Washington DC VA Medical Center
  • Washington, D.C., United States
Recent publications
This study is aimed to identify radiation-responsive RBC Membrane Associated Proteins (RMAPs) in Rabbits in vivo. Male New Zealand White rabbits were exposed to a single acute total body γ-radiation dose of 2 Gy at a dose rate of 0.746 Gy/min. Following this, at early time points of 6 h till the 7 d, RMAPs were collected and analyzed by MALDI-TOF-MS. Bioinformatics analysis was conducted to explore the biological functions of these proteins. Based on fold change, radiation responsiveness, GO, pathway enrichment, and hub position in the PPI network, we identified seven RMAPs as potential biomarker candidates viz., PVALB, PRKCB, GPD1, CP2G1, CSNK2B, ATP1B1, TPI1. As per KEGG enrichment, most of the proteins were implicated in cellular radiation response, oxidative damage, DNA repair, apoptosis, immune response, and cell signaling. This study forms the foundation for RMAPs-based Proteomic strategies for high throughput radiation bio-dosimetry for triage in the case of a radiological/nuclear incident.
Background Morning report is a core educational activity in internal medicine resident education. Attending physicians regularly participate in morning report and influence the learning environment, though no previous study has described the contribution of attending physicians to this conference. This study aims to describe attending comments at internal medicine morning reports. Methods We conducted a prospective, observational study of morning reports conducted at 13 internal medicine residency programs between September 1, 2020, and March 30, 2021. Each attending comment was described including its duration, whether the comment was teaching or non-teaching, teaching topic, and field of practice of the commenter. We also recorded morning report-related variables including number of learners, report format, program director participation, and whether report was scripted (facilitator has advance knowledge of the case). A regression model was developed to describe variables associated with the number of attending comments per report. Results There were 2,344 attending comments during 250 conferences. The median number of attendings present was 3 (IQR, 2–5). The number of comments per report ranged across different sites from 3.9 to 16.8 with a mean of 9.4 comments/report (SD, 7.4). 66% of comments were shorter than one minute in duration and 73% were categorized as teaching by observers. The most common subjects of teaching comments were differential diagnosis, management, and testing. Report duration, number of general internists, unscripted reports, and in-person format were associated with significantly increased number of attending comments. Conclusions Attending comments in morning report were generally brief, focused on clinical teaching, and covered a wide range of topics. There were substantial differences between programs in terms of the number of comments and their duration which likely affects the local learning environment. Morning report stakeholders that are interested in increasing attending involvement in morning report should consider employing in-person and unscripted reports. Additional studies are needed to explore best practice models of attending participation in morning report.
This chapter sets the task of outlining an approach to climate policy that is consistent with the classical liberal tradition in political philosophy and economics. It begins by applying John Locke’s theory of acquisition of property by first use to the case of carbon emissions. It argues that today, it is no longer possible to claim new emission rights while leaving “enough and as good for others.” It follows that under Locke’s theory of government, the remaining waste disposal capacity of the atmosphere should be managed as an unenclosed commons through the institutions of liberal government. Drawing on the work of Friedrich Hayek, it argues that science and the price system should play co-equal roles in the design of policies for managing emissions. It concludes by making a case that a target-consistent approach to climate policy is more suitable to one based on the social cost of carbon.
592 Background: Tumor-agnostic approvals of immune checkpoint inhibitors (ICI) include deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) and high tumor mutational burden (TMB) while in cancer like metastatic gastroesophageal cancers, ICI use has been predicated on PD-L1 expression. ICI are increasingly used for metastatic HCC, but without required markers. We aimed to examine the genomic landscape of HCC in context of PD-L1 expression, and to determine clinical responses to ICI in this setting. Methods: Next-generation sequencing of DNA (592 or WES) and RNA (WTS) was tested at Caris Life Sciences (Phoenix, AZ). PD-L1 expression was tested by IHC (SP142) and compared as high (2+,5%), low (1-2,1%) and negative (0). dMMR/MSI-H was tested by