Sampling and Definitions of Placental Lesions: Amsterdam Placental Workshop Group Consensus Statement.

CONTEXT: -The value of placental examination in investigations of adverse pregnancy outcomes may be compromised by sampling and definition differences between laboratories. OBJECTIVE: -To establish an agreed-upon protocol for sampling the placenta, and for diagnostic criteria for placental lesions. Recommendations would cover reporting placentas in tertiary centers as well as in community hospitals and district general hospitals, and are also relevant to the scientific research community. DATA SOURCES: -Areas of controversy or uncertainty were explored prior to a 1-day meeting where placental and perinatal pathologists, and maternal-fetal medicine specialists discussed available evidence and subsequently reached consensus where possible. CONCLUSIONS: -The group agreed on sets of uniform sampling criteria, placental gross descriptors, pathologic terminologies, and diagnostic criteria. The terminology and microscopic descriptions for maternal vascular malperfusion, fetal vascular malperfusion, delayed villous maturation, patterns of ascending intrauterine infection, and villitis of unknown etiology were agreed upon. Topics requiring further discussion were highlighted. Ongoing developments in our understanding of the pathology of the placenta, scientific bases of the maternofetoplacental triad, and evolution of the clinical significance of defined lesions may necessitate further refinements of these consensus guidelines. The proposed structure will assist in international comparability of clinicopathologic and scientific studies and assist in refining the significance of lesions associated with adverse pregnancy and later health outcomes.

[Neonaticide: frequently suspected, seldom proven]. / Neonaticide: vaak vermoed, zelden bewezen.

OBJECTIVE: To present an overview of pathological findings on neonaticide in the Netherlands. DESIGN: Retrospective descriptive study. METHOD: We analyzed all autopsy reports on neonates from the Netherlands Forensic Institute for the period 1994-2011. We collected data on gestational age, how the body had been discovered and autopsy results. RESULTS: We included details of 78 victims; 61 (78%) had been born at full term and 17 (22%) prematurely. Half of the victims were girls, 40% were boys and in 10% the state of the body meant that it was not possible to determine the sex. Minimal, moderate and severe putrefaction was observed in 29 bodies (37%), 15 bodies (19%) and 34 bodies (44%), respectively. In the cases with moderate or severe decomposition it was not possible to determine with certainty whether the child had been born alive and, if applicable, the cause of death. Of the remaining 29 cases with minimal decomposition, 1 had been stillborn; a possible cause of death could be determined in 12 cases. CONCLUSION: In the Netherlands 4 to 5 forensic autopsies are performed annually in cases of suspected neonaticide. In most cases decomposition is already too advanced to be able to determine whether there was any sign of life at birth and to establish the cause of death, if applicable.

Histological findings in unclassified sudden infant death, including sudden infant death syndrome.

Our objective was to study histological variations and abnormalities in unclassified sudden infant death (USID), including sudden infant death syndrome (SIDS), in The Netherlands. Two hundred Dutch USID cases between 1984 and 2005 were identified. The histology slides and autopsy reports of 187 cases were available for systematic review, including brain autopsy in 135 cases. An explanation for the cause of death in 19 patients (10.2%) was found. Twelve patients had bronchopneumonia, 3 showed extensive aspiration, 2 had signs of a metabolic disorder, 1 had sepsis, and 1 had meningitis. Frequent nonspecific findings were congestion (66%), edema (47%), small hemorrhages (18%), and lymphoid aggregates (51%) in the lungs; congestion of the liver (23%); and asphyctic bleeding in the kidney (44%), adrenal gland (23%), and thymus (17%). Statistical associations were found for infection with starry sky macrophages in the thymus (P  =  0.004), with calcification (P  =  0.023), or with debris in the Hassal's corpuscles (P  =  0.034). In this study, in 10.2% of cases the histological findings were incompatible with SIDS or USID. Furthermore, several frequent nonspecific histological findings in the thymus that point toward an infection were found.

Early versus late parenteral nutrition in ICU patients: cost analysis of the EPaNIC trial.

