Herzinsuffizienz im Kindesalter

BACKGROUND: In contrast to the adult age group epidemiologic studies on congestive heart failure (CHF) in infancy and childhood are lacking. METHODS: Retrospective study of all patients admitted to the University Children's Hospital Essen, Germany, between 1989 and 1998 with the ICD 9 code for congenital and acquired heart diseases, cardiomyopathies, arrhythmias, arterial und pulmonary hypertension, and other cardiovascular anomalies. CHF was defined by the typical symptoms, start and end of CHF by commencement and end of anticongestive therapy (ACE inhibitors and/or diuretics and/or digoxin). Prevalence and incidence of CHF were determined and related to all patients with congenital and acquired heart diseases and to all general pediatric inpatients at the Children's Hospital from 1989 to 1998. Within 10 years 1,755 children with heart diseases were admitted, 918 boys and 837 girls. 1,297 children suffered from congenital heart diseases, 167 from rhythm disturbances, 110 from cardiomyopathies and acquired heart diseases, while prematures and patients with systemic or pulmonary hypertension are not furthermore topic of this study. RESULTS: CHF occurred in 587 (33.4%) out of 1,755 children with all congenital and acquired heart diseases, and in 507 (39.1%) out of 1,297 children with congenital heart defects (CHD). When postoperative CHF was excluded, CHF occurred in 23.7% of children with CHD. Cumulative incidence of CHF was 334 out of 1,000 patients with all heart diseases and 233 out of 1,000 general pediatric inpatients. For patients with CHD the incidence of CHF was 289 out of 1,000 patients with all heart diseases and 20.1 out of 1,000 general pediatric inpatients. Prevalence of CHF for children with heart diseases was 279 in 1,000 and 17.3 in 1,000 general pediatric inpatients, for children with CHD 261 in 1,000 and 16.1 in 1,000 general pediatric inpatients. CHF occurred in 70.6% during the 1st year of life and lasted for a mean of 15 months. Only in patients with cardiomyopathies and acquired heart diseases the incidence in infancy was not so pronounced. In 78% of patients with CHD CHF ends after an operation. Mortality: during the 10-year interval 111 out of 1,755 patients with heart diseases died, 81 of them for CHF. That gives an overall mortality of 6.3%, 18% following heart surgery or cardiac catheterization, 74% with signs of CHF. In patients with CHD mortality was 6.2%. Out of the 587 children with CHF, 81 (14%) died. 67% of deaths occurred during the 1st year of life, in patients with CHD even in 71%. CONCLUSION: CHF is uncommon in infants and children with congenital or acquired heart disease, but has considerable mortality. As surgical or interventional therapy is well established in nearly all patients with CHD, prognosis is much better compared to adults. A prospective evaluation by a nationwide registry is necessary.     

CD8 tumor-infiltrating lymphocytes are predictive of survival in muscle-invasive urothelial carcinoma

Tumor-infiltrating cytotoxic T lymphocytes (TILs), including CD8 TILs, have been associated with favorable clinical outcomes in multiple tumor types. Tumor-infiltrating CD8 T cells and major histocompatibility complex (MHC) class I expression in urothelial carcinoma (UC) have not been previously reported. Most immune responses are mediated by local cytotoxic lymphocytes (CD8 T cells), which can eradicate tumor cells by recognizing tumor-associated antigens presented by MHC class I molecules. Here we analyzed the presence of intratumoral CD8 T cells, the expression of MHC class I antigen, and the expression of the NY-ESO-1 tumor antigen in UC samples and correlated our findings with clinical outcome. Immunohistochemical staining for intratumoral CD8 T cells in tissue samples from 69 patients with UC showed that patients with advanced UC (pT2, pT3, or pT4) and higher numbers of CD8 TILs within the tumor (> or =8) had better disease-free survival (P < 0.001) and overall survival (P = 0.018) than did patients with similar-staged UC and fewer intratumoral CD8 TILs. We conclude that the extent of intratumoral CD8 TILs is an important prognostic indicator in advanced UC.     

