Jacobs Institute of Women's Health
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Effect of Dialysis Modality on Mortality and Complications in Cardiovascular Surgery: Insights from a National Retrospective Cohort Study
No full textEmbedded Emergency Department Physical Therapy Practice: Essential Stakeholder Perspectives and Implementation Strategies
No full textBackground: Although international models demonstrate the value of Emergency Department Physical Therapy (EDPT), adoption within U.S. hospitals remains limited. This study explored the experiences of emergency department (ED) medical directors and lead physical therapists (PTs) to identify barriers, facilitators, and strategies for broader EDPT implementation.
Objective: To examine how ED medical directors and lead PTs describe the implementation of embedded EDPT practice, including barriers, facilitators, and alignment with ED goals and performance indicators, with the ultimate goal of co-developing a tailored implementation strategy for U.S. hospitals.
Methods: This national, multi-phase, mixed-methods study included a survey, semi- structured interviews, and a focus group. Data were collected from ED medical directors and lead PTs to describe current practices, identify implementation barriers and facilitators, and collaboratively develop tailored strategies. The research team (PVDW, NND, ML) used REDCap for data collection and conducted qualitative analysis through inductive and deductive reasoning/coding approaches.
Results: Over a ten-month period, 20 hospitals participated in the study. Survey and interview data revealed six key themes aligned with the Consolidated Framework for Implementation Research (CFIR), based on insights from four ED medical directors and four lead PTs. A subsequent focus group with six PTs and two medical directors identified four focus areas to guide future implementation. Key findings included the critical role of relationships, communication, and team dynamics in EDPT success; the positive impact of EDPT on ED operations and workflow; the need for increased stakeholder awareness; favorable patient and provider outcomes; and financial implications that benefit systems and patients but challenge PTs. Participants also described the need for a shared vision for change within hospital systems.
Discussion: Findings support five essential implementation strategies for advancing embedded EDPT practice in the US: fostering a gradual culture shift, cultivating interprofessional relationships, selecting and developing skilled EDPTs, using data-driven advocacy, and engaging leadership to ensure sustainability
Developing a manual clinical trials screening process in a diverse southern gynecologic oncology practice
No full textOBJECTIVE: There is no standard clinical trial screening process in gynecologic oncology. In our low resource, highly diverse gynecologic oncology patient population, we sought to create an equitable, adaptable, manual screening process. METHODS: Our objective is to describe our clinical trial screening process and success in improving trial enrollment. An Institutional Review Board (IRB) approved quality improvement (QI) project was implemented in July 2022 to evaluate trial access. Screenable events were defined. Potential patients were those with a screenable event: new patients or diagnoses, regimen changes, progressions, and recurrences. Events were categorized into screen positive or screened no trial available. Screen positives were further categorized as screen positive, enrollment failure events or enrollments. Data about patients were collected via weekly research team meetings. Monthly meetings occurred to review progress. The data were compared to trials available, number of patients with trail available, and those that enrolled. Reasons for enrollment fails were tracked. RESULTS: Over time, screen no trial available (SNTA) rates stayed stable, but enrollment rates increased. Patient preference accounted for 32.8 % of enrollment failures (n = 42), pre-existing symptoms 23.4 % (n = 30), and location 21.1 % (n = 27). During increased employee turnover, there was a rise in enrollment fails due to staffing (n = 6, 4.7 %). We describe an effective process of clearly defining and tracking our patient population and \u27screenable events\u27 for which all patients are screened and offered trial participation if eligible. CONCLUSIONS: We show that we improved understanding of the patient population, built a clinical trial portfolio better matched to population served, exceeded national averages for enrolling patients on trials, and are improving number eligible
Transcriptomic and functional characterization of megakaryocytic-derived platelet-like particles: impaired aggregation and prominent anti-tumor effects
No full textPlatelet-like particles (PLPs), derived from megakaryocytic cell lines MEG-01 and K-562, are widely used as a surrogate to study platelet formation and function. We demonstrate by RNA-Seq that PLPs are transcriptionally distinct from platelets. Expression of key genes in signaling pathways promoting platelet activation/aggregation, such as the PI3K/AKT, protein kinase A, phospholipase C, and α-adrenergic and GP6 receptor pathways, was missing or under-expressed in PLPs. Functionally, PLPs do not aggregate following epinephrine, collagen, or ADP stimulation. While PLPs aggregated in response to thrombin, they did not display enhanced expression of surface markers P-selectin and activated αβ, in contrast to platelets. We have previously demonstrated that platelets physically couple to MDA-PCa-2b and RC77T/E prostate cancer (PCa) cells via specific ligand-receptor interactions, leading to platelet-stimulated cell invasiveness and apoptotic resistance, and reciprocal cell-induced platelet aggregation. In contrast, PLP interactions with PCa cells inhibited both cell invasion and apoptotic resistance while failing to promote PLP aggregation. Moreover, PLPs reduced platelet-PCa cell interactions and antagonized platelet-stimulated oncogenic effects in PCa cells. RNA-Seq analysis identified candidate ligand-transmembrane protein combinations involved in anti-tumorigenic signaling of PLPs to PCa cells. Antibody neutralization of the TIMP3-MMP15 and VEGFB-FGFR1 signaling axes reversed PLP-mediated anti-invasion and apoptotic sensitization, respectively. In summary, PLPs lack many transcriptomic, molecular and functional features of platelets and possess novel anti-tumorigenic properties. These findings indicate that PLPs may have a potential therapeutic role in targeting and disrupting the oncogenic signaling between platelets and cancer cells, offering a new avenue for anti-cancer strategies
