Multivariate Cox Regression Model Research Articles

Constructing a Nomogram for Predicting Pelvic Osteosarcoma: A Retrospective Study Based on the SEER Database and a Chinese Cohort.

Aims/Background Generally, pelvic osteosarcoma has a worse prognosis compared with limb osteosarcoma. This study aims to create and validate a new nomogram for predicting the prognosis of pelvic osteosarcoma. Methods Clinical data of 62 patients derived from the Surveillance, Epidemiology, and End Results (SEER) database and 31 Chinese patients diagnosed with pelvic osteosarcoma were gathered. Kaplan-Meier survival analysis was utilized to calculate the median survival time for all variables. Univariate and multivariate Cox regression models were employed to identify the prognostic factors of pelvic osteosarcoma. A nomogram was constructed using data gleaned from the SEER cohort and verified using the receiver operating characteristic (ROC) curve and calibration plot in the Chinese cohort. Results Kaplan-Meier analysis revealed that individuals of other races (Asians) (hazard ratio (HR) = 0.24, 95% confidence interval (CI): 0.1-0.57, p = 0.001), aged ≤51 years old (HR = 0.4, 95% CI: 0.22-0.73, p = 0.003), and with tumor size ≤160 mm (HR = 0.37, 95% CI: 0.2-0.71, p = 0.03) had better survival outcomes. Conversely, factors such as no primary surgery (HR = 3.6, 95% CI: 1.81-7.15, p < 0.001), lung metastasis (HR = 1.96, 95% CI: 1.17-3.28, p = 0.010), and radiotherapy (HR = 1.89, 95% CI: 1.10-3.25, p = 0.021) were associated with poorer survival. Multivariate Cox analysis indicated that lung metastasis (HR = 2.57, 95% CI: 1.29-5.13, p = 0.008), other races (Asians) (HR = 0.23, 95% CI: 0.07-0.75, p = 0.015), tumor size (HR = 0.28, 95% CI: 0.13-0.62, p = 0.001) and age (HR = 0.3, 95% CI: 0.16-0.59, p < 0.001) were independent prognostic factors for pelvic osteosarcoma. Univariate and multivariate Cox regression models identified three independent variables in the training cohort: age, lung metastasis, and tumor size. A predictive nomogram was developed based on the data from the SEER cohort and validated in the Chinese cohort. The areas under the curves (AUCs) that are used to predict 1-year, 2-year, and 3-year survival rates were 0.81 (95% CI: 0.68-0.94), 0.75 (95% CI: 0.63-0.86), and 0.80 (95% CI: 0.70-0.89) in the training cohort, and 0.67 (95% CI: 0.30-1.04), 0.66 (95% CI: 0.43-0.90) and 0.71 (95% CI: 0.50-0.93) in the validation cohort. Conclusion The predictive nomogram constructed in this study facilitates accurate and effective prediction of the overall survival of patients with pelvic osteosarcoma and helps enhance the clinical decision-making process.

Assessing the Role of Primary Heart Failure Etiology on Cardiac Transplant Outcomes.

There are diverse indications for heart transplantation (HTx), often categorized into ischemic (ICM) and nonischemic (NICM) cardiomyopathy. Although there is extensive research comparing the outcomes for these disease processes following certain therapeutic interventions, there are limited data on how recipient etiology impacts post-HTx survival. Our investigation seeks to identify this relationship. We conducted a retrospective analysis using adult HTx patients from the United Network for Organ Sharing database between 2000 and 2021. Patients with a combined heart-lung transplant or previous HTx were excluded. ICM included coronary artery disease (CAD) and ischemic dilated cardiomyopathy. NICM included nonischemic dilated (NIDCM), hypertrophic (HCM), and restrictive (RCM) cardiomyopathy. Overall survival was analyzed using Kaplan-Meier curves, log-rank tests, and multivariable Cox regression models. A total of 42268 patients were included in our study. Recipients with ICM were older and more likely to be males, obese, diabetics, and smokers. We found that patients with ICM had an increased incidence of transplant CAD (OR=1.23, p<0.001) and risk of mortality (hazard ratio [HR]=1.22, p<0.001) compared to NICM. When NICM was expanded, RCM had a similar hazard risk compared to ICM (HR=1.03, p=0.650), whereas both NIDCM (HR=0.81, p<0.001) and HCM (HR=0.70, p<0.001) had improved survival. Our study provides evidence to suggest that ICM has decreased survival when compared to NICM. When NICM was expanded, RCM was found to have an increased mortality risk similar to ICM, whereas NIDCM and HCM both had superior outcomes. The clinical implication of this investigation will allow clinicians to better understand the prognosis of certain patient groups.

Preoperative Serum Lipids as Novel Predictors of Survival in 3575 Papillary Thyroid Cancer Patients.

