6-month Time Point Research Articles

Clinically significant outcome thresholds and rates of achievement by shoulder arthroplasty type and preoperative diagnosis

BackgroundClinically significant outcome (CSO) benchmarks have been previously established for shoulder arthroplasty by assimilating preoperative diagnoses and arthroplasty types. The purpose of this study was to establish unique CSO thresholds and compare the time-to-achievement of these for reverse shoulder arthroplasty (RSA) for osteoarthritis (GHOA), RSA for rotator cuff arthropathy (RCA), and total shoulder arthroplasty (TSA) for GHOA. Materials & MethodsConsecutive patients who underwent elective RSA for GHOA, TSA for GHOA, or RSA for RCA between February 2015 and May 2020, with 2-year minimum follow-up, were retrospectively identified from a prospectively maintained single surgeon registry. The American Shoulder and Elbow Surgeons (ASES) score was administered preoperatively and postoperatively at 2-week, 6-week, 3-month, 6-month, 1-year, and 2-year timepoints. Satisfaction and subjective overall improvement anchor questionnaires were administered at the time of final follow-up. Distribution-based methods was used to calculate the Minimal Clinically Important Difference (MCID), and anchor-based methods were used to calculate the Substantial Clinical Benefit (SCB) and the Patient Acceptable Symptom State (PASS) for each patient group. Median time to achievement, individual incidence of achievement at each time point, and cumulative incidence of achievement calculated using Kaplan-Meier survival curve analysis with interval censoring were compared between groups for each CSO. Cox-regression analyses were also performed to determine which patient factors were significantly associated with early or delayed achievement of CSOs. ResultsThere were 471 patients eligible for study analysis: 276 RSA for GHOA, 107 TSA for GHOA, 88 RSA for RCA. The calculated MCID, SCB, and PASS scores differed for each group. There were no significant differences in median time to achievement of any CSO between groups. Log-rank testing revealed that cumulative achievements significantly differed between groups for MCID (P = 0.014) but not for SCB (P = 0.053) or PASS (P = 0.620). On cox regression analysis, TSA patients had earlier achievement of SCB, whereas TSA and RSA for GHOA patients had earlier achievement of MCID. At two-years, a significantly higher percentage of RSA for GHOA patients achieved MCID and SCB compared to RSA for RCA (MCID:100%, 95.5%, P = 0.003, SCB:94.6%, 86.4%, P = 0.036). ConclusionCalculated CSO thresholds differ according to preoperative diagnosis and shoulder arthroplasty type. Patients undergoing TSA and RSA for GHOA achieve CSOs earlier than RSA for RCA patients, and a significantly higher percentage of RSA for GHOA patients achieve CSOs by 2 years compared to RSA for RCA patients.

Comparative analysis of the in vivo kinetic properties of various bone substitutes filled into a peri-implant canine defect model.

Deproteinized bovine bone or synthetic hydroxyapatite are 2 prevalent bone grafting materials used in the clinical treatment of peri-implant bone defects. However, the differences in bone formation among these materials remain unclear. This study evaluated osteogenesis kinetics in peri-implant defects using 2 types of deproteinized bovine bone (Bio-Oss® and Bio-Oss/Collagen®) and 2 types of synthetic hydroxyapatite (Apaceram-AX® and Refit®). We considered factors including newly generated bone volume; bone, osteoid, and material occupancy; and bone-to-implant contact. A beagle model with a mandibular defect was created by extracting the bilateral mandibular third and fourth premolars. Simultaneously, an implant was inserted into the defect, and the space between the implant and the surrounding bone walls was filled with Bio-Oss, Bio-Oss/Collagen, Apaceram-AX, Refit, or autologous bone. Micro-computed tomography and histological analyses were conducted at 3 and 6 months postoperatively (Refit and autologous bone were not included at the 6-month time point due to their rapid absorption). All materials demonstrated excellent biocompatibility and osteoconductivity. At 3 months, Bio-Oss and Apaceram-AX exhibited significantly greater volumes of formation than the other materials, with Bio-Oss having a marginally higher amount. However, this outcome was reversed at 6 months, with no significant difference between the 2 materials at either time point. Apaceram-AX displayed notably slower bioresorption and the largest quantity of residual material at both time points. In contrast, Refit had significantly greater bioresorption, with complete resorption and rapid maturation involving cortical bone formation at the crest at 3 months, Refit demonstrated the highest mineralized tissue and osteoid occupancy after 3 months, albeit without statistical significance. Overall, the materials demonstrated varying post-implantation behaviors in vivo. Thus, in a clinical setting, both the properties of these materials and the specific conditions of the defects needing reinforcement should be considered to identify the most suitable material.

A biomechanical assessment of tissue-engineered polymer neo-uteri after orthotopic implantation

To assess the invivo biomechanical maturation of tissue-engineered neo-uteri that have previously supported live births in a rabbit model. Nonclinical animal study. University-based research laboratory. Eighteen adult female rabbits. Biodegradable poly-DL-lactide-co-glycolide-coated polyglycolic acid scaffolds seeded with autologous uterine-derived endometrial and myometrial cells. Nonseeded scaffolds and seeded, tissue-engineered neo-uteri were implanted into one uterine horn of rabbits for 1, 3, or 6 months, excised, and biomechanically assessed in comparison to native uterine tissue. Tensile stress-relaxation testing, strain-to-failure testing, and viscoelastic modeling. By evaluating the biomechanical data with several viscoelastic models, it was revealed that tissue-engineered uteri were more mechanically robust than nonseeded scaffolds. For example, the 10% instantaneous stress of the tissue-engineered neo-uteri was 2.1 times higher than the nonseeded scaffolds at the 1-month time point, 1.6 times higher at the 3-month time point, and 1.5 times higher at the 6-month time point. Additionally, as the duration of implantation increased, the engineered constructs became more mechanically robust (e.g., 10% instantaneous stress of the tissue-engineered neo-uteri increased from 22 kPa at 1 month to 42 kPa at 6 months). Compared with native tissue values, tissue-engineered neo-uteri achieved or surpassed native tissue values by the 6-month time point. The present study evaluated the mechanical characteristics of novel tissue-engineered neo-uteri that have previously been reported to support live births in the rabbit model. We demonstrate that the biomechanics of these implants closely resemble those of native tissue, giving further credence to their development as a clinical solution to uterine factor infertility.

