Poor Outcome Research Articles

IMPACT OF SEX AND GENDER IN STROKE IN SOUTH-AND-SOUTHEAST ASIA: A RAPID SCOPING REVIEW.

South Asia and Southeast Asia account for more than 40% of the global stroke burden, with differences in stroke risk factors, mortality, and outcomes compared to high-income countries. Socio-cultural norms compound the pre-existing biological risk differences, resulting in a disproportionate burden of stroke in women in this region. This review summarizes the sex and gender differences across the stroke care continuum in South Asia and Southeast Asia over the past 20 years. Despite a higher incidence of stroke in men than women in South-and-Southeast Asia, women have greater stroke severity and poorer outcomes after stroke. Higher levels of pre-morbid disability and poor physical health at baseline may be contributory. There is a high prevalence of vascular risk factors such as hypertension, dyslipidemia, cardiac sources of embolism, as well as metabolic syndrome and insulin resistance, among the women in this region. Smoking is uncommon among women, however other forms of smokeless tobacco (SLT), such as tobacco leaf and betel nut chewing are more prevalent, especially in the rural areas in these countries. Women are more likely to have delayed presentations to the hospital due to untimely recognition of stroke symptoms, however, with regards to door-to-needle times or intravenous thrombolysis (IVT) rates, we found equivocal data. Wide gaps exist in stroke awareness and healthcare-seeking behaviors, with women more commonly opting for public hospitals and low-cost wards, more likely to discontinue treatment, and less likely to adhere to post-stroke rehabilitation. This review exposes the gender lacunae in stroke service provision across South Asia and Southeast Asia while acknowledging the many knowledge gaps in our understanding. Although the biological risk differences are non-modifiable, educational, policy, and economic measures to mitigate socio-cultural barriers are much needed in the region. Sound epidemiological data is needed from more countries to better understand these differences and bridge this gap. It is imperative to advocate and implement policies and programs for stroke care viable for women, cognizant of the gender and cost bias, as well as the interplay of social and cultural structures specific to the regions.

Contextual Factors Predictive of Social-Emotional Functioning Among Children of Mothers With and Without Low Intellectual Functioning

This study used Future of Families Child and Wellbeing Study data to examine community, family, and maternal predictors of social-emotional outcomes for kindergarten-aged children of mothers with and without low intellectual functioning. Multivariate analysis of variance and multivariate regression explored relationships between maternal intellectual functioning, covariates, and outcomes. As poverty was an important covariate, predictive of outcomes, marginal analysis was used to understand the interaction between poverty and intellectual functioning on each of the outcomes. Children whose mothers had low intellectual functioning had poorer outcomes than their peers regarding positive, anxious/depressed, and withdrawn behaviors regardless of poverty level. This research supports prioritizing these children for early social-emotional education as they enter elementary school, as well as prioritizing their families for supportive interventions in community-based settings.

Racial, Ethnic, and Socioeconomic Disparities in Pediatric Aquaporin-4-Positive Neuromyelitis Optica Spectrum Disorder

BackgroundOnly 5% of aquaporin-4-positive neuromyelitis optica spectrum disorder (AQP4+ NMOSD) cases emerge during childhood. Poorer outcomes have been suggested in black/African American (AA) adults with NMOSD; however, conflicting and limited data exist for pediatric-onset NMOSD. This study evaluates racial, ethnic, and socioeconomic disparities in pediatric AQP4+ NMOSD outcomes. MethodsThirty-eight pediatric patients with AQP4+ NMOSD cared for at three pediatric tertiary care centers between 2009 and 2021 were identified. Patient addresses connected to socioeconomic measures available from the US Census. Demographic characteristics, pertinent clinical outcomes, and health care utilization in the two years following diagnosis were captured. ResultsCompared with non-Hispanic White children, Black/AA children had a significantly higher Expanded Disability Status Scale (EDSS) (2.46 vs 0.33, P = 0.003), 2.37 more hospital admissions (P = 0.002), and 28.40 additional inpatient days (P = 0.002) in the two years following their NMOSD diagnosis. Additionally, children with public insurance had higher relapse rates than those with private insurance (P = 0.046). At two years and at the most recent follow-up, a significantly higher EDSS was correlated with children living in census tracts with a lower median income, higher deprivation index, and higher proportion of population on assisted income, in poverty, and with vacant housing (all P < 0.05). ConclusionsWe identified racial, ethnic, and socioeconomic disparities in clinical outcomes and health care utilization in pediatric AQP4+ NMOSD. Further prospective and household-level data are needed to dissect the interplay of genetics, structural racism, and social determinants of health so that interventions to optimize care and outcomes for this population may be developed.

