Bone marrow lesions (BMLs) are features detected on MRI that are important in the pathogenesis of knee osteoarthritis. Since BMLs reflect heterogeneous pathologies this prospective cohort study examined whether BMLs detected using different MRI sequences are associated with distinct structural and clinical endpoints.
A total of 297 community-based adults without knee pain were examined to identify BMLs visualised using three-dimensional T1-weighted gradient-echo fat-suppressed (T1-weighted sequences) fat-suppressed and fat-saturated FSE T2-weighted MRI sequences (T2-weighted sequences) at baseline. Cartilage volume was measured at baseline and follow-up, while incident knee pain was assessed at follow-up, an average of 2.3 years later.
At baseline, 46 BMLs were visualised in 39 participants. Of the 45 BMLs visualised on T2-weighted sequences, 34 (74 %) were also seen on T1-weighted sequences. One BML was seen on only T1-weighted sequences. Knees with BMLs visualised on both T1- and T2-weighted sequences had significantly higher medial tibial cartilage volume loss (45 mm3/annum, standard error of the mean (SEM) 14) than those with BMLs identified on only T2-weighted sequences (−13 mm3/annum SEM 19), after adjustment for age, gender and body mass index (p = 0.01). Incident knee pain was more likely in individuals with BMLs in the medial compartment visualised on both T1- and T2-weighted (eight participants, 53 %) compared to those with BMLs on only T2-weighted sequences (0 %) or no BMLs (76 participants, 31 %, p = 0.02).
BMLs present on both T1- and T2-weighted MRI sequences were associated with increased medial tibial cartilage loss and incident knee pain compared with those BMLs seen only on T2-weighted sequences. This suggests that combining different MRI sequences may provide more informative targets in the prevention and treatment of knee osteoarthritis.
Knee; Osteoarthritis; Bone marrow lesion; Pain
Exposure to Plasmodium falciparum is associated with circulating “atypical” memory B cells (atMBCs), which appear similar to dysfunctional B cells found in HIV-infected individuals. Functional analysis of atMBCs has been limited, with one report suggesting these cells are not dysfunctional but produce protective antibodies. To better understand the function of malaria-associated atMBCs, we performed global transcriptome analysis of these cells, obtained from individuals living in an area of high malaria endemicity in Uganda. Comparison of gene expression data suggested down-modulation of B cell receptor signaling and apoptosis in atMBCs compared to classical MBCs. Additionally, in contrast to previous reports, we found upregulation of Fc receptor-like 5 (FCRL5), but not FCRL4, on atMBCs. Atypical MBCs were poor spontaneous producers of antibody ex vivo, and higher surface expression of FCRL5 defined a distinct subset of atMBCs compromised in its ability to produce antibody upon stimulation. Moreover, higher levels of P. falciparum exposure were associated with increased frequencies of FCRL5+ atMBCs. Together, our findings suggest that FCLR5+ identifies a functionally distinct, and perhaps dysfunctional, subset of MBCs in individuals exposed to P. falciparum.
A subset of “atypical” memory B cells found in individuals with high exposure to P. falciparum has been hypothesized to be dysfunctional, based on phenotypic similarities to analogous cells found in HIV-infected individuals. However, the functional capabilities of these cells have been poorly characterized in the setting of malaria exposure, and previous reports have been controversial regarding whether these cells produce antibody. In our study, we analyze the molecular programming of atypical memory B cells, find that they are dysfunctional in a manner similar to that observed in B cells from HIV-infected individuals, and present data that may reconcile previously conflicting studies. By delineating the transcriptional landscape of atMBCs and identifying expression of FCRL5 as a key marker of dysfunction, we provide a foundation for improving our understanding of the role of these cells in immunity to malaria.
Although physical inactivity has been associated with numerous chronic musculoskeletal complaints, few studies have examined its associations with spinal structures. Moreover, previously reported associations between physical activity and low back pain are conflicting. This study examined the associations between physical inactivity and intervertebral disc height, paraspinal fat content and low back pain and disability.
Seventy-two community-based volunteers not selected for low back pain underwent magnetic resonance imaging (MRI) of their lumbosacral spine (L1 to S1) between 2011 and 2012. Physical activity was assessed between 2005 and 2008 by questionnaire, while low back pain and disability were assessed by the Chronic Pain Grade Scale at the time of MRI. Intervertebral disc height and cross-sectional area and fat content of multifidus and erector spinae were assessed from MRI.