The objective of this study is to investigate the association between preoperative serum lipids levels and papillary thyroid cancer (PTC) patients' outcomes. A retrospective cohort study including 3575 PTC patients from year 2012-2016 with follow-ups in our institute were enrolled. Preoperative serum lipids were divided into categorical variables by Receiver-operating curves. Univariable and multivariable cox regression models were developed and independent risk factors were used to construct a nomogram to predict disease-free survival (DFS) rate. Among the 3575 patients, the mean follow-up time was 56.7 months. Comparing with the patients with high level of triglycerides (TAG≥0.605 mmol/L) and high-density lipoprotein (HDL≥0.935 mmol/L), those with low level of TAG (hazard ratio [HR] 2.28 [95% CI, 1.35-3.83]) and HDL (HR 1.64, [1.02-2.62]) had a significantly higher risk of recurrence in PTCs. The 5-year DFS rate of patients with low level of TAG was 94.4%, which was much lower than that in the high level group (97.2%, P＜0.001). While TC (P = 0.13), LDL (P = 0.07) and VLDL (P = 0.15) were not statistically correlated with PTCs' recurrence. The nomogram model showed clinical predictive value with the c-index of 0.80 (95% CI 0.73-0.87) and 0.82 (95% CI 0.73-0.90) for 3- and 4-year DFS in the training cohorts. In the present study, we provide initial evidence that low levels of TAG and HDL were independently associated with the recurrence of PTC, indicating that preoperative serum concentrations of lipids are helpful in predicting PTC patients' prognosis in clinical practice.

Long-term outcomes among out-of-hospital cardiac arrest survivors with reversible versus non-reversible causes.

Reversible cause of out-of-hospital cardiac arrest (OHCA) is vaguely defined in international guidelines as an identifiable transient or potentially correctable condition. Moreover, studies evaluating long-term outcomes of patients experiencing OHCA due to reversible and non-reversible causes are lacking. We aimed to determine differences in long-term outcomes in OHCA-survivors according to different etiology. From the British Columbia Cardiac Arrest registry, adults with non-traumatic OHCA (2009-2016) surviving to hospital discharge were identified. Patients were categorized by OHCA etiology combining reversibility and underlying ischemic etiology. The primary outcome was a composite of all-cause mortality, recurrent OHCA, or re-hospitalization for sudden cardiac arrest or ventricular arrhythmias. Using the Kaplan-Meier method and multivariable Cox regression models, we compared the risk of the composite outcome according to different OHCA-etiology. Of 1,325 OHCA hospital-discharge survivors (median age 62.8, 77.9% male), 431 (32.5%) had reversible ischemic, 415 (31.3%) non-reversible ischemic, 99 (7.5%) reversible non-ischemic and 380 (28.7%) non-reversible non-ischemic etiology. At 3 years post-discharge, Kaplan-Meier event-free rate was highest in patients with a reversible ischemic etiology (91%, 95% CI 87-94%), and lowest in those with a reversible non-ischemic etiology (62%, 95% CI 51-72%). In multivariate analyses, compared to non-reversible non-ischemic cause, reversible ischemic cause was associated with a significantly lower hazard ratio (HR) (0.52, 95% confidence interval [CI], 0.33-0.81), reversible non-ischemic cause with a significantly higher HR (1.53, 95% CI, 1.03-2.32) and non-reversible ischemic cause with a non-significant HR 0.92 (95% CI, 0.64-1.33) for the composite outcome. The presence of a reversible ischemic cause is associated with long-term OHCA-outcomes.

Atherogenic lipid profile in patients with statin treatment after acute coronary syndrome: a real-world analysis from Chinese cardiovascular association database.

Adverse atherogenic lipid profile is associated with an increased risk of major adverse cardiac events in patients after acute coronary syndrome (ACS). Knowledge regarding the impact of statins on lipid profile remains limited. We retrospectively analysed multicenter, real-world data from the Chinese Cardiovascular Association Database-iHeart Project. Patients with a primary diagnosis of ACS from 2014 to 2021 during index hospitalisation and having at least one lipid panel record after discharge within 12 months were enrolled. We analysed target achievement of atherogenic lipid profile, including apolipoprotein B (< 80mg/dL), low-density lipoprotein cholesterol (LDL-C) (< 1.8 mmol/L), lipoprotein(a) [Lp(a)] (< 30mg/dL), triglycerides (< 1.7 mmol/L), remnant cholesterol (RC) (< 0.78 mmol/L), non-high-density lipoprotein cholesterol (< 2.6 mmol/L) at baseline and follow-up. Multivariate Cox regression models were employed to investigate the association between patient characteristics and target achievement. Among 4861 patients, the mean age was 64.9 years. Only 7.8% of patients had all atherogenic lipids within the target range at follow-up. The proportion of target achievement was for LDL-C 42.7%, Lp(a) 73.3%, and RC 78.5%. Patients with female sex, younger age, myocardial infarction, hypertension, and hypercholesteremia were less likely to control LDL-C, Lp(a), and RC. An increase in the burden of comorbidities was negatively associated with LDL-C and Lp(a) achievements but not with RC. A substantial gap exists between lipid control and the targets recommended by contemporary guidelines. Novel therapeutics targeting the whole atherogenic lipid profile will be warranted to improve cardiovascular outcomes.

Bioinformatics Analysis of the Expression and Prognostic Value of PLAU Gene in Wilms' Tumor.

