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We report on a case of a 35-year-old man who died suddenly and unexpectedly due to a 4-fluoroisobutyrylfentanyl (4-FIBF) mono-intoxication. Pathological, toxicological and chemical investigations were conducted at the Netherlands Forensic Institute. A full three-cavity forensic pathological examination was performed according to international guidelines. Biological samples obtained during autopsy were comprehensively investigated for the presence of toxic substances using headspace gas chromatography (GC) with flame ionization detection, liquid chromatography-time-of-flight mass spectrometry (LC-TOF-MS), GC-MS, high-performance LC with diode array detection and LC-tandem MS (LC-MS-MS). The seized crystalline substance found next to the body was investigated using a presumptive color test, GC-MS, Fourier-transform infrared spectroscopy and nuclear magnetic resonance. Pathological investigation identified minor lymphocytic infiltrates in the heart, considered irrelevant for the cause of death. Toxicological analysis of the victims' blood indicated the presence of a fluorobutyrylfentanyl (FBF) isomer, with no other compounds detected. The FBF isomer was identified in the seized crystalline substance as 4-FIBF. 4-FIBF concentrations were quantified in femoral blood (0.030 mg/L), heart blood (0.12 mg/L), vitreous humor (0.067 mg/L), brain tissue (>0.081 mg/kg), liver tissue (0.44 mg/kg) and urine (approximately 0.01 mg/L). Based on the outcomes of the pathological, toxicological and chemical investigations, the cause of death of the deceased was attributed to a fatal 4-FIBF mono-intoxication. The presented case underlines the added value of a combined bioanalytical and chemical investigative approach to identify and subsequently quantify fentanyl isomers in postmortem cases. Furthermore, it demonstrates the importance of investigating the postmortem redistribution of novel fentanyl analogs to establish reference values and to subsequently allow for correct interpretation of cause of death analysis in future casework., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Disaster victim identification (DVI) refers to the identification of multiple deceased persons following an event that has a catastrophic effect on human lives and living conditions. Identification methods in DVI are typically described as either being primary, which include nuclear genetic markers (DNA), dental radiograph comparisons, and fingerprint comparisons, or secondary, which are all other identifiers and are ordinarily considered insufficient as a sole means of identification. The aim of this paper is to review the concept and definition of so-called 'secondary identifiers" and draw on personal experiences to provide practical recommendations for improved consideration and use. Initially, the concept of secondary identifiers is defined and examples of publications where such identifiers have been used in human rights violation cases and humanitarian emergencies are reviewed. While typically not investigated under a strict DVI framework, the review highlights the idea that non-primary identifiers have proven useful on their own for identifying individuals killed as a result of political, religious, and/or ethnic violence. The use of non-primary identifiers in DVI operations in the published literature is then reviewed. Because there is a plethora of different ways in which secondary identifiers are referenced it was not possible to identify useful search terms. Consequently, a broad literature search (rather than a systematic review) was undertaken. The reviews highlight the potential value of so-called secondary identifiers but more importantly show the need to scrutinise the implied inferior value of non-primary methods which is suggested by the terms "primary" and "secondary". The investigative and evaluative phases of the identification process are examined, and the concept of "uniqueness" is critiqued. The authors suggest that non-primary identifiers may play an important role in providing leads to formulating an identification hypothesis and, using the Bayesian approach of evidence interpretation, may assist in establishing the value of the evidence in guiding the identification effort. A summary of contributions non-primary identifiers may make to DVI efforts is provided. In conclusion, the authors argue that all lines of evidence should be considered because the value of an identifier will depend on the context and the victim population. A series of recommendations are provided for consideration for the use of non-primary identifiers in DVI scenarios., Competing Interests: Conflict of interest The authors have no conflict of interest., (Crown Copyright © 2023. Published by Elsevier B.V. All rights reserved.)

Forensic pathologists and anthropologists are often asked in court for an opinion about the degree of force required to cause a specific injury. This paper examines and discusses the concept of 'degree of force' and why it is considered a pertinent issue in legal proceedings. This discussion identifies the implicit assumptions that often underpin questions about the 'degree of force'. The current knowledge base for opinions on the degree of force is then provided by means of a literature review. A critical appraisal of this literature shows that much of the results from experimental research is of limited value in routine casework. An alternative approach to addressing the issue is provided through a discussion of the application of Bayes' theorem, also called the likelihood ratio framework. It is argued that the use of this framework makes it possible for an expert to provide relevant and specific evidence, whilst maintaining the boundaries of their field of expertise.