Lower physical activity levels were associated with a more narrow average intervertebral disc height (β −0.63 mm, 95% confidence interval (CI) −1.17 mm to −0.08 mm, P = 0.026) after adjusting for age, gender and body mass index (BMI). There were no significant associations between physical activity levels and the cross-sectional area of multifidus or erector spinae. Lower levels of physical activity were associated with an increased risk of high fat content in multifidus (odds ratio (OR) 2.7, 95% CI 1.1 to 6.7, P = 0.04) and high-intensity pain/disability (OR = 5.0, 95% CI 1.5 to 16.4, P = 0.008) after adjustment for age, gender and BMI.
Physical inactivity is associated with narrower intervertebral discs, high fat content of the multifidus and high-intensity low back pain and disability in a dose-dependent manner among community-based adults. Longitudinal studies will help to determine the cause and effect nature of these associations.
Electronic supplementary material
The online version of this article (doi:10.1186/s13075-015-0629-y) contains supplementary material, which is available to authorized users.
Mexico is undergoing rapid population ageing as a result of its epidemiological transition. This study explores the interface between this rapid population ageing and the burden of cancer. The number of new cancer cases is expected to increase by nearly 75% by 2030 (107,000 additional cases per annum), with 60% of cases in the elderly (aged ≥ 65). A review of the literature was supplemented by a bibliometric analysis of Mexico’s cancer research output. Cancer incidence projections for selected sites were estimated with Globocan software. Data were obtained from recent national census, surveys, and cancer death registrations. The elderly, especially women and those living in rural areas, face high levels of poverty, have low rates of educational attainment, and many are not covered by health insurance schemes. Out of pocket payments and private health care usage remain high, despite the implementation of Seguro Popular that was designed to achieve financial protection for the lowest income groups. A number of cancers that predominate in elderly persons are not covered by the scheme and individuals face catastrophic expenditure in seeking treatment. There is limited research output in those cancer sites that have a high burden in the elderly Mexican population, especially research that focuses on outcomes. The elderly population in Mexico is vulnerable to the effects of the rising cancer burden and faces challenges in accessing high quality cancer care. Based on our evidence, we recommend that geriatric oncology should be an urgent public policy priority for Mexico.
geriatric oncology; low middle-income country; demographic transition; ageing; cancer burden
The mechanism by which obesity increases the risk of hip osteoarthritis is unclear. One possibility may be by mediating abnormalities in bony geometry, which may in turn be associated with early structural abnormalities, such as cartilage defects and bone marrow lesions.
One hundred and forty one older adults with no diagnosed hip osteoarthritis had weight and body mass index measured between 1990 and 1994 and again in 2009 to 2010. Acetabular depth and lateral centre edge angle, both measures of acetabular over-coverage, as well as femoral head cartilage volume, cartilage defects and bone marrow lesions were assessed with 3.0 T magnetic resonance imaging performed in 2009 to 2010.
Current body mass index, weight and weight gain were associated with increased acetabular depth and lateral centre edge angle (all P ≤ 0.01). For every 1 mm increase in acetabular depth, femoral head cartilage volume reduced by 59 mm3 (95% confidence interval (CI) 20 mm3 to 98 mm3, P < 0.01). Greater acetabular depth was associated with an increased risk of cartilage defects (odds ratio (OR) 1.22, 95% CI 1.03 to 1.44, P = 0.02) and bone marrow lesions (OR 1.29, 95% CI 1.01 to 1.64, P = 0.04) in the central region of the femoral head. Lateral centre edge angle was not associated with hip structure.
Obesity is associated with acetabular over-coverage. Increased acetabular depth, but not the lateral centre edge angle, is associated with reduced femoral head cartilage volume and an increased risk of cartilage defects and bone marrow lesions. Minimising any deepening of the acetabulum (for example, through weight management) might help to reduce the incidence of hip osteoarthritis.
Occupational exposure to heavy lifting and stair climbing are associated with radiographic hip osteoarthritis (OA). This study examined whether these activities are associated with early structural hip joint changes in a community-based population.
In total, 198 community-based people with no history of hip disease, including OA, had 3.0 T-magnetic resonance imaging (MRI) to assess hip cartilage volume, defects and bone marrow lesions (BMLs). Recall of occupational exposure to heavy lifting and stair climbing aged 18 to 30 years and in the previous 10 years were collected. A persistence score was defined as exposure at neither time point (0), at one time point (1) or at both time points (2).
