Unfavorable Group Research Articles

Long-Term Impairment of the Blood-Spinal Cord Barrier in Patients With Post-Traumatic Syringomyelia and its Effect on Prognosis.

Cohort study. The aim of this study was to explore the association between blood-spinal cord barrier (BSCB) markers and other factors associated with an unfavorable outcome among patients with post-traumatic syringomyelia (PTS) who achieved successful intradural adhesion lysis (IAL). Only approximately half of PTS patients receiving IAL have a favorable outcome. Forty-six consecutive patients with PTS and 19 controls (CTRL) were enrolled. All PTS patients underwent physical and neurological examinations and spinal magnetic resonance imaging before and 3 to 12 months after IAL. All patients underwent myelography before surgery. BSCB disruption was detected by increased intrathecal and serum concentrations of albumin, immunoglobulin (Ig)G, IgA, and IgM. A multivariable analysis was performed with a logistic regression model to identify factors associated with unfavorable outcomes. Receiver operating characteristic curves were calculated to investigate the diagnostic value of biomarkers. The ages and general health of the PTS and CTRL groups did not differ significantly. QAlb, IGAQ, IGGQ, and IGMQ was significantly higher in PTS patients than in controls ( P =<0.001). The degree of intradural adhesion was significantly higher in the unfavorable outcome group than in the favorable outcome group ( P <0.0001). QAlb, immunoglobulin (Ig)AQ, IGGQ, and IGMQ was significantly correlated with clinical status ( R =-0.38, P <0.01; R =-0.47, P =0.03; R =-0.56, P =0.01; R =-0.43, P =0.05, respectively). Higher QAlb before surgery (odds ratio=2.66; 95% CI: 1.134-6.248) was significantly associated with an unfavorable outcome. The receiver operating characteristic curve analysis demonstrated a cutoff for QAlb higher than 10.62 with a specificity of 100% and sensitivity of 96.3%. This study is the first to detect increased permeability and BSCB disruption in PTS patients. QAlb>10.62 was significantly associated with unfavorable clinical outcomes following intradural decompression. Level III-prognostic.

Hodgkin Lymphoma - Mitigating Toxicity While Preserving Cure - Eight Year Data from MIOT International, Chennai, India

Background One of the most treatable cancers, Hodgkin's lymphoma (HL), has a 5-year survival rate of approximately 85%.We still see relapse and refractoriness in a tiny percentage of patients despite the fact that our disease is largely curable, and we also have additional issues including secondary neoplasia and long-term consequences on the heart. Our Hodgkin lymphoma statistics from 2011 to 2019 have been given in this paper. Methodology Between 2011 and 2019, data on patients with newly diagnosed classical HL (CHL) who received treatment were gathered. Analysis was done on the presenting characteristics, IPS risk classification, treatment procedures, treatment response, and 3-year outcome data. Results At presentation, there were 97 patients with newly diagnosed CHL, with a median age of 24 years (range, 11-72). The ratio of men to women was 1.62:1. Mixed cellularity, lymphocyte-rich, and lymphocyte-depleted CHL (LD, CHL) were histological subtypes that were present in 80.40%, 12.40%, and 7.20% of cases, respectively. At presentation, 52% of patients had advanced illness, and 80% had B symptoms. The Hodgkin IPI score was high in 58% of individuals with advanced stages. ABVD was given as the first line of therapy to 92% of patients. According to interim PET-CT scan findings, around 7 advanced stage Hodgkin patients were started with EscBEACOPP and then switched to ABVD prior to 2017. The front line treatment's overall response rate was 94.8%. Complete response rates for early-stage favourable and unfavourable risk groups were 94% and 86%, respectively, whereas they were 81% and 67% for advanced-stage low- and high-risk groups. The median duration of event free survival was 36 months. The 3-year EFS showed a significant difference between the early- and advanced-stage diseases, 93% and 81%, respectively (p 0.04). Relapse was found in eight patients, all of whom had BEAM Autograft post platinum based salvage treatment. Following interim PET negativity, we discontinued Bleomycin according to RATHL protocol. Three of our patients had bleomycin lung injury. Three patients had post-autograft recurrence, one of whom passed away due to a subsequent non-Hodgkin lymphoma. With the Brentuximab Bendamustine regimen, two patients were successfully salvaged and they had Haplo-identical transplant as third line salvage. Conclusions In early and late stage Hodgkin lymphoma, the three year EFS of 93% and 81% is equivalent to most western literature. In light of our little experience with Indian patients, the effect of Brentuximab is overwhelmingly favorable. At our facility, post-Autograft Brentuximab maintenance is being tested. There is no information on how Nivolumab will be useful in our context. Although there is little evidence to draw a conclusion that is statistically significant, frontline ABVD protocol treatment across risk categories and discontinuing Bleomycin after interim PET negative are helpful in our patients to enhance prognosis and decrease toxicity. Reference: Adapted Treatment Guided by Interim PET-CT Scan in Advanced Hodgkin's Lymphoma N Engl J Med 2016; 374:2419-2429 DOI: 10.1056/NEJMoa1510093Mohty, R., Dulery, R., Bazarbachi, A.H. et al. Latest advances in the management of classical Hodgkin lymphoma: the era of novel therapies. Blood Cancer J. 11, 126 (2021). https://doi.org/10.1038/s41408-021-00518-z

