A critical review of the anthropological and paleopathological literature on osteopetrosis as an ancient rare disease (ARD).

OBJECTIVE: A reappraisal of the available evidence of osteopetrosis in the archaeological record as first step in promoting new approaches to rare diseases in paleopathology. MATERIALS AND METHODS: Three different approaches are combined: a survey of the last 50 years of bioarchaeological publications; an online search addressing six of the more widely used search engines; macroscopic and radiographic analyses of the human remains from the Neolithic site of Palata 2 (Italy). RESULTS: The combined results of the literature survey and the online search identified six cases of osteopetrosis. The majority of search hits place this disease into differential diagnoses. The investigation of the remains from Palata 2, one of the six cases in literature, indicates a non-specific sclerosis of the cranial vault. CONCLUSIONS: Of the six cases of osteopetrosis, only two, one of the autosomal-recessive type (ARO) and one of the autosomal-dominant type (ADO), are supported by direct osteoarchaeological evidence. Therefore, inaccurate differential diagnoses generate an inflated number of cases in the paleopathological record. SIGNIFICANCE: This reappraisal calls for a more informed and evidence-based approach to osteopetrosis and, more generally, to rare diseases in paleopathology. LIMITATIONS: Lack of specific publications on osteopetrosis; more case studies may be present in "gray literature". SUGGESTIONS FOR FURTHER RESEARCH: Cases of osteopetrosis from archaeological and historical collections as well as medical literature are needed to increase knowledge about this rare disease. More precise differential diagnoses are required, particularly when dealing with rare diseases.

Morphological cardiac changes in electrocution deaths: A literature review.

Electrical injury may lead to damage to the conducting tissue, myocardial changes and even sudden cardiac death. Victims of low-voltage electrocution may have no electric marks, burns or other signs typical of electrical injuries. In these cases, the absence of other specific findings could make the identification of the cause of death very difficult. A broad spectrum of cardiac changes in cases of electrocution has been described in the literature, including the break-up of myocardial fibres, cardiomyolysis, haemorrhagic areas, the separation of myofibres and alternating hypercontracted-hyperdistended myocytes. All the described alterations, however, cannot be exclusively attributed to electrocution, since no specific morphological cardiac findings have so far been identified in electrocution. However, a few histological patterns recur, and their knowledge may be important for the forensic pathologist. This literature review describes the main pathological patterns observed in cases of fatal electrocution based on a literature search carried out up to September 2019 in the databases PubMed and Scopus. The search criteria included the keywords for cardiac lesions and electrocution. On the grounds of the literature data, a list of major and minor diagnostic markers for the passage of the electrical current through the heart tissue was created.

Soft-tissue thickness values using cone beam computed tomography: A literature review.

When human remains are found, with no evidence of identity, facial approximation can be a useful technique to employ. The reconstruction of the ante-mortem appearance can reproduce the likely features of the face, starting from the skull, based on the overlying soft-tissue thickness. Over the years, many techniques have been developed to achieve soft-tissue thickness measurements, one of which is based on the use of cone beam computed tomography. This study aimed to review the status of this technique and to evaluate heterogeneity among studies undertaken in this field, with particular regard to determination of landmarks, sex and body mass index.

DNA extraction from sternum bone for identification of a saponified body: use of a modified protocol.

This paper discusses our approach and results obtained when attempting to identify a saponified human body recovered from the sea, without arms and legs. Bones, especially the long ones, are the only sources of DNA available in several cases involving unidentified bodies in advanced state of putrefaction. In this case, since the body was found without limbs, attempts were made to extract DNA from the sternum bone. The DNA was extracted using a modified version of the NucleoSpin® DNA Trace Kit (Macherey Nagel™) protocol and an STR analysis was performed. Thanks to this modified protocol a complete DNA profile was obtained from the sternum bone, while only partial results were obtained from blood and teeth. The DNA profile obtained from the sternum was compared with the DNA of the putative son searching for a genetic match. Five incompatibilities were detected so it was possible to exclude the kinship. In conclusion this could be a useful technique in personal identification through DNA analysis in case of poor quality and quantity of bone.

Head CT scan in emergency room: Is it still abused? Quantification and causes analysis of overprescription in an Italian Emergency Department.

In recent years, the increasing prescription of diagnostic imaging has been noted, due to advances in imaging technology and the development of defensive medicine. Overuse of diagnostic imaging significantly impacts the quality and costs of health care. Therefore, the purpose of this study was to quantify overprescription and investigate its causes through the evaluation of head computer tomography (CT) scan prescriptions. In this study, a set of 100 requests of CT scans was collected and analysed by three experts in guidelines and scientific evidences, evaluating prescription appropriateness. Then, the rate of overprescription was quantified and its causes identified as incorrect adoption of guidelines indications (32%) and as defensive medicine (6%). Therefore, in order to reduce inappropriate investigations, the findings of the present study suggest that the reduction in overprescription could be reached through the improvement of training of health personnel and the propagation of a no-blame culture aimed at minimizing defensive medicine.