Quality of life measures and cost analysis of biologic versus synthetic mesh for ventral hernia repair: The Preventing Recurrence in Clean and Contaminated Hernias randomized clinical trial

BackgroundAlthough the most durable method for ventral hernia repairs involves using mesh, whether to use biologic mesh versus synthetic mesh remains controversial. This study aimed to compare synthetic and biologic meshes with respect to patient-reported quality of life scores and costs after ventral hernia repair surgeries. MethodsThis study is part of the Preventing Recurrence in Clean and Contaminated Hernias (PRICE) pragmatic randomized control trial conducted from March 2014 through October 2018. Patients were randomized 1:1 to undergo ventral hernia repair using either a biologic or synthetic mesh. The coprimary outcomes were 2-year changes in Visual Analog Scale, Activities Assessment Scale, Hernia-Related Quality-of-Life Survey, and Short-Form 36 Health Survey (SF-36) quality-of-life scores from repair. The secondary outcome was the overall cost per patient. ResultsAmong the 165 patients included in the study, 82 were randomized to biologic meshes and 83 to synthetic meshes. There were no significant differences in the performance between the 2 mesh types with regard to quality-of-life measures using a mixed model approach. This result was consistent even when performing subgroup analysis based on wound contamination. However, nonparametric tests comparing the differences in quality-of-life measures from preoperative to 24-month postoperative timepoints revealed that the synthetic mesh group showed a greater reduction in disability than biologic mesh for the SF-36 (median [interquartile range] of 20 [5–30] vs 6 [1–20], P = .025). This difference was due to reductions in the physical role limitations (62 [0–100] vs 0 [0–50], P = .018) and the pain (38 [12–50] vs 12 [0–25], P = .012) domains of the SF-36. Overall cost per patient was greater for biologic meshes (mean [95% confidence interval] of $80,420 [$66,485–$94,355] vs $61,036 [$48,946–$73,125], P = .038), regardless of insurance type. ConclusionIn this randomized clinical trial, there were no differences in changes in quality-of-life scores at the 2-year timepoint except for the SF-36, where the synthetic mesh may be associated with less pain and physical role limitations than the biologic mesh. Overall costs per patient were less for synthetic than biologic mesh.

Influential factors of non-motor symptoms prognosis in Parkinson's disease patients undergoing deep brain stimulation

Objective: To investigate the effects of electrode activated contact location, volume of tissue activated (VTA) and age on non-motor symptoms, such as emotional symptoms and cognitive function, in Parkinson's disease (PD) patients with deep brain stimulation (DBS). Methods: PD patients who underwent DBS of subthalamic nucleus (STN) at the Department of Functional Neurosurgery of Beijing Tiantan Hospital from September 1, 2020 to August 31, 2022 were retrospectively enrolled. The International Parkinson and Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Hamilton Anxiety Scale (HAMA), Hamilton Depression Scale (HAMD), Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination Scales (MMSE) were used at the preoperative, 1-month and 12-month postoperative time points. In this study, patients were divided into middle-aged (age<60 years,n=39) and elderly (age≥60 years,n=62) groups to investigate the effect of age factor on the clinical outcome of surgery. Lead-DBS software was used to convert the patients' electrode reconstruction results into Montreal standard space, and the patients were divided into sensorimotor(n=43) and combined groups(n=53) according to the distribution of activation contact locations in the subzones of the STN. In addition, the patients were divided into a cognitive improvement group(n=57)and a cognitive deterioration group(n=44) based on the results of MoCA at 12 months. The positional information of the electrode activation contacts was collected and the VTA was calculated to analyze the effects on electrode activation electroshock location and activated tissue volume on patients' non-motor symptoms. Results: A total of 101 patients with PD were enrolled, including 46 males and 55 females, aged (62.6±8.4) years. Middle-aged patients had significantly higher MoCA scores, delayed recall scores, attention scores, and naming scores than older patients at 12 months postoperatively (all P<0.05). At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score were -1.77%±20.36%, 39.65%±42.91% and 36.23%±45.45% respectively in sensorimotor group. At 12-month follow-up, the improvement rate of MoCA score, HAMA score and HAMD score was 11.69%±22.24%, 16.62%±68.10% and 2.30%±95.04% respectively in the combined group, and the difference between the two groups was statistically significant (MoCA: P=0.002; HAMA: P=0.040; HAMD: P=0.033) The distribution of VTA in the sensory motor area and marginal area of the left hemisphere STN in patients with improved cognitive function was significantly smaller than that in the deterioration group [(60.53±52.04)mm³vs (84.55±61.00)mm³, P=0.035; (41.81±33.36)mm³vs (59.05±45.46)mm³, P=0.030]. Conclusion: The effect of STN-DBS on emotional symptoms and cognitive function in PD patients is influenced by various factors and is closely related to the patient's age, electrode activation contact location and VTA.

Outcomes and predictors of treatment failure after anti-reflux mucosectomy for management of gastroesophageal reflux disease

BackgroundAnti-reflux mucosectomy is a novel endoscopic treatment for gastroesophageal reflux disease that serves as an intermediate therapy between medical and surgical intervention. We aimed to evaluate outcomes and identify predictors of treatment failure in patients requiring anti-reflux mucosectomy. MethodsA prospective quality database was retrospectively reviewed. Upper endoscopy, pH testing, and functional luminal impedance planimetry were obtained at preop and 1 year post-operation. Quality of life outcomes were assessed by Gastroesophageal Reflux Disease–Health Related Quality of Life, Reflux Symptom Index, and dysphagia scores preoperatively and up to 5 years postoperatively. ResultsFifty-eight patients requiring anti-reflux mucosectomy were analyzed between 2016 and 2023. Preop Gastroesophageal Reflux Disease–Health Related Quality of Life mean scores improved at all time points 3 weeks to 2 years postoperatively (all P < .05). Preop mean Reflux Symptom Index scores also significantly improved at 6-month, 1-year, and 2-year timepoints (all P < .05). Dysphagia at 3 weeks was higher than preop scores (1.2 vs 2.1, P < .01) but returned to baseline. Upon follow-up, 43 patients (74.1%) had symptom improvement off proton pump inhibitors, 29 of whom reported complete symptom resolution. Out of 58 patients, 31 (53.4%) failed treatment due to DeMeester score (n = 22), erosive esophagitis (n = 2), Gastroesophageal Reflux Disease–Health Related Quality of Life ≥13 (n = 4), or <70% symptom resolution in the absence of pH or survey data (n = 3). Current smoking status was predictive of treatment failure (odds ratio 3.52, P < .031). Body mass index, DeMeester score, acid exposure time, and hiatal hernia ≤2 cm were not associated with treatment failure. ConclusionAnti-reflux mucosectomy is associated with significant improvement in quality of life; however, symptom resolution may not correlate with objective reflux control. Smoking is a predictor of treatment failure and should be considered in patient selection.

