A comprehensive MRI investigation to identify potential biomarkers of Osgood Schlatter disease in adolescents: a cross sectional study comparing Osgood Schlatter disease with controls

Background Osgood–Schlatter disease (OSD) is the most common knee pain complaint among adolescents playing sports. Despite this, there remains controversy over the pathophysiology and whether specific anatomical characteristics are associated with OSD. Purpose This study aimed to systematically and comprehensively characterize adolescents with OSD using magnetic resonance imaging (MRI) compared to pain-free controls, including both tissue abnormalities that may be associated with OSD, as well as anatomical characteristics. A secondary objective was to identify potential imaging biomarkers associated with pain. Study Design Cross-sectional study. Methods Adolescents with OSD and controls were recruited from 2020 to 2022. Following a clinical exam, demographics, pain, sports participation, and Tanner stage were collected. Knee MRI was conducted on the participants' most symptomatic knee (OSD) or the dominant leg (controls). Results Sixty-seven adolescents (46 with OSD and 30 controls) were included. 80% of participants with OSD had at least one tissue alteration compared to 54% of controls. Compared to controls, OSD had 36.3 (95%CI 4.5 to 289.7) higher odds of bony oedema at the tibial tuberosity, and 32.7 (95%CI 4.1 to 260.6) and 5.3 (95%CI 0.6 to 46.2) higher odds of bony oedema at the tibial epiphysis and metaphysis respectively. Participants with OSD also had higher odds of fluid/oedema at the patellar tendon (12.3 95%CI 3.3 to 46.6), and superficial infrapatellar bursitis (7.2). Participants with OSD had a more proximal tendon attachment (mean tibial attachment portion difference, −0.05, 95% CI: −0.1 to 0.0, p = 0.02), tendon thickness (proximal mean difference, −0.09, 95% CI: −0.4 to 0.2, p = 0.04; distal mean difference, −0.6, 95% CI: −0.9 to −0.2, p = 0.01). Those with bony/tendon oedema had 1.8 points (95% CI: 0.3 to 3.2) higher pain on palpation than those without (t = −2.5, df = 26.6, p = 0.019), but there was no difference between these groups in a functional single leg pain provocation. Conclusion Adolescents with OSD present with tissue and structural abnormalities on MRI that differed from age-matched controls. The majority had findings in the patellar tendon and bone, which often co-occurred. However, a small proportion of OSD also presents without alterations. It appears these findings may be associated with clinical OSD-related pain on palpation of the tibial tuberosity. Clinical Relevance Our highlight the pathophysiology on imaging, which has implications for understanding the mechanism and treatment of OSD

Effects of buprenorphine on acute pain and inflammation in the adjuvant-induced monoarthritis rat model

Background and aim: Animal modelling of arthritis is often associated with pain and suffering. Severity may be reduced with the use of analgesia which is, however, often withheld due to concerns of introducing a confounding variable. It is therefore important to design and validate pain relief protocols that reduce pain without compromising the scientific objectives. The present study evaluated the effect of buprenorphine analgesia in the immediate post-induction period of an adjuvant-induced monoarthritic rat model. The aim of this study was to extend previous work on refinement of the model by alleviating unnecessary pain. Methods: Male and female Sprague Dawley rats were injected with 20 μl of complete Freund's adjuvant (CFA) into the left ankle. Rats were treated with buprenorphine, either injected subcutaneously or ingested voluntarily, and were compared to rats given subcutaneous injections with vehicle (saline or pure nut paste) or carprofen the first three days post CFA-injection. Measurements of welfare, clinical model-specific parameters and pain-related behaviour were assessed. Results: Buprenorphine, administered either subcutaneously (0.10 or 0.15 mg/kg, twice daily) or by voluntary ingestion in nut paste (1.0 or 3.0 mg/kg, twice daily), improved mobility, stance, rearing and lameness scores significantly 7 h post CFA-injection. Mechanical hyperalgesia peaked at 7 h and was significantly lower in buprenorphine-treated animals, compared to vehicle-treated animals. Joint circumference was highest 24–72 h after CFA injection. Animals treated with buprenorphine did not decrease in joint circumference, opposite carprofen treated animals. Conclusion: Buprenorphine, administered either subcutaneously or by voluntary ingestion, provides adequate analgesia for both sexes within the first 24 h post CFA-injection. Buprenorphine treatment improved clinical scores and appeared not to suppress the inflammatory response. The present study supports previous findings that voluntarily ingested buprenorphine is an effective alternative to repeated injections

Candidate Genes Detected in Transcriptome Studies Are Strongly Dependent on Genetic Background

Whole genome transcriptomic studies can point to potential candidate genes for organismal traits. However, the importance of potential candidates is rarely followed up through functional studies and/or by comparing results across independent studies. We have analysed the overlap of candidate genes identified from studies of gene expression in Drosophila melanogaster using similar technical platforms. We found little overlap across studies between putative candidate genes for the same traits in the same sex. Instead there was a high degree of overlap between different traits and sexes within the same genetic backgrounds. Putative candidates found using transcriptomics therefore appear very sensitive to genetic background and this can mask or override effects of treatments. The functional importance of putative candidate genes emerging from transcriptome studies needs to be validated through additional experiments and in future studies we suggest a focus on the genes, networks and pathways affecting traits in a consistent manner across backgrounds

The liminal self in people with multiple sclerosis:An interpretative phenomenological exploration of being diagnosed

