Cross-sectional and short-term cohort studies have demonstrated an association between urinary incontinence and dementia, as well as lower performance on cognitive testing. The Health and Retirement ...Study, a longitudinal study of community-dwelling older adults, offers an opportunity to assess the temporal association between these conditions because it included an assessment of incontinence symptoms and biennial assessments of cognitive function.
This study aimed to evaluate if urinary incontinence before the age of 70 years had an effect on changes in cognitive function among women participating in the Health and Retirement Study.
This secondary analysis included data from female respondents in the Health and Retirement Study aged 58 to 67 years with ≥2 cognitive assessments. Urinary incontinence was defined as any involuntary loss of any urine in the preceding 12 months. A control group without incontinence was reweighted for better comparability using coarsened exact matching for age and comorbidities. Validated methods, including neuropsychological test data, estimated a memory score and dementia probability for each participant biennially. Coprimary outcomes were the changes in memory score and dementia probability. Linear regression models were used to estimate the association of urinary incontinence with change in memory score and dementia probability, adjusting for baseline demographics and comorbidities. A subgroup analysis was performed to assess the effects of urinary incontinence frequency on these outcomes. The infrequent subgroup reported <15 days of leakage per month and the frequent subgroup reported ≥15 days of leakage per month.
Among eligible female respondents, 40.6% reported urinary incontinence between the ages of 58 and 69 years. Baseline memory scores and dementia probability were similar between those with urinary incontinence (n=1706) and controls (n=2507). Memory score declined significantly in both cohorts, indicating poorer memory over time (−0.222 among those with incontinence 95% confidence interval, −0.245 to −0.199 vs −0.207 in controls 95% confidence interval, −0.227 to −0.188). The decline of memory score was not statistically significantly different between cases and controls (mean difference, −0.015; 95% confidence interval, −0.045 to 0.015). Dementia probability increased significantly in both groups, indicating a greater probability of developing dementia by 0.018 among those with incontinence (95% confidence interval, 0.015–0.020) and by 0.020 among controls (95% confidence interval, 0.017–0.022). The change in dementia probability was not significantly different between groups (mean difference, −0.002; 95% confidence interval, −0.006 to 0.002). Frequent urinary incontinence was reported in 105 of 1706 (6%) of those with urinary incontinence. Memory score declined and dementia probability increased with time (P<.001) in frequent and infrequent urinary incontinence subgroups. There was no dose–response relationship.
Measures of cognitive performance declined during approximately 10 years of observation. The changes in performance were not associated with the presence of urinary incontinence in the participants’ younger years.
Differentiating pancreatitis from pancreatic cancer would improve diagnostic specificity, and prognosticating pancreatitis that progresses to pancreatic cancer would also improve diagnoses of ...pancreas pathology. The high glycolytic metabolism of pancreatic cancer can cause tumor acidosis, and different levels of pancreatitis may also have different levels of acidosis, so that extracellular acidosis may be a diagnostic biomarker for these pathologies. AcidoCEST MRI can noninvasively measure extracellular pH (pHe) in the pancreas and pancreatic tissue. We used acidoCEST MRI to measure pHe in a KC model treated with caerulein, which causes pancreatitis followed by development of pancreatic cancer. We also evaluated the KC model treated with PBS, and wild-type mice treated with caerulein or PBS as controls. The caerulein-treated KC cohort had lower pHe of 6.85–6.92 before and during the first 48 h after initiating treatment, relative to a pHe of 6.92 to 7.05 pHe units for the other cohorts. The pHe of the caerulein-treated KC cohort decreased to 6.79 units at 5 weeks when pancreatic tumors were detected with anatomical MRI, and sustained a pHe of 6.75 units at the 8-week time point. Histopathology was used to evaluate and validate the presence of tumors and inflammation in each cohort. These results showed that acidoCEST MRI can differentiate pancreatic cancer from pancreatitis in this mouse model, but does not appear to differentiate pancreatitis that progresses to pancreatic cancer vs. pancreatitis that does not progress to cancer.
Introduction and aim
Observational studies have associated oral anticholinergic medications for overactive bladder (OAB) with cognitive impairment. This is the first pilot trial to compare the ...effects of two classes of OAB medications on brain activity in women. We evaluated the effect of anticholinergic versus non-anticholinergic (Non-Ach) interventions on regional brain activation during a cognitive task.
