A great enigma of the Italian Renaissance: paleopathological study on the death of Giovanni dalle Bande Nere (1498-1526) and historical relevance of a leg amputation.

The Medici project consisted in archeological and paleopathological researches on some members of the great dynasty of the Italian Renaissance. The remains of Giovanni de' Medici, so-called "dalle Bande Nere" (Forli 1498- Mantua 1526) has not been investigated yet. The enigma of the fatal injury and leg amputation of the famous Captain excited curiosity of paleopathologists, medical scientists and Italian Society of Orthopedic and Traumatology which contributed to realize the project of exhumation and study of his skeletal remains. The aim of the study is to report the first anthropological and paleopathological results. The tomb of Giovanni and his wife Maria Salviati was explored and the skeletal remains were investigated. Anthropological and paleopathological examination defined: age at death, physical constitution and activity, skeletal diseases. The bony fragments of the leg were studied macroscopically, under stereoscopic microscope, at X-ray and CT scans to detect type of injury and level of amputation. The skeleton and muscular insertions of Giovanni revealed a young-adult and vigorous man, subjected to stresses of military activity since adolescence. Right tibia was amputated below the proximal half of diaphysis leaving long tibio-fibular fragments with a horizontal cut only at the lateral portion. Thus, the surgeon limited to complete the traumatic hemi-amputation. Amputation in the Sixteenth Century technically consisted in guillotine incisions below the knee using crescent shaped knife and bony saw, usually leaving a quite long tibial fragment. Amputations in the Sixteenth Century were contaminated and grossly performed not providing vascular binding nor wound closure. The surgeon performed the procedure in conformity with surgical knowledge of that period

Correlates and reference limits of plasma gamma-glutamyltransferase fractions from the Framingham Heart Study.

Background: We assessed GGT fractions correlates and their reference values in the Offspring Cohort of the Framingham Heart Study. Methods: Correlates of GGT fractions were assessed by multivariable regression analysis in 3203 individuals [47% men, mean age (SD): 59 (10) years]. GGT fractions reference values were established by empirical quantile analysis in a reference group of 432 healthy subjects [45% men, 57 (10) years]. Results: Fractional GGT levels were higher in men than in women (Pb0.0001). In both sexes, fractions were associated with: triglycerides were associated with b-GGT, alcohol consumption with m-, s- and f-GGT. C-reactive protein with m- and s-GGT, while plasminogen activator inhibitor-1 with b- and f-GGT. Body mass index, blood pressure, glucose and triglycerides correlated with b- and f-GGT. In comparison with the reference group [b-GGT/s-GGT median (Q1–Q3): 0.51 (0.35–0.79)U/L], subjects affected by cardiovascular disease or diabetes showed no change of b/s ratio [0.52 (0.34–0.79)U/L, 0.57 (0.40–0.83)U/L, respectively]. The b/s ratio was higher in presence of metabolic syndrome [0.61 (0.42–0.87)U/L, Pb0.0001], while lower in heavy alcohol consumers [0.41 (0.28–0.64)U/L, Pb0.0001]. Conclusions: Metabolic and cardiovascular risk markers are important correlates of GGT fractions, in particular of b-GGT

Enlarged vascular foramina and lytic lesions in vertebral bodies: a diagnostic dilemma

Among the skeletal material from the sites of Alghero, Mesumundu and Sant’Antioco di Bisarcio (Sassari, Sardinia) and dated back to the period comprises between the 13th and the late 16th century 5 subadult individuals aged between 5 and 15 years and a mature male showed peculiar osteolytic phenomena of the vertebral bodies. These lesions have the appearance of enlarged vascular foramina, affecting several vertebrae mainly of the thoracic and lumbar spine, sometimes with involvement of the sacrum; on the same vertebral body several lesions are generally visible. In the literature similar features have been attributed to brucellosis or tuberculosis. As for the Sardinian skeletal material, an imaging study on the vertebrae of the adult individual was carried out in order to evaluate the appearance of the lesions within the body. Computed Tomography evidenced internal irregular elongated cavitations, sometimes joined together; erosive rounded lesions, whose presence is not detectable externally, were also showed. The molecular analysis has so far been performed on the subadult from Sant’Antioco di Bisarcio, but at initial analysis the DNA resulted degraded. Therefore, the nature of these lesions remains unclear, as it is not sure if they should be referred to tuberculosis, brucellosis or other pathological conditions [hemolytic anemias (eg. Thalassemia), lymphomas, multiple myeloma and infection by Echinococcus]. Further molecular analyses will be carried out on the remains belonging to the other five individuals in an attempt to clarify the etiology of the above mentioned lesions

Enlarged vascular foramina and lytic lesions in vertebral bodies: a diagnostic dilemma

Among the skeletal material from the sites of Alghero, Mesumundu and Sant’Antioco di Bisarcio (Sassari, Sardinia) and dated back to the period comprises between the 13th and the late 16th century 5 subadult individuals aged between 5 and 15 years and a mature male showed peculiar osteolytic phenomena of the vertebral bodies. These lesions have the appearance of enlarged vascular foramina, affecting several vertebrae mainly of the thoracic and lumbar spine, sometimes with involvement of the sacrum; on the same vertebral body several lesions are generally visible. In the literature similar features have been attributed to brucellosis or tuberculosis. As for the Sardinian skeletal material, an imaging study on the vertebrae of the adult individual was carried out in order to evaluate the appearance of the lesions within the body. Computed Tomography evidenced internal irregular elongated cavitations, sometimes joined together; erosive rounded lesions, whose presence is not detectable externally, were also showed. The molecular analysis has so far been performed on the subadult from Sant’Antioco di Bisarcio, but at initial analysis the DNA resulted degraded. Therefore, the nature of these lesions remains unclear, as it is not sure if they should be referred to tuberculosis, brucellosis or other pathological conditions [hemolytic anemias (eg. Thalassemia), lymphomas, multiple myeloma and infection by Echinococcus]. Further molecular analyses will be carried out on the remains belonging to the other five individuals in an attempt to clarify the etiology of the above mentioned lesions

Serum gamma-glutamyltransferase fractions in Myotonic Dystrophy type I: Differences with healthy subjects and patients with liver disease.