Modulation of food intake by glucose in patients with type 2 diabetes

OBJECTIVE: A gain in body weight is a common adverse effect of glucose-lowering therapies in patients with type 2 diabetes, the mechanisms of which are not completely understood. Blood glucose is considered to play a crucial role in the regulation of food intake. On this background, we hypothesized that a short-term reduction of blood glucose concentration to normal values acutely increases food intake in type 2 diabetic patients. RESEARCH DESIGN AND METHODS: To test this hypothesis, 12 patients with type 2 diabetes were examined twice, once during a euglycemic (5.0 mmol/l) clamp experiment and another time during a hyperglycemic (10.5 mmol/l) clamp. The experiments were performed in a single-blind fashion with the order of conditions balanced across patients. On both clamp conditions, insulin was infused at a constant rate of 2.5 mU/kg per min for 125 min. Simultaneously, a glucose solution was infused at a variable rate to achieve target glycemic levels. During the final 30 min of the clamps, the patients were allowed to eat as much as they liked from a standard breakfast buffet. RESULTS: Compared with the hyperglycemic condition, the patients ingested on average 25 +/- 10% more energy during euglycemia (645 +/- 75 vs. 483 +/- 37 kcal; P = 0.029). The increased energy intake during euglycemia was equally distributed across macronutrient components, i.e., during euglycemia the patients ate more carbohydrates (+27.1 +/- 11.4%; P = 0.037), fat (+22.5 +/- 10.0%; P = 0.046), and proteins (+25.2 +/- 11.2%; P = 0.046) than during hyperglycemia. Circulating levels of insulin, amylin, leptin, ghrelin, and glucagon-like peptide-1 did not differ between the euglycemic and hyperglycemia clamp, excluding a major contribution of these hormones to the difference in food intake. Summing up the glucose administered intravenously and the food ingested yielded a remarkably similar total energy influx in both conditions (794 +/- 64 vs. 790 +/- 53 kcal; P = 0.961). CONCLUSIONS: Together our data suggest that total energy supply to the organism is tightly regulated on a short-term basis independent of the route of influx. Alternatively, it can be hypothesized that euglycemia stimulated or that hyperglycemia suppressed food intake at the subsequent buffet meal in our type 2 diabetic patients. Regardless of these different interpretations, our data indicate an important regulatory role of glucose for food intake in type 2 diabetic patients that is of considerable clinical relevance.     

A trial of self-adhesive patch electrodes and hand-held paddle electrodes for external cardioversion of atrial fibrillation (MOBIPAPA).

AIMS: External electrical cardioversion is the method of choice to terminate persistent atrial fibrillation. Whether the type of shock electrode affects cardioversion success is not known. We tested whether hand-held steel electrodes improve cardioversion outcome with monophasic or biphasic shocks when compared with adhesive patch electrodes. METHODS AND RESULTS: Two hundred and one consecutive patients with persistent atrial fibrillation (147 male, mean age 63+/-1 years, duration of atrial fibrillation 6.3+/-1 months) were randomly assigned to cardioversion using either a sinusoidal monophasic or a truncated exponential biphasic shock wave form. The first half of patients were cardioverted using adhesive patch electrodes, the second half using hand-held steel paddle electrodes, and all patients using an anterior-posterior electrode position. Paddle electrodes successfully cardioverted 100/104 patients (96%) and patch electrodes 85/97 patients (88%, P=0.04). This effect was comparable to that of biphasic shocks: biphasic shocks cardioverted 102/104 patients (98%) and monophasic shocks 83/97 patients (86%, P=0.001). A beneficial effect of paddle electrodes was observed for both shock wave forms. After cross-over from an ineffective monophasic to a biphasic shock, cardioversion was successful in 198/201 (98.5%) patients. Unsuccessful cardioversion after cross-over (3/201 patients) only occurred with patch electrodes (P=0.07). CONCLUSION: Hand-held paddle electrodes increase success of external cardioversion of atrial fibrillation in this trial. This increase is of similar magnitude as the increase in cardioversion success achieved with biphasic shocks. A combination of biphasic shocks, paddle electrodes, and an anterior-posterior electrode position renders outcome of external cardioversion almost always successful (104/104 patients in this trial).     

Infection by the respiratory syncytial virus in infants and young children at high risk

The respiratory syncytial virus is the most common cause of infection of the lower respiratory tract in infants and young children, and is the leading cause of hospitalisation and death due to viral illness during the first year of life. In otherwise healthy infants, the virus usually causes only mild respiratory illness, but premature babies and infants with chronic lung disease, those with congenitally malformed hearts, or those who are immunodeficient, are at increased risk of serious illness, hospitalisation, and death. Recent infection with the virus is also associated with increased postoperative complications after corrective surgery for congenitally malformed hearts. No effective vaccine is currently available, and treatment is limited to supportive therapy. Prevention in groups deemed to be at high-risk, therefore, is essential. In addition to measures for control of infection, prophylactic immunotherapy is indicated in selected patients. Palivizumab (Synagis) is a monoclonal antibody indicated for the prevention of serious viral disease of the lower respiratory tract in premature infants, those with chronic lung disease, and those with haemodynamically significant congenital cardiac lesions. Palivizumab is given intramuscularly, usually as a monthly injection during the so-called "season". In a recent international, randomised, double-blind, placebo-controlled trial in 1,287 children less than or equal to 2 years old with haemodynamically significant congenital cardiac malformations, prophylaxis achieved a relative reduction of 45 per cent in the incidence of antigen-confirmed viral-related hospitalisation, and reduced the duration of hospital stay by 56 per cent. National and international guidelines, therefore, now recommend routine prophylaxis in the first year of life in children with haemodynamically significant congenital cardiac disease.     

