Use of a novel magnetically actuated compression system to study the temporal dynamics of axial and lateral strain in human osteochondral plugs.

The high water content of articular cartilage allows this biphasic tissue to withstand large compressive loads through fluid pressurization. The system presented here, termed the "MagnaSquish", provides new capabilities for quantifying the effect of rehydration on cartilage behavior during cyclic loading. An imbalanced rate of fluid exudation during load and fluid re-entry during recovery can lead to the accumulation of strain during successive loading cycles - a phenomenon known as ratcheting. Typical experimental systems for cartilage biomechanics use continuous contact between the platen and sample, which may affect tissue rehydration by compressing the top layer of cartilage and slowing fluid re-entry. To address this limitation, we developed a magnetically actuated device that provides full lift-off of the platen in between loading cycles. We investigated strain accumulation in cadaveric human osteochondral plugs during 750 loading cycles, with two dimensional profiles of the cartilage captured at 30 frames per second throughout loading and 10 min of additional free swelling recovery. Axial and lateral strain measurements were extracted from the tissue profiles using a UNet-based deep learning algorithm to circumvent manual tracing. We observed increased axial strain accumulation with shorter inter-cycle recovery, with static loading serving as the extreme case of zero recovery. The loading waveform during the 750 cycles dictated the pace of the recovery during the extended free swelling period, as shorter inter-cycle recovery led to more persistent axial strain accumulation for up to five minutes. This work showcases the importance of fluid re-entry in resisting strain accumulation during cyclical compression.

Concordance of peripheral blood and bone marrow measurable residual disease in adult acute lymphoblastic leukemia.

Monitoring of measurable residual disease (MRD) is essential to the management of acute lymphoblastic leukemia (ALL) and is typically performed through repeated bone marrow (BM) assessments. Using a next-generation sequencing (NGS) MRD platform, we performed a prospective observational study evaluating the correlation between peripheral blood (PB) and BM MRD in adults with ALL receiving cellular therapies (hematopoietic cell transplantation [HCT] and chimeric antigen receptor T-cell [CAR-T] therapies). Among the study cohort (N = 69 patients; 126 paired PB/BM samples), we found strong correlation between PB and BM MRD (r = 0.87; P < .001), with a sensitivity and specificity of MRD detection in the PB of 87% and 90%, respectively, relative to MRD in the BM. MRD became detectable in the PB in 100% of patients who subsequently relapsed following HCT, with median time from MRD+ to clinical relapse of 90 days, and in 85% of patients who relapsed following CAR T, with median time from MRD+ to clinical relapse of 60 days. In adult patients with ALL undergoing cellular therapies, we demonstrate strong concordance between NGS-based MRD detected in the PB and BM. Monitoring of ALL MRD in the PB appears to be an adequate alternative to frequent invasive BM evaluations in this clinical setting.

Prospective Randomized Study of Advance Directives in Allogeneic Hematopoietic Cell Transplantation Recipients.

Patients undergoing allogeneic hematopoietic cell transplantation (HCT) are at risk for high morbidity and mortality. Advance directives (AD) allow patients to express wishes regarding their care at the end of life, but these are not completed in the majority of patients undergoing HCT, with only 44% of deceased allogeneic HCT recipients at this institution completing an AD in the past decade. Increasing the AD completion rate can improve the quality of care for allogeneic HCT recipients. Our objective was to evaluate whether an alternative AD instrument can increase AD completion rate and patient satisfaction. We conducted a prospective, randomized controlled study of the traditional California AD versus a novel Letter AD, the Stanford What Matters Most Letter, in adult allogeneic HCT recipients. Patients age ≥18 years undergoing first allogeneic HCT at Stanford University were eligible. Prior to HCT conditioning, enrolled patients were assigned at random to complete either the traditional AD or the Letter AD. The primary endpoint was AD completion. The chi-square test was used to compare the AD completion rate between arms. The Wilcoxon rank-sum test was used to compare uncertainty, satisfaction with decision making, and satisfaction with the AD. Of the 212 patients who were eligible, 126 (59.4%) were enrolled and randomized. The mean age was 53.7 years, 57 (45.2%) were female, and 74 (58.7%) were non-Hispanic white. The overall AD completion rate was 71.4% and did not differ between the traditional and Letter AD arms (70.3% versus 72.6%; P = .78). Of those who completed the Letter AD, 66.7%, 42.2%, and 46.7% of patients wished to die gently/naturally, at home, and/or with hospice, respectively. In the traditional AD arm, 60.0% wished to not prolong life if recovery was unlikely. Opinion surveys did not find differences in levels of satisfaction between the traditional AD and Letter AD. Completion rates of AD on this study were high (71.4%) compared with historically reported completion rates and did not significantly differ based on AD version.

Menstrual cycle effects on cardiovascular drift and maximal oxygen uptake during exercise heat stress.

AIM: Compared to other modulators of physiological strain associated with exercise heat stress, hyperthermia results in the greatest magnitude of cardiovascular (CV) drift and associated decrements in maximal oxygen uptake ([Formula: see text]). PURPOSE: To determine if elevated core temperature in the luteal phase (LP) of the menstrual cycle results in greater CV drift and reductions in [Formula: see text] versus the follicular phase (FP). METHODS: Seven women performed 15- and 45-min cycling bouts on separate occasions (60% [Formula: see text], 35 °C) followed by a [Formula: see text] test during the FP and LP. CV drift was measured between 15 and 45 min during the 45-min bout, and the 15-min bout was for measuring [Formula: see text] over the same time interval that CV drift occurred. RESULTS: Core temperature during LP was ~ 0.3 °C higher than FP (P < 0.05), but changes from rest during exercise were similar between phases (all P > 0.05). Heart rate increased significantly over time but was not different between phases (P = 0.78). Stroke volume decreased more over time during LP compared to FP (P = 0.02), but the values were similar at the end of exercise between phases (both time points P > 0.05). [Formula: see text] decrements for FP (13%) and LP (16%) were also comparable (P = 0.97). CONCLUSIONS: The LP-FP difference in core temperature in this study was not sufficient to amplify CV strain and decrements in [Formula: see text]. Greater differences in core temperature may be required to independently modulate CV drift and accompanying decrements in [Formula: see text] during prolonged exercise heat stress.