Unadjusted Hazard Ratio Research Articles

Peripheral blood monocyte count and outcomes in patients with interstitial lung disease: a systematic review and meta-analysis.

Peripheral blood monocyte counts have been associated with poor outcomes in interstitial lung disease (ILD). However, studies are limited by variable biomarker thresholds, analytic approaches and heterogenous populations. This systematic review and meta-analysis characterised the relationship between monocytes and clinical outcomes in ILD. Electronic database searches were performed. Two reviewers screened abstracts and extracted data. Pooled estimates (hazard ratios (HRs)) of monocyte count thresholds were calculated for their association with mortality using ≥0.6×109 and >0.9×109 cells·L-1 for unadjusted models and ≥0.95×109 cells·L-1 for adjusted models, using random effects, with heterogeneity and bias assessed. Disease progression associated with monocytes >0.9×109cells·L-1 was also calculated. Of 3279 abstracts, 13 were included in the systematic review and eight in the meta-analysis. The pooled unadjusted HR for mortality for monocyte counts ≥0.6×109 cells·L-1 was 1.71 (95% CI 1.34-2.19, p<0.001, I2=0%) and for monocyte counts >0.90×109 cells·L-1 it was 2.44 (95% CI 1.53-3.87, p=0.0002, I2=52%). The pooled adjusted HR for mortality for monocyte counts ≥0.95×109 cells·L-1 was 1.93 (95% CI 1.24-3.01, p=0.0038 I2=69%). The pooled HR for disease progression associated with increased monocyte counts was 1.83 (95% CI 1.40-2.39, p<0.0001, I2=28%). Peripheral blood monocyte counts were associated with an increased risk of mortality and disease progression in patients with ILD.

Frailty in the chronic respiratory patient: association with mortality and clinical features in obstructive, restrictive, and mixed spirometric patterns.

Frailty associates with increased vulnerability to adverse health outcomes and reduced tolerance to medical interventions. Its impact on patients with chronic respiratory diseases, particularly beyond chronic obstructive pulmonary disease (COPD), remains poorly understood. To evaluate the association between frailty index and 5-year mortality across different "spirometric" patterns and the variation in their occurring frailty determinants. This study analyzed data from the SARA study, which enrolled 1968 older adults, to evaluate the association between frailty and 5-year mortality across different spirometric patterns. Frailty was assessed using the frailty index (FI), and spirometry was performed to determine lung function patterns. Hazard ratios (HRs) were calculated using Cox regression models, adjusting for age and sex. Among the study participants, 16% were classified as frail. Frailty was associated with a significantly increased risk of mortality across all spirometric patterns. The 5-year mortality rates were 34.3% in subjects with normal spirometry, 45.1% in those with obstructive defects, 55% in those with restrictive defects, and 42.6% in those with mixed airflow defects. The unadjusted HRs for mortality were 2.64 (95% CI 2.10-3.32) for the overall cohort, 2.24 (95% CI 1.48-3.40) for obstructive defects, 2.45 (95% CI 1.12-5.36) for restrictive defects, and 2.79 (95% CI 1.41-3.17) for mixed airflow defects. After adjusting for age and sex, the HRs remained statistically significant: 2.25 (95% CI 1.37-2.84) for the overall cohort, 2.08 (95% CI 1.37-3.18) for obstructive defects, 2.27 (95% CI 1.04-1.17) for restrictive defects, and 2.21 (95% CI 1.20-3.08) for mixed airflow defects. Frailty is a common syndrome and is associated with a significantly increased risk of mortality. The FI provides valuable information for risk profiling and personalized interventions beyond age and lung function parameters. Including frailty assessment in clinical evaluations can aid in resource allocation and improve patient care in respiratory diseases.

Higher docosahexaenoic acid levels lower the protective impact of eicosapentaenoic acid on long-term major cardiovascular events.

Long-chain omega-3 polyunsaturated fatty acids (OM3 PUFA) are commonly used for cardiovascular disease prevention. High-dose eicosapentaenoic acid (EPA) is reported to reduce major adverse cardiovascular events (MACE); however, a combined EPA and docosahexaenoic acid (DHA) supplementation has not been proven to do so. This study aimed to evaluate the potential interaction between EPA and DHA levels on long-term MACE. We studied a cohort of 987 randomly selected subjects enrolled in the INSPIRE biobank registry who underwent coronary angiography. We used rapid throughput liquid chromatography-mass spectrometry to quantify the EPA and DHA plasma levels and examined their impact unadjusted, adjusted for one another, and fully adjusted for comorbidities, EPA + DHA, and the EPA/DHA ratio on long-term (10-year) MACE (all-cause death, myocardial infarction, stroke, heart failure hospitalization). The average subject age was 61.5 ± 12.2 years, 57% were male, 41% were obese, 42% had severe coronary artery disease (CAD), and 311 (31.5%) had a MACE. The 10-year MACE unadjusted hazard ratio (HR) for the highest (fourth) vs. lowest (first) quartile (Q) of EPA was HR = 0.48 (95% CI: 0.35, 0.67). The adjustment for DHA changed the HR to 0.30 (CI: 0.19, 0.49), and an additional adjustment for baseline differences changed the HR to 0.36 (CI: 0.22, 0.58). Conversely, unadjusted DHA did not significantly predict MACE, but adjustment for EPA resulted in a 1.81-fold higher risk of MACE (CI: 1.14, 2.90) for Q4 vs. Q1. However, after the adjustment for baseline differences, the risk of MACE was not significant for DHA (HR = 1.37; CI: 0.85, 2.20). An EPA/DHA ratio ≥1 resulted in a lower rate of 10-year MACE outcomes (27% vs. 37%, adjusted p-value = 0.013). Higher levels of EPA, but not DHA, are associated with a lower risk of MACE. When combined with EPA, higher DHA blunts the benefit of EPA and is associated with a higher risk of MACE in the presence of low EPA. These findings can help explain the discrepant results of EPA-only and EPA/DHA mixed clinical supplementation trials.