High tension electrocution death: New histopathological cardiac tools by Confocal Laser Scanning Microscope.

In deaths due to electrocution intraepidermal separation, vacuolation of epidermal cells, "swiss cheese" aspect of the superficial part of epidermis (swollen and with multiple vescicles), metallization, necrosis of collagenous fibers, cardiomyocytes alterations are microscopically described. No cardiac nerve damage due to electricity is actually reported in literature. In this work we tried to find new morphological signs in the hearts of deaths due to electrocution. In three cases of deaths due to electrocution, in which forensic autopsies were performed within 36 h of the death, heart specimens were taken at the level of common trunk of the left coronary artery. The myocardium histological examination at optical microscope and Confocal Laser Scanning Microscope (CLSM) revealed fragmentation of cardiomyocytes, nerve trunks damage with hydropic swelling of the nerve fibers, interstitial and sub-nerve-sheath edema, very dishomogenous distribution of the natural fluorescence of the neurofilaments, coarctation of epicardial gangliar cells with cytoplasmic cleft and irregular fluorescence pattern. Identification of S-100 protein by immunohistochemistry can help to better observe the hydropic swelling of the nerve fibers and the central cytoplasmic clefts. These alterations could be used in future as specific signs of the passage of the electrical current through the heart. We recommend heart specimens at the level of common trunk of the left coronary artery in all the cases of suspected electrocution, to better evaluate cardiac nerve trunks damages and alterations.

Optimal multidisciplinary treatment of oral cavity mucosal melanoma: outcome analysis in a case series.

Oral cavity mucosal melanomas (OCMM) represent only 3% of all malignant melanomas. Surgery is the mainstay of treatments and it is often followed by adjuvant radiotherapy. The role of adjuvant immunotherapy and/or chemotherapy is still debated and to date neither treatment is routinely used. From January 1990 to January 2010, we have collected from our database data of 20 patients with a histologically proven diagnosis of OCMM. Upfront surgery, followed by adjuvant radiotherapy was performed in 16/20 (80%) patients. Immunohistochemical analysis was carried out on all tissue samples and the following markers were assessed: Ki-67, HMG-45, Melan-A, S-100, CD31, CD35, CD20, CD21, and CD3. Although Ki-67, HMG-45, Melan-A, and S-100 were assessed in tumor cells, the analysis of CD31, CD21, CD20, CD3, and CD35 was carried out on the tumor-infiltrating lymphocytes. Patient outcome was analyzed and associated with clinical and Immunohistochemical tumor characteristics. The median overall survival (OS) was 12 months, with a 2-year OS rate of 30%. The median progression-free survival (PFS) was 9 months, with a 2-year PFS rate of 25%. Grade of lymphocyte infiltration (CD20 and CD3 expression) correlated strongly with prognosis. Interestingly, overexpression of CD21 along with downregulation of CD31 was significantly associated with better OS and PFS, whereas the reversal features correlated with a poor prognosis. Our report shows that patients affected by OCMM have a poor prognosis despite the administration of multimodal treatments. Moreover, our analysis suggests that the evaluation of several biomarkers, especially in tumor-infiltrating lymphocytes, may identify categories of patients with distinct immune response against the tumor and possibly different treatment response and prognosis.

PHACES syndrome: Diode laser photocoagulation of intraoral hemangiomas in six young patients.

INTRODUCTION: The acronym PHACES describes the association of posterior fossa malformations, facial hemangiomas, arterial anomalies (cardiovascular or cerebrovascular), coarctation of the aorta and cardiac defects, eye abnormalities, and sternal or ventral defects. In this study we report on 6 patients affected by the PHACES syndrome and showing 34 intraoral hemangiomas (IH), treated by diode laser photocoagulation (DLP). CASE PRESENTATION: IH appeared as red-bluish soft masses, smooth or lobulated, from a few millimetre to several centimetres in size, covered by intact mucosa and blanching on pressure. IHs were treated by DLP with 320µm fibres at a wavelength of 800±10nm. The diode laser techniques applied were: Transmucosal DLP (DLTP), a no-contact technique in which laser energy is delivered by a flexible optic quartz fiber, which is kept 2-3mm apart from the lesion, and Intralesional DLP (DLIP), in which the fibre is introduced into the lesion through a transmucosal access. DLTP was used for 20 flat, superficial IHs and, after a variable number of laser sessions (average=3) depending on the size of the lesion, 65% completely regressed, while in the remaining 35% shrinkage of the lesion was achieved with minor and few complications. The remaining 14 deep/multi-lobulated IHs were treated by DLIP, resulting in complete regression of 79% of them. CONCLUSIONS: DLP techniques are an effective and minimally invasive procedure for IH in patients with PHACES, in consideration of the multiple lesions to treat, of the necessity of multiple interventions and the higher compliance of the patients.