Modern Cohort Research Articles

From bench to bedside and back to bench: investigating the role of platelet heterogeneity in coronary artery disease

Abstract Background/Introduction Platelets exhibit considerable heterogeneity in RNA content, size, and thrombogenicity. Our preliminary investigation of the transcriptome of the RNA-rich reticulated platelets(RPs) in healthy donors revealed an enrichment of prothrombotic transcripts compared to mature platelets(MPs). Recently, we validated the prognostic role of elevated RPs at clinical level in a modern cohort of ACS patients treated with potent P2Y12 inhibitors. However, the pathophysiology of RP hyperreactivity remains unclear, particularly its correlation with adverse events and cardiovascular death. Purpose To study the biology of RPs in patients with chronic coronary syndrome(CCS) and to elucidate their role in disease progression. Methods RPs were isolated from peripheral blood of CCS patients(N=20) and compared with MPs. Cell viability and reactivity of RPs were quantified by FACS. Deep transcriptomic profiling was performed using post-sorting bulk RNA sequencing of RPs and MPs and analyzed with ad-hoc bioinformatic pipelines. Proteomic profiling using mass cytometry(CyTOF) was used to validate the transcriptomic findings with single cell resolution. Results FACS analysis confirmed RPs hyperreactivity showing increased P-Selectin expression upon activation with TRAP, ADP and Collagen(Fig. 1A). Total RNA-sequencing detected 2213 differentially regulated genes with an enrichment in RPs of key functional transcript such as, the von Willebrand Factor VWF(p=3.06*10-33), the thromboxane receptor TBXA2R(p=2.07*10-29) and the collagen receptor GP6(p=1.29*10-38, Fig. 1B-C). Gene ontology and gene set enrichment analyses detected an upregulation of relevant categories as "Regulation of platelet activation" and "Platelet aggregation"(Fig. 1D-F). In addition, we detected a novel alternative splicing event on the collagen receptor transcript GP6 upregulated in RPs(Fig. 1G). We detected 33 differentially regulated miRNAs, including miR-409, miR-134 and miR-432, which have been already linked to prothrombotic phenotypes(Fig. 1H). Additionally, we detected an enrichment of circular RNAs in RPs compared to MPs with several circular RNA upregulated in RPs, that have not been described before(Fig. 1I-K). Mass cytometry detected a significant upregulation in RPs of relevant proteins including the collagen receptor GPVI(p=8.98*10-12, Fig.2) and the thrombin receptor PAR1(p=5.21*10-11). Validation assays in an independent cohort detected an upregulation of the PI3K/AKT pathway in RPs which is downstream of the receptor PAR1 and GP6. Conclusion This study represents the first comprehensive multiomic characterization of RPs in CCS patients, providing insights into their prothrombotic phenotype and into their correlation with cardiovascular events. These findings suggest potential avenues for tailored therapeutic interventions targeting the identified upregulated pathways in patients with elevated RPs, warranting further investigation at the clinical level.

Molecular and Seroepidemiologic Characteristics ofStaphylococcus aureus in Children with Cystic Fibrosis

Abstract Background Cystic fibrosis (CF), through altered sodium and chloride transport across the CF transmembrane receptor (CFTR), is associated with poor mucus clearance, bacterial colonization of the lower airway, chronic pulmonary disease punctuated by acute exacerbations, and chronic inflammation. With increased use of CFTR modulators, changes in the CF pulmonary microbiome have been observed, including decreased prevalence of Pseudomonas colonization; however, overall S. aureus prevalence remains largely unchanged. An important remaining question is whether changes in the CF pulmonary microbiome, while not affecting the overall prevalence of S. aureus colonization, has led to changes in S. aureus diversity or the strain types that are most frequently recovered from children with CF. It is also unknown whether the humoral immune response to S. aureus is altered in the presence of CFTR modulator therapy. Methods Genomic DNA was extracted from S. aureus isolates obtained from two cohorts: a historic cohort, comprised of children not receiving CFTR modulators, and a modern cohort, comprised of children receiving CFTR modulator therapy. Multilocus sequence typing (MLST) and whole genome sequencing (WGS) were used to identify clonotype and characterize virulence factors of interest. Serum was obtained from participants and antibody titers to the extracellular toxins LukAB and LukED were measured. Results One hundred participants were enrolled: 50 in cohort 1 (historic) and 50 in cohort 2 (modern). Compared to cohort 1, isolates identified in cohort 2 were less likely to contain ACME and mecA; similarly, cohort 2 isolates were more likely to contain PVL, sek, and sak. The frequency of specific clonotypes changed over time, with increased prevalence of CC8 and decreased prevalence of CC1, CC5, CC15, and CC30 in cohort 2 compared to cohort 1 (Figure 1A). Serum antibody concentrations to LukAB, a conserved toxin across S. aureus, were similar across cohorts (Figure 1B). Conclusion Over time, the clonotypes responsible for S. aureus colonization in patients receiving CFTR modulators have changed. Despite changes in clonotypes and receipt of CFTR modulators, serum concentrations of LukAB-specific antibodies did not differ. These data suggest that staphylococcal colonization in patients with CF is dynamic over time and may be modified based on the receipt of CFTR modulator therapy. Figure 1. (A) S. aureus clonal complexes, over time, demonstrating a relative increase in CC8 between 2012 and 2022; (B) serum concentrations of LukAB antibodies from 2012 (historic) and 2022 (modern) cohorts. No significant difference was observed in median anti-LukAB concentrations.