Autophagy and immunity play important roles in the growth of malignant tumors and are promising targets for tumor therapy. This study was conducted to identify differentially expressed immune genes related to autophagy in Wilms' tumor (WT) and analyze their correlation with the disease prognosis. The public data of WT and normal kidney tissues were downloaded from TCGA, ImmPort, and GeneCards databases to obtain differentially expressed immune genes associated with autophagy. Survival analysis, ROC curve, and clinical relevance filtering were used to screen the key gene plasminogen activator urokinase (PLAU). The univariable and multivariable Cox regression model analyses were used to analyze the prognostic factors of overall survival (OS) in patients with WT. Then, GO enrichment, KEGG pathway analysis and GSEA were used to enrich and analyze differentially expressed genes. The relationship between PLAU gene expression and tumor microenvironment and infiltration of immune cells was analyzed, as well as between the expression of PLAU and epigenetic modifications. PLAU gene expression was associated with survival and prognosis in WT patients and was an independent prognostic indicator of OS in patients. The GO, KEGG, and GSEA analysis results suggested that PLAU may be involved in RNA transcription and epithelial cell migration. High expression of PLAU was also associated with increased immune cell infiltration and a higher presence of antitumor immune cells. The low expression of PLAU in WT was related to DNA methylation and may be also co-regulated by miR-342-3p. PLAU can be used as an independent prognostic biomarker for WT. Low expression of PLAU is associated with poor prognosis in WT patients. Evidence on the prognostic value of PLAU gene and the pathways that may be associated with its expression is invaluable for the development of new therapies for WT.

Effect of mean heart rate on 30-day mortality in older patients with sepsis: Data from the MIMIC-IV database

BackgroundSepsis is a critical condition with a significant risk of mortality. Advanced age is one factor in increasing mortality in intensive care. ObjectivesThe aim of this study is to investigate the association between mean heart rate (MHR) and 30-day mortality among older patients with sepsis in the intensive care unit (ICU). MethodsAll older patients (age 65 or older) with sepsis for first time in ICU admission in Medical Information Mart for Intensive Care-IV (MIMIC-IV) were included in this retrospective study. The effect of MHR within 24 h of ICU admission on 30-day mortality was assessed according to multivariable Cox regression models, restricted cubic splines and two-piecewise Cox regression models. ResultsThe total number of participants was 6598 (mean heart rate, 83.8 ± 14.3 bpm). A total of 1295 (19.6 %) patients died within 30 days after ICU admission. MHR within 24 h of admission was associated with 30-day mortality (J-shaped association) in older patients with sepsis in the ICU, with an inflection point at about 74 bpm and a minimal risk observed at 73 to 82 bpm of MHR. ConclusionsIn this retrospective cohort study, there was a J-shaped association between MHR and 30-day mortality in older patients with sepsis admitted to the ICU and a minimal risk observed at 73 to 82 bpm of MHR. If further confirmed, this association may provide a theoretical basis for formulating the target strategy of heart rate therapy for these patients.

Mature MUC5AC Expression in Resected Pancreatic Ductal Adenocarcinoma Predicts Treatment Response and Outcomes.

Neoadjuvant therapy (NAT) for early-stage pancreatic ductal adenocarcinoma (PDA) has recently gained prominence. We investigated the clinical significance of mucin 5 AC (MUC5AC), which exists in two major glycoforms, a less-glycosylated immature isoform (IM) and a heavily glycosylated mature isoform (MM), as a biomarker in resected PDA. Immunohistochemistry was performed on 100 resected PDAs to evaluate the expression of the IM and MM of MUC5AC using their respective monoclonal antibodies, CLH2 (NBP2-44455) and 45M1 (ab3649). MUC5AC localization (cytoplasmic, apical, and extra-cellular (EC)) was determined, and the H-scores were calculated. Univariate and multivariate (MVA) Cox regression models were used to estimate progression-free survival (PFS) and overall survival (OS). Of 100 resected PDA patients, 43 received NAT, and 57 were treatment-naïve with upfront surgery (UpS). In the study population (n = 100), IM expression (H-scores for objective response vs. no response vs. UpS = 104 vs. 152 vs. 163, p = 0.01) and MM-MUC5AC detection rates (56% vs. 63% vs. 82%, p = 0.02) were significantly different. In the NAT group, MM-MUC5AC-negative patients had significantly better PFS according to the MVA (Hazard Ratio: 0.2, 95% CI: 0.059-0.766, p = 0.01). Similar results were noted in a FOLFIRINOX sub-group (n = 36). We established an association of MUC5AC expression with treatment response and outcomes.

Association of glucagon-like peptide-1 receptor agonists with suicidal ideation and self-injury in individuals with diabetes and obesity: a propensity-weighted, population-based cohort study.