IHC/NGS and TMB-High was defined as ³10 mutations/MB. QuantiSEQ was used to estimate the tumor microenvironment. X ² /Fisher-Exact were used and significance was determined as P-value adjusted for multiple comparison ( Q < 0.05). Real-world overall survival (rwOS) was obtained from insurance claims and calculated from tissue collection to last contact; time-on-treatment (TOT) was calculated from start to finish of ICI treatments. Results: Overall, 17.7% of HCC expressed PD-L1 by IHC; 79/1306 (6.1%) had high expression. The overall prevalence of dMMR/MSI-H was 0.2%; TMB was high in 5.1%. PD-L1 expression was not associated with MSI-H or high TMB. When comparing tumors that are PD-L1 high vs. negative vs. low, expression of several immuno-oncologic (IO) markers LAG3 (median TPM: 2.4, 0.8, 0.5), CTLA-4 (2.9, 1.2, 0.5), IDO1 (4.2, 1.3, 0.6) and others, as well as T-cell inflamed and IFNg scores all decreased significantly with PD-L1 (all q<0.05), similar trends were seen with B cells, M1 macrophages, CD8+ T cells and T regs while opposite differences seen in NK cells (q<0.05). Additionally, when PDL1-high tumors were compared to PDL1-negative, mutations in CTNNB1 trended lower (21% vs 35%) while amplifications of KRAS (4% vs 0%), PDCD1LG2 (4% vs 0%) and mutations in HNF1A (3% vs 0%), HOXB13 (6% vs 0%), STK11 (5% vs 0%) trended higher; when PDL1-low were compared to PDL1-negative, mutations in TP53 (45% vs 32%), ELF3 (3% vs 0%), TSC2 (6% vs 2%) and PIK3CA (5% vs 1%) and amplifications in BCL9 (2% vs 0%) and CCNE1 (2% vs 0%) trended higher. When investigating clinical outcome of a cohort of 908 HCC tumors, PD-L1 expression had no effect on prognosis, and was not associated with differences in TOT of ICI in HCC. Conclusions: Prevalence of dMMR/MSI-H and TMB-H is very low in HCC. PD-L1 is only expressed in <20%. Even with a finding of strong association of expression of several established IO biomarkers with PD-L1 expression, it’s still not predictive of response to ICI. New biomarkers or molecular signatures need to be identified and validated to objectively identify HCC patients most likely to benefit from ICI treatment.
TPS629 Background: The anti–PD-L1 antibody ATEZO prevents PD-L1 from interacting with PD-1 and B7.1, thus reinvigorating antitumor T cell activity. Anti-VEGF BEV can increase dendritic cell maturation, enhance T cell infiltration, and reduce myeloid-derived suppressor cells and regulatory T-cells in tumors. This combination has been FDA approved for first-line treatment of advanced HCC based on the IMbrave150 study. On the other hand, locoregional radiotherapy (e.g., Y90 TARE) enhances the diversity of the intratumoral T cell receptor repertoire. It is the standard of care for pts with intermediate-stage HCC (iHCC). Based on preclinical and clinical data, we hypothesize that the combination of Y90 TARE, BEV, and ATEZO induces synergistic tumor-killing. Methods: This is an open-label, multicenter, randomized phase II study of Y90 TARE and BEV plus ATEZO compared with Y90 TARE alone in pts with unresectable IHCC (NCT04541173). The primary study objective is to assess and compare the progression-free survival (PFS) (per mRECIST 1.1) of pts in each arm. The main secondary objective is to determine the safety and tolerability (CTCAE v5) of TARE combined with ATEZO and BEV in pts with HCC. Exploratory objectives are to assess the role of the immunoscore and PD-L1 expression levels in the prediction of improved clinical outcome in pts receiving Y-90 TARE and BEV plus ATEZO; the composition of tumor-infiltrating immune cell subtypes in predicting response to a chosen therapy; how Y90 therapy affects the proportion of antigen-presenting cells in the tumor; and symptoms experienced by pts receiving TARE and BEV plus ATEZO treatment, using patient-reported outcomes. Eligible pts have either HCC that is not amenable to surgical resection, confirmed by pathology review, or at least BCLC stage B HCC outside of downstaging criteria. Other standard eligibility criteria apply. Pts must have a pretreatment liver biopsy taken and then be randomized 1:1 to TARE (Arm A) or TARE followed by ATEZO and BEV (Arm B). Pts will have TARE mapping during week (wk) 1 and TARE treatment during wk 2. In Arm B, pts will start BEV plus ATEZO 4 wks (±1 wk) after TARE treatment. Pts will have abdominal MRI or CT scans every 12 weeks, CT scans of the chest every 24 wks. Disease progression will be captured by both RECIST 1.1 and mRECIST. We plan to assess the safety of TARE with BEV and ATEZO in the first 10 pts randomized to Arm B for two cycles. If there are no Grade ≥ 3 unexpected toxicities possibly, probably or definitely related to combined TARE plus BEV plus ATEZO, the study will continue to accrue 128 pts in total. Pts will continue study treatment (Arm B) for a total of 24 months from initiation of TARE or until intolerable toxicity or disease progression occur, whichever is earlier. Clinical trial information: NCT04541173 .
