Cox Regression Research Articles

Mediation effect analysis of lipoprotein levels on BMI and cardiovascular outcomes in patients with heart failure

BackgroundAmong heart failure patients with obesity, the prognosis is better than those with normal weight, a phenomenon known as the obesity paradox. However, it is unclear whether lipoprotein levels play a mediating role in the machine of the obesity paradox.MethodsThe study included 1663 heart failure patients hospitalized from January, 2019 through August, 2022. Kaplan-Meier survival analysis and Log-rank tests were performed for three endpoints in order to determine cumulative event-free survival. We investigated the correlation between Body Max Index (BMI) and outcomes by multifactorial Cox models. Mediation analysis was applied to study the presence and magnitude of mediation effects of triglyceride, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein A1 and apolipoprotein B, with the association between BMI and endpoints.ResultsIn MACCEs, the median follow-up period was 679 days. In Cox model, compared with the underweight group, a high BMI level was significantly associated with lower all-cause mortality (HR=0.47, 95%CI 0.31~0.69, p<0.001, obese vs underweight), cardiovascular mortality (HR=0.46, 95%CI 0.30~0.73, p<0.001, obese vs underweight) and the incidence of MACCEs (HR=0.68, 95%CI 0.53~0.88, p=0.003, obese vs underweight). Mediation analysis revealed that TG was the strongest mediator between BMI and endpoints, with proportions of mediated effects of 6.6% (95%CI 2.2%~18.0%, p=0.0258, in all-cause death),7.0% (95%CI 2.3%~18.9%, p=0.0301, in cardiovascular death) and 10.2% (95%CI 3.3%~27.4%, p=0.0185, in MACCEs).ConclusionsThere is an "obesity paradox" in patients with heart failure, and lipoprotein levels especially triglyceride mediate the association between BMI and cardiovascular outcomes.

Biofilm formation and increased mortality among cancer patients with candidemia in a Peruvian reference center

BackgroundCandidemia is an invasive mycosis with an increasing global incidence and high mortality rates in cancer patients. The production of biofilms by some strains of Candida constitutes a mechanism that limits the action of antifungal agents; however, there is limited and conflicting evidence about its role in the risk of death. This study aimed to determine whether biofilm formation is associated with mortality in cancer patients with candidemia.MethodsThis retrospective cohort study included patients treated at Peru’s oncologic reference center between June 2015 and October 2017. Data were collected by monitoring patients for 30 days from the diagnosis of candidemia until the date of death or hospital discharge. Statistical analyses evaluated the association between biofilm production determined by XTT reduction and mortality, adjusting for demographic, clinical, and microbiological factors assessed by the hospital routinary activities. Survival analysis and bivariate and multivariate Cox regression were used, estimating the hazard ratio (HR) as a measure of association with a significance level of p < 0.05.ResultsA total of 140 patients with candidemia were included in the study. The high mortality observed on the first day of post-diagnosis follow-up (81.0%) among 21 patients who were not treated with either antifungal or antimicrobial drugs led to stratification of the analyses according to whether they received treatment. In untreated patients, there was a mortality gradient in patients infected with non-biofilm-forming strains vs. low/medium and high-level biofilm-forming strains (25.0%, 66.7% and 82.3%, respectively, p = 0.049). In treated patients, a high level of biofilm formation was associated with increased mortality (HR, 3.92; 95% p = 0.022), and this association persisted after adjusting for age, comorbidities, and hospital emergency admission (HR, 6.59; CI: 1.87–23.24, p = 0.003).ConclusionsThe association between candidemia with in vitro biofilm formation and an increased risk of death consistently observed both in patients with and without treatment, provides another level of evidence for a possible causal association. The presence of comorbidities and the origin of the hospital emergency, which reflect the fragile clinical condition of the patients, and increasing age above 15 years were associated with a higher risk of death.

Association between preterm birth and asthma and atopic dermatitis in preschool children: a nationwide population-based study.