Novadaq SPY: intraoperative quality assessment in off-pump coronary artery bypass grafting

OBJECTIVES: Off-pump coronary artery bypass grafting may decrease operative morbidity when compared to on-pump bypass grafting; however, it is technically demanding and thus quality control is essential. This study assesses the clinical feasibility of a new, indocyanine green (ICG)-based imaging system (SPY; Novadaq Technologies; Toronto, ON, Canada) to monitor the quality of anastomoses and grafts in off-pump revascularization. SETTING: Thirty-eight consecutive patients undergoing nonemergent coronary artery bypass grafting without the use of extracorporeal circulation at two Swiss cardiac surgery clinics were included. On completion of bypass grafts, the quality of the grafts was assessed using the ICG-based imaging system. The imaging device comprises an 806-nm laser light source that is used to cause ICG to fluoresce and a near infrared-sensitive charged couple device videocamera that is used to capture the fluorescence images. ICG was administered through the central venous line, and images were acquired during the first pass of the ICG through the field of view. Graft flow (qualitative) and the quality of the grafts and anastomoses were assessed intraoperatively. RESULTS: Between March 2002 and September 2002, a total of 38 patients (26 men and 12 women; mean +/- SD age, 64.6 +/- 10.5 years; body mass index, 27.1 +/- 2.9) underwent surgery and imaging at two institutions. One hundred seven of 124 grafts (45 arteries and 62 veins) were analyzed. Seventeen grafts could not be assessed due to difficulties in positioning. The imaging system was easy to handle, and no adverse reactions to ICG were observed. Four of the 107 grafts imaged required revision (three anastomotic constrictions and one graft dissection). Each imaging sequence required approximately 1.25 to 2.5 mg of ICG. The images were equivalent to angiography without the need for radiographs and catheter insertion. In addition, the course of coronaries that would otherwise be difficult to locate in obese patients could be detected using the imaging system. Biochemical and ECG data demonstrated an absence of intraoperative or postoperative myocardial damage, and no liver enzyme elevation or renal dysfunction. CONCLUSIONS: This study supports the clinical utility of a ICG-based imaging system for the assessment of the quality of bypass grafts, which appears to be safe and simple to use.     

Effects of tiotropium with and without formoterol on airflow obstruction and resting hyperinflation in patients with COPD

BACKGROUND: The combination of short-acting beta(2)-agonists and anticholinergics in the treatment of COPD has been well documented, but data on combination of long-acting agents are lacking. METHODS: A randomized, open-label, placebo-controlled, three-way crossover study was conducted comparing 2-week treatment periods of tiotropium alone to tiotropium plus formoterol once or twice daily following a 2-week pretreatment period with tiotropium. Lung function (FEV(1), FVC, and resting inspiratory capacity [IC]) serially over 24 h was measured in 95 patients with stable COPD at baseline and after 2 weeks of each treatment. RESULTS: Mean baseline FEV(1) was 1.05 L (38% of predicted). There was a circadian variation in FEV(1), FVC, and IC at baseline that was maintained during all treatment periods. Average FEV(1) (0 to 24 h) improved by 0.08 L with tiotropium, by 0.16 L with tiotropium plus formoterol once daily, and by 0.20 L with tiotropium plus formoterol twice daily (p < 0.01 for all comparisons). Compared with tiotropium alone, add-on formoterol in the morning produced improvement in FEV(1), FVC, and IC for > 12 h. The second add-on dose of formoterol in the evening caused further improvement in FEV(1) for 12 h, but in FVC and IC for < 12 h. Peak increase in FEV(1) was 0.23 L (22% of baseline) with tiotropium and 0.39 L (37% of baseline) with tiotropium plus formoterol (p < 0.0001). Compared with tiotropium alone, add-on formoterol once and twice daily reduced the use of rescue salbutamol during the daytime (p < 0.01) and with add-on formoterol twice daily also during the nighttime (p < 0.05). The combination of tiotropium and formoterol was well tolerated. CONCLUSION: In the treatment of COPD, there is benefit from adding formoterol once or twice daily to tiotropium once daily in terms of improvement in airflow obstruction, resting hyperinflation, and the use of rescue salbutamol.     

