERK1/2 activation and TNF production in newborn monocytes exposed to E. coli. In agreement with the concept that once infection is established high levels of MIF are detrimental to the host, treatment with a small molecule inhibitor of MIF reduced systemic inflammatory response, bacterial proliferation, and mortality of septic newborn mice. Altogether, these data provide a mechanistic explanation for how newborns may cope with an immunosuppressive environment to maintain a certain threshold of innate defenses. However, the same defense mechanisms may be at the expense of the host in conditions of severe infection, suggesting that MIF could represent a potential attractive target for immune-modulating adjunctive therapies for neonatal sepsis.

Readjustment of abdominal computed tomography protocols in a university hospital: impact on radiation dose

AbstractObjective:To assess the reduction of estimated radiation dose in abdominal computed tomography following the implementation of new scan protocols on the basis of clinical suspicion and of adjusted images acquisition parameters.Materials and Methods:Retrospective and prospective review of reports on radiation dose from abdominal CT scans performed three months before (group A – 551 studies) and three months after (group B – 788 studies) implementation of new scan protocols proposed as a function of clinical indications. Also, the images acquisition parameters were adjusted to reduce the radiation dose at each scan phase. The groups were compared for mean number of acquisition phases, mean CTDIvol per phase, mean DLP per phase, and mean DLP per scan.Results:A significant reduction was observed for group B as regards all the analyzed aspects, as follows: 33.9%, 25.0%, 27.0% and 52.5%, respectively for number of acquisition phases, CTDIvol per phase, DLP per phase and DLP per scan (p < 0.001).Conclusion:The rational use of abdominal computed tomography scan phases based on the clinical suspicion in conjunction with the adjusted images acquisition parameters allows for a 50% reduction in the radiation dose from abdominal computed tomography scans.

Reduction in the use of diagnostic tests in infants with risk factors for early-onset neonatal sepsis does not delay antibiotic treatment

BACKGROUND: Despite a low positive predictive value, diagnostic tests such as complete blood count (CBC) and C-reactive protein (CRP) are commonly used to evaluate whether infants with risk factors for early-onset neonatal sepsis (EOS) should be treated with antibiotics. STUDY DESIGN: We investigated the impact of imple- menting a protocol aiming at reducing the number of dia- gnostic tests in infants with risk factors for EOS in order to compare the diagnostic performance of repeated clinical examination with CBC and CRP measurement. The primary outcome was the time between birth and the first dose of antibiotics in infants treated for suspected EOS. RESULTS: Among the 11,503 infants born at 35 weeks during the study period, 222 were treated with antibiotics for suspected EOS. The proportion of infants receiving an- tibiotics for suspected EOS was 2.1% and 1.7% before and after the change of protocol (p = 0.09). Reduction of dia- gnostic tests was associated with earlier antibiotic treat- ment in infants treated for suspected EOS (hazard ratio 1.58; 95% confidence interval [CI] 1.20-2.07; p <0.001), and in infants with neonatal infection (hazard ratio 2.20; 95% CI 1.19-4.06; p = 0.01). There was no difference in the duration of hospital stay nor in the proportion of infants requiring respiratory or cardiovascular support before and after the change of protocol. CONCLUSION: Reduction of diagnostic tests such as CBC and CRP does not delay initiation of antibiotic treat- ment in infants with suspected EOS. The importance of clinical examination in infants with risk factors for EOS should be emphasised.