The effect of selective decontamination on the intestinal microbiota as measured with IS-pro: a taxonomic classification tool applicable for direct evaluation of intestinal microbiota in clinical routine.

Selective decontamination of the digestive tract (SDD) is aimed at elimination of potential pathogenic microorganisms. In this study, the effect of SDD on gut microbiota was evaluated in a large homogenous group of elective colorectal cancer surgery patients. Rectal swabs were taken from 118 patients undergoing colorectal surgery. These patients were randomly assigned to receive perioperative SDD or to the control group (no SDD). Rectal swabs were taken prior to surgery, 3 days after commencing administration of SDD. Gut microbial profiles were obtained with the IS-pro technique, a standardized microbiota profiling assay applicable in clinical routine. Differences in abundance for different taxonomical groups and diversity between the groups were assessed. Unsupervised and supervised classification techniques were used to assess microbial signatures, differentiating between the SDD group and the control group. Patients in the SDD group had different gut microbial signatures than in the control group, also in phyla that are not a target for SDD. Escherichia coli, Sutterella spp., Faecalibacterium prausnitzii, and Streptococcus spp. were the species that differed the most between the two groups. The SDD group showed clustering into two subgroups. In one subgroup, a decrease in Proteobacteria was observed, whereas the other subgroup showed a shift in Proteobacteria species. This study shows that SDD not only decreases colonization of the gastrointestinal tract with potential pathogenic Gram-negative microorganisms, but also reduces the abundance of normal colonizers of our gastrointestinal system and leads to a shift in total microbiota composition.

Randomized clinical trial of selective decontamination of the digestive tract in elective colorectal cancer surgery (SELECT trial).

BACKGROUND: Infectious complications and anastomotic leakage affect approximately 30 per cent of patients after colorectal cancer surgery. The aim of this multicentre randomized trial was to investigate whether selective decontamination of the digestive tract (SDD) reduces these complications of elective colorectal cancer surgery. METHODS: The effectiveness of SDD was evaluated in a multicentre, open-label RCT in six centres in the Netherlands. Patients with colorectal cancer scheduled for elective curative surgery with a primary anastomosis were eligible. Oral colistin, tobramycin and amphotericin B were administered to patients in the SDD group to decontaminate the digestive tract. Both treatment and control group received intravenous cefazolin and metronidazole for perioperative prophylaxis. Mechanical bowel preparation was given for left-sided colectomies, sigmoid and anterior resections. Anastomotic leakage was the primary outcome; infectious complications and mortality were secondary outcomes. RESULTS: The outcomes for 228 patients randomized to the SDD group and 227 randomized to the control group were analysed. The trial was stopped after interim analysis demonstrated that superiority was no longer attainable. Effective SDD was confirmed by interspace DNA profiling analysis of rectal swabs. Anastomotic leakage was observed in 14 patients (6·1 per cent) in the SDD group and in 22 patients (9·7 per cent) in the control group (odds ratio (OR) 0·61, 95 per cent c.i. 0·30 to 1·22). Fewer patients in the SDD group had one or more infectious complications than patients in the control group (14·9 versus 26·9 per cent respectively; OR 0·48, 0·30 to 0·76). Multivariable analysis indicated that SDD reduced the rate of infectious complications (OR 0·47, 0·29 to 0·76). CONCLUSION: SDD reduces infectious complications after colorectal cancer resection but did not significantly reduce anastomotic leakage in this trial. Registration number: NCT01740947 ( https://www.clinicaltrials.gov).

The insulin-like growth factor type-2 receptor gene is imprinted in the mouse but not in humans.

In mouse, four genes have been found to undergo genomic imprinting resulting in differential expression of maternally and paternally inherited alleles. To determine whether the cognate genes are also subject to imprinting in humans, we have studied allele-specific expression patterns of insulin-like growth factor 2, IGF2-receptor and H19 in human fetal and adult tissues. In keeping with previous findings in mice, our results indicate that in human fetal tissues the paternal H19 alleles is inactive. IGF2 is monoallelically expressed in various tissues but surprisingly not in adult human liver. The human IGF2R gene, another classic example of imprinting in mice, was found to be expressed from both alleles. We provide the first direct evidence for differential imprinting in the human and murine genome.