Interpreting a myocardial inflammation as causal, contributory or as of no significance at all in the cause of death can be challenging, especially in cases where other pathologic and/or medico-legal findings are also present. To further evaluate the significance of myocardial inflammation as a cause of death we performed a retrospective cohort study of forensic and clinical autopsy cases. We revised the spectrum of histological inflammatory parameters in the myocardium of 79 adult autopsy cases and related these to the reported cause of death. Myocardial slides were reviewed for the distribution and intensity of inflammatory cell infiltrations, the predominant inflammatory cell type, and the presence of inflammation-associated myocyte injury, fibrosis, edema and hemorrhage. Next, the cases were divided over three groups, based on the reported cause of death. Group 1 ( n  = 27) consisted of all individuals with an obvious unnatural cause of death. Group 2 ( n  = 29) included all individuals in which myocarditis was interpreted to be one out of more possible causes of death. Group 3 ( n  = 23) consisted of all individuals in which myocarditis was reported to be the only significant finding at autopsy, and no other cause of death was found. Systematic application of our histological parameters showed that only a diffuse increase of inflammatory cells could discriminate between an incidental presence of inflammation (Group 1) or a potentially significant one (Groups 2 and 3). No other histological parameter showed significant differences between the groups. Our results suggest that generally used histological parameters are often insufficient to differentiate an incidental myocarditis from a (potentially) significant one., Competing Interests: The authors declare no conflict of interest., (© 2021 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science.)

Identified (documented) osteological collections represent an important resource in the development of forensic anthropology standards and methods as well as a precious tool for learning and training of practitioners. Even though the number of papers presenting identified collections worldwide increases, many of the collections have still not been divulged to the scientific community in sufficient detail to ascertain their exact number. The Forensic Anthropology Society of Europe (FASE) therefore developed a tool that goes beyond sporadic publications: the FASE Map of Identified Osteological Collections, which is freely accessible and continuously updated and revised. The online map is available at http://forensicanthropology.eu/osteological-collections/. The map of skeletal collections was created in 2017 and currently displays information on 153 identified osteological collections (43 of them categorized as contemporary) located in 41 different countries. This article offers a short analysis of the type, geographical location and content of the collections included in the map. The aim of this article and the map as such is to provide a useful resource to facilitate research planning and teaching in forensic anthropology and related disciplines., Competing Interests: Conflict of Interest None reported., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

For proximal femoral nailing, choosing the proper entry point with the aid of C-arm imaging is crucial. Therefore, obtaining accurate radiological views that facilitate sound identification of the tip of the greater trochanter (GT) is of utmost importance. The aim of this study was to define a radiological view characterised by reproducible radiographic landmarks which will allow the reliable identification of the tip of the GT in the anteroposterior view. Anatomical and radiographic features of 16 cadaveric femurs were analysed. The cortical overlap view (COV), characterised by the radiological overlap of the density line of the piriform fossa and the intertrochanteric crest, was identified. It marks the rotation of the proximal femur at which the GT can be accurately identified and used to determine the desired entry point for a proximal femoral nail. Trainees and fully qualified orthopedic trauma surgeons were asked to identify the correct COV in radiological imaging series. Mean internal rotation of the femur to achieve a COV was 17.5° (range 12.8°-21.8°). In the COV the tip of the GT is the highest visible point and the mean distance from the cortical overlap line to the tip of the GT is 4.45 mm. Intra- and inter-rater reliability was high with ICC(2,k) = 0.932 and ICC(2,k) = 0.987 respectively. Trainees achieved higher rates of correct COV identification than specialists. There was no significant correlation between the internal rotation of the femur to achieve the COV and femoral antetorsion. In conclusion, the COV is a highly reproducible radiological view that is characterised by radiographic landmarks easy to recognise. It allows for accurate identification of the tip of the GT, which can be used by the surgeon as a reference to determine the desired entry point for an intramedullary nail., (© 2021. The Author(s).)