Exposure to heavy lifting when aged 18 to 30 years was associated with BMLs of the central superolateral femoroacetabular region (odds ratio (OR) 3.9, 95% confidence interval (CI) 1.6 to 9.8, P <0.01), with persistence score associated with cartilage defects in the central superolateral region of the femoral head (OR 1.6, 95% CI 1.0 to 2.5, P = 0.04). Exposure to stair climbing aged 18 to 30 years and persistence score were associated with an increased risk of cartilage defects in the central superolateral femoral head and BMLs in the central superolateral and posterior femoroacetabular regions (OR range 2.1 to 3.2, all P ≤0.03).
Occupational exposure to heavy lifting and stair climbing are associated with hip structural abnormalities. If confirmed by longitudinal data, such associations may explain how occupational activities affect the hip joint and may identify new targets for the prevention of hip OA.
The South American country Chile now boasts a life expectancy of over 80 years. As a consequence, Chile now faces the increasing social and economic burden of cancer and must implement political policy to deliver equitable cancer care. Hindering the development of a national cancer policy is the lack of comprehensive analysis of cancer infrastructure and economic impact.
Evaluate existing cancer policy, the extent of national investigation and the socio-economic impact of cancer to deliver guidelines for the framing of an equitable national cancer policy.
Burden, research and care-policy systems were assessed by triangulating objective system metrics – epidemiological, economic, etc. – with political and policy analysis. Analysis of the literature and governmental databases was performed. The oncology community was interviewed and surveyed.
Chile utilizes 1% of its gross domestic product on cancer care and treatment. We estimate that the economic impact as measured in Disability Adjusted Life Years to be US$ 3.5 billion. Persistent inequalities still occur in cancer distribution and treatment. A high quality cancer research community is expanding, however, insufficient funding is directed towards disproportionally prevalent stomach, lung and gallbladder cancers.
Chile has a rapidly ageing population wherein 40% smoke, 67% are overweight and 18% abuse alcohol, and thus the corresponding burden of cancer will have a negative impact on an affordable health care system. We conclude that the Chilean government must develop a national cancer strategy, which the authors outline herein and believe is essential to permit equitable cancer care for the country.
Chile; Cancer policy; Investigation; Research and development; Statistics; Gallbladder cancer; Stomach cancer; Developing country
The magnitude of flooding in New York City by Hurricane Sandy is commonly believed to be extremely rare, with estimated return periods near or greater than 1000 years. However, the brevity of tide gauge records result in significant uncertainties when estimating the uniqueness of such an event. Here we compare resultant deposition by Hurricane Sandy to earlier storm-induced flood layers in order to extend records of flooding to the city beyond the instrumental dataset. Inversely modeled storm conditions from grain size trends show that a more compact yet more intense hurricane in 1821 CE probably resulted in a similar storm tide and a significantly larger storm surge. Our results indicate the occurrence of additional flood events like Hurricane Sandy in recent centuries, and highlight the inadequacies of the instrumental record in estimating current flood risk by such extreme events.
Few data are available concerning structural changes at the hip observed by magnetic resonance imaging (MRI) in people with or without hip osteoarthritis (OA). The aim of this study was to compare cartilage volume and the presence of cartilage defects and bone marrow lesions (BMLs) in participants with and without diagnosed hip OA.
Femoral head cartilage volume was measured by MRI for 141 community-based persons with no diagnosed hip OA, and 19 with diagnosed hip OA. Cartilage defects and BMLs were regionally scored at the femoral head and acetabulum.
Compared with those without diagnosed hip OA, people with diagnosed hip OA had less femoral head cartilage volume (1763 mm3 versus 3343 mm3; p <0.001) and more prevalent cartilage defects and BMLs (all p ≤0.05) at all sites other than the central inferomedial region of the femoral head. In those with no diagnosed hip OA, cartilage defects in the anterior and central superolateral region of the femoral head were associated with reduced femoral head cartilage volume (all p ≤0.02). Central superolateral BMLs at all sites were associated with reduced femoral head cartilage volume (all p ≤0.003), with a similar trend occurring when BMLs were located in the anterior region of the hip (all p ≤0.08).
