Scholarly Articles

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Open Access
We Are Not All the Same: Implications of Heterogeneity Among Latiné/e/x/o/a, Hispanic, and Spanish Origin People.
(Annals of family medicine, 2024-05) Carvajal, Diana N; Anaya, Yohualli B; McLean, Ivonne; Aragón, Miranda; Figueroa, Edgar; Plasencia, Gabriela; Martinez-Bianchi, Viviana; Rodríguez, José E
There is great variation in the experiences of Latiné/e/x/o/a, Hispanic, and/or Spanish origin (LHS) individuals in the United States, including differences in race, ancestry, colonization histories, and immigration experiences. This essay calls readers to consider the implications of the heterogeneity of lived experiences among LHS populations, including variations in country of origin, immigration histories, time in the United States, languages spoken, and colonization histories on patient care and academia. There is power in unity when advocating for community, social, and political change, especially as it pertains to equity, diversity, and inclusion (EDI; sometimes referred to as DEI) efforts in academic institutions. Yet, there is also a critical need to disaggregate the LHS diaspora and its conceptualization based on differing experiences so that we may improve our understanding of the sociopolitical attributes that impact health. We propose strategies to improve recognition of these differences and their potential health outcomes toward a goal of health equity.
Open Access
¿No Hay Racismo?: application of the levels of racism framework to Latinx perspectives on barriers to health and wellbeing.
(BMC public health, 2024-08) Plasencia, Gabriela; Kaalund, Kamaria; Gupta, Rohan; Martinez-Bianchi, Viviana; Gonzalez-Guarda, Rosa; Sperling, Jessica; Thoumi, Andrea
Background
The purpose of this study is to increase understanding of the forms of systemic racism experienced by Latinx communities in North Carolina during the COVID-19 pandemic as identified by Latinx community health workers (CHWs) and community-based organization (CBO) leaders.
Methods
We held three focus groups in July 2022 (N = 16) with CHWs and CBO leaders in Spanish to discuss policy and community interventions that improved access to resources during the COVID-19 pandemic; policy or community interventions needed to improve care of Latinx communities; and lessons learned to improve the health of Latinx communities in the future. We performed directed and summative qualitative content analysis of the data in the original language using the Levels of Racism Framework by Dr. Camara Jones to identify examples of implicitly and explicitly discussed forms of systemic racism.
Results
Latinx CHWs and CBO leaders implicitly discussed numerous examples of all levels of racism when seeking and receiving health services, such as lack of resources for undocumented individuals and negative interactions with non-Latinx individuals, but did not explicitly name racism. Themes related to institutionalized racism included: differential access to resources due to language barriers; uninsured or undocumented status; exclusionary policies not accounting for cultural or socioeconomic differences; lack of action despite need; and difficulties obtaining sustainable funding. Themes related to personally-mediated racism included: lack of cultural awareness or humility; fear-inciting misinformation targeting Latinx populations; and negative interactions with non-Latinx individuals, organizations, or institutions. Themes related to internalized racism included: fear of seeking information or medical care; resignation or hopelessness; and competition among Latinx CBOs. Similarly, CHWs and CBO leaders discussed several interventions with systems-level impact without explicitly mentioning policy or policy change.
Conclusion
Our research demonstrates community-identified examples of racism and confirms that Latinx populations often do not name racism explicitly. Such language gaps limit the ability of CHWs and CBOs to highlight injustices and limit the ability of communities to advocate for themselves. Although generally COVID-19 focused, themes identified represent long-standing, systemic barriers affecting Latinx communities. It is therefore critical that public and private policymakers consider these language gaps and engage with Latinx communities to develop community-informed anti-racist policies to sustainably reduce forms of racism experienced by this unique population.
