Rare Case of an Ancient Craniofacial Osteosarcoma with Probable Surgical Intervention

Osteosarcoma is the most common primary malignant bone tumor both today and in antiquity. Nevertheless, it is a comparatively rare tumor. This paper describes a case of a highly aggressive craniofacial lesion from the 11th–12th centuries AD, most likely representing osteosarcoma. During the paleopathological study, macroscopic, endoscopic, radiological, scanning-electron and light microscopic investigations were performed. The skull of the approximately 40–50 year-old female revealed several pathological findings. The most impressive macroscopic feature was an extensively spiculated periosteal reaction (“sunburst” pattern) in combination with a massive bone destruction most likely derived from a highly aggressive tumor originating in the ethmoidal area of the medial wall of the orbit. The central parts of the lesion showed excessive new and most probably neoplastic bone formation indicating an underlying high-grade osteosarcoma. The light microscopic examination revealed three different levels of bony structures representing different qualities of bone tissues. Besides the mass lesion, signs of a healed multiple incomplete trephination of the left parietal bone was observed. This case represents a unique example in which the concomitance of a tumor and an incomplete trephination could be observed from the skeletal remains of an ancient individual. The case opens new considerations as to whether surgical interventions, such as incomplete trephination, might have been used already in the Middle Ages as a therapeutic approach.     

Experience with miltefosine for persistent or relapsing visceral leishmaniasis in solid organ transplant recipients: A case series from Spain

The incidence of visceral leishmaniasis (VL) after solid organ transplantation (SOT) is increasing. The optimal therapy for post‐transplant VL remains unclear, as relapses after liposomal amphotericin B (L‐AmB) are common. Miltefosine has been shown to be effective for treating VL in immunocompetent patients, although data in the specific population of SOT recipients are lacking. In the setting of an outbreak of leishmaniasis occurring in Southwest Madrid, we reviewed our experience in 6 SOT recipients with persistent or relapsing VL who received a 28‐day course of miltefosine (2.5 mg/kg/day) as salvage therapy. All patients had been treated previously with L‐AmB as first‐line therapy. The incident episode of VL occurred at a median of 14 months after transplantation. Two patients experienced persistent infection and the remaining 4 had a relapse after a median interval of 168 days since the completion of the course of L‐AmB. All the patients had an apparent initial clinical improvement with miltefosine. However, VL relapsed in 3 of them (after a median interval of 46 days), which required retreatment with L‐AmB‐based regimens. Miltefosine therapy was followed by a prolonged secondary prophylaxis with L‐AmB in the only 2 cases with sustained clinical response and ongoing immunosuppression. No adverse effects associated with miltefosine were observed. Albeit limited, our experience suggests that miltefosine monotherapy likely has a limited utility to obtain a long‐lasting clinical response in complicated (persistent or relapsing) forms of post‐transplant VL, although its role in association with L‐AmB‐based secondary prophylaxis may merit further investigation.     

Comparative study of sickle cell anemia and hemoglobin SC disease: clinical characterization,laboratory biomarkers and genetic profiles

Background

In this study, we evaluate the association of different clinical profiles, laboratory and genetic biomarkers in patients with sickle cell anemia (SCA) and hemoglobin SC disease (HbSC) in attempt to characterize the sickle cell disease (SCD) genotypes.

Methods

We conducted a cross-sectional study from 2013 to 2014 in 200 SCD individuals (141 with SCA; 59 with HbSC) and analyzed demographic data to characterize the study population. In addition, we determined the association of hematological, biochemical and genetic markers including the β^S-globin gene haplotypes and the 3.7 Kb deletion of α-thalassemia (?α^3.7Kb-thal), as well as the occurrence of clinical events in both SCD genotypes.

Results

Laboratory parameters showed a hemolytic profile associated with endothelial dysfunction in SCA individuals; however, the HbSC genotype was more associated with increased blood viscosity and inflammatory conditions. The BEN haplotype was the most frequently observed and was associated with elevated fetal hemoglobin (HbF) and low S hemoglobin (HbS). The -α^3.7Kb-thal prevalence was 0.09 (9%), and it was associated with elevated hemoglobin and hematocrit concentrations. Clinical events were more frequent in SCA patients.

Conclusions

Our data emphasize the differences between SCA and HbSC patients based on laboratory parameters and the clinical and genetic profile of both genotypes.