Associations between pre-operative cholesterol levels with long-term survival after colorectal cancer surgery: a nationwide propensity score–matched cohort study

PurposeAltered lipid metabolism frequently occurs in patients with solid cancers and dyslipidemia has been associated with poorer outcomes in patients with colorectal cancer. This study sought to investigate whether cholesterol levels are associated with clinical outcomes and can serve as survival predictors.MethodsWe conducted a retrospective cohort study with Danish patients diagnosed with colorectal cancer who had surgery with curative intent for UICC stages I to III between 2015 and 2020. Using propensity score adjustment, we matched patients in a 1:1 ratio to examine the impact of total cholesterol (TC) > 4 mmol/L vs. ≤ 4 mmol/L within 365 days prior to surgery on overall survival (OS) and disease-free survival (DFS).ResultsA total of 3443 patients were included in the study. Median follow-up time was 3.8 years. Following propensity score matching, 1572 patients were included in the main analysis. There was no statistically significant difference in OS or DFS between patients with TC > 4 mmol/L compared with TC ≤ 4 mmol/L (HR: 0.82, 95% CI, 0.65–1.03, HR: 0.87, 95% CI, 0.68–1.12, respectively.). A subgroup analysis investigating TC > 4 mmol/L as well as low-density lipoprotein (LDL) > 3 mmol/L found a significant correlation with OS (HR: 0.74, 95% CI, 0.54–0.99).ConclusionTC levels alone were not associated with OS or DFS in patients with colorectal cancer. Interestingly, higher TC and LDL levels were linked to better overall survival, suggesting the need for further exploration of cholesterol's role in colorectal cancer.Trial registrationNot applicable.

Comparison of oronasal and nasal mask in home mechanical ventilation: observational cohort and bench study.

In patients with chronic respiratory failure, home non-invasive ventilation (NIV) is delivered through nasal or oronasal masks. Masks are a cornerstone for NIV success but can be associated with side effects. However, the type, the frequency and the consequences of these side effects are unknown. Here, we aimed to study the prevalence, nature, and impact of mask-related adverse events in a cohort of stable patients. We then investigated differences between oronasal and nasal masks both in our cohort and in a bench study. Prospective observational cohort including patients established on long-term non-invasive ventilation admitted for their elective review. Data regarding mask-related side effects were assessed using a structured questionnaire. Our bench study was performed using a 3-D printed head connected to an artificial lung. Eight hundred patients were included of whom, 84% had a oronasal mask. Moderate to very severe mask-related side effects occurred in 47% of patients and severe to very severe side effects occurred in 18%. Side effects were associated to a poorer daytime PaCO2 (p=0.005), poorer subjective sleep quality (p=0.003), poorer quality of life (p<0.001). Mask-related side effects were more frequently reported with the use of oronasal masks as compared to nasal masks (p=0.023). Our bench study showed that nasal masks were more stable than oronasal masks (p<0.001). Mask-related side effects are frequent and associated with poorer outcome. Our data suggest that nasal masks may have a better tolerance profile and should be used as a first-line interface.

Subtyping of pancreatic neuroendocrine tumors by transcription factors, hormones, histology, and patient outcome.

Pancreatic neuroendocrine tumors (PanNETs) show pronounced heterogeneity in terms of hormone and transcription factor (TF) expression. TFs such as ARX and PDX1 are related to alpha- and beta-cell-type features, respectively, and partly associate with patient outcome. However, detailed studies correlating hormone expression, histology, and clinical data are lacking. The aim of this study was to identify subtypes of PanNETs that associate with histological, hormonal, and prognostic findings. Atotal of 185resected PanNETs were divided into five subtypes (types A1, A2, B, C, and D) by cluster analysis based on expression of four TFs (ARX, PDX1, ISL1, and CDX2) and correlated to the expression of hormones and DAXX/ATRX as well as ALT activation status, histology, and progression-free survival. Subgroup A1 (ISL1+/ARX+/PDX-/CDX2-) was most frequent (46%), followed by typeB (18%; ISL1+/ARX-/PDX+/CDX2-), A2 (15%; ISL1+/ARX+/PDX+/CDX2-), C(15%; ISL1-/ARX-/PDX-/CDX2-), and D(5%; ISL1-/ARX-/PDX+/CDX2+). Subgroups A1 and A2 showed astrong association with atrabecular growth pattern and glucagon and pancreatic polypeptide (PP) expression (p < 0.001), while A2 was in addition associated with gastrin expression. SubgroupB was associated with insulin production (p < 0.001) and included all 17insulinomas. SubgroupC was associated with solid morphology and expression of serotonin, calcitonin, and adrenocorticotropic hormone (ACTH). SubgroupD showed solid morphology, expression of ACTH, somatostatin, or serotonin and had the shortest disease-free survival (p < 0.01). ALT positivity was associated with poorer outcome in types A1 and A2 but not in other types. PanNETs can be categorized into five subgroups based on different TF signatures, which associate strongly with histology, hormone production, functionality, and patient outcome.