Serial 18F-Florbetaben Positron Emission Tomography and Cardiac Magnetic Resonance Imaging in the Evaluation of Systemic Light Chain Cardiac Amyloidosis Enhances Diagnostic and Response Assessment Accuracy

Background: There is a need for improved assessment of cardiac involvement in systemic amyloidosis by non-invasive methods to increase accuracy of diagnosis and to assist with monitoring and prognostication of the condition. We have previously shown that 18F-florbetaben, a novel amyloid binding radiotracer, can identify the presence of cardiac amyloid in positron emission tomography (PET/CT) imaging. We aim to evaluate the role of imaging with 18F-florbetaben PET/CT, cardiac magnetic resonance (CMR) and transthoracic echocardiography (TTE) in the initial diagnosis and response assessments of patients with light chain (AL) cardiac amyloidosis (AL-CA). Methods: Twelve patients diagnosed with systemic AL amyloidosis and proven or suspected cardiac involvement, between June 2018 and December 2020, were prospectively recruited to undergo 18F-florbetaben PET/CT, CMR and TTE imaging prior to commencement and 6 months post systemic therapy. 40-minute dynamic and static PET/CT images were acquired following 18F-florbetaben radiotracer injection. Left ventricular myocardial standardised uptake values (SUV) were recorded and used to graph time activity curves (TAC). Percentage myocardial tracer retention (MTR) was derived from the dynamic data. CMR was performed using a 3.0T MRI system. The Modified Look-Locker Inversion recovery (MOLLI) method was utilized to generate native and gadolinium-enhanced T1 mappings, which were then used to calculate the global extracellular volume (ECV). PET and CMR indices were compared to 2D-speckled TTE metrics and cardiac biomarkers (BNP, cTnI) using Pearson Correlation for statistical analysis. Overall survival was calculated using the Kaplan-Meir method. Results: Participant characteristics were as per table 1. Five deaths occurred during the study, all due to progressive AL amyloidosis; with 4 of these occurring prior to the planned second imaging timepoint. Two-year survival was 58.3%, with a mean overall survival of 7.3 years (95% CI 4.08 - 10.52). All patients had a baseline PET/CT; 8 were able to have a concurrent CMR. The remaining 4 were unable have a CMR due to incompatible devices or were clinically unwell at the time. Seven patients went on to have a repeat PET/CT and 5 had comparative CMR imaging 6 months after commencing treatment. Baseline 18F-florbetaben PET/CT scans demonstrated characteristic AL-CA patterns of prolonged myocardial tracer retention TAC in 10 out of the 12 patients (Figure 1). Patients' 8 and 12 TACs (highlighted with arrows in Figure 1) did not follow the usual AL-CA MTR pattern and their MTRs were calculated to be below a previously defined threshold of ≥40% for the presence of cardiac amyloid. This prompted review of the diagnosis of AL-CA in these patients and both were found to have alternative causes for the TTE and cardiac biomarker abnormalities which were initially interpreted as AL-CA. Analysis of the different imaging metrics showed significant correlation between MTR and ECV (r=0.575; p=0.04) as well as ECV and GLS (r=0.62; p=0.024). ECV also correlated with BNP (r=0.637; p=0.019) as did GLS and BNP (r=0.678; p=0.002). There was no association between MTR and cardiac biomarkers. 8 patients were assessable at the 6-month timepoint; only 1 patient had a cardiac response at 6 months by the International Society of Amyloidosis (ISA) criteria and they demonstrated a &amp;gt;10% reduction in MTR on follow-up PET/CT. Two patients had stable cardiac disease as per ISA criteria: 1 had &amp;gt;10% reduction in MTR and went on to achieve subsequent cardiac response without further therapy; the other had an increase in MTR by 18.5% and went on to salvage ASCT for suboptimal haematological and cardiac responses (partial remission and stable organ disease). Four patients had cardiac progression by ISA criteria with a worsening of MTR by at least 15% (mean=19.1%). Conclusion: Patients with AL-CA display prolonged 18F-florbetaben retention on PET/CT imaging which also appears useful to exclude the presence of cardiac amyloidosis in patients with co-existent cardiac conditions. Preliminary data supports the role of 18F-florbetaben PET/CT in cardiac response assessment, but further studies are required to determine the optimal timing of follow up imaging, which is likely to be beyond the 6-month time point, and to determine clinically significant MTR ranges for monitoring and prognostication.

Post-Transplant T Cell Clonotype Diversity Is Associated with Survival in Patients with TP53-Mutated Acute Myeloid Leukemia

Background TP53 mutations are associated with unfavorable outcomes in various cancer types and present an obstacle to achieving sustained remission in acute myeloid leukemia (AML). Even with allogeneic hematopoietic stem cell transplantation (HSCT), the risk of relapse approximates 80%, with dismal long-term survival. This could imply methods of immune escape in TP53 mutated leukemias that allow them to evade the graft-versus-leukemia (GVL) effect, which is a critical mechanism of disease control with HSCT. This study investigates the dynamics of immune reconstitution at single-cell resolution in TP53-mutated AML at pre- and multiple post-HSCT timepoints in patients who either remain in long-term remission or relapse following HSCT. Methods We collected 26 longitudinal bone marrow aspirates and 1 peripheral blood sample from 12 patients with TP53-mutated AML who underwent HSCT at the Dana-Farber Cancer Institute between 2015-21. All patients received HLA-matched T-cell replete HSCT in morphologic remission, with standard tacrolimus/methotrexate-based prophylaxis and peripheral blood stem cells. We categorized the patients into two cohorts based on their treatment response: long-term remission (&amp;gt;3.5 years, cohort 1, n=4) or relapse (cohort 2, n=8). We performed paired 5' single-cell RNA and T cell receptor (TCR) sequencing on sorted viable mononuclear from each sample and CD3+ T cells from selected samples using 10x Genomics procedures. In total, we analyzed 44 samples (27 mononuclear, 17 CD3+), resulting in 250,640 high-quality single-cell transcriptomes, including 137,649 T cells and NK cells. Data analysis was performed using Cell Ranger Multi (10x Genomics) and R 4.3 with the tidyverse 2.0, Seurat 5.1, and scRepertoire 1.1 packages. Results We focused our initial analysis on the 2-6-month post-HSCT period that is critical for immune reconstitution. This included eight samples from seven patients in the two cohorts (1: remission, 2: relapse, pink box in Figure 1). Of these 7 patients, 4 were in the relapse cohort, with these relapses occurring &amp;gt;4 months post-HSCT. No significant difference in T-cell chimerism was seen between these 7 patients in this 2-6 month period. Based on canonical gene expression signatures, we annotated cell types and selected T cells for further evaluation (Figure 2). First, we found that the CD4/CD8 ratio differed between the cohorts, indicating a relative CD8+ T cell expansion in the relapse cohort (cohort 1: 1.69, cohort 2: 0.55, P&amp;lt;0.0001). Second, we found lower TCR diversity in the relapse cohort (inverse Simpson index, cohort 1: 234.6, cohort 2: 83.0, P&amp;lt;0.0001). This difference remained significant when subsampling the same number of T cells per patient and when restricting all samples to the 3 to 4-month timepoint. Considering the disparity in CD8 T cell numbers between the cohorts, we also analyzed repertoire diversity, specifically in CD8+ T cells, and found that the observed significance persisted. To further investigate TCR diversity, we overlaid T cell clonotypes (cells that share the same TCR sequence) in a UMAP visualization, which highlighted increased hyperexpanded CD8+ T cells in the relapse cohort (Figure 2). Finally, we found that greater clonotype expansion was correlated with the expression of key T cell genes, including CD8A, CD8B, PRF1, NKG7, and GZMA. These results suggest that cytotoxic CD8+ T cells link lower TCR diversity to the likelihood of disease relapse. Conclusions By performing deep analysis of single-cell gene expression linked to TCR clonotypes, we discover new insights into the biology of hematopoietic reconstitution after HSCT of patients with TP53-mutated AML. Despite having analyzed a limited number of samples, we find that patients who remain in long-term remission have significantly higher CD8+ TCR diversity between 2-6 months post-HSCT, while those who relapsed between 5-18 months post-HSCT showed lower TCR diversity and hyperexpanded CD8+ clones at the same timepoints. This work suggests that early post-HSCT TCR diversity could be a biomarker associated with GVL and warrants further study. In ongoing and future analyses, we will mine the current dataset for further insights into the factors influencing survival in TP53-mutated AML patients. We also plan to extend the measurement of TCR diversity as a predictor of survival for validation in a larger cohort.

