Protection against streptococcal cell wall-induced arthritis by pretreatment with the 65-kD mycobacterial heat shock protein

We report that streptococcal cell wall (SCW)-induced arthritis in rats, a T cell-dependent chronic, erosive polyarthritis, can be prevented by pretreatment of the rats with the mycobacterial 65-kD heat shock protein. This 65-kD protein shows extensive amino acid homology with prokaryotic and eukaryotic 65-kD heat shock proteins and is a ubiquitous bacterial common antigen. Both the clinical and histopathologic manifestations of the arthritis were prevented completely when rats were pretreated with 50 micrograms of 65-kD protein intraperitoneally at 35, 25, 15, or 5 d before administration of SCW. In such protected rats, SCW-specific T cell responses were suppressed, as compared with responses in arthritic rats. Pretreatment with 65-kD protein had no effect on the production of antibodies against SCW, on a nonspecific inflammatory reaction (zymosan-induced arthritis), or on general cellular immunity in vivo (delayed type hypersensitivity reaction to a nonrelated protein antigen). Furthermore, the protection against SCW arthritis was transferable by splenic T cells to naive recipients. Our data show that pretreatment with the 65-kD mycobacterial heat shock protein protects rats against a subsequent bacterium-induced arthritis. This protection is immunologically specific and resides in the lymphoid cell population.     

Value of prehospital assessment of spine fracture by paramedics

European Journal of Trauma and Emergency Surgery - Current guidelines state that trauma patients at risk of spine injury should undergo prehospital spine immobilization to reduce the risk of...     

A pilot randomized trial comparing symptomatic vs. hemoglobin-level- driven red blood cell transfusions following hip fracture

BACKGROUND: The indications for transfusion have never been evaluated in an adequately sized clinical trial. A pilot study was conducted to plan larger clinical trials. STUDY DESIGN AND METHODS: Hip fracture patients undergoing surgical repair who had postoperative hemoglobin levels less than 10 g per dL were randomly assigned to receive 1) symptomatic transfusion: that is, transfusion for symptoms of anemia or for a hemoglobin level that dropped below 8 g per dL or 2) threshold transfusion: that is, patients receive 1 unit of packed RBCs at the time of random assignment and as much blood as necessary to keep the hemoglobin level above 10 g per dL. Outcomes were 60-day mortality, morbidity, functional status, and place of residence. RESULTS: Among 84 eligible patients enrolled, mean (± SD) prerandomization hemoglobin was 9.1 (± 0.6) g/ dL. The median number of units transfused in the threshold transfusion group was 2 (interquartile range, = 1–2), and that in the symptomatic transfusion group was 0 (6; interquartile range, = 0–2) (p < 0.001). Mean hemoglobin levels were approximately 1 g per dL higher in the threshold group than in the symptomatic group: for example, on Day 2, 10.3 (± 0.9) g per dL versus 9.3 (± 1.2) g per dL, respectively (p < 0.001). At 60 days, death or inability to walk across the room without assistance occurred in 16 (39.0%) of the symptomatic transfusion group and 19 (45.2%) of the threshold transfusion group. Death occurred by 60 days in 5 (11.9%) of the symptomatic transfusion group and 2 (4.8%) in the threshold transfusion group (relative risk = 2.5; 95% CI, 0.5–12.2). Other outcomes were similar for the two groups. CONCLUSIONS: Symptomatic transfusion may be an effective blood-sparing protocol associated with the transfusion of appreciably fewer units of RBCs and lower mean hemoglobin levels than are associated with the threshold transfusion policy. However, it is unknown whether these two clinical strategies have comparable mortality, morbidity, or functional status. A definitive trial is needed.     

Is ultraviolet exposure acquired at work the most important risk factor for cutaneous squamous cell carcinoma? Results of the population‐based case–control study FB‐181

Squamous cell carcinoma (SCC) is a specific type of skin cancer. It is one of the most common cancers in Europe. SCC therefore causes a significant burden, both for the people affected and also in terms of costs to society. One main cause of SCC is exposure to natural sunlight. SCC can be prevented by avoiding sun exposure. When people go outside, they can protect themselves through clothes (e.g. long sleeves, hat) and using sunscreens. Until now, prevention programs for SCC and other skin cancers have mainly tried to reduce sun exposure during leisure time. However, there are many people working outdoors, e.g. farmers, construction workers and roofers. The role of occupational (work‐related) and leisure‐time sun exposure in causing SCC is still unclear. Our team of physicians and scientists from Germany investigated the association between occupational and leisure‐time sun exposure and the risk of SCC. More than 600 people with SCC were compared to the same number of healthy people without SCC, taking into account their sun exposure in the past. All study participants were medically examined by trained physicians. Lifetime sun exposure in occupation and leisure time was assessed by interviews. The interviews were tested before starting the study to ensure correct results. The study found that people with high levels of sun exposure at work have a 2‐fold risk of SCC. The more sun exposure people had at work, the more likely was the development of SCC. This result is important, as it indicates that sun protection is not only necessary in leisure‐time, but also at work to prevent skin cancer such as SCC.     

Tumor characteristics as an analytic tool for classifying genetic variants of uncertain clinical significance

It is important to identify a germline mutation in a patient with an inherited cancer syndrome to allow mutation carriers to be included in cancer surveillance programs, which have been proven to save lives. Many of the mutations identified result in premature termination of translation, and thus in loss-of-function of the encoded mutated protein. However, the significance of a large proportion of the sequence changes reported is unknown. Some of these variants will be associated with a high risk of cancer and have direct clinical consequence. Many criteria can be used to classify variants with unknown significance; most criteria are based on the characteristics of the amino acid change, on segregation data and appearance of the variant, on the presence of the variant in controls, or on functional assays. In inherited cancers, tumor characteristics can also be used to classify variants. It is worthwhile to examine the clinical, morphological and molecular features of a patient, and his or her family, when assessing whether the role of a variant is likely to be neutral or pathogenic. Here we describe the advantages and disadvantages of using the tumor characteristics of patients carrying germline variants of uncertain significance (VUS) in BRCA1, BRCA2, or in one of the mismatch repair (MMR) genes, MLH1, MSH2, or MSH6, to infer pathogenicity.     

Understanding the relationship between cognition and death: a within cohort examination of cognitive measures and mortality

Despite several studies demonstrating an independent and inverse association between cognition and mortality, the nature of this association still remains unclear. To examine the association of cognition and mortality after accounting for sociodemographic, health and lifestyle factors and to explore both test and population characteristics influencing this relationship. In a population based cohort of 8585 men and women aged 48–92 years, who had cognitive assessments in 2006–2011 and were followed up till 2016 for mortality, we examined the relationship between individual cognitive tests as well as a global cognition score to compare their ability in predicting mortality and whether these differed by population characteristics. Risk of death was estimated using Cox proportional hazard regression models including sociodemographic, lifestyle and health variables, and self-reported comorbidities, as covariates in the models. Poor cognitive performance (bottom quartile of combined cognition score) was associated with higher risk of mortality, Hazard Ratio?=?1.32 (95% Confidence Interval 1.09, 1.60); individual cognitive tests varied in their mortality associations and also performed differently in middle-age and older age groups. Poor cognitive performance is independently associated with higher mortality. This association is observed for global cognition and for specific cognitive abilities. Associations vary depending on the cognitive test (and domain) as well as population characteristics, namely age and education.