IRF4 Expression in Germinal Center and Lymphoma B Cells Regulates Antigen-Dependent Immune Response

A substantial subset of follicular lymphoma (FL) patients has an early relapse with a poor outcome. We showed that this unfavorable group displays increased expression of IRF4, dysregulated immune signaling and an immunosuppressive microenvironment. At the molecular level, IRF4 controls expression of antigen presentation and immune molecules (e.g. HLA-DR, CD40, PDL1). Furthermore, silencing of IRF4 triggers anti-lymphoma immunity ( Mondello P et al, Blood 2022;140 Suppl 1:168-169). However, little is known on the molecular mechanisms whereby IRF4 controls the crosstalk between B and T cells. To address this question, first we performed RNA-seq, ATAC-seq and CUT&amp;TAG of active (H3K27Ac, H3K4me3) and repressive (H3K27me3, H3K4me1) histone marks in TMD8 and HBL1 (lymphoma cells with high IRF4 expression) transfected with two pairs of siIRF4 or siCtr for 72 hours. Gene expression revealed a broad change in transcription, with 432 upregulated genes and 136 downregulated genes in siIRF4 compared to siCtr. Notably, the genes with increased expression following IRF4 silencing coded for antigen presentation, immune molecules and cytokines (e.g. HLA-DR, CD86, IL6, IL10). Accordingly, we observed significant enrichment of antigen presentation, interferon and immune response signatures ( Fig 1A). Integrating RNA-seq with chromatin accessibility showed a significant shift towards transcriptional upregulation at genes nearest to upregulated ATAC peaks, with significant enrichment at enhancers (n=771). Conversely, transcriptional suppression was enriched at enhancers (n=2,458) of downregulated peaks. k-means analyses of all union peaks, generated by merging ATAC with CUT&amp;TAG peaks, revealed a significant gain of H3K4me3, with concordant loss of H3K4me1 at enhancers with upregulated gene expression. In contrast, H3K4me3 was severely decreased at suppressed peaks. TF motif analysis revealed an enrichment for PU.1 and E2A at IRF4-bound regions, suggesting their cooperation in regulating immune signaling. Since antigen presentation and other immune molecules are critical components of the immune synapse, we explored the role of IRF4 on the interaction between germinal center (GC) B and T cells by crossing irf4 fl/fl mice with conditional deletion of irf4 ( Klein et al, Nat Immunol 2006) and Cγ 1cre mice ( Cγ 1cre; irf4 fl/fl) to induce recombination in GC B cells. After 10 days of immunization (GC reaction peak), Cγ 1cre; irf4 fl/fl and Cγ 1cre; irf4 fl/+ GC B cells showed significant increase of HLA-DR and CD40 expression compared to WT. As expected, Cγ 1cre; irf4 fl/fl mice displayed a significantly skewed light-zone:dark-zone ratio in favor of increased dark-zone, which are the cells that most reflect the action of BCL6, with concordant suppression of plasma cells. Additionally, we observed a significant increase of CD4 + T cells after partial or complete deletion of irf4, with upregulation of T FH cells and decrease of T reg cells ( Fig 1B). Notably, mice with loss of irf4 showed a significant decrease in exhausted T FH cells. To test if this effect was dependent on MHC:TCR interaction, we cocultured CD4 + T cells with TMD8 cells transfected with two siIRF4 or siCtr in presence of blocking antibodies for MHC class I, MHC class II or both. Blocking one or the other MHC class I or II partially rescued the IRF4 effect on T reg and T FH cells respectively as well as reduced anti-lymphoma cytotoxicity. Further experiments blocking IRF4-dependent IL6 and IL10 identified these two cytokines as responsible for the additional effects on T cells. To confirm this as an antigen-dependent immune response we coculture sorted GC B cells from NP-OVA-immunized Cγ 1cre; irf4 fl/fl, Cγ 1cre; irf4 fl/+ and WT mice with CSFE-labeled OVA-specific OT-II CD4 + T cells at a ratio of 2:1 in an organoid system for 5 days. We observed induced antigen specific proliferation of CD4 + T cells in the presence of Cγ 1cre; irf4 fl/fl and Cγ 1cre; irf4 fl/+ GC B cellscompared to WT,as indicated by decrease in CSFE expression . We confirmed an increase of T FH cells and a decrease of T reg cells, supporting the conclusion that IRF4 directly controls the antigen-dependent immune response . In summary, IRF4 expression in GC and lymphoma B cells regulates immune signaling with PU.1 and E2A, thereby modulating antigen-dependent immune responses with potential implications for lymphomagenesis. Future studies investigating targeting of IRF4 in lymphoma are warranted.