NCOG-36. IMPACT OF COLLAGEN TILE BRACHYTHERAPY AS TREATMENT FOR RECURRENT GLIOBLASTOMAS ON FUNCTIONAL STATUS AND QUALITY OF LIFE

Abstract BACKGROUND Recurrent glioblastoma is an aggressive disease with dismal prognosis despite advances in standard therapy, making the maintenance of functional status and quality of life (QOL) in patients an important endpoint during treatment. Here, we report functional status (KPS) and QOL metrics (LASA and FACT-Br) at 6-months post-treatment for recurrent glioblastoma patients treated with maximal safe resection followed by intraoperative placement of collagen tile brachytherapy with Cesium-131 (Surgically Targeted Radiation Therapy or STaRT), a novel brachytherapy carrier. OBJECTIVE To assess the impact of STaRT on KPS and QOL among patients with recurrent glioblastoma (rGBM) at 6-months post-treatment. METHODS Patients were treated between 10/2020 and 05/2023 as part of a multi-institutional registry study (NCT#04427384). KPS was used to measure functional status. Linear Analog Self-Assessment (LASA) and Functional Assessment of Cancer Therapy – Brain (FACT-Br) were used to measure QOL. All assessments were collected at pre-surgery, and 1,3, and 6-months post-treatment. RESULTS 57 rGBM patients were treated on the Registry between 10/2020 and 05/2023. Of the 57 participants, 47 participants remain in the study, with 21 participants reaching the 6-month time point (5 exits, 5 deaths). Median age was 60 years (range 28-81). Methylguanine methyltransferase (MGMT) promoter was methylated in 17.5%, unmethylated in 38.5%, and unknown in 44%. Gross total resection was achieved in 72% of participants. Median KPS was 80% (range 40%-100%) at screening versus 70% (range 40%-90%) at 6 months post-treatment. Median LASA was 37 (range 8-50) at pre-surgery versus 34 (range 5-48) at 6-months post-treatment. Minimally important differences (MID) were noted between pre-surgery (136.9 ± 29.5) and 6-months post-treatment (112.5 ± 35.7) for the FACT-Br Total Score. CONCLUSION This interim data analysis supports further investigation of STaRT as a treatment for recurrent glioblastomas as a means of providing stable functional status and quality of life.

Noninfectious Outcomes of Intravitreal Antibiotic Steroid Injection and Topical Nonsteroidal Antiinflammatory Drugs Versus Triple Drop Therapy After Cataract Surgery

To compare noninfectious outcomes of intravitreal antibiotic steroid (IVAS) injection (moxifloxacin-triamcinolone) and postoperative topical nonsteroidal antiinflammatory drugs (NSAID) with a standard 3-drop therapy (TDT) regimen (topical antibiotic, steroid, and NSAID) in patients after cataract surgery. Retrospective comparative clinical cohort study. In 3 study centers in the United States, a total of 2143 eyes (N = 2143 patients) underwent cataract surgery with IVAS-NSAID or TDT between 2017 and 2022. Preoperative data were included, including patients' age, iris color, medical history, and ocular history. Postoperative data, including best-corrected visual acuity, intraocular pressure (IOP), and the need for IOP-lowering medications, were recorded at 1-week, 1-month, and 6-month time points. The primary outcome measures were postoperative complications, defined as persistent anterior chamber inflammation, persistent corneal edema (PCE), rebound inflammation, and cystoid macular edema, were compared between the 2 groups. There were 1079 eyes in the IVAS-NSAID group and 1064 eyes in the TDT group. Best-corrected visual acuity and IOP were similar between IVAS-NSAID and TDT eyes at all time points. A portion (11.6%) of TDT eyes experienced postoperative complications compared with 6.5% in IVAS-NSAID eyes (P < .001). Femtosecond laser-assisted cataract surgery was associated with increased rates of PCE in IVAS-NSAID eyes, and eyes with dark irides had a higher incidence of cystoid macular edema, PCE, and rebound inflammation in the IVAS-NSAID group. The IVAS-NSAID regimen overall had similar postoperative outcomes and fewer complications compared with the TDT regimen. IVAS-NSAID may be considered a safe alternative to topical regimens in non-femtosecond laser-assisted cataract surgery and patients with light irides.

One-year antibody durability induced by EuCorVac-19, a liposome-displayed COVID-19 receptor binding domain subunit vaccine, in healthy Korean subjects

ObjectiveEuCorVac-19 (ECV-19), an adjuvanted liposome-displayed receptor binding domain (RBD) COVID-19 vaccine, previously reported interim Phase 2 trial results showing induction of neutralizing antibodies 3 weeks after prime-boost immunization. The objective of this study was to determine the longer-term antibody response of the vaccine. MethodsTo assess immunogenicity 6 and 12 months after vaccination, participants in the Phase 2 trial (NCT04783311) were excluded if they: 1) withdrew, 2) reported COVID-19 infection or additional vaccination, or 3) exhibited increasing Spike (S) antibodies (representing possible non-reported infection). Following exclusions, of the 197 initial subjects, anti-S IgG antibodies and neutralizing antibodies were further assessed in 124 subjects at the 6-month timepoint, and 36 subjects at the 12-month timepoint. ResultsMedian anti-S antibody half-life was 52 days (interquartile range [IQR]:42-70), in the “early” period from 3 weeks to 6 months, and 130 days (IQR:97-169) in the “late” period from 6 to 12 months. There was a negative correlation between initial antibody titer and half-life. Anti-S and neutralizing antibody responses were correlated. Neutralizing antibody responses showed longer half-lives; the early period had a median half-life of 120 days (IQR:81-207), and the late period had a median half-life of 214 days (IQR:140-550). ConclusionThese data establish antibody durability of ECV-19, using a framework to analyze COVID-19 vaccine-induced antibodies during periods of high infection.