Background/aim/objective: Late side effects of radiotherapy (RT) in the treatment for head and neck (HN) malignancies involve an inadequate healing response of the distressed tissue due to RT-induced hypovascularity. The aim of this study was to develop a pilot model in which vascular alterations associated with the onset of late irradiation (IR) injury could be measured in rabbit oral mucosa and mandibular bone., Materials and Methods: Eight male New Zealand white rabbits were divided over four treatment groups. Group I-III received four fractions of RT (5.6 Gy, 6.5 Gy, and 8 Gy, respectively) and Group IV received 1 fraction of 30 Gy. Oral microcirculatory measurements were performed at baseline (before RT) and once a week during 11 consecutive weeks after RT assessing perfusion parameters, that is, total vessel density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI). Post-mortem histopathology specimens were analyzed., Results: Five weeks after RT, TVD, and PVD in all groups showed a decrease of >10% compared to baseline, a significant difference was observed for Groups I, II, and IV ( P <0.05). At T11, no lasting effect of decreased vessel density was observed. PPV and MFI remained unaltered at all-time points. Group IV showed a marked difference in scattered telangiectasia such as microangiopathies, histological necrosis, and loss of vasculature., Conclusion: No significant lasting effect in mucosal microcirculation density due to IR damage was detected. Observed changes in microcirculation vasculature and histology may align preliminary tissue transition towards clinical pathology in a very early state associated with late IR injury in the oral compartment., Relevance for Patients: Enhancing knowledge on the onset of late vascular IR injury in the HN region could help the development, monitoring, and timing of therapies that act on prevention, discontinuation, or repair of radiation pathology., (Copyright: © Whioce Publishing Pte. Ltd.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) targets multiple organs and causes severe coagulopathy. Histopathological organ changes might not only be attributable to a direct virus-induced effect, but also the immune response. The aims of this study were to assess the duration of viral presence, identify the extent of inflammatory response, and investigate the underlying cause of coagulopathy., Methods: This prospective autopsy cohort study was done at Amsterdam University Medical Centers (UMC), the Netherlands. With informed consent from relatives, full body autopsy was done on 21 patients with COVID-19 for whom autopsy was requested between March 9 and May 18, 2020. In addition to histopathological evaluation of organ damage, the presence of SARS-CoV-2 nucleocapsid protein and the composition of the immune infiltrate and thrombi were assessed, and all were linked to disease course., Findings: Our cohort (n=21) included 16 (76%) men, and median age was 68 years (range 41-78). Median disease course (time from onset of symptoms to death) was 22 days (range 5-44 days). In 11 patients tested for SARS-CoV-2 tropism, SARS-CoV-2 infected cells were present in multiple organs, most abundantly in the lungs, but presence in the lungs became sporadic with increased disease course. Other SARS-CoV-2-positive organs included the upper respiratory tract, heart, kidneys, and gastrointestinal tract. In histological analyses of organs (sampled from nine to 21 patients per organ), an extensive inflammatory response was present in the lungs, heart, liver, kidneys, and brain. In the brain, extensive inflammation was seen in the olfactory bulbs and medulla oblongata. Thrombi and neutrophilic plugs were present in the lungs, heart, kidneys, liver, spleen, and brain and were most frequently observed late in the disease course (15 patients with thrombi, median disease course 22 days [5-44]; ten patients with neutrophilic plugs, 21 days [5-44]). Neutrophilic plugs were observed in two forms: solely composed of neutrophils with neutrophil extracellular traps (NETs), or as aggregates of NETs and platelets.., Interpretation: In patients with lethal COVID-19, an extensive systemic inflammatory response was present, with a continued presence of neutrophils and NETs. However, SARS-CoV-2-infected cells were only sporadically present at late stages of COVID-19. This suggests a maladaptive immune response and substantiates the evidence for immunomodulation as a target in the treatment of severe COVID-19., Funding: Amsterdam UMC Corona Research Fund., (© 2020 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license.)

In this position statement, the Board members of the Forensic Anthropology Society of Europe (FASE) argue that forensic anthropology methods can be used as means of personal identification, particularly in situations with limited availability of traditional identification methods (i.e. dactyloscopy, odontology, and molecular genetic analysis). This statement has been issued taking into account the international migration crises related to thousands of deaths worldwide, in which the utility of these traditional means of identification has been sporadic to non-existent. The statement is however not limited to deaths related to the migration crises, as similar problems may occur in fatalities en masse such as in natural disasters and armed conflicts, and on a smaller scale in cases of homeless or otherwise socioeconomically disadvantaged persons. The number of reports on personal identification based on sound anthropological methodology is increasing in the scientific literature. However, more research is needed to develop evidence-based standard operating procedures and statistical frameworks. It remains essential to raise awareness among forensic practitioners, law enforcement, and judiciary professionals on the utility of forensic anthropology in cases where it can provide sufficient information for identification., (Copyright © 2020. Published by Elsevier B.V.)