Asthma and atopic dermatitis (AD) are representative chronic diseases in childhood. This study aimed to investigate the impact of preterm birth on the incidence and severity of asthma and AD in children, as well as to identify neonatal risk factors for asthma and AD. We used health claims data recorded between 2007 and 2014 in the Korean National Health Insurance Service database. We recruited 2,224,476 infants born between 2007 and 2014 and divided them into three groups: 3518 of extremely preterm (EP) infants (< 28weeks of gestational age (GA)), 82,579 of other preterm (OP) infants (28-36weeks of GA), and 2,138,379 of full-term (FT) infants (> 37weeks of GA). We defined asthma as > 3 episodes of clinical visits in a year before 6years of age, early asthma as onset at < 2years of age, and severe asthma as > 1 event of status asthmaticus or admission to a hospital via an emergency room. AD was defined as ≥ 3 diagnoses in a year before 6years of age, early AD as onset at < 2years of age, and severe AD as prescription of high-potency topical steroids or immunosuppressants. An association of preterm birth with asthma and AD was assessed using inverse probability of treatment-weighted multivariable Cox regression analysis. Cardiorespiratory conditions, such as respiratory distress syndrome, bronchopulmonary dysplasia, patent ductus arteriosus, and pulmonary hypertension, significantly increased the risk of asthma. Specifically, bronchopulmonary dysplasia emerged as a significant risk factor for both severe and early-onset asthma (odds ratio (OR) 1.36, 95% CI 1.21-1.37 for severe asthma; OR 1.55, 95% CI 1.30-1.85 for early asthma), while it was associated with a decreased risk of AD (OR 0.86, 95% CI 0.80-0.92). Neonatal sepsis, jaundice, and retinopathy of prematurity were also identified as significant risk factors for later asthma. A stepwise increase in the risk of asthma with an increasing degree of prematurity was observed, with the OP group showing an adjusted hazard ratio (aHR) of 1.24 (95% CI: 1.22-1.26) and the EP group showing an aHR of 1.51 (95% CI: 1.41-1.63). Conversely, preterm birth was inversely associated with the risk of AD, with aHRs of 0.73 (95% CI: 0.67-0.79) for the OP group and 0.88 (95% CI: 0.87-0.89) for the EP group. Conclusion Preterm children have a significantly higher risk of asthma and lower risk of AD, with cardiorespiratory conditions significantly increasing the risk of asthma. Thus, we highlight the need for targeted respiratory management strategies for this high-risk population. What is Known: •Asthma and atopic dermatitis are prevalent chronic diseases in childhood, reducing the quality of life of children. •Preterm birth was associated with an increased risk of asthma, but few large nationwide studies. •Research on the relationship between preterm birth and pediatric atopic dermatitis is controversial, with few large nationwide studies. What is New: • Preterm children, especially born before 28weeks of gestational age, had a significantly higher risk of asthma and lower risk of atopic dermatitis. • Cardiorespiratory comorbidities such as RDS, BPD, PDA, and pulmonary hypertension in neonatal period are prominent risk factors for asthma. • Preterm children are vulnerable to both early-onset and severe asthma.

Body mass index and sarcopenia and mortality risk among older hypertensive outpatients; the Nambu Cohort Study.

Maintaining ideal body weight and muscle strength through lifestyle modification is essential for improving activities of daily living (ADL) and life expectancy in hypertensive patients. The effect of weight reduction in older patients with hypertension, however, is controversial. We evaluated the prognostic significance of body mass index (BMI) and handgrip strength (HG) in older patients with hypertension. Patients were stratified by the combination of BMI and HG. COX regression analysis was used to assess the mortality risk. A total of 563 patients (age 77 [71-84] years, 50% male, 40% frailty) were followed for a median duration of 41 (34-43) months. In total, 59 deaths occurred during the follow-up period. Validation of mortality by BMI level revealed that patients with BMI < 22 kg/m2 were likely to have higher mortality risk. Low HG, however, was associated with a 3.7-fold increased mortality risk. The risk of all-cause mortality using BMI combined with HG (adjusted hazard ratio [95% confidence interval]) was as follows: (1) Normal HG + 22 kg/m2 ≤ BMI, reference; (2) Normal HG + BMI < 22 kg/m2, 2.39 (0.12-16.46); (3) Low HG + 22 kg/m2 ≤ BMI, 4.01 (1.42-14.38); and (4) Low HG + BMI < 22 kg/m2, 4.55 (1.33-18.13). These findings demonstrate that weight reduction may deteriorate the mortality risk in older patients with hypertension, and new lifestyle modification strategies for improving ADL, quality of life, and prognosis are warranted for older patients with hypertension. We assessed the association between BMI, handgrip strength, and risk of all-cause mortality to evaluate the validity of weight reduction in older patients with hypertension.