Firstline Treatment with Ruxolitinib Versus Best Available Therapy in Patients with Polycythemia Vera: Pre-Specified Interim Analysis of the Randomized Phase 2b Ruxobeat Clinical Trial of the German Study Group for Myeloproliferative Neoplasms (GSG-MPN)

Introduction: Polycythemia vera (PV) is characterized by trilineage blood cell expansion, PV-associated symptoms, and the risk of thromboembolic complications, progression to post-PV myelofibrosis, and acute leukemia. Cytoreductive treatment with hydroxyurea (HU) or ropeginterferon-alpha is approved in EU for the treatment of high-risk patients (pts) with PV. In addition, ruxolitinib (RUX) is approved for HU-intolerant/-resistant PV. However, RUX vs. best available therapy (BAT) has not been investigated as first-line treatment of pts with untreated PV. We hypothesized that RUX may have higher efficacy in such early-line PV pts. Methods: The clinical trial entitled “Ruxolitinib versus Best Available Therapy in pts with high-risk PV or high-risk ET” (RuxoBEAT; NCT02577926) is a multicenter, open-label, two-arm phase-IIb trial with a target population of 190 pts in each stratum. Crossover from BAT to RUX is possible in eligible pts after 6 months. Pts with PV in the RUX arm received a starting dose of 10 mg BID and may increase their dose up to 20 mg BID. The primary endpoint is the clinicohematologic complete response (CR) rate at month 6, as defined by Barosi et al (Blood 2009), using a strict score of zero for the four symptoms by patient-reported outcome measures (PROM, Table 2) and an adjusted level alpha = 0.005 at a power of 80%. Secondary endpoints include overall response rate (CR+PR), freedom from phlebotomy, changes in blood counts, spleen size, and PROM, using p values descriptively. The interim trial data were recently reviewed by the DMC, and, due to the low likelihood of reaching the primary endpoint (CR rate improvement), the DMC has recommended that the trial should continue without recruitment of new pts. Therefore, this pre-specified interim analysis was performed after 78 (instead of 95) PV pts were randomized 1:1 to RUX vs. BAT. A maximum of 6 weeks of previous PV-directed therapy was allowed. Differences between RUX and BAT at month 6 and between baseline and end of month 6 data for each treatment were calculated using Fisher´s exact test/ McNemar Test (for unpaired/ paired binary variables) or the Mann-Whitney-U test/ Wilcoxon signed-rank test (for unpaired/ paired ordered or continuous variables). Results: 78 first-line pts (33% were pre-treated for a median of 22 days [range 1-42]) were included in the intention-to-treat set (n=44 vs 34 randomized to RUX vs. BAT, resp.) and analyzed at the 6-month time point. Baseline characteristics are listed in Table 1. In pts on RUX or BAT, CR rates at 6 months were comparable (2.3% and 2.9%, p=1.0), while overall response (CR+PR) rates were 77.3% with RUX and 55.9% with BAT (p=0.054). Also, at month 6 (Table 2), pts on RUX showed significantly lower hematocrit (40.8% vs 42.1%, p=0.046), and PROM symptom points for pruritus (1 vs 4, p=0.001) and fatigue (2.5 vs 5, p=0.031), and a trend towards less headache, abdominal discomfort, and weight loss, while the number of platelets was lower with BAT vs. RUX (254/nl vs 386/nl, p=0.013). There was no difference between RUX and BAT in the number of white blood cells (WBC), spleen size, or other symptoms at this time point. When each treatment arm was analyzed separately for changes between baseline and month 6, RUX treatment significantly reduced platelet counts, WBC, hemoglobin and hematocrit, phlebotomy rates, spleen size and fraction of pts with splenomegaly (Table 2), and significantly improved PROMs for pruritus, early satiety, and quality of life. During the same time period, BAT significantly reduced platelet counts, WBC, hematocrit, and phlebotomy rates, but failed to impact on hemoglobin, spleen size, fraction of pts with splenomegaly, or any of the symptoms (Table 2). Safety analysis revealed 301 adverse events (AE) in both assigned treatment groups, including 153 AE in the RUX and 148 AE in the BAT group (11.8% and 8.1% grade ≥3, resp.). There was no significant difference in the percentage of grade ≥3 AE between both groups (p=0.358), and there were no consistent patterns of grade ≥3 AE in either of the two arms. Conclusion: In this interim analysis, first-line treatment with ruxolitinib for 6 months in high-risk pts with PV led to clinically meaningful improvements in overall response, hemoglobin and hematocrit, phlebotomy rates, splenomegaly, and patient-reported pruritus and fatigue severity, while BAT only improved platelet counts, WBC, hematocrit, and phlebotomy rates, without having an impact on symptoms.

Mitochondrial Reprogramming By Bcl-2 Inhibitor Venetoclax Enhances αCD19 CAR-T Cell Fitness and Anti-Tumor Efficacy