Human-made and natural disasters can result in severely fragmented, compromised, and commingled human remains. The related disaster victim identification (DVI) operations are invariably challenging, with the state of the remains potentially precluding some identifications. Practitioners involved in these DVI operations will routinely face logistical, practical, and ethical challenges. This review provides information and guidance derived from first-hand experiences to individuals tasked with managing DVI operations with fragmented human remains. We outline several key issues that should be addressed during disaster preparedness planning and at the outset of an operation, when incident-specific strategies are developed. Specific challenges during recovery and examination of fragmented remains are addressed, highlighting the importance of experienced specialists at the scene and in the mortuary. DNA sample selection and sampling techniques are reviewed, as well as downstream effects of commingling and contamination, which can complicate reconciliation and emphasise the need for rigorous quality control. We also touch on issues that may arise during communication with families. While recommendations are provided, they are not intended as proscriptive policy but rather as an addition to the general recommendations given in the International Criminal Police Organization (INTERPOL) DVI Guide, to inform preparative discussions between government officials, judiciary, police, and forensic specialists.Key pointsA DVI operation for an incident characterised by many fragmented and otherwise compromised human remains poses specific challenges that may prolong and complicate identifications.Specialists should be consulted at the outset to address key issues related to the aim and extent of the operation.Specialist expertise in handling compromised human remains is indispensable at the scene, in the mortuary, during reconciliation, and for quality control.Continuous consultation between representatives from government, the judiciary, law enforcement, the media, and various forensic specialists will prevent unnecessary delay and facilitate accurate and timely communication., Competing Interests: The authors declare that they have no conflict of interest and that this work has not received any funding., (© 2020 The Author(s). Published by Taylor & Francis Group on behalf of the Academy of Forensic Science.)

Clinical radiology is increasingly used as a source of data to test or develop forensic anthropological methods, especially in countries where contemporary skeletal collections are not available. Naturally, this requires analysis of the error that is a result of low accuracy of the modality (i.e. accuracy of the segmentation) and the error that arises due to difficulties in landmark recognition in virtual models. The cumulative effect of these errors ultimately determines whether virtual and dry bone measurements can be used interchangeably. To test the interchangeability of virtual and dry bone measurements, 13 male and 14 female intact cadavers from the body donation program of the Amsterdam UMC were CT scanned using a standard patient scanning protocol and processed to obtain the dry os coxae. These were again CT scanned using the same scanning protocol. All CT scans were segmented to create 3D virtual bone models of the os coxae ('dry' CT models and 'clinical' CT models). An Artec Spider 3D optical scanner was used to produce gold standard 'optical 3D models' of ten dry os coxae. The deviation of the surfaces of the 3D virtual bone models compared to the gold standard was used to calculate the accuracy of the CT models, both for the overall os coxae and for selected landmarks. Landmark recognition was studied by comparing the TEM and %TEM of nine traditional inter-landmark distances (ILDs). The percentage difference for the various ILDs between modalities was used to gauge the practical implications of both errors combined. Results showed that 'dry' CT models were 0.36-0.45mm larger than the 'optical 3D models' (deviations -0.27mm to 2.86mm). 'Clinical' CT models were 0.64-0.88mm larger than the 'optical 3D models' (deviations -4.99mm to 5.00mm). The accuracies of the ROIs were variable and larger for 'clinical' CT models than for 'dry' CT models. TEM and %TEM were generally in the acceptable ranges for all ILDs whilst no single modality was obviously more or less reliable than the others. For almost all ILDs, the average percentage difference between modalities was substantially larger than the average percentage difference between observers in 'dry bone' measurements only. Our results show that the combined error of segmentation- and landmark recognition error can be substantial, which may preclude the usage of 'clinical' CT scans as an alternative source for forensic anthropological reference data., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In antemortem fractures, the estimation of the amount of time that has lapsed between the traumatic event and eventual death (the socalled 'posttraumatic survival time' or PTST) can have substantial implications in legal proceedings. It might for instance help to corroborate witness testimonies, to reconstruct the chain of events leading to eventual death or to establish a sequence when multiple traumata in a single individual are encountered. However, PTST estimation of bone trauma is impeded by a myriad of theoretical and practical issues, and is therefore almost invariably considered challenging. A few years ago, a method that combines radiological and histological analysis of fractures to estimate the minimum amount of lapsed PTST in skeletonized remains was proposed. This study aims to test its accuracy on a set of five rib fractures and four skull lesions fractures with known and varying amounts of posttraumatic survival time. In addition, it explores the differences between the assessment on ribs and skull bones and it expands on the proposed method by including computed tomography (CT) scanning. Using conventional radiology and histology, the minimum amount of PTST was accurately estimated in 8 out of 9 of the cases (89%). The one discrepancy between the estimated and known PTST was minimal, being just one day. The precision of the method diminishes as healing advances. It was noted that skull lesions showed less advanced and less well-developed healing features than the lapsed PTST would suggest. Of the three used modalities, conventional radiology proved to be the least accurate. CT scanning proved to be a valuable, sometimes even superior alternative to conventional radiology. Histology was superior to both conventional radiology and CT scanning. The results of our study illustrate the potential of the combined application of radiology and histology to estimate the PSTS in skeletonized human fractures., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Forensic anthropological knowledge has been used in disaster victim identification (DVI) for over a century, but over the past decades, there have been a number of disaster events which have seen an increasing role for the forensic anthropologist. The experiences gained from some of the latest DVI operations have provided valuable lessons that have had an effect on the role and perceived value of the forensic anthropologist as part of the team managing the DVI process. This paper provides an overview of the ways in which forensic anthropologists may contribute to DVI with emphasis on how recent experiences and developments in forensic anthropology have augmented these contributions. Consequently, this paper reviews the value of forensic anthropological expertise at the disaster scene and in the mortuary, and discusses the way in which forensic anthropologists may use imaging in DVI efforts. Tissue-sampling strategies for DNA analysis, especially in the case of disasters with a large amount of fragmented remains, are also discussed. Additionally, consideration is given to the identification of survivors; the statistical basis of identification; the challenges related to some specific disaster scenarios; and education and training. Although forensic anthropologists can play a valuable role in different phases of a DVI operation, they never practice in isolation. The DVI process requires a multidisciplinary approach and, therefore, has a close collaboration with a range of forensic specialists., (© 2018 The Author(s). Published by Taylor & Francis of the Academy of Forensic Science.)

