Raffaele Gaeta
University of Pisa, Paleopatology, Post-Doc
During the Renaissance and Early Modern Age dissection began to be practiced for medico-legal purposes, in order to investigate the causes of death. In particular, during the 15th century evidences of autopsies performed by doctors on... more
During the Renaissance and Early Modern Age dissection began to be practiced for medico-legal purposes, in order to investigate the causes of death. In particular, during the 15th century evidences of autopsies performed by doctors on their private patients emerge. These dissections were requested by those families who can afford the expenses, in order to search the possible presence of hereditary diseases and to predispose a prevention and cure. The diffusion of this practice is attested also by the work of Antonio Benivieni (1443- 1502), who is considered a pioneer of the pathological anatomy. The extremely rich documentary archives of the Medici family, one of the most important family of the Italian Renaissance, report several description of necropsies carried out on the bodies of the members of the family. The analysis of these reports offers important direct information on the autopsy practices performed by court surgeons of the members of an aristocratic class in a period comprised between the 16th and the first half of the 18th century, and allows in some cases also to propose a retrospective diagnosis on the diseases that afflicted the Medici. In this paper the analysis will be focused on the evidences about autopsies carried out during the 16th century. An evolution through time can be observed, as from the first very brief notes
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Osteosarcoma is a high-grade bone-forming neoplasm, with a complex genome. Tumours frequently show chromothripsis, many deletions, translocations and copy number alterations. Alterations in the p53 or Rb pathway are the most common... more
Osteosarcoma is a high-grade bone-forming neoplasm, with a complex genome. Tumours frequently show chromothripsis, many deletions, translocations and copy number alterations. Alterations in the p53 or Rb pathway are the most common genetic alterations identified in osteosarcoma. Using spontaneously transformed murine mesenchymal stem cells (MSCs) which formed sarcoma after subcutaneous injection into mice, it was previously demonstrated that p53 is most often involved in the transformation towards sarcomas with complex genomics, including osteosarcoma. In the current study, not only loss of p53 but also loss of p16Ink4a is shown to be a driver of osteosarcomagenesis: murine MSCs with deficient p15Ink4b, p16Ink4a, or p19Arf transform earlier compared to wild-type murine MSCs. Furthermore, in a panel of nine spontaneously transformed murine MSCs, alterations in p15Ink4b, p16Ink4a, or p19Arf were observed in eight out of nine cases. Alterations in the Rb/p16 pathway could indicate that...
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The well-preserved skeleton of Maria Salviati (1499-1543), wife of Giovanni de' Medici, named " Giovanni of the Black Bands " , was exhumed in the Medici Chapels in Florence in 2012. Many lytic lesions affected... more
The well-preserved skeleton of Maria Salviati (1499-1543), wife of Giovanni de' Medici, named " Giovanni of the Black Bands " , was exhumed in the Medici Chapels in Florence in 2012. Many lytic lesions affected the skull of Maria on the frontal bone and on the parietal bones. These lesions are pathognomonic for syphilis. An ancient diagnosis of syphilis for Maria Salviati does not emerge from the historical sources, although the symptoms manifested in her last years of life are compatible with a colorectal localization, with severe haemorrhages caused by syphilitic infection. Paleopathology allows to directly observe " a secret illness " of the Renaissance to which noblewomen were subject as a consequence of the sexual conduct of their husbands.
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Dedifferentiated chondrosarcoma is a well-recognized entity, but its occurrence in the distal extremities is exceedingly rare. We present the case of a 49-year-old woman who experienced local recurrence of an “enchondroma” of the proximal... more
Dedifferentiated chondrosarcoma is a well-recognized entity, but its occurrence in the distal extremities is exceedingly rare. We present the case of a 49-year-old woman who experienced local recurrence of an “enchondroma” of the proximal phalanx of the fourth finger of the left hand, which had been initially treated with intralesional curettage at another hospital 4 years before, and 1 year before for a local recurrence. The imaging findings indicated an aggressive behavior, and an incisional biopsy showed a highly cellular proliferation of spindle and pleomorphic elements without evidence of matrix production intermixed with few fragments of a well-differentiated cartilaginous neoplasm with bland cellular atypia, focal nuclear hyperchromatism, and binucleation. An isocitrate dehydrogenase 2 R172S mutation was detected. The final diagnosis was dedifferentiated chondrosarcoma. Despite amputation of the fourth finger, the patient developed lung metastases and further local relapse. R...
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Dedifferentiated chondrosarcoma is a well-recognized entity, but its occurrence in the distal extremities is exceedingly rare. We present the case of a 49-year-old woman who experienced local recurrence of an “enchondroma” of the proximal... more
Dedifferentiated chondrosarcoma is a well-recognized entity, but its occurrence in the distal extremities is exceedingly rare. We present the case of a 49-year-old woman who experienced local recurrence of an “enchondroma” of the proximal phalanx of the fourth finger of the left hand, which had been initially treated with intralesional curettage at another hospital 4 years before, and 1 year before for a local recurrence. The imaging findings indicated an aggressive behavior, and an incisional biopsy showed a highly cellular proliferation of spindle and pleomorphic elements without evidence of matrix production intermixed with few fragments of a well-differentiated cartilaginous neoplasm with bland cellular atypia, focal nuclear hyperchromatism, and binucleation. An isocitrate dehydrogenase 2 R172S mutation was detected. The final diagnosis was dedifferentiated chondrosarcoma. Despite amputation of the fourth finger, the patient developed lung metastases and further local relapse. R...