Single-cell dissection reveals promotive role of ENO1 in leukemia stem cell self-renewal and chemoresistance in acute myeloid leukemia.

Quiescent self-renewal of leukemia stem cells (LSCs) and resistance to conventional chemotherapy are the main factors leading to relapse of acute myeloid leukemia (AML). Alpha-enolase (ENO1), a key glycolytic enzyme, has been shown to regulate embryonic stem cell differentiation and promote self-renewal and malignant phenotypes in various cancer stem cells. Here, we sought to test whether and how ENO1 influences LSCs renewal and chemoresistance within the context of AML. We analyzed single-cell RNA sequencing data from bone marrow samples of 8 relapsed/refractory AML patients and 4 healthy controls using bioinformatics and machine learning algorithms. In addition, we compared ENO1 expression levels in the AML cohort with those in 37 control subjects and conducted survival analyses to correlate ENO1 expression with clinical outcomes. Furthermore, we performed functional studies involving ENO1 knockdown and inhibition in AML cell line. We used machine learning to model and infer malignant cells in AML, finding more primitive malignant cells in the non-response (NR) group. The differentiation capacity of LSCs and progenitor malignant cells exhibited an inverse correlation with glycolysis levels. Trajectory analysis indicated delayed myeloid cell differentiation in NR group, with high ENO1-expressing LSCs at the initial stages of differentiation being preserved post-treatment. Simultaneously, ENO1 and stemness-related genes were upregulated and co-expressed in malignant cells during early differentiation. ENO1 level in our AML cohort was significantly higher than the controls, with higher levels in NR compared to those in complete remission. Knockdown of ENO1 in AML cell line resulted in the activation of LSCs, promoting cell differentiation and apoptosis, and inhibited proliferation. ENO1 inhibitor can impede the proliferation of AML cells. Furthermore, survival analyses associated higher ENO1 expression with poorer outcome in AML patients. Our findings underscore the critical role of ENO1 as a plausible driver of LSC self-renewal, a potential target for AML target therapy and a biomarker for AML prognosis.

Molecular Classification of Large B-Cell Lymphoma and High-Grade B-Cell Lymphoma Cases and Association with Outcomes in Morocco

Background: High-grade B-cell lymphoma with c-MYC and BCL2 and/or BCL6 rearrangements (HGBL-DHL/THL) is a recently identified category in the most recent World Health Organization (WHO) classification. For all tumors displaying the appearance of diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL), it is necessary to perform fluorescence in situ hybridization (FISH) in order to achieve an accurate diagnosis. The findings of FISH and immunohistochemistry (IHC) examinations from 50 DLBCL/HGBL samples obtained from Hassan II University Hospital in Fez/Morocco are reported. Methods: This retrospective study included 50 patients diagnosed with DLBCL/HGBL over a period of nine years (2013–2022) and treated with RCHOP chemotherapy protocol. All patients underwent a histological study followed by an immunohistochemical study to confirm the diagnosis and to classify patients according to cell of origin into non-GCB and GCB subtypes; then, a cytogenetic study using FISH was performed to classify patients according to the presence or absence of rearrangements in the c-MYC, BCL2 and BCL6 genes. A comparison was made between the molecular subtypes of DLBCL/HGBL in relation to clinicopathological features and outcomes. Results: Among the 50 cases studied in our population, we found 5 cases of HGBL with DLBCL morphology and 45 cases of DLBCL, which consisted of 13 cases (28.89%) of GCB subtype and 32 cases (71.11%) of non-GCB subtype based on the immunohistochemistry Hans algorithm. After FISH testing of all cases, we found three cases of double-hit lymphoma (DHL) and one case of triple-hit lymphoma (THL). Thus, HGBL-DHL/THL accounted for 8% of the cases. Furthermore, two cases were detected with only one rearrangement in the BCL2 gene and one case harboring a rearrangement in the BCL6 gene. DHL and THL patients and patients with a single rearrangement (BCL2 or BCL6) have a worse prognosis than patients with no rearrangement. Conclusions: DHL and THL are an aggressive entity of HGBL with poorer outcomes in comparison to DLBCL/HGBL NOS. First-line treatment with the RCHOP chemotherapy protocol may not be effective for all aggressive DLBCL cases. More targeted treatment is crucial for better patient outcomes.

Safety and efficacy of up to 60h of iv istaroxime in pre-cardiogenic shock patients: Design of the SEISMiC trial.

Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre-CS patients. The SEISMiC study is a multinational, multicentre, randomized, double-blind, placebo-controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre-CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70-100mmHg for at least 2h] and clinically confirmed congestion, NT-proBNP ≥1400pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies. The study results will contribute to our understanding of the role of istaroxime in pre-CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population.

