Incidence Rate Research Articles

Comparison of Effects between Nasal Bi-Level Positive Airway Pressure and Nasal Synchronized Intermittent Mandatory Ventilation in Neonatal Respiratory Distress Syndrome

Aims/Background Neonatal respiratory distress syndrome (NRDS) is characterized by progressive aggravation and rapid progression of respiratory distress, with a high incidence rate among premature infants. If left untreated, NRDS results in a poor prognosis. In recent years, various respiratory support modalities have received extensive attention in clinical practice. The therapeutic effect of different respiratory support modes on NRDS has gradually become the focus of clinical research. The aim of this study was to explore the therapeutic effects of nasal bi-level positive airway pressure (nBiPAP) and nasal synchronized intermittent mandatory ventilation (nSIMV) on NRDS. Methods This study retrospectively analyzed the clinical data of 157 newborns with NRDS in the Mudanjiang Medical University Affiliated Second Hospital from January 2021 to December 2023, finally including 153 cases after excluding 4 cases with missing clinical data. According to the non-invasive ventilation method, these newborns were categorized into a nBiPAP group (receiving nBiPAP treatment, n = 77) and an nSIMV group (receiving nSIMV treatment, n = 76). The blood gas indices, using time of ventilator, hospitalization time, therapeutic effects, and incidence of complications were compared between the two groups. Results The PaCO2, PaO2, and pH levels in the nBiPAP group were basically consistent with those in the nSIMV group before and after treatment (p > 0.05). The use time of ventilator, hospitalization time, and therapeutic effects in the nBiPAP group were similar to those in the nSIMV group (p > 0.05). Additionally, both groups demonstrated no significant difference in the incidence of complications such as intraventricular hemorrhage, apnea, necrotizing enterocolitis, and feeding intolerance (p > 0.05). The incidence rates of ventilator-associated lung injury and neonatal bronchopulmonary dysplasia in the nBiPAP group were lower than those in the nSIMV group, with a significant difference (p < 0.05). Conclusion Both nBiPAP and nSIMV have shown good effects in treating NRDS, with nBiPAP showing a significant advantage in reducing the incidence rates of complications such as ventilator-associated lung injury and neonatal bronchopulmonary dysplasia.

A combination of clinical, electrocardiographic, and echocardiographic parameters predicts pulmonary hypertension occurrence in patients with end-stage renal disease

BackgroundPulmonary hypertension (PH) in patients with end-stage renal disease (ESRD) has a high incidence rate and mortality and its early identification is critical. However, whether a combination of clinical, electrocardiographic, and echocardiographic parameters can predict the occurrence of PH in patients with ESRD remains to be elucidated. Herein, we evaluated the predictive value of the combined score of these parameters.MethodsData from 370 patients with newly diagnosed ESRD who underwent routine echocardiography and electrocardiography between May 2016 and May 2017 were retrospectively evaluated. The incidence of PH during a 60-month follow-up period was investigated. Twenty-one patients were excluded due to incomplete data among other reasons. Finally, 349 patients were included in the analysis, of whom, 158 (45%) developed PH.ResultsAnalysis of electrocardiogram reports suggested that a corrected Q-T interval (QTc) of >438.5 ms was associated with PH. Echocardiographic reports suggest that left atrial diameter (LAD), interventricular septum thickness in end-diastole (IVSd), stroke volume (SV), and pericardial effusion are also associated with PH development. Results of multivariate Cox analysis showed that LAD >3.785 cm, IVSd >1.165 cm, SV >79.5 ml, QTc >438.5 ms, and pericardial effusion were independent predictors of PH in patients with ESRD. The incidence of new-onset PH increased significantly with increasing composite scores, that is, the sum of risk scores determined using hazard ratios.ConclusionsA total score that includes a combination of parameters such as LAD >3.785 cm, IVSd>1.165 cm, SV >79.5 ml, QTc >438.5 ms, and pericardial effusion can help describe the risk of new-onset PH.

Characterizing Lipid Changes and Use of Lipid-Lowering Medications in Patients With Alopecia Areata Treated With Baricitinib: Integrated Results From the BRAVE-AA1 and -AA2 Clinical Trials

Introduction. Elevations in total cholesterol, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) can occur with baricitinib treatment, consistent with a class effect of JAK inhibitors. In this analysis, we characterized changes in lipid levels and use of lipid-lowering medication among patients with severe alopecia areata (AA) treated with baricitinib through 152-weeks of treatment. Methods. Two integrated datasets from the BRAVE-AA1 (NCT03570749) and BRAVE-AA2 (NCT03899259) trials were analyzed: 1. Extended BARI AA includes patients treated with continuous baricitinib 2 mg (N=383) and 4 mg (N=565) from baseline and censored at dose change: 2. ALL BARI AA (N=1303) includes data for patients who received ≥1 dose of baricitinib at any time. Outcomes included abnormal changes in lipid parameters, mean change from baseline in lipids, and concomitant use of lipid-lowering medications. Results. At time of enrollment, 43% of patients had hypercholesterolemia. Incidence rates for categorical increases in total cholesterol (TC; ≥240mg/dL), LDL-C (≥130 mg/dL), and HDL-C (>60 mg/dL) were 11.8, 13.3, and 12.9 per 100 patients-years of exposure, respectively in the ALL BARI AA dataset. In the Extended BARI AA the mean maximal increase in lipids (mg/dL) for baricitinib 4 mg was 20.9 for TC, 12.4 for LDL-C, and 8.5 for HDL-C. Changes occurred early and stabilized by one year for TC and LDL-C and by 12 weeks for HDL-C. 6.1% (n=79) of patients in the ALL BARI AA dataset used lipid-lowering medication at baseline; post-baseline, 3.9% (n=51) discontinued this medication and 4.7% (n=61) initiated lipid lowering medication. No patients discontinued baricitinib treatment due to treatment-emergent adverse events related to hyperlipidemia. Conclusions. Elevations in TC, LDL-C, and HDL-C, but not triglycerides were associated with baricitinib treatment in patients with AA, consistent with a class effect of JAK inhibitors. The relatively low use of lipid-lowering medications at baseline despite the prevalence of hypercholesterolemia may reflect undermanagement of this condition in the population. Notably, the mean maximal magnitude of increase in lipid levels on baricitinib was modest. Initiation of lipid-lowering medication was infrequent, and no patients discontinued due to lipid abnormalities.