250 Background: Tissue factor (TF), a component of the coagulation cascade, transmembrane receptor, and cofactor for factor VII/VIIa is expressed by subendothelial cells and critical to hemostasis, thrombosis, cell proliferation, angiogenesis, and metastasis. TF is suggested to have a critical role in colorectal cancer (CRC). Here we assessed the clinico-molecular features associated with TF expression (exp) in CRC. Methods: Tumor molecular profiling was performed for 14,0786 samples by NextGen Sequencing on DNA (592 genes or WES) and RNA (WTS) and immunohistochemistry (IHC) at Caris Life Sciences (Phoenix, AZ). TF-high (TF-H) and TF-low (TF-L) RNA exp were defined as ≥ 75 th - and < 25 th -percetile of TF transcripts per million (TPM), respectively. X ² /Fisher-exact and Mann Whitney U tests were used for comparison, and P-values were adjusted for multiple comparisons. Cell infiltration in the tumor microenvironment (TME) was estimated by quanTIseq. Real-world overall survival (OS) information was obtained from insurance claims data and Kaplan-Meier estimates were calculated for molecularly defined patients (pts). Results: TF exp was higher in primary tumors compared to metastatic sites (2.3-fold, P < 0.001); higher in lung vs. liver metastases (0.6-fold and 0.3-fold, p < 0.001); higher in rectal (1.4-fold), right-sided (1.3-fold), and transverse (1.2-fold) compared to left-sided (P < 0.001); and highest in CMS1 tumors (CMS2 0.4-fold, CMS3 0.7-fold, CMS4 0.8-fold, P < 0.001). TF exp was higher in tumors with high TMB (TMB ≥ 10 Mut/Mb) (1.6-fold), dMMR/MSI-H (1.9-fold), and PD-L1 exp (1.8-fold) (P < 0.001 each). Compared to WT tumors, mutations in KRAS (1.2-fold, P < 0.001), BRAF (1.5-fold, P < 0.001) and ERBB2 (1.2-fold, P < 0.01) were associated with higher TF exp. In pMMR/MSS CRC, TF-L tumors were associated with TP53, APC, and NRAS mutations, and TF-H was associated with KRAS, PIK3CA, SMAD4, FBXW7, BRAF, ARID1A, GNAS, SMAD2, RNF43, KMT2D and BRCA1 mutations. TF exp was positively associated with most immune cell populations, most strongly with endothelial cells. In pMMR/MSS KRAS WT CRC, TF-H was associated with worse OS than TF-L. TF-H was also associated with worse OS for pMMR/MSS CRC pts treated with FOLFOX (HR: 1.5, CI:1.2-1.8, p < 0.0001), FOLFIRI (HR:1.7, CI:1.3-2.1, p < 0.0001), VEGF (HR:1.3, CI:1.1-1.6, p = 0.002) and EGFR inhibitors (HR:1.6, CI:1.1-2.3, p = 0.009) than TF-L. TF-H was associated with greater median days on pembrolizumab compared to TF-L in dMMR/MSI-H CRC (HR: 0.6, CI: 0.4-0.9, p = 0.018). Conclusions: Our data show TF exp is associated with distinct clinical and molecular features, including tumor sidedness and metastatic pattern, as well as CMS subtype and KRAS, BRAF and ERBB2 mutations. TME cell infiltration and IO-related biomarkers were enriched in TF-H, with TF exp correlating with endothelial cell abundance. These findings and associations with patient outcomes suggest that TF may be a relevant biomarker and target in CRC.
594 Background: A blood-based biomarker to predict the risk of hepatocellular carcinoma (HCC), and its recurrence is needed. Previously, we showed that γ-OHPdG, a mutagenic DNA adduct formed by lipid peroxidation, in liver biopsies from HCC patients, as detected by IHC, is inversely associated with overall survival (p<0.0001) and recurrence-free survival (p<0.007) after surgical resection. This finding suggests that γ-OHPdG may serve as a prognostic biomarker of HCC and its recurrence. A non-invasive method to detect γ-OHPdG is needed. Liquid biopsy is preferred over tissue biopsy because it is non-invasive, allows repeated sampling, lower risk to patient, and lower medical care cost. We developed a non-invasive method for detecting and quantifying γ-OHPdG using CTCs from HCC patient. Methods: The method involved following steps. First, CTCs from blood samples were isolated using a RosetteSep CD45 Depletion Cocktail and Ficoll Paque-based method. Isolated cells were identified as liver CTCs using asialoglycoprotein receptor 1 (ASGPR1), a cell surface protein expressed solely on the surface of hepatic cells, and γ-OHPdG by immunocytochemistry. The percentage of ASGPR1 and γ-OHPdG-positive stained CTCs and γ-OHPdG staining intensity was quantified using Metamorph software. The staining intensities in livers CTCs will be compared with that found in liver biopsies by IHC. Results: To determine the sensitivity and specificity of testing -γ-OHPdG level in circulating tumor cells using an-anti γ-OHPdG antibody, we showed that the proportion of γ-OHPdG-positively stained cells and staining intensity increased in HepG2 liver cancer cells upon acrolein treatment at increasing concentration. Furthermore, when the HepG2 was used to spike blood of healthy volunteers’, the recovery rate of γ-OHPdG positivity was > 50-60%. CTCs from 32 HCC patients, detected at a positivity rate of ~97%, were tested for γ-OHPdG levels using the method developed in this project. The clinical factors including demographics, risk factors, alpha-fetoprotein (AFP), HCC size, multifocality, vascular invasion, extrahepatic metastasis have been correlated with the levels of γ-OHPdG in CTCs. Conclusions: The CTC method developed for detecting and quantifying γ-OHPdG warrant validations as a prognostic biomarker for predicting HCC risk and recurrence in clinical trials.
