Erdheim–Chester disease: An unusual presentation of an uncommon disease

Erdheim–Chester disease (ECD) is a rare, non-Langerhans cell histiocytosis with classic radiographic findings of patchy or diffuse osteosclerosis predominantly involving the long bones in a bilaterally symmetrical pattern. A 49-year-old woman presented with diffuse lymphadenopathy, painful skin lesions, and constitutional symptoms. Recent history was significant for a nontraumatic fracture of the tibia 3 weeks prior to admission. Physical examination and laboratory studies were notable for lower extremity pain and swelling, nodular lesions on the skin, and normocytic, normochromic anemia. Plain radiographs showed a lytic pattern of destruction with a superimposed fracture in the left proximal tibia. MRI showed focal bone marrow replacement extending from the subchondral bone to the tibial diaphysis. Excisional lymph node and skin biopsies of the lesions demonstrated a CD-68 positive, S-100 variable, and CD1a-negative histiocytic cell proliferation filling the dermis and completely replacing the sampled lymph node with an accompanying chronic inflammatory infiltrate and fibrosis, pathognomonic for ECD. We report an unusual case of ECD presenting initially as diffuse, painful lymphadenopathy, and subsequently demonstrating a lytic lesion of the tibia underlying a nontraumatic fracture.     

Elite triathletes in ‘Ironman Hawaii’ get older but faster

The age of peak performance has been well investigated for elite athletes in endurance events such as marathon running, but not for ultra-endurance (>6 h) events such as an Ironman triathlon covering 3.8 km swimming, 180 km cycling and 42 km running. The aim of this study was to analyze the changes in the age and performances of the annual top ten women and men at the Ironman World Championship the ‘Ironman Hawaii’ from 1983 to 2012. Age and performances of the annual top ten women and men in overall race time and in each split discipline were analyzed. The age of the annual top ten finishers increased over time from 26 ± 5 to 35 ± 5 years (r² = 0.35, P < 0.01) for women and from 27 ± 2 to 34 ± 3 years (r² = 0.28, P < 0.01) for men. Overall race time of the annual top ten finishers decreased across years from 671 ± 16 to 566 ± 8 min (r² = 0.44, P < 0.01) for women and from 583 ± 24 to 509 ± 6 min (r² = 0.41, P < 0.01) for men. To conclude, the age of annual top ten female and male triathletes in the ‘Ironman Hawaii’ increased over the last three decades while their performances improved. These findings suggest that the maturity of elite long-distance triathletes has changed during this period and raises the question of the upper limits of the age of peak performance in elite ultra-endurance performance.     

Single-dose vaccine against tick-borne encephalitis

Tick-borne encephalitis (TBE) virus is the most important human pathogen transmitted by ticks in Eurasia. Inactivated vaccines are available but require multiple doses and frequent boosters to induce and maintain immunity. Thus far, the goal of developing a safe, live attenuated vaccine effective after a single dose has remained elusive. Here we used a replication-defective (single-cycle) flavivirus platform, RepliVax, to generate a safe, single-dose TBE vaccine. Several RepliVax-TBE candidates attenuated by a deletion in the capsid gene were constructed using different flavivirus backbones containing the envelope genes of TBE virus. RepliVax-TBE based on a West Nile virus backbone (RV-WN/TBE) grew more efficiently in helper cells than candidates based on Langat E5, TBE, and yellow fever 17D backbones, and was found to be highly immunogenic and efficacious in mice. Live chimeric yellow fever 17D/TBE, Dengue 2/TBE, and Langat E5/TBE candidates were also constructed but were found to be underattenuated. RV-WN/TBE was demonstrated to be highly immunogenic in Rhesus macaques after a single dose, inducing a significantly more durable humoral immune response compared with three doses of a licensed, adjuvanted human inactivated vaccine. Its immunogenicity was not significantly affected by preexisting immunity against WN. Immunized monkeys were protected from a stringent surrogate challenge. These results support the identification of a single-cycle TBE vaccine with a superior product profile to existing inactivated vaccines, which could lead to improved vaccine coverage and control of the disease.