In disaster victim identification (DVI), DNA profiling is considered to be one of the most reliable and efficient means to identify bodies or separated body parts. This requires a post mortem DNA sample, and an ante mortem DNA sample of the presumed victim or their biological relative(s). Usually the collection of an adequate ante mortem sample is technically simple, but the acquisition of a good quality post mortem sample under unfavourable DVI circumstances is complicated due to the variable degree of preservation of the human remains and the high risk of DNA (cross) contamination. This paper provides the community with an efficient method to collect post-mortem DNA samples from muscle, bone, bone marrow and teeth, with a minimal risk of contamination. Our method has been applied in a recent, challenging DVI operation (i.e. the identification of the 298 victims of the MH17 airplane crash in 2014). 98,2% of the collected PM samples provided the DVI team with highly informative DNA genotyping results without the risk of contamination and consequent mistyping the victim's DNA. Moreover, the method is easy, cheap and quick. This paper provides the DVI community with a step-wise instructions with recommendations for the type of tissue to be sampled and the site of excision (preferably the upper leg). Although initially designed for DVI purposes, the method is also suited for the identification of individual victims., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Early diagnosis of deep tissue injury remains problematic due to the complicated and multifactorial nature of damage induction and the many processes involved in damage development and recovery. In this paper, we present a comprehensive assessment of deep tissue injury development and remodeling in a rat model by multiparametric magnetic resonance imaging (MRI) and histopathology. The tibialis anterior muscle of rats was subjected to mechanical deformation for 2 h. Multiparametric in vivo MRI, consisting of T 2 , T 2 *, mean diffusivity (MD), and angiography measurements, was applied before, during, and directly after indentation as well as at several time points during a 14-day follow-up. MRI readouts were linked to histological analyses of the damaged tissue. The results showed dynamic change in various MRI parameters, reflecting the histopathological status of the tissue during damage induction and repair. Increased T 2 corresponded with edema, muscle cell damage, and inflammation. T 2 * was related to tissue perfusion, hemorrhage, and inflammation. MD increase and decrease was reported on the tissue's microstructural integrity and reflected muscle degeneration and edema as well as fibrosis. Angiography provided information on blockage of blood flow during deformation. Our results indicate that the effects of a single damage-causing event of only 2 h of deformation were present up to 14 days. The initial tissue response to deformation, as observed by MRI, starts at the edge of the indentation. The quantitative MRI readouts provided distinct and complementary information on the extent, temporal evolution, and microstructural basis of deep tissue injury-related muscle damage. NEW & NOTEWORTHY We have applied a multiparametric MRI approach linked to histopathology to characterize damage development and remodeling in a rat model of deep tissue injury. Our approach provided several relevant insights in deep tissue injury. Response to damage, as observed by MRI, started at some distance from the deformation. Damage after a single indentation period persisted up to 14 days. The MRI parameters provided distinct and complementary information on the microstructural basis of the damage.