Compared with community-based adults with no diagnosed hip OA, people with diagnosed hip OA have less femoral head cartilage volume and a higher prevalence of cartilage defects and BMLs. For people with no diagnosed hip OA, femoral head cartilage volume was reduced where cartilage defects and/or BMLs were present in the anterior and central superolateral regions of the hip joint. Cartilage defects and BMLs present in the anterior and central superolateral regions may represent early structural damage in the pathogenesis of hip OA.
Patellar tendinopathy is a common cause of activity-related anterior knee pain. Evidence is conflicting as to whether obesity is a risk factor for this condition. The aim of this study was to determine the relationship between obesity and prevalence of magnetic resonance imaging (MRI) defined patellar tendinopathy in community-based adults.
297 participants aged 50–79 years with no history of knee pain or injury were recruited from an existing community-based cohort. Measures of obesity included measured weight and body mass index (BMI), self-reported weight at age of 18–21 years and heaviest lifetime weight. Fat-free mass and fat mass were measured using bioelectrical impedance. Participants underwent MRI of the dominant knee. Patellar tendinopathy was defined on both T1- and T2-weighted images.
The prevalence of MRI defined patellar tendinopathy was 28.3%. Current weight (OR per kg = 1.04, 95% CI 1.01-1.06, P = 0.002), BMI (OR per kg/m2 = 1.10, 95% CI 1.04-1.17, P = 0.002), heaviest lifetime weight (OR per kg = 1.03, 95% CI 1.01-1.05, P = 0.007) and weight at age of 18–21 years (OR per kg = 1.03, 95% CI 1.00-1.07, P = 0.05) were all positively associated with the prevalence of patellar tendinopathy. Neither fat mass nor fat-free mass was associated with patellar tendinopathy.
MRI defined patellar tendinopathy is common in community-based adults and is associated with current and past history of obesity assessed by BMI or body weight, but not fat mass. The findings suggest a mechanical pathogenesis of patellar tendinopathy and patellar tendinopathy may be one mechanism for obesity related anterior knee pain.
Obesity; Patellar tendinopathy; Body mass index; Weight; Fat mass; Magnetic resonance imaging
Libertarian paternalism is a concept derived from cognitive psychology and behavioural science. It is behind policies that frame information in such a way as to encourage individuals to make choices which are in their best interests, while maintaining their freedom of choice. Clinicians may view their clinical consultations as far removed from the realms of cognitive psychology but on closer examination there are a number of striking similarities.
Evidence has shown that decision making is prone to bias and not necessarily rational or logical, particularly during ill health. Clinicians will usually have an opinion about what course of action represents the patient’s best interests and thus may “frame” information in a way which “nudges” patients into making choices which are considered likely to maximise their welfare. This may be viewed as interfering with patient autonomy and constitute medical paternalism and appear in direct opposition to the tenets of modern practice. However, we argue that clinicians have a responsibility to try and correct “reasoning failure” in patients. Some compromise between patient autonomy and medical paternalism is justified on these grounds and transparency of how these techniques may be used should be promoted.
Overall the extremes of autonomy and paternalism are not compatible in a responsive, responsible and moral health care environment, and thus some compromise of these values is unavoidable. Nudge techniques are widely used in policy making and we demonstrate how they can be applied in shared medical decision making. Whether or not this is ethically sound is a matter of continued debate but health care professionals cannot avoid the fact they are likely to be using nudge within clinical consultations. Acknowledgment of this will lead to greater self-awareness, reflection and provide further avenues for debate on the art and science of clinical communication.
Nudge; Libertarian paternalism; Communication; Framing; Shared decision making; Medical consultation
The media plays a vital role in informing the public about new developments in cancer research and influencing cancer policy. This is no easy task, in view of the myriad of trials and wonder drugs that purport to be the ‘magic bullet’. However, misrepresentation can have profound consequences. In this qualitative study, we sought to understand the interaction between the media and cancer through the perspective of European science journalists by defining their attitudes towards current cancer research and challenges faced when reporting science news. A total of 67 respondents took part in this online survey, which was distributed by the European CanCer Organisation (ECCO) to all its media contacts between June and September 2013. Fifty-three per cent had over 20 years experience in reporting science news stories. The respondents utilised a number of media formats, including newsprint, online services, and radio.