Sarcopenia predicts 5-year mortality in older adults with intellectual disabilities.

People with intellectual disabilities (ID) have a lower life expectancy than their peers without ID. A contributing factor to the lower life expectancy and early mortality could be sarcopenia: low muscle mass and low muscle function. In the general population, sarcopenia strongly predicts early mortality, but this association is unknown in people with ID. Therefore, this study aims to explore the association between sarcopenia and 5-year mortality in older adults with ID. In the Healthy Ageing and Intellectual Disabilities (HA-ID) study, the prevalence of sarcopenia was measured at baseline among 884 older adults (≥50years) with ID. All-cause mortality was measured over a 5-year follow-up period. Univariable and multivariable Cox proportional hazard models were applied to determine the association between sarcopenia (no sarcopenia, pre-sarcopenia, sarcopenia, severe sarcopenia) and early mortality, adjusted for age, sex, level of ID, presence of Down syndrome, and co-morbidity (chronic obstructive pulmonary disease, diabetes type 2 and metabolic syndrome). The unadjusted hazard ratio (HR) for sarcopenia was 2.28 [95% confidence interval (CI) 1.48-3.42], P<0.001), and 2.40 (95% CI 1.40-4.10, P=0.001) for severe sarcopenia. When adjusted for age, sex, level of ID, and Down syndrome, sarcopenia (HR=1.72, 95% CI 1.08-2.75, P=0.022) and severe sarcopenia (HR=1.86, 95% CI 1.07-3.23, P=0.028) were significantly associated with early mortality. When additionally adjusted for co-morbidity, the adjusted HR decreased to 1.62 (95% CI 1.02-2.59, P=0.043) and 1.81 (95% CI 1.04-3.15, P=0.035) for sarcopenia and severe sarcopenia, respectively. Sarcopenia is an independent risk factor for early mortality in older adults with ID over a 5-year follow-up period. Our results stress the need to delay the incidence and development of sarcopenia in older adults with ID.

The association between all-cause mortality and HIV acquisition risk groups in the United States, 2001-2014.

To investigate associations between all-cause mortality and human immunodeficiency virus (HIV) acquisition risk groups among people without HIV in the United States. We used data from 23,657 (NHANES) participants (2001-2014) and the Linked Mortality File to classify individuals without known HIV into HIV acquisition risk groups: people who ever injected drugs (ever-PWID); men who have sex with men (MSM); heterosexually active people at increased risk for HIV (HIH), using low income as a proxy for increased risk. We used Cox proportional hazards models to estimate adjusted and unadjusted all-cause mortality hazard ratios (HR) with 95% confidence intervals (CI). Compared with sex-specific heterosexually active people at average risk for HIV (HAH), the adjusted HR (95% CI) were: male ever-PWID 1.67 (1.14, 2.46), female ever-PWID 3.50 (2.04, 6.01), MSM 1.51 (1.00, 2.27), male HIH 1.68 (1.04, 2.06), female HIH 2.35 (1.87, 2.95), and male ever-PWID 1.67 (1.14, 2.46). Most people at increased risk for HIV in the US experience higher all-cause mortality than people at average risk. Strategies addressing social determinants that increase HIV risk should be incorporated into HIV prevention and other health promotion programs.

Brief report: risk stratification following curative therapy for stage I NSCLC.