Antidiabetic Medication and Asthma Attacks

ImportanceElevated body mass index (BMI) and type 2 diabetes are prevalent in asthma and are associated with an increase in the risk of asthma attacks. In experimental studies, the diabetes medications metformin and glucagon-like peptide-1 receptor agonists (GLP-1RA) have mitigated airway inflammation, hyperresponsiveness, and remodeling. However, epidemiological evidence is limited.ObjectiveTo estimate the association of metformin and add-on antidiabetic medications (GLP-1RA, dipeptidyl peptidase-4 inhibitors, sulphonylureas, sodium-glucose cotransporter-2 inhibitors, and insulin) with asthma attacks.Design, Setting, and ParticipantsThe study used data from the UK Clinical Practice Research Datalink (CPRD) Aurum linked hospital admissions and mortality data from 2004 to 2020. A triangulation approach was used that applied 2 distinct approaches to enhance robustness: a self-controlled case series (SCCS) and a metformin new user cohort with inverse probability of treatment weighting (IPTW). Eligible participants were new users of metformin with type 2 diabetes. To evaluate the association between metabolic phenotypes (BMI, glycemic control) and asthma phenotypes (type 2 inflammation, asthma severity), interaction analyses were conducted. Negative control analyses were conducted to assess for bias.ExposureThe primary exposure was metformin; secondary exposures included add-on antidiabetic medications.Main OutcomesThe primary outcome was first asthma exacerbation (short course of oral corticosteroids, unscheduled asthma-related hospital attendance, or death) during 12-month follow-up. Incidence rate ratios (IRRs) with 95% CIs were estimated using fixed-effect conditional Poisson models in the SCCS, and hazard ratios (HRs) were estimated using weighted Cox proportional hazards models in the cohort.ResultsOf more than 2 million adults with asthma, 4278 patients (2617 women [61.2%]; mean [SD] age, 52.9 [13.6] years) were identified for the SCCS and 8424 patients (4690 women [55.7%]; unexposed: mean [SD] age, 61.6 [13.2] years; exposed: mean [SD] age, 59.7 [13.7] years) for the IPTW cohort. Metformin was found to be associated with fewer asthma attacks of similar magnitude in both approaches (SCCS: IRR, 0.68; 95% CI, 0.62-0.75; IPTW: HR, 0.76; 95% CI, 0.67-0.85). Negative control analyses did not find evidence of significant bias. Hemoglobin A1c levels, BMI, blood eosinophil cell counts, and asthma severity did not modify the association. The only add-on antidiabetic medication to have an additive association was GLP-1RA (SCCS: IRR, 0.60; 95% CI, 0.49-0.73).Conclusions and RelevanceThe results of this cohort study suggest that metformin was associated with a lower rate of asthma attacks, with further reductions with the use of GLP-1RA. This appeared to be associated with mechanisms other than through glycemic control or weight loss and occurred across asthma phenotypes.

Bimekizumab Efficacy and Safety in Patients With Psoriatic Arthritis Who Had Skin and Nail Psoriasis at Baseline: Up to 2-year Results From Two Phase 3 Studies