Regulators worldwide are reviewing safety data on glucagon-like peptide-1 receptor agonists (GLP-1RA), following reports by the Icelandic Medicines Agency in July 2023 of suicidal ideation and self-injury (SIS) in individuals taking liraglutide and semaglutide. We aimed to assess the risk of SIS in new users of GLP-1RA when compared with sodium-glucose cotransporter 2 inhibitors (SGLT-2i) users, prescribed to treat type 2 diabetes in individuals with obesity. This is a cohort study combining several population-wide databases and covering a Spanish population of five million inhabitants, including all adults with obesity who initiated treatment with either GLP-1RA or SGLT-2i for type 2 diabetes from 2015 to 2021. To estimate the comparative effect of GLP-1RA on the risk of SIS, we employed a new user, active comparator design and we carried out multivariable Cox regression modelling with inverse probability of treatment weighting (IPTW) based on propensity scores. We performed several stratified and sensitivity analyses. We included 3040 patients initiating treatment with GLP-1RA and 11,627 with SGLT-2i. When compared with patients treated with SGLT-2i, those in the GLP-1RA group were younger (55 vs 60 years old, p<0.001), had more anxiety (49.4% vs 41.5%, p<0.001), sleep disorders (43.2% vs 34.1%, p<0.001) and depression (24.4% vs 19.0%, p<0.001), and were more obese (35.1% of individuals with BMI ≥40 vs 15.1%, p<0.001). After propensity score weighting, standardised mean differences between groups were <0.1 for all covariates, showing adequate balance between groups at baseline after adjustment. In the main per-protocol analyses we found no evidence that GLP-1RA increased the incidence of SIS (HR 1.04; 95% CI 0.35, 3.14). Intention-to-treat analyses resulted in an HR of 1.36 (95% CI 0.51, 3.61). In analyses excluding individuals with no BMI information and using imputation for BMI missing values, respective HRs were 0.89 (95% CI 0.26, 3.14) and 1.29 (95% CI 0.42, 3.92). Stratified analyses showed no differences between subgroups. Our findings do not support an increased risk of SIS when taking GLP-1RA in individuals with type 2 diabetes and obesity; however, the rarity of SIS events and the wide uncertainty of effect size (although null, effect may be compatible with a risk as high as threefold) calls for a cautious interpretation of our results. Further studies, including final evaluations from regulatory bodies, are called for to discard a causal link between GLP-1RA and suicidality.

The effect of hsCRP on TyG index-associated cardiovascular risk in patients with acute coronary syndrome undergoing PCI

The effect of systemic inflammation, represented by high-sensitivity C-reactive protein (hsCRP), on triglyceride glucose (TyG) index-associated cardiovascular risk in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) has not yet been determined. This study was a retrospective analysis of a single-center prospective registry and finally included 1701 patients (age, 60 ± 10 years; male, 76.7%). The primary endpoint was defined as major adverse cardiovascular events (MACE), including cardiovascular mortality, non-fatal stroke, and non-fatal myocardial infarction. In the multivariate COX regression model that included the GRACE risk score, higher TyG index was significantly associated with a greater incidence of MACE in patients with hsCRP levels less than 2 mg/L but not 2 mg/L or more (P for interaction = 0.039). Each unit increase in the TyG index was independently associated with a 52% increased risk of MACE only in patients with hsCRP levels less than 2 mg/L (P = 0.021). After adjustment for other confounding factors, including the GRACE risk score, compared with those in the group of TyG index < 8.62 and hsCRP < 2 mg/L, patients in the group of TyG index ≥ 8.62 and hsCRP ≥ 2 mg/L had a 3.9 times higher hazard ratio for developing MACE. The addition of both TyG index and hsCRP had an incremental effect on the predictive ability of the GRACE risk score-based prognostic model for MACE (C-statistic: increased from 0.631 to 0.661; cNRI: 0.146, P = 0.012; IDI: 0.009, P < 0.001). In conclusion, there was a significant interaction between the TyG index and hsCRP for the risk of MACE, and the TyG index was reliably and independently associated with MACE only when hsCRP levels were less than 2 mg/L. Furthermore, high TyG index and high hsCRP levels synergistically increased the risk of MACE, suggesting that the prognostic value of TyG index combined with hsCRP might be promising in patients with ACS undergoing PCI.

46 Radiological tumor burden is an independent risk factor for survival in patients with metastatic clear cell renal cell carcinoma (mccRCC) treated with first line immunotherapy (IO)-based regimens