Health dialogue intervention versus opportunistic screening in primary care for type 2 diabetes and cardiovascular disease prevention in settings with low socioeconomic status (DETECT): study protocol for a pragmatic cluster-randomized trial

BackgroundMeta-analyses of randomized trials suggest that health checks and health promotion interventions targeting behavior change in primary care do not prevent cardiovascular morbidity and mortality in the general population. However, whether such interventions are more effective in high-risk populations, such as people living in low socioeconomic settings, remains unclear, as they have been poorly represented in previous trials. Therefore, we aim to evaluate the effectiveness, cost-effectiveness, and implementation of systematic screening followed by an individually oriented, lifestyle-focused, health dialogue intervention for prevention of type 2 diabetes and cardiovascular disease, as compared to opportunistic screening, in primary care in socioeconomically disadvantaged areas.MethodsUsing an overall pragmatic approach and a cluster-randomized design with two arms, we aim to enroll 3000 participants aged 50–59 years from 30 primary care centers (PCCs) with an above-average level of Care Need Index in Stockholm Region, Sweden. PCCs will be randomized (1:1) either to a health dialogue intervention, which includes inviting enlisted patients to a systematic screening of risk factors followed by an individually oriented lifestyle-focused health dialogue, or to opportunistic screening, which includes screening patients for a smaller set of risk factors during an appointment at their PCC taking place for other reasons. The main outcome will be change in systolic blood pressure during 6- and 12-month follow-ups. Additional short-term outcomes will be changes in other biological risk factors, health-related quality-of-life, and lifestyle habits, as well as process and implementation outcomes, and unintended side effects. The long-term effect on type 2 diabetes and cardiovascular disease incidence and mortality will be examined using regional and nationwide registers. Changes in systolic blood pressure and other health outcomes will be analyzed using mixed-effect generalized linear modeling and mixed-effect Cox regression to capture variability between and within PCCs. A health economic evaluation will assess resource use and costs in the short- and long-term.DiscussionThis trial of lifestyle-focused health dialogues and opportunistic screening in primary care in socioeconomically disadvantaged areas in the largest region of Sweden has the potential to yield valuable insights that could support evidence-based policymaking.Trial registrationClinicalTrials.gov (NCT06067178). Prospectively registered September 27, 2023.

Role of neoadjuvant chemotherapy in patients with locally advanced and clinically positive nodes Upper Tract Urothelial Carcinoma treated with Nephroureterectomy: real-world data from the ROBUUST 2.0 Registry.

To assess the impact of neoadjuvant and adjuvant chemotherapy on survival outcomes, within a large multicenter cohort of Upper tract urothelial carcinoma patients treated with Nephroureterectomy. A multicenter retrospective analysis utilizing the Robotic surgery for Upper Tract Urothelial Cancer Study registry was performed. Baseline, preoperative, perioperative, and pathologic variables of three groups of patients receiving surgery only, neoadjuvant or adjuvant chemotherapy were compared. Categorical and continuous variables among the three subgroups were compared with Chi square and ANOVA tests. The impact of perioperative chemotherapy on survival outcomes was assessed with the Kaplan Meier method. Univariable and multivariable Cox regression analyses were performed to identify predictors of survival. Overall, 1,994 patients were included. Overall and Clavien grade ≥3 complications rates were comparable among the three subgroups (p = 0.65 and p = 0.92). At Kaplan Meier analysis, neoadjuvant chemotherapy significantly improved cancer-specific survival (p = 0.03) and overall survival (p = 0.03) probabilities of patients with cT ≥ 3 tumors and of those with positive cN (p = 0.03 and p = 0.02). On multivariable analysis, neoadjuvant chemotherapy was independently associated with an improvement of cancer-specific survival in cT ≥ 3 patients (HR 0.44; p = 0.04), and of both cancer-specific survival (HR 0.50; p = 0.03) and overall survival (HR 0.53; p = 0.02) probabilities in positive cN patients. This large multicenter retrospective analysis suggests significant survival benefit in Upper tract urothelial carcinoma patients with either locally advanced or clinically positive nodes disease receiving neoadjuvant chemotherapy. These findings can be regarded as "hypothesis generating", stimulating future trials focusing on such advanced stages.

