The pressure exerted on the tracheal wall by two endotracheal tube cuffs: A prospective observational bench-top, clinical and radiological study

Background

Recent studies have questioned our previous understanding on the effect of nitrous oxide on muscle relaxants, since nitrous oxide has been shown to potentiate the action of bolus doses of mivacurium, rocuronium and vecuronium. This study was aimed to investigate the possible effect of nitrous oxide on the infusion requirements of cisatracurium.

Methods

70 ASA physical status I-III patients aged 18-75 years were enrolled in this randomized trial. The patients were undergoing elective surgery requiring general anesthesia with a duration of at least 90 minutes. Patients were randomized to receive propofol and remifentanil by target controlled infusion in combination with either a mixture of oxygen and nitrous oxide (Nitrous oxide/TIVA group) or oxygen in air (Air/TIVA group). A 0.1 mg/kg initial bolus of cisatracurium was administered before tracheal intubation, followed by a closed-loop computer controlled infusion of cisatracurium to produce and maintain a 90% neuromuscular block. Cumulative dose requirements of cisatracurium during the 90-min study period after bolus administration were measured and the asymptotic steady state rate of infusion to produce a constant 90% block was determined by applying nonlinear curve fitting to the data on the cumulative dose requirement during the study period.

Results

Controller performance, i.e. the ability of the controller to maintain neuromuscular block constant at the setpoint and patient characteristics were similar in both groups. The administration of nitrous oxide did not affect cisatracurium infusion requirements. The mean steady-state rates of infusion were 0.072 +/- 0.018 and 0.066 +/- 0.017 mg * kg-1 * h-1 in Air/TIVA and Nitrous oxide/TIVA groups, respectively.

Conclusions

Nitrous oxide does not affect the infusion requirements of cisatracurium.

Trial registration

ClinicalTrials.gov NCT01152905; European Clinical Trials Database at http://eudract.emea.eu.int/2006-006037-41.     

External jugular vein cutdown approach for chronic indwelling central venous access in cancer patients: A potentially useful alternative

Background

Survival in colorectal cancer may correlate with the degree of systemic inflammatory response to the tumour. Atrial fibrillation may be regarded as an inflammatory complication. We aimed to determine if atrial fibrillation is a prognostic factor in colorectal cancer.

Patients and methods

A prospective colorectal cancer patient database was cross-referenced with the hospital clinical-coding database to identify patients who had underwent colorectal cancer surgery and were in atrial fibrillation pre- or postoperatively.

Results

A total of 175 patients underwent surgery for colorectal cancer over a two-year period. Of these, 13 patients had atrial fibrillation pre- or postoperatively. Atrial fibrillation correlated with worse two-year survival (p = 0.04; log-rank test). However, in a Cox regression analysis, atrial fibrillation was not significantly associated with survival.

Conclusion

The presence or development of atrial fibrillation in patients undergoing surgery for colorectal cancer is associated with worse overall survival, however it was not found to be an independent factor in multivariate analysis.     

Taurolidine reduces the tumor stimulating cytokine interleukin-1beta in patients with resectable gastrointestinal cancer: a multicentre prospective randomized trial

Background

The effect of additional treatment strategies with antineoplastic agents on intraperitoneal tumor stimulating interleukin levels are unclear. Taurolidine and Povidone-iodine have been mainly used for abdominal lavage in Germany and Europe.

Methods

In the settings of a multicentre (three University Hospitals) prospective randomized controlled trial 120 patients were randomly allocated to receive either 0.5% taurolidine/2,500 IU heparin (TRD) or 0.25% povidone-iodine (control) intraperitoneally for resectable colorectal, gastric or pancreatic cancers. Due to the fact that IL-1beta (produced by macrophages) is preoperatively indifferent in various gastrointestinal cancer types our major outcome criterion was the perioperative (overall) level of IL-1beta in peritoneal fluid.