Thoracoabdominal aortic aneurysm repair: results of conventional open surgery.

OBJECTIVES: The aim of this study is to report our experience in the surgical repair of thoracoabdominal aortic aneurysms (TAAAs) over the last 27 years against the background of evolving surgical techniques. METHODS: We reviewed the prospectively collected data of 571 patients who underwent open TAAA repair between 1981 and 2008. Data were analysed using univariate and multivariate analysis (logistic regression). Pre-, intra- and postoperative risk factors were used to develop risk models for in-hospital mortality, spinal cord deficit and renal failure. Recent published series were used to highlight the different treatment modalities and explore results. RESULTS: Seventy patients (12.3%) died in the hospital, the 30-day mortality was 8.9%, 37 patients (6.5%) required postoperative dialysis and 47 patients (8.3%) developed paraplegia or paraparesis. The incidence of paraplegia in the left heart bypass group was 4.4%. The predictors for hospital mortality were increasing age (odds ratio 1.096 per year, 95% confidence interval (CI): 1.05-1.14) and the need for haemodialysis (odds ratio 10, 95% CI: 4.7-21.1). For postoperative spinal cord deficit, we found three protecting factors: age above 75 years (odds ratio 0.14, 95% CI: 0.19-1.09), the presence of a post-dissection aneurysm (odds ratio 0.4, 95% CI: 0.17-0.94) and the combined use of cerebrospinal fluid drainage and motor-evoked potentials (odds ratio 0.28, 95% CI: 0.14-0.56). The urgency of procedure (odds ratio 4, 95% CI: 1.8-9) and preoperative serum creatinine level (odds ratio 1.007 per micromole per litre, 95% CI: 1.0-1.01) were significant risk factors for renal failure. CONCLUSIONS: Open TAAA repair intrinsically has substantial complications, of which spinal cord ischaemia and renal failure are the most devastating, despite major progress in our understanding of the pathophysiology and operative strategy. An overview of the results of recently published series is given along with an analysis of our data.

Revascularization strategy in patients with severe concurrent severe carotid and coronary artery disease: ''failure to move forward is reason to regress''.

In the absence of randomized trials, the optimal management of patients with concomitant carotid and coronary artery disease remains disputable. The initial studies of combined or staged carotid endarterectomy in these patients were conceived in an attempt to reduce perioperative mortality. Although encouraging results have been reported with combined carotid endarterectomy and cardiac surgery, this combination requires long operative times and remains a surgical challenge. Recent studies have shown that carotid angioplasty and stenting prior to cardiac surgery is a feasible and effective minimal invasive technique. However, the effect of carotid stenting on the incidence of death and stroke after cardiac surgery is indistinct. Carotid stenting followed by cardiac surgery may provide a valuable treatment for patients with combined carotid and cardiac disease. The high rate of freedom from death and stroke during follow-up supports the long-term durability of this strategy. In the present review, we highlight the available data on carotid stenting and cardiac surgery.

How should we manage type B aortic dissections?

Dissection of the descending aorta is a serious and potentially lethal event. Treatment options consist of medical therapy, open surgical replacement of the affected aorta and thoracic endovascular repair. In acute cases, medical treatment is started initially. When complicated, endovascular repair is generally considered as first choice treatment, except for connective tissue disorders where open surgery remains the standard. In stable, uncomplicated patients with risk factors for future aortic growth pre-emptive endovascular repair should be considered in the sub-acute phase of the dissection. The treatment strategy in chronic dissections is somewhat debated. Long-term results and aortic remodeling of endovascular repair are disappointing and open surgery remains the standard.

Will carotid angioplasty become the preferred alternative to staged or synchronous carotid endarterectomy in patients undergoing cardiac surgery?