Objectives: Elevation of serum gamma-glutamyltransferase (GGT), in absence of a clinically significant liver damage, is often found in Myotonic Dystrophy type-1 (DM1). In this study we investigated if a specific GGT fraction pattern is present in DM1. Designs and methods: We compared total and fractional GGT values (b-, m-, s-, f-GGT) among patients with DM1 or liver disease (LD) and healthy subjects (HS). Results: The increase of GGT in DM1 and LD, vs HS, was mainly due to s-GGT (median: 32.7; 66.7; and 7.9 U/L, respectively), and b-GGT (8.5; 18.9; and 2.1 U/L). The subset of DM1 patients matched with HS with corresponding serum GGT showed higher b-GGT (6.0 vs 4.2 U/L). Conclusions: DM1 patients with normal total GGT values showed an alteration of the production and release in the blood of GGT fractions. Since increased s-GGT is also found in LD, a sub-clinical liver damage likely occurs in DM1 subjects apparently free of liver disease

Case Report: Could Hennebert's Sign Be Evoked Despite Global Vestibular Impairment on Video Head Impulse Test? Considerations Upon Pathomechanisms Underlying Pressure-Induced Nystagmus due to Labyrinthine Fistula

We describe a case series of labyrinthine fistula, characterized by Hennebert's sign (HS) elicited by tragal compression despite global hypofunction of semicircular canals (SCs) on a video-head impulse test (vHIT), and review the relevant literature. All three patients presented with different amounts of cochleo-vestibular loss, consistent with labyrinthitis likely induced by labyrinthine fistula due to different temporal bone pathologies (squamous cell carcinoma involving the external auditory canal in one case and middle ear cholesteatoma in two cases). Despite global hypofunction on vHIT proving impaired function for each SC for high accelerations, all patients developed pressure-induced nystagmus, presumably through spared and/or recovered activity for low-velocity canal afferents. In particular, two patients with isolated horizontal SC fistula developed HS with ipsilesional horizontal nystagmus due to resulting excitatory ampullopetal endolymphatic flows within horizontal canals. Conversely, the last patient with bony erosion involving all SCs developed mainly torsional nystagmus directed contralaterally due to additional inhibitory ampullopetal flows within vertical canals. Moreover, despite impaired measurements on vHIT, we found simultaneous direction-changing positional nystagmus likely due to a buoyancy mechanism within the affected horizontal canal in a case and benign paroxysmal positional vertigo involving the dehiscent posterior canal in another case. Based on our findings, we might suggest a functional dissociation between high (impaired) and low (spared/recovered) accelerations for SCs. Therefore, it could be hypothesized that HS in labyrinthine fistula might be due to the activation of regular ampullary fibers encoding low-velocity inputs, as pressure-induced nystagmus is perfectly aligned with the planes of dehiscent SCs in accordance with Ewald's laws, despite global vestibular impairment on vHIT. Moreover, we showed how pressure-induced nystagmus could present in a rare case of labyrinthine fistulas involving all canals simultaneously. Nevertheless, definite conclusions on the genesis of pressure-induced nystagmus in our patients are prevented due to the lack of objective measurements of both low-acceleration canal responses and otolith function

The Italian arm of the PREPARE study: an international project to evaluate and license a maternal vaccine against group B streptococcus.

BACKGROUND: Group B streptococcus (GBS) is a leading cause of sepsis, pneumonia and meningitis in infants, with long term neurodevelopmental sequelae. GBS may be associated with poor pregnancy outcomes, including spontaneous abortion, stillbirth and preterm birth. Intrapartum antibiotic prophylaxis (IAP) is currently the only way to prevent early-onset disease (presenting at 0 to 6 days of life), although it has no impact on the disease presenting over 6 days of life and its implementation is challenging in resource poor countries. A maternal vaccine against GBS could reduce all GBS manifestations as well as improve pregnancy outcomes, even in low-income countries. MAIN BODY: The term "PREPARE" designates an international project aimed at developing a maternal vaccination platform to test vaccines against neonatal GBS infections by maternal immunization. It is a non-profit, multi-center, interventional and experimental study (promoted by the St George University of London. [UK]) with the aim of developing a maternal vaccination platform, determining pregnancy outcomes, and defining the extent of GBS infections in children and mothers in Africa. PREPARE also aims to estimate the protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa and to conduct two trials on candidate GBS vaccines. PREPARE consists of 6 work packages. In four European countries (Italy, UK, Netherlands, France) the recruitment of cases and controls will start in 2020 and will end in 2022. The Italian PREPARE network includes 41 centers. The Italian network aims to collect: GBS isolates from infants with invasive disease, maternal and neonatal sera (cases); cord sera and GBS strains from colonized mothers whose infants do not develop GBS infection (controls). SHORT CONCLUSION: PREPARE will contribute information on protective serocorrelates against the main GBS serotypes that cause diseases in Europe and Africa. The vaccine that will be tested by the PREPARE study could be an effective strategy to prevent GBS disease