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Derived dicynodonts, including Lystrosaurus murrayi, have edentulous lower jaws. As an interesting exception to this conventional wisdom, a well-preserved specimen of L. murrayi (MGGC- 8850/1RE13 F) has abnormal, paired mandibular structures similar in overall morphology to dental teeth. The specimen pertains to the historical collections of the Museo G. Capellini (Bologna, Italy) and was collected in 1929 by M. Gortani during prospecting activities near Harrismith, South Africa. The specimen is articulated and includes a nearly complete skull, the first eight vertebrae and the proximal end of the right scapula. Reconstruction based on a Dual-Beam CT revealed unusual, paired structures similar to mandibular teeth, encased within the lower jaw, lingual to maxillary tusks. Different interpretations are possible for the abnormal mandibular structures in MGGC-8850/1RE13 F: 1) the dental lamina in the lower jaw, which would normally degenerate in derived dicynodonts, remained active and potentiated the odontogenesis; 2) the dental lamina was potent in the lower jaw throughout the ontogeny across dicynodonts but activated differentially; or 3) the mandibular patterning in our specimen was dorsalized, which resulted in an ectopic formation of upper jaw dentition in the lower jaws. Supranumerary or ectopic teeth are a commonly screened phenotype in modern mammalian models. Such variation distributes in a continuum – rarely does an edentulous jaw develop fully functional teeth that are present in outgroups. The absence of mandibular dentition in other specimens of L. murrayi and in most other bidentalian dicynodonts suggests that MGGC- 8850/1RE13 F represents a rare developmental abnormality or a case of atavism.

Purpose: To evaluate the outcome of selective arterial embolization with N-2-butyl-cyanoacrylate for aneurysmal bone cysts. Methods: We retrospectively studied 102 patients (72 male, 30 female; mean age, 16 years; range, 3–60 years) with aneurysmal bone cysts treated with embolization with N-2-butyl-cyanoacrylate. Mean follow-up was seven years (range, 3–13 years); no patient was lost to follow-up. We evaluated healing and recurrences of the lesions, complications and cost of the procedures, and recurrences with respect to age and gender of the patients, and size and location of the lesions. Results: Embolization was feasible in 88 patients (86.3%), and not feasible in 14 patients (13.6%) because feeding arteries were not identified or the spinal artery of Adamkiewicz was recognized at the embolization field. Seventy two patients (81.8%) experienced complete healing of their lesions after a single (50 patients, 56.8%), a second (17 patients, 19.3%) or a third embolization (5 patients, 5.7%). Sixteen patients (18.2%) experienced recurrence within four months (range, 3–9 months) after embolization; these patients underwent surgical treatment. Recurrences were more common in patients younger than 15 years of age and cysts larger than 6 cm, without any difference with respect to gender and location. Four patients (4.5%) experienced a complication including skin necrosis, sciatic nerve paresthesias, and femoral artery pseudoaneurysm. The cost estimate was 3000 euro per procedure. Conclusion: Embolization of aneurysmal bone cysts with N-2-butyl-cyanoacrylate is associated with good results and low complication rates, however, experience, technical skills, and knowledge of the vascular anatomy of the area is necessary. © 2016, SICOT aisbl.