Sex estimation techniques are frequently applied in forensic anthropological analyses of unidentified human skeletal remains. While morphological sex estimation methods are able to endure population differences, the classification accuracy of metric sex estimation methods are population-specific. No metric sex estimation method currently exists for the Dutch population. The purpose of this study is to create Dutch population specific sex estimation formulae by means of osteometric analyses of the proximal femur. Since the Netherlands lacks a representative contemporary skeletal reference population, 2D plane reconstructions, derived from clinical computed tomography (CT) data, were used as an alternative source for a representative reference sample. The first part of this study assesses the intra- and inter-observer error, or reliability, of twelve measurements of the proximal femur. The technical error of measurement (TEM) and relative TEM (%TEM) were calculated using 26 dry adult femora. In addition, the agreement, or accuracy, between the dry bone and CT-based measurements was determined by percent agreement. Only reliable and accurate measurements were retained for the logistic regression sex estimation formulae; a training set (n=86) was used to create the models while an independent testing set (n=28) was used to validate the models. Due to high levels of multicollinearity, only single variable models were created. Cross-validated classification accuracies ranged from 86% to 92%. The high cross-validated classification accuracies indicate that the developed formulae can contribute to the biological profile and specifically in sex estimation of unidentified human skeletal remains in the Netherlands. Furthermore, the results indicate that clinical CT data can be a valuable alternative source of data when representative skeletal collections are unavailable., (Copyright © 2017 Elsevier B.V. All rights reserved.)

A 68-year-old woman, previously treated with embolization of the thoracic duct with Lipiodol (an ethiodized oil injection) and cyanoacrylate glue (a topical tissue adhesive), was admitted with an asymptomatic mass in the inferior vena cava (IVC) and right atrium. The mass was surgically removed, and pathologic analysis revealed a Lipiodol-containing thrombus. To our knowledge, this is the first clinicopathologic report of Lipiodol-induced thrombus presenting as an intracavitary mass., (Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

This paper describes an investigation of the sudden and unexpected death of a five-and-a-half-month-old boy. As in every Dutch case of sudden unexpected death in infancy (SUDI), a multidisciplinary diagnostic approach was used. This included post-mortem radiography, showing a linear discontinuity of the parietal bone. Originally this was interpreted as a skull fracture, but autopsy indicated no signs of mechanical trauma. Instead the defect was defined as a unilateral accessory suture of the parietal bone. The initial erroneous diagnosis had severe adverse consequences and thus every health care professional or forensic specialist dealing with paediatric mechanical traumas should be cautious of this rare anomaly., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

In the Netherlands dapsone is used for the treatment of dermatitis herpetiformis, leprosy and Pneumocystis jiroveci pneumonia and prophylaxis in case of cotrimoxazole allergy. An idiosyncratic drug reaction, known as the dapsone hypersensitivity syndrome (DHS), appears in about 0.5-3.6% of persons treated with dapsone. DHS can be associated with fever, rash and systemic involvement. We present a 35-year-old woman who developed severe DHS seven weeks after starting dapsone. Six weeks after being discharged in a good clinical condition she died from fulminant myocarditis, 11 weeks after the first DHS symptoms and the discontinuation of dapsone.