Results

Cytokine values were significantly lower after TRD lavage for IL-1beta, IL-6, and IL-10. Perioperative complications did not differ. The median follow-up was 50.0 months. The overall mortality rate (28 vs. 25, p = 0.36), the cancer-related death rate (17 vs. 19, p = .2), the local recurrence rate (7 vs. 12, p = .16), the distant metastasis rate (13 vs. 18, p = 0.2) as well as the time to relapse were not statistically significant different.

Conclusion

Reduced cytokine levels might explain a short term antitumorigenic intraperitoneal effect of TRD. But, this study analyzed different types of cancer. Therefore, we set up a multicentre randomized trial in patients undergoing curative colorectal cancer resection.

Trial registration

ISRCTN66478538     

Evaluation of safe and effective administration of nitrous oxide after a postgraduate training course

Background

Conscious sedation is used in dentistry to improve access and quality of care in patients who have difficulty coping with treatment. The aim of this prospective study was to describe a postgraduate training course in conscious sedation for dentists, with specific evaluation of the safe and effective administration of a 50% nitrous oxide in oxygen premix.

Methods

45 practitioners were trained between 2002 and 2004. They carried out 826 sessions of inhalation sedation in 662 patients. The clinical competency of this group was compared with an expert group.

Results

There was no difference between trainees and experts in ability to complete the planned dental treatment under sedation (89.6% vs 93.2%). Trainees were less successful than experts for patients with intellectual disability (87.4% vs 94.2%, p < 0.01). For both groups, the degree of cooperation improved between initial induction and each perioperative step (Wilcoxon test, p < 0.01). However, for trainees, Venham behaviour scores varied with the type of patient (Kruskal Wallis test, p < 0.001). No major adverse effects were recorded. Trainees reported more minor adverse effects than experts (13% vs. 5.3% respectively, Fisher exact test, p < 0.001)

Conclusion

The trainee practitioners provided effective and safe inhalation sedation. This challenges the current French restriction of the 50% nitrous oxide in oxygen premix to the hospital setting. Further emphasis is required on the teaching of behaviour management skills for patients with intellectual disability.     

Surgical outcomes for colon and rectal cancer over a decade: results from a consecutive monocentric experience in 902 unselected patients

Background

This study evaluates the surgical morbidity and long-term outcome of colorectal cancer surgery in an unselected group of patients treated over the period 1994–2003.

Methods

A consecutive series of 902 primary colorectal cancer patients (489 M, 413 F; mean age: 63 years ± 11 years, range: 24–88 years) was evaluated and prospectively followed in a university hospital (mean follow-up 36 ± 24 months; range: 3–108 months). Perioperative mortality, morbidity, overall survival, curative resection rates, recurrence rates were analysed.

Results

Of the total, 476 colorectal cancers were localized to the colon (CC, 53%), 406 to the rectum (RC, 45%), 12 (1%) were multicentric, and 8 were identified as part of HNPCC (1%). Combining all tumours, there were 186 cancers (20.6%) defined as UICC stage I, 235 (26.1%) stage II, 270 (29.9%) stage III and 187 (20.6%) stage IV cases. Twenty-four (2.7%) cases were of undetermined stage. Postoperative complications occurred in 38% of the total group (37.8% of CC cases, 37.2% of the RC group, 66.7% of the synchronous cancer patients and 50% of those with HNPCC, p = 0.19) Mortality rate was 0.8%, (1.3% for colon cancer, 0% for rectal cancer; p = 0.023). Multivisceral resection was performed in 14.3% of cases. Disease-free survival in cases resected for cure was 73% at 5-years and 72% at 8 years. The 5- and 8-year overall survival rates were 71% and 61% respectively (total cases). At 5-year analysis, overall survival rates are 97% for stage I disease, 87% for stage II, 73% for stage III and 22% for stage IV respectively (p < 0.0001). The 5-year overall survival rates showed a marked difference in R0, R1+R2 and non resected patients (82%, 35% and 0% respectively, p < 0.0001). On multivariate analysis, resection for cure and stage at presentation but not tumour site (colon vs. rectum) were independent variables for overall survival (p < 0.0001).

Conclusion

A prospective, uniform follow-up policy used in a single institution over the last decade provides evidence of quality assurance in colorectal cancer surgery with high rates of resection for cure where only stage at presentation functions as an independent variable for cancer-related outcome.     