Deep Neural Network-Based Accelerated Failure Time Models Using Rank Loss.

An accelerated failure time (AFT) model assumes a log-linear relationship between failure times and a set of covariates. In contrast to other popular survival models that work on hazard functions, the effects of covariates are directly on failure times, the interpretation of which is intuitive. The semiparametric AFT model that does not specify the error distribution is sufficiently flexible and robust to depart from the distributional assumption. Owing to its desirable features, this class of model has been considered a promising alternative to the popular Cox model in the analysis of censored failure time data. However, in these AFT models, a linear predictor for the mean is typically assumed. Little research has addressed the non-linearity of predictors when modeling the mean. Deep neural networks (DNNs) have received much attention over the past few decades and have achieved remarkable success in a variety of fields. DNNs have a number of notable advantages and have been shown to be particularly useful in addressing non-linearity. Here, we propose applying a DNN to fit AFT models using Gehan-type loss combined with a sub-sampling technique. Finite sample properties of the proposed DNN and rank-based AFT model (DeepR-AFT) were investigated via an extensive simulation study. The DeepR-AFT model showed superior performance over its parametric and semiparametric counterparts when the predictor was nonlinear. For linear predictors, DeepR-AFT performed better when the dimensions of the covariates were large. The superior performance of the proposed DeepR-AFT was demonstrated using three real datasets.

No Effect of Low-Dose Glucocorticoid Maintenance Therapy on Damage in SLE Patients in Prolonged Remission: A Propensity Score Analysis of the Longitudinal Lupus-Cruces-Bordeaux Inception Cohort

Background/Objectives: Prolonged remission on low-dose glucocorticoids (GC) is a main goal in patients with systemic lupus erythematosus (SLE). The aim of this study is to assess whether GC ≤ 5 mg/d increases the risk of damage accrual in patients with SLE in prolonged remission. Methods: Observational study of routine clinical care data of the inception Lupus Cruces-Bordeaux cohort. Only patients in DORIS remission during five consecutive yearly visits were included. The endpoint was damage accrual during the 5-year follow-up, either global or specific damage: GC-induced, cardiovascular (CV), lupus and other. Patients no longer on GC therapy by year 5 (GC5-Off) were compared with those who continued GC therapy (GC5-On). Comparisons were made by Cox and Poisson regressions, which were adjusted with propensity score (PE) in order to control for confounding by indication. Results: 132 patients were included, 56 in the GC5-On and 76 in the GC5-Off groups. All patients were on GC ≤ 5 mg/d for the whole follow-up, the mean prednisone dose in the GC5-On group being 2.96 mg/d during the whole study period and 2.6 mg/d during the 5th year. Fourteen patients (10.6%) accrued damage. More patients in the GC5-On group accrued global damage, 16% vs. 7% in the GC5-Off group, p = 0.08, mainly at CV domains (7% vs. 1%, respectively, p = 0.16). In the PS-adjusted Cox and Poisson regressions, the GC5-On group was not significantly associated with global (p = 0.39) or CV damage accrual (p = 0.62), nor with the absolute (p = 0.40) or CV-restricted final SDI scores (p = 0.63). The C-index of the propensity score model was 0.79. Conclusions: Maintaining doses of prednisone &lt; 5 mg/d in lupus patients in prolonged remission is not associated with an increased risk of damage accrual.