Open Access
Systemic changes in Immune System-Related Plasma Extracellular Vesicles During Healthy Aging
(Journal of Extracellular Vesicles, 2024-07-13) Zhang, Xin; Ma, Sisi; Syeda Iffat, Naz; Huebner, Janet; Soderblom, Erik; Alnemer, Noor; Aliferis, Constantin; Kraus, Virginia
Open Access
Systemic EBV‐positive T‐cell lymphoma of childhood with unusual cytogenetic findings and family history of Still's disease‐associated recurrent macrophage activation syndrome
(Pediatric Blood & Cancer) Jimenez, Adam; Carrillo, Luis F; Carlsen, Eric D
Open Access
Burnout, Personal, and Occupational Factors as Predictors of Physician Assistant Faculty Intent to Leave After the COVID-19 Pandemic
(The Journal of Physician Assistant Education, 2024-09) Stouder, April; Ayars, Candace L
Introduction This study addressed whether burnout, personal, or occupational factors predicted physician assistant (PA) faculty intent to leave and established a new postpandemic national benchmark for PA faculty burnout and intent to leave. Methods In spring 2023, a nonexperimental, cross-sectional survey was emailed to 2031 PA faculty drawn from program faculty listings and the PA Education Association member database. Descriptive statistics were used to describe the sample, and a multiple regression analysis was conducted to analyze the predictive ability of the independent variables on intent to leave. Results The response rate was 30% (609 of 2031), with 496 responses (24.4%) included in the analysis. The sample reflected the population of PA faculty. The regression model significantly predicted intent leave (P < .001). The adjusted R 2 was 0.46, indicating the combination of independent variables predicted 46% of the variance in PA faculty intent to leave. Significant predictors included emotional exhaustion and identifying as multiracial (P < .001), control and values (P < .01), and depersonalization, fairness, rewards, and clinical year faculty role (P < .05). The sample had moderate levels of burnout and experienced burnout at higher rates than in prepandemic studies. Physician assistant faculty in administrative leadership roles had the highest levels of burnout and intent to leave. Despite this, PA faculty intent to leave measures were similar to prepandemic levels. Discussion Several of the predictive variables were related to well-being and social-emotional aspects of the workplace. These findings have implications for institutional policies and practices that support faculty well-being and workplace culture to enhance retention.
Open Access
The Registration of Ginling College and the Role of Wu Yi-fang, 1925–1930
(Religions) Chen, Maria
This paper examines the role of Wu Yi-fang in the registration process at Ginling College. It explores the initial resistance exhibited by the missionary faculty and the Ginling College Committee toward registration, contrasting it with their subsequent change in attitude following the 1927 Nanking Incident. This incident forced Ginling to adhere to government regulations, appointing Wu Yi-fang as the Chinese president of the college. Through her exceptional negotiation strategies, Wu not only ensured Ginling’s smooth registration and prosperity after the political upheaval but also successfully claimed decision-making authority for herself. This paper argues that Wu’s contributions to Ginling’s registration demonstrate how Christian schools and liberal education played a significant role in nurturing the development of Chinese female leaders and preparing them for leadership roles. Simultaneously, these institutions benefited from the achievements of their graduates.
Open Access
Spinal cord injury in high-risk complex adult spinal deformity surgery: review of incidence and outcomes from the Scoli-RISK-1 study
(Spinal Cord Series and Cases, 2024) Jiang, F; Joshi, H; Badhiwala, JH; Wilson, JRF; Lenke, LG; Shaffrey, CI; Cheung, KMC; Carreon, LY; Dekutoski, MB; Schwab, FJ; Boachie-Adjei, O; Kebaish, KM; Ames, CP; Berven, SH; Qiu, Y; Matsuyama, Y; Dahl, BT; Mehdian, H; Pellisé, F; Lewis, SJ; Fehlings, MG
Abstract Study design Clinical case series. Objective To describe the cause, treatment and outcome of 6 cases of perioperative spinal cord injury (SCI) in high-risk adult deformity surgery. Setting Adult spinal deformity patients were enrolled in the multi-center Scoli-RISK-1 cohort study. Methods A total of 272 patients who underwent complex adult deformity surgery were enrolled in the prospective, multi-center Scoli-RISK-1 cohort study. Clinical follow up data were available up to a maximum of 2 years after index surgery. Cases of perioperative SCI were identified and an extensive case review was performed. Results Six individuals with SCI were identified from the Scoli-RISK-1 database (2.2%). Two cases occurred intraoperatively and four cases occurred postoperatively. The first case was an incomplete SCI due to a direct intraoperative insult and was treated postoperatively with Riluzole. The second SCI case was caused by a compression injury due to overcorrection of the deformity. Three cases of incomplete SCI occurred; one case of postoperative hematoma, one case of proximal junctional kyphosis (PJK) and one case of adjacent segment disc herniation. All cases of post-operative incomplete SCI were managed with revision decompression and resulted in excellent clinical recovery. One case of incomplete SCI resulted from infection and PJK. The patient’s treatment was complicated by a delay in revision and the patient suffered persistent neurological deficits up to six weeks following the onset of SCI. Conclusion Despite the low incidence in high-risk adult deformity surgeries, perioperative SCI can result in devastating consequences. Thus, appropriate postoperative care, follow up and timely management of SCI are essential.