Introduction Patients undergoing anti-CD19 chimeric antigen receptor T cell (CAR T) therapy for the treatment of aggressive B-cell non-Hodgkin lymphomas (B-NHL) can expect a complete response rate of merely 43-68%. Insubstantial clinical responses to CAR T therapy and a small window of survival for patients facing relapsed/refractory (R/R) disease highlights the critical need for improvement of CAR T therapy in aggressive B-NHL cases. Recent findings suggest that enriching for a CD8 + T Stem Cell Memory (T SCM) population within adoptive cell therapies translates to enhanced antitumor function and persistence in vivo, and thus produces favorable clinical outcomes. T SCM cells display heightened self-renewal, low mitochondrial membrane potential (∆Ψm), and are metabolically dependent upon oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Selection of CD8 + T SCM subsets is therefore necessary to ensure a robust antitumor response. Previously, we revealed synergy between the Bcl-2 inhibitor, Venetoclax, and CAR T cells in the context of B-NHL. Venetoclax exposure increased CD8 + T SCM cell frequency, decreased ∆Ψm, reduced T Regulatory (T REG) cell frequency, and bolstered effector cytokine production. Though the role of Bcl-2 inhibition within B-NHLs is well characterized (FDA-approved for frontline and relapsed/refractory chronic lymphocytic leukemia [CLL] treatment), further investigation regarding the impact of Venetoclax on the patient T cell compartment is needed. In this study, we demonstrate a role for Venetoclax as a qualitative enhancer of bulk CAR T cell product using both healthy-donor and B-NHL patient-derived T cells, and implicate modulation of mitochondrial pathways as a likely mechanism of action. Methods Whole peripheral blood mononuclear cells were collected from consenting healthy human donors or CLL patients undergoing ramp-up with Venetoclax (BDR 164122) at Roswell Park Comprehensive Cancer Center, and activated with αCD3/αCD28. CLL samples were collected at baseline, 1 day, 7 days, and 1-month timepoints. Transduction was performed with lentiviral vectors encoding CD28 or 4-1BB-based α-CD19 CAR constructs 24 hours post-activation. Transduced cells were cultured in RPMI with hIL-2 and hIL-7. In vivo studies were performed on 7-week-old SCID mice using Raji-Luc, Rec-1, and U2932. Venetoclax was given daily [100mg/kg] via oral gavage. CAR T cells were delivered by single infusion via tail-vein injection at a dose of either 1x10 6 or 3x10 6 cells total.Mice were imaged via IVIS spectrum. Western blot was performed on stimulated untransduced T cells or CAR T cells exposed to Venetoclax. Total protein was quantified, and membranes were probed for apoptotic and mitochondrial protein expression. Patient sample immunophenotyping was performed on CLL patient samples using panels interrogating memory differentiation, exhaustion, and T REG populations. Results Consistent with our hypothesis, a significant increase in mitochondrial proteins associated with FAO and OXPHOS - ACC, PDH, and AMPKα - was observed in exposed CAR T cells, as well increased expression of transcription factor FOXO1 - an essential driver of CD8 + memory differentiation. Voltage-dependent anion channel (VDAC) expression increased, suggesting heightened efflux of respiratory substrates into the tricarboxylic acid cycle. Hexokinase-I, a critical glycolytic enzyme, was significantly downregulated. We next investigated our combination therapy in vivo and observed extended survival outcome by 15 days. Further in vivo studies investigating preclinical models of mantle cell lymphoma and activated B-cell diffuse large B-cell lymphoma are currently ongoing. Within our CLL patient samples, 24-hour and 7-day timepoints reflected a favorable population increase in CD8 + T SCM cells as compared to baseline samples, and marginally restored CD8 + T cell frequencies. Conclusion Metabolic properties guide T cell memory differentiation and fitness. There exists potential to manipulate this mechanism and select the most metabolically fit T cell population for adoptive cell therapies. In addition to answering fundamental questions of CAR T cell biology, the combination of Venetoclax and CAR T cell therapy may provide a solution to the observed clinical gap, in which CAR T therapy as a single agent does not afford favorable response rates in the context of aggressive and R/R B-NHLs.

Efficacy and Safety of BCMA-Specific CAR T Cell-Based Therapy in Relapsed/Refractory Multiple Myeloma Patients with Extramedullary Disease

Background Extramedullary disease (EMD) is an aggressive subentity of multiple myeloma (MM), characterized by the ability of a subclone to grow independent of the bone marrow microenvironment, resulting in a high-risk state associated with increased proliferation, evasion of immune surveillance and treatment resistance. Relapsed/refractory multiple myeloma (R/R MM) patients with EMD have unfavorable prognoses and no effective treatment options. B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapies have shown promising efficacy in R/R MM; however, data on patients with EMD remain limited. We aimed to assess the efficacy and safety of CAR T-cell therapy in R/R MM patients with EMD. Methods We conducted a retrospective multi-institutional study of 55 R/R MM patients confirmed with EMD at referral. The definition of EMD included (1) soft tissue masses in extraosseous locations resulting from hematogenous spread (EM-E) and (2) bone-related plasmacytomas that extend via disruption of cortical bones into contiguous soft tissues (EM-B). The overall response, long-term outcomes, and safety were assessed. We also characterized differential response between medullary and extramedullary disease, analyzed unique attributes of compartmental toxicity, and explored patterns of relapse in the setting of EMD. Gene expression profiling was performed using nCounter Human CAR-T Characterization Panel (NanoString, #XT-CSO-HCART1-12) on 40 biopsy specimens from patients enrolled in this study, including EMD and bone marrow biopsy specimens at pretreatment or/and at relapse. Results were analyzed based on outcome (no durable response [progression within 6 months, NDR] vs durable response [progression beyond 6 months, DR]). Multiplex immunofluorescence (mIF) was performed for detection of populations and phenotyping of infiltrated CD8 + T cells (Panel A: CD8/PD-1/LAG-3/TIM-3) and macrophages (Panel B: CD68/CD86/CD163) with EMD biopsies. Results The infusion resulted in an overall response rate of 90.9% (95% confidence interval [CI], 80.4-96.1) in medullary disease and 70.9% (95% CI, 57.9-81.2) in EMD ( P = 0.008). Discrepant outcomes between medullary and extramedullary response were observed, with suboptimal and delayed overall response and shortened duration of response achieved in EMD. With a median follow-up of 27.3 months, the median progression-free survival was 8.7 months (95% CI, 3.7-18.8), and the median overall survival was 16.0 months (95% CI, 13.5-20.1). Landmark analysis was conducted to compare OS in patients who progressed versus remained progression-free at the 6-month landmark time point. We demonstrated that progression before 6 months post-infusion is strongly associated with an increased risk of death (HR = 11.15 [95% CI, 3.49 to 35.60]; P &amp;lt; 0.001). Local cytokine release syndrome (CRS) was depicted in 21.8% patients and was moderately associated with the occurrence of systemic CRS (r = 0.322; P = 0.017). 78.2% patients experienced post-infusion progression in EMD, and BCMA + progression constituted the main pattern of EMD progression. At the time of EMD progression, peripheral CAR + cells were detectable, and 50% patients had ongoing documented B cell aplasia. We next interrogated NanoString gene expression data of tumor microenvironment (TME) genes for possible association with clinical response and toxicity. Pretreatment TME enriched for immune checkpoint, and type I interferon signaling were associated negatively with clinical outcomes. We found that the infiltration of type 2 macrophages (CD68 +CD163 +) in pretreatment TME is associated with the density of activated or exhausted CD8 + T cell ( PD-1 +LAG-3 +/-), and is associated with no durable response in EMD. We interrogated TME dynamic changes of patients developing EMD progression between cohorts of DR and NDR. An increase in immune counter-regulatory marker and lower diversity of T-cell receptor (TCR) repertoire, was observed at relapse in cohort of NDR. Discussion Our study shows that anti-BCMA CAR-T therapy has provided apparent therapeutic advantage over the existing drugs in response rate and long-term survival. Compared with medullary disease, BCMA-specific CAR T cell-based therapy showed limited and discrepant efficacy in EMD, perhaps due to the the properties of EMD-specific microenvironment.