Surveillance with computed tomography (CT) imaging following curative treatment of stage I non-small cell lung cancer (NSCLC) is important to identify recurrence or second primary lung cancers (SPLC). The pattern and risks of recurrence following curative therapy and optimal duration of surveillance scans remain unknown. The objective of our study is to assess the pattern of recurrence and development of SPLC to risk stratify patients with stage I NSCLC following curative therapy. We identified 261 patients who received curative therapy for stage I NSCLC at Mayo Clinic Florida. Data was collected on clinical and demographic features including gender, smoking history, stage, treatment, histologic subtype, and tumor grade. Kaplan-Meier method was used to evaluate the disease free survival (DFS). Cox proportional hazard model was used to identify risk factors for recurrence. Negative tobacco history and stage IA tumors were associated with significantly prolonged DFS after adjusting for co-variates (p=0.001 and p=0.005). Univariate Cox proportional hazards model identified tobacco history and stage 1B as risk factors for recurrence with unadjusted hazard ratio (HR) of 2.8 and 2.0, respectively. After adjusting for covariates, only stage IB was statistically significant predictor of recurrence with a hazard ratio of 2.1 (Confidence Interval (CI) 95% 1.2-3.6; p=0.007). An individualized approach that considers risk factors of stage and smoking history may be useful in determining whether to continue annual CT surveillance after five years post curative therapy for stage I NSCLC.

Risk of dementia in primary aldosteronism compared with essential hypertension: a nationwide cohort study

BackgroundAlthough hypertension is a critical risk factor for dementia, the association between primary aldosteronism (PA) and dementia has been scarcely reported. We aimed to investigate whether the risk of dementia in patients with PA was elevated compared with patients with essential hypertension (EH).MethodsFrom the National Health Insurance Claim database in Korea (2003–2017), 3,687 patients with PA (adrenalectomy [ADX], n = 1,339, mineralocorticoid receptor antagonist [MRA] n = 2,348) with no prior dementia were age- and sex-matched at a 1:4 ratio to patients with EH (n = 14,741). The primary outcomes were all-cause dementia events, including Alzheimer’s disease, vascular dementia, or other dementia combined with a prescription of one or more medications for dementia (donepezil, galantamine, memantine, or rivastigmine). Multivariable Cox regression models were used to evaluate the hazard ratios (HRs) and 95% confidence intervals for the outcome incidence rates between patients with PA and their EH matches.ResultsDuring a median follow-up of 5.2 years, there were 156 cases of all-cause dementia (4.2%), 140 cases of Alzheimer's disease (3.8%), and 65 cases of vascular dementia (1.8%). Compared with EH, the risk of all-cause dementia was increased in treated PA (unadjusted hazard ratio [HR] 1.26; p < 0.011). Among PA, MRA group had higher risks of all-cause dementia, especially vascular dementia, adjusted for age, sex, income, comorbidities, and concurrent medication (adjusted HR 1.31; p = 0.027 and adjusted HR 1.62; p = 0.020, respectively) compared to EH. ADX group seemed to have a lower dementia risk than the EH group, but there was no statistical significance after full adjustment. This trend became more prominent when the dementia risks were evaluated from the time of hypertension diagnosis rather than treatment initiation for PA.ConclusionThe findings of this cohort study suggest that PA, especially the MRA group, is associated with an increased risk of dementia. Monitoring cognitive function in PA patients even after treatment initiation might be warranted to prevent dementia.

Mechanisms and treatment outcomes of ostial right coronary artery in-stent restenosis.

Despite a high rate of in-stent restenosis (ISR) after stenting the right coronary artery (RCA) ostium, the mechanism of ostial RCA ISR is not well understood. We aimed to clarify the cause of ostial RCA ISR using intravascular ultrasound (IVUS). Overall, 139 ostial RCA ISR lesions were identified with IVUS, pre-revascularisation. Primary ISR mechanisms were classified as follows: 1) neointimal hyperplasia (NIH); 2) neoatherosclerosis; 3) ostium not covered by the stent; 4) stent fracture or deformation; 5) stent underexpansion (old minimum stent area <4.0 mm2 or stent expansion <50%); or 6) a protruding calcified nodule. The median duration from prior stenting was 1.2 (first quartile 0.6, third quartile 3.1) years. The primary mechanisms of ISR were NIH in 25% (n=35) of lesions, neoatherosclerosis in 22% (n=30), uncovered ostium in 6% (n=9) (biological cause 53%, n=74), stent fracture or deformation in 25% (n=35), underexpansion in 11% (n=15), and protruding calcified nodules in 11% (n=15) (mechanical cause 47%, n=65). Including secondary mechanisms, 51% (n=71) of ostial RCA ISRs had stent fractures that were associated with greater hinge motion of the ostial-aorta angle during the cardiac cycle. The Kaplan-Meier rate of target lesion failure at 1 year was 11.5%. When the mechanically caused ISRs were treated without new stents, they suffered a higher subsequent event rate (41.4%) compared with non-mechanical causes or mechanical causes treated without restenting (7.8%, unadjusted hazard ratio 6.44, 95% confidence interval: 2.33-17.78; p<0.0001). Half of the ostial RCA ISRs were due to mechanical causes. Subsequent event rates were high, especially in mechanically caused ISRs treated without the implantation of a new stent.