Impact of COVID-19 on Psychiatric Patients: The Role of Vaccination, Comorbidities, and Biomarkers in Clinical Outcomes

Background/Objectives: The COVID-19 pandemic has posed significant challenges, particularly for individuals residing in psychiatric facilities. This study aims to investigate the impact of COVID-19 on psychiatric patients, focusing on factors such as their vaccination status, comorbidities, medication regimens, and biomarkers like C-reactive protein (CRP) and ferritin. Methods: This retrospective study analyzed 100 patients with confirmed SARS-CoV-2 infections admitted to the private psychiatric clinic “Asclepius of Upper Volos” from March 2020 to March 2023. The data collected included sociodemographic characteristics, vaccination status, symptom severity, medication regimens, and levels of CRP and ferritin. Statistical analyses using IBM SPSS Statistics version 29 included Pearson’s chi-square tests, Student’s t-tests, and a survival time analysis via the log-rank test to assess associations between clinical characteristics and outcomes. Results: Among the participants, 64% were female and 74% received two doses of the COVID-19 vaccine. The majority experienced mild symptoms, with a survival rate of 74%. Statistically significant findings include a higher survival rate among vaccinated individuals (98.6%) versus unvaccinated individuals (1.4%, p &lt; 0.001). Comorbidities like chronic obstructive pulmonary disease (COPD), coronary artery disease, and renal failure were associated with severe symptoms and higher mortality rates. Higher ferritin levels were significantly associated with poorer outcomes, with survivors having a mean ferritin level of 246.2 (SD = 150.3) compared to the 416.9 (SD = 215.9) seen in non-survivors (p &lt; 0.001). Similarly, mean CRP levels were lower in survivors (1.58, SD = 1.96) than in non-survivors (3.46, SD = 2.92), with a p-value of 0.002. Conclusions: The findings underscore the importance of tailored health protocols and continued support for this vulnerable population. Enhanced strategies for managing comorbidities and utilizing biomarkers can aid in better predicting and improving psychiatric patient outcomes.

7833 Gestational Diabetes Mellitus (GDM): A Weighted Spectrum of Clinical Outcomes

Abstract Disclosure: M. Moazzami: None. N. Venkatesan: None. K.S. Rajagopalan: None. A.V. Vella: None. A. Egan: None. Gestational diabetes mellitus (GDM) affects approximately 10% of pregnancies, with rates almost doubling in minority subgroups. Higher body mass index (BMI) is a significant GDM risk factor, and BMI ≥ 25kg/m2 is often used as a criterion in risk factor-based screening programs. However, up to 60% of individuals with GDM have a normal BMI, and it is unclear if this offers protection against associated adverse outcomes. Furthermore, many prior studies fail to address the fact that those of Asian descent require a lower BMI cut-off, given their different distribution of body fat. Our study evaluated GDM pregnancy outcomes using BMI as a risk indicator. We compared individuals with BMIs &amp;lt; 25 kg/m2, 25-30 kg/m2, and &amp;gt; 30 kg/m2. For individuals that self-identified as Asian, we adjusted BMI categories: &amp;lt;23 kg/m2 for normal weight, 23-30 kg/m2 for overweight, and &amp;gt;30 kg/m2 for obese. We identified 2212 subjects diagnosed with GDM via universal screening and Carpenter and Coustan criteria at our institution from 2018 - 22. In total, 508 (23.0%) were normal weight, 611 (27.6%) overweight, and 1093 (49.4%) obese. The average maternal age was 31 years. Higher proportions identified as Hispanic and non-White race in overweight and obese categories. Maternal adverse outcomes were higher in obese compared to overweight or normal BMI categories (cesarian delivery: normal 26.7 v overweight 28.3 v obese 22.7%, p&amp;lt;0.001; hypertensive disorders: normal 13.2 v overweight 12.5 v obese 22.7%, p &amp;lt;0.001). Pharmacological therapy was required in 50% with obesity versus 24.8% in normal, and 28.7% in overweight categories (p&amp;lt;0.001). While there were no differences in live birth rates across categories, infants born to mothers with obesity had a higher birthweight (normal 3.30 v overweight 3.38 v obese 3.45kg, p&amp;lt;0.001) and were more likely to have neonatal hypoglycemia (normal 28.7 v overweight 25.5 v obese 43.8%, p&amp;lt;0.001) and require intensive care unit admission (normal 8.4 v overweight 5.5 v obese 12.7%, p&amp;lt;0.001). Attendance at postpartum glucose testing varied across BMI categories with lower attendance in mothers with obesity followed by normal weight BMI (normal 40.75 v overweight 45.99 v obese 36.2%, p&amp;lt;0.001). Compared to overweight individuals, those with normal weight exhibited higher rates of postpartum glucose intolerance (12.4 v 6.9%, p =0.002). However, those with obesity had the highest rates of glucose intolerance (20.7%, p&amp;lt;0.0002). Individuals with normal weight had the highest rates of breastfeeding (normal 95.9 v overweight 92.8 v obese 91.4% p=0.006). This study highlights the nuanced relationship between BMI and pregnancy outcomes in GDM. While maternal obesity was associated with the poorest outcomes, those with normal BMI were not protected compared to overweight individuals, and experience higher rates of postpartum glucose intolerance. Presentation: 6/2/2024

