Small Cohort Research Articles

Outcomes of patients treated with chemotherapy for breast cancer during pregnancy compared with nonpregnant breast cancer patients treated with systemic therapy.

Prior studies of patients treated for breast cancer during pregnancy (PrBC) report mixed outcomes and are limited by substandard treatment, small cohorts, and short follow-up. This study compared survival outcomes of PrBC patients treated with chemotherapy during pregnancy with nonpregnant patients matched by age, year of diagnosis, stage, and subtype. PrBC patients treated from 1989 to 2022 on prospective institutional protocols were eligible. Disease-free survival (DFS), overall survival (OS), and progression-free survival (PFS) were estimated using the Kaplan-Meier method and multivariable Cox proportional hazards regression. Among 143 PrBC and 285 nonpregnant patients, median follow-up was 11.4 years. Survival differences were statistically significant, with median DFS and OS not attained for PrBC patients versus 5.6 years (95% confidence interval [CI], 3.6-15.4; p=.0001) and 19.3 years (95% CI, 14.1-not estimated; p=.0262) for nonpregnant patients, respectively. Median PFS was 24.1 years (95% CI, 15.8-not estimated) for PrBC patients versus 8.4 years (95% CI, 6.4-10.9) for the nonpregnant cohort (p=.0008). Study cohort was associated with DFS, PFS, and OS in multivariable analyses, with the nonpregnant cohort having increased risks of disease recurrence (hazard ratio [HR], 1.91; 95% CI, 1.33-2.76; p=.0005) and disease progression or death (HR, 1.68; 95% CI, 1.19-2.39; p=.0035), and shorter OS (HR, 1.52; 95% CI, 1.01-2.29; p=.0442). These data suggest that PrBC patients treated with chemotherapy during pregnancy have at least comparable, if not superior, outcomes than nonpregnant patients with similar age, cancer stage, and subtype. Analyses excluding patients with postpartum breast cancer were unable to be performed and are a priority for future confirmatory studies.

Early risk stratification of patients after successfully resuscitated out-of-hospital cardiac arrest without ST-segment elevation - the TOMAHAWK risk score

Abstract Background Mortality after out-of-hospital cardiac arrest (OHCA) remains high. Early risk stratification is crucial to make adequate treatment decisions. Existing OHCA risk scores are either medically outdated, limited to registry data, small cohorts, certain healthcare systems only or include complex calculations. Purpose The aim of this study was to develop an easy-to-use, readily available risk prediction score for short-term mortality in patients with successfully resuscitated OHCA without ST-segment elevation, derived from the TOMAHAWK (Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation) trial. Methods The risk score was developed using a backward stepwise regression analysis. The risk score was externally validated in the COACT (Coronary Angiography after Cardiac Arrest Trial) cohort, which included patients with shockable rhythms only. Results Development and validation of the risk score was performed across 50 centres in three countries. Five variables emerged as independent predictors for 30-day mortality and were used as risk score parameters: age ≥72 years, known diabetes, unshockable initial electrocardiogram rhythm, time until return of spontaneous circulation ≥23 minutes and admission serum lactate level above 7.9 mmol/L. Between 1 and 4 points were attributed to each variable, leading to a score with three risk categories: low (0 to 2), intermediate (3 to 6) and high (7 to 10). The observed 30-day mortality rates were 23.6%, 68.8% and 86.2%, respectively (p<0.001) with a very good discrimination at an area under the curve of 0.82. Kaplan-Meier analysis revealed a stepwise increase in mortality between the different risk score categories (p<0.001 for low vs. intermediate, intermediate vs. high and low vs. high; see Figure). External validation in the COACT cohort showed short-term mortality rates of 23.1% (score 0 to 2), 44.8% (score 3 to 6) and 78.9% (score 7 to 10), respectively (each p<0.001). Conclusion The TOMAHAWK risk score can be easily calculated in daily clinical practice and is strongly correlated with mortality in patients with successfully resuscitated OHCA without ST-segment elevation. It may help stratify patient risk for short-term mortality and facilitate clinical decision making.