202 Background: Large studies have identified immune checkpoint inhibitors (ICI) as an effective therapy for deficient mismatch repair/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC). However, a subset of dMMR/MSI-H CRC patients exist that do not benefit from ICI and show rapid cancer progression within the first 6 months of therapy. Genetic alterations of the host immune system, including loss of β2M and single copy loss of HLA molecules, can contribute to innate resistance to ICI. In this study, we sought to analyze the role of expression of HLA genes and β2M as determinants of innate resistance to ICI by analyzing an extensive clinico-genomic database. Methods: Next-generation sequencing (NGS) of DNA (592-gene or whole exome) and RNA (whole transcriptome) was performed on CRC patient samples (n = 24,394) submitted to a CLIA-certified laboratory (Caris Life Sciences, Phoenix, AZ). dMMR/MSI-H was assessed by IHC/NGS. PD-L1 expression was tested by IHC (SP142; positive (+): ≥2+, ≥%5). Real world overall survival and treatment data were obtained from insurance claims data. Time-To-Next-treatment (TTNT) was calculated from start of ICI monotherapy to the start of next therapy, or death. Kaplan-Meier estimates were used for comparison. A composite signature of MHC II gene expression was tested for molecular associations. Immune cell infiltration was estimated by RNA deconvolution using quanTIseq. Statistical significance was determined using Fisher’s Exact/Mann Whitney/X ² tests. Results: We identified 1549 patients with dMMR/MSI-H CRC; 242 patients of these had received pembrolizumab or nivolumab. Using TTNT as a proxy for progression on treatment, we divided the patients into two cohorts: >180 days TTNT and <180 days TTNT. Following manual curation of the cases by two oncologists and limiting the patients to those who had received ≥ 2 doses of either ICI and at least 180 days of recorded follow up, we generated cohorts of 77 patients (>180 days TTNT; good responders) and 34 patients (<180 days TTNT; poor responders). High expression of HLA genes (HLA-DRB1, HLA-B, HLA-DQB1, HLA-DPB1, HLA-DPA1- p<0.02; fold change 2.1-3) was found in the good responder group. No β2M alterations were detected in either subgroup. After dividing the entire cohort into quartiles, patients in the highest quartile of expression for either CD74, HLA-DQA1, HLA-DQB1, HLA-DPB1 or HLA-DRB1 had improved survival when compared to lower expressors (p< 0.05). High MHC II signature expression was associated with an increased rate of PD-L1+ (34 vs 8%, p<0.0001) and infiltration of M1 macrophages (9.1 vs 4.9%, p<0.0001). Conclusions: We identify elevated expression of HLA genes involved in formation of the MHC-II complex as a potential biomarker of improved response to immunotherapy that could, if further validated, optimize patient selection for ICI in CRC.