In the absence of randomized trials, the optimal management of patients who present with concomitant carotid and coronary artery disease remains an enduring controversy, with much of the debate revolving around whether staged or synchronous carotid endarterectomy (CEA) will reduce peri-operative morbidity and mortality after cardiac surgery. Although encouraging results have been reported using either strategy, there remains no consensus as to which is preferable. More recently, however, carotid artery angioplasty with stenting (CAS) has emerged as a potential alternative to CEA. In 'high-risk for CEA' patients, CAS has shown comparable short and long-term outcome rates to CEA. Accordingly, CAS followed by cardiac surgery could offer a less invasive (and safer) therapeutic option in cardiac patients. This paper reviews the evidence to date supporting the use of CAS+CABG, while highlighting potential situations where such a strategy might be harmful. In particular, it will focus on how the need for dual antiplatelet therapy after CAS can be balanced with avoiding unnecessary bleeding complications after cardiac surgery.

Ascending-descending aortic bypass for the treatment of concomitant severe co-arctation, aortic valve disease and hypoplastic aortic arch.

This report describes a one-stage treatment of a 30-year-old patient suffering from severe aortic valve insufficiency, aortic co-arctation, dilatation of the ascending aorta and arcus hypoplasia. The patient underwent aortic valve, ascending aorta and arch replacement through median sternotomy. The aorta was ligated at the level of the co-arctation, which was located in the proximal part of the descending aorta, and an ascending-descending bypass was created using a transhiatic approach. The postoperative course was complicated by a cerebrovascular accident.

[Incidence of incontinence after radical prostatectomy using claims-based data]. / Hoe vaak incontinentie na radicale prostatectomie?

OBJECTIVE: To determine the effect of radical prostatectomy (RP) hospital volume on the probability of post-RP incontinence. DESIGN: Retrospective research based on claims-based data of health insurers. METHOD: For every patient with RP the probability of incontinence was determined, based on the definition of claims of one or more incontinence pads per day. Casemix corrections were made based on indicators available in claims-data: age, lymph node dissection, and radiotherapy. No casemix corrections could be made for tumour stage and surgical technique. RESULTS: A total of 1590 patients were included in this study; for 26.0% of these patients, an average of one or more incontinence pads per day were claimed for. A significant relation between the volume of RP per hospital and the claims of incontinence material was observed. The probability of incontinence was significantly lower in hospitals with a volume of more than 100 RP patients per year when compared to hospitals with less than 100 RP patients per year. CONCLUSION: The probability of post-RP incontinence decreases as hospitals conduct more RP procedures. The casemix factors included in the analysis only had a limited impact on this observation.

Molecular mechanisms underlying the MiT translocation subgroup of renal cell carcinomas.

Renal cell carcinomas (RCCs) represent a heterogeneous group of neoplasms, which differ in histological, pathologic and clinical characteristics. The tumors originate from different locations within the nephron and are accompanied by different recurrent (cyto)genetic anomalies. Recently, a novel subgroup of RCCs has been defined, i.e., the MiT translocation subgroup of RCCs. These tumors originate from the proximal tubule of the nephron, exhibit pleomorphic histological features including clear cell morphologies and papillary structures, and are found predominantly in children and young adults. In addition, these tumors are characterized by the occurrence of recurrent chromosomal translocations, which result in disruption and fusion of either the TFE3 or TFEB genes, both members of the MiT family of basic helix-loop-helix/leucine-zipper transcription factor genes. Hence the name MiT translocation subgroup of RCCs. In this review several features of this RCC subgroup will be discussed, including the molecular mechanisms that may underlie their development.

Glutamatergic stimulation of the basal forebrain elevates extracellular adenosine and increases the subsequent sleep.