12210 Prognostic Determinants of Aggressive Histology Papillary Thyroid Carcinoma: A Pathway to Personalized Treatment

Abstract Disclosure: M. Almaghrabi: None. G. Sindi: None. H. Sasseville: None. S. Radi: None. M. Tamilia: None. Background: Papillary thyroid carcinoma (PTC), the most common form of thyroid malignancy, generally presents with a favorable prognosis. However, aggressive variants of Papillary Thyroid Carcinoma (AV-PTC), such as tall cell, hobnail, columnar, and solid forms, pose significant challenges in prognosis and treatment, due to their unique pathological behaviors and increased risks of recurrence and mortality. The management debate for AV-PTC without invasive characteristics is ongoing. It's argued that aggressive histology alone should not dictate the clinical management of PTC patients lacking aggressive features. Objectives: This study aims to investigate the prognostic impact of invasive features in AV-PTC and their implications on clinical outcomes. Methods: We conducted a retrospective cohort study of AV-PTC patients treated from 2008 to 2022, analyzing medical records to identify prognostic factors related to disease recurrence, persistence, and overall survival. This involved distinguishing between groups with invasive characteristics—identified as one of the following: extrathyroidal extension, lymphovascular invasion, the presence of positive lymph nodes, or the detection of distant metastases upon diagnosis, and non-invasive AV-PTC groups. Results: Key findings from our comparison between invasive and non-invasive groups of AV-PTC highlighted significant factors associated with poorer outcomes in the invasive group. These included multifocality (P=0.001), larger tumor size (P=0.047), extra thyroid extension (P=0.002), lymph vascular invasion (P&amp;lt;0.001), the presence of contralateral nodules (P=0.018), and positive surgical margins (P=0.003). Moreover, advanced tumor stage and increased lymph node involvement were more common in invasive cases (P=0.012, P=0.040). Despite no significant differences in genetic mutations between groups (P=0.396), the Ki-67 index was numerically higher in the invasive group. Hemithyroidectomy followed by completion thyroidectomy, performed in 12 patients (22.2%). Survival analysis further highlighted the significance of these invasive features, with Kaplan-Meier curves indicating a 5-year freedom from recurrence rate of 77.18% and a 10-year rate of 68.61%. Univariable Cox regression revealed that the tumor size, positive margins, and tumor stage predicted recurrence. Seven patients had distant metastasis, and all were in the invasion group (18.92%) p= 0.088. Conclusion: Our study emphasizes the critical role of certain invasive features in determining the prognosis of AV-PTC. The adoption of more extensive treatments for patients without invasive features highlights the complexity of treating AV-PTC and the importance of personalized treatment plans. This research advances our understanding of AV-PTC, advocating for individualized approaches to enhance patient outcomes. Presentation: 6/3/2024

Effect of body mass index on ovarian reserve and ART outcomes in infertile women: a large retrospective study

BackgroundObesity poses a significant global health challenge, with profound implications for women’s reproductive health. The relationship between ovarian reserve and body mass index (BMI) remains a subject of debate. While obesity is generally associated with poorer outcomes in assisted reproductive technology (ART), the evidence remains inconclusive. This study aimed to investigate the effect of pre-pregnancy BMI on ovarian reserve and ART outcomes in infertile patients.MethodsWe conducted a retrospective cohort study involving women who underwent in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) procedures at Tongji Hospital between 2016 and 2023. The study included 30,746 initial fresh cycles and 5,721 singleton deliveries. Patients were stratified by age and further categorized into four BMI groups: lean (< 18.5 kg/m²), normal weight (18.5–24.9 kg/m²), overweight (25.0–29.9 kg/m²), and obese (≥ 30.0 kg/m²). The primary endpoints of the study were pregnancy and perinatal outcomes. To explore the association between BMI and these outcomes, we adjusted for relevant confounding factors and utilized multivariate linear regression models, complemented by multifactorial logistic regression analyses.ResultsAnti-Müllerian hormone (AMH) levels were significantly lower in the overweight and obese groups compared to the normal weight group. After adjusting for age, a negative correlation was found between AMH and BMI in the age subgroups of 20–30 and 30–35 years. Among women aged 20–35 years, those in the overweight and obese groups had significantly fewer retrieved oocytes, mature oocytes, and two-pronuclear (2PN) embryos than their normal weight counterparts. Despite these differences, pregnancy outcomes in the overweight and obese groups were comparable to those in the normal weight group across all age categories. Additionally, obesity was linked to an increased risk of gestational diabetes mellitus, hypertensive disorders of pregnancy, and macrosomia.ConclusionsAn age-related decrease in AMH levels was evident with increasing BMI. Although being overweight or obese is associated with poorer embryo and perinatal outcomes, it does not seem to have a substantial impact on fertility.