Pseudophakic cystoid macular oedema and posterior capsular opacification rates after combined phaco-trabeculectomy vs. phaco alone.

To assess the risk for pseudophakic cystoid macular oedema (PCME) and posterior capsular opacification (PCO) associated with combined cataract surgery and trabeculectomy compared to cataract surgery alone. Data analysis of subjects who underwent routine cataract surgery without and with concomitant trabeculectomy at the Department of Ophthalmology, Bristol Eye Hospital, the UK, between January 2008 and December 2017. Odds ratios (ORs) for PCME between the types of surgeries were calculated using univariate and multivariate regression analysis. Multivariate Cox regression controlling for age and gender was used to estimate the hazard ratio (HR) for neodymium-doped yttrium aluminium garnet (Nd:YAG) laser capsulotomies. This study included 56 973 cataract surgeries without and 288 with concomitant trabeculectomy (phaco-trab) with a mean follow-up time of 6.9 ± 4.2 years. Baseline variables (age and gender, diabetes, pseudoexfoliation, use of pupil expansion device and postoperative follow-up time) were comparable between the groups. Postoperative rates of PCME remained non-significant between the cataract surgery and phaco-trabe groups both in uni- and multi-variate analysis (OR 0.347, 95%CI 0.049-2.477, p = 0.291). Furthermore, in Cox regression analysis adjusted for the patients' age and gender, Nd:YAG laser capsulotomy rates remained non-significant between the cataract surgery and phaco-trabe groups (HR 1.250, 95%CI 0.883-1.769, p = 0.209). In our large cohort study, combining trabeculectomy with cataract surgery did not predispose to an increased PCME or Nd:YAG laser capsulotomy rates.

Investigating PPT2’s role in ovarian cancer prognosis and immunotherapy outcomes

Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.

How Morphology Shapes Survival in Invasive Squamous Cell Carcinoma of the Lung

Background and Objectives: Squamous cell carcinoma (SQCC) represents a significant proportion of human malignancies affecting various anatomical sites, including the lung. Understanding the prognostic factors is crucial for establishing effective risk stratification in these patients, as multiple critical aspects significantly impact overall survival. Materials and Methods: A retrospective study was conducted on 99 patients with operable lung SQCC treated at a tertiary center. The exclusion criteria included patients under 18, those with in situ or metastatic SQCC, and those who received neoadjuvant therapy. The surgical specimens were re-analyzed, and data were collected on multiple variables, including pTNM staging, tumor characteristics, and overall survival (OS). The Kaplan–Meier survival analysis and Cox regression models were used to identify significant prognostic factors. Results: The Kaplan–Meier analysis showed a median survival of 36 months with a 65.65% mortality rate. Significant factors influencing survival included keratinization, histological grading, tumor size and stage, pleural invasion, tumor cell arrangement, tumor budding, spread through air space (STAS), and mitotic index. A multiple Cox regression highlighted the nonkeratinizing tumors, advanced pT stages, single-cell invasion, and high mitotic index as key predictors of poorer outcomes. The nonkeratinizing tumors showed higher mortality and shorter median survival rates compared to keratinizing tumors. The tumor staging, cell arrangement, and tumor budding significantly impacted the survival curves. Conclusions: The study underscores the importance of detailed histopathological evaluations in lung SQCC. The nonkeratinizing tumors, advanced pT stage, single-cell invasion, and high mitotic index were associated with higher hazard rates, emphasizing the need for a comprehensive grading system incorporating these factors to improve prognostic accuracy and guide treatment strategies.

Frailty or sarcopenia: which is a better indicator of mortality risk in older adults?

BackgroundDespite the different conditions, frailty and sarcopenia overlap regarding their common link: the assessment of walking speed and muscle strength. This study aimed to compare the frailty phenotype to the...