Introduction: Bimekizumab (BKZ), a humanized anti-IL17F anti-IL17A antibody has demonstrated efficacy and tolerability to 1 year in patients with psoriatic arthritis (PsA) and psoriasis.1 Nail psoriasis is associated with increased PsA risk, more severe disease and decreased quality of life, in patients with psoriasis.2,3 Here, efficacy and safety of BKZ treatment are reported to 2 years in patients with PsA, skin involvement and nail psoriasis in two phase 3 trials. Methods: BE OPTIMAL (NCT03895203; bDMARD-naïve) and BE COMPLETE (NCT03896581; TNFi‑IR) assessed subcutaneous BKZ 160 mg Q4W in patients with PsA. Placebo (PBO) patients switched to BKZ (PBO/BKZ) at Wk16. BE OPTIMAL included a reference arm (adalimumab [ADA] 40 mg Q2W); ADA patients switched to BKZ at Wk52 (ADA/BKZ). BE OPTIMAL Wk52 and BE COMPLETE Wk16 completers could enter BE VITAL (open-label extension; NCT04009499), where all patients received BKZ. Post-hoc data reported for patients with baseline skin involvement (≥3% body surface area) and nail psoriasis (modified Nail Psoriasis Severity Index >0). Efficacy reported to Wk104 of BE OPTIMAL/Wk100 of BE COMPLETE. Missing data imputed using non‑responder, multiple or worst-category imputation. Safety data are reported for all patients treated with BKZ. Results: Of 263/852 (30.9%) bDMARD-naïve and 159/400 (39.8%) TNFi-IR patients with baseline skin and nail psoriasis, 230 (87.5%) and 136 (85.5%) patients completed Wk104/Wk100. Efficacy responses at Wk52 on BKZ were sustained to Wk104/Wk100 across joint, skin, nail, physical function and composite outcomes. ADA/BKZ cohort showed sustained responses after switch. For bDMARD-naïve and TNFi-IR patients on BKZ, the exposure-adjusted incidence rates per 100 patient-years (EAIR/100 PY) for ≥1 treatment-emergent adverse event (TEAE) were 154.9 and 78.8, respectively; and for serious TEAEs, 6.6 and 5.2 respectively. None of the reported Candida infections were serious or systemic; all 3 deaths were deemed unrelated to treatment. Conclusions: BKZ treatment demonstrated sustained clinical efficacy to 2 years in patients with PsA, skin involvement and nail psoriasis, regardless of prior TNFi treatment. BKZ was well tolerated; consistent safety profile to previous reports.1

Deucravacitinib in Plaque Psoriasis: 4-year Safety and Efficacy Results from the Phase 3 POETYK PSO-1, PSO-2, and LTE Trials

Introduction: Deucravacitinib, an oral, selective, allosteric TYK2 inhibitor, is approved in multiple countries for treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy. Deucravacitinib was superior to placebo and apremilast in the global, 52-week, phase 3 POETYK PSO-1 and PSO-2 parent trials in moderate to severe plaque psoriasis. Upon completion, patients could enroll in the ongoing POETYK long-term extension (LTE) trial. Here, deucravacitinib safety/efficacy are reported through 4 years. Methods: PSO-1/PSO-2 randomized patients 1:2:1 to oral placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. At Week 52, patients enrolled in the LTE received open-label deucravacitinib. Safety was evaluated in patients receiving ≥1 deucravacitinib dose. Exposure-adjusted incidence rate (EAIR) per 100 person-years (PY) was used to assess adverse events (AEs). Efficacy outcomes included PASI 75, PASI 90, and sPGA 0/1 and were analyzed using mNRI in LTE patients receiving continuous deucravacitinib from Day 1 of the parent trials. Results: 1519 patients received ≥1 deucravacitinib dose; cumulative exposure was 4392.8 PY. EAIRs/100 PY were decreased/comparable from the 1-year to 4-year cumulative period, respectively, for AEs (229.2, 131.7), serious AEs (5.7, 5.0), deaths (0.2, 0.3), discontinuation due to AEs (4.4, 2.2), herpes zoster (0.8, 0.6), malignancies (1.0, 0.9), major adverse cardiovascular events (0.3, 0.3), and venous thromboembolism (0.2, 0.1). Clinical response rates with continuous deucravacitinib (n=513) were maintained from Year 3 (PASI 75, 73.8% [95% CI, 69.6-78.0]; PASI 90, 49.0% [44.4-53.7]; sPGA 0/1, 55.2% [50.5-59.9]) to Year 4 (PASI 75, 71.7% [67.0-76.3]; PASI 90, 47.5% [42.6-52.4]; sPGA 0/1, 57.2% [52.1-62.2]) by mNRI. Conclusion: Deucravacitinib demonstrated a safety profile through 4 years consistent with 3 years with no emergence of new or long-term safety signals. Efficacy was maintained through 4 years in patients receiving continuous deucravacitinib from Day 1 in PSO-1/PSO-2.

Management of people after stroke in 383 Victorian general practices, 2014-2018: analysis of linked stroke registry and general practice data.

To evaluate the management in Victorian general practice of people who have been hospitalised with stroke or transient ischaemic attacks (TIA). Retrospective observational study; analysis of linked Australian Stroke Clinical Registry (AuSCR) and general practice data. 383 general practices in the Eastern Melbourne, South Eastern Melbourne, and Gippsland primary health networks (Victoria), 1 January 2014 - 31 December 2018. Adults who had been hospitalised with acute stroke or TIA and had at least two encounters with the same general practice during the observation period (7-18 months after the acute event). Assessment of cardiometabolic risk factors (blood pressure, serum lipids, blood glucose, urinary protein); prescribing of guideline-recommended prevention medications (blood pressure-, lipid-, or glucose-lowering, antithrombotic agents); attainment of guideline targets for cardiometabolic risk factors at final assessment during observation period. During 2014-2018, 3376 eligible AuSCR registrants (1465 women, 43.4%) had at least two encounters with one of the 383 general practices during the observation period; median age at stroke onset was 73.9 (interquartile range, 64.4-81.9) years, 737 events were TIAs (21.8%). Blood pressure was assessed in 2718 patients (80.5%), serum lipids in 1830 (54.2%), blood glucose in 1708 (50.6%). Prevention medications were prescribed for 2949 patients (87.4%), including lipid-lowering (2427, 71.9%) and blood pressure-lowering agents (2363, 70.0%). Blood glucose targets had been achieved by 1346 of 1708 patients assessed for this risk factor (78.8%), blood pressure targets by 1935 of 2717 (71.2%), and serum lipid targets by 765 of 1830 (41.8%). The incidence of having risk factors assessed was lower among patients aged 60 years or younger (incidence rate ratio [IRR], 0.97; 95% confidence interval [CI], 0.92-1.03) and those over 80 years of age (IRR, 0.92; 95% CI 0.88-0.97) than for those aged 61-80 years, and for women (IRR, 0.91; 95% CI, 0.87-0.95) and people with dementia (IRR, 0.89; 95% CI, 0.81-0.98). The likelihood of having classes of prevention medication prescribed was lower for patients aged 60 years or younger (IRR, 0.92; 95% CI, 0.88-0.97) and those over 80 years of age (IRR, 0.96; 95% CI, 0.92-0.997) than for patients aged 61-80 years, and for women (IRR, 0.95; 95% CI, 0.91-0.98) and people with dementia (IRR, 0.88; 95% CI, 0.78-0.98). The general practice management of people who have been hospitalised with stroke or TIA could be improved. Effective monitoring of cardiometabolic risk factors will enable general practitioners to optimise care for people who need careful attention to prevent adverse secondary events.

