Research Spotlight

Swanson, G. P., W. Chen, S. Trevathan and M. Hermans (2020). “Long-Term Follow-Up after Prostatectomy for Prostate Cancer and the Need for Active Monitoring.” Prostate Cancer 2020: 7196189.

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Background: Only truly long-term follow-up can determine the ultimate outcome in prostate cancer. Most studies have a median follow-up of less than 10 years and then project outcomes out to 15 and 20 years. We sought to follow patients for at least 20 years. Materials and Methods. We followed 754 prostate cancer patients treated with radical prostatectomy from 1988 to 1995 for a median follow-up (in survivors) of 23.9 years. We excluded lymph node and seminal vesicle positive patients and an additional 47 patients that did not have baseline prostate-specific antigen (PSA). This left 581 patients for analysis. Results: With the factors of PSA, Gleason score, and extraprostatic extension/margin positivity, we could partition patients into three risk groups for biochemical failure (low, intermediate, and high). In further analysis, we found that the risk of metastatic disease in the first two groups was almost identical (4% and 5%, respectively), while it was 19% in the high-risk group. High-risk patients were those with PSA >20 ng/ml and/or Gleason >7, or Gleason 7 + PSA 10-20 + epe (and or margin) positive. They had a 22% prostate cancer mortality. Conclusion: In patients with truly long-term follow-up after prostatectomy for prostate cancer, the risk of metastatic disease and cancer death is very low. Patients with the lower risk findings do not appear to benefit from routine follow-up after 10 years free of biochemical recurrence. With a higher risk of later failure, we recommend that the higher risk patients be followed at least intermittently for another 5 years (out to 15 years).

Swank, C., M. Trammell, L. Callender, M. Bennett, K. Patterson, J. Gillespie, P. Kapoor and S. Driver (2020). “The impact of a patient-directed activity program on functional outcomes and activity participation after stroke during inpatient rehabilitation-a randomized controlled trial.” Clin Rehabil 34(4): 504-514.

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OBJECTIVE: Individuals post stroke are inactive, even during rehabilitation, contributing to ongoing disability and risk of secondary health conditions. Our aims were to (1) conduct a randomized controlled trial to examine the efficacy of a “Patient-Directed Activity Program” on functional outcomes in people post stroke during inpatient rehabilitation and (2) examine differences three months post inpatient rehabilitation discharge. DESIGN: Randomized control trial. SETTING: Inpatient rehabilitation facility. SUBJECTS: Patients admitted to inpatient rehabilitation post stroke. INTERVENTIONS: Patient-Directed Activity Program (PDAP) or control (usual care only). Both groups underwent control (three hours of therapy/day), while PDAP participants were prescribed two additional 30-minute activity sessions/day. MAIN MEASURES: Outcomes (Stroke Rehabilitation Assessment of Movement Measure, Functional Independence Measure, balance, physical activity, Stroke Impact Scale) were collected at admission and discharge from inpatient rehabilitation and three-month follow-up. RESULTS: Seventy-three patients (PDAP (n = 37); control (n = 36)) were included in the primary analysis. Patients in PDAP completed a total of 23.1 +/- 16.5 sessions (10.7 +/- 8.5 upper extremity; 12.4 +/- 8.6 lower extremity) during inpatient rehabilitation. No differences were observed between groups at discharge in functional measures. PDAP completed significantly more steps/day (PDAP = 657.70 +/- 655.82, control = 396.17 +/- 419.65; P = 0.022). The Stroke Impact Scale showed significantly better memory and thinking (PDAP = 86.2 +/- 11.4, control = 80.8 +/- 16.7; P = 0.049), communication (PDAP = 93.6 +/- 8.3, control = 89.6 +/- 12.4; P = 0.042), mobility (PDAP = 62.2 +/- 22.5, control = 53.8 +/- 21.8; P = 0.038), and overall recovery from stroke (PDAP = 62.1 +/- 19.1, control = 52.2 +/- 18.7; P = 0.038) for PDAP compared to control. At three months post discharge, PDAP (n = 11) completed significantly greater physical activity (P = 0.014; 3586.5 +/- 3468.5 steps/day) compared to control (n = 10; 1760.9 +/- 2346.3 steps/day). CONCLUSION: Functional outcome improvement was comparable between groups; however, PDAP participants completed more steps and perceived greater recovery.

Szerlip, M., S. Anwaruddin, H. D. Aronow, M. G. Cohen, M. J. Daniels, P. Dehghani, D. E. Drachman, S. Elmariah, D. N. Feldman, S. Garcia, J. Giri, P. Kaul, N. Kapur, D. J. Kumbhani, P. M. Meraj, B. Morray, K. R. Nayak, S. A. Parikh, R. Sakhuja, J. M. Schussler, A. Seto, B. Shah, R. V. Swaminathan, D. A. Zidar and S. S. Naidu (2020). “Considerations for Cardiac Catheterization Laboratory Procedures During the COVID-19 Pandemic Perspectives from the Society for Cardiovascular Angiography and Interventions Emerging Leader Mentorship (SCAI ELM) Members and Graduates.” Catheter Cardiovasc Interv Mar 25. [Epub ahead of print].