789 Background: Cape is an oral fluoropyrimidine (FP) used as maint therapy in CRC and PC. While the standard FDA dosing is 1250 mg/m ² twice daily (BID) for 14 days followed by 7 days off in a 21-day cycle, there are variations across institutions as to the preferred schedule. To improve tolerability and convenience, our institution adopted a “continuous” dosing schedule where cape is taken BID Monday-Friday (M-F) with a treatment break on Saturday and Sunday. Here, we describe our institution’s experience with continuous maint dosing in advanced CRC and PC patients (pts) and explore real-world outcomes. Methods: Pts ≥ 18 years of age treated with continuous maint cape (+/- bevacizumab) after any line of therapy for stage 4 CRC/PC or locally advanced PC between 1/2016-12/2020 were identified in the COTA real-world database. The final study population included 35 PC and 85 CRC pts. Pt characteristics were analyzed descriptively and progression-free survival (PFS) was calculated using Kaplan Meier methods. Results: Among the 35 PC pts, the median age was 66 years (IQR: 61-73), 57.1% were females, and 65.7% were Caucasian. Among the 85 CRC pts, the median age was 54 years (IQR: 47-66), 47.1% were females, and 55.3% were Caucasian. Most PC (71.4%) and CRC (57.7%) pts were initially prescribed a total daily cape dose of 2 g (range 0.5-4 g). Dose adjustments, including dosage/schedule changes, occurred 11 times amongst PC and 36 times amongst CRC pts, and the leading cause was toxicity (72.7% in PC, 55.6% in CRC). Among PC pts, 14.3% had a dose reduction, 3% had a dose increase, and 11.4% switched to an alternative dosing schedule. Among CRC pts, these rates were 32.9%, 12.9%, and 9.4%, respectively. The leading cause of maint discontinuation was progression of disease (POD) (55.6% in PC, 59.3% in CRC). Additional outcomes are summarized in the table. Conclusions: Although maint FP is an established standard of care, it is often underutilized due to inherent inconveniences and toxicities associated with FDA cape dosing or intravenous FP therapy. The PFS reported here using a continuous cape dosing (predominantly starting at 2 g daily dosing) was in range with those previously reported in PC/CRC 1 st -line maint studies using FDA cape dosing or intravenous FP. The rates of cape discontinuation attributed to toxicity we report may be confounded by not controlling for the treatment setting. We argue fixed cape dosing (1 g BID) M-F should be considered a standard maint regimen based on efficacy, convenience, tolerability, and feasibility of dose adjustments.[Table: see text]
805 Background: Studying CTC cultures (cx) ex-vivo can provide valuable insights into cancer metastases (mets). However, current immunoaffinity- and size-based-methods used to isolate and expand these cells have low success rates for culturing CTCs (6-20%). Here, we report our experience using a novel technology developed at Georgetown for culturing CTCs from patients (pts) with metastatic (m) CC, mPC, and locally advanced PC (LAPC). Methods: 44 peripheral blood samples were prospectively collected from 35 pts with adenocarcinoma across 3 cohorts (18 samples from 15 mCC pts, 21 samples from 15 mPC pts, and 5 samples from 5 LAPC pts). Pts were previously treated, treatment-naïve, or actively undergoing treatment. FiColl-Paque-based separation of red blood cells was performed, plasma and buffy coat cells were resuspended in cx medium, and successfully grown CTC cxs were processed and injected subcutaneously (subQ) in the flanks of mice. A single predetermined sample from each pt was used in assessing the clinicopathologic associations with experiment outcomes and survival analyses. Results: CTC cxs were successfully grown from 81.8% (36/44) of all samples. Cxs grew from 72.2% (13/18) of mCC, 85.7% (18/21) of mPC, and 100% (5/5) of LAPC samples. At the time of analysis, 25 injected mice were evaluable for subQ tumor growth. 4 mice failed to grow tumor, 10 were still under monitoring, and 11 grew tumor, 9 of which also developed mets. These were mostly macro-mets and partially mirrored the met pattern seen in the matched pt. Across all cohorts, samples were predominantly collected from pts during systemic treatment (79.5%), during 2 nd - (36.4%) and 1 st -line treatment (20.5%), at a median of 15 (0-111) and 5 (1-20) months after diagnosis in mPC/mCC and LAPC pts, respectively, after scans with new/progressing disease (72.7%), and with a median of 3 (1-9) sites of disease on scans done within 2 months of collection . In all pts, no clinicopathologic or genomic factor predicted for cx growth. In the mCC subgroup, female sex (p=0.044), longer time from diagnosis to CTC collection (p=0.033), and presence of lung mets (p=0.022) were associated with cx growth. With cohorts combined, the median pt progression-free survival was 174 days (95% CI 97-220) and median overall survival was not reached. There was no statistically significant relationship between cx growth and pt survival. Conclusions: This novel platform demonstrated historically high rates of successful CTC cx and xenograft tumor growth using samples from advanced CC and PC pts. Studies to elucidate reasons for mice failing to grow tumor and others with matched tumor-CTC molecular analyses are ongoing to validate this promising technology to ultimately use to identify biomarkers for metastases, uncover novel therapeutic targets, and inform clinical decisions.
Objectives: The transition from military to civilian life may present increased exposure to various stressful life events (SLEs) that can increase the risk of homelessness (eg, loss of employment, dissolution of romantic relationships). We assessed the extent to which exposure to SLEs occurring proximal to US Army soldier transitions out of active duty was associated with risk of homelessness. Methods: A total of 16 589 respondents who were no longer on active duty but participated while on active duty during 2011-2014 baseline surveys completed follow-up surveys during 2016-2018 and 2018-2019. The follow-up surveys assessed SLEs and homelessness occurring in the past 12 months. We used modified Poisson regression models to evaluate how much differential SLE exposure and effects explained the aggregate association of a risk index with homelessness among a sample of 6837 respondents, weighted to represent the full sample. Results: More than half (n = 3510, 52.8%) of respondents reported experiencing any SLEs in the past 12 months. Most (60.5%) of the difference in prevalence of homelessness among respondents defined as being at high risk of homelessness (vs lower risk) was explained by differential exposure to, and/or effects of, these SLEs. Personal betrayal by a loved one and economic problems played the largest roles in adjusted risk differences (0.045 and 0.074, respectively). Conclusions: Homelessness might be reduced by gearing interventions toward soldiers at high risk of homelessness who are transitioning out of active duty to reduce exposure to and effects of modifiable SLEs on experiencing homelessness.
