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1.
Hepatol Commun ; 7(4)2023 04 01.
Article in English | MEDLINE | ID: mdl-36972380

ABSTRACT

BACKGROUND: Using dynamic contrast-enhanced (DCE) MR perfusion and MR spectroscopy this study aimed to characterize the blood-brain barrier permeability and metabolite changes in patients with cirrhosis and without covert HE. METHODS: Covert HE was defined using psychometric HE score (PHES). The participants were stratified into 3 groups: cirrhosis with covert HE (CHE) (PHES<-4); cirrhosis without HE (NHE) (PHES≥-4); and healthy controls (HC). Dynamic contrast-enhanced MRI and MRS were performed to assess KTRANS, a metric derivative of blood-brain barrier disruption, and metabolite parameters. Statistical analysis was performed using IBM SPSS (v25). RESULTS: A total of 40 participants (mean age 63 y; male 71%) were recruited as follows: CHE (n=17); NHE (n=13); and HC (n=10). The KTRANS measurement in the frontoparietal cortex demonstrated increased blood-brain barrier permeability, where KTRANS was 0.01±0.02 versus 0.005±0.005 versus 0.004±0.002 in CHE, NHE, and HC patients, respectively (p = 0.032 comparing all 3 groups). Relative to HC with a value of 0.28, the parietal glutamine/creatine (Gln/Cr) ratio was significantly higher in both CHE 1.12 mmoL (p < 0.001); and NHE 0.49 (p = 0.04). Lower PHES scores correlated with higher glutamine/Cr (Gln/Cr) (r=-0.6; p < 0.001) and lower myo-inositol/Cr (mI/Cr) (r=0.6; p < 0.001) and lower choline/Cr (Cho/Cr) (r=0.47; p = 0.004). CONCLUSION: The dynamic contrast-enhanced MRI KTRANS measurement revealed increased blood-brain barrier permeability in the frontoparietal cortex. The MRS identified a specific metabolite signature with increased glutamine, reduced myo-inositol, and choline, which correlated with CHE in this region. The MRS changes were identifiable in the NHE cohort.


Subject(s)
Blood-Brain Barrier , Hepatic Encephalopathy , Humans , Male , Middle Aged , Blood-Brain Barrier/diagnostic imaging , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/pathology , Brain/metabolism , Glutamine/metabolism , Magnetic Resonance Spectroscopy , Liver Cirrhosis/pathology , Permeability , Inositol/metabolism , Choline/metabolism
2.
Rheumatology (Oxford) ; 60(10): 4624-4632, 2021 10 02.
Article in English | MEDLINE | ID: mdl-33502488

ABSTRACT

OBJECTIVE: Use of specific medications may accelerate the progression of radiographic knee OA (RKOA). Our aim was to examine the effect of medication use on the progression of RKOA. METHODS: We used longitudinal data from the Osteoarthritis Initiative (OAI), an observational study of risk factors for knee OA. At baseline, we selected participants with RKOA (Kellgren-Lawrence grade ≥2) and excluded those with a history of knee-related injury/surgery and other musculoskeletal disorders. Current medication use (use/non-use in the previous 30 days) and radiographic medial minimum joint space width (mJSW) data were available at baseline and annually up to 96 months follow-up. We used random effects, panel regression to assess the association between current medication use (non-users as reference group) and change in mJSW. RESULTS: Of 2054 eligible participants, 2003 participants with baseline mJSW data were included [55.7% female, mean age 63.3 (s.d. 8.98) years]. Of seven medication classes, at baseline NSAIDs were the most frequently used analgesia (14.7%), anti-histamine (10.4%) use was frequent and the following comorbidity medications were used most frequently: statins (27.4%), anti-hypertensives (up to 15.0%), anti-depressant/anxiolytics/psychotropics (14.0%), osteoporosis-related medication (10.9%) and diabetes-related medication (6.9%). Compared with current non-users, current use of NSAIDs was associated with a loss of mJSW (b = -0.042, 95% CI -0.08, -0.0004). No other associations were observed. CONCLUSIONS: In current users of NSAIDs, mJSW loss was increased compared with current non-users in participants with RKOA. Clinical trials are required to assess the potential disease-modifying effects of these medications.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Knee Joint/drug effects , Knee Joint/diagnostic imaging , Osteoarthritis, Knee/diagnostic imaging , Radiography , Aged , Antihypertensive Agents/adverse effects , Bone Density Conservation Agents/adverse effects , Disease Progression , Female , Histamine Antagonists/adverse effects , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Hypoglycemic Agents/adverse effects , Knee Joint/pathology , Longitudinal Studies , Male , Middle Aged , Osteoarthritis, Knee/pathology , Psychotropic Drugs/adverse effects , Risk Factors , Severity of Illness Index
3.
Best Pract Res Clin Rheumatol ; 33(1): 16-32, 2019 02.
Article in English | MEDLINE | ID: mdl-31431270

ABSTRACT

Low-value care is receiving substantial attention in many fields of medicine but little-to-none in sports medicine. Common interventions for sport and exercise-related injuries include medical imaging, medication, surgery and rehabilitation, but there is emerging evidence of the inappropriate use of these interventions. This chapter aims to increase awareness of low-value care in sports medicine by answering four key clinical questions: Does my patient need imaging? When is it appropriate to prescribe opioids? Does my patient need surgery? Does it matter how rehabilitation is delivered? Increasing awareness of low-value care in sports medicine will ensure patients with sport or exercise-related injuries avoid care that provides little-to-no benefit or causes harm and receive care that is evidence based and truly necessary. There are many situations when imaging, opioids, surgery and supervised rehabilitation are entirely appropriate. However, this chapter considers contexts where use of these interventions could be considered unnecessary and potentially harmful.


Subject(s)
Athletic Injuries/psychology , Exercise/psychology , Athletic Injuries/diagnostic imaging , Humans
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