Application of Submandibular Intubation as Alternative to Elective Short-Term Tracheotomy for Particular Cases of Oral and Maxillofacial Tumors Resection and Defects Reconstruction

Objective: To describe the cases of oral and maxillofacial tumors (OMFT) resection and defects reconstruction under submandibular intubation (SMI) performed in our institution; secondly, to systematically review and analyze the characteristics of studies about SMI in oral and maxillofacial surgery to estimate the incidence rate of complication. Method: Data related to all 6 patients included in this study were prospectively collected from November 2016 to November 2023. The tract for endotracheal tube was created by bluntly dissection from the submandibular area to the floor of mouth. We performed an exhaustive search for studies about SMI using Pubmed, Embase, Proquest, and Chinese Biomedical Literature Database. Meta-analysis of the incidence rate of complication and infection was performed using STATA 14.1. Results: There was a male predominance (87.3%); the mean age was 47.8±16.8 years; squamous cell carcinoma (SCC) was the most frequent diagnosis (33.3%); the mean time of the operation was 237.0±65.2 minutes; the SMI procedure mean time was 5.5±0.9 minutes; and the mean time to extubation 133.3±12.5 minutes. No accident or complication was observed intraoperatively and postoperatively. The systematic review included 22 out of 234 studies screened. The meta-analysis showed an overall complication rate and superficial infection rate of 5.7% and 3.7% in the last 15 years versus 20.2% and 10.6% in over 15 years ago. Conclusion: Submandibular intubation was found technically easy, safe, and effective alternative of elective short-term tracheotomy, orotracheal and nasotracheal intubations in our series of OMFT resection and defects reconstruction.

ANÁLISE DO PERFIL EPIDEMIOLÓGICO DAS INTERNAÇÕES E ÓBITOS POR LEUCEMIA NO BRASIL NA FAIXA ETÁRIA PEDIÁTRICA: UMA ANÁLISE DO ANO DE 2017 ATÉ A ATUALIDADE.

The present study is based on the epidemiological analysis of leukemia, the most common childhood cancer, which has a high prevalence and incidence rate in the pediatric population, as well as a significant impact on mortality in this age group. The objective of this research is to analyze the national profile of hospital admissions and deaths due to leukemia from 2017 to the present. For this purpose, secondary data from the Hospital Information System (SIH) and the Mortality Information System (SIM), collected from the DATASUS digital platform, were used. The selected variables included age groups under 1 to 19 years, male and female gender, and racial/ethnic categories of white, mixed-race, black, Asian, and indigenous populations. The results revealed a higher prevalence and incidence of hospitalizations for leukemia over the years, particularly in the Southeast, Northeast, and South regions, with a significant concentration in the 1 to 9-year age group, among males, and in the mixed-race and white populations. Regarding the number of deaths, substantial data were observed in the Southeast, Northeast, and North regions, predominantly in individuals aged 10 to 19 years, among males, and in the white and mixed-race populations. Given the above, the urgency of addressing leukemia in the pediatric population in Brazil is evident, as it impacts patients’ quality of life, the vital statistics of this population, and the healthcare system. The data highlight the need for public health actions to reduce regional disparities in specialized cancer care, late diagnoses, and ineffective and limited treatments.

Abstract B007: Identification of Asporin as a HER3 ligand exposes a therapeutic vulnerability in metastatic prostate cancer

