Bela Kubat

Prolonged C1 Inhibitor Administration Improves Local Healing of Burn Wounds and Reduces Myocardial Inflammation in a Rat Burn Wound Model

In a previous study, the authors found persistent presence of acute inflammation markers such as C-reactive protein and complement factors locally in burn wounds. This persistence of acute inflammation may not only delay local burn wound healing but also have a systemic effect, for instance on the heart. Here, the effects of C1 esterase inhibitor (C1inh), an inhibitor of complement activation, on burn wound progression and the heart were analyzed in rats. Dorsal full-thickness burn wounds (2 × 4 cm) were induced on female Wistar rats (n = 14). The rats were divided into two groups (n = 7): a control group (just burns) and a C1inh group. C1inh was administered daily intravenously for 14 days. The burn wound, healthy skin from the hind leg (internal control), and the heart were then fixed in formalin. Tissues were analyzed for granulation tissue formation, reepithelialization, amount and type of infiltrating inflammatory cells (granulocytes and macrophages), and inflammatory markers (complement factors C3 and C4). C1inh treatment significantly reduced the amount of granulation tissue and significantly increased reepithelialization. C1inh also significantly reduced macrophage infiltration. Burns induced infiltration of macrophages into the ventricles of the heart and remarkably also into the atria of the heart. This effect could be counteracted by C1inh. These data show that systemic treatment with C1inh acts at different levels resulting in improved healing locally in burn wounds and systemically reduced inflammation in the heart. Therefore, C1inh might be a possible therapeutic intervention for burn wound patients.

Cerebral arterial air embolism in a child after intraosseous infusion

Cerebral arterial air embolism (CAAE) has been reported as a rare complication of medical intervention. There has been one reported case of CAAE after the use of an intraosseous infusion (IO) system. We report on a case of CAAE after tibial IO infusion in a 7-month-old girl during resuscitation.

Using the table in the Swedish review on shaken baby syndrome will not help courts deliver justice

1.Department of Forensic Medicine, Section on Forensic Pediatrics, Netherlands Forensic Institute, The Hague, The Netherlands 2.Institute of Legal Medicine/University Hospital of Cologne, Cologne, Germany 3.Department for Pediatric and Adolescent Medicine, Child Protection Center, Klinikum Kassel, Germany 4.Department of Forensic Medicine, Netherlands Forensic Institute, The Hague, The Netherlands 5.Forensic Pathology, University Medical Center, Maastricht, The Netherlands 6.Forensic (Paediatric) Radiology, Amsterdam Medical Center, Amsterdam, The Netherlands 7.Department of Legal Medicine, University Medical Center, Hamburg-Eppendorf, Germany 8.Forensic Pathology and Clinical Forensic Medicine, Oslo University Hospital and Institute of Clinical Medicine, University of Oslo, Oslo, Norway

Atrial Fibrillation Coincides with the Advanced Glycation End Product Nε-(Carboxymethyl)Lysine in the Atrium

Presence of advanced glycation end products (AGEs) in the heart induces a proinflammatory phenotype. However, the presence of AGEs within atrial tissue of atrial fibrillation (AF) patients is unknown and was analyzed here. Left atrial appendage tissue from 33 AF patients and 9 controls was analyzed for the presence of the major AGEs N(ε)-(carboxymethyl)lysine (CML), VCAM-1, neutrophilic granulocytes, lymphocytes, and macrophages in both the fat tissue and myocardium separately. The total amount of fibrosis was also analyzed. Presence of CML was significantly higher in blood vessels of the left atrial appendage in AF patients as compared to controls, independent of diabetes mellitus. In AF patients, VCAM-1 expression in blood vessels and the numbers of infiltrated neutrophilic granulocytes, lymphocytes, and macrophages significantly increased compared to controls, and were highest in the fat tissue; there was no significant difference in fibrosis compared to controls. Interestingly, total amount of CML and fibrosis in AF and control patients correlated positively. Finally, there was no difference between AF patients based on AF type or surgical indication in the presence of CML, VCAM-1 expression, inflammatory cells, and fibrosis. Our results indicate that in AF the intramyocardial blood vessels of the left atrial appendage have an increased CML presence and proinflammatory status coinciding with a local increase in the number of inflammatory cells.

