Histotripsy of the Prostate in a Canine Model: Characterization of Post-Therapy Inflammation and Fibrosis

Introduction: Histotripsy is a nonthermal, noninvasive, pulsed ultrasound technology that homogenizes tissue within the targeted volume. From previous experiments, it appeared that the resultant fibrotic response from histotripsy was limited compared with the typical tissue response seen after thermoablation. The objective of this study was to characterize the inflammatory response and quantify patterns of collagen deposition 6 weeks after in vivo canine prostate histotripsy. Methods: Histotripsy was applied to the left half of eight canine prostates to produce an intraparenchymal zone of tissue homogenization. Six weeks after treatment, prostates were harvested, sectioned, and stained with hematoxylin and eosin for histologic evaluation, CD3, CD20, and Mac387 immunohistochemistry to characterize the inflammatory components, and picrosirius red staining to identify collagen. Results: Seven of eight treated prostates exhibited only minimal residual inflammation. Visual microscopic analysis of picrosirius red slides revealed a band of dense collagen (0.5?mm wide) immediately adjacent to the cavity produced by histotripsy. This was surrounded by a second band (1?mm wide) of less dense collagen interspersed among glandular architecture. A lobar distribution of epithelial atrophy and basal cell hyperplasia reminiscent of periurethral glands and ducts was apparent surrounding the margin of the treatment cavities. Tissue loss (-31%) was apparent on the treated side of all prostates while four demonstrated a net decrease in collagen content. Conclusions: In vivo histotripsy of canine prostate produced a decrease in prostate volume coupled with a limited inflammatory and fibrotic response. A narrow (1.5?mm) band of fibrosis around the empty, reepithelialized treatment cavity was observed 6 weeks after treatment. In four cases, an overall reduction in collagen content was measured. Further studies are planned to correlate these histologic findings with alteration in mechanical tissue properties and to explore histotripsy strategies for treatment of benign prostatic hyperplasia that optimize tissue volume removal with minimization of fibrosis.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140079/1/end.2014.0585.pd

Histotripsy of Rabbit Renal Tissue in Vivo: Temporal Histologic Trends

Background and Purpose: Histotripsy is defined as noninvasive, nonthermal, mechanical (cavitational) tissue ablation. We previously demonstrated the predictable acute tissue effects of histotripsy in rabbit kidney and other tissues. We sought to characterize the appearance and natural history of renal tissue after histotripsy. Materials and Methods: Following Institutional Animal Care Committee approval, the left kidneys of 29 rabbits were treated with 60,000 750-kHz, 15-cycle bursts of ultrasound energy from an 18-element phased-array transducer at a 1-kHz pulse-repetition frequency. The treated kidneys were harvested at 0, 1, 2, 7, 21, or 60 days; fixed in Formalin; then prepared for microscopic analysis with hematoxylin and eosin and trichrome stains. Results: For kidneys harvested acutely (day 0), a contiguous area of finely disrupted tissue was observed containing no recognizable cells or cellular components. Along the boundary of architectural disruption, a border several tubules wide contained cells that were not visibly disrupted but appeared damaged (pyknotic nuclei). At subsequent time intervals, an inflammatory response developed in association with a steadily decreasing area of cellular and architectural disruption. By day 60, only a small fibrous scar persisted adjacent to a wedge of tubular dilation and fibrosis underlying a surface-contour defect. Conclusions: Histotripsy produces mechanical fractionation of cellular and architectural structures. The resultant acellular material appears to be readily reabsorbed within 60 days in the rabbit. This may prove to be a significant advantage for imaging assessment of residual tumor after ablation of renal malignancy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63123/1/end.2007.9915.pd

Histotripsy Effects on the Bladder Trigone: Functional and Histologic Consequences in the Canine Model

Background: Histotripsy is an extracorporeal therapeutic ultrasound (US) technology, where high-amplitude acoustic energy is applied to targeted tissue. Previous research has demonstrated the feasibility, safety, and effectiveness of histotripsy tissue homogenization and debulking of the prostate in the canine model. Before translating this technology for human use, it is prudent to examine the susceptibility of critical periprostatic structures to cavitation injury in the event of histotripsy mistargeting. In this study, we sought to characterize the tissue effects and biologic response of directly treating the bladder trigone with histotripsy. Materials and Methods: In eight anesthetized canines, 750,000 histotripsy pulses were applied uniformly across a 2?1.5-cm area encompassing the bladder trigone and ureteral orifices. Prostate and bladder trigone were harvested immediately after treatment (2 subjects) or at 14 days (6 subjects). Flexible cystourethroscopy, US imaging, and creatinine levels were obtained at intervals until harvest, 14 days after treatment. In one control subject, harvested at 2 days, the same treatment algorithm was applied to the prostate. Results: Transrectal US imaging revealed a cavitation bubble cloud on the surface of the bladder trigone and progressive development of tissue edema during treatment. Flexible cystourethroscopy immediately after treatment confirmed edema and erythema of the trigone. In the six subjects survived 2 weeks after treatment, one incidence of transient, self-limited ureteral obstruction was noted based on hydronephrosis and creatinine levels. At harvest, ureteral orifices were confirmed patent by passage of a guide wire. Histologic evaluation revealed hemorrhage acutely with mild localized fibrosis at 14 days. Conclusions: In this study, designed along the lines of a worst-case, destructive testing scenario, direct targeting of the bladder trigone with supratherapeutic histotripsy failed to induce significant tissue damage or clinical complication. These results are reassuring and will guide treatment strategy in upcoming human clinical trials of histotripsy treatment for benign prostatic hyperplasia.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140374/1/end.2013.0234.pd