Surgical Management of Fibroids: A Changing Landscape.

Background: Uterine fibroids affect patients' quality of life and contribute significantly to health care costs. Studies from 2009 to 2011 demonstrated that fibroids disproportionately affect Black women, with lower odds of uterine preservation and minimally invasive approaches. Objective: This is a retrospective cohort study of data abstracted from the National Surgical Quality Improvement Program database from 2015 to 2019 examining trends in surgical management of uterine fibroids and exploring disparities in surgical approach in a modern cohort. Results: In total, 52,909 women underwent hysterectomy and 15,485 women underwent myomectomy between 2015 and 2019. Over the study period, the overall number of surgeries for fibroids increased by 44.2% with minimally invasive hysterectomy responsible for the majority of this increase. The proportion of patients who underwent myomectomy significantly increased (20.85% to 24.62%, p value <0.0001), whereas hysterectomy significantly decreased (79.15% to 75.38%, p value <0.0001). Bivariate analysis identified younger age, non-White race, and body mass index (BMI) <25 as significantly associated with performance of myomectomy. Non-Hispanic Black (adjusted odds ratio [aOR]: 3.55, 95% confidence interval [CI]: 3.23-3.89), Asian (aOR: 3.26, 95% CI: 2.80-3.80), and Hispanic Black (aOR: 5.50, 95% CI: 3.29-9.25) women were more likely to undergo myomectomy than non-Hispanic White women. Conclusion: Surgical treatment for fibroids increased over time, shifting toward uterine preservation. Myomectomy performance is associated with lower age and BMI and identifying as a racial and/or ethnic minority. These trends may represent improved access to surgical treatment of fibroids, resulting from the growth of minimally invasive gynecological surgery as a specialty and advocacy for equitable health care for all patients.

Upper tract dilation is an independent risk factor for febrile UTI in children with primary vesicoureteral reflux

BackgroundChildren with vesicoureteral reflux (VUR), particularly high-grade VUR, are known to be at increased risk for urinary tract infection (UTI). Current guidelines highlight certain clinical factors in the management of children with VUR; however, the clinical utility of upper tract dilation in the setting of VUR remains unclear. ObjectiveThe purpose of this study is to evaluate risk factors for febrile UTI (fUTI) in children with primary VUR in a modern cohort with emphasis on upper tract dilation parameters, including hydronephrosis and hydroureter. MethodsA prospectively maintained database of children with VUR at a single academic institution from July 2013 to February 2023 was reviewed. Demographic and clinical data were included. Ultrasounds closest to initial VCUG were reviewed for upper tract dilation, including the presence of hydronephrosis, Society of Fetal Urology (SFU) hydronephrosis grade, presence of hydroureter, and anterior-posterior renal pelvic diameter (APRPD). The primary outcome of interest was the development of a fUTI after VUR diagnosis. Patients were censored after their first fUTI or after VUR surgery. ResultsA total of 235 children with primary VUR were evaluated, including 125 (53.2%) females and 110 (46.8%) males. The median age of VUR diagnosis was 10.8 months (IQR: 2.3-63.6 months). A total of 41 (17.4%) children developed a fUTI after VUR diagnosis with a median follow up of 2.3 years (IQR: 0.9-4.6 years). On univariate analysis, variables found to be associated with fUTI included age < 1 year at VUR diagnosis (p=0.021), female sex (p=0.013), high-grade VUR (p=0.024), APRPD ≥ 7 mm (p=0.007), high-grade hydronephrosis (p=0.004), presence of hydronephrosis (p=0.029), and hydroureter (p=0.008). In children with VUR and high-grade hydronephrosis, a larger APRPD was associated with higher fUTI rates (p=0.008). On multivariate analysis controlling for age, sex, and VUR grade, APRPD ≥ 7 mm (OR 2.8, p=0.009), high-grade hydronephrosis (OR 2.5, p=0.025), and presence of hydronephrosis (OR 2.3, p=0.049) were independent risk factors for fUTI. On multivariate models controlling for other upper tract dilation parameters, APRPD ≥ 7 mm was the most significant parameter associated with increased fUTI risk in primary VUR. ConclusionUpper tract dilation is a novel, independent risk factor for fUTI in children with primary VUR, with APRPD being the strongest predictor. Clinicians may consider upper tract dilation parameters in addition to age, sex, and VUR grade when individualizing care in children with primary VUR.