Distinct immunogenicity outcomes of DNA vaccines encoding malaria transmission-blocking vaccine target antigens Pfs230D1M and Pvs230D1
No full textTransmission-blocking vaccines (TBVs) targeting sexual-stage antigens represent a critical tool for malaria control and elimination through inhibiting parasite development within mosquitoes. P230, displayed on the surface of gametocytes and gametes, plays a crucial role in gamete fertilization and is one of the leading TBV candidates for both Plasmodium falciparum and P. vivax. Antibodies induced by immunization with a recombinant P. falciparum protein encompassing a portion of N-terminal prodomain and domain 1 (Pfs230D1M) have revealed strong transmission-reducing activity (TRA) in preclinical studies. While a recombinant Pvs230D1, the P. vivax homolog of Pfs230D1M, has not been evaluated in preclinical immunogenicity studies, both Pfs230D1M and Pvs230D1 are currently scheduled for evaluation in clinical trials. In this study, we developed DNA vaccines encoding Pfs230D1M and Pvs230D1 for a side-by-side comparison of their immunogenicity. Potent antibody responses were induced in mice immunized with each DNA vaccine delivered by in vivo electroporation (EP). Anti-Pfs230D1M IgG exhibited potent dose-dependent TRA in a complement-dependent manner in standard membrane feeding assays (SMFA). In contrast, anti-Pvs230D1 IgG exhibited only moderate TRA in direct membrane feeding assay (DMFA) using blood from multiple P. vivax-infected donors. Antibodies induced by the Pfs230D1M DNA vaccine revealed a strong IgG1 bias and higher avidity as compared to a balanced IgG1/IgG2 response and lower antibody avidity by the Pvs230D1 DNA vaccine. Our results demonstrate the potential of both Pfs230D1M and Pvs230D1 DNA vaccines as TBV candidates against P. falciparum and P. vivax, and provide a rationale for future optimization to enhance the efficacy of DNA vaccines based on Pfs230 and Pvs230
Treatment Strategies for Intermediate Spinal Instability Neoplastic Score Patients: A Systematic Review
No full textBACKGROUND: The Spinal Instability Neoplastic Score (SINS) is used in determining instability in patients with spinal metastases. Intermediate scores of 7 to 12 suggest possible instability, but there are no clear guidelines to address patients with these scores. METHODS: We searched in PubMed, EMBASE, and Cochrane databases for studies that included patient demographics, tumor histology, surgical or radiotherapy management, and outcomes of patients with intermediate SINS. We reported mean differences and odds ratios (ORs) to assess differences between patients managed surgically versus with radiotherapy alone. RESULTS: Thirteen articles, totaling 1822 patients with intermediate SINS were analyzed. In 5 studies (38.4%), the management decision was based on a tumor board review. There was no significant difference between surgical management versus radiotherapy (P = 0.24). When dichotomized into SINS 7-9 and 10-12, the OR for surgical management in the 10-12 group compared to the 7-9 group was 6.88 (95% confidence interval [CI] 2.31-20.5, P = 0.0005). More renal cell carcinomas were managed surgically instead of with radiotherapy alone than other tumor types (OR = 1.87, 95% CI = 1.14-3.05, P = 0.01). There was no statistical difference in overall complications between the 2 treatment groups (OR = 1.12, 95% CI = 0.49-2.54, P = 0.79). Vertebral fracture rates after any radiotherapy type ranged between 20% and 66%. The need for a surgical procedure, including stabilization, vertebroplasty, or kyphoplasty after radiotherapy ranged from 5% to 34.2%. CONCLUSIONS: Complication rates after surgery versus radiotherapy in the intermediate SINS category are similar, but the complication types differ. Patients in the 10-12 SINS subgroup, due to larger lytic area and higher probability of vertebral body fracture, could benefit from stabilization before radiotherapy
Definition of cage subsidence in transforaminal lumbar interbody fusion (TLIF) approach and posterior lumbar interbody fusion (PLIF) approach - A systematic review
No full textBACKGROUND: Although cage subsidence is one of the most common phenomenona associated with interbody fusions and was characterized more than 70 years ago, a standardized method for its measurement, detection, and reporting among different lumbar fusion procedures does not exist. Here, we review previously published literature on cage subsidence to present the most common methods for defining subsidence in the posterior lumbar interbody fusion (PLIF) and transforaminal lumbar interbody fusion (TLIF) techniques. METHODS: A search was completed in PubMed and Embase with inclusion criteria focused on identifying any study that provided descriptions of the method, imaging modality, and subsidence threshold used to define the presence of cage subsidence in study articles published between January 1, 2001 and December 31, 2022. RESULTS: A total of 54 studies were included in the final analysis. Among them, 32 (59.2 %) reported on TLIF, 20 (37.1 %) reported on PLIF, and 2 studies (3.7 %) reported on both approaches. For TLIF and PLIF procedures, the preferred method to determine subsidence was cage migration into the vertebral bodies rather than changes in disc height. In the TLIF group, the predominant criteria for defining subsidence were thresholds of ≥ 2 mm and \u3e 2 mm utilized in each of 10 of the 34 studies (58.8 %). Similarly, in the PLIF group, the common criterion for defining subsidence was also ≥ 2 mm, observed in 5 of 22 studies (22.7 %), with \u3e 2 mm observed in 4 studies (18.2 %). The methods for assessing cage migration or disc height change varied substantially among studies, with none of the measurements being consistently applied in more than 50 % of the studies. CONCLUSIONS: Inconsistency persists in the methods used to determine, report, or measure the degree of subsidence. Surgeons and researchers should standardize these methods to ensure consistency and generalizability in reporting and studying subsidence