A common brain network links development,aging, and vulnerability to disease

Several theories link processes of development and aging in humans. In neuroscience, one model posits for instance that healthy age-related brain degeneration mirrors development, with the areas of the brain thought to develop later also degenerating earlier. However, intrinsic evidence for such a link between healthy aging and development in brain structure remains elusive. Here, we show that a data-driven analysis of brain structural variation across 484 healthy participants (8–85 y) reveals a largely—but not only—transmodal network whose lifespan pattern of age-related change intrinsically supports this model of mirroring development and aging. We further demonstrate that this network of brain regions, which develops relatively late during adolescence and shows accelerated degeneration in old age compared with the rest of the brain, characterizes areas of heightened vulnerability to unhealthy developmental and aging processes, as exemplified by schizophrenia and Alzheimer’s disease, respectively. Specifically, this network, while derived solely from healthy subjects, spatially recapitulates the pattern of brain abnormalities observed in both schizophrenia and Alzheimer’s disease. This network is further associated in our large-scale healthy population with intellectual ability and episodic memory, whose impairment contributes to key symptoms of schizophrenia and Alzheimer’s disease. Taken together, our results suggest that the common spatial pattern of abnormalities observed in these two disorders, which emerge at opposite ends of the life spectrum, might be influenced by the timing of their separate and distinct pathological processes in disrupting healthy cerebral development and aging, respectively.Many phylogenetic or ontogenetic models attempt to relate development and aging at genetic, molecular, or cognitive systems levels (1–4). In neuroscience, one of the most popular hypotheses in this respect postulates that the process of healthy age-related brain decline mirrors developmental maturation. This concept was first introduced in 1881 as a “loi de régression” (Ribot’s law) when Théodule Ribot, a French philosopher, observed that the destruction of memories progresses in reverse order to that of their formation: from the unstable to the stable, from the newly formed memories to older “sensory, instinctive” memories (5). More generally, this hypothesis postulates that the sequence of events associated with brain decline should present itself in reverse order to the series of events related to brain development, with brain regions thought to develop relatively late—at both ontogenetic and phylogenetic levels—also degenerating relatively early (2, 6, 7).One way of tracking this hypothesized mirroring pattern of development and aging in the human brain is to use the information provided at a macroscopic level by structural MRI in large-scale, lifespan human populations. Although structural MRI does not distinguish between the various cellular mechanisms underpinning development and aging processes [e.g., dendritic and synaptic remodeling, neurogenesis and neuronal death, astrogliosis, (de)myelination], this technique is sensitive to detect the overall contribution of these mechanisms to macroscopic age-related changes in brain structure (8–10).In 2000, Raz (11) presented for the first time MRI data suggesting that the chronological order of completion of intracortical fibers myelination was associated with age-related differences in cortical volume. In particular, Raz (12) later noted that “the pattern of differential brain aging suggests that phylogenetically newer and ontogenetically less precocious brain structures such as association cortices and the neostriatum show increased vulnerability to the effects of aging … follow(ing) the rule of (phylogenetically and ontogenetically) last-in, first-out” (12). Direct and intrinsic evidence for a clear link between brain structural development and aging lending support to this evolutionary–developmental “retrogenesis” model [or the “last-in, first-out” model as Raz (12) and others call it] is needed, however. Most of the structural imaging studies investigating relationships between development and aging have so far led to different, and sometimes contradictory, results (13, 14). One possible explanation for this inconsistency is that these studies have tested only one specific pattern of age-related change and have focused on age subgroups or on predefined regions of the brain.Here, we took a purely data-driven approach to assess the intersubject brain structure variability among 484 healthy participants covering most of the lifespan (8–85 y). We analyzed the structural brain images of these healthy subjects using a linked independent component analysis (ICA) (SI Materials and Methods) (15). This approach provides an automatic decomposition of the images into spatial components characterizing the intersubject brain structural variability, i.e., each spatial component represents a mode of variation of brain structure across all participants.     

High definition plus colonoscopy combined with i-scan tone enhancement vs. high definition colonoscopy for colorectal neoplasia: A randomized trial

Background

High definition endoscopy is the accepted standard in colonoscopy. However, an important problem is missed polyps.

Aims

Our objective was to assess the additional adenoma detection rate between high definition colonoscopy with tone enhancement (digital chromoendoscopy) vs. white light high definition colonoscopy.

Methods

In this prospective randomized trial patients were included to undergo a tandem colonoscopy. The first exam was a white light colonoscopy with removal of all visualized polyps. The second examination was randomly assigned in a 1:1 ratio as either again white light colonoscopy (Group A) or colonoscopy with tone enhancement (Group B). Primary endpoint was the adenoma detection rate during the second withdrawal (sample size calculation – 40 per group).

Results

67 lesions (Group A: n = 34 vs. Group B: n = 33) in 80 patients (mean age 61 years, male 64%) were identified on the first colonoscopy. The second colonoscopy detected 78 additional lesions: n = 60 with tone enhancement vs. n = 18 with white light endoscopy (p < 0.001). Tone enhancement found more additional adenomas (A n = 20 vs. B n = 6, p = 0.006) and identified significantly more missed adenomas per subject (0.5 vs. 0.15, p = 0.006).

Conclusions

High definition plus colonoscopy with tone enhancement detected more adenomas missed by white light colonoscopy.