Introduction: Evidence-based rehabilitation and secondary prevention interventions improve post-stroke functional recovery and reduce secondary complications. However, stroke rehabilitation expertise, processes of care, and educational resources vary among sites where post-acute care (PAC) is delivered. Purpose: The American Heart Association (AHA) developed quality standards based on the AHA 2016 Guidelines for Adult Stroke Rehabilitation and Recovery to address these gaps. Methods: An interdisciplinary PAC standards writing committee identified key areas for PAC: quality improvement, medical management, care coordination, patient/caregiver and personnel education, and program management. Subgroups developed draft standards, combining results from a national landscape survey of PAC sites with clinical practice guidelines. The committee then refined the draft standards using a consensus-based process. AHA staff and PAC sites in Montana (MT) convened a learning collaborative to gather feedback and provide gap analyses of the standards relative to current practices. Qualitative input from beta testing in MT, and quantitative results from the nationwide survey and MT sites were analyzed and used to refine the standards further. Results: The national landscape survey demonstrated that most sites do not meet the proposed standards: stroke program oversight structure (78% fall short), stroke rehabilitation leadership (70%), stroke-specific order sets/protocols (61%), and policies requiring staff stroke education (66%). Regarding MT findings, 41% of the PAC sites have no mechanisms to identify areas of quality improvement specific to their stroke rehabilitation programs, and 59% do not use standardized tools to ensure performance improvement initiatives are followed. However, with adequate support and resources, most MT sites stated they would be able to meet the proposed standards. Conclusions: The Stroke PAC Program Standards are applicable in diverse PAC settings and provide a pathway to improving access to high-quality care for stroke survivors. Outcome studies are needed to confirm anticipated improvements in medical and functional outcomes.
Background Infants with bronchiolitis are at high risk for developing childhood asthma. While genome-wide association studies suggest common genetic susceptibilities between these conditions, the mechanisms underlying the link remain unclear. Objective Through integrated genetics-metabolomics analysis in this high-risk population, we sought to identify genetically driven metabolites associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility. Methods In a multicenter prospective cohort study of infants hospitalized for bronchiolitis, we profiled the nasopharyngeal metabolome and genotyped the whole genome at hospitalization. We identified asthma-related metabolites from 283 measured compounds and conducted metabolite quantitative trait loci (mtQTL) analyses. We further examined the mtQTL associations by testing shared genetic loci for metabolites and asthma using colocalization analysis and the concordance between the loci and known asthma-susceptibility genes. Results In 744 infants hospitalized with bronchiolitis, 28 metabolites (e.g., docosapentaenoate [DPA], 1,2-dioleoyl-sn-glycero-3-phosphoglycerol, sphingomyelin) were associated with asthma risk. A total of 349 loci were associated with these metabolites—161 for non-Hispanic white, 120 for non-Hispanic black, and 68 for Hispanics. Of these, there was evidence for 30 shared loci between 16 metabolites and asthma risk (colocalization posterior probability ≥0.5). The significant SNPs within loci were aligned with known asthma-susceptibility genes (e.g., ADORA1 , MUC16 ). Conclusion The integrated genetics-metabolomics analysis identified genetically driven metabolites during infancy that are associated with asthma development and genetic loci associated with both these metabolites and asthma susceptibility. Identifying these metabolites and genetic loci should advance research into the functional mechanisms of the infant bronchiolitis-childhood asthma link.
We present different findings on 18F-fluciclovine (Axumin) PET/CT and 18F-NaF PET/CT images in a patient with prostate cancer metastasis. 18F-Fluciclovine PET/CT scan showed intense uptake in left adrenal gland metastasis, only faint to mild uptake in multiple sclerotic osseous metastasis where 18F-NaF bone PET/CT demonstrated intense uptake at these sites. Both examinations are needed to accurately evaluate visceral and osseous metastasis from prostate cancer.