Effects of nitrate concentration on the denitrification potential of a calcic cambisol and its fractions of N2, N2O and NO

Background and aims

The direct measurement of denitrification dynamics and its product fractions is important for parameterizing process-oriented model(s) for nitrogen cycling in various soils. The aims of this study are to a) directly measure the denitrification potential and the fractions of nitrogenous gases as products of the process in laboratory, b) investigate the effects of the nitrate (NO ₃ ^? ) concentration on emissions of denitrification gases, and c) test the hypothesis that denitrification can be a major pathway of nitrous oxide (N₂O) and nitric oxide (NO) production in calcic cambisols under conditions of simultaneously sufficient supplies of carbon and nitrogen substrates and anaerobiosis as to be found to occur commonly in agricultural lands.

Methods

Using the helium atmosphere (with or without oxygen) gas-flow-soil-core technique in laboratory, we directly measured the denitrification potential of a silt clay calcic cambisol and the production of nitrogen gas (N₂), N₂O and NO during denitrification under the conditions of seven levels of NO ₃ ^? concentrations (ranging from 10 to 250 mg N kg^?1 dry soil) and an almost constant initial dissolved organic carbon concentration (300 mg C kg^?1 dry soil).

Results

Almost all the soil NO ₃ ^? was consumed during anaerobic incubation, with 80–88 % of the consumed NO ₃ ^? recovered by measuring nitrogenous gases. The results showed that the increases in initial NO ₃ ^? concentrations significantly enhanced the denitrification potential and the emissions of N₂ and N₂O as products of this process. Despite the wide range of initial NO ₃ ^? concentrations, the ratios of N₂, N₂O and NO products to denitrification potential showed much narrower ranges of 51–78 % for N₂, 14–36 % for N₂O and 5–22 % for NO.

Conclusions

These results well support the above hypothesis and provide some parameters for simulating effects of variable soil NO ₃ ^? concentrations on denitrification process as needed for biogeochemical models.     

Reconsidering low-dose aspirin therapy for cardiovascular disease: a study protocol for physician and patient behavioral change

Background

Opinion leaders represent one way to disseminate new knowledge and influence the practice behaviors of physicians. This study explored the stability of opinion leaders over time, whether opinion leaders were polymorphic (i.e., influencing multiple practice areas) or monomorphic (i.e., influencing one practice area), and reach of opinion leaders in their local network.

Methods

We surveyed surgeons and pathologists in Ontario to identify opinion leaders for colorectal cancer in 2003 and 2005 and to identify opinion leaders for breast cancer in 2005. We explored whether opinion leaders for colorectal cancer identified in 2003 were re-identified in 2005. We examined whether opinion leaders were considered polymorphic (nominated in 2005 as opinion leaders for both colorectal and breast cancer) or monomorphic (nominated in 2005 for only one condition). Social-network mapping was used to identify the number of local colleagues identifying opinion leaders.

Results

Response rates for surgeons were 41% (2003) and 40% (2005); response rates for pathologists were 42% (2003) and 37% (2005). Four (25%) of the surgical opinion leaders identified in 2003 for colorectal cancer were re-identified in 2005. No pathology opinion leaders for colorectal cancer were identified in both 2003 and 2005. Only 29% of surgical opinion leaders and 17% of pathology opinion leaders identified in the 2005 survey were considered influential for both colorectal cancer and breast cancer. Social-network mapping revealed that only a limited number of general surgeons (12%) or pathologists (7%) were connected to the social networks of identified opinion leaders.

Conclusions

Opinion leaders identified in this study were not stable over a two-year time period and generally appear to be monomorphic, with clearly demarcated areas of expertise and limited spheres of influence. These findings may limit the practicability of routinely using opinion leaders to influence practice.     

Colovaginal anastomosis: an unusual complication of stapler use in restorative procedure after Hartmann operation

Background

To support decisions about surgical treatment of elderly patients with cancer, population-based estimates of postoperative mortality (POM) rates are required.