Prognostic value of [18F]FDG PET/CT in metastatic hormone-sensitive prostate cancer at initial diagnosis: a retrospective cohort study

Introduction This retrospective study aimed to evaluate the prognostic value of [18F]FDG parameters in patients with visceral and bone metastatic hormone-sensitive prostate cancer (mHSPC). Patients and methods This analysis included the mHSPC patients who underwent [18F]FDG PET/CT at the initial diagnosis. Baseline characteristics were analyzed, and the uptake of [18F]FDG was quantified using SUVmax. Kaplan–Meier and Cox proportional hazard regression analysis were employed to evaluate the correlation between SUVmax and patient survival. Results Among the 267 patients enrolled, 90 (33.7%) presented with visceral metastases and 177 (66.3%) had bone metastases. The median follow-up for the visceral metastasis group was 35.5 months (IQR 26–53.8 months). The median overall survival for patients with lung, liver, or both metastases were 30, 21 and 17 months, respectively. Patients exhibiting higher [18F]FDG uptake in metastatic lesions experienced shorter overall survival (OS) in comparison to those with lower [18F]FDG uptake, both in the visceral metastases group (17 vs. 31 months, p = 0.002) and the bone metastases group (27.5 vs. 34.5 months, p < 0.001). Cox regression analysis further revealed that increased [18F]FDG uptake in metastatic lesions emerged as a significant risk factor in both OS and progression-free survival (PFS). In contrast, the variability in [18F]FDG uptake in primary lesions did not provide a reliable indicator for predicting prognosis. Conclusions In mHSPC patients, higher [18F]FDG uptake in metastatic lesions indicates shorter survival and increased risk of disease progression. The [18F]FDG SUVmax in primary tumors did not show significant prognostic value. Our study underscores the unique prognostic potential of [18F]FDG PET/CT in mHSPC patients, highlighting its importance in the management of both bone and visceral metastases.

Cardiac MRI in infarct-like myocarditis: transmural extension of late gadolinium enhancement is associated with worse outcomes

ObjectivesTo assess the prognostic value of cardiac MRI (CMR) parameters for the occurrence of major adverse cardiac events (MACE) in patients with infarct-like myocarditis.MethodsIn this retrospective single-center study, patients with CMR-confirmed acute myocarditis with infarct-like presentation were identified (2007–2020). Functional and structural parameters were analyzed including late gadolinium enhancement (LGE). The primary endpoint was the occurrence of MACE up to 5 years after discharge.ResultsIn total, 130 patients (mean age, 40 ± 19 years; 97 men, 75%) with infarct-like myocarditis were included. CMR was conducted a median of 3 days (interquartile range [IQR], 1–5) after symptom onset. MACE occurred in 18/130 patients (14%) during a median follow-up of 19.3 months (IQR, 4.5–53). The median extent of LGE was 7% (IQR, 4–10). LGE affected the subepicardium in 111/130 patients (85%), the midwall in 45/130 patients (35%), and both the subepicardium and midwall in 27/130 patients (21%). Transmural extension of non-ischemic LGE lesions was observed in 15/130 patients (12%) and septal LGE in 42/130 patients (32%). In univariable Cox regression analysis, a significant association was found between the occurrence of MACE and both, quantified LGE extent and transmural LGE pattern. In multivariable analysis, transmural extension of LGE was an independent predictor for MACE (hazard ratio, 6.34; 95% confidence interval: 2.29–17.49; p < 0.001). Patients with the transmural extension of LGE had a shorter event-free time on Kaplan–Meier analysis (log-rank p < 0.001).ConclusionsMACE occurred in 14% of patients with infarct-like myocarditis during follow-up. A transmural extension of non-ischemic LGE was associated with a worse long-term prognosis.Critical relevance statementCMR-based assessment of transmural extension of non-ischemic LGE holds the potential to serve as an easily assessable marker for risk stratification in patients with infarct-like myocarditis.Key PointsThe prognostic value of CMR was studied in patients with infarct-like myocarditis.The extent of LGE and transmural extension were linked to adverse cardiac events.Transmural non-ischemic LGE can serve as an easily assessable prognostic marker.Graphical

Outcomes of Watchful Waiting Strategy and Predictors of Postoperative Prognosis in Asymptomatic or Equivocally Symptomatic Chronic Severe Aortic Regurgitation With Preserved Left Ventricular Function.