Efficient sensory processing of spatial information is facilitated through the organization of neuronal connections into topographic maps of space. In integrative sensory centers, converging topographic maps must be aligned to merge spatially congruent information. The superior colliculus (SC) receives topographically ordered visual inputs from retinal ganglion cells (RGCs) in the eye and layer 5 neurons in the primary visual cortex (L5-V1). Previous studies suggest that RGCs instruct the alignment of later-arriving L5-V1 inputs in an activity-dependent manner. However, the molecular mechanisms underlying this remain unclear. Here, we explored the role of NMDA receptors in visual map alignment in the SC using a conditional genetic KO approach. We leveraged a novel knock-in mouse line that expresses tamoxifen-inducible Cre recombinase under the control of the Tal1 gene (Tal1 CreERT2 ), which we show allows for specific recombination in the superficial layers of the SC. We used Tal1 CreERT2 mice of either sex to conditionally delete the obligate GluN1 subunit of the NMDA receptor (SC-cKO) during the period of visual map alignment. We observed a significant disruption of L5-V1 axon terminal organization in the SC of SC-cKO mice. Importantly, retinocollicular topography was unaffected in this context, suggesting that alignment is also disrupted. Time-course experiments suggest that NMDA receptors may play a critical role in the refinement of L5-V1 inputs in the SC. Together, these data implicate NMDA receptors as playing a critical mediator of activity-dependent visual map alignment in the SC. Significance Statement: Alignment of topographic inputs is critical for integration of spatially congruent sensory information; however, little is known about the mechanisms underlying this complex process. Here, we took a conditional genetic approach to explore the role of NMDA receptors in the alignment of retinal and cortical visual inputs in the superior colliculus. We characterize a novel mouse line providing spatial and temporal control of recombination in the superior colliculus and reveal a critical role for NMDA expression in visual map alignment. These data support a role for neuronal activity in visual map alignment and provide mechanistic insight into this complex developmental process.
Context: Massage therapy is increasingly used in palliative settings to improve quality of life and symptom burden; however, the optimal massage "dosage" remains unclear. Objective: To compare three massage dosing strategies among inpatients receiving palliative care consultation. Methods: At an urban academic hospital, we conducted a three-armed randomized trial examining three different doses of therapist-applied massage to test change in overall quality of life and symptoms among hospitalized adult patients receiving palliative care consultation for any indication (Arm I: 10-min massage daily x 3 days; Arm II: 20-min massage daily x 3 days; Arm III: single 20-min massage). Primary outcome measure was single-item McGill Quality of Life question. Secondary outcomes measured pain/symptoms, rating of peacefulness, and satisfaction with intervention. Data were collected at baseline, pre- and post-treatment, and 1-day post-last treatment (follow-up). Repeated measure analysis of variance and paired t-test were used to determine significant differences. Results: N=387 patients were 55.7 (±15.49) years old, mostly women (61.2%) and African-American (65.6%). All three arms demonstrated within-group improvement at follow-up for McGill quality of life (all p<0.05). No significant between-group differences were found. Finally, repeated measure analyses demonstrated time to predict immediate improvement in distress (p≤0.003) and pain (p≤0.02) for all study arms; however, only improvement in distress sustained at follow-up measurement in arms with three consecutive daily massages of 10 or 20 minutes. Conclusion: Massage therapy in complex patients with advanced illness was beneficial beyond dosage. Findings support session length (10 or 20 minutes) was predictive of short-term improvements while treatment frequency (once or three consecutive days) predicted sustained improvement at follow-up.
Urea cycle disorders (UCDs) comprise a group of inborn errors of metabolism with impaired ammonia clearance and an incidence of ~1:35 000 individuals. First described in the 1970s, the diagnosis and management of these disorders has evolved dramatically. We report on a 59‐year‐old woman with a UCD who contributed to advances in the understanding and treatment of this group of disorders. This individual was diagnosed with carbamoyl phosphate synthetase 1 deficiency based on a biochemical assay under a research context predating genetic sequencing, treated longitudinally as having this metabolic disorder, and was among the first participants to trial UCD pharmaceutical therapies. She ultimately succumbed to a SARS‐CoV‐2 infection while maintaining unexpectedly normal ammonium levels. Postmortem genetic testing revealed ornithine transcarbamylase deficiency. This individual's contributions to the field of UCDs is discussed herein.