Trends in General Surgeon Operative Practice Patterns in a Modern Cohort

IntroductionAnalyzing general surgeons’ operative case mix can provide an update on contemporary practice patterns and inform pragmatic residency training. MethodsWe performed a retrospective cohort study of general surgeons in Florida, Iowa, and Maryland, 2016-2020. Cases were identified using billing codes. The Cochran-Armitage test of trends was used to evaluate the proportion of practice devoted to specific case types and operative setting over time. ResultsGeneral surgeons (n=1300) performed 1,287,745 cases. The mean (± SD) annual volume per surgeon for all procedures was 356 (± 250), with 198 (± 152) general surgery operations, 57 (± 142) endoscopic procedures, and 101 (±109) other cases. On average, surgeons operated on 7.1 (± 2.6) different organ systems. Trends toward a lower proportion of general surgery operations, and a greater proportion of subspecialty procedures and surgery in the outpatient setting over time were demonstrated (p<0.001). ConclusionThe practice pattern of the general surgeon continues to be heterogeneous, reflecting the persistent need for a broad training paradigm that permits specialization.

Multimodal Imaging Characteristics and Correlation to Outcomes in Patients with CRAO Presenting to a Large Academic Center

PurposeTo characterize a large modern cohort of patients with central retinal artery occlusion (CRAO) by describing presenting features and outcomes relating to manually segmented optical coherence tomography (OCT) features, angiographic reperfusion, and visual recovery. DesignRetrospective clinical cohort study. MethodsPatients with CRAO (ICD-10: H34.1) initially presenting to a tertiary referral center between January 2017 and December 2021 were included. Demographics, eye exam findings, fundus photographs, OCT, and fluorescein angiography (FA) were analyzed. Main outcome measures included total and inner retinal thickness on macular OCT, reperfusion, visual outcomes, and development of neovascularization. Results145 eyes of 144 patients with mean age at of 69.4±13.6 years were included. The mean time to presentation was 1.6±4.2 days, with 19% examined within 4.5 hours and 26% within 6 hours of vision loss. 19% had cilioretinal artery (CLRA) sparing. Mean initial visual acuity (VA) was 1.68±1.10 LogMAR (CLRA sparing) compared to 2.53±0.58 LogMAR (non-CLRA sparing), P<0.001. 32% had elevated inflammatory makers. Out of 47 eyes with final fluorescein angiography, one-third showed some reperfusion. Final vision was 1.40±1.16 LogMAR (CLRA sparing) compared to 2.46±0.81 (non-CLRA sparing), P<0.001. A third of patients improved in VA in both groups, 27% of patients gained more than 2 lines of vision in the CLRA sparing group and 36% in the non-CLRA sparing group. 17% improved to better than 20/200 in CLRA-sparing and 4% in non-CLRA sparing. 11% developed neovascularization all in non-CLRA sparing. In a multiple linear regression, VA at presentation was associated with regaining vision of 2 lines or more (OR=2.603, P=0.007). OCT showed progressive thinning over time, reaching lowest measurements at 6 months, and stabilizing thereafter. ConclusionsIn this modern cohort of acute CRAO patients, presentation to a tertiary facility within 12 hours of symptoms was seen in almost half of the patients. Final visual acuity improved in almost a third of the patients, however, vision better than the legal blindness limit was rare (∼5%). Interestingly, a third of patients had some mild elevation of systemic inflammatory markers. Better visual acuity at presentation was associated with visual gain, while baseline OCT values had poor correlation with final outcome.

Utilization of Partial Cytoreductive Nephrectomy in Patients with Metastatic Renal Cell Carcinoma.