Fifty per cent ranked public interest as the greatest influence on their selection of cancer research topics, followed by topicality. Respondents were conscious of being fed ambiguous and exaggerated results from trials by the research community. Sixty-five per cent of respondents would appreciate access to a forum of experts willing to provide comment on new research findings. Seventy per cent highlighted the importance of prompt responses from scientists and researchers during correspondence, and the need to have advance warning of new developments (49%). To conclude – coverage of cancer related issues and scientific advances require greater collaboration between the press and cancer healthcare community to provide both credibility and accountability for the health information disseminated. Key areas include a more precise definition of the research context and differentiation of absolute and relative risks, as well as individual and population risks and an informed discussion about the realities and limitations of cancer care and research.
Cancer; health information; media; public reporting; research; trials
The European Cancer Concord is a unique patient-centered partnership that will act as a catalyst to achieve improved access to an optimal standard of cancer care and research for European citizens. In order to provide tangible benefits for European cancer patients, the partnership proposes the creation of a “European Cancer Patient’s Bill of Rights,” a patient charter that will underpin equitable access to an optimal standard of care for Europe’s citizens.
This study aimed to critically appraise translational research models for suitability in performance assessment of cancer centers. Process models, such as the Process Marker Model and Lean and Six Sigma applications, seem to be suitable for performance assessment of cancer centers. However, they must be thoroughly tested in practice.
Translational research is a complex cumulative process that takes time. However, the operating environment for cancer centers engaged in translational research is now financially insecure. Centers are challenged to improve results and reduce time from discovery to practice innovations. Performance assessment can identify improvement areas that will help reduce translational delays. Currently, no standard method exists to identify models for use in performance assessment. This study aimed to critically appraise translational research models for suitability in performance assessment of cancer centers.
We conducted a systematic review to identify models and developed a set of criteria based on scientometrics, complex adaptive systems, research and development processes, and strategic evaluation. Models were assessed for linkage between research and care components, new knowledge, systems integration, performance assessment, and review of other models.
Twelve models were identified; six described phases/components for translational research in different blocks (T models) and six described the process of translational research (process models). Both models view translational research as an accumulation of new knowledge. However, process models more clearly address systems integration, link research and care components, and were developed for evaluating and improving the performance of translational research. T models are more likely to review other models.
Process models seem to be more suitable for performance assessment of cancer centers than T models. The most suitable process models (the Process Marker Model and Lean and Six Sigma applications) must be thoroughly tested in practice.
Translational medical research; Models; Performance assessment; Cancer centers; Performance improvement
Cancer is predicted to be an increasingly important cause of morbidity and mortality in Bangladesh in the next few decades. The estimated incidence of 12.7 million new cancer cases will rise to 21.4 million by 2030. More than two-thirds of the total expenditure on health is through out-of-pocket payments. According to the Bangladesh Bureau of Statistics, cancer is the sixth leading cause of death. International Agency for Research on Cancer has estimated cancer-related death rates in Bangladesh to be 7.5% in 2005 and 13% in 2030. The two leading causes are in males are lung and oral cancer and in females are breast cancer and cervical cancer. Bangladesh is now in severe shortage of radiation therapy machines, hospital bed, trained oncologists, medical radiation physicists and technologists. Bangladesh having different cancers associated with smoking and smokeless tobacco use, Human papilloma virus infection, Hepatitis B and C infection, Helicobacter Pylori infection, arsenic contaminated groundwater, availability of chemical carcinogens mainly formalin treated fruits, fish and vegetables at open market, tannery waste contaminated with chromium (which is used for poultry feed and fish feed preparation). A World Health Organization study revealed the annual cost of illnesses in Bangladesh attributable to tobacco usage is US$ 500 million and the total annual benefit from the tobacco sector is US$ 305 million as tax revenue. Bangladesh has developed a National Cancer Control Strategy and Action Plan with the aim of delivering a universal, quality-based and timely service. Cancer prevention through tobacco control, health promotion and vaccination program, cancer early detection program for oral cavity, breast and cervix has initiated. Cancer detection and diagnostic facilities will be made available at medical colleges and district- hospitals and establish a referral chain. National capacity development, more cancer research will allow Bangladesh to deal effectively and efficiently with the cancer problems through evidence-based decision making.
cancer control; Bangladesh
Streptococcus mutans is considered a major causative of tooth decay due to it’s ability to rapidly metabolize carbohydrates such as sucrose. One prominent excreted end product of sucrose metabolism is lactic acid. Lactic acid causes a decrease in the pH of the oral environment with subsequent demineralization of the tooth enamel. Biologically relevant bacteria-induced enamel demineralization was studied.