HPB P12 Do Chemotherapy Factors or Treatment Intervals Influence Pathological Tumour Response during Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma? A Bi-Institutional Study

Abstract Background Pathological response of pancreatic ductal adenocarcinoma (PDAC) to neoadjuvant chemotherapy (NAT) can be assessed using grading systems such as the College of American Pathologists (CAP) system, with favourable regression being associated with improved oncological outcomes. The aim of the study was to investigate factors associated with favourable tumour regression in patients undergoing pancreatoduodenectomy (PD) for PDAC. Methods Patients who received NAT before undergoing PDAC resection at two institutions in the United Kingdom between 2013 and 2021 were reviewed. Interactions between chemotherapy regimens, tumour staging, carbohydrate antigen 19-9 (Ca19-9) levels, perioperative factors and tumour regression grading (TRG) were explored. Results 54 patients were identified who were suitable for inclusion. 12 (22%) patients had a favourable response to NAT according to the CAP grading system. A significantly greater reduction in Ca19-9 observed in the favourable TRG group [mean -2359 U/mL] compared to the unfavourable TRG group [mean -569 U/mL (p&amp;lt;0.001). The type of chemotherapy agent received, the number of cycles or whether the patient had a dose reduction during their NAT course did not differ significantly between the groups. The time from diagnosis to chemotherapy and time from end of chemotherapy to surgery were also similar between the groups. Conclusions In this bi-institutional retrospective study, neither chemotherapy factors nor treatment intervals were not found to be significantly related to pathological tumour response to NAT in PDAC patients undergoing resection. Given that a favourable pathological response has been related to improved oncological outcomes, future research should concentrate on further mechanisms that may influence the response of PDAC tumours to NAT, such as gene expression and the tumour microbiome. Given that NAT is also a relatively new approach, further multicentre collaboration should be encouraged to increase numbers of patients for study.

Poor response to first intravitreal injection for predicting unfavorable outcomes of retinal vein occlusion related macular edema.

To screen key indicators leading to unfavorable outcomes of retinal vein occlusion related macular edema (RVO-ME) within long-term follow-up duration and to evaluate their predictive values. A study involving patients with RVO-ME was conducted between April 2021 and September 2022. All eligible patients were divided into two groups (favorable and unfavorable group) according to their final best corrected visual acuity (BCVA) and whether neovascular glaucoma (NVG) occurred. The unfavorable group was further divided into subgroups 1 (with BCVA of ≥ 20/400 and < 20/60 and without NVG) and 2 (blindness group, with BCVA of < 20/400 or with NVG). Demographic, past medical history, ocular characteristics and blood parameters were compared between the groups. A total of 73 eyes from 73 Chinese Han patients (34 males vs. 39 females) with RVO-ME were enrolled. In multivariable regression analysis of continuous variables for unfavorable results, 1-month BCVA after the first intravitreal injection (IVI) was an independent risk factor (odds ratios (ORs) = 2.313, 95% confidence interval (CI) 1.387-3.858, P = 0.001). The area under the curve (AUC) of 1-month BCVA after the first IVI for predicting low vision and blindness was 0.948 (95% CI 0.859-1.000, P < .001) and 0.892 (95% CI 0.744-1.000, P < .001), with a cut-off value of 0.65 logarithm of the minimum angle of resolution (log MAR) (Snellen 20/90) and 1.15 log MAR (Snellen 20/300), respectively. The most valuable indicator for predicting low vision and blindness was poor 1-month BCVA after first IVI compared with favorable group.

The predictive role of left ventricular cathode topography relative to CMR-determined latest mechanical activation and scar segments on response to cardiac resynchronisation therapy

Abstract Background Cardiac resynchronisation therapy (CRT) is still burdened by considerable rates of non-response. Herein left ventricular cathode (LVC) positioning has the greatest room for optimisation. Nonetheless, a purely CMR-based approach exploring LVC topography relative to both mechanical delay and tissue viability is yet to be investigated. Purpose To retrospectively analyse the effect on reverse remodelling of CMR-determined LVC topography relative to latest mechanical activation (LMA) and scar segments in a CRT population. Methods This is a retrospective single-centre analysis of 104 CRT-D/P consecutive patients with CMR performed within 6 months before implantation. Electrical delay (Q-LV time) was mapped on all suitable veins with LV lead positioning and cathode programming set in the region of latest electrical activation. Through CART-Tech® software analysis of CMR images, 36-segment 3D anatomical models of radial strain and scar were superimposed on their corresponding fluoroscopy images (Figure 1). Patients were then stratified based on LVC concordance (within), semi-concordance (adjacent) or non-concordance (at least one segment away) with LMA and scar segments (defined as segments with &amp;gt;50% scar transmurality). Follow-up echocardiography was performed at least 6 months after implantation and the degree of reverse remodelling expressed as percentage reduction in end-systolic volume (ESV). Results Of the 104 patients, 36 were excluded due to suboptimal CMR quality (8), switch to conduction system pacing (5), loss to follow-up (18) or death within 6 months of implantation (5), leaving a total of 68 (63 CRT-D and 5 CRT-P). LVC concordance with LMA was associated with a statistically significant improvement in reverse remodelling (Figure 2, A), while the contrary occurred with regards to scar (Figure 2, B). A greater impact of distance from scar compared to LMA proximity was observed, thus a combined analysis of LVC topography relative to both was developed accordingly. Patients were stratified into 4 categories of LVC optimality: optimal (LVC-LMA concordance + LVC-scar non-concordance), semi-optimal (LVC-LMA semi-concordance + LVC-scar non-concordance), suboptimal (LVC-LMA non-concordance + LVC-scar non-concordance), and unfavourable (LVC-scar semi-concordance or concordance regardless of LVC-LMA). The unfavourable group had higher rates of atrial fibrillation, non-LBBB QRS morphology and higher scar burden, while no significant differences were observed in the other 3 groups. This classification appears to predict the degree of reverse remodelling, ESV reduction being more pronounced the more optimal the group (Figure 2, C). Conclusions CMR-determined LVC topography relative to LMA and scar segments predicts left ventricular reverse remodelling in Q-LV-guided CRT implants. Optimisation of CRT response may thus benefit from a CMR-based approach assessing mechanical delay and tissue viability to guide LVC positioning.Figure 1Figure 2