Abstract Background IO-based regimens (IO + IO or IO + VEGF inhibitor) represent current standard of care systemic therapies for the management of patients with mRCC. IMDC is the current standard to assess prognosis in patients with mRCC of clear cell histology. Baseline radiological tumor burden (BRTB) is a readily available measurement to calculate using routine CT-scans. Here we describe the utility of BRTB as prognostic factor in patients with mccRCC treated with first line IO-based regimens. Methods We reviewed data of 183 patients with mccRCC treated at Dana-Farber Cancer Institute from August 2014 to October 2023 and who received ≥ 1 dose of an IO-based regimen (IO + IO or IO + VEGF inhibitor). Patients with available CT-scan reports within 1 month prior to first line treatment initiation were included in our analysis. BRTB was assessed by a single operator as the sum of all measurable lesions as listed on the RECIST v1.1 report. The primary outcome was overall survival (OS), and secondary outcomes were time to treatment failure (TTF) and time to next therapy (TTNT). To evaluate the impact of BRTB on OS, TTF and TTNT, we used univariable and multivariable Cox regression models accounting for IMDC risk group, history of nephrectomy, and presence of either bone, liver, or brain metastases prior to first line initiation. Results A total of 150 patients satisfied the inclusion criteria and were included in our final analysis, of which 80% of patients were male (120/150). 9% (13/150) had favorable risk, 51% (77/150) had intermediate risk and 20% (30/150) had poor risk by IMDC criteria. Overall, 73% (109/150) of patients had nephrectomy prior to first line therapy initiation and 41% (61/150) had either brain, bone, or liver metastasis. Median follow-up was 44.8 months. Every 1 cm increase in BRTB was associated with a 5% increase in risk of death (HR: 1.05; 95% CI: 1.03 – 1.08; p &amp;lt; 0.0001). On multivariable analysis, radiological tumor burden was significantly associated with OS (HR: 1.04; 95%CI: 1.00 – 1.08; p = 0.03). After categorizing BRTB by tertiles, tertile 1 included 0 - 7.5 cm, tertile 2: 7.6– 15.3 cm and tertile 3: 15.4 – 47.7 cm. The 4-year OS estimates were 84% (95%CI: 74 – 97%), 60% (95%CI: 45 – 81%) and 43% (95%CI: 29 – 66%), respectively, for the 1st, 2nd and 3rd tertile (log-rank P &amp;lt; 0.0001). BRTB did not show a significant association with TTF on univariable (HR: 1.00; 95%CI: 0.99 – 1.01; p = 0.783), or multivariable analysis (HR: 0.99; 95%CI: 0.97 – 1.01; p = 0.428). As for TTNT, BRTB also did not show a significant association on univariable (HR: 1.01; 95%CI: 1.0 – 1.02; p = 0.234) or multivariable analysis (HR: 1.01; 95%CI: 0.99 – 1.03; p = 0.453). Conclusions Baseline radiological tumor burden is an independent prognostic factor for OS in patients with mccRCC treated with first line immunotherapy-based regimens. However, tumor burden is not significantly associated with TTF or TTNT. Figure: Kaplan-Meier curves representing OS based on baseline radiological tumor burden assessed by RECIST v1.1 (Tertile 1: 0 - 7.5 cm; Tertile 2: 7.6 - 15.3 cm; Tertile 3: 15.4 – 47.7 cm). P value is derived from the log-rank test.

GLIM criteria validation and reliability in critically ill patients with cancer: A prospective study.

The present study aims to assess the interrater reliability of the Global Leadership Initiative on Malnutrition (GLIM) criteria, a framework to provide a consensus diagnosis of malnutrition. We also aimed to investigate its concurrent and predictive validity in the context of patients with cancer admitted to the intensive care unit (ICU). Individuals aged ≥19 years with cancer who were admitted to the ICU within 48 h of their initial hospital admission were included. Nutrition status was assessed with the Nutritional Risk Screening 2002, the Subjective Global Assessment (SGA), and the GLIM criteria. Interrater reliability was assessed by the kappa test (>0.80). The SGA served as the established benchmark for assessing concurrent validity. To evaluate predictive validity, the occurrence of mortality within 30 days was the outcome, and Cox regression models were applied. A total of 212 patients were included: 66.9% were at nutrition risk, and 45.8% were malnourished according to the SGA. According to the GLIM criteria, 68.4% and 66% were identified as malnourished by evaluators 1 and 2, respectively (κ = 0.947; P < 0.001). The GLIM combination incorporating weight loss and the presence of inflammation exhibited sensitivity (82.4%) and specificity (92%). In the multivariate Cox regression models, most GLIM combinations emerged as independent predictors of complications. The GLIM criteria demonstrated satisfactory interrater reliability, and the combination involving weight loss and the presence of inflammation exhibited noteworthy sensitivity and specificity. Most GLIM combinations emerged as independent predictors of 30-day mortality.

Monoclonal antibodies against SARS-CoV-2 to prevent COVID-19 worsening in a large multicenter cohort

ObjectiveMonoclonal antibodies (mAbs) against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) reduced Coronavirus Disease 2019 (COVID-19) hospitalizations in people at risk of clinical worsening. Real-world descriptions are limited. MethodsCONDIVIDIAMO, a two-year multicenter observational study, consecutively enrolled SARS-CoV-2 outpatients with ≥1 risk factor for COVID-19 progression receiving mAbs. Demographic data, underlying medical condition, type of mAbs combination received, duration of symptoms before mAbs administration, COVID-19 vaccination history, were collected upon enrolment and centrally recorded. Data on outcomes (hospitalizations, reasons of hospitalization, deaths) were prospectively collected. The primary endpoint was the rate of hospitalization or death in a 28-day follow-up, whichever occurred first; subjects were censored at the day of last follow-up or up to 28 days. The Kaplan-Meier method was used to estimate the incidence rate curve in time. The Cox regression model was used to assess potential risk factors for unfavorable outcome. Results were shown as hazard ratio (HR) along with the corresponding 95 % Confidence Interval (95%CI). ResultsAmong 1534 subjects (median [interquartile range, IQR] age 66.5 [52.4–74.9] years, 693 [45.2 %] women), 632 (41.2 %) received bamlanivimab ± etesevimab, 209 (13.6 %) casirivimab/imdevimab, 586 (38.2 %) sotrovimab, 107 (7.0 %) tixagevimab/cilgavimab. After 28-day follow-up, 87/1534 (5.6 %, 95%CI: 4.4%–6.8 %) met the primary outcome (85 hospitalizations, 2 deaths). Hospitalizations for COVID-19 (52, 3.4 %) occurred earlier than for other reasons (33, 2.1 %), after a median (IQR) of 3.5 (1–7) versus 8 (3–15) days (p = 0.006) from mAbs administration.In a multivariable Cox regression model, factors independently associated with increased hospitalization risk were age (hazard ratio [HR] 1.02, 95%CI 1.00–1.03, p = 0.021), immunodeficiency (HR 1.78, 95%CI 1.11–2.85, p = 0.017), pre-Omicron calendar period (HR 1.66, 95%CI 1.02–2.69, p = 0.041). ConclusionsMAbs real-world data over a 2-year changing pandemic landscape showed the feasibility of the intervention, although the hospitalization rate was not negligible. Immunosuppressed subjects remain more at risk of clinical worsening.