     

Organization of alpha‐transducin immunoreactive system in the brain and retina of larval and young adult Sea Lamprey (Petromyzon marinus), and their relationship with other neural systems

We employed an anti‐transducin antibody (Gαt‐S), in combination with other markers, to characterize the Gαt‐S‐immunoreactive (ir) system in the CNS of the sea lamprey, Petromyzon marinus. Gαt‐S immunoreactivity was observed in some neuronal populations and numerous fibers distributed throughout the brain. Double Gαt‐S‐ and opsin‐ir neurons (putative photoreceptors) are distributed in the hypothalamus (postoptic commissure nucleus, dorsal and ventral hypothalamus) and caudal diencephalon, confirming results of García‐Fernández et al. (Cell and Tissue Research, 288, 267–278, 1997). Singly Gαt‐S‐ir cells were observed in the midbrain and hindbrain, increasing the known populations. Our results reveal for the first time in vertebrates the extensive innervation of many brain regions and the spinal cord by Gαt‐S‐ir fibers. The Gαt‐S innervation of the habenula is very selective, fibers densely innervating the lamprey homologue of the mammalian medial nucleus (Stephenson‐Jones et al., Proceedings of the National Academy of Sciences of the United States of America, 109, E164–E173, 2012), but not the lateral nucleus homologue. The lamprey neurohypophysis was not innervated by Gαt‐S‐ir fibers. We also analyzed by double immunofluorescence the relation of this system with other systems. A dopaminergic marker (TH), serotonin (5‐HT) or GABA do not co‐localize with Gαt‐S‐ir neurons although codistribution of fibers was observed. Codistribution of Gαt‐S‐ir fibers and isolectin‐labeled extrabulbar primary olfactory fibers was observed in the striatum and hypothalamus. Neurobiotin retrograde transport from the spinal cord combined with immunofluorescence revealed spinal‐projecting Gαt‐S‐ir reticular neurons in the caudal hindbrain. Present results in an ancient vertebrate reveal for the first time a collection of brain targets of Gαt‐S‐ir neurons, suggesting they might mediate non‐visual modulation by light in many systems.     

Activity of weekly paclitaxel−cetuximab chemotherapy in unselected patients with recurrent/metastatic head and neck squamous cell carcinoma: prognostic factors

Background

Standard treatment for recurrent/metastatic head and neck squamous cell carcinoma (RM-SCCHN) is based in on platinum and cetuximab combination therapy. Unfortunately, not all patients are candidates to receive platinum-based treatment, because of different conditions as comorbidity and poor performance status. Weekly paclitaxel and cetuximab (WPC) is an active therapeutic alternative, based on a phase II study, with less toxicity. Our main objective is to confirm its activity in unselected patients, mostly unfit for aggressive therapies, analysing also some clinically relevant prognostic factors (PFs).

Methods

Retrospective data was collected for RM-SCCHN patients, treated at our institution between January 2008 and July 2014 with weekly paclitaxel (80 mg/m²) and cetuximab (400/250 mg/m²).

Results

148 patients were treated. The objective response rate (OR) was as follows: 13 patients (8.78%) complete response (CR); 57 patients (38.51%) partial response (PR) and 30 patients (20.3%) stable disease (SD). Median overall survival (OS) was 10 months (95% CI 8.31–11.69) and median progression free survival (PFS) was 7 months (95% CI 5.88–8.12). Response to treatment showed independent prognosis relevance as PF in multivariate analysis for PFS and OS. Furthermore, decline in serum magnesium during the treatment was also an independent PF for OS.

Conclusions

WPC activity was confirmed as a useful therapy on real-life unselected RM-SCCHN patients, with similar benefit to that obtained in the phase II study, and comparable to platinum and cetuximab based treatment, confirming its value in unfit patients. In addition to treatment response, a change in serum magnesium values during treatment was proved as independent PF on OS.

     

Putative Risk Factors for Non‐Suicidal Self‐Injury in Eating Disorders

Evidence suggests a common association between eating disorders (EDs) and non‐suicidal self‐injury (NSSI). The present study aimed to investigate the potential risk factors for NSSI among ED patients. We assessed 245 ED patients with the Oxford Risk Factor Interview for ED. The results showed that 33% of ED patients reported NSSI in their lifetime. NSSI appeared to occur more frequently among binge eating/purging type ED patients than among patients with other ED and to be related to a more severe eating pathology. A younger age at the onset of eating problems, more negative self‐evaluation, suicide attempts, substance abuse, parents' low weight, family tension at mealtime, parental alcohol problems, childhood abuse, peer aggression, and negative antecedent life events were more common among patients with co‐occurring EDs and NSSI than among patients without NSSI. The results may inform the risk assessment and treatment of NSSI in EDs in the early detection period. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.     

American tegumentary leishmaniasis: an uncommon clinical and histopathological presentation

We report a case of an unusual presentation of American Tegumentary Leishmaniasis involving a male patient with a solitary lesion on the ear lobe, persisting with minimal increase for at least six months without ulceration or related symptoms. The histological sections showed epithelial atrophy and a large number of structures consistent with Leishmania sp. amastigotes within macrophages. Treatment commenced with meglumine antimoniate resulting in regression of the condition. This report is of importance given the unusual clinical manifestation and histopathological findings in this case and the fact that there was low correlation with the extended duration of the disease.     

Mycotic brain aneurysm and cerebral hemorrhagic stroke: a pediatric case report

Endocarditis due to Abiotrophia spp. is rare and often associated with negative blood cultures, infection relapse, and high rates of treatment failure and mortality (Lainscak et al., J Heart Valve Dis 14(1):33–36, 2005). The authors describe a case of an adolescent with cerebral hemorrhagic stroke due to mycotic brain aneurysm rupture.