Background: Although the Absorb bioresorbable vascular scaffold is increasingly used in daily clinical practice for the treatment of coronary artery disease, the exact vascular healing pattern and the resorption process in humans is unknown because histological data are derived only from animal studies., Methods and Results: We have obtained 4 autopsies (5 scaffolds) since August 2013. Duration of bioresorbable vascular scaffold implantation ranged from 3 to 501 days. All autopsies and histological assessments were performed by dedicated cardiovascular pathologists. At 1 week after bioresorbable vascular scaffold implantation, struts were covered with a fine layer of fibrin and platelets. At 113 days, the scaffold struts were fully covered with smooth muscle cells. Hyaline eosinophilic and proteoglycan material infiltrating the scaffold struts was observed at 501 days after implantation. At all time points, we observed the presence of multinuclear foreign body giant cells adjacent to the scaffold struts., Conclusions: Resorption and healing processes after bioresorbable vascular scaffold implantation in human patients mirror those observed in porcine models. The presence of multinucleated foreign body giant cells at both short- and long-term follow-up needs further investigation and may be related to a low-grade absorptive inflammatory response to the polymer., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Assessment of trauma on skeletal remains can be very difficult, especially when it comes to the estimation of posttraumatic survival time in partially healed lesions. The ability to reliably estimate the time an individual has survived after sustaining an injury is especially important in cases of child abuse and torture, but can also aid in determining the association between an injury and eventual death. Here a case from South Africa is reported, where the skeletal remains of an unknown individual were found with cranial and scapular fractures. These fractures all presented with macroscopic features indicative of healing. Using recently published data on the timing of fractures by De Boer et al., the two sets of cranial trauma and the scapular fracture were assessed by means of radiology, histology and microCT scanning. This was primarily done in order to obtain more information on the events surrounding the death of this individual, but also to assess the usability of the published methods on cranial fractures. It was found that the initial trauma was most likely sustained at least two weeks before death, whilst a neurosurgical procedure was performed at least one week before death. It seems that cranial fractures, especially if stable, may show some different healing features than postcranial fractures. The individual has since been identified, but unfortunately as is often the case in South Africa, limited information is available and the medical records could not be found., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Short-term caloric restriction increases plasma levels of nonesterified fatty acids (NEFAs) and is associated with increased myocardial triglyceride (TG) content and decreased myocardial function in healthy subjects. Whether this flexibility of myocardial TG stores and myocardial function is also present in patients with type 2 diabetes mellitus (T2DM) is yet unknown. Myocardial TG content and left ventricular (LV) ratio between the early (E) and atrial (A) diastolic filling phase (E/A) were determined using magnetic resonance (MR) spectroscopy and MR imaging, respectively, before and after a 3-day very low-calorie diet (VLCD) in 11 patients with T2DM. In addition, we studied patients after a 3-day VLCD combined with the antilipolytic drug acipimox. The VLCD induced myocardial TG accumulation [from 0.66 +/- 0.09% (mean +/- SE, baseline) to 0.98 +/- 0.16%, P = 0.028] and a decrease in E/A ratio [from 1.00 +/- 0.05 (baseline) to 0.90 +/- 0.06, P = 0.002]. This was associated with increased plasma NEFA levels (from 0.57 +/- 0.08 mmol/l at baseline to 0.92 +/- 0.12, P = 0.019). After the VLCD with acipimox, myocardial TG content, diastolic function, and plasma NEFA levels were similar to baseline values. In conclusion, in patients with T2DM, a VLCD increases myocardial TG content and is associated with a decrease in LV diastolic function. These effects were not observed when a VLCD was combined with acipimox, illustrating the physiological flexibility of myocardial TG stores and myocardial function in patients with T2DM.

Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to improve in the later phases of wound healing. It was not affected by the administration of antineoplastic agents; neither were muscularis repair, epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue, fibroblasts and macrophages were present in maximal amounts after 7 days appearing later or showing this maximum at a different moment in time when antineoplastic agents were given. The processes of epithelial and muscularis repair were not influenced by the relative position of the wound edges. Granulation tissue, macrophages, and fibroblasts were the best parameters for measuring the histologic evolution of intestinal wound healing, and the effects of antineoplastic agents upon it.

We investigated the effect of two doses of cytostatics, administered intraperitoneally during 5 consecutive days, on the healing of ileal and colonic anastomoses constructed on the third day. The cytostatics regimen consisted of a combination of 5-fluorouracil, bleomycin and cisplatin at 10, 2 and 0.35 mg kg-1d-1, respectively, or at twice higher doses. The lower dose was similar to that given intravenously in previous experiments. Rats were sacrificed 3 or 7 days after operation. No effects of cytostatics were observed after 3 days, neither on anastomotic bursting pressure nor on hydroxyproline concentration (microgram/mg dry weight) or content (microgram cm-1). Profound effects were seen at 7 days. In the high dose group, bursting pressures in both anastomoses were greatly reduced with respect to the control group. Concurrently, collagen synthesis was severely impaired, as indicated by sustained decreased hydroxyproline concentrations and content. The lower dose of cytostatics showed essentially similar effects on hydroxyproline parameters, but affected anastomotic strength less dramatically. The data indicate that, while intraperitoneal chemotherapy may show less detrimental systemic toxicity and thus allow higher doses, its application as an adjunct to gastrointestinal surgery may be limited because of its severe effects on anastomotic repair.