A New Ferroptosis-Related Long Non-Coding RNA Risk Model Predicts the Prognosis of Patients With Papillary Thyroid Cancer.

Ferroptosis is a novel form of regulated cell death that involves in cancer progression. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in papillary thyroid cancer (PTC) remains to be elucidated. The purpose of this paper was to clarify the prognostic value of ferroptosis-related lncRNAs in PTC. The transcriptome data and clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. The correlation between ferroptosis-related genes (FRGs) and lncRNA was determined using Pearson correlation analysis. Multivariate Cox regression model (P < 0.01) was performed to establish a ferroptosis-related lncRNAs risk model. Kaplan-Meier survival analysis, receiver operating characteristic (ROC) curves, risk curve and nomograms were then performed to assess the accuracy and clinical applicability of prognostic models. The correlations between the prognosis model and clinicopathological variables, immune and m6A were analyzed. Finally, in vitro assays were performed to verify the role of LINC00900, LINC01614 and PARAL1 on the proliferation, migration and invasion in TPC-1 and BCPAP cells, as well as the relationship between three lncRNAs and ferroptosis. A five-ferroptosis-related lncRNAs (PARAL1, LINC00900, DPH6-DT, LINC01614, LPP-AS2) risk model was constructed. Based on the risk score, samples were divided into the high- and low-risk groups. Patients in the low-risk group had better prognosis than those in high-risk group. Compared to traditional clinicopathological features, risk score was more accurate in predicting prognosis in patients with PTC. Additionally, the difference of immune cell, function and checkpoints was observed between two groups. Moreover, experiments showed that LINC00900 promoted the proliferation, migration and invasion in TPC-1 and BCPAP cells, while LINC01614 and PARAL1 revealed opposite effects, all of which were related to ferroptosis. In summary, we identified a five-ferroptosis-related lncRNAs risk model to predict the prognosis of PTC. Furthermore, our study also revealed that LINC00900 functioned as a tumor suppressor lncRNA, LINC01614 and PARAL1 as an oncogenic lncRNA in PTC.

Impact of PM2.5 exposure in old age and its interactive effect with smoking on incidence of diabetes

PurposeTo determine the impact of PM2.5 exposure in old age and its interactive effect with smoking on incident diabetes. MethodsA total of 2766 participants aged ≥60 years in China were interviewed at baseline for disease risk factors in 2001–03 and were then followed up for 10 years to document incident diabetes. They were assessed for daily PM2.5 exposure in 2005. Multivariate Cox regression models were used to examine the association of PM2.5 exposure with incident diabetes and interactive effect between PM2.5 and smoking on incident diabetes. ResultsDuring the cohort follow-up, 176 participants developed diabetes. The incidence of diabetes increased with PM2.5 exposure; the multiple-adjusted hazard ratio (HR) of diabetes was 2.27 (95 % CI 1.36–3.77) in participants with PM2.5 at ≥62.0 μg/m3 compared to those with <62.0 μg/m3. There was a significant interaction effect of PM2.5 with smoking on increased risk of diabetes. The adjusted HR for participants exposed to PM2.5 levels ≥62.0 μg/m3 who smoked was 4.39 (95 % CI 1.72–11.21), while for non-smokers it was 1.65 (95 % CI 0.88–3.09), compared to those with <62.0 μg/m3. ConclusionsExposure to PM2.5 in old age was associated with an increased incidence of diabetes and smoking enhanced the impact of PM2.5 on diabetic risk. These findings underscore the urgent need for air quality improvement measures and smoking cessation programs to mitigate the risk of diabetes in aging populations.

Exploring the Association Between Heart Rate Control and Rehospitalization: A Real-World Analysis of Patients Hospitalized with Heart Failure with Reduced Ejection Fraction.

