Paget's disease of bone in two medieval skeletons from Poulton Chapel, Cheshire, UK

Paget's disease of bone (PDB) is a chronic, metabolic disease disrupting normal bone turnover and is reported as one of the most common bone diseases after osteoporosis. PDB is characterised by excessive bone remodelling resulting in bone enlargement, fragility, deformity and additional complications. Typically, PDB affects one or a few bones of the axial skeleton and is commonly recorded in older individuals (over 55 years of age) affecting more males than females. Although PDB has been reported worldwide, there is a high concentration of reported cases in the UK, with a regional hotspot in the northwest of England. This study reviews an adult male (SK463) and female (SK750) with skeletal lesions of PDB from Poulton Chapel, Cheshire. Full macroscopic and radiographic analysis has identified the skeletal distribution of PDB, with up to 75% of both skeletons affected. SK463 presents noticeable anterior bowing to both tibiae, likely the result of PDB. AMS radiocarbon dating and stable isotope analysis performed on teeth samples confirmed that both individuals' dates were medieval, had a mixed/varied diet and were local to the northwest of England. This research adds to the emerging paleopathological literature on PDB, while providing additional support for the identification of a geographical hotspot observed in contemporary populations

Advancing the understanding of treponemal disease in the past and present

Syphilis was perceived to be a new disease in Europe in the late 15th century, igniting a debate about its origin that continues today in anthropological, historical, and medical circles. We move beyond this age-old debate using an interdisciplinary approach that tackles broader questions to advance the understanding of treponemal infection (syphilis, yaws, bejel, and pinta). How did the causative organism(s) and humans co-evolve? How did the related diseases caused by Treponema pallidum emerge in different parts of the world and affect people across both time and space? How are T. pallidum subspecies related to the treponeme causing pinta? The current state of scholarship in specific areas is reviewed with recommendations made to stimulate future work. Understanding treponemal biology, genetic relationships, epidemiology, and clinical manifestations is crucial for vaccine development today and for investigating the distribution of infection in both modern and past populations. Paleopathologists must improve diagnostic criteria and use a standard approach for recording skeletal lesions on archaeological human remains. Adequate contextualization of cultural and environmental conditions is necessary, including site dating and justification for any corrections made for marine or freshwater reservoir effects. Biogeochemical analyses may assess aquatic contributions to diet, physiological changes arising from treponemal disease and its treatments (e.g., mercury), or residential mobility of those affected. Shifting the focus from point of origin to investigating who is affected (e.g., by age/sex or socioeconomic status) and disease distribution (e.g., coastal/ inland, rural/urban) will advance our understanding of the treponemal disease and its impact on people through time

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

An osseous lesion in the maxillary sinus-Tumour or tumour-like?

In the bioarchaeological analysis of burials from a medieval graveyard at Hettstedt, Central Germany, a male skeleton of about 40 to 50 years at death with an unusual bony structure in the left maxillary sinus was discovered. Macroscopic examination exhibited a balloon-shaped osseous lesion with solid cortical surface 2.5 × 1.5 cm in size. Micro-CT scans revealed trabecular structures around a central cavity. The margins of the osseous lesion were well defined without infiltration of normal maxillary bone tissue. The histopathological analysis showed the presence of lamellar and woven bone. The structure and localisation of the tumour-like lesion suggest that the formation was the result of chronic inflammation and that chronic dental sinusitis seems to have triggered a large reactive ossification