Open Access
The Copernican Revolution in the History of Interpretation of Job 28
(Jewish Studies Quarterly, 2020) Mizrahi, Aslan Cohen
Open Access
The Impact of Persistent Gastrointestinal Symptoms on Completion of Oral Immunotherapy in Clinical Trials
(Journal of Allergy and Clinical Immunology, 2023-02) Lim, Joshua; Cao, Shu; Chinthrajah, Sharon; Sindher, Sayantani
Open Access
Classifying Drosophila olfactory projection neuron boutons by quantitative analysis of electron microscopic reconstruction
(iScience, 2022-05) Yang, Kai; Liu, Tong; Wang, Ze; Liu, Jing; Shen, Yuxinyao; Pan, Xinyi; Wen, Ruyi; Xie, Haotian; Ruan, Zhaoxuan; Tan, Zixiao; Chen, Yingying; Guo, Aike; Liu, He; Han, Hua; Di, Zengru; Zhang, Ke
Open Access
Lipid nanoparticle-based mRNA vaccines: a new frontier in precision oncology
(Precision Clinical Medicine) Jacob, Eden M; Huang, Jiaoti; Chen, Ming
Abstract The delivery of lipid nanoparticle (LNP)-based mRNA therapeutics has captured the attention of the vaccine research community as an innovative and versatile tool for treating a variety of human malignancies. mRNA vaccines are now in the limelight as an alternative to conventional vaccines owing to their high precision, low-cost, rapid manufacture, and superior safety profile. Multiple mRNA vaccine platforms have been developed to target several types of cancer, and many have demonstrated encouraging results in animal models and human trials. The effectiveness of these new mRNA vaccines depends on the efficacy and stability of the antigen(s) of interest generated and the reliability of their delivery to antigen-presenting cells (APCs), especially dendritic cells (DCs). In this review, we provide a detailed overview of mRNA vaccines and their delivery strategies and consider future directions and challenges in advancing and expanding this promising vaccine platform to widespread therapeutic use against cancer.
Open Access
Telomerase ribonucleoprotein and genome integrity-An emerging connection in protozoan parasites.
(Wiley interdisciplinary reviews. RNA, 2022-09) Davis, Justin Alexander; Chakrabarti, Kausik
Telomerase has an established role in telomere maintenance in eukaryotes. However, recent studies have begun to implicate telomerase in cellular roles beyond telomere maintenance. Specifically, evidence is emerging of cross-talks between telomerase mediated telomere homeostasis and DNA repair pathways. Telomere shortening due to the end replication problem is a constant threat to genome integrity in eukaryotic cells. This poses a particular problem in unicellular parasitic protists because their major virulence genes are located at the subtelomeric loci. Although telomerase is the major regulator of telomere lengthening in eukaryotes, it is less studied in the ancient eukaryotes, including clinically important human pathogens. Recent research is highlighting interplay between telomerase and the DNA damage response in human parasites. The importance of this interplay in pathogen virulence is only beginning to be illuminated, including the potential to highlight novel developmental regulation of telomerase in parasites who transition between multiple developmental stages throughout their life cycle. In this review, we will discuss the telomerase ribonucleoprotein enzyme and DNA repair pathways with emerging views in human parasites to give a broader perspective of the possible connection of telomere, telomerase, and DNA repair pathways across eukaryotic lineages and highlight their potential role in pathogen virulence. This article is categorized under: RNA Structure and Dynamics > Influence of RNA Structure in Biological Systems RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution RNA Interactions with Proteins and Other Molecules > Protein-RNA Interactions: Functional Implications.
