Forensic Toxicological and Medico-Legal Evaluation in a Case of Incongruous Drug Administration in Terminal Cancer Patients.

BACKGROUND: In most cases, palliative care is prescribed to adults diagnosed with cancer. The definition of the most suitable therapy for an effective sedation in terminal cancer patients still represents one of the most challenging goals in medical practice. Due to their poor health, the correct dosing of drugs used for deep palliative sedation in terminal cancer patients, often already on polypharmacological therapy, can be extremely complicated, also considering possible drug-to-drug interactions that could lead to an increased risk of overdose and/or incongruous administration with fatal outcomes. The case of a terminal cancer patient is presented, focusing on the "adequacy" of administered therapy. MATERIALS AND METHODS: A young male, affected by Ewing sarcoma, attending a palliative care at his own home, died soon after midazolam administration. Toxicological and histological analyses were performed on body fluids and organ fragments. RESULTS AND DISCUSSION: Morphological reliefs evidenced a neoplastic mass, composed of lobulated tissue with a lardy, pinkish-gray consistency, extending from the pleural surface to the lung parenchyma, also present at the sacrum region (S1-S5), at the anterior mediastinum level, occupying the entire left pleural cavity, and infiltrating the ipsilateral lung. Metastatic lesions diffused to rachis and lumbar structures. The brain presented edema and congestion. Toxicological analyses evidenced blood midazolam concentrations in the range of 0.931-1.690 µg/mL, while morphine was between 0.266 and 0.909 µg/mL. Death was attributed to cardiorespiratory depression because of a synergic action between morphine and midazolam. The pharmacological interaction between midazolam and morphine is discussed considering the clinical situation of the patient. The opportunity to proceed with midazolam administration is discussed starting from guidelines recommendation. Finally, professional liability outlines are highlighted.

Sudden Death from Primary Cerebral Melanoma: Clinical Signs and Pathological Observations.

Primary cerebral tumors rarely provoke sudden death. The incidence is often underestimated with reported frequencies in the range of 0.02 to 2.1% in medicolegal autopsy series. Furthermore, primary cerebral melanoma is an uncommon neoplasm. It represents approximately 1% of all melanoma cases and 0.07% of all brain tumors. This neoplasm is very aggressive, and its annual incidence is about 1 in 10 million people. In the present study, a 20-year-old male was admitted to hospital with vomiting, headache, paresthesia and aggressive behavior. A computed tomography (CT) scan of the head was performed showing a hyperdense nodule in the right parietal lobe with inflammation of the Silvian fissure. A complete autopsy was performed 48 h after death. A blackish material was displayed on the skull base, and posterior fossa. Microscopic examination diagnosed primary brain melanoma. A systematic review of the literature was also performed where no previous analogous cases were found. The forensic pathologist rarely encounters primary cerebral melanoma, and for these reasons, it seemed appropriate to describe this case as presenting aspecific clinical symptoms and leading to sudden unexpected death. Histopathological observations are reported and discussed to explain this surprising sudden death caused by a primary cerebral melanoma.

Retroperitoneal Hemorrhage Caused by Trephine Biopsy.

The bone marrow biopsy is usually a safe procedure; however, it can occasionally present important complications. These complications are not always immediately evident or quickly diagnosed and may include pain at the biopsy site, trauma to neighboring structures, vascular injuries, infection, transient pressure neuropathies, pneumoretroperitoneum, and hemorrhage. Several risk factors are recognized, including thrombocytopenia, concurrent use of anticoagulants, and the presence of an underlying myeloproliferative disorder. While several reports of adverse events have been published, only 2 deaths attributable to this procedure have been reported. We present 2 cases of fatal hemorrhage after bone marrow biopsy.

Pulmonary macrophages activity in CO intoxication.

The presence of macrophages and their activation on the pulmonary tissues of 21 subjects deceased after CO intoxication has been studied. A notable number of activated macrophages, especially in the interstitial level, have been evidenced, and such phenomenon supports the hypothesis of a possible association between CO intoxication and pulmonary macrophages activity. The highlighted association could be mediated by changes of the surfactant, by impairing of mitochondrial respiration and by release of pro-inflammatory cytokines.