What is the true normal: comparison of different equations for estimating peak oxygen uptake for outcome prediction in heart failure

Abstract Background and Objectives One of the strongest prognostic parameters obtained during Cardiopulmonary exercise testing (CPET) in patients with heart failure (HF) is the peak oxygen uptake (pVO2), as a standalone or as a percentage of the predicted peak oxygen uptake (ppVO2) reached. However, traditional standards by which ppVO2 is calculated have limitations, having been derived from small cohorts, lacking portability and poorly represented by women. Thus, we aim to compare the FRIEND Registry equation to previously used methods of calculating ppVO2 as it relates to prognostic value imparted by the percentage of ppVO2 (%ppVO2) reached during CPET and portability to the Portuguese HF population. Methods Single centre retrospective study of patients with HF with LVEF < 50% who underwent CPET between 2015-2021. Patients who did not reach RER≥ 1.05 were excluded from our analysis. All tests were evaluated and ventilatory thresholds determined by 3 independent, experienced operators. ppVO2 was calculated according to 1) the Wasserman equation; 2) the Wasserman equation using ideal body weight; 3) the Neder equation, 4) the SHIP equation and 5) the FRIEND equation. Our primary endpoint was a composite of CV death, urgent transplant or left ventricular assist device implantation and HF hospitalization. Results We included 238 patients (mean age 59 ± 11 years, 83% males). The HF aetiology was mostly ischemic in nature (68%), with LVEF of 34 ± 9% and median NTproBNP of 776 (2566 – 2342) pg/mL. Most patients (67%) were in class NYHA I-II and with high prevalence of GDMT (93% ACEi/ARB; 97% beta-blockers and 64% on MRA). Mean BMI in this group was 27.3 ± 4.7 kg/min. Patients performed CPET on a treadmill with a protocol adjusted to their predicted exercise capacity. Mean pVO2 was 18.1 ± 6.2mL/kg/min, corresponding to a median %ppVO2 that ranges from 51 ± 16% to 71 ± 22%, depending on the equation that is used. Mean VE/VCO2 Slope was 42 ± 13 and 48 % (n = 98) of patients showed exercise oscillatory ventilation (EOV). Mean ppVO2 as per the FRIEND and Wasserman equations was 18.9 ± 6.6 and 21.2 ± 4.5 mL/kg/min, with no statistically significant difference between both. %ppVO2 as calculated through all equations was an independent predictor of prognosis on multivariate analysis adjusted for LVEF, NTproBNP and VE/VCO2 Slope (p < 0.001 for values derived from all equations). However, the FRIEND and Wasserman equations showed a slight advantage over the remaining 2 equations, with higher AUC on ROC curve analysis (see figure). Conclusions In our population of Portuguese patients with HF, both the FRIEND registry and Wasserman equations for predicting pVO2 yielded strong prognostic power. However, these equations provide different absolute predicted VO2 values for the same patients and thus should not be used interchangeably. Standardisation of the type ppVO2 equation used should be recommended by local scientific societies.

Echocardiographic findings in newborns with inadequate intrauterine growth during pregnancy

Abstract Background Infants born small for gestational age (SGA) or diagnosed with fetal growth restriction (FGR) are at increased risk of neonatal mortality as well as cardiovascular disease later in life. Previous studies based on smaller cohorts (n<200) of newborns with SGA and FGR (n<200) have demonstrated structural and morphological alterations in the heart compared to infants born appropriate for gestational age (AGA). However, to our knowledge no previous study has systematically investigated the effect of SGA and FGR on echocardiographic parameters in the infant heart. Purpose To investigate whether echocardiographic parameters differ among infants born SGA or with FGR, in comparison to infants born AGA. Methods This study is a population-based cohort study of infants (n>25,000) offering postnatal cardiac examination including transthoracic echocardiography (TTE) between 2016-2018. We compared left ventricular (LV) TTE parameters in infants born SGA (birthweight ≥3rd and <10th percentile, n=2,106) and with FGR (birthweight <3rd percentile, n=972) with infants born AGA (birthweight ≥10th and <90th percentile, n=20,468) using a multiple linear regression analysis. We have investigated LV volumes, systolic function, diastolic function, and LV structure. All analyses were adjusted for sex, gestational age at birth, weight, length, and age at cardiac examination. Results Infants born SGA had higher heart rates compared with infants born AGA. Both infants born SGA and infants with FGR had significantly smaller LV dimensions including septal and posterior wall thicknesses (IVSd and LVPWd), and LV internal diameters (LVIDd and LVIDs). Infants born SGA had smaller end-diastolic and end-systolic volumes compared with infants born AGA (Table 1). Infants born SGA or with FGR had significantly higher mitral valve early peak velocities, compared with infants born AGA, and infants born SGA showed increased mitral valve atrial peak velocities indicating altered diastolic function (Table 1). Conclusion Infants born with inadequate intrauterine growth had smaller LV dimensions compared with infants born AGA, even when adjusting for infant size and age. Infants born SGA and with FGR both exhibited altered diastolic function. Longitudinal studies of children with inadequate intrauterine growth are needed to determine the impact on adult cardiac health.