Open Access
Proteomic analysis defines the interactome of telomerase in the protozoan parasite, Trypanosoma brucei.
(Frontiers in cell and developmental biology, 2023-01) Davis, Justin A; Reyes, Andres V; Nitika; Saha, Arpita; Wolfgeher, Donald J; Xu, Shou-Ling; Truman, Andrew W; Li, Bibo; Chakrabarti, Kausik
Telomerase is a ribonucleoprotein enzyme responsible for maintaining the telomeric end of the chromosome. The telomerase enzyme requires two main components to function: the telomerase reverse transcriptase (TERT) and the telomerase RNA (TR), which provides the template for telomeric DNA synthesis. TR is a long non-coding RNA, which forms the basis of a large structural scaffold upon which many accessory proteins can bind and form the complete telomerase holoenzyme. These accessory protein interactions are required for telomerase activity and regulation inside cells. The interacting partners of TERT have been well studied in yeast, human, and Tetrahymena models, but not in parasitic protozoa, including clinically relevant human parasites. Here, using the protozoan parasite, Trypanosoma brucei (T. brucei) as a model, we have identified the interactome of T. brucei TERT (TbTERT) using a mass spectrometry-based approach. We identified previously known and unknown interacting factors of TbTERT, highlighting unique features of T. brucei telomerase biology. These unique interactions with TbTERT, suggest mechanistic differences in telomere maintenance between T. brucei and other eukaryotes.
Open Access
In vivo architecture of the telomerase RNA catalytic core in Trypanosoma brucei.
(Nucleic acids research, 2021-12) Dey, Abhishek; Monroy-Eklund, Anais; Klotz, Kaitlin; Saha, Arpita; Davis, Justin; Li, Bibo; Laederach, Alain; Chakrabarti, Kausik
Telomerase is a unique ribonucleoprotein (RNP) reverse transcriptase that utilizes its cognate RNA molecule as a template for telomere DNA repeat synthesis. Telomerase contains the reverse transcriptase protein, TERT and the template RNA, TR, as its core components. The 5'-half of TR forms a highly conserved catalytic core comprising of the template region and adjacent domains necessary for telomere synthesis. However, how telomerase RNA folding takes place in vivo has not been fully understood due to low abundance of the native RNP. Here, using unicellular pathogen Trypanosoma brucei as a model, we reveal important regional folding information of the native telomerase RNA core domains, i.e. TR template, template boundary element, template proximal helix and Helix IV (eCR4-CR5) domain. For this purpose, we uniquely combined in-cell probing with targeted high-throughput RNA sequencing and mutational mapping under three conditions: in vivo (in WT and TERT-/- cells), in an immunopurified catalytically active telomerase RNP complex and ex vivo (deproteinized). We discover that TR forms at least two different conformers with distinct folding topologies in the insect and mammalian developmental stages of T. brucei. Also, TERT does not significantly affect the RNA folding in vivo, suggesting that the telomerase RNA in T. brucei exists in a conformationally preorganized stable structure. Our observed differences in RNA (TR) folding at two distinct developmental stages of T. brucei suggest that important conformational changes are a key component of T. brucei development.
Open Access
Molecular and Evolutionary Analysis of RNA-Protein Interactions in Telomerase Regulation.
(Non-coding RNA, 2024-06) Davis, Justin A; Chakrabarti, Kausik
Telomerase is an enzyme involved in the maintenance of telomeres. Telomere shortening due to the end-replication problem is a threat to the genome integrity of all eukaryotes. Telomerase inside cells depends on a myriad of protein-protein and RNA-protein interactions to properly assemble and regulate the function of the telomerase holoenzyme. These interactions are well studied in model eukaryotes, like humans, yeast, and the ciliated protozoan known as Tetrahymena thermophila. Emerging evidence also suggests that deep-branching eukaryotes, such as the parasitic protist Trypanosoma brucei require conserved and novel RNA-binding proteins for the assembly and function of their telomerase. In this review, we will discuss telomerase regulatory pathways in the context of telomerase-interacting proteins, with special attention paid to RNA-binding proteins. We will discuss these interactors on an evolutionary scale, from parasitic protists to humans, to provide a broader perspective on the extensive role that protein-protein and RNA-protein interactions play in regulating telomerase activity in eukaryotes.