Aims and objectives: To explore the lived experience of the meaning of being diagnosed with multiple sclerosis on the individual's sense of self. Background: The time leading up to and immediately following the diagnosis of multiple sclerosis has been identified as a time period shrouded by uncertainty and one where individuals have a heightened desire to seek accurate information and support. The diagnosis brings changes to the way one views the self which has consequences for biographical construction. Design: A hermeneutic phenomenological study. Methods: In-depth qualitative interviews were conducted with 10 people recently diagnosed with multiple sclerosis. The data were analysed using interpretative phenomenological analysis. Findings: This study presents the three master themes: the ‘road to diagnosis’,‘the liminal self’ and ‘learning to live with multiple sclerosis’. The diagnosis of multiple sclerosis may be conceptualised as a ‘threshold moment’ where the individual's sense of self is disrupted from the former taken-for-granted way of being and propose a framework which articulates the transition. Conclusion: The findings highlight the need for healthcare professionals to develop interventions to better support people affected by a new diagnosis of multiple sclerosis. The conceptual framework which has been developed from the data and presented in this study provides a new way of understanding the impact of the diagnosis on the individual's sense of self when affected by a new diagnosis of multiple sclerosis. This framework can guide healthcare professionals in the provision of supportive care around the time of diagnosis. Relevance for Clinical Practice: The findings provide practitioners with a new way of understanding the impact of the diagnosis on the individual’s sense of self and a framework which can guide them in the provision of supportive care around the time of diagnosis

A Prospective Study of Organochlorines in Adipose Tissue and Risk of Non-Hodgkin Lymphoma

Background: Exposure to organochlorines has been examined as a potential risk factor for non-Hodgkin lymphoma (NHL), with inconsistent results that may be related to limited statistical power or to imprecise exposure measurements

Cause-Specific Excess Mortality in Siblings of Patients Co-Infected with HIV and Hepatitis C Virus

BACKGROUND: Co-infection with hepatitis C in HIV-infected individuals is associated with 3- to 4-fold higher mortality among these patients' siblings, compared with siblings of mono-infected HIV-patients or population controls. This indicates that risk factors shared by family members partially account for the excess mortality of HIV/HCV-co-infected patients. We aimed to explore the causes of death contributing to the excess sibling mortality. METHODOLOGY AND PRINCIPAL FINDINGS: We retrieved causes of death from the Danish National Registry of Deaths and estimated cause-specific excess mortality rates (EMR) for siblings of HIV/HCV-co-infected individuals (n = 436) and siblings of HIV mono-infected individuals (n = 1837) compared with siblings of population controls (n = 281,221). Siblings of HIV/HCV-co-infected individuals had an all-cause EMR of 3.03 (95% CI, 1.56-4.50) per 1,000 person-years, compared with siblings of matched population controls. Substance abuse-related deaths contributed most to the elevated mortality among siblings [EMR = 2.25 (1.09-3.40)] followed by unnatural deaths [EMR = 0.67 (-0.05-1.39)]. No siblings of HIV/HCV co-infected patients had a liver-related diagnosis as underlying cause of death. Siblings of HIV-mono-infected individuals had an all-cause EMR of 0.60 (0.16-1.05) compared with siblings of controls. This modest excess mortality was due to deaths from an unknown cause [EMR = 0.28 (0.07-0.48)], deaths from substance abuse [EMR = 0.19 (-0.04-0.43)], and unnatural deaths [EMR = 0.18 (-0.06-0.42)]. CONCLUSIONS: HCV co-infection among HIV-infected patients was a strong marker for family-related mortality due to substance abuse and other unnatural causes. To reduce morbidity and mortality in HIV/HCV-co-infected patients, the advances in antiviral treatment of HCV should be accompanied by continued focus on interventions targeted at substance abuse-related risk factors

The impact of comorbidity and stage on ovarian cancer mortality: A nationwide Danish cohort study

<p>Abstract</p> <p>Background</p> <p>The incidence of ovarian cancer increases sharply with age, and many elderly patients have coexisting diseases. If patients with comorbidities are diagnosed with advanced stages, this would explain the poor survival observed among ovarian cancer patients with severe comorbidity. Our aims were to examine the prevalence of comorbidity according to stage of cancer at diagnosis, to estimate the impact of comorbidity on survival, and to examine whether the impact of comorbidity on survival varies by stage.</p> <p>Methods</p> <p>From the Danish Cancer Registry we identified 5,213 patients (> 15 years old) with ovarian cancer diagnosed from 1995 to 2003. We obtained information on comorbidities from the Danish National Hospital Discharge Registry. Vital status was determined through linkage to the Civil Registration System. We estimated the prevalence of comorbidity by stage and computed absolute survival and relative mortality rate ratios (MRRs) by comorbidity level (Charlson Index score 0, 1–2, 3+), using patients with Charlson Index score 0 as the reference group. We then stratified by stage and computed the absolute survival and MRRs according to comorbidity level, using patients with Charlson score 0 and localized tumour/FIGO I as the reference group. We adjusted for age and calendar time.</p> <p>Results</p> <p>Comorbidity was more common among patients with an advanced stage of cancer. One- and five-year survival was higher in patients without comorbidity than in patients with registered comorbidity. After adjustment for age and calendar time, one-year MRRs declined from 1.8 to 1.4 and from 2.7 to 2.0, for patients with Charlson scores 1–2 and 3+, respectively. After adjustment for stage, the MRRs further declined to 1.3 and 1.8, respectively. Five-year MRRs declined similarly after adjustment for age, calendar time, and stage. The impact of severe comorbidity on mortality varied by stage, particularly among patients with tumours with regional spread/FIGO-stages II and III.</p> <p>Conclusion</p> <p>The presence of severe comorbidity was associated with an advanced stage of ovarian cancer. Mortality was higher among patients with comorbidities and the impact of comorbidity varied by stage.</p