Association of Latino Ethnicity with Cytogenetic Subtype in Pediatric Acute Lymphoblastic Leukemia: A Report from the Reducing Ethnic Disparities in Acute Leukemia Consortium

Introduction: Acute lymphoblastic leukemia (ALL) is the most common childhood cancer, and is a heterogeneous group of bone marrow diseases with multiple cytogenetic subtypes leading to distinct clinical outcomes. Despite advances in treatments that improve survival, racial and ethnic disparities continue to persist. Latino children have a higher incidence of ALL and poorer overall survival compared with non-Latino white children. Although several studies conducted have identified cytogenetic differences in Latinos, larger studies are needed to confirm and further elaborate these findings. The aim of our study was to analyze cytogenic profiles of a large, diverse cohort of children with ALL to assess the associate between cytogenic subtypes in Latino ethnicity. Methods: We analyzed the distribution of ALL subtypes and self-reported race/ethnicity in the Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium retrospective registry, which includes patients (age 0-24 at diagnosed) with newly diagnosed ALL from six pediatric cancer centers in the southwest region that were diagnosed between 2017 - 2021. The demographic and clinical factors included self-reported race/ethnicity, sex, age at diagnosis, immunophenotype, and cytogenetic aberration. Cytogenetic subtypes evaluated included double trisomies (DT; trisomies chromosomes 4 and 10), BCR::ABL (Ph+), ETV6::RUNX1 KMT2A ( MLL) rearrangements, hypodiploidy, intrachromosomal amplification of chromosome 21 ( iAMP21) TCF3::PBX1, IGH, and CRLF2 rearrangements. Multivariable logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (95% CIs), accounting for sex and age at diagnosis. Results: Of the 2,388 ALL patients evaluated, 90.2% had B-cell ALL and 64.4% self-identified as Latino and the mean age at diagnosis was 6.6 years. Compared with non-Latino white patients, the cytogenetic findings associated with favorable prognosis, DT and ETV6:: RUNX1 t(12;21), were less frequent in Latino patients (aOR: 0.80, 95% CI: 0.65-0.98 for DT and aOR: 0.67, 95% CI: 0.53-0.85 for ETV6:: RUNX1). Overall, favorable cytogenetics were less frequent among Latino children compared with non-Latino white children (aOR: 0.82, 95% CI: 0.67-0.99). The neutral cytogenetic subtype TCF3:: PBX1 was also less frequent clinically among Latino patients (aOR: 0.39, 95% CI: 0.18 - 0.85). Among unfavorable cytogenetic alterations, iAMP21 was significantly less frequent among Latino children compared with non-Latino white children (aOR: 0.57, 95% CI: 0.32-0.99). There was no significant association between other unfavorable cytogenetic subtypes and Latino ethnicity, either individually or for the overall unfavorable group. Conclusions: Overall, our findings indicate that Latino children are significantly less likely to have favorable cytogenetic subtypes, TCF3:: PBX1 and iAMP21 and prognostically neutral cytogenetics. Further evaluation of cytogenetic subtypes and race/ethnicity may elucidate their contribution to outcome disparities.

Association of Latino Ethnicity with Cytogenetic Subtypes in Pediatric Acute Myeloid Leukemia