Introduction: Comprehensive understanding of oncologic treatment is essential for shared decision-making. However, comprehension of information in radiation oncology consults is poorly understood, particularly among Spanish-speaking patients at safety-net hospitals. The purpose of this pilot study was to examine post-consultation radiation oncology knowledge and health literacy among breast cancer patients from culturally diverse backgrounds. Methods: After consultation for curative breast radiotherapy (cT1-4N1-3M0), the Radiation Oncology Knowledge Assessment Survey (ROKAS) was administered to Spanish- and English-speaking patients ≥ 18 years old, from January 2021 to January 2022 at a safety-net hospital. Radiation knowledge was assessed using the ROKAS which included eight radiation-specific multiple-choice questions and two separate questions regarding short- and long-term side effects. Additional independent variables included validated questionnaires related to health literacy, health numeracy, acculturation, primary language, and sociodemographic factors. Bivariate Pearson correlations and T-test analyses were conducted to examine the relationship between the independent variables and post-consultation radiation knowledge. Results: Fifty ROKAS were obtained from 25 English- and 25 Spanish-speaking breast cancer patients (median age 57 [IQR 49.75-62.25]). When compared to English-speaking patients, Spanish-speaking patients had lower health literacy, health numeracy, and acculturation. There was no difference in the multiple-choice ROKAS score between English- and Spanish-speakers, or correlation with the other independent factors. Higher health numeracy correlated with a higher accuracy for identifying short-term side effects. Lower accuracy of identifying long-term side effects was seen in patients with lower education levels, health literacy, health numeracy, and acculturation, with the most missed long-term side effects being arm swelling, skin toxicity, and heart toxicity. Conclusion: Patients with low health literacy, health numeracy, acculturation, and education levels as well as Spanish-speaking patients were associated with poor understanding of radiotherapy long-term side effects. Determining barriers to radiation knowledge is crucial to improve shared decision-making between patients and providers in a culturally diverse population.
Our nation’s military veterans share a connection through their service, making them a distinctive community with unique information requirements. Community-based solutions are crucial to meet veterans where they are, and libraries of all types are in a position to help. In recognition of this, the Institute of Museum and Library Services (IMLS) awarded a grant to Texas A&M University, which held a forum attended by 250 librarians from across the United States. The discussions covered how veterans are currently being engaged, what services and programs are working, and where improvements could be made. Toolkit committees were then formed to brainstorm service and program ideas for veterans that can be utilized in various library settings, including medical facilities. These toolkits were uploaded to a freely available repository so that librarians can use and adapt these resources to develop their own veteran-oriented programming. Results from this collaboration among librarians have led to new connections, friendships being formed, and the generation of even more creative solutions to reach veteran populations. While considerations such as respecting copyright and dealing with grant funding appropriations are present, this should not keep librarians from utilizing these resources. This project is meant to be an ongoing and evolving effort. New ideas and collaborations are not just welcomed but encouraged to best serve these veterans who have so selflessly sacrificed for their country.
OBJECTIVE Closed suction drains, often used after posterior spinal surgery, pose a potential risk of infection. To combat this risk, many surgeons opt for a prolonged prophylactic antibiotic regimen. Since 2015, several studies have shown that prolonged prophylactic systemic antibiotics (PPSA) for drains provides no additional benefit in reducing surgical site infection (SSI) rates. However, most of these studies lacked sufficient power to make reliable conclusions. To date, there has been no meta-analysis conducted to further investigate this issue. The aim of this study was to investigate whether a regimen of PPSA reduces the incidence of deep SSIs in adult patients with closed suction drains following posterior spinal surgeries. METHODS The protocol of the current systematic review was registered with PROSPERO. A systematic review of the literature in PubMed (Medline), Europe PMC, Embase, and Cochrane Review databases was conducted for all relevant literature with the keywords "spine," "antibiotics," "surgical site infection," "prophylaxis," and "drain." Retrospective and prospective studies investigating the effectiveness of PPSA in patients 18 years or older who underwent posterior cervical or thoracolumbar surgery and had postoperative wound drains were included. The primary outcome was the odds ratio for deep SSI based on the intervention (PPSA vs non-PPSA). The secondary outcomes were the rates of superficial and overall SSIs. RESULTS From a total of 2558 titles identified from the search, 7 studies were chosen for final analysis. Three were randomized controlled trials (RCTs), and 4 were retrospective reviews. A total of 2446 patients were analyzed; 1149 received a PPSA regimen and 1297 received a non-PPSA regimen. Deep SSIs occurred in 45 patients (3.9%) and 46 patients (3.5%) in the PPSA and non-PPSA groups, respectively. The odds ratio for deep SSIs in the PPSA group compared with the non-PPSA group was 1.10 (95% CI 0.69–1.74), which was not statistically significant. Additionally, there were no differences in the rates of superficial and overall SSIs. There was a trend toward increased infections with multidrug-resistant bacteria ( Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus ) in the PPSA group; however, it was not possible to perform a durable statistical analysis because of the small number of reported organisms in the selected publications. CONCLUSIONS This meta-analysis demonstrates that there is no reduction in rate of deep, superficial, and overall SSIs with prolonged prophylactic antibiotics after posterior spinal surgery involving the use of closed suction drains.
Institution pages aggregate content on ResearchGate related to an institution. The members listed on this page have self-identified as being affiliated with this institution. Publications listed on this page were identified by our algorithms as relating to this institution. This page was not created or approved by the institution. If you represent an institution and have questions about these pages or wish to report inaccurate content, you can contact us here.
56 members
Washington, D.C., United States