Clinical and MRI findings in patients with pediatric optic pathway glioma presenting with initial leptomeningeal dissemination

AIMAlthough leptomeningeal dissemination (LMD) is a hallmark of malignant brain tumors, optic pathway glioma (OPG) of various grades can initially present with LMD, which is thenceforth interpreted as an aggressive tumor. In this study, we aimed to evaluate the clinical and imaging findings of pediatric OPG (POPG) patients who presented with initial LMD to ensure a prompt diagnosis and better outcomes. MATERIALS AND METHODSBetween 2000 and 2022, 35 pediatric patients with pathologically proven OPG who presented with and without LMD at our institute were retrospectively reviewed. We compared the demographic and histopathology characteristics, MRI features, and clinical outcomes of the initial LMD group and the non-LMD group. RESULTSCompared with those in the non-LMD group (n=27), POPGs in the LMD group (n=8) were more symmetrically midline-positioned (75% versus 22.2%, p=0.006) and had more ill-defined tumor borders (25% versus 0%, p=0.007), and patients were more likely to develop hydrocephalus (100% versus 63%, p=0.042). There was no significant difference regarding the histopathology (p=0.686) and outcome of tumor recurrence/progression (p=0.341). However, the mortality rate was higher in the LMD group than in the non-LMD group (62.5% versus 18.5%, p=0.016). CONCLUSIONSFeatures of a more symmetrical midline-positioned POPG with indistinct tumor borders and hydrocephalus are risk factors for initial LMD regardless of histopathology. Compared with those without initial LMD, patients with POPG with initial LMD had poorer outcomes, which may suggest the need for a more aggressive treatment protocol.

Leveraging electronic medical record (EMR) changes and virtual care towards improving tobacco screening and referral rates.

426 Background: Continued smoking after a cancer diagnosis is associated with poorer outcomes. Ontario Regional Cancer Centres are required to screen all new cancer patients for tobacco use and offer referrals for cessation support to patients using tobacco. At Princess Margaret Cancer Centre (Toronto, Canada), we leveraged an EMR change to Epic along with uptake in virtual care strategies from COVID-19, to improve both tobacco screening and referral rates for new patients. Methods: Following the EMR transition to Epic in June 2022, we piloted EMR and virtual care strategies from Jan 2023 to Mar 2024 to improve both tobacco screening and referral rates. Due to precautions during COVID-19, screening and referrals were completed using a hybrid pre-visit electronic tobacco use assessment questionnaire and in clinic paper-based referral system. Our interventions were co-developed by a team of hospital leadership, IT team members and clinicians. These included: 1) Collation of tobacco assessment data sources on Epic (Jan 2023); 2) Creation of an Epic referral inbox to track referrals (Aug 2023); 3) Assignment of electronic pre-visit tobacco assessments questionnaires to correct visit types (Sep 2023); 4) Creation of a half-day virtual nursing clinic to offer referrals for cessation support to patients initially declining support or those who were not offered using monthly reports from Epic (Nov 2023). Screening and referral rates were tracked monthly and quarterly during this period. Results: From Jan 2023 to March 2024, 15,063 new patients presented to our cancer centre. Baseline screening and referral rates before COVID-19 were 47% and 16%, respectively. Prior to this QI initiative, screening and referral rates were 18% and 1%, respectively. Post implementation, screening and referral rates improved to 42% and 25% (Table); rates of current tobacco use remained consistent from 12-16%. Collation of tobacco use assessments data on Epic had the greatest impact on improving screening rates from 18% to 39% (p&lt;0.001), while the virtual nursing clinic helped to improve referral rates from 3% to 25% (p&lt;0.001), with the greatest referral rate in Jan 2024 at 36%. Our virtual nursing clinic was feasible, where among patients contacted who initially declined or were not offered cessation support, 90% were contacted within 1-3 phone calls. Among patients contacted, 20% accepted a referral, while 41% of patients had already quit smoking by the time of contact. Conclusions: Both EMR and virtual care strategies helped to successfully improve both tobacco screening and referral rates for smoking cessation support; with the greatest impact from the collation of EMR data sources on tobacco use and development of a virtual nurse led clinic. Quarterly tobacco screening and referral rates. Jan-Mar 2023 Apr-Jun 2023 Jul-Sep 2023 Oct-Dec 2023 Jan-Mar 2024 Screening 33% 38% 39% 41% 42% Referrals 0% 1% 3% 20% 25%

Clinical utility and impact of a diagnostic oncology clinic.