Abstract Background: Rates of prostate cancer incidence and advanced-stage diagnoses are increasing. Despite curative-intent therapies, nearly all patients with advanced disease progress to metastatic castration-resistant prostate cancer (mCRPC), a lethal form of the disease. There is an urgent unmet need to understand the mechanisms driving prostate cancer progression and identify alternative therapies for patients with mCRPC. It is well-established that cancer-associated fibroblasts (CAF) in the tumor microenvironment secrete factors that enable cancer cells to establish metastases. Asporin (ASPN) is an extracellular protein secreted by a subset of CAF and is associated with worse oncologic outcomes, yet the mechanisms remain poorly understood. In this study, we sought to identify the molecular interactions between the CAF-secreted ASPN and metastatic prostate cancer cells. Methods: ASPN-induced HER2/HER3 activation and downstream signaling was identified by RNA-sequencing and then confirmed by immunoblotting in multiple human metastatic prostate cancer cell lines. Binding interactions were assessed computationally by AlphaFOld2 with Rosetta refinement and substantiated by co-immunoprecipitation assays. CRISPR-cas9 targeting of HER2 and HER3 and therapeutic inhibition of HER2 with Tucatinib were used to determine the role of HER2/HER3 in ASPN-induced signaling and migration. The efficacy of Tucatinib and antibody-drug conjugates (ADC) targeting HER2 (Trastuzumab-deruxtecan) and HER3 (Patritumab-deruxtecan) were assessed in multiple metastatic prostate cancer cell lines in vitro. Trastuzumab-deruxtecan was assessed in PC3 xenografts in vivo. Prostate cancer metastases from 33 patients were assessed by IHC for HER2 and HER3 and by RNAscope for ASPN. Results: We report that ASPN is a novel ligand of HER3 and induces HER3 heterodimerization with its preferred dimerization partner, HER2. ASPN activates established ErbB-associated pathways including Phosphoinositide 3-kinase (PI3K), Mitogen-activated protein kinase (MAPK), and calcium signaling, in multiple metastatic prostate cancer cell lines to promote cell migration. Genetic and molecular inhibition of HER2/HER3 mitigates ASPN-induced signaling and cell migration, suggesting these receptors are required for paracrine activation by ASPN. Importantly, small molecule and ADC therapies targeting HER2/HER3 significantly diminished prostate cancer cell growth in vitro, with enzalutamide-resistant cells showing increased sensitivity. Trastuzumab-deruxtecan nearly resolved tumors in an in vivo xenograft model. Lastly, ASPN+ CAF in the TME of HER2/HER3-expressing metastatic prostate cancer is frequently observed in patient samples, supporting the clinical relevance of these findings. Conclusions: Collectively, these findings indicate ASPN functions as a HER3 ligand to induce cellular migration, and inhibition with anti-HER2/HER3 therapies highlights potential clinical utility for patients with HER2-expressing metastatic prostate cancer. Citation Format: Amanda B. Hesterberg, Hong Yuen Wong, Jorgen Jackson, Monika Antunovic, Brenda L. Rios, Evan Watkins, Riley E. Bergman, Brad A. Davidson, Sarah E. Ginther, Diana Graves, Elliott F. Nahmias, Jared A. Googel, Lillian B. Martin, Violeta Sanchez, Paula Gonzalez Ericsson, Quanhu Sheng, Benjamin P. Brown, Jens Meiler, Ben H. Park, Kerry R. Schaffer, Jennifer B. Gordetsky, Paula J. Hurley. Identification of Asporin as a HER3 ligand exposes a therapeutic vulnerability in metastatic prostate cancer [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr B007.

Abstract C015: IL-27R signaling modulates protective versus pathogenic T cell responses in hepatocellular carcinoma

Abstract Liver cancer is the 3rd leading cause of cancer death. Hepatocellular carcinoma (HCC) is the major form of primary liver cancer, with a growing incidence rate estimated to surge by 50% in the coming twenty years. Although some success has been achieved with immune checkpoint blockade inhibitors, many HCC patients do not respond well to the treatments. Therefore, it is critical to better understand immune mechanisms regulating HCC to identify new biomarkers and develop novel immunotherapies for HCC patients. HCC is driven by chronic liver diseases and is frequently associated with chronic inflammation in the liver. Cytokines are small mediators of inflammation that play an essential role in inflammatory diseases and tumorigenesis. IL27 is a member of the IL6/IL12 superfamily with context-dependent roles in various inflammatory disorders and cancer. IL27 receptor (R) is expressed by most immune cells and several non-immune cells and plays pivotal roles in the regulation of immune responses. Recent work from our lab shows that IL27R signaling suppresses anti-cancer immune response in HCC, acting via the control of innate cytotoxic cells, and Il27ra -/- mice develop significantly less HCC. However, how IL27R signaling regulates T cell subsets in HCC in vivo remains elusive. Here, using diethylnitrosamine (DEN)-induced mouse model of HCC we found a reduction of regulatory T cells (Tregs) in tumor-bearing Il27ra-/-mice along with lowered HCC burden. ScRNA sequencing of CD45+ cells isolated from HCC tumors indicated a less proliferative phenotype of Tregs and more cytotoxic and less exhausted CD8 T cells in mice with Il27ra deficiency. Pathway analysis suggested that IL27R-deficient Tregs were more quiescent, as characterized by the downregulation of various metabolic pathways. Our newly generated Foxp3 cre Il27ra flox mice show a significant reduction of DEN-driven HCC accompanied by an increase of tumor-infiltrating activated CD8 T cells compared to IL27R sufficient controls. Treg-specific deletion of IL27R caused the upregulation of TCF1 in Tregs which has been recently demonstrated to control Treg immune-suppressive functions in colorectal cancer. Meanwhile, tumor-infiltrating effector CD8 T cells were increased in Foxp3 cre+ Il27ra flox mice relative to their Foxp3 cre- Il27ra flox littermate controls. Interestingly, CD8 T cell specific deletion of IL27R did not impact HCC growth in CD8 cre Il27ra flox mice. Overall, our data suggest that IL27R signaling suppresses anti-HCC immunity by enhancing the pro-tumorigenic Tregs and suppressing anti-tumor effector CD8 T cell functions. Citation Format: Zhengzheng Shi, Jiani Zhu, Aleksandra Mazitova, Anastasiia Marchenko, Sergei Grivennikov, Ekaterina Koltsova. IL-27R signaling modulates protective versus pathogenic T cell responses in hepatocellular carcinoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr C015.