Cytoreductive nephrectomy for metastatic renal cell carcinoma (mRCC) is a standard of care. Partial nephrectomy (PN) in the setting of metastatic disease is an uncommon occurrence, and we aimed to characterize its utilization in a modern cohort. The National Cancer Database was reviewed for patients with mRCC from 2010 to 2017. Patients with cTanyNanyM1 who underwent cytoreductive surgery in the form of PN or radical nephrectomy (RN) were compiled. Our primary outcome was survival outcome for patients who underwent PN compared to RN. Secondary outcomes included 30-day readmission, length of stay, and survival outcomes. A total of 13,896 patients with mRCC who underwent cytoreductive surgery were identified. In total, 13,242 underwent RN and 654 underwent PN. The RN population was more likely to have cN positive disease, while the PN population was more likely to have cT1 disease. Length of stay, readmission and 30-day mortality were not significantly different between PN and RN, but overall mortality and 90-day mortality favored PN (p < 0.001). Cox regression for death showed PN with improved overall survival (HR 0.782, p < 0.001). Logistic regression for predictors of cytoreductive PN revealed cT1 and cN0 as significant factors. Overall survival, as seen on KM analysis, identified that PN exhibited improved 2-year (67.1% vs. 52.0%) and 5-year (40.7% vs. 29.2%) overall survival relative to RN (p < 0.001). PN is an infrequent treatment with mRCC and its utilization is stable from 2010 to 2017. Overall survival is significantly better for those undergoing PN, likely due to their favorable oncologic disease characteristics.

High bone fracture risk in a large modern cohort of liver transplant recipients.

Liver transplantation (LT) has historically been associated with a high prevalence of osteoporosis, but most of the available data date back to late 1990s-early 2000s with limited sample size. Our aim was to assess the prevalence of bone fragility fractures and contributing factors in a large modern cohort of liver transplant recipients. Retrospective study of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015. Final cohort included 366 patients. Electronic radiological images (lateral views of spine X-rays or Scout CT abdominal scans) performed within 6months from LT, were blinded reviewed to screen for morphometric vertebral fractures. Symptomatic clinical fragility fractures were recorded from the medical records. Patients with fragility fractures in the cohort were 155/366 (42.3%), with no significant differences between sexes. Most sustained vertebral fractures (145/155, 93.5%), mild or moderate wedges, with severe fractures more frequently observed in women. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and independent of diabetes or glucocorticoids exposure. Kidney function was significantly worse in women with fractures. Independently of age, sex, alcohol use, eGFR, and etiology of liver disease, low BMI was significantly associated with an increased risk for fractures (adjusted OR 1.058, 95%CI 1.001-1.118, P = 0.046). Our study shows a considerable fracture burden in a large and modern cohort of liver transplant recipients. Given the very high prevalence of bone fractures, a metabolic bone disease screening should be implemented in patients awaiting liver transplantation.

Association of early post-transplant hyperglycaemia and diabetes mellitus on outcomes following heart transplantation.

Early post-transplant hyperglycaemia (EPTH) and post-transplant diabetes mellitus (PTDM) are common following solid organ transplantation and may be associated with adverse outcomes. We studied the prevalence of EPTH and cumulative 5-year prevalence of PTDM in a modern cohort of heart transplant recipients who were free from diabetes at baseline as well as the association of EPTH, PTDM and pre-transplant T2DM with adverse transplant-related outcomes. Retrospective cohort study of heart transplant recipients followed for 5 years at a single centre in Sydney, Australia. A total of 141 patients were included, of whom 25 had pre-existing type 2 diabetes mellitus (T2DM) and 116 were free from diabetes at baseline. In patients without pre-existing T2DM, 88 of 116 (76%) experienced EPTH, which was associated with higher rates of acute rejection and hospitalizations, and lower 5-year survival. PTDM developed in 45 of 116 (39%) patients, all of whom had experienced EPTH. Both PTDM and pre-existing T2DM were associated with increased rates of graft rejection and hospitalization, and greater than three-fold increased likelihood of death compared to patients that remained free from diabetes. EPTH and PTDM are highly prevalent following cardiac transplantation. EPTH develops within days of transplant and is strongly associated with progression to PTDM. Pre-existing T2DM, PTDM and EPTH are associated with greater hospitalization, increased episodes of rejection and worse 5-year survival compared to patients who remained free from diabetes during follow-up.

Placental tissue metals levels, gross placental and fetal morphometry and placental efficiency in a modern birth cohort in Brooklyn NY.

Placental tissue metals levels, gross placental and fetal morphometry and placental efficiency in a modern birth cohort in Brooklyn NY.