Background: While advances in molecular cytogenetic assessment and incorporation of recurrent chromosomal abnormalities with prognostic significance into risk stratification have improved outcomes for children with acute myeloid leukemia (AML), outcome disparities persist. Specifically, Latino children are noted to have inferior outcomes compared with their non-Latino peers. These disparities may be related in part to ethnic-based differences in cytogenetic features, but the prevalence of AML cytomolecular subtypes within specific demographic populations is a relatively understudied area. Our aim is to evaluate the association between self-reported race/ethnicity and recurrent prognostic cytogenetic features in pediatric AML. Methods: We analyzed data from the multi-institutional Reducing Ethnic Disparities in Acute Leukemia (REDIAL) Consortium between 2007 to 2022. REDIAL includes children newly diagnosed with AML at six major pediatric cancer centers in the Southwestern U.S. Demographic and clinical characteristics include self-reported race/ethnicity, sex, and age at diagnosis. Cytogenetic subtypes evaluated included KMT2A rearrangements, FLT3 mutation, PML::RARA, RUNX1::RUNX1T1, CBFβ::MYH11, CEBPA, DEK::NUP21, RBM15::MKL1, RPN::1EV11, del5q, monosomy 5, monosomy 7, and BCR::ABL1. Features were dichotomized as present or absent in those that were tested, and subtypes categorized into favorable, unfavorable, and neutral groups. Multivariate logistic regression models were used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs), adjusting for sex and age at diagnosis. Results: Among the 665 AML patients included in this analysis, 46.3% self-reported as Latino, 32.6% as non-Latino White (NLW), 9.4% as Black, 6.4% as Asian/Pacific Islander (API), and 5.1% as other/unknown. The mean age at diagnosis was 7.9 years (standard deviation 6.3); a majority were male (51.6%). Among all patients that were tested, 20.8% (134/644) had at least one favorable subtype, and 27.3% (161/590) had at least one unfavorable subtype. Adjusted logistic regression models showed Latino children had 1.59 times greater odds of having at least one favorable subtype compared to NLW children (aOR 1.59, 95% CI 1.01-2.51) but were not at increased odds of having at least one unfavorable subtype (aOR 1.03, 95% CI 0.68-1.56) or a neutral subtype (aOR 0.84, 95% CI 0.-57-1.23) compared to patients of other race/ethnicity. While multivariable analyses of specific subtypes did not meet the threshold for statistical significance, there were some notable trends. For instance, compared with NLW children, Latino and Black children had a higher prevalence of the favorable RUNX1::RUNX1T1 translocation (aOR: 1.40, 95% CI: 0.70-2.83; 1.90, 0.69-5.20, respectively). Compared with NLW children, Latino and Black children also had a higher prevalence of the favorable CEBPA mutation (aOR 1.02, 95% CI 0.15-6.56; 1.36, 0.11-16.6, respectively), and were more likely to have unfavorable KMT2A rearrangements (aOR 1.18, 95% CI 0.67-2.08; 1.23, 0.47-3.1, respectively). Additionally, Latino children were more likely to have the favorable translocation CBFβ::MYH11 compared with Black and NLW children (aOR 2.2, 95% CI 0.27-18.1; 1.20, 0.42-3.37, respectively), and less likely to carry the unfavorable FLT3 activating mutation compared with their NLW peers (aOR 0.56, 95% CI 0.26-1.21). Conclusions: Our findings suggest Latino children are more likely to have a favorable cytogenetic subtype than NLW children, which suggests disparities in outcomes are not primarily due to underlying differences in prognostic subtypes. Additional analyses of pediatric AML as it relates to cytogenetic subtypes and race/ethnicity is ongoing, including the incorporation of disease response and treatment outcomes, to understand how these factors may impact disparities in outcomes.

Increased plasma miR-370-3p expression in poor-outcome patients with pancreatic ductal adenocarcinoma

ObjectiveTo determine whether circulating microRNAs (miRNAs) can be used as prognostic biomarkers for pancreatic ductal adenocarcinoma (PDAC). MethodsPatients with PDAC (N = 120) who underwent surgical resection at Hiroshima University Hospital between November 2006 and January 2020 were enrolled in this study and grouped based on their overall survival (OS) into two groups: favorable prognosis group (F group; OS ≥ 18 months) and unfavorable prognosis group (U group; OS < 18 months). Blood plasma samples were collected prior to surgery. To identify candidate prognostic miRNAs, next-generation sequencing (NGS) analysis was used to evaluate the expression levels of miRNAs in seven of the plasma samples. Using quantitative real-time PCR (qRT-PCR), the expression levels of the selected miRNAs were determined in the remaining 113 patient plasma samples, and the relationship between miRNA expression and survival was statistically evaluated. ResultsNGS analysis and qRT-PCR revealed significantly upregulated plasma miR-370-3p expression in the U group compared to that in the F group (p = 0.028 and p = 0.005, respectively). Moreover, miR-370-3p expression and lymph node metastasis showed a statistically significant association (p = 0.028). In a multivariate analysis of OS and recurrence-free survival (RFS), the upregulation of miR-370-3p expression in plasma was identified as an independent risk factor for poor OS (HR2.13, p = 0.004) and RFS (HR1.84, p = 0.015). ConclusionsPlasma miR-370-3p expression upregulation correlates with poor prognosis in patients with PDAC.

Metabolomic profiles, polygenic risk scores and risk of rheumatoid arthritis: a population-based cohort study in the UK Biobank

ObjectiveTo investigate the relationship between metabolomic profiles, genome-wide polygenic risk scores (PRSs) and risk of rheumatoid arthritis (RA).Methods143 nuclear magnetic resonance-based plasma metabolic biomarkers were measured among 93 800 participants...

Social Determinants of Health, Cardiovascular Health, and Outcomes in Community-Dwelling Adults Without Cardiovascular Disease