Nutritional supplementation to prevent tuberculosis incidence in household contacts of patients with pulmonary tuberculosis in India (RATIONS): a field-based, open-label, cluster-randomised, controlled trial

In India, tuberculosis and undernutrition are syndemics with a high burden of tuberculosis coexisting with a high burden of undernutrition in patients and in the population. The aim of this study was to determine the effect of nutritional supplementation on tuberculosis incidence in household contacts of adults with microbiologically confirmed pulmonary tuberculosis. In this field-based, open-label, cluster-randomised controlled trial, we enrolled household contacts of 2800 patients with microbiologically confirmed pulmonary tuberculosis across 28 tuberculosis units of the National Tuberculosis Elimination Programme in four districts of Jharkhand, India. The tuberculosis units were randomly allocated 1:1 by block randomisation to the control group or the intervention group, by a statistician using computer-generated random numbers. Although microbiologically confirmed pulmonary tuberculosis patients in both groups received food rations (1200 kcal, 52 grams of protein per day with micronutrients) for 6 months, only household contacts in the intervention group received monthly food rations and micronutrients (750 kcal, 23 grams of protein per day with micronutrients). After screening all household contacts for co-prevalent tuberculosis at baseline, all participants were followed up actively until July 31, 2022, for the primary outcome of incident tuberculosis (all forms). The ascertainment of the outcome was by independent medical staff in health services. We used Cox proportional hazards model and Poisson regression via the generalised estimating equation approach to estimate unadjusted hazard ratios, adjusted hazard ratios (aHRs), and incidence rate ratios (IRRs). This study is registered with CTRI-India, CTRI/2019/08/020490. Between Aug 16, 2019, and Jan 31, 2021, there were 10 345 household contacts, of whom 5328 (94·8%) of 5621 household contacts in the intervention group and 4283 (90·7%) of 4724 household contacts in the control group completed the primary outcome assessment. Almost two-thirds of the population belonged to Indigenous communities (eg, Santhals, Ho, Munda, Oraon, and Bhumij) and 34% (3543 of 10 345) had undernutrition. We detected 31 (0·3%) of 10 345 household contact patients with co-prevalent tuberculosis disease in both groups at baseline and 218 (2·1%) people were diagnosed with incident tuberculosis (all forms) over 21 869 person-years of follow-up, with 122 of 218 incident cases in the control group (2·6% [122 of 4712 contacts at risk], 95% CI 2·2-3·1; incidence rate 1·27 per 100 person-years) and 96 incident cases in the intervention group (1·7% [96 of 5602], 1·4-2·1; 0·78 per 100 person-years), of whom 152 (69·7%) of 218 were patients with microbiologically confirmed pulmonary tuberculosis. Tuberculosis incidence (all forms) in the intervention group had an adjusted IRR of 0·61 (95% CI 0·43-0·85; aHR 0·59 [0·42-0·83]), with an even greater decline in incidence of microbiologically confirmed pulmonary tuberculosis (0·52 [0·35-0·79]; 0·51 [0·34-0·78]). This translates into a relative reduction of tuberculosis incidence of 39% (all forms) to 48% (microbiologically confirmed pulmonary tuberculosis) in the intervention group. An estimated 30 households (111 household contacts) would need to be provided nutritional supplementation to prevent one incident tuberculosis. To our knowledge, this is the first randomised trial looking at the effect of nutritional support on tuberculosis incidence in household contacts, whereby the nutritional intervention was associated with substantial (39-48%) reduction in tuberculosis incidence in the household during 2 years of follow-up. This biosocial intervention can accelerate reduction in tuberculosis incidence in countries or communities with a tuberculosis and undernutrition syndemic. Indian Council of Medical Research-India TB Research Consortium.

Heart age gap estimated by explainable advanced electrocardiography is associated with cardiovascular risk factors and survival.

Deep neural network artificial intelligence (DNN-AI)-based Heart Age estimations have been presented and used to show that the difference between an electrocardiogram (ECG)-estimated Heart Age and chronological age is associated with prognosis. An accurate ECG Heart Age, without DNNs, has been developed using explainable advanced ECG (A-ECG) methods. We aimed to evaluate the prognostic value of the explainable A-ECG Heart Age and compare its performance to a DNN-AI Heart Age. Both A-ECG and DNN-AI Heart Age were applied to patients who had undergone clinical cardiovascular magnetic resonance imaging. The association between A-ECG or DNN-AI Heart Age Gap and cardiovascular risk factors was evaluated using logistic regression. The association between Heart Age Gaps and death or heart failure (HF) hospitalization was evaluated using Cox regression adjusted for clinical covariates/comorbidities. Among patients [n = 731, 103 (14.1%) deaths, 52 (7.1%) HF hospitalizations, median (interquartile range) follow-up 5.7 (4.7-6.7) years], A-ECG Heart Age Gap was associated with risk factors and outcomes [unadjusted hazard ratio (HR) (95% confidence interval) (5 year increments): 1.23 (1.13-1.34) and adjusted HR 1.11 (1.01-1.22)]. DNN-AI Heart Age Gap was associated with risk factors and outcomes after adjustments [HR (5 year increments): 1.11 (1.01-1.21)], but not in unadjusted analyses [HR 1.00 (0.93-1.08)], making it less easily applicable in clinical practice. A-ECG Heart Age Gap is associated with cardiovascular risk factors and HF hospitalization or death. Explainable A-ECG Heart Age Gap has the potential for improving clinical adoption and prognostic performance compared with existing DNN-AI-type methods.