Risk Factors and Outcomes of Mucorales Infection in a Modern Cohort of Solid Organ Transplant, Hematopoietic Cell Transplant, and Chimeric Antigen Receptor T-cell Therapy Recipients

Mucorales infections continue to cause significant morbidity and mortality in immunocompromised hosts despite the advent of new approaches for diagnosis and treatment of fungal infections. We aimed to evaluate risk factors and outcomes of Mucorales infection in solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell therapy recipients. This single-center retrospective study included solid organ transplant, hematopoietic cell transplant, and chimeric antigen receptor T-cell patients with cultures positive for Mucorales. Forty-three patients were included for analysis; 34 solid organ transplant (79%) and 9 hematopoietic stem cell transplant or chimeric antigen receptor T-cell (21%). Infection with Mucorales occurred a median of 184 days after transplant. At the time of diagnosis, 36 patients were on antifungal prophylaxis with the majority receiving posaconazole (53%). Thirty-three had clinically significant disease; 30 received definitive anti-Mucorales therapy and 3 empiric antifungal therapy. Isavuconazole was the most common azole used for treatment in monotherapy recipients. All-cause mortality was 64% and, of these deaths, 18 (75%) were directly related to Mucormycosis. The highest mortality was seen in disseminated and intra-abdominal disease (100%), followed by pulmonary disease (50%). There was no significant association with mortality and transplant type or number of immunosuppressive agents. Mucormycosis is an important cause of morbidity and mortality in immunocompromised patients. Breakthrough infection was not uncommon in this study. Data regarding the incidence of infection at approximately 6 months after transplantation can inform prophylaxis and treatment regimens. The spectrum of antifungal regimens used reflects the lack of consensus on ideal regimens for these organisms and a need for more studies.

Impact of Race and Ethnicity on Outcomes After Umbilical Cord Blood Transplantation

BackgroundUmbilical cord blood transplant (UCBT) improves access to transplant for patients lacking a fully matched donor. Previous Center for International Blood and Marrow Transplant Research (CIBMTR) showed that Black patients had a lower overall survival (OS) than White patients following single UCBT. The current study draws on a larger modern cohort and compares outcomes among White, Latinx, Black, and Asian patients. ObjectiveTo compare outcomes by social determinants of health. Study DesignWe designed a retrospective study using CIBMTR data. US patients were between ages 1 and 80; 983 received single and 1529 double UCBT as reported to CIBMTR, following either a myeloablative (N = 1752) or reduced intensity conditioning (N = 759) for acute myeloid leukemia, acute lymphoid leukemia, or myelodysplasia. The primary outcome was 2-year OS. Secondary outcomes included disease free survival, transplant related mortality (TRM), acute and chronic graft vs host disease (GVHD), and GVHD free, relapse free survival (GRFS). ResultsFor 1705 adults, in univariate analysis, 2-year OS was 41.5% (99% CI, 37.6 to 45.3) for Whites, 36.1% (99% CI, 28.2 to 44.5) for Latinx, 45.8% (99% CI, 36.7 to 55.1) for Blacks, and 44.5% (99% CI, 33.6 to 55.6) for Asians. In multivariate analysis of adults, Latinx patients had inferior OS compared to black patients (p = .0005, HR 1.45, 99% CI 1.18 to 1.79). OS improved over time for all racial/ethnic groups. GVHD rates were comparable among the different racial/ethnic groups. In the 807 children, the 2-year OS in univariate analysis was 66.1% (99% CI, 59.7 to 72.2) for Whites, 57.1% (99%CI, 49 to 64.9) for Latinx, 46.8% (99%CI, 35.3 to 58.4) for Blacks, and 53.8% (99%CI, 32.7 to 74.2) for Asians. In multivariate analysis, no difference in OS was observed among racial/ethnic groups (p = .051). Grade III/IV acute GVHD was higher in Blacks compared with Whites (p = .0016, HR 2.25, 99% CI 1.36 to 3.74) and Latinx (p = .0016, HR 2.17, 99% CI 1.43 to 3.30). There was no survival advantage to receiving a UCB unit from a donor of similar race and ethnicity, for any racial/ethnic groups, for both children and adults.Black and Latinx adult patients were more likely to live in areas defined as high poverty. Patients from high poverty level areas had worse OS (p = .03), due to a higher rate of TRM (p=0.04). Educational level, and type of insurance did not impact overall survival, GVHD, TRM or other transplant outcomes. Children from areas with a higher poverty level had higher TRM, regardless of race and ethnicity (p = .02). Public health insurance, such as Medicaid, was also associated with a higher TRM (p = .02). However, poverty did not impact pediatric OS, DFS, or other post-transplant outcomes. ConclusionsOS for UCBT has improved over time. In adults, OS is comparable among Whites, Blacks, and Asians and lower for Latinx patients. In children, OS is comparable among Whites, Blacks, Latinx, and Asians, but Grade III/IV acute GVHD was higher in Black patients. There was no survival benefit to matching UCB unit and patient by race and ethnicity for adults and children.