Ventricular myocarditis coincides with atrial myocarditis in patients

INTRODUCTION Atrial fibrillation (AF) is a common complication in myocarditis. Atrial inflammation has been suggested to play an important role in the pathophysiology of AF. However, little is known about the occurrence of atrial inflammation in myocarditis patients. Here, we analyzed inflammatory cell numbers in the atria of myocarditis patients without symptomatic AF. METHODS Cardiac tissue was obtained postmortem from lymphocytic myocarditis patients (n=6), catecholamine-induced myocarditis patients (n=5), and control patients without pathological evidence of heart disease (n=5). Tissue sections of left and right ventricle and left and right atrium were stained for myeloperoxidase (neutrophilic granulocytes), CD45 (lymphocytes), and CD68 (macrophages). These cells were subsequently quantified in atrial and ventricular myocardium and atrial adipose tissue. RESULTS In lymphocytic myocarditis patients, a significant increase was observed for lymphocytes in the left atrial adipose tissue. In catecholamine-induced myocarditis patients, significant increases were found in the atria for all three inflammatory cell types. Infiltrating inflammatory cell numbers in the atrial myocardium correlated positively with those in the ventricles, especially in catecholamine-induced myocarditis patients. CONCLUSIONS To a varying extent, atrial myocarditis occurs concurrently with ventricular myocarditis in patients diagnosed with myocarditis of different etiology. This provides a substrate that potentially predisposes myocarditis patients to the development of AF and subsequent complications such as sudden cardiac death and heart failure.

Radiological analysis of hand and foot injuries after small aircraft crashes

Medico-legal investigation of fatal aviation accidents should contribute to the reconstruction of the accident in addition to providing the usual information about cause and manner of death. In cases with more than one fatality, the question of who was flying the plane at the time of the crash may need to be answered. In such cases the identification of “control injuries” plays an important role. This study aims to investigate whether specific patterns of skeletal hand and foot injuries could assist in the identification of the pilot. The analysis of radiological investigations of hands and feet of 27 fatalities from 18 accidents showed that foot injuries are more frequent than hand injuries in pilots and passengers, dislocations of feet were more frequent in passengers, and right-sided injuries were more frequent in pilots. Injuries of the distal parts of the hand were slightly more frequent in the pilot group. The limited numbers in the study do not allow definitive conclusions and further investigations are needed. However, the study yields interesting results and shows that radiological examination should be included in the medico-legal air crash investigation.

Multicystic encephalopathy in abusive head trauma

OBJECTIVE The proof of abusive head trauma (AHT) in infants is difficult, especially in cases with a long posttraumatic survival period. In the acute phase, injury to the cranio-cervical junction causes disturbances in respiratory and cardiac control, leading to apnea and bradycardia. Infants who survive the acute phase may subsequently develop multicystic encephalopathy. Because some types of changes are age-dependent, examination of the patterns of brain damage in these cases could provide information about the time in which they were inflicted. In particular, this could apply to the extent of the cystic changes, namely that the severity thereof may decrease with older age upon infliction of the trauma. This could potentially date the injury and thereby help to identify the perpetrator. We present an analysis of the patterns of brain damage in cases of AHT-induced multicystic encephalopathy and comment on the possible etiology and the implications thereof. MATERIALS Nine archival cases of trauma-induced multicystic encephalopathy, originating between the years 2005 and 2011, were identified. In 8 of these cases, hematoxilin-eosin-stained whole-hemisphere histologic slides, as well as small histologic slides of cerebellar hemispheres, were available for the evaluation of the topographic distribution of the macroscopic and microscopic changes. RESULTS The cerebral hemispheres were more affected than the cerebellum. The magnitude of the cystic changes did not correlate with the age at which the trauma had occurred, nor the surviva period. All cases showed asymmetrical affection of the cerebral hemispheres, which in 3 cases was very pronounced. The analysis revealed both ischemia- and hypoperfusion-induced injury patterns. CONCLUSION Analysis of the magnitude and the distribution of the damage do not assist in the estimation of the period at which the trauma had occurred. The evaluation showed that ischemia, and to a lesser extent, hypoperfusion, were the major mechanisms of brain injury in these cases, which does not narrow the differential diagnosis of the underlying problem. However, in cases of multicystic encephalopathy, in the absence of a plausible medical explanation for the development of this condition, a remote (abusive) head trauma should be considered.