Methods

Electronic records from the Rotterdam Cancer Registry were retrieved for octogenarians and nonagenarians who underwent resection in the period 1987–2000. POM was defined as death within 30 days of resection and both elective and emergency operations were included.

Results

In a series of 5.390 operated patients aged 80 years and older, POM rates were 0.5% for breast cancer, 1.7% for endometrial cancer and 4.2% for renal cancer. For patients with colorectal cancer, POM increased from 8% for the age group 80–84 to 13% for those 85–89 to 20% in nonagenarians. For stomach cancer, the respective figures were 11%, 20% and 44%.

Conclusion

These results show that resections can be performed at acceptable risk in selected elderly patients with cancer.     

Constitutive basal and stimulated human small bowel contractility is enhanced in obesity

Background

Between 5 and 10% of the patients undergoing a colonoscopy cannot have a complete procedure mainly due to stenosing neoplastic lesion of rectum or distal colon. Nevertheless the elective surgical treatment concerning the stenosis is to be performed after the pre-operative assessment of the colonic segments upstream the cancer. The aim of this study is to illustrate our experience with the Computed Tomographic Colonography (CTC) for the pre-operative assessment of the entire colon in the patients with stenosing colorectal cancers.

Methods

From January 2005 till March 2009, we observed and treated surgically 43 patients with stenosing colorectal neoplastic lesions. All patients did not tolerate the pre-operative colonoscopy. For this reason they underwent a pre-operative CTC in order to have a complete assessment of the entire colon. All patients underwent a follow-up colonoscopy 3 months after the surgical treatment. The CTC results were compared with both macroscopic examination of the specimen and the follow-up coloscopy.

Results

The pre-operative CTC showed four synchronous lesions in four patients (9.3% of the cases). The macroscopic examination of the specimen revealed three small sessile polyps (3 - 4 mm in diameter) missed in the pre-operative assessment near the stenosing colorectal cancer. The follow-up colonoscopy showed four additional sessile polyps with a diameter between 3 - 11 mm in three patients. Our experience shows that CTC has a sensitivity of 83,7%.

Conclusion

In patients with stenosing colonic lesions, CTC allows to assess the entire colon pre-operatively avoiding the need of an intraoperative colonoscopy. More synchronous lesions are detected and treated at the time of the elective surgery for the stenosing cancer avoiding further surgery later on.     

Statin consumption as a risk factor for developing colorectal cancer: a retrospective case study

Background

Statins are the backbone of lipid-lowering therapy and are among the most commonly prescribed drugs in the elderly population in Sweden today. Colorectal cancer is the second most common cancer in men and women, after prostate and breast cancer, respectively, with a median age of 72 years at diagnosis. Statins induce mitochondrial damage leading to accumulation of reactive oxygen species in the cell. Reactive oxygen species can cause mutations in mitochondrial as well as nuclear DNA leading to the development of cancer. Our hypothesis was that statins increase the risk for colorectal cancer.

Methods

A case study was performed on consecutive cases of colorectal cancer diagnosed at Norrlands University Hospital (NUS) in Umeå between 2012 and 2015 (n?=?325). Patients diagnosed with diabetes mellitus type II (DM II n?=?65) were excluded in the primary endpoint analysis (occurrence of colorectal cancer). As control, three databases were used to create an age-matched population in order to calculate the proportion of inhabitants using statins in the county of Västerbotten, Sweden. A secondary endpoint was cancer-specific survival among our study group of colorectal cancer patients, including those with DM II, investigating whether there was a difference if the patient was a ‘recent’ statin user or not at the time of diagnosis.

Results

Statin use at the time of colorectal cancer diagnosis in the study group was 23.8%. The corresponding figure in an age-matched population in Västerbotten was 24.6%. Using a one-proportional one-sided z test, there was no significant difference between these (23.8%, 95% CI 18.6–29.0%, p?=?0.601). When comparing groups 20–64 years of age, the difference was greater with recent statin use in 17.8% in the study population and 11.9% in Västerbotten (17.8%, 95% CI 9.0–26.6%, p?=?0.059). When considering cancer-specific survival, no significant difference in survival was seen when comparing ‘former/never’ statin users as reference category with ‘recent’ users diagnosed with colorectal cancer (HR 1.39, 95% CI 0.89–2.16).