In patients with heart failure with reduced ejection fraction (HFrEF), lower discharge heart rate (HR) is known to be associated with better outcomes. However, the effect of HR control on patient outcomes, and the demographic and clinical determinants of this association, are not well documented. The purpose of this work was to evaluate the association between the HR control and the risk of post-discharge rehospitalization in patients hospitalized with HFrEF. Data were collected using a retrospective medical record review in the USA. Reduction in HR between admission and discharge ("HR control") defined the primary exposure, categorized as no reduction, > 0 to < 20% reduction, and ≥ 20% reduction. Time to first rehospitalization in the post-discharge follow-up defined the study outcome and was analyzed using multivariable Cox regression modeling. A total of 1002 patients were analyzed (median age, 63 years; median follow-up duration, 24.2 months). At admission, 59.1% received beta-blockers, 57.4% received diuretics, and 47.5% received angiotensin-converting enzyme (ACE) inhibitors. Most patients (90.5%) achieved some HR control (38.4% achieved > 0 to < 20% reduction, and 52% achieved ≥ 20% reduction). Approximately 39% were rehospitalized during the follow-up (14% within 30 days). In multivariable analysis, patients with > 0 to < 20% reduction in HR had a 39% lower risk of rehospitalization [hazard ratio 0.61; 95% confidence interval (CI) 0.43-0.85]; patients with ≥ 20% reduction in HR had a 38% lower rehospitalization risk (hazard ratio 0.62; 95% CI 0.45-0.87) than those with no HR reduction. Reduction in HR between admission and discharge was associated with reduced risk for rehospitalization. Findings indicate HR control as an important goal in the management of patients hospitalized for HFrEF.

TIME TO RECOVERY FROM SEVERE PNEUMONIA AND ITS PREDICTORS AMONG PEDIATRIC PATIENTS ADMITTED IN SOUTH WEST REGION GOVERNMENTAL HOSPITALS, SOUTH WEST ETHIOPIA: PROSPECTIVE FOLLOW-UP STUDY

BackgroundThe Ethiopian Federal Ministry of Health has been working by introducing vaccines, and integrating the management of newborn and child illnesses to prevent pneumonia, pneumonia-related hospitalization, and mortality. Despite these attempts, the prevalence of pneumonia and the proportion of hospitalizations have increased. Little is known about recovery time from severe pneumonia and its predictors in pediatric patients in the study area. Therefore, this study aimed to determine the time to recovery from severe pneumonia and its predictors in pediatric patients admitted to government hospitals in the southwest Region. Methods and MaterialsA hospital-based prospective follow-up study was conducted among 791 pediatric patients admitted with severe pneumonia at a governmental hospital in the South West Region, of Ethiopia. A systematic sampling technique was used to recruit participants. Data were entered into Epi-data 4.4.2.1 and exported to STATA 14 for analysis. The assumptions of Cox proportional hazard models and goodness of fit were assessed using the Shoenfield residual and Cox-Snell, respectively. Bivariate and multivariable Cox regression models were used to identify the predictors of time to recovery. Variables with a p-value of <0.05 at a 95% confidence level in multivariable Cox regression model analysis were declared statistically significant predictors of time to recovery. ResultsThis study revealed that 641 (81.04 %) participants recovered with an incidence rate of 12.48 per 100 person-day observations. The median time to recovery was 5 days. Rural residence [AHR=0.82; 95% CI 0.69-0.97], hypoxemia [AHR=1.25; 95% CI 1.01- 1.55], danger sign, [AHR=1.77; 95% CI 1.28- 2.45], comorbidity [AHR=0.60; 95% CI 0.50- 0.7] and history of previous respiratory infections [AHR=0.76; 95% CI 0.64- 0.90] were found significant predictors of time to recovery from severe pneumonia. ConclusionIn this study, the recovery rate from severe pneumonia among pediatric patients was low and the time to recovery was slightly prolonged with a median time to recovery of five days. Rural residence, hypoxemia, danger signs, comorbidity, and history of previous respiratory infections were independent predictors of time to recovery among pediatric patients. Therefore, the Ethiopian Federal Ministry of Health, family, community leaders, healthcare providers, and other stakeholders should provide timely initiation of advanced diagnosis, appropriate therapeutic interventions, and proper follow-up for pediatric patients with severe pneumonia to reduce mortality.

Transcarotid Artery Revascularization Outperforms Transfemoral Carotid Artery Stenting Regardless of Aortic Arch Type or Degree of Atherosclerosis

