Non-invasive cardiac assessment in high risk patients (The GROUND study): rationale, objectives and design of a multi-center randomized controlled clinical trial

Background: Peripheral arterial disease (PAD) is a common disease associated with a considerably increased risk of future cardiovascular events and most of these patients will die from coronary artery disease (CAD). Screening for silent CAD has become an option with recent non-invasive developments in CT (computed tomography)-angiography and MR (magnetic resonance) stress testing. Screening in combination with more aggressive treatment may improve prognosis. Therefore we propose to study whether a cardiac imaging algorithm, using non-invasive imaging techniques followed by treatment will reduce the risk of cardiovascular disease in PAD patients free from cardiac symptoms. Design: The GROUND study is designed as a prospective, multi-center, randomized clinical trial. Patients with peripheral arterial disease, but without symptomatic cardiac disease will be asked to participate. All patients receive a proper risk factor management before randomization. Half of the recruited patients will enter the 'control group' and only undergo CT calcium scoring. The other half of the recruited patients (index group) will undergo the non invasive cardiac imaging algorithm followed by evidence-based treatment. First, patients are submitted to CT calcium scoring and CT angiography. Patients with a left main (or equivalent) coronary artery stenosis of > 50% on CT will be referred to a cardiologist without further imaging. All other patients in this group will undergo dobutamine stress magnetic resonance (DSMR) testing. Patients with a DSMR positive for ischemia will also be referred to a cardiologist. These patients are candidates for conventional coronary angiography and cardiac interventions (coronary artery bypass grafting (CABG) or percutaneous cardiac interventions (PCI)), if indicated. All participants of the trial will enter a 5 year follow up period for the occurrence of cardiovascular events. Sequential interim analysis will take place. Based on sample size calculations about 1200 patients are needed to detect a 24% reduction in primary outcome. Implications: The GROUND study will provide insight into the question whether non-invasive cardiac imaging reduces the risk of cardiovascular events in patients with peripheral arterial disease, but without symptoms of coronary artery disease. Trial registration: Clinicaltrials.gov NCT0018911

Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology.

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented

Severe Pediatric COVID-19 and Multisystem Inflammatory Syndrome in Children from Wild-type to Population Immunity: A Prospective Multicenter Cohort Study with Real-time Reporting

Background: SARS-CoV-2 variant evolution and increasing immunity altered the impact of pediatric SARS-CoV-2 infection. Public health decision-making relies on accurate and timely reporting of clinical data. Methods: This international hospital-based multicenter, prospective cohort study with real-time reporting was active from March 2020 to December 2022. We evaluated longitudinal incident rates and risk factors for disease severity. Results: We included 564 hospitalized children with acute COVID-19 (n = 375) or multisystem inflammatory syndrome in children (n = 189) from the Netherlands, Curaçao and Surinam. In COVID-19, 134/375 patients (36%) needed supplemental oxygen therapy and 35 (9.3%) required intensive care treatment. Age above 12 years and preexisting pulmonary conditions were predictors for severe COVID-19. During omicron, hospitalized children had milder disease. During population immunity, the incidence rate of pediatric COVID-19 infection declined for older children but was stable for children below 1 year. The incidence rate of multisystem inflammatory syndrome in children was highest during the delta wave and has decreased rapidly since omicron emerged. Real-time reporting of our data impacted national pediatric SARS-CoV-2 vaccination- and booster-policies. Conclusions: Our data supports the notion that similar to adults, prior immunity protects against severe sequelae of SARS-CoV-2 infections in children. Real-time reporting of accurate and high-quality data is feasible and impacts clinical and public health decision-making. The reporting framework of our consortium is readily accessible for future SARS-CoV-2 waves and other emerging infections

Degradation of haloaromatic compounds

An ever increasing number of halogenated organic compounds has been produced by industry in the last few decades. These compounds are employed as biocides, for synthetic polymers, as solvents, and as synthetic intermediates. Production figures are often incomplete, and total production has frequently to be extrapolated from estimates for individual countries. Compounds of this type as a rule are highly persistent against biodegradation and belong, as "recalcitrant" chemicals, to the class of so-called xenobiotics. This term is used to characterise chemical substances which have no or limited structural analogy to natural compounds for which degradation pathways have evolved over billions of years. Xenobiotics frequently have some common features. e.g. high octanol/water partitioning coefficients and low water solubility which makes for a high accumulation ratio in the biosphere (bioaccumulation potential). Recalcitrant compounds therefore are found accumulated in mammals, especially in fat tissue, animal milk supplies and also in human milk. Highly sophisticated analytical techniques have been developed for the detection of organochlorines at the trace and ultratrace level

Influence of unequal ventilation on the single breath K(CO) in COPD revealed by comparison with the rebreathing K(CO).