Methods
Twelve cognitively normal women seeking OAB therapy were recruited to a randomized, double-blind, parallel, controlled pilot trial. Whole-brain regional activity at baseline and 29 ± 1 days postintervention was assessed with functional magnetic resonance imaging during a working memory task. Average activation strength by region was compared after anticholinergic, beta-3 agonist, or placebo. Two-way ANOVA compared effects of group and time on average activation strength in anticholinergic versus Non-Ach (beta-3 agonists or placebo) groups.
Results
The mean (SD) age and body mass index of 12 women were 61 (7) years and 36 (7) kg/m
2
. Baseline depression and learning scores differed in the anticholinergic group (
n
= 3) versus the Non-Ach group (
n
= 9). Right mamillary body activation postintervention was higher after Non-Ach exposure (F 4.9,
p
< 0.04). In the full sample of participants at follow-up, there was less activation of the right middle frontal gyrus (
p
= 0.02), superior frontal gyrus (
p
< 0.01), and supramarginal (
p
< 0.01) gyrus.
Conclusion
Activation strength in brain regions underlying working memory was lower over time, and recognition scores improved. A powered trial is needed to adequately evaluate for differential effects of OAB oral medications on regional brain activation.
Lung cancer diagnosis via imaging may be confounded by the presence of indolent infectious nodules in imaging studies. This issue is pervasive in the southwestern US where coccidioidomycosis (Valley ...Fever) is endemic. AcidoCEST MRI is a noninvasive imaging method that quantifies the extracellular pH (pHe) of tissues in vivo, allowing tumor acidosis to be used as a diagnostic biomarker. Using murine models of lung adenocarcinoma and coccidoidomycosis, we found that average lesion pHe differed significantly between tumors and granulomas. Our study shows that acidoCEST MRI is a promising tool for improving the specificity of lung cancer diagnosis.
The goal of this study was to demonstrate feasibility of measuring extracellular pH in cartilage and meniscus using acidoCEST technique with a 3-dimensional ultrashort echo time readout ...(acidoCEST-UTE) magnetic resonance imaging (MRI).
Magnetization transfer ratio asymmetry, radiofrequency (RF) power mismatch, and relative saturation transfer were evaluated in liquid phantoms for iopromide, iopamidol, and iohexol over a pH range of 6.2 to 7.8, at various agent concentrations, temperatures, and buffer concentrations. Tissue phantoms containing cartilage and meniscus were evaluated with the same considerations for iopamidol and iohexol. Phantoms were imaged with the acidoCEST-UTE MRI sequence at 3 T. Correlation coefficients and coefficients of variations were calculated. Paired Wilcoxon rank-sum tests were used to evaluate for statistically significant differences.
The RF power mismatch and relative saturation transfer analyses of liquid phantoms showed iopamidol and iohexol to be the most promising agents for this study. Both these agents appeared to be concentration independent and feasible for use with or without buffer and at physiologic temperature over a pH range of 6.2 to 7.8. Ultimately, RF power mismatch fitting of iohexol showed the strongest correlation coefficients between cartilage, meniscus, and fluid. In addition, ratiometric values for iohexol are similar among liquid as well as different tissue types.
Measuring extracellular pH in cartilage and meniscus using acidoCEST-UTE MRI is feasible.
Introduction and hypothesis
Microscopic hematuria (MH) has many etiologies in women and requires specific gynecologic evaluation. We created a standardized MH pathway to serve as an evidence-based ...decision aid for providers in our practice.
Methods
Using a modified Delphi process, a multidisciplinary team reviewed existing guidelines for MH diagnosis and treatment to reach consensus on care pathway components.
Results
Entry into the care pathway by an advanced practice provider is determined by the finding of ≥3 red blood cells per high-power field (RBC/HPF) on microscopic urinalysis. Initial evaluation includes history and physical exam. If there are signs of a gynecologic cause of MH, the conditions are treated and repeat urinalysis is performed in 6 months. If repeat urinalysis shows persistent MH or there are no other apparent causes for MH, we proceed with risk stratification. Through shared decision-making, low-risk patients may undergo repeat urinalysis in 6 months or cystoscopy with urinary tract ultrasound. For intermediate-risk patients, cystoscopy and urinary tract ultrasound are recommended. For high-risk patients, cystoscopy and axial upper urinary tract imaging are recommended. If evaluation is positive, urology referral is provided. If evaluation is negative, low-risk patients are released from care, but intermediate-risk or high-risk patients undergo repeat urinalysis in 12 months. If repeat urinalysis is positive, shared decision-making is used to determine a plan.