Finerenone in Women and Men With Heart Failure With Mildly Reduced or Preserved Ejection Fraction: A Secondary Analysis of the FINEARTS-HF Randomized Clinical Trial.

Sex is associated with the clinical presentation, outcomes, and response to treatment in patients with heart failure (HF). However, little is known about the safety and efficacy of treatment with finerenone according to sex. To estimate the efficacy and safety of finerenone compared with placebo in both women and men. Prespecified analyses were conducted in the phase 3 randomized clinical trial Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure (FINEARTS-HF). The trial was conducted across 653 sites in 37 countries. Participants were adults aged 40 years and older with symptomatic HF and left ventricular ejection fraction (LVEF) of 40% or greater randomized between September 2020 and January 2023. Finerenone (titrated to 20 mg or 40 mg) or placebo. The primary outcome was a composite of cardiovascular death and total (first and recurrent) HF events (unplanned HF hospitalizations or urgent HF visits). A total of 6001 patients were randomized in FINEARTS-HF, of whom 2732 were women (45.5%), with a mean (SD) age of 73.6 (9.1) years. Women had higher rates of any obesity, higher LVEF (54.6 [7.6%] vs 50.9 [7.6] for men), lower mean (SD) estimated glomerular filtration rate than men (59.7 [19.1] vs 64.1 [20.0] for men; P<.001) , worse New York Heart Association functional class, and lower Kansas City Cardiomyopathy Questionnaire-Total Symptom Scores (KCCQ-TSS) (mean [SD] 62.3 [24.0] vs 71.0 [23.1]). The incident rate of the primary outcome was slightly lower in women (15.7; 95% CI, 14.3-17.3) than in men (16.8; 95% CI, 15.4-18.3) per 100 person-years. Compared with placebo, finerenone reduced the risk of the primary end point similarly in women and men: rate ratio 0.78 (95% CI, 0.65-0.95) in women and 0.88 (95% CI, 0.74-1.04) in men (P = .41 for interaction). Consistent effects were observed for the components of the primary outcome and all-cause mortality. The mean increase (improvement) in KCCQ-TSS from baseline to 12 months was greater with finerenone, regardless of sex (P = .73 for interaction). Finerenone had similar tolerability in women and men. In FINEARTS-HF, finerenone reduced the risk of the primary end point similarly in women and men with heart failure with mildly reduced or preserved ejection fraction. Finerenone had similar tolerability in women and men. ClinicalTrials.gov Identifier: NCT04435626.

Adverse drug reactions and its associated factors among geriatric hospitalized patients at selected comprehensive specialized hospitals of the Amhara Region, Ethiopia: a multicenter prospective cohort study.

Adverse drug reactions are more prevalent in geriatric patients and are frequently associated with a range of polypharmacy-related issues as well as some physiological aging-related alterations. These affect the pharmacokinetic and pharmacodynamic properties of drugs. This study aimed to assess the magnitude of ADRs and their contributing factors among geriatric patients admitted at Comprehensive Specialized Hospitals of the Amhara Region. A multicenter prospective cohort study was carried out from May 2023 to August 2023 on geriatric patients admitted to four randomly selected comprehensive hospitals in the Amhara region. We used logistic regression to find the factors influencing the occurrence of ADRs. A P value of less than 0.05 was deemed statistically significant. During the study's follow-up period, 373 patients in total were included. An incidence rate of 31.10% (95% CI: 26.38-35.82) was obtained from the identification of 121 ADRs in total. The organ most frequently affected by ADRs was the gastrointestinal tract (28.92%), followed by the cardiovascular system (19.01%), and the drug class most often implicated in ADRs was antibiotics (21.49%), then anticoagulants (12.40%). ADRs were substantially linked to being overweight (P < 0.001), having been hospitalized in the previous six months (P = 0.000), and hyperpolypharmacy (p = 0.047). 93.39% of all ADRs received the interventions. 85.12% of the adverse drug reactions were successfully resolved. This study found that over one-third of older people and individuals admitted to the hospital experienced ADRs. Overweight, hyperpolypharmacy, and patients who had previously been admitted during the preceding six months were significantly linked with the occurrence of ADRs. Improving the drug safety of elderly patients, particularly those who are admitted, should be a greater priority for healthcare professionals.

Dose-Related Effects and Bleeding Risk of Ketorolac in Pediatric Tonsillectomy.

To investigate the safety and effectiveness of dose-related ketorolac administration in children who underwent tonsillectomy. Data sourced from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases, encompassing literature from their inception until June 2024. The perioperative administration of ketorolac in comparison with a control group was included in this analysis. The outcomes assessed were postoperative pain levels; utilization patterns of analgesic medication in terms of quantity and frequency; and the incidence rates of postoperative nausea, vomiting, and bleeding. Eighteen studies with 11,729 patients that investigated. The ketorolac treatment group with postoperative bleeding had a higher incidence of primary bleeding (significant bleeding and operative bleeding control) compared to the control group. However, ketorolac treatment did not affect the risk of secondary bleeding. Subgroup analysis showed that 0.9 to 1 mg/kg of ketorolac significantly increases primary operative control (odds ratio [OR] = 4.0700 [1.6352; 10.1302]; I2 = 0.0%) and primary significant bleeding (OR = 2.3200 [1.1322; 4.7538]; I2 = 0.0%). On the other hand, 0.5 mg/kg ketorolac did not show any influence on primary operative control. The administration of ketorolac (both 0.9-1 and 0.5 mg/kg) led to a significant decrease in postoperative pain (2-24 hours), nausea, and vomiting compared to the control group. Low-dose (0.5 mg/kg) ketorolac administration to children could significantly reduce the risk of primary significant bleeding and surgical hemostasis compared to high-dose administration (0.9-1.0 mg/kg). In addition, low-dose ketorolac administration could provide sufficient pain control and reduce postoperative nausea and vomiting.