Open Access
Mechanisms of lumbar spine “flattening” in adult spinal deformity: defining changes in shape that occur relative to a normative population
(European Spine Journal, 2024-01-01) Lafage, R; Mota, F; Khalifé, M; Protopsaltis, T; Passias, PG; Kim, HJ; Line, B; Elysée, J; Mundis, G; Shaffrey, CI; Ames, CP; Klineberg, EO; Gupta, MC; Burton, DC; Lenke, LG; Bess, S; Smith, JS; Schwab, FJ; Lafage, V
Purpose: Previous work comparing ASD to a normative population demonstrated that a large proportion of lumbar lordosis is lost proximally (L1-L4). The current study expands on these findings by collectively investigating regional angles and spinal contours. Methods: 119 asymptomatic volunteers with full-body free-standing radiographs were used to identify age-and-PI models of each Vertebra Pelvic Angle (VPA) from L5 to T10. These formulas were then applied to a cohort of primary surgical ASD patients without coronal malalignment. Loss of lumbar lordosis (LL) was defined as the offset between age-and-PI normative value and pre-operative alignment. Spine shapes defined by VPAs were compared and analyzed using paired t-tests. Results: 362 ASD patients were identified (age = 64.4 ± 13, 57.1% females). Compared to their age-and-PI normative values, patients demonstrated a significant loss in LL of 17 ± 19° in the following distribution: 14.1% had “No loss” (mean = 0.1 ± 2.3), 22.9% with 10°-loss (mean = 9.9 ± 2.9), 22.1% with 20°-loss (mean = 20.0 ± 2.8), and 29.3% with 30°-loss (mean = 33.8 ± 6.0). “No loss” patients’ spine was slightly posterior to the normative shape from L4 to T10 (VPA difference of 2°), while superimposed on the normative one from S1 to L2 and became anterior at L1 in the “10°-loss” group. As LL loss increased, ASD and normative shapes offset extended caudally to L3 for the “20°-loss” group and L4 for the “30°-loss” group. Conclusion: As LL loss increases, the difference between ASD and normative shapes first occurs proximally and then progresses incrementally caudally. Understanding spinal contour and LL loss location may be key to achieving sustainable correction by identifying optimal and personalized postoperative shapes.
Open Access
Thoracolumbar fusions for adult lumbar deformity show superior QALY gain and lower costs compared with upper thoracic fusions
(Spine Deformity, 2024-01-01) Kim, AH; Hostin, RA; Yeramaneni, S; Gum, JL; Nayak, P; Line, BG; Bess, S; Passias, PG; Hamilton, DK; Gupta, MC; Smith, JS; Lafage, R; Diebo, BG; Lafage, V; Klineberg, EO; Daniels, AH; Protopsaltis, TS; Schwab, FJ; Shaffrey, CI; Ames, CP; Burton, DC; Kebaish, KM
Purpose: Adult spinal deformity (ASD) patients with sagittal plane deformity (N) or structural lumbar/thoraco-lumbar (TL) curves can be treated with fusions stopping at the TL junction or extending to the upper thoracic (UT) spine. This study evaluates the impact on cost/cumulative quality-adjusted life year (QALY) in patients treated with TL vs UT fusion. Methods: ASD patients with > 4-level fusion and 2-year follow-up were included. Index and total episode-of-care costs were estimated using average itemized direct costs obtained from hospital records. Cumulative QALY gained were calculated from preoperative to 2-year postoperative change in Short Form Six-Dimension (SF-6D) scores. The TL and UT groups comprised patients with upper instrumented vertebrae (UIV) at T9-T12 and T2-T5, respectively. Results: Of 566 patients with type N or L curves, mean age was 63.2 ± 12.1 years, 72% were female and 93% Caucasians. Patients in the TL group had better sagittal vertical axis (7.3 ± 6.9 vs. 9.2 ± 8.1 cm, p = 0.01), lower surgical invasiveness (− 30; p < 0.001), and shorter OR time (− 35 min; p = 0.01). Index and total costs were 20% lower in the TL than in the UT group (p < 0.001). Cost/QALY was 65% lower (492,174.6 vs. 963,391.4), and 2-year QALY gain was 40% higher, in the TL than UT group (0.15 vs. 0.10; p = 0.02). Multivariate model showed TL fusions had lower total cost (p = 0.001) and higher QALY gain (p = 0.03) than UT fusions. Conclusion: In Schwab type N or L curves, TL fusions showed lower 2-year cost and improved QALY gain without increased reoperation rates or length of stay than UT fusions. Level of evidence: III.