BackgroundLimited data exist regarding the prognostic implications of social determinants of health (SDOH) and cardiovascular health (CVH) in Chinese community populations. ObjectivesThe aim of this study was to evaluate the associations of SDOH and CVH with major adverse cardiovascular events (MACE) and all-cause death. MethodsIndividuals without cardiovascular disease were obtained from the China Patient-Centered Evaluative Assessment of Cardiac Events Million Persons Project. SDOH (educational attainment, economic stability, health care access, social support, and neighborhood) and CVH components were extracted. Participants were divided into groups with low and high burden of unfavorable SDOH and groups with poor, intermediate, and ideal CVH. MACE (a composite of coronary heart disease or myocardial infarction, stroke, heart failure, and cardiovascular death) and all-cause death were identified by linking hospital records with resident identity card number. ResultsAmong the cohort (n = 38,571, median age 54 years, 60.5% women), the proportion of individuals with a high burden of unfavorable SDOH was 68.9%, and that with poor CVH was 30.7%. In reference to the group with a low burden of unfavorable SDOH, the adjusted HRs for MACE and all-cause death in the high burden group were 1.18 (95% CI: 1.08-1.30) and 1.35 (95% CI: 1.09-1.68), respectively. In reference to the group with ideal CVH, poor CVH was associated with higher risks for MACE and all-cause death. A high burden of unfavorable SDOH and poor CVH exerted joint effects on all-cause death (HR: 2.20; 95% CI: 1.08-4.48). ConclusionsA high burden of unfavorable SDOH and poor CVH were associated with increased risks for MACE and mortality. Dedicated efforts are needed to address these health disparities.

Association of a healthy lifestyle with mortality in older people

BackgroundUnhealthy lifestyle behaviours such as smoking, high alcohol consumption, poor diet or low physical activity are associated with morbidity and mortality. Public health guidelines provide recommendations for adherence to these four factors, however, their relationship to the health of older people is less certain.MethodsThe study involved 11,340 Australian participants (median age 7.39 [Interquartile Range (IQR) 71.7, 77.3]) from the ASPirin in Reducing Events in the Elderly study, followed for a median of 6.8 years (IQR: 5.7, 7.9). We investigated whether a point-based lifestyle score based on adherence to guidelines for a healthy diet, physical activity, non-smoking and moderate alcohol consumption was associated with subsequent all-cause and cause-specific mortality.ResultsIn multivariable adjusted models, compared to those in the unfavourable lifestyle group, individuals in the moderate lifestyle group (Hazard Ratio (HR) 0.73 [95% CI 0.61, 0.88]) and favourable lifestyle group (HR 0.68 [95% CI 0.56, 0.83]) had lower risk of all-cause mortality. A similar pattern was observed for cardiovascular related mortality and non-cancer/non-cardiovascular related mortality. There was no association of lifestyle with cancer-related mortality.ConclusionsIn a large cohort of initially healthy older people, reported adherence to a healthy lifestyle is associated with reduced risk of all-cause and cause-specific mortality. Adherence to all four lifestyle factors resulted in the strongest protection.

Tumour-agnostic plasma assay for circulating tumour DNA predicts outcome in recurrent and/or metastatic squamous cell carcinoma of the head and neck treated with a PD-1 inhibitor

BackgroundOnly 15–20% of recurrent and/or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) patients derive long-term benefit from nivolumab or pembrolizumab. We developed a circulating tumour DNA (ctDNA) tumour-agnostic assay aimed at the early prediction of single agent programmed cell death 1 (PD1) inhibitor efficacy in R/M SCCHN. Patients and methodsOur tumour-agnostic assay included 37 genes frequently mutated in R/M SCCHN and two HPV16 genes. Primary endpoint was the concordance between ctDNA kinetics (ΔctDNA) and the best overall response according to Response Evaluation Criteria in Solid Tumors version 1.1. ΔctDNA was defined as the difference in mean variant allele frequency (VAF) between the on-treatment sample harvested 6–10 weeks (FU1) after PD1 inhibitor initiation and the pre-treatment plasma sample (ΔctDNA = mean FU1 VAF - mean pre-treatment VAF). ResultsctDNA was detected in 35/44 (80%) of the pre-treatment plasma samples. The concordance between ΔctDNA and imaging response was observed in 74%. Median progression-free survival was 8.6 months in the favourable ΔctDNA group and 2.5 months in the unfavourable ΔctDNA group (p = 0.057). Median overall survival (OS) was 18.1 and 8.2 months in the favourable and unfavourable ΔctDNA groups, respectively (p = 0.13). In patients with PD-L1 expressing SCCHN (Combined Positive Score ≥1), OS was significantly better in patients with favourable ΔctDNA compared with patients with unfavourable ΔctDNA: median OS was 41.5 and 8.4 months (p = 0.033), respectively. ConclusionsTumour-agnostic ctDNA analysis for human papillomavirus (HPV)-negative and HPV-positive R/M SCCHN is feasible. ctDNA kinetics show promising results in predicting the efficacy of PD1 inhibitors in R/M SCCHN.

Impact of Treatment Modalities on Discharge Disposition in Blunt Splenic Injuries.

Management of blunt splenic trauma has evolved over several decades, trending towards nonoperative management and splenic artery embolization. Extensive research has been conducted regarding the management of blunt splenic injuries, but there is little data on the association of treatment modality with discharge disposition. This is an observational retrospective study conducted at a level-one trauma center with blunt splenic trauma patients of age ≥18 years between January 2010 and December 2021. The primary outcome of unfavorable discharge was defined as discharge to an acute care facility, intermediate care facility, long-term care facility, rehabilitation (inpatient) facility, or skilled nursing facility. Five hundred seventy-nine patients were included in the analysis, with 108 (18.7%) in the unfavorable group and 471 (81.3%) in the favorable group. Most patients were managed nonoperatively (69.3%), followed by splenectomy (25.0%) and embolization (5.7%). Due to the low number of embolizations performed during the study period, treatment modalities were grouped into two broad categories: intervention (embolization and splenectomies) and nonintervention. The treatment modality was found to have no significant impact on unfavorable discharge. Independent risk factors for unfavorable discharge included age >55 years, injury severity score (ISS) >15, hospital-acquired pneumonia, and in-hospital complications of sepsis. This study provides an understanding of specific demographic and clinical factors that may predispose blunt splenic injury trauma patients to an unfavorable discharge. Providers may apply these data to identify at-risk patients and subsequently adapt the care they provide in an effort to prevent the development of in-hospital pneumonia and sepsis.