Haemolytic uremic syndrome as a cause of chronic kidney disease stage 5 in children is in retreat: results from the Polish Registry of Kidney Replacement Therapy in children (2000-2023).

Haemolytic uremic syndrome (HUS) is a life-threatening disease with a historically poor prognosis in children receiving maintenance kidney replacement therapy (KRT). This study aimed to analyse the incidence and outcome of chronic kidney disease stage 5 (CKD5) due to Escherichia coli-HUS (STEC-HUS) and complement-mediated HUS (CM-HUS) in children, compared with controls with non-HUS CKD5 over the last 24years. The study included 1488 children undergoing KRT in Poland between 2000 and 2023. Thirty-nine patients with CM-HUS and 18 with STEC-HUS were identified and analysed for incidence, KRT modality and survival. The incidence rate of CKD5 was 0.09 cases/million age-related population (marp) for STEC-HUS and 0.23/marp for CM-HUS, while no new cases have been observed in recent years. CKD5 due to CM-HUS developed significantly earlier from initial HUS manifestation than in STEC-HUS (median 0.2 vs. 9.8years). CM-HUS was associated with younger age at initiation of KRT compared to STEC-HUS and non-HUS controls (median 6.0years vs. 10.9 and 10.9years), with higher risk of death (Hazard Ratio 1.92, 95% confidence interval 0.9-4.13) and worse 5-year kidney graft survival at 77%, 93% and 90%, respectively (p < 0.001). In recent years, both CM-HUS and STEC-HUS have become increasingly rare causes of CKD5 in children. CKD5 due to CM-HUS in the eculizumab era and due to STEC-HUS after improving supportive treatment is exceptional. Children on KRT due to STEC-HUS had a significantly better survival, shorter waiting time for kidney transplantation and better kidney graft survival compared to the CM-HUS group.

Epidemiology of Orofacial Clefts: A Spatio-Temporal Descriptive Analysis in Tripoli, Libya, 2017-2021

Orofacial clefts are the most common congenital anomalies affecting the orofacial region. An abnormal facial development causes this congenital deformity during gestation; its aetiology is multifactorial. It is crucial to understand the prevalence of craniofacial anomalies in each community to determine the size of the problem, enhance the life standards for the patients, and assess the efficacy of interventions. In this study, we aimed to provide a picture of the prevalence of orofacial clefts in Tripoli, Libya. Also, it provides a useful reference for cleft-type distribution with their etiological risk factors. The data was collected from the archives of cleft babies referred to major specialized hospitals in Tripoli, Libya, from 2017 to 2021. Variables were collected and analyzed, including data related to cleft cases and their parents. During the study period, the incidence of orofacial clefts was 1.06 per 1,000 live births. The prevalence of cleft lip was 38.3%, cleft palate was 42.2%, and cleft lip with palate was 19.6%. The results showed that 2017 had the highest incidence rate, reaching 32.2%, while it was 8.3% in 2021. The prevalence was generally higher among males than females, at a difference rate of 3.47%. A history of folic acid deficiency and unsupervised drug intake during pregnancy was noted (58.3% and 61.7%, respectively). In addition, the higher prevalence was more common among mothers older than 34. Moreover, it has observed that 46.8% of patients` fathers were smokers. The study concluded that the incidence of cleft defects in Tripoli, Libya, was relatively low, and the role of the predisposing factors in increasing the incidence of cleft deformity remains uncertain. Further studies are recommended to find out the root cause.

Projected epidemiological trends and burden of liver cancer by 2040 based on GBD, CI5plus, and WHO data.

Incidence of liver cancer as one of the most common cancers worldwide and become the significant contributor for the mortality among cancer patients. The disease burden, risk factors, and trends in incidence and mortality of liver cancer globally was described subsequently estimated the projections of liver cancer incidence or mortality by 2040. Data regarding age-standardized incidence and mortality rates for liver cancer was obtained from multiple databases, including GLOBOCAN 2020, CI5 volumes I-XI, WHO mortality database, and Global Burden of Disease (GBD)-2019. Concentrating on worldwide variations, this thorough analysis offers insights into patterns of incidence and mortality based on gender and age. Our findings encompass significant indicators, including age-standardized rates (ASRs), average annual percentage change (AAPC), and future projections extending up to the year 2040. Liver cancer holds the sixth position in terms of most frequently diagnosed cancers and stands as the sixth leading cause of cancer-related deaths worldwide in 2020, accounting for 905,677 new cases and 782,000 fatalities. Additionally, liver cancer contributed to 12,528,421 age-standardized disability-adjusted life years (DALYs), with an age-standardized DALYs rate of 161.92 in 2019 worldwide. The age-specific incidence rates exhibited significant variations across different regions, showing a fivefold difference in males and females. A significant increase in incidence was observed in North Europe and Asia, while North African countries reported a higher mortality burden (ASR, 10 per 100,000) compared to developed countries. Since last few years, the incidence and mortality rates have increased and attained Annual Average Percentage Change (AAPC) incidence rate of 7.7 (95% CI 3.9-11.6) for men and the highest AAPC mortality rate of 12.2 (95% CI 9.5-15.0) for women. In 2019, Western Europe emerged as the high-risk region for DALYs related to smoking and alcohol consumption, while high-income North America carried a high risk for DALYs associated with a high body-mass index. The projected trend indicates a surge in new liver cancer incident cases, expected to rise from around 905,347 to an estimated 1,392,474 by 2040. This study described the evidence pertinent to higher incidence trends in liver cancer, particularly among both young and older adults, encompassing males and females, as well as those who are HIV-infected and HBsAg positive. A significant rise in the young population poses a significant public health concern that warrants attention from healthcare professionals to prioritize the promotion of health awareness and the development of effective cancer prevention strategies, particularly in many developing countries.