Open Access
Expectations of clinical improvement following corrective surgery for adult cervical deformity based on functional disability at presentation.
(Spine deformity, 2024-07) Passias, Peter G; Onafowokan, Oluwatobi O; Joujon-Roche, Rachel; Smith, Justin; Tretiakov, Peter; Buell, Thomas; Diebo, Bassel G; Daniels, Alan H; Gum, Jeffrey L; Hamiltion, D Kojo; Soroceanu, Alex; Scheer, Justin; Eastlack, Robert K; Fessler, Richard G; Klineberg, Eric O; Kim, Han Jo; Burton, Douglas C; Schwab, Frank J; Bess, Shay; Lafage, Virginie; Shaffrey, Christopher I; Ames, Christopher; International Spine Study Group
Purpose
To assess impact of baseline disability on HRQL outcomes.
Methods
CD patients with baseline (BL) and 2 year (2Y) data included, and ranked into quartiles by baseline NDI, from lowest/best score (Q1) to highest/worst score (Q4). Means comparison tests analyzed differences between quartiles. ANCOVA and logistic regressions assessed differences in outcomes while accounting for covariates (BL deformity, comorbidities, HRQLs, surgical details and complications).
Results
One hundred and sixteen patients met inclusion (Age:60.97 ± 10.45 years, BMI: 28.73 ± 7.59 kg/m², CCI: 0.94 ± 1.31). The cohort mean cSVA was 38.54 ± 19.43 mm and TS-CL: 37.34 ± 19.73. Mean BL NDI by quartile was: Q1: 25.04 ± 8.19, Q2: 41.61 ± 2.77, Q3: 53.31 ± 4.32, and Q4: 69.52 ± 8.35. Q2 demonstrated greatest improvement in NRS Neck at 2Y (-3.93), compared to Q3 (-1.61, p = .032) and Q4 (-1.41, p = .015). Q2 demonstrated greater improvement in NRS Back (-1.71), compared to Q4 (+ 0.84, p = .010). Q2 met MCID in NRS Neck at the highest rates (69.9%), especially compared to Q4 (30.3%), p = .039. Q2 had the greatest improvement in EQ-5D (+ 0.082), compared to Q1 (+ 0.073), Q3 (+ 0.022), and Q4 (+ 0.014), p = .034. Q2 also had the greatest mJOA improvement (+ 1.517), p = .042.
Conclusions
Patients in Q2, with mean BL NDI of 42, consistently demonstrated the greatest improvement in HRQLs whereas those in Q4, (NDI 70), saw the least. BL NDI between 39 and 44 may represent a disability "Sweet Spot," within which operative intervention maximizes patient-reported outcomes. Furthermore, delaying intervention until patients are severely disabled, beyond an NDI of 61, may limit the benefits of surgery.
Open Access
Predictors of Delayed Clinical Benefit Following Surgical Treatment for Low Grade Spondylolisthesis.
(Spine, 2024-08) Djurasovic, Mladen; Carreon, Leah Y; Bisson, Erica F; Chan, Andrew K; Bydon, Mohamad; Mummaneni, Praveen V; Foley, Kevin T; Shaffrey, Christopher I; Potts, Eric A; Shaffrey, Mark E; Coric, Domagoj; Knightly, John J; Park, Paul; Wang, Michael Y; Fu, Kai-Ming; Slotkin, Jonathan R; Asher, Anthony L; Virk, Michael S; Chou, Dean; Haid, Regis W; Glassman, Steven D
Study design
Retrospective review of prospectively collected data.