INTRODUCTION: The EPaNIC randomized controlled multicentre trial showed that postponing initiation of parenteral nutrition (PN) in ICU-patients to beyond the first week (Late-PN) enhanced recovery, as compared with Early-PN. This was mediated by fewer infections, accelerated recovery from organ failure and reduced duration of hospitalization. Now, the trial's preplanned cost analysis (N = 4640) from the Belgian healthcare payers' perspective is reported. METHODS: Cost data were retrieved from individual patient invoices. Undiscounted total healthcare costs were calculated for the index hospital stay. A cost tree based on acquisition of new infections and on prolonged length-of-stay was constructed. Contribution of 8 cost categories to total hospitalization costs was analyzed. The origin of drug costs was clarified in detail through the Anatomical Therapeutic Chemical (ATC) classification system. The potential impact of Early-PN on total hospitalization costs in other healthcare systems was explored in a sensitivity analysis. RESULTS: ICU-patients developing new infection (24.4%) were responsible for 42.7% of total costs, while ICU-patients staying beyond one week (24.3%) accounted for 43.3% of total costs. Pharmacy-related costs represented 30% of total hospitalization costs and were increased by Early-PN (+608.00 EUR/patient, p = 0.01). Notably, costs for ATC-J (anti-infective agents) (+227.00 EUR/patient, p = 0.02) and ATC-B (comprising PN) (+220.00 EUR/patient, p = 0.006) drugs were increased by Early-PN. Sensitivity analysis revealed a mean total cost increase of 1,210.00 EUR/patient (p = 0.02) by Early-PN, when incorporating the full PN costs. CONCLUSIONS: The increased costs by Early-PN were mainly pharmacy-related and explained by higher expenditures for PN and anti-infective agents. The use of Early-PN in critically ill patients can thus not be recommended for both clinical (no benefit) and cost-related reasons. TRIAL REGISTRATION: ClinicalTrials.gov NCT00512122.

A case of extreme agitation and death after the use of mephedrone in The Netherlands.

A 36-year old man, having injured himself severely by smashing windows in a rage of fury, was arrested by the police. He died despite resuscitation attempts. The forensic autopsy showed many superficial skin lacerations, bruises and minor brain swelling, but there was no definitive cause of death. Toxicological analysis showed a high concentration of mephedrone in femoral blood (5.1mg/L) and traces of cocaine, MDMA and oxazepam. The remaining dose of mephedrone in the stomach contents was estimated at 113 mg. Tablets that were found in the house of the deceased also contained mephedrone. We attribute this man's death to a fatal oral intake of mephedrone, which probably led to a state of excited delirium. This was aggravated by blood loss from multiple wounds.

[Unnatural death due to child abuse--forensic autopsies 1996-2009]. / Niet-natuurlijk overlijden door kindermishandeling; gerechtelijke secties 1996-2009.

OBJECTIVE: To evaluate the number of cases of fatal child abuse in minors on whom forensic autopsy was carried out in the Netherlands during the period 1996-2009 and to compare the 1996 data with Dutch data published earlier by Kuyvenhoven et al. (a questionnaire study among general practitioners and paediatricians). DESIGN: Descriptive retrospective study. METHOD: Cases of unnatural death from all forensic autopsies on fetuses, children and young adults (> 24 weeks and < 18 years; n = 688) over the past 14 years (1996-2009) were retrospectively analyzed for child abuse. By means of death certificates and suspected cause of death, the actual outcomes of the 1996 data were compared with those of the study of Kuyvenhoven et al. RESULTS: Over the past 14 years, in 445 of 688 forensic cases (65%) in this study population, cause of death was demonstrated to be unnatural. Of these deaths, 54% (n = 239/445) were unnatural and non-accidental due to child abuse. This corresponded with an annual average of 15 (30%) 'proven' and 2 (5%) 'highly probable' cases of fatal child abuse. The total number of abandoned babies, foundlings and otherwise, was on average 4 per year. In 1996 57% (13/23) of fatal child abuse cases were not represented in the data published by Kuyvenhoven et al. CONCLUSION: Of the 49 foetuses, children and young adults on whom forensic autopsy was carried out in the Netherlands each year, 17 (35%) died due to proven or highly probable child abuse. In 1996 more than half of the number of fatal cases of child abuse of the Netherlands Forensic Institute were not represented in the study of Kuyvenhoven et al. In both this study and in the one of Kuyvenhoven underreporting is highly probable.

Post-mortem cases involving amphetamine-based drugs in The Netherlands. Comparison with driving under the influence cases.