Definite spectra of point mutations in the Bcr-Abl kinase domain (KD) are known to confer resistance to the tyrosine kinase inhibitors (TKIs) imatinib (IM), dasatinib (DAS) and nilotinib (NIL) in Philadelphia-positive (Ph+) leukemias. Until the recent advent of next-generation sequencing (NGS) technologies, no method was available that could conjugate high sensitivity, possibility to screen for any known or unknown sequence variation and accurate quantitation of mutated subclones. Because of these key technical limitations, the clinical relevance of early detection of small mutated subclones could never be fully elucidated. We have set up and optimized a Bcr-Abl KD mutation screening assay taking advantage of the Roche 454 NGS technology on a GS Junior instrument, that allows parallel pyrosequencing of a hundred thousand clonally amplified DNA molecules of 400 bp average length. We have thus designed 4 partially overlapping amplicons covering the whole KD of the Bcr-Abl transcript (a.a. 240–520) to be generated by nested RT-PCR using sequence-specific primers conjugated with multiplex identifiers – allowing to pool and sequence different samples from one or multiple patients (pts) in a single run. The assay proved capable to identify, characterize and quantitate sequence variations in samples from pts already known to harbour mutations as assessed by conventional Sanger sequencing with 100% concordance. Given that the number of sequence reads generated in each run is relatively constant, the lower detection limit is inversely correlated with the number of samples that can simultaneously be analyzed. Sensitivity could thus be easily modulated – analyzing a single sample per run allowed to routinely achieve lower detection limits ranging between 0.02 and 0.05% (that is, to detect as little as 2 to 5 mutated Bcr-Abl transcripts in a total of 10,000 Bcr-Abl transcripts). With this target sensitivity, we first retrospectively analyzed samples collected at the time of diagnosis from selected chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL) cases known to have developed a T315I mutation 3 to 9 months after TKI start. We found that the T315I could not always be traced back to the time of diagnosis. We also found that, both in CML and in Ph+ ALL pts, several low-level mutations (in the range of 0.05 to 1%) with apparently no clinical relevance (e.g., never reported in association with TKI resistance) were routinely detectable – and appeared not to be predictors of a higher level of genetic instability. More interestingly, when used for mutation monitoring of de novo Ph+ ALL pts enrolled in clinical trials with DAS or NIL, NGS could highlight emerging resistant clones far earlier than D-HPLC or conventional sequencing. Also, some IM-resistant CML and Ph+ ALL pts who had been scored as unmutated by conventional sequencing could be shown by NGS to harbour DAS- or NIL-resistant mutations at 1–10% level – a phenomenon that is known to happen because of the clonal deselection resulting from the temporary lack of any TKI selective pressure in the interval between IM discontinuation and DAS or NIL start. Analyses will be presented in detail. We can conclude that: 1) the 454 NGS technology on the GS Junior instrument is a reliable and cost-effective method to perform Bcr-Abl KD mutation screening of Ph+ leukemia pts – with a target sensitivity of 0,1%, 4 samples can simultaneously be analyzed with costs comparable to those of conventional Sanger sequencing and the advantage to quantitatively follow the dynamics of mutated subclones over time; 2) in line with a recent report, small mutated subclones with apparently no clinical relevance can be detected both in newly diagnosed CML and Ph+ ALL pts before TKI start – which further underlines that mutation screening of pts at diagnosis is uninformative, if not misleading; 3) during TKI therapy, the high sensitivity of NGS allows to detect emerging Bcr-Abl mutant subclones earlier than D-HPLC or conventional sequencing; this is particularly relevant: i) for mutation monitoring of Ph+ ALL pts, that are highly prone to develop resistance and mutations while on TKI therapy, and ii) in IM-resistant CML and Ph+ ALL pts, where NGS may uncover the presence of DAS- or NIL-insensitive mutations, and may thus help choosing the second-line therapeutic strategy most likely to be successful.

Fragestellung/Einleitung: Der nationale kompetenzorientierte Lernzielkatalog (NKLM) soll zukünftig in Deutschland das Rahmenwerk für die medizinische Ausbildung sein. Aktuelle Curricula müssen analysiert werden, um vorhandene und noch fehlende Kompetenzen zu identifizieren. Komplexität[for full text, please go to the a.m. URL], Jahrestagung der Gesellschaft für Medizinische Ausbildung (GMA)

In this paper the osteobiography of an elderly woman recovered from a cemetery tomb where she was buried in 1850, affected by hip fracture and osteoporosis, is described. The overall anthropological characteristics of the individual have been investigated. Macroscopic, radiographic, tomographic, microscopic, and chemical and structural examinations have been performed to give a detailed account of the condition of the skeleton. A non-union pertrochanteric fracture not surgically treated and probably due to senile osteoporosis was diagnosed. The consequences of the fracture to the bones show that this individual likely survived several years following the injury. The osseous features we describe (remodelled bone at the fracture site, asymmetry of entheseal changes likely related to the particular walking pattern of the individual) may be useful in personal identification of skeletons of legal interest. Regarding the recognition of osteoporosis in unearthed skeletons, our study underlines that the cortical thickness, microscopic features, degree of crystallinity and Ca/P ratio represent more useful elements than the mean bone density, mineral/matrix ratio and mineral maturity, which are more sensitive to diagenetic changes that affect the mineral phase post-mortem.