Conclusions

No significant increase in risk for developing colorectal cancer among patients (type II diabetics excluded) medicated with statins was found. We found no correlation between ‘recent’ statin use at the time of diagnosis and cancer-specific survival.

     

The influence of different anticoagulants and sample preparation methods on measurement of mCD14 on bovine monocytes and polymorphonuclear neutrophil leukocytes

Background

Brief tobacco intervention has been used in promoting smoking cessation and preventing the initiation of smoking. We used a cohort born in 1979 (n = 2 586) from four cities in Finland. Those born on odd days received up to four brief tobacco interventions during their annual school dental check-ups in 1992-1994 (at the age of 13-15). Those who were born on even days were used as a control group. In 2008 a follow-up questionnaire was sent to the cohort. The aim of this study was to ascertain the long-term effectiveness of brief tobacco intervention given in dental health care during school age.

Findings

Responses were received from 529 people in the intervention group and 491 in the control group. In the intervention group and control group by the age of 29 there were 15.3% and 18.5% smokers respectively. This difference was not statistically significant. The difference between groups was similar to that observed when they were 14 years old.

Conclusions

Brief tobacco intervention performed in dental health care in adolescence did not show effectiveness in the long-term follow-up. This type of intervention alone is insufficient to prevent smoking but supports other anti-smoking activities.

Trial Registration

This study was registered at http://clinicaltrials.gov (NCT01348646).     

Estimating the impact of changing fertilizer application rate, land use, and climate on nitrous oxide emissions in Irish grasslands

Aim

This study examines the impact of changing nitrogen (N) fertilizer application rates, land use and climate on N fertilizer-derived direct nitrous oxide (N₂O) emissions in Irish grasslands.

Methods

A set of N fertilizer application rates, land use and climate change scenarios were developed for the baseline year 2000 and then for the years 2020 and 2050. Direct N₂O emissions under the different scenarios were estimated using three different types of emission factors and a newly developed Irish grassland N₂O emissions empirical model.

Results

There were large differences in the predicted N₂O emissions between the methodologies, however, all methods predicted that the overall N₂O emissions from Irish grasslands would decrease by 2050 (by 40–60 %) relative to the year 2000. Reduced N fertilizer application rate and land-use changes resulted in decreases of 19–34 % and 11–60 % in N₂O emission respectively, while climate change led to an increase of 5–80 % in N₂O emission by 2050.

Conclusions

It was observed in the study that a reduction in N fertilizer and a reduction in the land used for agriculture could mitigate emissions of N₂O, however, future changes in climate may be responsible for increases in emissions causing the positive feedback of climate on emissions of N₂O.      

Chromothripsis is a common mechanism driving genomic rearrangements in primary and metastatic colorectal cancer

Background

Structural rearrangements form a major class of somatic variation in cancer genomes. Local chromosome shattering, termed chromothripsis, is a mechanism proposed to be the cause of clustered chromosomal rearrangements and was recently described to occur in a small percentage of tumors. The significance of these clusters for tumor development or metastatic spread is largely unclear.

Results

We used genome-wide long mate-pair sequencing and SNP array profiling to reveal that chromothripsis is a widespread phenomenon in primary colorectal cancer and metastases. We find large and small chromothripsis events in nearly every colorectal tumor sample and show that several breakpoints of chromothripsis clusters and isolated rearrangements affect cancer genes, including NOTCH2, EXO1 and MLL3. We complemented the structural variation studies by sequencing the coding regions of a cancer exome in all colorectal tumor samples and found somatic mutations in 24 genes, including APC, KRAS, SMAD4 and PIK3CA. A pairwise comparison of somatic variations in primary and metastatic samples indicated that many chromothripsis clusters, isolated rearrangements and point mutations are exclusively present in either the primary tumor or the metastasis and may affect cancer genes in a lesion-specific manner.