In 16 patients with chronic obstructive pulmonary disease (COPD) we investigated the relation between unequal ventilation and diffusion by means of lung volumes and Krogh factors (K(CO)) using the single breath (SB) and the rebreathing (RB) methods. We used both methods because the SB measurement is sensitive to unequal ventilation and diffusion whereas the RB measurement is not. Because K(CO) depends on inspired volume (VI), the SB and RB measurement have to be performed at the same VI. We therefore determined K(CO)SBm by making a SB measurement at VI equal to the mean inspired volume during the RB measurement and then calculated K(CO)RBm by dividing the RB transfer factor for CO by the mean RB lung volume. In 10 patients K(CO)SBm/K(CO)RBm, a parameter determined by the combined effect of unequal ventilation and diffusion, was almost equal to unequal ventilation, the quotient of the SB and mean RB lung volumes (VSBm/VRBm), just as in normal subjects (Jansons et al., Respiration 67 (2000) 383). This finding means that we can correct for the effects of unequal ventilation by dividing K(CO)SBm by VSBm/VRBm. We suggest that the SB measurement of K(CO) at vital capacity can be corrected in a similar way

Complicaties na okselkliertoilet wegens mammacarcinoom

Axillary dissection in breast cancer is performed to stage the tumor and to obtain regional tumour control. It is associated with some morbidity. Recently mention was made of post-axillary dissection pain of the arm following damage to one or more of the intercostobrachial nerves. In the University Hospital of Utrecht a radical axillary dissection is routinely performed for breast cancer with transection of the sensory intercostobrachial nerve(s). To evaluate the inherent morbidity of this operation, we interviewed and examined 71 women (75 axillae) who had undergone an axillary dissection for carcinoma of the breast between January 1987 and January 1990. In almost all cases a sensory deficit was present in the axilla and/or arm. In 23 patients (26 sides; 35%) there was pain in the arm, always in the innervation area of the intercostobrachial nerves. One-third of these cases had a NRS score of 5 or higher, indicating moderate to severe pain. Seroma and lymphedema were found in 21 patients. In 6 shoulders abduction was reduced to 90 degrees. The several complaints were non-invalidating to 48 patients, slightly invalidating to 13 and moderately invalidating to 10 patients. At present, histological examination of the axillary nodes is still the best way to detect metastases, and it has implications for adjuvant therapies. The results of this study indicate that routinely sacrificing the intercostobrachial nerves during axillary dissection may result in annoying sensory changes and that efforts should be made to preserve one or two of these nerves during the operation

Salivary gland carcinomas: prognostic factors for local control and distant metastasis, the role of radiotherapy.

Contains fulltext : 24848___.PDF (publisher's version ) (Open Access

Role of atrial fibrillation and atrioventricular conduction (including Wolff-Parkinson-White Syndrome) in sudden death

A short refractory period of the accessory pathway is considered a major threat for sudden death in patients with Wolff-Parkinson-White syndrome and atrial fibrillation. RR interval and QRS signal analysis together with signal analysis of a bipolar high right atrial electrogram were obtained in six patients with Wolff-Parkinson-White syndrome and either induced or spontaneous atrial fibrillation. A record of a sufficiently long episode of atrioventricular (AV) conduction by way of the bypass tract that could be used for satisfactory RR interval sequence and QRS analysis was obtained from only one patient. The results were compared with those of a representative patient with atrial fibrillation and normal AV nodal-His conduction. In a patient with Wolff-Parkinson-White syndrome, atrial fibrillation and AV conduction by way of the bypass tract may exhibit high ventricular rates (median RR intervals of about 300 ms) and long/short RR interval ratios of just over 1 (RR intervals not exceeding 400 ms). The right atrial electrogram showed a noiselike excitation pattern. This study suggests that rather than a short refractory period of the bypass tract, it is lack of concealed conduction, responsible for the presence of long RR intervals, that allows the ventricles to reach very high ventricular rates and at times to fibrillate. The normal AV nodal-His system seems to protect the heart against high ventricular rates and ventricular fibrillation during atrial fibrillation by its relatively long refractory period and capacity to in duce long RR intervals by means of concealed conduction

The sensitivity to X rays of mouse spermatogonia that are committed to differentiate and of differentiating spermatogonia

In the CBA mouse the radiosensitivity of the undifferentiated spermatogonia that are committed to differentiate was determined by counting their more developed descendants 10 days after graded doses of X rays. Decreasing D0 values were found when these differentiating spermatogonia were derived from undifferentiated spermatogonia that were located in all likelihood in chains of increasing length. In stages IX and X of the epithelial cycle the radiosensitivity of these undifferentiated spermatogonia was characterized by a D0 of 2.2 Gy. This D0 value most likely belongs to the Asingle spermatogonia that form repopulating colonies which give rise to differentiating spermatogonia within the same epithelial cycle. In stages XII/I, where a D0 of 1.0 Gy was found, the dose-response curve is likely dominated by the Apaired spermatogonia present in these stages. In stages III to VII, the Aaligned spermatogonia transforming into A1 spermatogonia determine the radiosensitivity. During this period the D0 decreased from 0.7 to 0.4 Gy. Differentiating A1 to A3 and B spermatogonia had rather similar radiosensitivities of 0.4 to 0.5 G