Optical profiling was used to measure tooth enamel decay with vertical resolution under one nanometer and lateral features with optical resolution as a result of S. mutans biofilm exposure. Comparison measurements were made using AFM.
After 72 hr of biofilm exposure the enamel displayed an 8-fold increase in the observed roughness average, (Ra), as calculated over the entire measured array. Similarly, the average root mean square (RMS) roughness, RRMS, of the enamel before and after biofilm exposure for 3 days displayed a 7-fold increase. Further, the direct effect of chemically induced enamel demineralization using biologically relevant organic acids was shown. Optical profiles of the enamel surface after addition of a 30% lactic acid solution showed a significant alteration in the surface topography with a corresponding increase in respective surface roughness statistics. Similar measurements with 10% citric acid over seconds and minutes give insight into the demineralization process by providing quantitative measures for erosion rates: comparing surface height and roughness as metrics.
The strengths of optical profilometry as an analytical tool for understanding and analyzing biologically relevant processes such as biofilm induced tooth enamel demineralization were demonstrated.
enamel erosion; optical profilometry; biofilm; Streptococcus mutans; enamel demineralization; citric acid; lactic acid; AFM
Although obesity is widely accepted as a risk factor for knee osteoarthritis, whether weight per se or the specific components of body composition are the major determinants of properties of articular knee cartilage is unclear.
To examine associations between anthropometric and body composition measures and knee cartilage properties in healthy adults.
297 healthy adults with no clinical knee osteoarthritis were recruited from an existing community‐based cohort. Anthropometric measures and body composition, including fat‐free mass and fat mass assessed using bioelectrical impedance analysis, were measured at baseline (1990–4) and current follow‐up (2003–4). Tibial cartilage volume and tibiofemoral cartilage defects were assessed using MRI at follow‐up.
After adjustment for potential confounders, baseline and current fat‐free mass, independent of fat mass, were positively associated with tibial cartilage volume (all p<0.001). Increased fat‐free mass over the time period was positively associated with tibial cartilage volume (p<0.001). Current fat mass was negatively associated with tibial cartilage volume (p = 0.004). Baseline and current fat mass were weakly associated with increased tibiofemoral cartilage defects (p = 0.06 and p = 0.07, respectively), independent of fat‐free mass.
The findings suggest a beneficial effect of fat‐free mass, but a deleterious effect of fat mass, on knee cartilage properties in healthy adults. This suggests that weight‐loss programmes aimed at reducing fat mass but maintaining muscle mass may be important in preventing the onset and/or progression of knee osteoarthritis.
fat‐free mass; fat mass; cartilage; cartilage defects; osteoarthritis
To examine the relationship between development or resolution of bone marrow lesions (BMLs) and knee cartilage properties in a 2 year prospective study of asymptomatic middle-aged adults.
271 adults recruited from the Melbourne Collaborative Cohort Study, underwent a magnetic resonance imaging scan (MRI) of their dominant knee at baseline and again approximately 2 years later. Cartilage volume, cartilage defects and BMLs were determined at both time points.
Among 234 subjects free of BMLs at baseline, 33 developed BMLs over 2 years. The incidence of BMLs was associated with progression of tibiofemoral cartilage defects (OR 2.63 (95% CI 0.93, 7.44), P = 0.07 for medial compartment; OR 3.13 (95% CI 1.01, 9.68), P = 0.048 for lateral compartment). Among 37 subjects with BMLs at baseline, 17 resolved. Resolution of BMLs was associated with reduced annual loss of medial tibial cartilage volume (regression coefficient -35.9 (95%CI -65, -6.82), P = 0.02) and a trend for reduced progression of medial tibiofemoral cartilage defects (OR 0.2 (95% CI 0.04, 1.09), P = 0.06).
In this cohort study of asymptomatic middle-aged adults the development of new BMLs was associated with progressive knee cartilage pathology while resolution of BMLs prevalent at baseline was associated with reduced progression of cartilage pathology. Further work examining the relationship between changes and BML and cartilage may provide another important target for the prevention of knee osteoarthritis.
Fatty acids have been implicated in osteoarthritis (OA), yet the mechanism by which fatty acids affect knee structure and consequently the risk of knee OA has not been fully elucidated. Higher intakes of fatty acids have been shown to be associated with the risk of bone marrow lesions (BMLs) in a healthy population. The aim of this study was to examine the association between fatty acid consumption and the incidence of BMLs in healthy middle-aged adults without clinical knee OA.