Chronic liver disease after allogeneic hematopoietic cell transplantation

There are few descriptions of the epidemiology of chronic liver disease (CLD) after allogeneic hematopoietic stem cell transplantation (allo-HCT). Among those transplanted before 2000, viral hepatitis was the dominant cause of CLD. Recently, the prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD, previously known as nonalcoholic fatty liver disease) is increasing in the general population. In addition, survivors of allo-HCT are known to be at increased risk of metabolic syndrome. We set out to describe the epidemiology of CLD in a modern cohort of allo-HCT recipients. We hypothesized that MASLD would be the most common cause of CLD in the cohort. We undertook a retrospective cohort and nested case-control study of 2-year survivors of allo-HCT in Alberta transplanted between 2008 and 2018. Among 392 2-year survivors of allo-HCT between 2008 and 2018, the prevalence of CLD was 41.8% and MASLD was identified in 56% of those with CLD, followed by iron overload in 47% of those with CLD. The prevalence of MASLD among the entire cohort was 46%. Although most patients developed CLD before 2 years post-transplant, there was a 13% cumulative incidence of new CLD after 2 years posttransplant. Grade 2-4 acute graft-versus-host disease and/or moderate-to-severe chronic graft-versus-host disease and pretransplant CLD were strongly associated with CLD. In the case-control study examining the association between cardiovascular risk factors and CLD, type 2 diabetes was associated with CLD. Cirrhosis developed in 1.5% of survivors, and MASLD was an underlying etiology in one half of these cases. There was no difference in overall survival and non-relapse mortality between those who did and did not develop CLD. MASLD is the main cause of CLD in recent long-term survivors of allo-HCT and may be associated with post-transplant corticosteroid exposure and type 2 diabetes. We note a shift in the underlying etiology of CLD post-HCT: previous studies describe viral hepatitis as the most common cause of CLD. The high prevalence of MASLD in allo-HCT recipients has important implications for survivorship care.

Prevalence of pain-related presentations in Canadian pediatric emergency departments.

Pain is a common reason for attendance to the emergency department; however, pediatric specific data on the prevalence, location, and etiology of painful presentations are limited in the literature. Therefore, the objective of this study was to determine the prevalence of pain-related presentations to pediatric emergency departments during the triage process and characterize the anatomical locations and organ systems most affected by pain in a modern cohort. A two-center health record review of triage documentation was conducted at Canadian pediatric emergency departments. All children (< 18years) were eligible for inclusion. Data were extracted from administrative sources with one week of consecutive patients included every 3months over a one-year timeframe. Regression analyses were completed to identify variables associated with painful presentations and analgesia provision during the triage process. A total of 7208 emergency department presentations were included. Median [IQR] child age was 5.2 [1.9, 11.8] years and 53.2% were male. 58.8% of children were found to have pain as a component of their triage presentation. Of those with pain (n = 4237), 24.1% had a pain score documented and 13.8% had analgesia provided at triage. Location of pain (n = 4523) was predominantly in the head (38.0%), extremities (27.8%), and abdomen (22.8%). Primary organ systems most affected (n = 4237) included the musculoskeletal (31.1%), gastrointestinal (18.3%), and cutaneous (including lacerations) (14.4%) systems. In this study, pain was identified in almost 60% of all pediatric emergency department presentations at the time of triage. Suboptimal documentation of pain scores and provision of analgesia at triage were found for children with pain. These results support early assessment and implementation of pain management strategies at triage. Results can also focus further research efforts to the management of the most commonly presenting types of pediatric pain.

Validation of the graded prognostic assessment and recursive partitioning analysis as prognostic tools using a modern cohort of patients with brain metastases

Abstract Background Prognostic indices for patients with brain metastases (BM) are needed to individualize treatment and stratify clinical trials. Two frequently used tools to estimate survival in patients with BM are the recursive partitioning analysis (RPA) and the diagnosis-specific graded prognostic assessment (DS-GPA). Given recent advances in therapies and improved survival for patients with BM, this study aims to validate and analyze these 2 models in a modern cohort. Methods Patients diagnosed with BM were identified via our institution’s Tumor Board meetings. Data were retrospectively collected from the date of diagnosis with BM. The concordance of the RPA and GPA was calculated using Harrell’s C index. A Cox proportional hazards model with backwards elimination was used to generate a parsimonious model predictive of survival. Results Our study consisted of 206 patients diagnosed with BM between 2010 and 2019. The RPA had a prediction performance characterized by Harrell’s C index of 0.588. The DS-GPA demonstrated a Harrell’s C index of 0.630. A Cox proportional hazards model assessing the effect of age, presence of lung, or liver metastases, and Eastern Cooperative Oncology Group (ECOG) performance status score of 3/4 on survival yielded a Harrell’s C index of 0.616. Revising the analysis with an uncategorized ECOG demonstrated a C index of 0.648. Conclusions We found that the performance of the RPA remains unchanged from previous validation studies a decade earlier. The DS-GPA outperformed the RPA in predicting overall survival in our modern cohort. Analyzing variables shared by the RPA and DS-GPA produced a model that performed analogously to the DS-GPA.