Symptomatic Carotid Atheroma Inflammation Lumen-stenosis score compared with Oxford and Essen risk scores to predict recurrent stroke in symptomatic carotid stenosis.

The Oxford Carotid Stenosis tool (OCST) and Essen Stroke Risk Score (ESRS) are validated to predict recurrent stroke in patients with and without carotid stenosis. The Symptomatic Carotid Atheroma Inflammation Lumen stenosis (SCAIL) score combines stenosis and plaque inflammation on fluorodeoxyglucose positron-emission tomography (18FDG-PET). We compared SCAIL with OCST and ESRS to predict ipsilateral stroke recurrence in symptomatic carotid stenosis. We pooled three prospective cohort studies of patients with recent (<30 days) non-severe ischaemic stroke/TIA and internal carotid artery stenosis (>50%). All patients had carotid 18FDG-PET/CT angiography and late follow-up, with censoring at carotid revascularisation. Of 212 included patients, 16 post-PET ipsilateral recurrent strokes occurred in 343 patient-years follow-up (median 42 days (IQR 13-815)).Baseline SCAIL predicted recurrent stroke (unadjusted hazard ratio [HR] 1.96, CI 1.20-3.22, p = 0.007, adjusted HR 2.37, CI 1.31-4.29, p = 0.004). The HR for OCST was 0.996 (CI 0.987-1.006, p = 0.49) and for ESRS was 1.26 (CI 0.87-1.82, p = 0.23) (all per 1-point score increase). C-statistics were: SCAIL 0.66 (CI 0.51-0.80), OCST 0.52 (CI 0.40-0.64), ESRS 0.61 (CI 0.48-0.74). Compared with ESRS, addition of plaque inflammation (SUVmax) to ESRS improved risk prediction when analysed continuously (HR 1.51, CI 1.05-2.16, p = 0.03) and categorically (ptrend = 0.005 for risk increase across groups; HR 3.31, CI 1.42-7.72, p = 0.006; net reclassification improvement 10%). Findings were unchanged by further addition of carotid stenosis. SCAIL predicted recurrent stroke, had discrimination better than chance, and improved the prognostic utility of ESRS, suggesting that measuring plaque inflammation may improve risk stratification in carotid stenosis.

Prognostic value of myocardial perfusion imaging by cadmium zinc telluride single-photon emission computed tomography in patients with suspected or known coronary artery disease: a systematic review and meta-analysis

BackgroundAim of this study was to define the prognostic value of stress myocardial perfusion imaging by cadmium zinc telluride (CZT) single-photon emission computed tomography (SPECT) for prediction of adverse cardiovascular events in patients with known or suspected coronary artery disease (CAD).Methods and resultsStudies published until November 2022 were identified by database search. We included studies using stress myocardial perfusion imaging by CZT-SPECT to evaluate subjects with known or suspected CAD and providing primary data of adverse cardiovascular events. Total of 12 studies were finally included recruiting 36,415 patients. Pooled hazard ratio (HR) for the occurrence of adverse events was 2.17 (95% confidence interval, CI, 1.78–2.65) and heterogeneity was 66.1% (P = 0.001). Five studies reported data on adjusted HR for the occurrence of adverse events. Pooled HR was 1.69 (95% CI, 1.44–1.98) and heterogeneity was 44.9% (P = 0.123). Seven studies reported data on unadjusted HR for the occurrence of adverse events. Pooled HR was 2.72 (95% CI, 2.00–3.70). Nine studies reported data useful to calculate separately the incidence rate of adverse events in patients with abnormal and normal myocardial perfusion. Pooled incidence rate ratio was 2.38 (95% CI, 1.39–4.06) and heterogeneity was 84.6% (P < 0.001). The funnel plot showed no evidence of asymmetry (P = 0.517). At meta-regression analysis, we found an association between HR for adverse events and presence of angina symptoms and family history of CAD.ConclusionsStress myocardial perfusion imaging by CZT-SPECT is a valuable noninvasive prognostic indicator for adverse cardiovascular events in patients with known or suspected CAD.