A prolonged period of waking accumulates sleep pressure, increasing both the duration and the intensity of the subsequent sleep period. Delta power, which is calculated from the slow range electroencephalographic (EEG) oscillations (0.1-4 Hz), is regarded as the marker of sleep intensity. Recent findings indicate that not only the duration but also the quality of waking, determines the level of increase in the delta activity during the subsequent sleep period. Elevated levels of extracellular adenosine in the basal forebrain (BF) during prolonged waking have been proposed to act as the molecular signal of increased sleep pressure, but the role of BF neuronal activity in elevating adenosine has not been previously explored. We hypothesized that an increase in neuronal discharge in the BF would lead to increase in the extracellular adenosine and contribute to the increase in the subsequent sleep. To experimentally increase neuronal activity in the rat BF, we used 3 h in vivo microdialysis application of glutamate or its receptor agonists N-methyl-D-aspartate (NMDA) or AMPA. Samples for adenosine measurement were collected during the drug application and the EEG was recorded during and after the treatment, altogether for 24 h. All treatments increased the duration of the subsequent sleep following the application. In contrast, delta power was elevated only if both the waking EEG theta (5-9 Hz) power (which can be regarded as a marker of active waking) and the extracellular adenosine in the BF were increased during the application. These results indicate that increased neuronal activity in the BF, and particularly the type of neuronal activity coinciding with active waking, is one of the factors contributing to the buildup of the sleep pressure.

[Diagnostic image (307). A man with dysphagia]. / Diagnose in beeld (307). Een man met dysfagie.

A 51-year-old man suffered from longstanding dysphagia due to a large aneurysm of the thoracoabdominal aorta.

[Trachea compression due to a Kommerell diverticulum in a patient with a right-sided aorta]. / Tracheacompressie door divertikel van Kommerell bij een rechtszijdige aorta.

A 64-year-old man who was evaluated for a long history of a discontinuous barking cough with difficulty in coughing up sputum was found to have 90% stenosis of the trachea. Further imaging studies revealed a right-sided descending aorta with an aberrant left subclavian artery arising from a Kommerell diverticulum. This caused the compression of the trachea. The compression was relieved by transposition of the aberrant left subclavian artery to the ascending aorta and replacement of the aneurysmatic part of the aorta by an endoprosthesis.

Progressive disseminated histoplasmosis mimicking a flare of systemic lupus erythematosus: a European case report.

INTRODUCTION: Diagnosing progressive disseminated histoplasmosis (PDH) in patients with systemic lupus erythematosus (SLE) is diagnostically challenging. Since PDH is lethal when untreated, awareness of this infection in patients with SLE is of utmost importance. To the best of our knowledge, this is the first description of a case of PDH in a patient with SLE in Europe. CASE PRESENTATION: A 56-year-old woman of Surinamese descent with a history of SLE, presented with fever and polyarthritis. Although a flare of SLE was suspected initially, cultures of bone marrow and broncho-alveolar lavage fluid grew Histoplasma capsulatum. CONCLUSION: This case report highlights that physicians should be aware of progressive disseminated histoplasmosis in patients with SLE treated with immunosuppressive agents. The signs and symptoms can easily mimic a SLE flare, which would then be treated with more aggressive immunosuppression. Failure to recognize the infection will therefore invariably lead to death of the patient. Progressive disseminated histoplasmosis is usually not recognized by doctors in non-endemic areas such as Europe. However, globalisation and more frequent intercontinental traffic of immunocompromised patients currently increases the incidence of histoplasmosis in these areas. It is therefore of life-saving importance that doctors are aware of the features of the infection in areas where H. capsulatum is not endemic.

Surgical treatment of thoracoabdominal aortic aneurysms by simple crossclamping. Risk factors and late results.