Association of Accelerometry-Measured Physical Activity and Cardiovascular Events in Mobility-Limited Older Adults: The LIFE (Lifestyle Interventions and Independence for Elders) Study.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500

An assessment of American Indian women's mammography experiences

<p>Abstract</p> <p>Background</p> <p>Mortality from breast cancer has increased among American Indian/Alaskan Native (AI/AN) women. Despite this alarming reality, AI/AN women have some of the lowest breast cancer screening rates. Only 37% of eligible AI/AN women report a mammogram within the last year and 52% report a mammogram within the last two years compared to 57% and 72% for White women. The experiences and satisfaction surrounding mammography for AI/AN women likely are different from that of women of other racial/ethnic groups, due to cultural differences and limited access to Indian Health Service sponsored mammography units. The overall goals of this study are to identify and understand the mammography experiences and experiential elements that relate to satisfaction or dissatisfaction with mammography services in an AI/AN population and to develop a culturally-tailored AI/AN mammography satisfaction survey.</p> <p>Methods and Design</p> <p>The three project aims that will be used to guide this work are: 1) To compare the mammography experiences and satisfaction with mammography services of Native American/Alaska Native women with that of Non-Hispanic White, Hispanic, and Black women, 2) To develop and validate the psychometric properties of an American Indian Mammography Survey, and 3) To assess variation among AI/AN women's assessments of their mammography experiences and mammography service satisfaction. Evaluations of racial/ethnic differences in mammography patient satisfaction have received little study, particularly among AI/AN women. As such, qualitative study is uniquely suited for an initial examination of their experiences because it will allow for a rich and in-depth identification and exploration of satisfaction elements.</p> <p>Discussion</p> <p>This formative research is an essential step in the development of a validated and culturally tailored AI/AN mammography satisfaction assessment. Results from this project will provide a springboard from which a maximally effective breast cancer screening program to benefit AI/AN population will be developed and tested in an effort to alter the current breast cancer-related morbidity and mortality trajectory among AI/AN women.</p

Rehydrating efficacy of maple water after exercise-induced dehydration

Abstract Dehydration impairs physiological function and physical performance, thus understanding effective rehydration strategies is paramount. Despite growing interest in natural rehydrating beverages, no study has examined maple water (MW). Purpose To investigate the rehydrating efficacy of MW after exercise-induced dehydration. Methods Using a single-blind, counterbalanced, crossover design, we compared the rehydrating efficacy of MW vs. maple-flavored bottled water (control) in 26 young healthy (22 ± 4 yrs., 24 ± 4 kg/m2) males (n = 13) and females (n = 13) after exercise-induced dehydration (~ 2.0%ΔBody Weight [BW]) in the heat (30 °C, 50% relative humidity [RH]). Hydration indicators (BW, salivary and urine osmolality [SOsm/UOsm], urine specific gravity [USG], urine volume [UV], urine color [UC]), thirst, fatigue, and recovery (heart rate [HR)], and HR variability [HRV]) were taken at baseline, post-exercise, 0.5, 1, and 2 h post-consumption of 1 L of MW or control. Results Following similar dehydration (~ 2%ΔBW), MW had no differential (p > 0.05) impact on any measure of rehydration. Likely due to greater beverage osmolality (81 ± 1.4 vs. 11 ± 0.7 mOsmol/kg), thirst sensation remained 12% higher with MW (p <  0.05). When sex was considered, females had lower UV, elevated UOsm (p < 0.05), trends for higher ΔBW, USG, but similar SOsm. Analysis of beverages and urine for antioxidant potential (AP) revealed a four-fold greater AP in MW, which increased peak urine AP (9.4 ± 0.7 vs. 7.6 ± 1.0 mmol, MW vs. control, p <  0.05). Conclusion Electrolyte-containing MW, was similar in effectiveness to water, but has antioxidant properties. Furthermore, trends for sex differences were discovered in urinary, but not salivary, hydration markers, with discrepancies in kinetics between fluid compartments both warranting further study

Impact of Providing a Tape Measure on the Provision of Lung-protective Ventilation

Introduction: Emergency department (ED) patients are frequently ventilated with excessively large tidal volumes for predicted body weight based on height, which has been linked to poorer patient outcomes. We hypothesized that supplying tape measures to respiratory therapists (RT) would improve measurement of actual patient height and adherence to a lung-protective ventilation strategy in an ED-intensive care unit (ICU) environment.Methods: On January 14, 2019, as part of a ventilator-associated pneumonia prevention bundle in our ED-based ICU, we began providing RTs with tape measures and created a best practice advisory reminding them to record patient height. We then retrospectively collected data on patient height and tidal volumes before and after the intervention.Results: We evaluated 51,404 tidal volume measurements in 1,826 patients over the 4 year study period; of these patients, 1,579 (86.5%) were pre-intervention and 247 (13.5%) were post-intervention. The intervention was associated with a odds of the patient’s height being measured were 10 times higher post-intervention (25.1% vs 3.2%, P &lt;0.05). After the bundle was initiated, we observed a significantly higher percentage of patients ventilated with mean tidal volumes less than 8 cubic centimeters per kilogram (93.9% vs 84.5% P &lt; 0.05).Conclusion: Patients in an ED-ICU environment were ventilated with a lung-protective strategy more frequently after an intervention reminding RTs to measure actual patient height and providing a tape measure to do so. A significantly higher percentage of patients had height measured rather than estimated after the intervention, allowing for more accurate determination of ideal body weight and calculation of lung-protective ventilation volumes. Measuring all mechanically ventilated patients’ height with a tape measure is an example of a simple, low-cost, scalable intervention in line with guidelines developed to improve the quality of care delivered to critically ill ED patients