The Relationship between Maternal Characteristics and Folic Acid Intake with the Incidence of Anemia in Pregnant Women in Percut Sei Tuan District

Anemia is a nutritional problem with a high prevalence. Anemia often occurs in teenagers, women of childbearing age, and pregnant women. This study aims to determine the relationship between maternal characteristics and folic acid intake with the incidence of anemia in pregnant women. The design of this study is cross sectional. The population is all pregnant women in the second and third trimesters in three villages in the Percut Sei Tuan sub-district. The sampling in this research was porpusive sampling. Data collection was carried out through interviews using questionnaires and food recall tables as research instruments. Data processing through editing, entering and tabulating. Data analysis used the Chi Square test with Ci 95%. The results of the study showed that 87.8% of mothers in the good age group did not experience anemia and 12.1% of mothers in the unfavorable age group experienced anemia. 90.2% of mothers in the good parity group were not anemic and 9.8% of mothers in the poor parity group were anemic. 90.2% of mothers with good ANC group experienced anemia and 9.8% of mothers with poor ANC group did not experience anemia. 9.8% of pregnant women in the good folic acid intake group were not anemic and 48.8% of pregnant women in the not good folic acid intake group were anemic. There is a relationship between parity, ANC visits and folic acid intake in pregnant women in Percut Sei Tuan District. And there is no relationship between maternal age and the incidence of anemia in Percut Sei Tuan District.

Serum immunoglobulin G level reduction is a predictor of short-term improvement in patients with myasthenia gravis undergoing plasmapheresis.

The aim of the study was to investigate the serological factors in predicting symptom improvement in myasthenia gravis (MG) patients who underwent plasmapheresis (PP). The relationship between symptom improvement and change in immunoglobin G (IgG) and acetylcholine receptor antibody (AchR-Ab) levels in 21 MG patients after PP was analyzed. Patients were divided into two groups: the favorable (n = 11) or unfavorable (n = 10) response groups around the median MG composite improvement rate (50 [29, 56]%) 2 weeks after a PP course. In all patients, the IgG reduction rate before and after PP was higher in the favorable than the unfavorable response group. In AChR-Ab-positive patients, IgG and AChR-Ab reduction rates were higher in the favorable than the unfavorable response group. IgG reduction rate is a predictor of symptom improvement in MG patients who underwent PP.

Cerebral artery signal intensity gradient from Time-of-Flight Magnetic Resonance Angiography and clinical outcome in lenticulostriate infarction: a retrospective cohort study.

Lenticulostriate infarction requires further research of arterial hemodynamic factors, as the disease is diagnosed in the absence of major arterial stenosis or cardioembolism. In this multicenter retrospective cohort study, we included patients who were hospitalized for lenticulostriate infarction from January 2015 to March 2021 at three stroke centers in South Korea. We obtained hemodynamic information on cerebral arteries using signal intensity gradient (SIG), an in-vivo approximated wall shear stress (WSS) derived from Time-of-Flight Magnetic Resonance Angiography (TOF-MRA). A favorable outcome was defined as a modified Rankin Scale of 0 to 2 at hospital discharge. A total of 294 patients were included, of whom 146 (49.7%) had an unfavorable outcome. The unfavorable outcome group showed significantly lower SIG in both middle cerebral arteries (MCAs) than the favorable group (5.2 ± 1.2 SI/mm vs. 5.9 ± 1.2, p < 0.001), and similar findings were observed in other cerebral arteries. The SIGs in both MCAs were independently associated with favorable outcome, with an odds ratio of 1.42 (95% confidence interval, 1.11-1.80; p = 0.005) for the right MCA and 1.49 (95% CI, 1.15-1.93; p = 0.003) for the left MCA, after adjusting for potential confounders. Similar findings were observed in other cerebral artery SIGs. Cerebral artery SIG from TOF-MRA was significantly associated with short-term functional outcomes in patients with lenticulostriate infarction. Further studies are needed to investigate the temporal relationships of SIG in patients with cerebral infarction.

Which Patients With Rhabdomyosarcoma Need Radiotherapy? Analysis of the Radiotherapy Strategies of the CWS-96 and CWS-2002P Studies and SoTiSaR Registry.