Association of lactate-to-albumin ratio with in-hospital and intensive care unit mortality in patients with intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is a severe stroke subtype with a high mortality rate; the lactate-to-albumin ratio (LAR) is a new biomarker for predicting clinical outcomes in patients with ICH. However, the relationship between LAR and mortality in patients with ICH treated in the intensive care unit (ICU) remains controversial. Therefore, in this study, we aimed to investigate the association between LAR and in-hospital and ICU mortality in patients with ICH. Patients with ICH were selected from the Medical Information Mart for Intensive Care III (MIMIC-III) database; their clinical information, including baseline characteristics, vital signs, comorbidities, laboratory test results, and scoring systems, was extracted. Univariate and multivariate Cox proportional hazards analyses were used to investigate the association of LAR with in-hospital and ICU mortality. The maximum selection statistical method and subgroup analysis were used to investigate these relationships further. Kaplan-Meier (KM) analysis was used to draw survival curves. This study enrolled 237 patients with ICH whose lactate and albumin levels, with median values of 1.975 and 3.6 mg/dl, respectively, were measured within the first 24 h after ICU admission. LAR had an association with increased risk of in-hospital mortality [unadjusted hazards ratio (HR), 1.79; 95% confidence interval (CI), 1.32-2.42; p < 0.001] and ICU mortality (unadjusted HR, 1.88; 95% CI, 1.38-2.55; p < 0.001). A cut-off value of 0.963 mg/dl was used to classify patients into high LAR (≥0.963) and low LAR (<0.963) groups, and survival curves suggested that those two groups had significant survival differences (p = 0.0058 and 0.0048, respectively). Furthermore, the high LAR group with ICH had a significantly increased risk of in-hospital and ICU mortality compared to the low LAR group. Our study suggests that a high LAR is associated with an increased risk of in-hospital and ICU mortality in patients with ICH. Thus, the LAR is a useful prognostic predictor of clinical outcomes in patients with ICH.

Maternal androgen excess increases the risk of metabolic syndrome in female offspring in their later life: A long-term population-based follow-up study.

Hyperandrogenic intrauterine environment may lead to the development of metabolic disorders in offspring in their later life. In this study, we aimed to determine the impact of maternal hyperandrogenism (MHA) on metabolic syndrome (MetS) risk in female offspring in their later life. In this cohort study conducted in Tehran, Iran, female offspring with MHA (n = 323) and without MHA (controls) (n = 1125) were selected. Both groups of female offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. We used age-scaled unadjusted and adjusted Cox regression models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in female offspring. The software package STATA was used for statistical analysis, and the significance level was set at P < 0.05. We observed a higher risk of MetS (unadjusted HR (95% CI), 1.36 (1.05-1.77)), (P = 0.02) and (adjusted HR (95% CI), 1.34 (1.00-1.80)), (P = 0.05, borderline)), in female offspring with MHA, compared to controls. The results were adjusted for the potential confounders including body mass index (BMI) at baseline, net changes of BMI, physical activity, education status, and birth weight. Our results suggest that MHA increases the risk of developing MetS in female offspring in their later life. Screening of these female offspring for MetS may be recommended.

Patients with non-ischemic cardiomyopathy and mid-wall striae have similar arrhythmic outcomes as ischemic cardiomyopathy.

While implantable cardioverter-defibrillator (ICD) therapy provides clear benefit in patients with ischemic cardiomyopathy (ICM), this is less clear in patients with non-ischemic cardiomyopathy (NICM). Mid-wall striae (MWS) fibrosis is an established cardiovascular magnetic resonance (CMR) risk marker observed in patients with NICM. We evaluated whether patients with NICM and MWS have similar risk of arrhythmia-related cardiovascular events as patients with ICM. We studied a cohort of patients undergoing CMR. The presence of MWS was adjudicated by experienced physicians. The primary outcome was a composite of implantable cardioverter-defibrillator (ICD) implant, hospitalization for ventricular tachycardia, resuscitated cardiac arrest, or sudden cardiac death. Propensity-matched analysis was performed to compare outcomes for patients NICM with MWS and ICM. A total of 1,732 patients were studied, 972 NICM (706 without MWS, 266 with MWS) and 760 ICM. NICM patients with MWS were more likely to experience the primary outcome versus those without MWS (unadjusted subdistribution hazard ratio (subHR) 2.26, 95% confidence interval [CI] 1.51-3.41) with no difference versus ICM patients (unadjusted subHR 1.32, 95% CI 0.93-1.86). Similar results were seen in a propensity-matched population (adjusted subHR 1.11, 95% CI 0.63-1.98, p = 0.711). Patients with NICM and MWS demonstrate significantly higher arrhythmic risk compared to NICM without MWS. After adjustment, the arrhythmia risk of patients with NICM and MWS was similar to patients with ICM. Accordingly, physicians could consider the presence of MWS when making clinical decisions regarding arrhythmia risk management in patients with NICM.

Cardiac Cachexia in Left Ventricular Assist Device Recipients and the Implications of Weight Gain Early After Implantation.