Two hundred ninety-seven middle-aged adults without clinical knee OA underwent magnetic resonance imaging (MRI) of their dominant knee at baseline. BMLs were assessed. Of the 251 participants with no BMLs in their knee at baseline, 230 underwent MRI of the same knee approximately 2 years later. Intakes of fatty acids were estimated from a food frequency questionnaire.
Increased consumption of saturated fatty acids was associated with an increased incidence of BMLs over 2 years after adjusting for energy intake, age, gender, and body mass index (odds ratio of 2.56 for each standard deviation increase in dietary intake, 95% confidence interval 1.03 to 6.37, P = 0.04). Intake of monounsaturated or polyunsaturated fatty acids was not significantly associated with the incidence of BMLs.
Increased fatty acid consumption may increase the risk of developing BMLs. As subchondral bone is important in maintaining joint integrity and the development of OA, this study suggests that dietary modification of fatty acid intake may be one strategy in the prevention of knee OA which warrants further investigation.
Epidemiological and pedigree studies suggest that lung cancer results from the combined effects of age, smoking, impaired lung function and genetic factors. In a case control association study of healthy smokers and lung cancer cases, we identified genetic markers associated with either susceptibility or protection to lung cancer.
We screened 157 candidate single nucleotide polymorphisms (SNP) in a discovery cohort of 439 subjects (200 controls and 239 lung cancer cases) and identified 30 SNPs associated with either the healthy smokers (protective) or lung cancer (susceptibility) phenotype. After genotyping this 30 SNP panel in a validation cohort of 491 subjects (248 controls and 207 lung cancers) and, using the same protective and susceptibility genotypes from our discovery cohort, a 20 SNP panel was selected based on replication of SNP associations in the validation cohort. Following multivariate logistic regression analyses, including the selected SNPs from runs 1 and 2, we found age and family history of lung cancer to be significantly and independently associated with lung cancer. Numeric scores were assigned to both the SNP and demographic data, and combined to form a simple algorithm of risk.
Significant differences in the distribution of the lung cancer susceptibility score was found between normal controls and lung cancer cases, which remained after accounting for differences in lung function. Validation in other case-control and prospective cohorts are underway to further define the potential clinical utility of this model.
Immunologic tolerance to endogenous antigens reduces antitumor responses. Gp70 is an endogenous tumor-associated antigen (TAA) of the BALB/c-derived colon carcinoma CT26. We found that expression of gp70 mRNA is detectable in tissues of mice 8 months of age and older. We showed that expression of gp70 establishes immunologic tolerance and affects antitumor immunity in a similarly age-dependent manner using gp70-deficient mice. We found that tumors grew in all gp70-sufficient mice, while approximately half of gp70-deficient mice controlled tumor growth with endogenous T cell responses. Protection in gp70-deficient mice correlated with more robust gp70-specific CTL responses, and increased numbers and avidity of responding antigen-specific T cells after vaccination. We conclude that immunosurveillance may decline with age due to increased or de novo peripheral expression of endogenous TAAs.
Tumor-associated antigen; immunologic tolerance; immunosurveillance
Magnetic resonance imaging (MRI) is increasingly used to examine joints for research purposes. It may detect both suspected and unsuspected abnormalities. This raises both clinical and ethical issues, especially when incidental abnormalities are detected. The prevalence of incidental, potentially clinically significant abnormalities identified by MRI and their clinical significance in a population undergoing knee MRI in research studies are unknown.
We examined the prevalence of such lesions in healthy asymptomatic adults and those with symptomatic knee osteoarthritis (OA) undergoing knee MRI with limited sequences for the purpose of research. The MRI findings in 601 asymptomatic subjects and 132 with knee OA who underwent at least one limited knee MRI scan for cartilage volume measurement were examined by an MRI radiologist for the presence of potentially clinically significant abnormalities.
These were present in 2.3% of healthy and 2.3% of OA subjects. All required further investigation to exclude non-benign disease, including four with bone marrow expansion (0.7%), requiring further investigation and management. A single potentially life-threatening lesion, a myeloma lesion, was identified in a subject with symptomatic knee OA on their second MRI scan in a longitudinal study.
As musculoskeletal MRI is increasingly used clinically and for research purposes, the potential for detecting unsuspected abnormalities that require further investigation should be recognized. Incorporating a system to detect these, to characterize unexpected findings, and to facilitate appropriate medical follow-up when designing studies using this technology should be considered ethical research practice.