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The COVID-19 pandemic will impact many patients we care for with cardiovascular
disease. The preparedness of healthcare providers is critical in providing the best quality of care with soon to be limited resources, while keeping all personnel as safe as possible. The current key elements include 1) rescheduling of all non-urgent, elective CCL procedures, 2) careful patient selection for urgent and emergent CCL procedures with recognition of potential shifts in risk/benefit ratios in the setting of a highly contagious virus, 3) meticulous donning and doffing of PPE along with cleaning of CCL areas, 4) performance of bedside procedures when possible, and 5) staffing modifications to limit infectivity and preserve staff availability. (Excerpt from text, no abstract available)

Womack, K. B., R. Dubiel, L. Callender, C. Dunklin, M. Dahdah, T. S. Harris, M. Devous, S. Juengst, K. Bell, R. Diaz-Arrastia and K. Ding (2020). “¹²³I-iofluopane SPECT as An Imaging Biomarker of Presynaptic Dopaminergic System after Moderate to Severe TBI.” J Neurotrauma Mar 26. [Epub ahead of print].

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The dopaminergic (DA) system function is frequently disrupted after traumatic brain injury (TBI). However, published interventions that target the DA system with the hope of enhancing functional outcomes are inconclusive, partially due to the lack of DA signaling biomarkers that can be used to select patients likely to benefit from DA-directed therapies or to monitor treatment efficacy. The goal of this study was to evaluate the feasibility of using ¹²³I-iofluopane single photon emission computerized tomography (SPECT) to assess presynaptic DA system dysfunction following severe TBI. Eighteen patients with severe TBI were enrolled in this study. ¹²³I-iofluopane SPECT imaging was performed at baseline and again 2.5 hours after a single dose of methylphenidate (MP) administered enterally. DA transporter (DAT) specific binding ratio (SBR) before and after MP was measured. Functional outcomes included the Disability Rating Scale, JFK Coma Recovery Scale-Revised, Functional Independence Measure, and Functional Assessment Measure. Thirteen out of 18 patients completed the study. The average time from injury to SPECT scan was 48 days (SD 24 days, median 31 days). The baseline ioflupane striatal SBR was 1.51 +/- 0.46 (median 1.67). A 43.1% (SD 16%, median 46.5%) displacement of ioflupane from presynaptic DAT was observed after MP administration. Baseline SBR positively correlated with functional status at baseline and 4 weeks after completion of the study. Serum MP levels correlated with the relative change in SBR (rs=0.68, p=0.011). Our findings suggests that ¹²³I-iofluopane SPECT is a promising tool to determine the severity of presynaptic DA terminal disruption and for monitoring pharmacokinetics and pharmacodynamics of therapeutic interventions targeting the DA system.

Ye, M., C. Goudot, T. Hoyler, B. Lemoine, S. Amigorena and E. Zueva (2020). “Specific subfamilies of transposable elements contribute to different domains of T lymphocyte enhancers.” Proc Natl Acad Sci U S A 117(14): 7905-7916.

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Transposable elements (TEs) compose nearly half of mammalian genomes and provide building blocks for cis-regulatory elements. Using high-throughput sequencing, we show that 84 TE subfamilies are overrepresented, and distributed in a lineage-specific fashion in core and boundary domains of CD8(+) T cell enhancers. Endogenous retroviruses are most significantly enriched in core domains with accessible chromatin, and bear recognition motifs for immune-related transcription factors. In contrast, short interspersed elements (SINEs) are preferentially overrepresented in nucleosome-containing boundaries. A substantial proportion of these SINEs harbor a high density of the enhancer-specific histone mark H3K4me1 and carry sequences that match enhancer boundary nucleotide composition. Motifs with regulatory features are better preserved within enhancer-enriched TE copies compared to their subfamily equivalents located in gene deserts. TE-rich and TE-poor enhancers associate with both shared and unique gene groups and are enriched in overlapping functions related to lymphocyte and leukocyte biology. The majority of T cell enhancers are shared with other immune lineages and are accessible in common hematopoietic progenitors. A higher proportion of immune tissue-specific enhancers are TE-rich compared to enhancers specific to other tissues, correlating with higher TE occurrence in immune gene-associated genomic regions. Our results suggest that during evolution, TEs abundant in these regions and carrying motifs potentially beneficial for enhancer architecture and immune functions were particularly frequently incorporated by evolving enhancers. Their putative selection and regulatory cooption may have accelerated the evolution of immune regulatory networks.