Aortic dimensions in a large Australian adult cohort. New normal range?

Abstract Background There is little published data worldwide about the normal range of aortic dimensions in adults. Guidelines for dilated aortic dimensions and recommendations for surgery are based on small population cohorts and absolute values. Adjustment for BSA and height are becoming more accepted, however the normal range of aortic dimensions for a large population has not been previously published. We present the distribution of aortic dimensions in a large Australian population, with indexation for BSA and height as well as centiles of age. Methods All patients >18 years of age attending for routine echocardiography at our institution from 2007-2022 were included in the database. Measurements of aortic root, sinotubular junction and ascending aorta using ASE criteria were collated. Dimensions were adjusted for BSA and height. Data was analysed for centiles of weight and height and across decades of age. Results A total of 117,912 patients were included in the analysis, aged 62.8+17.6 years (range 18-107), 59% male, 83.7+21.1 kgs (range 32-337) and 169.8+10.3 cm (range 107-218). The aortic root and ascending aortic dimensions are presented in absolute values (average + SD), and height adjusted (cm/m) and BSA adjusted (cm/m2) values. Data was expressed per centile of height, age and weight. There was a progressive increase in aortic dimensions as expected for increasing height, however a robust relationship was identified when dimensions were indexed according to height at all centiles regardless of age and body weight. In contrast, when adjusted for BSA, the aortic dimensions were progressively and predictably under-reported in patients over 80kg for assessment for normal vs dilated. When analysed for centiles of age, there was a small progressive increase in dimensions observed with increasing age. The indexation for height was independently robust across patients of all centiles of height. Conclusion Aortic dimensions are consistently 2.0+0.5 cm/m when adjusted for patient height across all body weight and age centiles. Adjustment for BSA in patients over 80kg tends to under-represent aortic dimensions when assessing for dilatation. Dimensions tend to increase gently with increasing age. We propose a new nomogram for normal aortic dimensions in adults.

Lipoprotein(a) levels in acute myocardial infarction patients and their associations with prior events and coronary artery disease severity: a real-world cohort study

Abstract Introduction Circulating lipoprotein(a) [Lp(a)] has been associated with the risk of atherosclerotic coronary artery disease (CAD) and is an emergent therapeutic target. The objective of this study is to explore the association between serum levels of Lp(a) and previous myocardial infarction (MI) and/or coronary revascularization and the extension of obstructive CAD in patients with acute MI undergoing coronary angiography. Methods All consecutive patients with MI who underwent coronary angiography and Lp(a) measurement between May and November 2023 were included. Patient data were either registered prospectively or completed retrospectively using electronic health records. Lp(a) was measured using the Immunoturbidimetric Assay method with reaction intensification by particles, employing the World Health Organization/International Federation of Clinical Chemistry and Laboratory Medicine (WHO/IFCC) International Reference Reagent (SRM2B), on the "Roche Cobas C702" chemistry analyzer. The number of major coronary arteries (left main, left anterior descending, left circumflex and right coronary arteries) with stenosis >50% on the coronary angiography were registered. In the primary analysis we explored the association between Lp(a) levels using tertiles and previous occurrence of MI/revascularization, as well as the extension of obstructive CAD. In the secondary analysis we compared Lp(a) levels in patients with and without previous MI/revascularization and patients with 3-4 major vessels CAD vs. 0-2 vessels. Results A total of 116 patients were enrolled, with a mean age of 62±13 years, 79% males, 29% with known coronary artery disease, 71% with dyslipidemia, 24% with diabetes, 65% with hypertension, and 58% were either active or former smokers. The median Lp(a) level was 72 (20-183) nmol/L. In the primary analysis (table 1), the number of previous MI/revascularizations was significantly higher in the third tertile of Lp(a) (T3) versus T1 (p=0.044). No significant differences were found for the remaining analyses. In the secondary analysis (figure 1) the level of Lp(a) was significantly higher in patients with 3-4 vessel CAD vs. 0-2 vessel (158.4±145.2 nmol/L vs. 103.16±104.6 p=0.044). Conclusion In this small real-world cohort population with acute MI, the number of previous MI or coronary revascularization was higher in patients with increased levels of Lp(a) and this marker of atherosclerotic disease was greater in patients with more extensive CAD.