Evaluation of the osteoarthritis disease burden in China from 1990 to 2021: based on the Global Burden of Disease Study 2021

ObjectiveThis study aims to understand the current status and trend of the disease burden of osteoarthritis (OA) in people over 30 years old in China from 1990 to 2021 and identify the priority population groups, to provide reference data for the prevention and treatment of OA in China.MethodsThe Global Burden of Disease Study 2021 was used to describe the incidence, prevalence, and disability-adjusted life years (DALYs) of OA in adult aged 30 years or older in China by sex and age groups, which was used to analyze the disease burden of OA from 1990 to 2021. The joinpoint regression model and age-period-cohort model were used to characterize the temporal trend.ResultsIn 2021, the number of OA prevalence in China was about 152.85 million, and the number of incidences was about 11.65 million. The age-standardized prevalence rate (ASPR), age-standardized incidence rate (ASIR) and age-standardized DALYs rate (ASDR) of OA in China are lower than those in developed countries such as Korea, the United States of America and Japan, but higher than those in India. Knee osteoarthritis had the highest ASPR and ASDR. The highest incidence rate was 50–54 years, and the highest prevalence and DALYs rate were in the age group of patients over 95 years old. The incidence rate of women in all age groups is higher than that of men. From 1990 to 2021, the ASIR, ASPR and ASDR of OA in China roughly showed an increasing trend year by year. The age-period-cohort analysis showed that the peak age groups for longitudinal age incidence of OA in China from 1992 to 2021 were 50–54 years and 80–84 years. We found that the OA incidence was highest in the period 2017–2021.ConclusionThe disease burden of OA in those over 30 years old in China from 1990 to 2021 will become more and more serious, and the target population for primary prevention is the female population under 50 years old. The development of a scientific and effective comprehensive prevention and treatment program for OA is imminent.

Time trends of cancer incidence in young adults (20-49 years) in Italy. A population - based study, 2008-2017.

To evaluate short-term (2008-2017) cancer incidence trends in Italy for individuals aged 20-49 years by sex and cancer type. Observational study from population-based data collected by 20 Italian Cancer Registries, covering 33% of the Italian population. The age-standardized incidence rates (ASRs), overall and stratified by area, sex, cancer site or type, and major age groups (i.e., 20-39, 40-49), were computed. In 2008-2017, cancer incidence rates were almost two times higher in Italian women aged 20-49 than in age-corresponding men (202.2 vs 112.4 per 100,000) on account of elevated rates of breast and thyroid cancers. Contrasting trends emerged according to cancer sites/types. ASRs for female breast cancer increased steadily from 2008 (82.4) to 2014 (86.2) and remained unchanged thereafter (i.e., 86.5 in 2017). During the study period, there was an increase for testicular cancer, skin melanoma in both sexes, and thyroid cancer until 2013 (followed by a slight decrease from 2014 to 2017). Conversely, ASRs consistently declined for colorectal cancer and were substantially stable or slightly decreasing for cervix uteri (from 8.1 to 7.7), ovary (from 7.5 to 6.9) and non-Hodgkin lymphoma (from 8.3 to 7.6 in men and from 5.9 to 5.5 in women). Study findings do not support a unique temporal pattern for the incidence of early-onset cancer in Italy until 2017, as reported in other countries. Increases in incidence documented in both sexes for some tumor sites was counterbalanced by a decrease in other sites. The importance of supporting prevention strategies from the youngest of ages must be emphasized, and the role of anticipated screening should be carefully addressed.

Estimating the rates of dementia using administrative data linked to cohort studies.

Current estimates of dementia and Alzheimer's disease incidence and prevalence are required to understand the health needs of the elderly. We used two Australia cohort studies, administrative datasets, and data linkage techniques to estimate dementia rates in Australia. The study used Australian Longitudinal Study on Women's Health and the Health in Men Cohort Study. Records of dementia were obtained from linked sources and incidence and prevalence estimates were produced. Capture-recapture methods were used to estimate numbers of dementia cases not identified through data linkage. There were 3399 (28.5%) men with dementia identified from any source and 3767 (34.8%) women. Rates of dementia incidence and prevalence were similar between sexes but were raised in men once estimates of unidentified cases were included. Cohort studies and linked administrative data can be used together to produce current estimates of dementia prevalence and incidence comparable to other population estimates.