Background Severe cardiac cachexia or malnutrition are commonly considered relative contraindications to left ventricular assist device (LVAD) implantation, but post-LVAD prognosis for patients with cachexia is uncertain. Methods and Results Intermacs (Interagency Registry for Mechanically Assisted Circulatory Support) 2006 to 2017 was queried for the preimplantation variable cachexia/malnutrition. Cox proportional hazards modeling examined the relationship between cachexia and LVAD outcomes. Of 20 332 primary LVAD recipients with available data, 516 (2.54%) were reported to have baseline cachexia and had higher risk baseline characteristics. Cachexia was associated with higher mortality during LVAD support (unadjusted hazard ratio [HR], 1.36 [95% CI, 1.18-1.56]; P<0.0001), persisting after adjustment for baseline characteristics (adjusted HR, 1.23 [95% CI, 1.0-1.42]; P=0.005). Mean weight change at 12 months was +3.9±9.4 kg. Across the cohort, weight gain ≥5% during the first 3 months of LVAD support was associated with lower mortality (unadjusted HR, 0.90 [95% CI, 0.84-0.98]; P=0.012; adjusted HR, 0.89 [95% CI, 0.82-0.97]; P=0.006). Conclusions The proportion of LVAD recipients recognized to have cachexia preimplantation was low at 2.5%. Recognized cachexia was independently associated with higher mortality during LVAD support. Early weight gain ≥5% was independently associated with lower mortality during subsequent LVAD support.

Higher estimated plasma volume status is associated with increased thrombotic risk and impaired survival in patients with primary myelofibrosis

Blood plasma represents a large reservoir of cytokines and other mediators of inflammation. Higher estimated plasma volume status (ePVS) has been shown to correlate with increased thrombotic risk in polycythemia vera patients, but its clinical and prognostic associations in patients with myelofibrosis are unknown which we aim to evaluate in this study. We retrospectively analysed a multicentric cohort of 238 patients with primary (PMF) and secondary myelofibrosis (SMF). Estimated plasma volume status was calculated using the Strauss-derived Duarte formula. Overall survival (OS) and time to thrombosis (TTT) considering both arterial and venous thromboses were primary endpoints of interest. Median ePVS was 5.8 dL/g and it did not significantly differ between PMF and SMF patients. Patients with more advanced disease features, more pronounced inflammation and higher comorbidity burden had higher ePVS. Higher ePVS (> 5.6 dL/g) was associated with shorter OS in PMF (unadjusted hazard ratio, HR = 2.8, 95% confidence interval, CI (1.79-4.41), P < 0.001) and SMF (unadjusted HR = 2.55, 95% CI (1.1-5.71), P =0.025) and with shorter TTT in PMF (> 7 dL/g, unadjusted HR = 4.1, 95% CI (1.44-11.59), P = 0.009) patients. Associations with OS diminished in multivariate analyses after adjustments for the dynamic-international-prognostic-scoring-system (DIPSS) and myelofibrosis-secondary-to-PV-and ET-prognostic-model (MYSEC-PM), respectively. Association with TTT remained significant independently of JAK2 mutation, white blood cell count and chronic kidney disease. Myelofibrosis patients with more advanced disease features and more pronounced inflammation have higher ePVS, indicative of expanded plasma volume. Higher ePVS is associated with impaired survival in PMF and SMF and higher thrombotic risk in PMF patients.

Fatty acid binding protein 4 has prognostic value in peripheral artery disease

ObjectivePeripheral artery disease (PAD) remains undertreated, despite its association with major amputation and mortality. This is partly due to a lack of available disease biomarkers. The intracellular protein fatty acid binding protein 4 (FABP4) is implicated in diabetes, obesity, and metabolic syndrome. Given that these risk factors are strong contributors to vascular disease, we assessed the prognostic ability of FABP4 in predicting PAD-related adverse limb events. MethodsThis was a prospective case-control study with 3 years of follow-up. Baseline serum FABP4 concentrations were measured in patients with PAD (n = 569) and without PAD (n = 279). The primary outcome was major adverse limb event (MALE; defined as a composite of vascular intervention or major amputation). The secondary outcome was worsening PAD status (drop in ankle-brachial index ≥0.15). Kaplan-Meier and Cox proportional hazards analyses adjusted for baseline characteristics were conducted to assess the ability of FABP4 to predict MALE and worsening PAD status. ResultsPatients with PAD were older and more likely to have cardiovascular risk factors compared with those without PAD. Over the study period, MALE and worsening PAD status occurred in 162 (19%) and 92 (11%) patients, respectively. Higher FABP4 levels were significantly associated with 3-year MALE (unadjusted hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.04-1.27; adjusted HR, 1.18; 95% CI, 1.03-1.27; P = .022) and worsening PAD status (unadjusted HR, 1.18; 95% CI, 1.13-1.31; adjusted HR, 1.17; 95% CI, 1.12-1.28; P < .001). Three-year Kaplan-Meier survival analysis demonstrated that patients with high FABP4 levels had a decreased freedom from MALE (75% vs 88%; log rank = 22.6; P < .001), vascular intervention (77% vs 89%; log rank = 20.8; P < .001), and worsening PAD status (87% vs 91%; log rank = 6.16; P = .013). ConclusionsIndividuals with higher serum concentrations of FABP4 are more likely to develop PAD-related adverse limb events. FABP4 has prognostic value in risk-stratifying patients for further vascular evaluation and management.