ObjectivesThe Centers for Medicare and Medicaid Services (CMS) now approve reimbursement for Transfemoral Carotid Artery Stenting (TFCAS) in the treatment of standard-risk patients with carotid artery occlusive disease. TFCAS in patients with complex aortic arch anatomy is known to be challenging with worse outcomes. Transcarotid Artery Revascularization (TCAR) could be a preferable alternative in these patients owing to avoiding the aortic arch and using flow reversal during stent deployment. We aim to compare the outcomes of TCAR versus TFCAS across all aortic arch types and degrees of arch atherosclerosis. MethodsAll patients undergoing Carotid Artery Stenting (CAS) between September 2016 and October 2023 were identified in the VQI database. Patients were stratified into four groups: Group-A (Mild Atherosclerosis and Type I/II Arch), Group-B (Mild Atherosclerosis and Type III Arch), Group-C (Moderate/Severe Atherosclerosis and Type I/II Arch), Group-D (Moderate/Severe Atherosclerosis and Type III Arch). The primary outcome was in-hospital composite stroke or death. ANOVA and χ2tests analyzed differences for baseline characteristics. Logistic regression models were adjusted for potential confounders, and backward stepwise selection was implemented to identify significant variables for inclusion in the final models. Kaplan Meier survival estimates, Log Rank test, and multivariable Cox regression models analyzed hazard ratios for one-year mortality. ResultsA total of 20,114 patients were included [Group-A:12,980 (64.53%); Group-B: 1,175 (5.84%); Group-C: 5,124 (25.47%); Group-D: 835 (4.15%)]. TCAR was more commonly performed across the four groups (72.21%, 67.06%, 74.94% 69.22%; p<0.001). Compared to patients with mild arch atherosclerosis, patients with advanced arch atherosclerosis in Group-C and Group-D were more likely to be female, hypertensive, smokers, and have CKD. Patients with Type-III arch in Group-B and Group-D were more likely to present with stroke preoperatively. On multivariable analysis, TCAR had less than half the risk of stroke/death and one-year mortality compared to TFCAS in the patients with the mildest atherosclerosis and simple arch anatomy (group A) (OR=0.43,95%CI:0.31-0.61, p<0.001; HR=0.42,95%CI:0.32-0.57, p<0.001). Group-B patients with similar atherosclerosis but more complex arch anatomy had 70% lower odds of stroke/death with TCAR compared to TFCAS (OR=0.30,95%CI:0.12-0.75, p=0.01). Similar findings were also evident in patients with more severe atherosclerosis and simple arch anatomy (OR=0.66,95%CI:0.44-0.97, p=0.037). There was no significant difference in odds of stroke/death in patients with advanced arch atherosclerosis and complex arch (Group-D) (OR=0.91,95%CI:0.39-2.16, p=0.834). ConclusionsTCAR is safer than TFCAS in patients with simple and advanced arch anatomy. This could be related to the efficiency of flow reversal vs distal embolic protection. Current CMS decision will likely increase stroke and death outcomes of carotid stenting nationally if multidisciplinary approach and appropriate patient selection are not implemented.

Missed Follow-up is associated with worse survival in stage I lung cancer: results from a large multi-site academic hospital system

The purpose of this study is to examine the effect of early incomplete follow-up on overall survival among stage I lung cancer patients. Patients with clinical stage I lung cancer at our institution between 2007 and 2016 were identified (N = 1111). Exclusions included < 18 years of age (N = 2), missing stage or demographics (N = 56), incomplete appointment data or had only one scheduled appointment (N = 351), or did not survive for at least 1 year after diagnosis (N = 120). Missed appointments were defined as unattended follow-up appointments within the first year of diagnosis without an attended appointment in the subsequent 60 days. The primary outcome was the hazard ratio (HR) for death associated per 10% increase in missed oncology follow-up appointments. Univariable and descriptive statistics were performed, and a multivariable landmark Cox regression model was created to examine the effect of missed oncology follow-up on survival. A total of 582 patients were analyzed with median follow-up of 3.2 years and median age of 69 years. On multivariable analysis controlling for age, sex, race, insurance status, and definitive treatment type the HR for death was 1.44 (95% CI 1.05–1.97) for every 10% increase in missed appointments. Incomplete oncologic follow-up may negatively impact overall survival among survivors of early-stage lung cancer.

The Impact of D2 Versus D1 Lymphadenectomy in Siewert II Gastroesophageal Junction (GEJ) Cancer.

Although multiple treatment options exist for gastroesophageal junction (GEJ) cancer, surgery remains the mainstay for potential cure. Extended nodal dissection with a D2 lymphadenectomy (LAD) remains controversial for Siewert II GEJ cancer. Although D2 LAD may lead to a greater lymph node harvest, its effect on survival remains elusive. The authors hypothesized that additional D2 dissection in Siewert II GEJ cancer does not lead to increased survival. This study reviewed Siewert II patients who received a D1 or D2 LAD in addition to minimally invasive esophagectomy (MIE) after receiving neoadjuvant chemoradiation or perioperative chemotherapy (2012-2022). The patients were followed for up to 5 years. The outcomes measured were survival, number of nodes sampled, and operative time. The association between D1 or D2 LAD and overall survival was analyzed with Kaplan-Meier methods and a multivariable Cox regression model. Among 155 patients, 74 % underwent D1 and 26 % underwent D2 LAD. The patients with D2 had more than 15 lymph nodes harvested more frequently than those who had D1 (83 % vs 48 %; p < 0.001), with no difference in positive nodes (2.8 ± 5.2 vs 2.1 ± 4.2; p = 0.4). The patients with D2 LAD had a longer median operative time than those who with D1 LAD (362 vs 244 min; p < 0.001). In Kaplan-Meier and multivariable Cox regression models, overall survival differed significantly between the patients undergoing D2 and those who had D1 (adjusted hazard ratio [aHR], 0.52; 95 % confidence interval [CI], 0.25-1.00; p = 0.067). Little consensus exists regarding the optimal lymph node harvest for GEJ cancers. In Siewert II cancer, D2 LAD may not be mandatory and may lead to increased operative morbidity with no significant difference in survival.