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The Spanish flu pandemic spread in 1918-19 and infected about 500 million people, killing 50 to 100 million of them. People were suffering from severe poverty and malnutrition, especially in Europe, due to the First World War, and this... more
The Spanish flu pandemic spread in 1918-19 and infected about 500 million people, killing 50 to 100 million of them. People were suffering from severe poverty and malnutrition, especially in Europe, due to the First World War, and this contributed to the diffusion of the disease. In Italy, Spanish flu appeared in April 1918 with several cases of pulmonary congestion and bronchopneumonia; at the end of the epidemic, about 450.000 people died, causing one of the highest mortality rates in Europe. From the archive documents and the autoptic registers of the Hospital of Pisa, we can express some considerations on the impact of the pandemic on the population of the city and obtain some information about the deceased. In the original necroscopic registers, 43 autopsies were reported with the diagnosis of grippe (i.e. Spanish flu), of which the most occurred from September to December 1918. Most of the dead were young individuals, more than half were soldiers, and all of them showed conflu...
Research Interests: Epidemiology and Medicine
The Spanish flu pandemic spread in 1918-19 and infected about 500 million people, killing 50 to 100 million of them. People were suffering from severe poverty and malnutrition, especially in Europe, due to the First World War, and this... more
The Spanish flu pandemic spread in 1918-19 and infected about 500 million people, killing 50 to 100 million of them. People were suffering from severe poverty and malnutrition, especially in Europe, due to the First World War, and this contributed to the diffusion of the disease. In Italy, Spanish flu appeared in April 1918 with several cases of pulmonary congestion and bronchopneumonia; at the end of the epidemic, about 450.000 people died, causing one of the highest mortality rates in Europe. From the archive documents and the autoptic registers of the Hospital of Pisa, we can express some considerations on the impact of the pandemic on the population of the city and obtain some information about the deceased. In the original necroscopic registers, 43 autopsies were reported with the diagnosis of grippe (i.e. Spanish flu), of which the most occurred from September to December 1918. Most of the dead were young individuals, more than half were soldiers, and all of them showed conflu...
Research Interests: Epidemiology and Medicine
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Background Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature. Case presentation We report the case of a 65-year-old male... more
Background Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature. Case presentation We report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases an...
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Background Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature. Case presentation We report the case of a 65-year-old male... more
Background Soft tissue dedifferentiated leiomyosarcoma with heterologous osteosarcomatous component is an extremely rare entity described in only few cases in the literature. Case presentation We report the case of a 65-year-old male patient who, after initial inadequate surgery of a tumor of the left forearm, developed local recurrence that was treated with neoadjuvant chemotherapy, surgery and postoperative radiation therapy. Histologically the tumor showed an abrupt separation of two different patterns. One component consisted of interlacing fascicles of spindle cells with cigar-shaped nuclei strongly positive for smooth muscle actin, desmin and H-caldesmon. The other component consisted of a high-grade pleomorphic sarcoma with osteoid and chondroid matrix production, which positive for SATB2. Thus, a final diagnosis of dedifferentiated leiomyosarcoma was rendered. Fifteen months after treatment, the patient presented further local and distant relapse with pulmonary metastases an...
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The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy... more
The use of zebrafish embryos for personalized medicine has become increasingly popular. We present a co-clinical trial aiming to evaluate the use of zPDX (zebrafish Patient-Derived Xenografts) in predicting the response to chemotherapy regimens used for colorectal cancer patients. zPDXs are generated by xenografting tumor tissues in two days post-fertilization zebrafish embryos. zPDXs were exposed to chemotherapy regimens (5-FU, FOLFIRI, FOLFOX, FOLFOXIRI) for 48 h. We used a linear mixed effect model to evaluate the zPDX-specific response to treatments showing for 4/36 zPDXs (11%), a statistically significant reduction of tumor size compared to controls. We used the RECIST criteria to compare the outcome of each patient after chemotherapy with the objective response of its own zPDX model. Of the 36 patients enrolled, 8 metastatic colorectal cancer (mCRC), response rate after first-line therapy, and the zPDX chemosensitivity profile were available. Of eight mCRC patients, five achieved a partial response and three had a stable disease. In 6/8 (75%) we registered a concordance between the response of the patient and the outcomes reported in the corresponding zPDX. Our results provide evidence that the zPDX model can reflect the outcome in mCRC patients, opening a new frontier to personalized medicine.