Traditional dual-chamber right ventricular pacing versus conduction system pacing in the US medicare population

Abstract Introduction Conduction system pacing (CSP) has emerged as an alternative therapy to traditional right ventricular (RV) pacing. However, the majority of CSP studies reflect small cohorts or single-center experience. Purpose This analysis aimed to compare CSP to dual chamber (DC) RV pacing in a large, population-based cohort utilizing data from the Micra Coverage with Evidence Development (CED) study. Methods Medicare administrative claims data were used to identify patients implanted with a DC RV pacemaker. Lead placement data from Medtronic’s device registration system was used to identify patients with treated with CSP (N=6,197) using a 3830 catheter-delivered lead or DC RV (non-3830 lead, non-CSP placement) (N=16,989) at the same centers. CSP patients were stratified into left bundle branch area pacing (LBBAP) (N=4,738) and His-bundle pacing (HBP) (N=1,459). Incident heart failure hospitalizations (iHFH), all-cause mortality, complication rates and reinterventions at 6 months were analyzed. Results CSP (LBBAP and HBP) patients with a 3830 catheter-delivered lead experienced significantly lower rates of iHFH (HR: 0.70, P=0.02) and all-cause mortality at 6 months compared with DC RV patients (HR: 0.66, P<.0001) (figure). There was no difference in complications (HR: 0.89, P=0.06) or need for reintervention (HR: 0.83, P=0.08) with LBBAP compared to DC RV, though HBP patients experienced significantly higher rates of complications (HR: 1.41, P=0.001) compared to LBBAP. Conclusion Patients treated with CSP with a 3830 catheter-delivered lead experienced significant all-cause mortality and HFH benefits compared to DC RV pacing. LBBAP had lower complications compared to HBP. These real-world results in a large cohort of Medicare patients align with findings in small clinical studies demonstrating the benefits of LBBAP. Future research will focus on understanding patient selection for CSP.Figure

Intramyocardial fatty infiltration lesion in sporadic inclusion body myositis: a case report.

Sporadic inclusion body myositis (sIBM), the most common inflammatory muscle disorder in adults over 50 years, is often misdiagnosed due to its gradual onset and its common but unspecific muscle weakness in older adults. Diagnosis relies on clinical, radiological, and pathological features. Cardiac involvement is rare, prompting this case description and a comprehensive literature analysis. A 73-year-old woman diagnosed with sIBM in 2021 through muscle biopsy had been experiencing muscular symptoms since 2015. Her condition progressively worsened, affecting daily activities. Annual follow-ups revealed a moderate obstructive syndrome on respiratory testing, prompting a cardiac evaluation. Cardiac magnetic resonance (CMR) imaging identified intramyocardial lesions consistent with fatty infiltration, highlighting the interest of advanced imaging in sIBM management. Cardiac involvement in sIBM is presumed rare compared to other idiopathic inflammatory myopathies, though the exact frequency remains unclear. Early identification of heart alterations by CMR in sIBM can be prognostically valuable, guiding follow-up and interventions. However, literature on this subject is limited to small cohort studies and case reports describing complications. Given the slow progression of sIBM and the limited efficacy of current treatments, the discovery of myocardial lesions could warrant closer cardiological monitoring. Larger cohort studies are needed to explore potential new therapeutic approaches. Our case underscores the importance of CMR in detecting subtle cardiac manifestations in sIBM and illustrates the potential prognostic value of cardiac assessment in the management of sIBM.