Between 1981 and 1987, 88 consecutive patients were operated on for a thoracoabdominal aortic aneurysm by simple crossclamping and a graft inclusion technique (without shunts or heparin). This article presents an analysis of the operative outcome and long-term follow-up. Patient- and operation-related variables are age (mean 64.3 years, range 28 to 82 years), sex (82% men), rupture (20.5%), diabetes (2.3%), renal insufficiency (34.1%), chronic obstructive pulmonary disease (27.3%), previous aortic operation (31.8%), arterial hypertension (66%), postdissection (18.2%) versus degenerative (80.7%) origin, preoperative shock (11.4%), ischemic cerebrovascular (12.5%) or ischemic heart (17%) disease, peripheral vascular disease (14.8%), renal (mean 48 minutes, range 0 to 83 minutes) and lower spinal cord (mean 21 minutes, range 0 to 68 minutes) ischemic time, number of reattached intercostals, blood loss, and extent of the aneurysm (Crawford classification: type I, 16 patients [18.2%]; type II, 21 patients [23.8%]; type III, 29 patients [33%]; and type IV, 22 patients [25%]. Intraoperative mortality is 1.1% (n = 1). Thirty-day mortality is 5.9% (n = 5). Hospital mortality is 11.4% (n = 10): 7% for elective cases and 28% for ruptured aneurysms (p = 0.014). The survival at 2 years is 78% +/- (4.4%) and at 5 years 54% +/- (5.3%). Postoperative spinal cord injury occurred in 12 patients (13.8%) (5 had paraplegia and 7 had paraparesis) and postoperative renal dysfunction necessitating dialysis in 12 patients (14.1%). Risk stratification for hospital death, late death, renal failure, and spinal cord dysfunction was performed by means of multivariate logistic regression and Cox proportional hazard regression as appropriate. The best fitting model to predict hospital death includes preoperative shock (p = 0.02), female sex (p = 0.06), preoperative elevated serum creatinine level (p = 0.06), and preoperative myocardial infarction (p = 0.08). Variables predictive for late death are postoperative dialysis (p = 0.002), age (p = 0.008), and rupture (p = 0.04). The risk factors of postoperative dialysis are age (p = 0.003) and preoperative serum creatinine level (p = 0.04). The risk of postoperative spinal cord dysfunction increases with longer lower spinal cord ischemic time (p = 0.02) and with the presence of preoperative shock (p = 0.06).

Reoperations on the ascending aorta and aortic root: pitfalls and results in 134 patients.

BACKGROUND: This analysis was performed to evaluate the results of reoperations on the ascending aorta and aortic root. METHODS: All reoperations (n = 134) on the aortic root and ascending aorta performed between February 1981 and April 1998 were retrospectively analyzed. Indications for reintervention were a true or false aneurysm (35%), acute dissection (3.0%), aortic valve stenosis and/or insufficiency (23.1%), prosthetic valve endocarditis (32.8%), and combinations (4.5%). The principal reoperations performed were aortic root replacement (composite graft, freestyle, aortic allograft, or pulmonary autograft) in 116 patients, ascending aortic replacement in 10 patients, and closure of a false aneurysm in 5 patients. Results were analyzed using univariate statistical methods. RESULTS: Hospital mortality was 6.6% (8 patients). Univariate predictors of hospital death were preoperative functional class III or IV (p = 0.02), an interval of less than 6 months between the primary and actual operation (p = 0.02), preoperative creatinine level of more than 200 micromol/L (p = 0.001), acute aortic dissection (p = 0.001), intraoperative technical problems (p = 0.001), and postoperative dialysis (p = 0.001). Freedom from repetitive reoperation was 99% at 1 year and 98% at 5 and 10 years. CONCLUSIONS: Reoperations on the aortic root and ascending aorta can be performed with an early mortality which is very acceptable.

Risk stratification in acute type A dissection: proposition for a new scoring system.

BACKGROUND: The aim of this study was to develop a scoring system for operative mortality of patients with acute type A aortic dissection. METHODS: Between 1974 and 1999, a total of 252 patients were operated on for an acute type A aortic dissection. We reviewed retrospectively preoperative and intraoperative records to conduct an analysis of risk factors associated with surgery. Multivariate analysis was used to predict operative mortality and to provide a preoperative risk profile of each individual patient that could be used for future patients. RESULTS: Operative mortality was 25.0% (n = 63). A logistic regression model with three explanatory variables to predict operative death showed a good fit: the risk factors associated with operative mortality were preoperative cardiopulmonary resuscitation (p = 0.0013, odds ratio = 15.7) and iatrogenic dissection (p = 0.0014, odds ratio = 9.8). Drained pericardial tamponade (p = 0.0386, odds ratio = 0.12) appeared to be a protective factor associated with decreased mortality. CONCLUSIONS: Because existing scoring systems do not fit this pathologic condition, we propose the use of this Antonius Dissection Scoring System, based on the logistic regression model, to predict the chances of operative mortality for each patient before operation. The survival of patients with concomittant pericardial tamponade may benefit from pericardial drainage.