Incidence of brain metastases within the VA Healthcare System.

e14691 Background: Advancements in cancer detection and treatment are thought to underlie decreasing cancer mortality rates. The influence of these on the development of brain metastases, which can be a driving factor for mortality, has not been addressed in a modern cohort. Methods: The age adjusted incidence (AAI) of brain metastases (BMs) from any primary and those with an underlying breast, colorectal, lung, kidney, or melanoma primary were calculated by federal fiscal year from 2005 through 2019 in the VA Healthcare System (VAHS) based on the timing of the first documentation of ICD9 or ICD10 codes in the patient’s medical record, The AAI rates were calculated based on the age distribution in VAHS and US census in 2020. Incidence proportions (IPs) were calculated by dividing the number of brain metastases with an underlying primary by the number of cases of that primary from 2005-2009. Results: 36,598 new BM cases of any underlying primary were diagnosed from 2005-2019. 96.2% of diagnoses were in men, 17.9% in African-Americans. The median age at diagnosis was 66.4 years old. 67.9% of BMs cases had a prior lung cancer diagnosis. The IP of lung, colorectal, kidney, melanoma, and breast cancer were 13.7%, 1.87%, 3.67%, 4.31%, and 3.08%, respectively. Overall, the AAI of BMs in the VAHS increased from 22.5 in 2005 to 24.6 in 2012 then decreased to 16.8 in 2019. Similar trends in the AAI of BMs with a lung, colorectal, kidney, or melanoma primary were observed (Table). The AAI of BMs with a breast primary increased from 2005 to 2019 (Table 1). The decrease in BM AAI from 2005 to 2019 paralleled decreases in lung (104.6 to 73.4), colorectal (63.9 to 37.5), kidney (27.5 to 26.4) and breast (140.5 to 136.1) cancer AAI as well as melanoma (28.2 to 21.7) AAI over the same time, respectively. Conclusions: In a modern cohort from the largest integrated health care system in the United States, the IPs of BMs from five primary sites associated with BMs were lower compared to older cohorts and the AAI rates decreased over time. Future studies will assess the impact of modern screening and treatment on BM incidence. [Table: see text]

Association of Safety-Net Hospital Status With Outcomes Following Head and Neck Cancer Operations.

To assess perioperative and readmission outcomes of patients undergoing head and neck cancer (HNCA) surgery at safety-net hospitals (SNHs) in a modern cohort. Retrospective cohort study. Nationwide Readmissions Database (NRD), 2010 to 2019. All elective adult (≥18 years) admissions involving HNCA resection were identified from the NRD. To calculate safety-net burden, the proportion of Medicaid or uninsured patients admitted to each hospital for any indication was tabulated annually, with centers in the highest quartile defined as SNHs. To perform risk adjustment in assessing perioperative and readmission outcomes, multivariable regression models were developed. Of an estimated 133,018 head and neck surgical patients, 26.5% (n = 35,268) received treatment at a SNH. Utilization of SNHs increased over the decade-long study period, with 29.8% of individuals treated at these sites in 2019. After multivariable adjustment, several patient factors were noted to be associated with SNHs, including younger age, lower comorbidity burden, and income within the lowest quartile. Although incidence of adverse events decreased at both SNHs and non-SNHs during the study period, treatment at SNHs remained associated with these events after risk adjustment (adjusted odds ratio: 1.17, 95% confidence interval: 1.08-1.28, P < .001). SNHs continue to provide valuable specialty care to underserved populations, often with limited financial resources. Despite promising results from prior decades demonstrating comparable perioperative outcomes, the present study noted increased adverse events following HNCA surgery at these sites. Such findings underscore the need for continued advocacy to secure necessary funding for these centers.

Dermoid cyst management and outcomes: a review of over 1000 cases at a single institution

BackgroundMature cystic teratomas represent nearly 60% of benign ovarian neoplasms across all age groups. We aim to update existing descriptive studies of ovarian teratomas including the epidemiology, rate of torsion/malignancy, and treatment modalities in a large modern cohort of patients. Study DesignThis is a retrospective cross-sectional study of all pathology-confirmed cases of ovarian teratoma who underwent surgery at one tertiary care institution from 2004–2015. Patient demographics, ovarian cyst characteristics, surgical approach and timing, rate of spillage, and surgical complications were examined. Results1,054 cases of ovarian teratoma were identified during the study period. There were 113 cases of bilateral teratoma (10.7%). Mean age at diagnosis was 38 years. Average cyst size was 6.26cm. The overall rate of torsion was 5.6%, with a higher rate of torsion with increasing cyst size. Over 70% of cases were treated with minimally invasive surgery, which was associated with decreased perioperative complications but an increased risk of cyst spillage. Among 394 patients with cyst spillage, only one developed chemical peritonitis. The malignant transformation rate of mature cystic teratoma in this cohort was 1.1%. This cohort included 100 pregnant women with mature teratoma. Pregnant patients were more likely to have minimally invasive surgery in the 1st trimester and more likely to undergo laparotomy in the 2nd or 3rd trimester. ConclusionsIn this large modern cohort, we found similar rates of bilaterality, torsion, malignant transformation, and struma ovarii in ovarian teratomas when compared to previous literature. Most cases of ovarian teratoma can be managed laparoscopically, which is associated with a lower surgical complication rate. Despite increased risk of cyst spillage with a minimally invasive approach, chemical peritonitis is a rare complication.