Conclusions

We conclude that chromothripsis is a prevalent mechanism driving structural rearrangements in colorectal cancer and show that a complex interplay between point mutations, simple copy number changes and chromothripsis events drive colorectal tumor development and metastasis.     

Les prothèses gonflables dans le traitement de l'impuissance: résultats de 80 implantations

Objective

The goal of this study is the evaluation of the functionnal results and the complications of this type of surgery. Such questions have been poorly discussed in the literature.

Methods

We report our experience on 80 inflatable prostheses that were implanted between october 1987 and october 1994. The mean follow-up is 3 years and the assessment of the objective (mechanical functioning of the prosthesis and complications) and sujective results (sexuality of the patients) is carried out on 68 patients.

Results

The results are the following:

? 54.5% of functioning disturbances,

? 7% of infections,

? 27.5% of prosthesis removals.

Most of the patients considered they were satisfied although only 65% returned to a regular sexual activity.     

Osteopathic manipulative treatment and its relationship to autonomic nervous system activity as demonstrated by heart rate variability: a repeated measures study

Background

Osteopathic manipulative treatment (OMT) and ultrasound physical therapy (UPT) are commonly used for chronic low back pain. Although there is evidence from a systematic review and meta-analysis that OMT generally reduces low back pain, there are no large clinical trials that specifically assess OMT efficacy in chronic low back pain. Similarly, there is a lack of evidence involving UPT for chronic low back pain.

Methods

The OSTEOPAThic Health outcomes In Chronic low back pain (OSTEOPATHIC) Trial is a Phase III randomized controlled trial that seeks to study 488 subjects between August 2006 and June 2010. It uses a 2 × 2 factorial design to independently assess the efficacy of OMT and UPT for chronic low back pain. The primary outcome is a visual analogue scale score for pain. Secondary outcomes include back-specific functioning, generic health, work disability, and satisfaction with back care.

Conclusion

This randomized controlled trial will potentially be the largest involving OMT. It will provide long awaited data on the efficacy of OMT and UPT for chronic low back pain.

Trial registration

http://www.clinicaltrials.gov, NCT00315120     

Anti-tumor activity of a novel monoclonal antibody, NPC-1C, optimized for recognition of tumor antigen MUC5AC variant in preclinical models

Purpose

NPC-1C is a chimeric immunoglobulin IgG1 developed from antigen tested in the Hollinshead tumor vaccine trials that recognizes an immunogenic MUC5AC-related tumor-associated antigen. In this article, we describe the pre-clinical characterization of this antibody that is currently being tested in human clinical trials.

Experimental design

The specificity of NPC-1C for pancreatic and colorectal cancer cell lines was tested by flow cytometry assays and immunohistochemical staining. Antibody-dependent cell cytotoxicity was measured using a tumor cell line lysis assay. Anti-tumor efficacy and biodistribution were assessed in nude mice bearing human pancreatic tumor xenografts.

Results

Human tumor cell binding measured by flow cytometry ranged from 52 to 94 % of cells stained positive with NPC-1C in three colorectal and one pancreatic cell lines, while IHC demonstrated staining of 43 % of colon cancers and 48 % of pancreatic cancer tissues, with little or no cross-reactivity of NPC-1C with normal colon or pancreas tissues. In vitro NPC-1C-mediated tumor cell killing occurred in a median of 44.5 % of four colorectal and three pancreatic tumor cell lines. In vivo anti-tumor efficacy in a human pancreatic CFPAC-1 tumor xenograft model was demonstrated with a twofold to threefold reduction in tumor growth in the NPC-1C-treated mice compared to saline and human IgG controls. Pharmacodynamic studies indicate NPC-1C localizes in antigen-positive tumors and has minimal uptake in normal mouse tissues.

Conclusions

NPC-1C, a chimeric monoclonal antibody that reacts with a MUC5AC-related antigen expressed by pancreatic and colorectal tumor tissues, has promising preclinical activity in pancreatic and colorectal adenocarcinoma.     