To analyze and compare the indications, doses, and application methods of radiotherapy (RT) and their influence on prognosis of patients with localized rhabdomyosarcoma (RMS). One thousand four hundred seventy patients with localized RMS 21 years and younger entered on CWS-96, CWS-2002P, and SoTiSaR were eligible for the analysis. The median follow-up was 6.5 years (IQR, 3.3-9.5). The 5-year event-free survival (EFS) and local control survival (LCS) for 910 (62%) irradiated versus nonirradiated patients were 71% versus 69% and 78% versus 73% (P = .03), respectively. Ninety-five percent of patients in IRS I (90% embryonal RMS [eRMS]) were nonirradiated (EFS, 87%). Irradiated patients with IRS II had improved LCS (91% v 80%; P = .01) and EFS (not significant). In IRS III, EFS and LCS were significantly better for RT patients: 71% versus 56% (P = 3.1e-06) and 76% versus 61% (P = 4.1e-07). Patients with tumors in the head and neck region (orbita, parameningeal, and nonparameningeal) and in other sites had significantly better EFS and LCS and in parameningeal also overall survival (OS). The efficacy of low RT doses of 32 Gy (hyperfractionated, accelerated RT [HART]) and 36 and 41.4 Gy (conventional fractionated RT [CFRT]) in the favorable groups and higher doses of 44.8 Gy (HART) and 50.4 and 55.4 Gy (CFRT) in the unfavorable groups was comparable. Proton RT was used predominantly in head/neck-parameningeal (HN-PM) tumors, with similar EFS and LCS to photon RT. RT can be omitted in patients with IRS I eRMS. RT improves LCS and EFS in IRS II and III. RT improves OS in patients with HN-PM, with proton RT comparable with photon RT. Doses of 32 Gy (HART) or 36 and 41.4 Gy (CFRT) had comparable efficacy in patients with favorable risk profiles and 44.8 Gy (HART) or 50.4 and 55.8 Gy (CFRT) in the unfavorable groups.

5-Years Analysis of Effectivity and Toxicity of Ultra-Hypofractionated Proton Radiotherapy in the Treatment of Low- and Intermediate-Risk Prostate Cancer-A Retrospective Analysis.

We retrospectively analyzed the 5-year biochemical disease-free survival (bDFS) and occurrence of late toxicity in prostate cancer patients treated with pencil beam scanning (PBS) proton radiotherapy. In the period from January 2013 to June 2018, 853 patients with prostate cancer were treated with an ultra-hypofractionated schedule (36.25 GyE/five fractions). The mean PSA value was 6.7 (0.7-19.7) µg/L. There were 318 (37.3%), 314 (36.8%), and 221 (25.9%) patients at low (LR), favorable intermediate (F-IR), and unfavorable intermediate risk (U-IR), respectively. Neoadjuvant hormonal therapy was administered to 197 (23.1%) patients, and 7 (0.8%) patients had adjuvant hormonal therapy. The whole group of patients reached median follow-up time at 62.7 months, and their mean age was 64.8 (40.0-85.7) years. The bDFS rates and late toxicity profile were evaluated. Median treatment time was 10 (7-38) days. Estimated 5-year bDFS rates were 96.5%, 93.7%, and 91.2% for low-, favorable intermediate-, and unfavorable intermediate-risk groups, respectively. Cumulative late toxicity (CTCAE v4.0) of G2+ was as follows: gastrointestinal (GI)-G2: 9.1%; G3: 0.5%; genitourinary (GU)-G2: 4.3%, and no G3 toxicity was observed. PSA relapse was observed in 58 (6.8%) patients: 16 local, 22 lymph node, 4 bone recurrences, and 10 combined sites of relapse were detected. Throughout the follow-up period, 40 patients (4.7%) died, though none due to prostate cancer. Ultra-hypofractionated proton beam radiotherapy is an effective treatment for low- and favorable intermediate-risk prostate cancer, with long-term bDFS rates comparable to other techniques. It is promising for unfavorable intermediate-risk prostate cancer and has acceptable long-term GI and favorable GU toxicity.

985 The Temporal Changes in the Urine of Severe Traumatic Brain Injury Patients

Abstract Aim Neuroinflammation is a secondary injury mechanism that contributes to significant mortality and morbidity with severe traumatic brain injury (TBI). This study aimed to evaluate the temporal neuroinflammatory pattern of the ionised calcium-binding adaptor molecule 1 (Iba1) and transmembrane Protein 119 (TMEM119) microglia marker proteins in the urine of severe TBI patients for 7 days post-injury. Method Urine samples were acquired from fifteen patients with severe TBI upon hospital admission and the subsequent 7 days post-injury. Western blot analysis was used to quantify the urinary levels of Iba-1 and TMEM119 expression in each sample. The patients were stratified by functional outcomes (group 1, death- vegetative state; group 2, moderate-to- severe disability; group 3, good outcomes). Results Iba1 was detected in all (100%) whilst TMEM119 was detected in 65% of acquired urine samples. The mean total normalised Iba1 expression increased for group 2 whilst the opposite response was observed for groups 1 and 3. The mean total normalised TMEM119 expression decreased for group 3 whilst the opposite response was observed for groups 1 and 2. However, these findings were not statistically significant. No significant differences were found in Iba1 or TMEM119 expression between favourable and unfavourable outcome groups. Conclusions Overall, this study cannot associate urinary Iba1 or TMEM119 expression with functional outcomes. However, the presence and temporal patterns of the urinary microglia markers suggest it may be reflective of the underlying neuroinflammatory process and merits further studies.