Eye Tumors in Childhood as First Sign of Tumor Predisposition Syndromes: Insights from an Observational Study Conducted in Germany and Austria.

Retinoblastoma and other eye tumors in childhood are rare diseases. Many eye tumors are the first signs of a genetic tumor predisposition syndrome and the affected children carry a higher risk of developing other cancers later in life. Clinical and genetic data of all children with eye tumors diagnosed between 2013-2018 in Germany and Austria were collected in a multicenter prospective observational study. In five years, 300 children were recruited into the study: 287 with retinoblastoma, 7 uveal melanoma, 3 ciliary body medulloepithelioma, 2 retinal astrocytoma, 1 meningioma of the optic nerve extending into the eye. Heritable retinoblastoma was diagnosed in 44% of children with retinoblastoma. One child with meningioma of the optic nerve extending into the eye was diagnosed with neurofibromatosis 2. No pathogenic constitutional variant in DICER1 was detected in a child with medulloepithelioma while two children did not receive genetic analysis. Because of the known association with tumor predisposition syndromes, genetic counseling should be offered to all children with eye tumors. Children with a genetic predisposition to cancer should receive a tailored surveillance including detailed history, physical examinations and, if indicated, imaging to screen for other cancer. Early detection of cancers may reduce mortality.

Exudate macrophages attenuate lung injury by the release of IL-1 receptor antagonist in gram-negative pneumonia.

RATIONALE: Exudate macrophages are key players in host defense toward invading pathogens. Their antiinflammatory and epithelial-protective potential in gram-negative pneumonia, however, remains elusive. OBJECTIVES: We investigated whether exudate macrophages contributed to preservation of alveolar epithelial barrier integrity and analyzed the molecular pathways involved. METHODS: We evaluated the antiinflammatory and epithelial-protective effects of exudate macrophages in a model of LPS- and Klebsiella pneumoniae-induced lung injury comparing wild-type and CC-chemokine receptor 2 (CCR2)-deficient mice with defective lung macrophage recruitment and in in vitro studies using primary alveolar epithelial cells. MEASUREMENTS AND MAIN RESULTS: CCR2(-/-) mice exhibited enhanced alveolar epithelial cell apoptosis and lung leakage on intratracheal LPS treatment, which could be attributed to lack of exudate macrophage recruitment from the circulating pool as demonstrated in a model of wild-type/CCR2(-/-) bone-marrow chimeric mice. Among various antiinflammatory and proliferative mediators analyzed, the endogenous counterpart of resident macrophage-expressed IL-1ß, IL-1 receptor antagonist (IL-1ra), was highly up-regulated in flow-sorted exudate macrophages in LPS-treated wild-type mice. LPS/IL-1ß-induced impairment of alveolar epithelial cell integrity was antagonized by IL-1ra in vitro. Finally, intratracheal substitution of IL-1ra or intravenous adoptive transfer of IL-1ra(+/+) but not IL-1ra(-/-) blood mononuclear cells attenuated alveolar inflammation, epithelial apoptosis, and loss of barrier function in LPS-challenged or K. pneumoniae-infected CCR2(-/-) mice and enhanced survival after K. pneumoniae infection. CONCLUSIONS: We conclude that recruited lung macrophages attenuate IL-1ß-mediated acute lung injury in gram-negative pneumonia by release of IL-1ra.

[Deep incisional neck injuries caused by an electric knife]. / Tiefgreifende Halsschnittverletzungen durch ein elektrisches Messer.

Electric knives, due to the double blades swinging in opposite directions, have a high injury potential. Tissues such as skin can be cut smoothly without cutting motion and with only little pressure. Authors report on the case of a woman of 47 years who cut herself deeply on both sides of her neck with an electric knife, slightly carving a notch into the larynx and a cervical vertebra and opening large blood vessels. With respect to the extent of injuries the capacity to act had to be questioned. However, considering the absence of venous air embolism and the peculiarity of the tool it had to be assumed that the capacity to act lasted for a short time.

[Thoracic stab wound caused by a grilling scewer with defomration of the tool]. / Thoraxstich durch einen Grillspiess mit Verformung des Werkzeugs.

Injuries by meat- or barbecue-skewers are rarely relevant as cause of death. Besides accidental injuries they are used as coincidental tools in capital crimes. Skewers are non-typical stabbing tools of pointed-squared structure, which need considerable force to penetrate the skin. The authors report on a 42-year-old man's fatal thorax stab injury, which he sustained during a barbecue and which stretched from the left mamilla into the back right shoulder tissue. Death was caused by exanguination following stabbing through the superior vena cava. At issue was the question what amount of force was necessary to inflict the wound. Based on the deformation of the stabbing tool, as a result of a material-technical expertise, compressive load application in longitudinal direction and a stabbing force of between 120 to 665 N were to be assumed. Furthermore, in addition to the features of a non-typical tool, the autopsy findings allowed to conclude a powerful stabbing.

[An unusual area of injury in postmortem animal feeding beneath clothing]. / Ungewöhnliche Verletzungslokalisation bei postmortalem Tierfrass unter der Bekleidung.

The authors report on a woman who died on the age of 75 years and who was found dead in her dwelling with an extensive injury of the left thigh two days after the last sign of life. Together with the corpse a poodle was present in the dwelling. Due to the unusual localization totally beneath the clothes (trousers) and the morphology of the injury an unnatural cause of death was suspected. According to the autopsy findings and the histological results, postmortal animal scavenging caused by the poodle remained the only explanation for the injury. Supplementary DNA testing yielded final certainty.

[Evaluation of atypical stab and incision wounds in a case of combined suicidal injuries]. / Zur Bewertung atypischer Stich- und Schnittverletzungen bei einem kombinierten Suizid.

A fatal case of stabbing and cutting is reported which involved a 37-year-old male who suffered from depressive disorder and had already attempted suicide in the past. The postmortem examination revealed 12 lacerations of the scalp, 5 deep incised wounds on the flexor surface of the right forearm, 3 stab wounds of the back of the head, 12 stab wounds of the chest (with cutting of ribs but no injury of heart and lungs), 35 stab wounds of the abdomen and deep incised wounds of both sides of the neck with hesitation marks and incision of the left internal jugular vein. The significance of criteria to properly establish the manner of death like localization, axis and pattern of the wounds, hesitation marks, defense wounds, pulling aside the clothing to expose the target area, sustained capacity of physical activity and potential lethal effects of the single injuries as well as conclusions from the scene of death are discussed.

About morphological findings in fatal railway collisions.

The autopsy findings in fatal cases of railway collisions of the Bonn Institute of Legal Medicine in 1992-1999 were investigated and compared to the statements in the investigation files of the public prosecutor with regard to classification as accident or suicide as well as with regard to type and speed of collision. Of the 38 deaths, 10 were hit in an upright position, 11 fatal collisions affected persons lying outside the track and 13 were hit and overrun lying inside the track. According to the investigation classification 21 persons committed suicide (56%), while 10 died in an accident (26%). Our survey confirmed the leading role of being over-rolled in a lying position as an indication for suicides, while in accidents the upright hit was most important. With exception of the persons primarily affected between the rails in upright position and over-rolled consecutively an unequivocal assignment of injury patterns to the hit categories was possible. In cases of persons being primarily over-rolled in a lying position especially the criteria (i) opening of body cavities, (ii) organ injuries and (iii) loss of parts of the body allowed for careful conclusion on hit, respectively, overrunning speed.