In this study we reviewed the post-mortem cases in the years 1999-2004 that were presented at the Netherlands Forensic Institute. The concentrations of amphetamine-based drugs in femoral blood from cases of suspected unnatural death were compared with concentrations in whole blood from non-fatal cases of driving under the influence (DUI cases) and with literature. Furthermore, the combinations with other drugs and/or alcohol were investigated. Amphetamine-based drugs were present in 70 post-mortem cases and 467 DUI cases. The most detected amphetamine-based drug was MDMA, followed by amphetamine. The presence of MDA could usually be explained by metabolism of MDMA. Methamphetamine and MDEA were rarely present. Frequently, the amphetamine-based drugs were taken in combination with alcohol and/or other non-amphetamine-based drugs such as cocaine or cannabinoids. The 70 post-mortem cases were divided into 38 amphetamine-based drug caused (i.e. the amphetamine-based drug directly caused or contributed to the death) and 32 amphetamine-based drug related deaths (i.e. death was not directly caused by the amphetamine-based drug). In the latter category, other (poly)drug intoxications and death by violence or drowning were the most frequent causes of death. In 30 cases, MDMA caused death directly. The range in blood concentrations of MDMA in these cases was substantial, i.e. 0.41-84 mg/L with a median concentration of 3.7 mg/L (n=30). MDMA blood concentrations in the MDMA related deaths (n=20) and in the DUI cases (n=360) varied up to 3.7 and 4.0 mg/L, respectively. Seven victims died from the direct effects of amphetamine; the blood concentration of amphetamine ranged from 0.24 to 11.3 mg/L, with a median concentration of 1.7 mg/L (n=7). The median concentrations of amphetamine in the amphetamine related deaths (n=13) and the DUI cases (n=208) were much lower, i.e. 0.28 and 0.22 mg/L, respectively. Amphetamine blood concentrations up to 6.0 and 2.3 mg/L were seen in the drug related deaths and DUI cases, respectively. The most frequently encountered amphetamine-based drugs in the investigated deaths were MDMA and amphetamine. The majority of MDMA- and amphetamine-caused deaths, i.e. 90% of these deaths, occurred with blood concentrations above 1.5 and 0.80 mg/L, respectively. MDMA and amphetamine blood concentrations in drug related deaths and DUI cases, however, overlap the range of fatal concentrations. Therefore, MDMA or amphetamine concentrations should never be used alone to establish the cause of death.

Transport and activity of Desulfitobacterium dichloroeliminans strain DCA1 during bioaugmentation of 1,2-DCA-contaminated groundwater.

The transport and activity of Desulfitobacterium dichloroeliminans strain DCA1 in 1,2-dichloroethane (1,2-DCA)-contaminated groundwater have been evaluated through an in situ bioaugmentation test at an industrial site (Belgium). The migration of strain DCA1 was monitored from an injection well toward a monitoring well, and the effect of the imposed groundwater flow on its distribution was assessed by means of transport model MOCDENS3D. The results of the real-time PCR (16S rRNA gene) quantification downstream from the injection point were used to evaluate the bacterial distribution pattern simulated by MOCDENS3D. In the injection well, the 1,2-DCA concentration in the groundwater decreased from 939.8 to 0.9 microM in a 35 day time interval and in the presence of a sodium lactate solution. Moreover, analyses from the monitoring well showed that the cells were still active after transport through the aquifer, although biodegradation occurred to a lesser extent. This study showed that strain DCA1 can be successfully applied for the removal of 1,2-DCA under field conditions and that its limited retardation offers perspectives for large-scale cleanup processes of industrial sites.

Real time PCR quantification in groundwater of the dehalorespiring Desulfitobacterium dichloroeliminans strain DCA1.

Quantifying microorganisms responsible for bioremediation can provide insight in their behavior and can help to obtain a better understanding of the physicochemical parameters monitored during bioremediation. A real time PCR (RTm PCR) assay based on the detection with SYBR Green I was optimized in order to quantify the 1,2-dichloroethane dehalorespiring Desulfitobacterium dichloroeliminans strain DCA1. A primer pair targeting unique regions of the 16 S rRNA gene was designed and tested in silico for its specificity. Selectivity was furthermore evaluated and a Limit of Quantification of 1.5 x 10(4) cells/microL DNA extract was obtained for spiked groundwater. Real time measurements of groundwater samples retrieved from a bioaugmented monitoring well and which had an average concentration lying in the range of the Limit of Quantification were evaluated positively with regards to reproducibility. Validation of the RTm PCR assay on groundwater samples originating from different sites confirmed the specificity of the designed primer pair. This RTm PCR assay can be used to survey the abundance and kinetics of strain DCA1 in in situ bioaugmentation field studies.

Histological age prediction from the femur in a contemporary Dutch sample. The decrease of nonremodeled bone in the anterior cortex.

This paper presents an uncomplicated and minimally invasive method for age-at-death determination in a contemporary Dutch (West European) population, by modifying the approach of assessment based on the age-related remodeling of bone tissue. In contrast to the usual "osteon count," a "non-remodeled tissue count" is undertaken. To optimize the method, proper zeroing of the polarization filter set of the microscope is essential. Instructions for setting the filters are given. A sample of femoral shaft segments totaling 162 individuals with ages ranging from 15 to 96 years is analyzed. Subperiosteal quantitative assessments are recorded at the most anterior point of the femoral shaft and also at points 25 degrees to the left and to the right of that point. Interobserver agreement in the assessments shows an acceptable degree of correlation. Bone remodeling with age does not progress in a linear, but in a curvilinear manner. Dependence of predicted age on nonremodeled surface counts in the analyzed areas of the anterior cortex of the femur appears to be significant. A set of regression equations is given. Sex can be ignored in age prediction. The small but statistically significant dependence of predicted age on cadaver length corresponds with the present strong secular increase in stature in the Netherlands. A concise catalogue with micrograph examples for every 10-year period in life is available upon request.