Accelerated versus standard epirubicin followed by cyclophosphamide, methotrexate, and fluorouracil or capecitabine as adjuvant therapy for breast cancer (UK TACT2; CRUK/05/19): quality of life results from a multicentre, phase 3, open-label, randomised, controlled trial

Adjuvant chemotherapy for patients with early breast cancer improves outcomes but its toxicity affects patients' quality of life (QOL). The UK TACT2 trial investigated whether accelerated epirubicin improves time to recurrence and if oral capecitabine is non-inferior to cyclophosphamide, methotrexate, and fluorouracil (CMF) for efficacy with less toxicity. Results showed no benefit for accelerated epirubicin and capecitabine was non-inferior. As part of the QOL substudy, we aimed to assess the effect of chemotherapies on psychological distress, physical symptoms, and functional domains. TACT2 was a multicentre, phase 3, open-label, parallel-group, randomised, controlled trial done in 129 UK centres. Participants were aged 18 years or older with histologically confirmed node-positive or high-risk node-negative invasive primary breast cancer, who had undergone complete excision, and due to receive adjuvant chemotherapy. Patients were randomly assigned (1:1:1:1) to four cycles of 100 mg/m2 epirubicin either every 3 weeks (standard epirubicin) or every 2 weeks with 6 mg pegfilgrastim on day 2 of each cycle (accelerated epirubicin), followed by four 4-week cycles of either CMF (600 mg/m2 cyclophosphamide intravenously on days 1 and 8 or 100 mg/m2 orally on days 1-14; 40 mg/m2 methotrexate intravenously on days 1 and 8; and 600 mg/m2 fluorouracil intravenously on days 1 and 8 of each cycle) or four 3-week cycles of 2500 mg/m2 capecitabine (1250 mg/m2 given twice daily on days 1-14 of each cycle). The randomisation schedule was computer generated in random permuted blocks, stratified by centre, number of nodes involved (none vs 1-3 vs ≥4), age (≤50 years vs >50 years), and planned endocrine treatment (yes vs no). QOL was one of the secondary outcomes and is reported here. All patients from a subset of 44 centres were invited to complete QOL questionnaires (Hospital Anxiety and Depression Scale [HADS] and European Organisation for Research and Treatment of Cancer [EORTC] Quality of Life Questionnaire 30-item core module [QLQ-C30] and Quality of Life Questionnaire breast module [QLQ-BR23]) at baseline, end of standard or accelerated epirubicin, end of CMF or capecitabine, and at 12 and 24 months after randomisation. The QOL substudy prespecified two coprimary QOL outcomes assessed in the intention-to-treat population: overall QOL (reported elsewhere) and HADS total score. Prespecified secondary QOL outcomes were EORTC QLQ-C30 subscales of physical function, role function, and fatigue and EORTC QLQ-BR23 subscales of sexual function and systemic therapy side-effects. This trial is registered with ISRCTN, ISRCTN68068041, and ClinicalTrials.gov, NCT00301925. From Dec 16, 2005, to Dec 5, 2008, 4391 patients (20 [0·5%] of whom were male) were enrolled in TACT2; 1281 (85·8%) of 1493 eligible patients were included in the QOL substudy. Eight (0·6%) participants in the QOL substudy were male and 1273 (99·4%) were female. Median follow-up was 85·6 months (IQR 80·6-95·9). Analysis was performed on the complete QOL dataset (as of Sept 15, 2011) when all participants had passed the 24-month timepoint. Prerandomisation questionnaires were completed by 1172 (91·5%) patients and 1179 (92·0%) completed at least one postrandomisation questionnaire. End-of-treatment HADS depression score (p=0·0048) and HADS total change score (p=0·0093) were worse for CMF versus capecitabine. Accelerated epirubicin led to worse physical function (p=0·0065), role function (p<0·0001), fatigue (p=0·0002), and systemic side-effects (p=0·0001), but not sexual function (p=0·36), compared with standard epirubicin during treatment, but the effect did not persist. Worse physical function (p=0·0048), sexual function (p=0·0053), fatigue (p<0·0001), and systemic side-effects (p<0·0001), but not role functioning (p=0·013), were seen for CMF versus capecitabine at end of treatment; these differences persisted at 12 months and 24 months. Accelerated epirubicin was associated with worse QOL than was standard epirubicin but only during treatment. These findings will help patients and clinicians make an informed choice about accelerated chemotherapy. CMF had worse QOL effects than did capecitabine, which were persistent for 24 months. The favourable capecitabine QOL compared with CMF supports its use as an adjuvant option after neoadjuvant chemotherapy in patients with triple-negative breast cancer. Cancer Research UK, Amgen, Pfizer, and Roche.

A Novel Composite Endpoint of Toxicity- and Progression-Free Survival after B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Multiple Myeloma

Introduction: BCMA-directed chimeric antigen receptor T-cell therapy (CAR T), idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), are approved for patients with relapsed and/or refractory (R/R) multiple myeloma (MM). Pivotal KaRMMA and CARTITUDE-1 trials as well as real-world data demonstrated heterogeneity in toxicity and efficacy between ide-cel and cilta-cel. To account for such differences, we have established a novel composite endpoint of toxicity-free, progression-free survival within 3 months (TPFS3) after anti-BCMA CAR T therapy. We also studied factors associated with TPFS3 across ide-cel and cilta-cel and the impact of TPFS3 on overall survival (OS) after CAR T. Methods: We analyzed a retrospective cohort of 133 consecutive recipients of ide-cel or cilta-cel at Moffitt Cancer Center (05/2021-03/2023). TPFS3 was defined as absence of severe (Grade≥3) cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), cytopenia(s), myeloma progression/stable disease (PD/SD), and non-relapse mortality (NRM) within 3 months after CAR-T infusion. CRS and ICANS were graded according to ASTCT Consensus grading. Cytopenias were graded according to CTCAE v5.0 and defined as two (or more) timepoint uni- or multilineage cytopenia, including any Grade≥2 cytopenia at post-CAR T Day 30 deepening to at least Grade≥3 at Day 60 and/or Day 90. Factors associated with TPFS3 were assessed via multivariate logistic regression analysis (MVA). Landmark Cox survival analysis at the 3-month timepoint examined the impact of TPFS3 on subsequent overall survival (OS). All analyses were performed using SAS and R. Results: In total, 48.1% (N= 64; median age=66 years [range, 45-82]; male=44%) of the patients were alive, toxicity- and progression-free by 3 months after CAR T infusion. TPFS3 components included PD/SD (N=30, 43.5%), severe cytopenias (N=26, 37.7%), ICANS (N=8, 11.6%), CRS (N=3, 4.3%), and NRM (N=2, 2.9%) (Figure 1A). In the univariate analysis, TPFS3 patients differed from the rest of the cohort according to lower marrow burden ( p=0.025), revised international staging system (R-ISS) (I/II vs III; p=0.015), CRP ( p=0.019) and ferritin ( p=0.002) levels at lymphodepletion (LD). The use of ide-cel (N=109) vs cilta-cel (N=24) was not significantly associated with TPFS3 ( p=0.119). In the MVA logistic regression, lower ferritin level (median cut off=228 ng/mL) at LD was associated with TPFS3 (odds ratio [OR]=0.37 [95%CI, 0.18-0.78], p=0.008] after adjusting for age, myeloma marrow burden, presence of extramedullary disease, R-ISS, CAR T product (all p&amp;gt;0.1), and CRP (median cut off=0.41mg/dL) at LD (OR=0.51 for lower vs higher, [95%CI, 0.25-1.05], p=0.069) included in the final model together with ferritin. In the landmark Cox survival analysis at 3 months, TPFS3 was associated with 6.54-fold superior OS (hazard ratio [HR]=0.15, 95%CI 0.05-0.52, p=0.003) (Figure 1B) after adjustment for potential confounders (age, gender, CRP, CAR-T product, marrow burden, R-ISS, extramedullary disease; all p&amp;gt;0.1). Other prognostic risks associated with inferior OS in the final model of the landmark analysis included the use of bridging therapy (HR=3.98 [95%CI, 1.30-12.20], p=0.016), ECOG≥2 at LD (HR=4.53 [95%CI, 1.57-13.07], p=0.005) and higher ferritin level at LD (HR=2.60 [95%CI, 0.95-7.13], p=0.063). Conclusions: We found that 48.1% of anti-BCMA CAR T recipients with R/R MM were alive and free of TPFS3-defining events. Myeloma response failure, cytopenias and severe ICANS were the top leading components of TPFS3 which was best predicted by ferritin level at LD. TPFS3 independently predicted long-term OS. Thus, TPFS3 may serve as an ideal composite safety and efficacy endpoint in future myeloma trials with BCMA-directed CAR T.