The optimal surgical timing for asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction remains controversial. Two hundred ten consecutive patients (median age 65 years) with asymptomatic or equivocally symptomatic chronic severe aortic regurgitation and left ventricular ejection fraction ≥50% were registered. First, the treatment plans (aortic valve replacement or watchful waiting) after initial diagnosis were investigated. Then, 2 studies were set: Study A (n=144) investigated the prognosis of patients who were managed under the watchful waiting strategy after initial diagnosis; Study B (n=99) investigated the postoperative prognosis in patients who underwent aortic valve replacement at initial diagnosis or after watchful waiting. The primary outcomes were all-cause death in Study A and postoperative cardiovascular events in Study B. In Study A, 3 died of noncardiovascular causes during a median follow-up of 3.2 years. In Kaplan-Meier analysis, the survival curve was similar to that of an age-sex-matched general population in Japan. In Study B, 9 experienced the primary outcome during a median follow-up of 5.0 years. In Cox regression analysis, preoperative left ventricular end-systolic diameter enlargement (hazard ratio, 1.11; P=0.048) and left ventricular end-systolic diameter >45 mm (hazard ratio, 12.75; P=0.02) were significantly associated with poor postoperative prognosis. In Kaplan-Meier analysis, left ventricular end-systolic diameter >45 mm predicted a higher risk of the primary outcome (P <0.01). Watchful waiting was achieved safely in asymptomatic or equivocally symptomatic chronic severe aortic regurgitation with preserved left ventricular ejection fraction. Preoperative left ventricular end-systolic diameter >45 mm predicted a poor postoperative outcome and may be an optimal cut-off value for surgical indication.

Plasma bioactive adrenomedullin predicts mortality and need for dialysis in critical COVID-19

COVID-19 is a severe respiratory disease affecting millions worldwide, causing significant morbidity and mortality. Adrenomedullin (bio-ADM) is a vasoactive hormone regulating the endothelial barrier and has been associated with COVID-19 mortality and other adverse events. This prospective cohort pilot study included 119 consecutive patients with verified SARS-CoV-2 infection admitted to two intensive care units (ICUs) in Southern Sweden. Bio-ADM was retrospectively analysed from plasma on ICU admission, and days 2 and 7. Information on comorbidities, adverse events and mortality was collected. The primary outcome was 90-day mortality, and secondary outcomes were markers of disease severity. The association between bio-ADM and outcomes was analysed using survival analysis and logistic regression. Bio-ADM on admission, day 2, and day 7 only moderately predicted 90-day mortality in univariate and multivariate Cox regression. The relative change in bio-ADM between sample times predicted 90-day mortality better even when adjusting for the SAPS3 score, with an HR of 1.09 (95% CI 1.04–1.15) and a C-index of 0.82 (95% CI 0.72–0.92) for relative change between day 2 and day 7. Bio-ADM had a good prediction of the need for renal replacement therapy in multivariate Cox regression adjusting for creatinine, where day 2 bio-ADM had an HR of 3.18 (95% CI 1.21–8.36) and C-index of 0.91 (95% CI 0.87–0.96). Relative changes did not perform better, possibly due to a small sample size. Admission and day 2 bio-ADM was associated with early acute kidney injury (AKI). Bio-ADM on ICU admission, day 2 and day 7 predicted 90-day mortality and dialysis needs, highlighting bio-ADM’s importance in COVID-19 pathophysiology. Bio-ADM could be used to triage patients with a risk of adverse outcomes and as a potential target for clinical interventions.

Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

SIRS criteria versus qSOFA score in patients with severe alcohol-related hepatitis.