Longitudinal Assessment of Circulating Tumor Cells and Outcome in Small Cell Lung Cancer: A Sub-Study of RASTEN-A Randomized Trial with Low Molecular Weight Heparin.

Circulating tumor cells (CTCs) may provide a liquid biopsy approach to disease monitoring in small cell lung cancer (SCLC), a particularly aggressive tumor subtype. Yet, the prognostic role of CTCs during and after treatment in relation to baseline remains ill-defined. Here, we assessed the value of longitudinal CTC analysis and the potential of low-molecular-weight heparin (LMWH) to reduce CTC abundance in SCLC patients from a randomized trial (RASTEN). Blood samples were collected at baseline, before chemotherapy Cycle 3, and at 2-month follow-up from 42 patients in total, and CTCs were quantified using the FDA-approved CellSearch system. We found a gradual decline in CTC count during and after treatment, independently of the addition of LMWH to standard therapy. Detectable CTCs at baseline correlated significantly to reduced survival compared to undetectable CTCs (unadjusted hazard ratio (HR) of 2.75 (95% CI 1.05-7.20; p = 0.040)). Furthermore, a persistent CTC count at 2-month follow-up was associated with a HR of 4.22 (95% CI 1.20-14.91; p = 0.025). Our findings indicate that persistently detectable CTCs during and after completion of therapy offer further prognostic information in addition to baseline CTC, suggesting a role for CTC in the individualized management of SCLC.

Outcomes for patients with high-risk endometrial cancer undergoing sentinel lymph node assessment versus full lymphadenectomy

ObjectiveThe objective of this study was to determine the progression free survival (PFS) and overall survival (OS) among patients with high-risk endometrial cancer (EC) who underwent sentinel lymph node (SLN) mapping and dissection compared to patients who underwent pelvic +/− para-aortic lymphadenectomy (LND). MethodsPatients with newly diagnosed high-risk EC were identified. Inclusion criteria included patients who underwent primary surgical management from January 1, 2014 to September 1, 2020 at our institution. Patients were categorized into either the SLN or LND group based on their method of planned lymph node assessment. Patients in the SLN group had dye injected followed by successful bilateral lymph node mapping, retrieval, and processing per our institutional protocol. Clinicopathological and follow-up data were extracted from patient's medical records. The t-test or Mann-Whitney test was used to compare continuous variables and Chi-squared or Fisher's exact test were used for categorical variables. Progression-free survival (PFS) was calculated from the date of initial surgery to the date of progression, death, or last follow-up. Overall survival (OS) was calculated from the date of surgical staging to the date of death or last follow-up. Three-year PFS and OS were calculated using the Kaplan-Meier method, and the log-rank test was used to compare cohorts. Multivariable Cox regression models were used to assess the relationship between nodal assessment cohort and OS/PFS while adjusting for age, adjuvant therapy, and surgical approach. A result was considered statistically significant at the p < 0.05 level of significance and all statistical analysis was done using SAS version 9.4 (SAS Institute, Cary, NC). ResultsOut of 674 patients diagnosed with EC during the study period, 189 were diagnosed with high-risk EC based on our criteria. Forty-six (23.7%) patients underwent SLN assessment and 143 (73.7%) underwent LND. No difference was observed between the two groups in regards to age, histology, stage, body mass index, tumors myometrial invasion, lymphovascular space invasion, or peritoneal washing positivity. Patients in the SLN group underwent robotic-assisted procedures more frequently than those in the LND group (p < 0.0001). The three-year PFS rate was 71.1% (95% CI 51.3–84.0%) in the SLN group and 71.3% (95% CI 62.0–78.6%) in the LND group (p = 0.91). The unadjusted hazard ratio (HR) for recurrence in the SLN versus LND group was 1.11 (95% CI 0.56–2.18; p = 0.77), and after adjusting for age, adjuvant therapy, and surgical approach, the HR for recurrence was 1.04 (95% CI 0.47–2.30, p = 0.91). The three-year OS rate was 81.1% (95% CI 51.1–93.7%) in the SLN group and 95.1% (95% CI 89.4–97.8%) in the LND group (p = 0.009). Although the unadjusted HR for death was 3.74 in the SLN vs LND group (95% CI 1.39–10.09; p = 0.009), when adjusted for age, adjuvant therapy, and surgical approach, it was no longer significant with a HR of 2.90 (95% CI 0.94–8.95, p = 0.06). ConclusionsThere was no difference in three-year PFS in patients diagnosed with high-risk EC who underwent SLN evaluation compared to those who underwent full LND in our cohort. The SLN group did experience shorter unadjusted OS; however, when adjusting for age, adjuvant therapy and surgical approach, there was no difference OS in patients who underwent SLN compared to LND.