Feasibility and acceptability of mobile phone-based triage tool to identify discharged trauma patients in need of further care in Cameroon

BackgroundLack of routine follow-up for trauma patients after hospital discharge likely contributes to high rates of injury-related complications in Cameroon. Mobile phone contact may facilitate timely follow-up and reduce disability...

Systemic Inflammation Response Index Predicts Clinical Outcomes in Patients With Acute Ischemic Stroke (AIS) After the Treatment of Intravenous Thrombolysis.

Intravenous thrombolysis (IVT) is one of the most important means of therapy for patients with acute ischemic stroke (AIS). After cerebral infarction, the inflammatory response fulfills an essential role in the pathobiology of stroke, affecting the process of recanalization. Hence, we evaluated the usefulness of the systemic inflammatory response index (SIRI) for the prognosis of patients with AIS. A total of 161 patients suffering from AIS were retrospectively analyzed. SIRI was introduced and calculated using the absolute neutrophil, monocyte, and lymphocyte numbers from the admission blood work. The study outcomes were determined using a modified Rankin Scale (mRS) at the 3-month timepoint, and a favorable clinical outcome was calculated in the mRS score range of 0 to 2. The analysis of receiver operating characteristic (ROC) curves was performed to determine the values of the optimal cutoff of SIRI for the prediction of clinical outcomes. In addition, multivariate analyses were performed to investigate the association between clinical outcomes and SIRI. The ROC curve analysis revealed that the ideal SIRI cutoff was at 2.54 [area under the curve, 78.85%; 95% CI, 71.70% to 86.00%; sensitivity, 70.89%; and specificity, 84.14%]. Multivariate analysis indicated that SIRI ≤2.54 (odds ratio, 1.557, 95% CI, 1.269 to 1.840; P=0.021) was an independent predictor of favorable clinical outcomes in patients suffering from AIS after treatment with IVT. We preliminary speculate that SIRI may serve as an independent predictor of clinical outcomes with AIS following IVT.

Mindful practice with medical interpreters.

Medical interpreters experience emotional burdens from the complex demands at work. Because communication access is a social determinant of health, protecting and promoting the health of medical interpreters is critical for ensuring equitable access to care for language-minority patients. The purpose of this study was to pilot a condensed 8-h program based on Mindful Practice® in Medicine addressing the contributors to distress and psychosocial stressors faced by medical sign and spoken language interpreters. Using a single-arm embedded QUAN(qual) mixed-methods pilot study design, weekly in-person 1-h sessions for 8 weeks involved formal and informal contemplative practice, didactic delivery of the week's theme (mindfulness, noticing, teamwork, suffering, professionalism, uncertainty, compassion, and resilience), and mindful inquiry exercises (narrative medicine, appreciative interviews, and insight dialog). Quantitative well-being outcomes (mean±SEM) were gathered via survey at pre-, post-, and 1-month post-intervention time points, compared with available norms, and evaluated for differences within subjects. Voluntary feedback about the workshop series was solicited post-intervention via a free text survey item and individual exit interviews. A thematic framework was established by way of qualitative description. Seventeen medical interpreters (46.2 ± 3.1 years old; 16 women/1 man; 8 White/9 Hispanic or Latino) participated. Overall scores for teamwork (p ≤ 0.027), coping (p ≤ 0.006), and resilience (p ≤ 0.045) increased from pre- to post-intervention and pre- to 1-month post-intervention. Non-judging as a mindfulness component increased from pre- to post-intervention (p = 0.014). Compassion satisfaction (p = 0.021) and burnout (p = 0.030) as components of professional quality of life demonstrated slightly delayed effects, improving from pre- to 1-month post-intervention. Themes such as workshop schedule, group size, group composition, interactivity, topics to be added or removed, and culture are related to the overarching topic areas of intervention logistics and content. Integration of the findings accentuated the positive impact of the intervention. The results of this research demonstrate that mindful practice can serve as an effective resource for medical interpreters when coping with work-related stressors. Future iterations of the mindful practice intervention will further aspire to address linguistic and cultural diversity in the study population for broader representation and subsequent generalization.

Effect of a Second Pregnancy on the HPV Serology in Mothers Followed Up in the Finnish Family HPV Study.

The impact of pregnancy on human papillomavirus (HPV) natural antibody levels is not fully understood. We tested the seroprevalence and levels of HPV 6, 11, 16, 18 and 45 antibodies at different time points among 89 women with a second pregnancy and 238 nonpregnant women during their 36-month followup. All participants were unvaccinated for HPV and pregnant at the enrollment of the study. Serum samples were collected from the mothers at baseline and at the 12-month, 24-month, and 36-month followup visits. No statistically significant differences in mean antibody levels were observed in women who developed a second pregnancy compared to their nonpregnant counterparts. Between these two groups, statistically significant differences in serostatus were observed, particularly if the second pregnancy was ongoing at the 24-month timepoint. Accordingly, women with a second pregnancy were more likely to be seronegative for HPV 6, 11, 18, and 45 as compared to the nonpregnant women, the reverse being true for HPV16. In contrast, the women with an ongoing second pregnancy showed a higher prevalence of HPV16 seropositivity at the 36-month followup. These data suggest that a second pregnancy does not seem to have a major impact on the levels of HPV antibodies, but it might influence the serological outcomes.