Contemporary trends in breast cancer in females under the age of fifty: An NCDB study

IntroductionBreast cancer among patients under 50 years old accounts for 18% of new cases. Few studies have reported current trends in clinical-pathologic features and treatment patterns for young patients. We evaluated these trends in a modern cohort of breast cancer patients under 50. MethodsWe identified women with breast cancer from the National Cancer Database from 2004–2017. Patients were grouped into 18–29, 30–39, 40–49, and ≥ 50-year cohorts. Proportions and temporal comparisons between demographic, clinicopathologic features, and treatment types were evaluated. Temporal trends across sequential periods were performed. ResultsOf the 2387,902 patients selected, 554,941 (23.3%) were younger than 50. During 2004–2017, the proportions remained stable in the 18–29 (0.5–0.6%) and 30–39 (4.5–5%) age groups, while decreasing in the 40–49 group (absolute difference: −4.8%, p < 0.001). Overall, in those younger than 50, early-stage breast cancer (clinical stage 0-II) increased by 3.9%, while stages III and IV decreased by 2.7% and 1.3% (p < 0.001), respectively. Mastectomy rates and neoadjuvant systemic therapy use increased by 10.4% and 9.8%, respectively (p < 0.001) in all groups under 50. ConclusionsDespite stable proportions in the youngest age groups (18–29 and 30–39), a noteworthy decrease in the 40–49 age group was observed, suggesting potential shifts in disease detection. The rise in early-stage disease and neoadjuvant systemic therapies should theoretically translate into an increase in the number of breast-conserving candidates. However, the increase in mastectomies highlights the need to better understand the factors influencing treatment decisions in this population.

Risk Factors Associated with Thromboembolic Complications After total Hip Arthroplasty: An Analysis of 1,129 Pulmonary Emboli.

Venous thromboembolism (VTE) remains a dangerous complication after total hip arthroplasty (THA), despite advances in chemoprophylactic measures. This study aimed to identify risk factors of developing pulmonary embolism (PE) and deep vein thrombosis (DVT) after THA using a modern cohort of patients reflecting contemporary practices. The Premier Healthcare Database was queried for primary, elective THAs from January 1st, 2015, to December 31st, 2021. Patients who developed PE or DVT within 90 days of THA were compared with patients who did not develop any postoperative VTE. Differences in patient demographics, comorbidities, hospital factors, perioperative medications, chemoprophylactic agents, and allogeneic blood transfusion were compared between cohorts. Multivariable logistic regression models were used to identify independent risk factors of PE and DVT. In total, 544,298 THAs were identified, of which 1,129 (0.21%) developed a PE and 1,799 (0.33%) developed a DVT. Patients diagnosed with a PE had significantly higher rates of in-hospital death (2.6% vs 0.1%, P < 0.001) compared with those without a PE. Age (adjusted odds ratio: 1.02 per year, 95% confidence interval [CI]: 1.01 to 1.03) and Black race (aOR: 1.52, 95% CI: 1.24 to 1.87) were associated with an increased risk of PE. Comorbidities associated with increased risk of PE included chronic pulmonary disease (aOR: 1.58, 95% CI: 1.36 to 1.84), pulmonary hypertension (aOR: 2.06, 95% CI: 1.39 to 3.04), and history of VTE (aOR: 2.38, 95% CI: 1.98 to 2.86). Allogeneic blood transfusion (aOR: 2.40, 95% CI: 1.88 to 3.06) was also associated with an increased risk of PE while dexamethasone utilization was associated with a reduced risk (aOR: 0.83, 95% CI: 0.73 to 0.95). Increasing age; Black race; allogeneic blood transfusion; and comorbidities, including chronic pulmonary disease, pulmonary hypertension, and history of VTE, were independent risk factors of PE after THA. Given the increased mortality associated with PE, patients should be carefully evaluated for these factors and managed with an appropriate chemoprophylactic regimen.