Hemihepatectomy along with portal vein or hepatic artery replacement in dogs was well tolerated, but combined with replacement of both vessels it was lethal because of outflow block and shock. Total liver blood flow should be kept as high as possible during such procedures in man.

Four patients with neurofibromatosis and a dysplastic type of congenital pseudarthrosis of the tibia were treated by resection of the lesion and reconstruction of the extremity with a free vascularized fibular graft. Solid union of the graft was achieved within 3 months in 3 children. However, valgus malalignment of the tibia progressed in all 3. One child was treated with resection of a lateral fibrotic band and another with distal tibial epiphysial distraction and realignment. In the fourth patient, who was skeletally mature, a nonunion developed proximally.

Since 1971, 151 nonpalpable breast cancers (100 invasive carcinomas, 39 in situ ductal carcinomas, and twelve lobular carcinomas in situ) have been diagnosed and treated at the St. Radboud University Hospital. Of the 100 clinically occult invasive carcinomas, 53 had pathologic diameters of more than 10 mm, 29 were of sizes between 6 and 10 mm, and 18 were tumors of 5 mm or less. Residual tumor outside the "excisional" biopsy cavity was encountered in 76 of the 118 mastectomy specimens (64.4%) fully capable of evaluation. Invasive residual tumor would have been left behind in 34 of 86 mastectomy specimens (39.5%). Of 27 axillas studied, no patient with in situ carcinoma had evidence of axillary lymph node metastases. Invasive carcinoma, however, showed axillary lymph node involvement in 7.7% of mastectomy specimens when the size of the primary tumor was not more than 5 mm, in 12.5% when the size was between 6 and 10 mm, and in 29.5% when the primary tumor was more than 10 mm in diameter. The 10-year recurrence-free survival (RFS) of patients with clinically occult invasive carcinomas greater than 10 mm in size was 71.9% and differed significantly from the 90.9% for patients with the invasive tumors less than or equal to 5 mm, as well as from the 100% RFS of patients with invasive tumors of between 6 and 10 mm and noninvasive tumors. Although the 10-year RFS was 92.6% for the patients with negative axillary nodes and 80.0% for the patients with positive axillary nodes, this difference did not reach statistical significance. However, the disease-specific overall survival after 10 years was significantly different between node-negative patients (96.4%) and node-positive patients (78.8%). Multivariate analysis disclosed that the relationship between size of the primary tumor and RFS was independent of the presence of axillary lymph node metastases. In conclusion, the validity of the concept of minimal breast cancer has been re-enforced. However, the results of this study suggest that the upper limit of the original definition of minimal breast cancer is too narrow and should be extended, so that, apart from the noninvasive tumors--regardless of their size--all invasive tumors having a maximum diameter less than or equal to 10 mm should be regarded as minimal breast cancers.

Various histological parameters of wound repair have been studied in intestinal anastomoses in the rabbit in order to compare the healing processes in ileum and colon. The sequentional appearance of granulocytes, macrophages and fibroblasts has been studied from 3 h to 7 days after operation. Also, degree of necrosis, formation of capillaries and mucosal repair were analysed semi-quantitatively. Significant differences were observed between ileal and colonic anastomoses with respect to occurrence of granulocytes, necrosis and mucosal repair, particularly 7 days after operation. At that time, granulocytes and necrosis were virtually absent from ileal anastomoses, while mucosal integrity was restored in the majority of cases examined. In contrast, granulocytes and necrosis were still abundantly present in colonic anastomoses and mucosal repair was poor. These results support biochemical evidence that wounds in the ileum heal more rapidly than wounds in the colon. Possibly, the sustained presence of granulocytes, which are a potential source of collagenase activity, is important in this respect. Investigation of the same features of intestinal wound healing in rabbits with peritonitis induced by infection showed similar results and no differences were found between infected and non-infected animals.