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Anisakiasis is a fish-borne zoonosis caused by Anisakis spp. larvae. One challenging issue in the diagnosis of anisakiasis is the molecular detection of the etiological agent even at very low quantity, such as in gastric or intestinal... more
Anisakiasis is a fish-borne zoonosis caused by Anisakis spp. larvae. One challenging issue in the diagnosis of anisakiasis is the molecular detection of the etiological agent even at very low quantity, such as in gastric or intestinal biopsy and granulomas. Aims of this study were: 1) to identify three new cases of invasive anisakiasis, by a species-specific Real-time PCR probe assay; 2) to detect immune response of the patients against the pathogen. Parasite DNA was extracted from parasites removed in the three patients. The identification of larvae removed at gastric and intestinal level from two patients was first obtained by sequence analysis of mtDNA cox2 and EF1 α-1 of nDNA genes. This was not possible in the third patient, because of the very low DNA quantity obtained from a single one histological section of a surgically removed granuloma. Real-time PCR species-specific hydrolysis probe system, based on mtDNA cox2 gene, was performed on parasites tissue of the three cases. I...
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The medieval chapel of Notre Dame-des-Fontaines (Our Lady of the Fountains), in the French Maritime Alps, is entirely covered by the fresco cycle of the Passion (15th century) that depicts the last days of Jesus from the Last Supper to... more
The medieval chapel of Notre Dame-des-Fontaines (Our Lady of the Fountains), in the French Maritime Alps, is entirely covered by the fresco cycle of the Passion (15th century) that depicts the last days of Jesus from the Last Supper to the Resurrection. Under a small window, there is the brutal representation of the suicide of Judas Iscariot, hanging from a tree, with the abdomen quartered from which his soul, represented by a small man, is kidnapped by a devil. The author, Giovanni Canavesio, represented the traitor's death with very detailed anatomical structures, differently thus from other paintings of the same subject; it is therefore possible to assume that the artist had become familiar with the human anatomy. In particular, the realism of the hanged man's posture, neck bent in an unnatural way, allows us to hypothesize that it probably comes from direct observation of the executions of capital punishment, not infrequently imposed by the public authorities in low medi...
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We performed a histopathological study on the mummified tissue specimens of seven pre-Columbian mummies which arrived in Italy in the second half of the 19th century and are housed in the Section of Anthropology and Ethnology of the... more
We performed a histopathological study on the mummified tissue specimens of seven pre-Columbian mummies which arrived in Italy in the second half of the 19th century and are housed in the Section of Anthropology and Ethnology of the Museum of Natural History of the University of Florence. The results confirm that the modern techniques ofpathological anatomy can be successfidly applied on mummifed tissues, so as to perform important paleopathological diagnoses. Among the results obtained from this study there is the only known complete paleopathological study of Chagas' disease (American Trypanosomiasis), comprising macroscopic, microscopic and ultrastructural data, as well as information on atherosclerosis, anthracosis, emphysema and pneumonia.
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The well-preserved skeleton of Maria Salviati (1499-1543), wife of Giovanni de' Medici, named " Giovanni of the Black Bands " , was exhumed in the Medici Chapels in Florence in 2012. Many lytic lesions affected the skull of Maria on the... more
The well-preserved skeleton of Maria Salviati (1499-1543), wife of Giovanni de' Medici, named " Giovanni of the Black Bands " , was exhumed in the Medici Chapels in Florence in 2012. Many lytic lesions affected the skull of Maria on the frontal bone and on the parietal bones. These lesions are pathognomonic for syphilis. An ancient diagnosis of syphilis for Maria Salviati does not emerge from the historical sources, although the symptoms manifested in her last years of life are compatible with a colorectal localization, with severe haemorrhages caused by syphilitic infection. Paleopathology allows to directly observe " a secret illness " of the Renaissance to which noblewomen were subject as a consequence of the sexual conduct of their husbands.
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Trichinella has been a companion of humanity for thousands of years, so that some religious taboos on the consumption of pork probably derive from the risk of getting sick that is associated with its ingestion. However, man has only... more
Trichinella has been a companion of humanity for thousands of years, so that some religious taboos on the consumption of pork probably derive from the risk of getting sick that is associated with its ingestion. However, man has only managed to give a face and a name to the pathogen in modern times when, thanks to the intuition of great scientists and their pioneering experiments, it was possible to understand the pathogenic mechanisms of the parasite. Their observations and discussions, sometimes very vibrant, have led to the adoption by the authorities of stricter rules on food quality control which have helped to drastically reduce the outbreaks of trichinellosis raging in Europe and the United States. In this chapter we describe the troubled history of the discovery of the parasite (certainly comparable to a 19th century romance novel) and illustrate the major contributions that great scientists have made to the understanding of the pathogen. Furthermore, the presence of Trichinella in antiquity has not only been hypothesized in theory, but has been concretely identified by analysis of paleopathology, which is the science that studies ancient human remains. Lastly, therefore, we illustrate the five mummies infected by the parasite, as described in literature.