74 Background: Oncologists have expertise in the work-up and management of patients with a suspected diagnosis of cancer. Patients diagnosed with cancer during acute care hospitalization often have poorer outcomes than those diagnosed as outpatients. For these patients, time to appropriate cancer diagnosis, management of cancer-related symptoms, and timely initiation of treatment are key to improved outcomes. Outpatient new diagnosis clinics may improve patient outcomes by improving access to subspecialty care. Methods: Patients seen by the inpatient oncology consult service over a two-month period (8/1/23-8/31/23 and 10/1/23-10/31/23) were included in this analysis. Inpatient management of disease was defined as an invasive procedure to treat the disease or a complication of the disease, initiation of systemic anti-neoplastic treatment, or radiation therapy. Surveys regarding perceived barriers to timely outpatient oncology care were distributed to oncology fellows and attendings. A Diagnostic Oncology Clinic (DOC) was started 2/1/2024 with the goal to decrease time to first outpatient oncology by a median of 12 days to less than 10 days, decrease hospital length of stay (LOS), improve outpatient management of cancer related symptoms, and improve time to treatment. Results: A total of 95 patients were evaluated. 74 (78%) of patients had a new diagnosis of cancer. Most patients had gastrointestinal cancer (n = 40, 42%) or thoracic cancer (n = 24, 25%). 51 patients (53.7%) had metastatic disease. 48 patients (50.5%) had an ECOG performance status of 0 or 1 at the time of consultation. The median hospital LOS was 11 days (IQR, 5-19). 13 patients (13.7%) had an inpatient PET scan and 43 patients (45.3%) required inpatient management of their disease or disease-related complication. 57 patients (60%) were discharged home, 21 (22%) to an extended care facility, and 17 (18%) expired or transitioned to hospice. 35 patients (37%) were seen as new outpatients with a median time to visit of 12 days (IQR 7-20). The median time to initiation of anti-neoplastic therapy as an outpatient was 24 days (IQR 18-33). There were 29 survey respondents corresponding to a response rate of 69%. 16 (55%) felt that about half the time or less patients will have timely follow-up with an oncologist after discharge, and 19 (65%) felt half the time or less patients will have appropriate cancer-related symptom management after discharge. Conclusions: Most patients seen by the inpatient oncology consult service with a new diagnosis of cancer have advanced and symptomatic disease. Historically, there has been significant time to outpatient care and cancer-specific management led by an oncologist. Creation of a diagnostic oncology clinic may shift some diagnostic testing and symptom management from the inpatient to outpatient setting, decrease time to first outpatient visit, and improve provider workflow for a vulnerable patient population. Analysis of this intervention is ongoing.

A Four-Gene Autophagy-Related Prognostic Model Signature and Its Association With Immune Phenotype in Lung Squamous Cell Carcinoma.

In the era of immunotherapy, there is a critical need for effective biomarkers to improve outcome prediction and guide treatment decisions for patients with lung squamous cell carcinoma (LUSC). We hypothesized that the immune contexture of LUSC may be influenced by tumor intrinsic events, such as autophagy. We aimed to develop an autophagy-related risk signature and assess its predictive value for immune phenotype. Expression profiles of autophagy-related genes (ARGs) in LUSC samples were obtained from the TCGA and GEO databases. Survival analyses were conducted to identify survival-related ARGs and construct a risk signature using the Random Forest algorithm. Four ARGs (CFLAR, RGS19, PINK1, and CTSD) with the most significant prognostic value were selected to construct the risk signature. Patients in the high-risk group exhibited worse prognosis than those in the low-risk group (p < 0.0001 in TCGA; p < 0.01 in GEO) and the risk score was identified as an independent prognostic factor. We observed that the high-risk group displayed an immune-suppressive status and showed higher levels of infiltrating regulatory T cells and macrophages, which are associated with poorer outcomes. Additionally, the risk score exhibited a significantly positive correlation with the expression of PD-1 and CTLA4, as well as the estimate score and immune score. This study provided an effective autophagy-related prognostic signature, which could also predict the immune phenotype.

Linking social determinants of health to mental health, movement behaviors, and cognitive function among U.S. youth

BackgroundFew studies have focused on a comprehensive view of social determinants of health (SDOH) domains as influences on the health of young people. This study aimed to investigate the associations between the Healthy people 2030 SDOH-related domains (i.e., economic stability, education access and quality, health care access and quality, neighborhood and built environment, and social and community context) with mental health, movement behaviors, and cognitive function among U.S. youth. MethodsThis cross-sectional study used nationally representative data from the 2020–2021 National Survey of Children's Health, covering 54,595 youth aged 6–17 years. The associations of indicators of SDOH-related domains with mental health (depression and anxiety), movement behaviors (physical activity and screen-based sedentary behavior), and cognitive function were estimated using multivariable logistic regression models, adjusting for age, sex, and race. ResultsEconomic stability, education access and quality, health care access and quality, and social and community context were associated with at least one outcome measure of mental health, movement behaviors, and cognitive function, while neighborhood and built environment was associated with mental health and movement behaviors. The social and community context domain stood out, with friendship difficulty and household-based adverse childhood experiences being associated with poorer outcomes on most health indicators. ConclusionAll five SDOH-related domains are related to aspects of youth health, with the social and community context domain showing the most associations, highlighting the need for interventions to improve social connection and address adverse childhood experiences, which may be more impactful in ameliorating many health-related challenges.