Conclusions
We developed an MH care pathway to standardize care of women with MH across a multidisciplinary group. This pathway serves as a component of value-based care and supports evidence-based care by providers.
•Controlled rotator cuff degeneration can be simulated in vitro using collagenase.•Both quantitative MRI and US can quantify the extent of rotator cuff degeneration.•MRI-derived macromolecular ...fraction shows the highest correlation with collagen loss.
Quantitative imaging methods could improve diagnosis of rotator cuff degeneration, but the capability of quantitative MR and US imaging parameters to detect alterations in collagen is unknown. The goal of this study was to assess quantitative MR and US imaging measures for detecting abnormalities in collagen using an in vitro model of tendinosis with biochemical and histological correlation.
36 pieces of supraspinatus tendons from 6 cadaveric donors were equally distributed into 3 groups (2 subjected to different concentrations of collagenase and a control group). Ultrashort echo time MR and US imaging measures were performed to assess changes at baseline and after 24 h of enzymatic digestion. Biochemical and histological measures, including brightfield, fluorescence, and polarized microscopy, were used to verify the validity of the model and were compared with quantitative imaging parameters. Correlations between the imaging parameters and biochemically measured digestion were analyzed.
Among the imaging parameters, macromolecular fraction (MMF), adiabatic T1ρ, T2*, and backscatter coefficient (BSC) were useful in differentiating between the extent of degeneration among the 3 groups. MMF strongly correlated with collagen loss (r=-0.81; 95% confidence interval CI: -0.90,-0.66), while the adiabatic T1ρ (r = 0.66; CI: 0.42,0.81), T2* (r = 0.58; CI: 0.31,0.76), and BSC (r = 0.51; CI: 0.22,0.72) moderately correlated with collagen loss.
MMF, adiabatic T1ρ, and T2* measured and US BSC can detect alterations in collagen. Of the quantitative MR and US imaging measures evaluated, MMF showed the highest correlation with collagen loss and can be used to assess rotator cuff degeneration.
CaCO
nanoparticles (nano-CaCO
) can neutralize the acidic pHe of solid tumors, but the lack of intrinsic imaging signal precludes noninvasive monitoring of pH-perturbation in tumor microenvironment. ...We aim to develop a theranostic version of nano-CaCO
to noninvasively monitor pH modulation and subsequent tumor response.
We synthesized ferromagnetic core coated with CaCO
(magnetite CaCO
). Magnetic resonance imaging (MRI) was used to determine the biodistribution and pH modulation using murine fibrosarcoma and breast cancer models.
Magnetite CaCO
-MRI imaging showed that nano-CaCO
rapidly raised tumor pHe, followed by excessive tumor-associated acid production after its clearance. Continuous nano-CaCO
infusion could inhibit metastasis.
Nano-CaCO
exposure induces tumor metabolic reprogramming that could account for the failure of previous intermittent pH-modulation strategies to achieve sustainable therapeutic effect.
Objective
To evaluate if age and comorbidities are associated with progression from trial phase to implantation of an implantable pulse generator in women with overactive bladder.
Methods
This ...multisite retrospective cohort included women with overactive bladder with or without urinary incontinence who had a trial phase for sacral neuromodulation. The primary outcome was progression to implantation. A sub-analysis of implanted patients was performed for the outcome of additional therapies or “implant only” for the duration of follow-up. Multivariate logistic regression models including potential predictors of implantation and post-implantation addition of therapies were performed.
Results
At six academic institutions, 91% (785/864) of patients progressed to implantation. Post-implantation success was achieved by 69% (536/782) of patients at median follow-up of 2 (range 0.3 to 15) years. Odds of implantation OR 0.73 (CI 0.61, 0.88) and post-implantation success OR 0.78 (CI 0.98, 0.97) were lower with increasing decades of age. Medical comorbidities evaluated did not affect implantation rates or post-implant success.
Conclusions
Most women have successful sacral neuromodulation trials despite older age and comorbidities. Higher decade of age has a negative effect on odds of implantation and is associated with addition of therapies post-implantation. Comorbidities assessed in this study did not affect implantation or addition of therapies post-implantation. Most women add therapies to improve efficacy post-implantation, and explantation rates are low.
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