High CEA levels in a case of resected colorectal cancer: delayed diagnosis of metachronous medullary thyroid cancer

Background

Carcinoembryonic antigen (CEA) is one of the most widely used tumor markers, and its value in the surveillance of post-operative colorectal cancer is well established. Fluorodeoxyglucose-positron emission tomography (FDG-PET) has been clinically used in colorectal cancer imaging including preoperative staging, evaluation of therapeutic response, detection of disease recurrence, and investigation of unexplained rising tumor markers.

Case presentation

We report a case of resected colorectal cancer presented with rising CEA levels in 5 years, and FDG-PET revealed no definitive evidence of recurrence except abnormal focal FDG uptake in the right thyroid lobe. However, fine needle aspiration cytology (FNAC) of the thyroid nodule showed negative for malignancy. Progressively rising CEA levels were noted over the following 5 years, but serial follow-up examinations did not find evidence of recurrence. Fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT) was performed subsequently and again showed focal FDG uptake in the right thyroid lobe. This time, FNAC revealed positive for malignancy, in favor of medullary thyroid carcinoma (MTC). The patient underwent total thyroidectomy and modified radical neck dissection, and MTC with cervical nodal metastasis (pT3N1) was diagnosed. He had cervical lymph nodes recurrence 2 years later, which was resected.

Conclusions

This case reminded us that FDG-PET/CT may detect occult tumors resulting in CEA elevation other than colorectal cancer. Moreover, FNA has a higher false negative rate in detecting MTC than other forms of thyroid cancer. Repeat FNAC for the initial negative cytology result and measure of serum calcitonin for the early MTC detection could be more helpful to avoid the delay in MTC diagnosis.

     

A benefit-finding intervention for family caregivers of persons with Alzheimer disease: study protocol of a randomized controlled trial

Background

Patients with ST-elevation myocardial infarction (STEMI) not treated with primary or rescue percutaneous coronary intervention (PCI) are at risk for recurrent ischemia, especially when viability in the infarct-area is present. Therefore, an invasive strategy with PCI of the infarct-related coronary artery in patients with viability would reduce the occurrence of a composite end point of death, reinfarction, or unstable angina (UA).

Methods

Patients admitted with an (sub)acute myocardial infarction, who were not treated by primary or rescue PCI, and who were stable during the first 48 hours after the acute event, were screened for the study. Eventually, we randomly assigned 216 patients with viability (demonstrated with low-dose dobutamine echocardiography) to an invasive or a conservative strategy. In the invasive strategy stenting of the infarct-related coronary artery was intended with abciximab as adjunct treatment. Seventy-five (75) patients without viability served as registry group. The primary endpoint was the composite of death from any cause, recurrent myocardial infarction (MI) and unstable angina at one year. As secondary endpoint the need for (repeat) revascularization procedures and anginal status were recorded.

Results

The primary combined endpoint of death, recurrent MI and unstable angina was 7.5% (8/106) in the invasive group and 17.3% (19/110) in the conservative group (Hazard ratio 0.42; 95% confidence interval [CI] 0.18-0.96; p = 0.032). During follow up revascularization-procedures were performed in 6.6% (7/106) in the invasive group and 31.8% (35/110) in the conservative group (Hazard ratio 0.18; 95% CI 0.13-0.43; p < 0.0001). A low rate of recurrent ischemia was found in the non-viable group (5.4%) in comparison to the viable-conservative group (14.5%). (Hazard-ratio 0.35; 95% CI 0.17-1.00; p = 0.051).

Conclusion

We demonstrated that after acute MI (treated with thrombolysis or without reperfusion therapy) patients with viability in the infarct-area benefit from a strategy of early in-hospital stenting of the infarct-related coronary artery. This treatment results in a long-term uneventful clinical course. The study confirmed the low risk of recurrent ischemia in patients without viability.

Trial registration

ClinicalTrials.gov: NCT00149591.     

Proteomic profiling of urine for the detection of colon cancer

Background

Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome (<15 kDa). There have been several reports that colorectal cancer is associated with changes in the serum proteome that are detectable by SELDI and we hypothesised that proteomic changes would also be detectable in urine.

Results

We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20) or ELISA (β2-microglobulin).

Conclusion

Changes in the urine proteome may aid in the early detection of colorectal cancer.