A meta-analysis of the effects of sacubitril-valsartan on surrogate markers of systemic right ventricular dysfunction in congenital heart disease

Abstract Introduction Dysfunction of systemic right ventricle (sRV) in adult congenital heart disease (ACHD) patients is expectable and often associated with heart failure and other dismal cardiovascular events. Despite limited evidence, several neurohormonal modulators approved for heart failure with reduced ejection fraction (HFrEF) have been used off-label in patients with RV dysfunction1. Sacubitril-valsartan (ARNI) effects on sRV remains poorly studied, with current evidence being limited to small cohorts. Purpose Review and summarize current evidence about the effects of ARNI in ACHD patients with sRV. Methods We performed a systematic review on MEDLINE, EMBASE, COCHRANE, and SCOPUS for articles that included "systemic right ventricle" and "sacubitril valsartan" until January 2024. Two investigators screened the literature and extracted data. Treatment effects were measured by Cohen's d effect-size (EZ) pre and post-ARNI, with a 95% confidence interval (CI), using a restricted maximum likelihood model. Results From 197 publications screened, five studies fulfilled our criteria, comprising a total of 135 patients. Follow-up after ARNI therapy ranged from 12 to 27 months. No randomized clinical trials were found, and only two studies had a prospective design. Dextro-transposition of the great arteries (D-TGA) after atrial switch operation was the most common type of congenital heart disease with sRV (n=95; 70%). Meta-analysis demonstrates that ARNI reduced NT-proBNP levels during follow-up (EZ= -0.34, CI -0.59 to 0.08; p=0.01; I2=4.0%). Regarding RV function, ARNI improved RV fractional area change (RVFAC) (EZ= 0.75, CI 0.01 to 1.50; p= 0.048; I2=85.0%). A trend for RV global longitudinal strain improvement was also observed with ARNI (EZ= 1.74, CI -0.05 to 3.54; p=0.06; I2=95.9%) but not for tricuspid annular plane systolic excursion (EZ= -0.07, CI -0.33 to 0.20; p=0.62; I2=0.0%). RV diastolic diameter did not change significantly with ARNI (EZ= 0.07, CI -0.43 to 0.56; p=0.79; I2=68.2%). A trend for improvement on the 6-minute walk test was observed (EZ= 1.89, CI -0.13 to 3.91; p=0.07; I2=96.3%), but no effect on exercise oxygen consumption (VO2) (EZ= -0.09, CI -1.32 to 1.15; p=0.89; I2=91.4%). During follow-up ARNI did not change significantly systolic blood pressure (EZ= -0.32, CI -0.74 to 0.11; p=0.15; I2=58.4%) or serum creatinine (EZ= 0.23, CI -0.04 to 0.49; p=0.09; I2=0.0%). Conclusions Despite heterogeneity among these studies, this meta-analysis demonstrates that ARNI might improve NT-proBNP levels and RV function. ARNI seems safe and well tolerated, with no significant effect on blood pressure and renal function. More well-powered studies are needed to confirm the beneficial effects of ARNI in ACHD with sRV.

A systematic review and meta-analysis to determine the biological sex ratio in monogenic genetic and non-genetic dilated cardiomyopathy