A 23-year experience with composite valve graft replacement of the aortic root.

BACKGROUND: This is a retrospective study of early and long-term results of composite valve graft replacement of the aortic root. METHODS AND RESULTS: Between July 1974 and July 1997, 244 patients underwent aortic root replacement with a composite valve graft. Mean age was 54+/-15 years. The inclusion technique was used in 178 patients (73.0%), the open technique in 65 (26.5%), and the Cabrol II technique in 1 patient (0.5%). Hospital mortality was 7.8% (70% confidence limit, 6.1% to 9.5%). Independent determinants of hospital mortality were preoperative creatinine level more than 150 micromol/L (p = 0.04), prolonged cardiopulmonary bypass time (p = 0.006), intraoperative technical problems (p = 0.048), and year of operation (p = 0.015). Follow-up was 99.6% complete, median 96 months (range, 2 to 256 months). Fifty-seven patients (25.3%; 70% confidence limit, 22.4% to 28.2%) died during follow-up. Cumulative survival at 5, 10, and 20 years was 76%, 62%, and 33%. Independent risk factors for late death were postoperative complications (p = 0.027), technique for coronary reattachment (p = 0.028), and concomitant aortic arch operation (p = 0.01). Twenty patients (8.8%; 70% confidence limit, 7.0% to 10.6%) underwent reoperation on the aortic root. Estimated freedom from reoperation for pseudoaneurysms at 3 years was 96% in the inclusion group and 94% in the open group (p = 0.236). CONCLUSIONS: Aortic root replacement with a composite valve graft can be performed with low hospital mortality and morbidity. Pseudoaneurysms did occur in the inclusion group, but also in the open group.

Cryopreserved aortic allografts for aortic root reconstruction: a single institution's experience.

BACKGROUND: An evaluation of early and long-term results of aortic root replacement with cryopreserved aortic allografts and echocardiographic follow-up of allograft valve function was performed. METHODS: From September 1989 through May 1998, 132 patients aged 17 to 77 years (mean, 50.8 +/- 14.8 years) underwent freestanding aortic root replacement with a cryopreserved aortic allograft. Eighty-six (65.1%) patients had New York Heart Association class III or IV functional status before operation, and 27 (20.5%) patients underwent emergency operation. Fifty-nine (44.7%) patients had undergone previous cardiac operations. The cause of aortic disease was acute endocarditis in 63 (47.7%) patients, healed endocarditis in 15 (11.3%), degenerative in 20 (15.2%), congenital in 20 (15.2%), failed prosthesis in 10 (7.6%) and rheumatic in 4 (3.0%). Follow-up was complete, with a mean of 42 months. RESULTS: There were 12 hospital deaths (9.1%; 70% confidence limits [CL], 6.6% and 11.6%); 9 of them were operated on for active endocarditis (p = 0.062). Multivariate analysis determined age older than 65 years (p = 0.012) and emergency operation (p = 0.009) as independent risk factors for hospital mortality. During follow-up, 6 (5.0%; 70% CL, 3.0% and 7.0%) patients died. Cumulative survival rate for the entire group was 81.8% +/- 5.4% at 8 years. Freedom from reoperation for structural valve failure was 100%, freedom from reoperation for any cause was 96.3% +/- 1.8% at 8 years. Freedom from endocarditis at 8 years was 97.9% +/- 1.4%. Follow-up of allograft valve function showed no or trivial aortic regurgitation in 97% of patients and absence of stenosis of the allograft in 100%. CONCLUSIONS: Aortic root replacement with cryopreserved aortic allografts can be performed with acceptable hospital mortality and long-term results. The durability of cryopreserved aortic allografts is good, and reoperation for structural valve failure is absent at 8 years.