Outcomes of Liner Exchange Versus Component Revision for the Treatment of Stiffness Following Primary Total Knee Arthroplasty

BackgroundThis study aimed to compare outcomes of revision total knee arthroplasty (rTKA) with liner exchange (LE) versus component revision (CRev) for stiffness post-TKA. MethodsWe retrospectively identified all rTKA performed for stiffness after primary TKA using our institutional database (2003 to 2021). Cases with infection, loosening, or < two years follow-up were excluded. There were 129 rTKA included, 91 in the LE, and 38 in the CRev cohorts. The mean follow-up was 8.5 years (range, two to 21). The LE and CRev cohorts had similar baseline demographics (P > 0.05), previous manipulation (P = 0.45), time from primary TKA (P = 0.14), and pre-rTKA arc of motion (AOM) (P = 0.08). The primary outcomes were the achievement of a successful range of movement (ROM), defined as flexion ≥ 90⁰ with an extension deficit of ≤ 10⁰, and AOM improvement. Kaplan-Meier analysis was used to compare survival free from re-revision between cohorts. ResultsFor the entire cohort, 69% achieved a successful ROM, and the mean AOM improved (P < 0.001). Achievement of successful ROM was comparable between LE (72%) and CRev (62%) cohorts (P = 0.29). The mean gain in AOM was similar between LE (24.9⁰) and CRev (25.4⁰) cohorts (P = 0.45). Preoperative extension deficit was associated with poorer outcomes (P = 0.006). The 10-year re-revision-free survival was similar between the LE (86.2%) and CRev (81.1%) cohorts (P = 0.55). Survival from re-revision for stiffness at 10-years was also similar (P = 0.6). The CRev group had increased surgical times (P < 0.0001), blood loss (P < 0.0001), and length of stay (P = 0.01). ConclusionsLE resulted in similar achievement of a successful ROM and re-revision-free survival compared with CRev. In properly selected patients, LE is a reasonable option for the treatment of stiffness after TKA.

Clinical outcomes of primary total knee arthroplasty in non-syphilitic neuroarthropathy of the knee.

Total knee arthroplasty (TKA) in syphilitic neuroarthropathy using earlier implant designs was associated with poorer outcomes. Literature on TKA for non-syphilitic neuroarthropathy using modern contemporary prosthesis is scarce. We aim to analyse the clinical and radiological outcomes of TKA in neuropathic joints. A final cohort of 17 patients (21 knees) with the diagnosis of neuropathic joint undergoing primary TKA between January 2013 to January 2019 were included in the study. The preoperative ambulatory status, range of motion, type of prosthesis, level of constraint and any augmentation used were retrieved from medical records. Radiological evaluation includes Koshino's staging, the magnitude of deformity defined by the Hip-Knee-Ankle (HKA) angle, and any progressive loosening. Pre and postoperative functional scores were obtained by the Knee Society (KSS) and Knee Society Functional Score (KSS-F). Any complications or reoperation were noted till the final follow-up. Preoperative and follow-up functional scores, HKA and range of motion were compared using the paired Samples test. The mean follow-up was 40.2 months (range, 15 to 75 months). Preoperatively, according to the Koshino staging, five knees were in stage 3 (23.8%). The mean HKA angle in valgus knees was 23.60 (range, 11.10 to 42.50) and for the varus knees was 19.30 (range, 4.90 to 39.60). The prosthesis used were posterior stabilized in 7 knees (33.3%), varus-valgus constrained in five knees (23.8%) and a rotating hinge was required in nine knees (42.8%). Metaphyseal sleeves were used along with hinge prosthesis in six knees (28.6%). The mean arc of motion improved from 102.4 ± 22.7 degrees to 105.7 ± 15.5 degrees postoperatively (p = 0.27). The knee society and knee society functional scores improved from 23.3 ± 9.3 and 28.3 ± 12.2 preoperatively to 81.1 ± 5.4 and 80.4 ± 8.5 during the follow up respectively (p < 0.001). There were no progressive radiolucent lines in any knees at the final follow-up. One patient had intraoperative bony medial collateral ligament injury, one patient had deep vein thrombosis after five days from the index surgery and another had postoperative periprosthetic tibial shaft fracture. According to our study, the clinical outcomes of TKA for neuroarthropathy show significant improvement with the diagnosis of non-syphilitic neuroarthropathy, utilization of modern constrained prostheses, and early rehabilitation, at medium-term follow-up. Tibial and femoral stems are preferred for equal stress distribution and to prevent early loosening.