Objective
To investigate what factors predict delayed improvement after surgical treatment of low grade spondylolisthesis.
Summary of background data
Lumbar surgery leads to clinical improvement in the majority of patients with low grade spondylolisthesis. Most patients improve rapidly after surgery, but some patients demonstrate a delayed clinical course.
Methods
The Quality and Outcomes Database (QOD) was queried for grade 1 spondylolisthesis patients who underwent surgery who had patient reported outcome measures (PROMs) collected at baseline, 3-, 6- and 12-months, including back and leg pain numeric rating scale (NRS), Oswestry Disability Index (ODI), and EuroQol-5D (EQ-5D). Patients were stratified as "Early responders" reaching MCID at 3 months and maintaining improvement through 12 months and "Delayed responders" not reaching MCID at 3 months but ultimately reaching MCID at 12 months. These two groups were compared with respect to factors which predicted delayed improvement.
Results
Of 608 patients enrolled, 436 (72%) met inclusion criteria for this study. Overall, 317 patients (72.7%) reached MCID for ODI at 12 months following surgery. Of these patients, 249 (78.5%) exhibited a rapid clinical improvement trajectory and had achieved ODI MCID threshold by the 3-month postop follow-up. 68 patients (21.4%) showed a delayed trajectory, and had not achieved ODI MCID threshold at 3 months, but did ultimately reach MCID at 12-month follow-up. Factors associated with delayed improvement included impaired preoperative ambulatory status, better baseline back and leg pain scores, and worse 3-month leg pain scores (P<0.01).
Conclusions
The majority of patients undergoing surgery for low grade spondylolisthesis reach ODI MCID threshold rapidly, within the first three months after surgery. Factors associated with a delayed clinical course include impaired preoperative ambulation status, relatively better preoperative back and leg pain, and persistent leg pain at 3 months.
Open Access
Population-level impact of adjuvant trastuzumab emtansine on the incidence of metastatic breast cancer: an epidemiological prediction model of women with HER2-positive early breast cancer and residual disease following neoadjuvant therapy.
(Breast cancer (Tokyo, Japan), 2024-01) Williamson, Mellissa; Press, David J; Hansen, Svenn Alexander; Tomar, Akanksha; Jhuti, Gurleen Singh; Revil, Cedric; Gururaj, Kaustubh
Purpose
Treating early-stage breast cancer (eBC) may delay or prevent subsequent metastatic breast cancer (mBC). In the phase 3 KATHERINE study, women with human epidermal growth factor receptor 2 (HER2)-positive eBC with residual disease following neoadjuvant therapy containing trastuzumab and a taxane experienced 50% reductions in disease recurrence or death when treated with adjuvant trastuzumab emtansine (T-DM1) vs adjuvant trastuzumab. We predicted the population-level impact of adjuvant T-DM1 on mBC occurrence in five European countries (EU5) and Canada from 2021-2030.
Methods
An epidemiological prediction model using data from national cancer registries, observational studies, and clinical trials was developed. Assuming 80% population-level uptake of adjuvant treatment, KATHERINE data were extrapolated prospectively to model projections. Robustness was evaluated in alternative scenarios.
Results
We projected an eligible population of 116,335 women in Canada and the EU5 who may be diagnosed with HER2-positive eBC and have residual disease following neoadjuvant therapy from 2021-2030. In EU5, the cumulative number of women projected to experience relapsed mBC over the 10-year study period was 36,009 vs 27,143 under adjuvant trastuzumab vs T-DM1, a difference of 8,866 women, equivalent to 25% fewer cases with the use of adjuvant T-DM1 in EU5 countries from 2021-2030. Findings were similar for Canada.
Conclusion
Our models predicted greater reductions in the occurrence of relapsed mBC with adjuvant T-DM1 vs trastuzumab in the indicated populations in EU5 and Canada. Introduction of T-DM1 has the potential to reduce population-level disease burden of HER2-positive mBC in the geographies studied.