Severe alcohol-related hepatitis (sAH) is a potentially life-threatening complication of alcohol-related liver disease. SIRS criteria have been related to disease severity and may be a prognostic factor. Recently, qSOFA has been shown to be more prognostically accurate than SIRS in other inflammatory conditions. To determine whether qSOFA is a better prognostic score than SIRS criteria in sAH. We included 62 consecutive patients admitted for sAH, defined by modified Maddrey DF ≥32. MELD-Na, SIRS criteria and qSOFA score were calculated. Survival at 180 days was assessed. Twenty-four patients (38.7%) died after 180days. Three or more SIRS criteria and two or more qSOFA criteria were associated with 180-day mortality (LR=12.09, p=0.001; LR=4.81, p=0.028, respectively). Patients with MELD-Na >30 points died during follow-up more frequently (LR=5.997; p=0.014). SIRS respiratory criterion (B=5.113; p=0.023) and qSOFA respiratory criterion (B=5.985; p=0.05), bilirubin (>10mg/dL; LR=5.43, p=0.006), creatinine (>1mg/dL; B=5.885, p=0.015) and hyponatraemia (LR=5.75, p=0.018) were associated with mortality. Cox Regression model revealed that only SIRS and MELD-Na were independent prognostic factors. SIRS criteria seem to be more useful for patients with sAH, as well as MELD-Na. In contrast, qSOFA has no independent prognostic value in patients with sAH.

Effects of dietary habits and catheterization type on breast cancer-related lymphedema: a retrospective cohort study

BackgroundUnderstanding the factors that contribute to variability in breast cancer-related lymphedema (BCRL) is an important first step in developing targeted interventions to improve quality of life in breast cancer patients. Although previous research studies have has identified many risk factors for BCRL, dietary habits and catheterization type have rarely been studied until the present.AimThis study aims to explore the effects of nursing factors such as dietary habits and catheterization type on breast cancer-related lymphedema (BCRL).MethodsThis retrospective cohort study included 1,476 breast cancer patients who underwent surgery between January 1, 2012, and September 1, 2020. Lymphedema was assessed with a validated self-report questionnaire. All research data were obtained from medical records and a follow-up database. Multivariate Cox regression was conducted to explore the effects of dietary habits and catheterization type on BCRL.ResultsThe results showed an increased risk for BCRL among breast cancer patients who followed a high-fat diet prehospitalization (HR = 2.47; 95% CI = 1.55–3.94; P < 0.001), indwelling totally implantable venous access ports (TIVAPs) compared with indwelling needles (HR = 0.56; 95% CI = 0.35–0.90;P = 0.017) or indwelling peripherally inserted central catheters (PICCs) (HR = 0.69; 95% CI = 0.45–1.05; P = 0.086).ConclusionHigh-fat diet pre-hospitalization was an independent risk factor for lymphedema. The TIVAPs did not exert a protective effect on lymphedema compared with the PICC and indwelling needle. This study finding offers new insights to develop targeted interventions to decrease the incidence of lymphedema.

Utilizing the glucose challenge test during pregnancy as a predictor of future diabetes risk

BackgroundGestational Diabetes Mellitus (GDM) presents a significant health concern during pregnancy, predisposing individuals to future diabetes. Despite established postpartum diabetes screening guidelines, adherence to follow-up remains inadequate.AimsThis study aimed to assess the predictive value of the 50-gram glucose challenge test (GCT) for post-pregnancy diabetes development.Materials and methodsA population-based retrospective cohort study was conducted on pregnant women aged 18–45 who underwent GCT screening between November 2007 and July 2017 in a large Israeli community medical organization. Baseline characteristics, GCT results, and diabetes development during follow-up were analyzed using univariate and multivariate Cox regression analyses.ResultsAmong 8,675 women included, 2.4% developed diabetes over a median follow-up of 73.23 months. Elevated GCT results correlated with a higher risk of future diabetes, with a 4% rise in risk per 1 mg/dL increase in glucose above 140 mg/dL. Multivariate analysis revealed a 60-fold rise in the risk of future diabetes in women with GCT results ≥ 200 mg/dL compared to those with GCT < 140 mg/dL, adjusting for age, body mass index, pre-pregnancy glucose, cholesterol, and triglycerides. A GCT result between 140 and 199 mg/dL was a predictor of future diabetes, even when adjusted for GDM based on a subsequent GTT if performed.ConclusionsGCT results during pregnancy strongly predict future diabetes development, with higher GCT values significantly increasing risk. Recognizing abnormal GCT results as indicative of a prediabetic state offers a practical approach for risk stratification, facilitating early diagnosis, and intervention in post-pregnancy care.