10q25.3 (DMBT1) copy number changes in astrocytoma grades II and IV.

In the literature, it has been suggested that loss of the 10q25‐26 region, including the DMBT1 gene (10q25.3), is correlated with initiation and/or malignant progression of astrocytomas, although the results of the studies on the loss of heterozygosity that led to this assumption are not unequivocal. For this reason, using double‐target fluorescence in situ hybridization, we compared copy number changes of 10q25.3 to those of the pericentromeric region (10q12) in 10 cases each of astrocytoma grades II and IV. The same specimens were analyzed for copy number changes of chromosome 1, as a marker for polyploidy, and chromosome 7, which is often gained in astrocytomas of all grades. Our results show that selective loss of the 10q25.3 region was present in 2 of 10 specimens in both astrocytoma grade II and grade IV, occurring only in tumors with polysomy for 10q12. Furthermore, astrocytoma grade II often showed polyploidy for chromosomes 1, 7, and 10 (8 of 10 specimens). In addition, astrocytoma grade IV frequently exhibited losses of chromosome 10 in a high percentage of nuclei. Although based on a small number of cases, the results clearly show that loss of the 10q25.3 region is uncommon in astrocytoma grade II and mostly coincident with loss of chromosome 10 in grade IV tumors. These data indicate that selective loss of the 10q25.3 region, including the DMBT1 gene, is not an initiating event in the genesis of astrocytoma grade II.

Persistent Retinal Iron in Abusive Head Trauma

Retinal hemosiderin deposition is a histologic indicator of sustained hemorrhage but cannot be used to precisely estimate the elapsed time since an episode of trauma. A 5‐month‐old male infant was admitted to hospital after acute deterioration. Examination revealed encephalopathy, subdural hematomas, and retinal hemorrhages consistent with abusive head trauma (AHT). At the age of 3, he was readmitted to hospital with spontaneous osteopenic fracture of the right femur. The patient deteriorated and died after unsuccessful resuscitation. Ophthalmopathological investigation showed atrophy of the retina and optic nerve and hemosiderin deposition in both eyes. Retinal hemosiderin deposition is currently generally assumed to disappear within 6–8 weeks after the occurrence of hemorrhage in AHT. This case report describes an infant with bilateral retinal hemosiderin depositions due to hemorrhages sustained from AHT occurring 32 months prior to death. Implications of this finding for the interpretation of retinal hemosiderin depositions in AHT are discussed.

Traumatic vertebral artery injury: proposal for classification of the severity of trauma and likelihood of fatal outcome

Vertebral artery injury (VAI) occurs after (blunt) trauma as well as spontaneously. The risk of incurring VAI from a blunt trauma probably parallels the severity of trauma, often referred to as major- and minor-trauma. However, the literature does not provide concrete definitions of these terms. This study aims to define minor- and major-trauma and to analyze the likelihood of fatal outcome in VAI. For this purpose, classification criteria of major- and minor-trauma were developed and a PubMed database search was performed for articles on VAI published prior to 2013. The definitions of minor- and major-trauma, derived mainly from radiological screening criteria in cervical spine injury and based on the mechanism leading to the injury, were used in the analysis of the literature. The search produced 241 VAI cases with sufficiently detailed data for the comparison of major-trauma (52 cases, 50 lethal), minor-trauma (8 cases, none lethal), and no-trauma (182 cases, 69 lethal). The numbers of lethal cases in the total study population and subgroups differed significantly between the groups (Fisher’s exact test) and the likelihood ratios (LRs) of lethal outcome were substantially higher in the major-trauma group compared to the other groups. The highly significant p values show that the proposed criteria differentiate between trauma types with regard to fatal outcome. The presented results can assist in the evaluation of forensic cases of VAI.