Abstract Background Dilated cardiomyopathy (DCM) is characterised by left ventricular or biventricular systolic dysfunction and dilatation, in the absence of abnormal loading conditions or coronary artery disease (1). Up to 30% of cases have an identified monogenic cause, usually with autosomal dominant (AD) inheritance (2). The disease appears to be twice as common in males, suggesting either a sex specific penetrance or a potential difference in expressivity. This sex ratio has not been systematically evaluated for genetic forms of DCM. Purpose To assess the sex ratio in patients with all-cause DCM compared to genetic (monogenic) and gene-elusive subtypes, defined by the presence or absence of a pathogenic variant in DCM-associated genes. Methods A literature search was conducted to identify cohorts of DCM patients with identifiable sex ratios. Exclusion criteria were patients with syndromic, X-linked, mitochondrial, or autosomal recessive (AR) DCM. Studies with a small cohort size (n<100), a paediatric population, unidentifiable sex ratio, or ischaemic and peripartum DCM were excluded. 98 studies with a total of 36,662 participants were included in this study. A random-effects meta-analysis generated a pooled proportion of female participants with a 95% confidence interval (95% CI) for an overall DCM cohort as well as for the subtypes – all genetic DCM, individual gene level for 10 key DCM genes (including titin, TTN, and lamin, LMNA), and gene elusive DCM. Results The overall DCM cohort had a 0.30 female proportion (95% CI: 0.28-0.32; Figure 1). This corresponds to a male:female (M:F) ratio of 2.38:1. This ratio did not significantly change in patients with an identified causative DCM variant (0.31 [95% CI 0.26-0.36]; M:F ratio of 2.22:1; p=0.563). There was also no significant difference when compared to patients who had been genetically tested with no identified variant (0.30 [95% CI 0.24-0.37]; M:F ratio of 2.29:1; p=0.814). Furthermore, the ratio within participants with AD gene variants was not significantly different for the specific genes of TTN (0.28 [95% CI 0.22-0.36]; M:F ratio of 2.51:1) and LMNA (0.35 [95% CI 0.27-0.44]; M:F ratio of 1.84:1). Overall, the sex ratio amongst patients with these AD gene variants was similar to the all-cause group (0.34 [95% CI 0.28-0.40]; M:F ratio of 1.98:1; p=0.18); Figure 2. Conclusions This meta-analysis suggests that DCM is twice as prevalent in males than females, even in pooled monogenic genetic subtypes with an equally prevalent genetic risk factor, indicating a difference in penetrance between the sexes. Further studies are required to determine the drivers of this sex specific penetrance.Forest plots: overall DCM cohortForest plots: gene-specific DCM cohort

Racial and ethnic disparities in the incidence of stroke and mortality in atrial fibrillation: a US nationwide study

Abstract Background Atrial fibrillation (AF) is the most common arrhythmia globally and is associated with increased risks of cardiovascular mortality and ischemic stroke. Prior research has demonstrated racial/ethnic disparities in AF outcomes yet this work has been limited to small cohorts and did not adjust for anticoagulant therapy. Purpose We compared incidence of ischemic stroke and death by race/ethnicity for patients with AF in the Veterans Health Administration (VA), the largest integrated, low-cost, national healthcare system in the US. Methods In this retrospective cohort study we identified those with an outpatient diagnosis of AF and a confirmatory diagnosis ≦ 180 days of their index AF diagnosis enrolled in VA from January 1, 2014 to December 31, 2021, with follow-up for outcomes from the index AF diagnosis date until May 31, 2022. To create a cohort of incident AF cases, we excluded patients with an AF diagnosis or anticoagulant therapy in the 2 years prior to their index AF diagnosis. We also excluded patients with pre-existing valvular heart disease, prior stroke, receiving hospice care or who died within 180 days of index AF diagnosis. We categorized our independent variable as race (i.e., non-Hispanic American Indian / Alaska Native [AI/AN], Asian, Black, or White [reference group]), and ethnicity (i.e., Hispanic). Our primary outcomes were incidence of stroke or death at any point within the study follow-up period. To compare these outcomes by race/ethnicity we conducted a survival analysis, adjusting for anticoagulant use as a time-varying covariate along with sociodemographic factors (age, sex, region, area deprivation index), clinical factors (CHADS2VA2Sc stroke risk and HAS-BLED bleeding risk), and facility type. Results There were 187,080 patients in the final cohort including 0.5% AI/AN, 1% Asian, 9% Black, 4% Hispanic, 85% White; mean age was 73 years. Over a mean study follow-up period of 4.43 years, 65,375 (34.9%) patients died and 24,910 (13.3%) developed stroke. The adjusted hazard ratio [95% CI] for death was lower for Hispanic (0.84 [0.78, 0.91]) and Black (0.94 [0.91, 0.97]) patients than White patients. In contrast, the adjusted hazard ratio for stroke incidence was higher for Black (1.21 [1.16, 1.27]) and Hispanic (1.10 [1.03, 1.17]) patients than White patients. There was no difference observed between AI/AN or Asian and White patients in either outcome. Conclusions In a national cohort of patients with incident AF, we identified significantly higher rates of stroke in Black and Hispanic than White patients even controlling for myriad factors including anticoagulant use. Conversely, racial/ethnic disparities in mortality appear to be eliminated in VA, counter to prior data. Understanding the factors, beyond anticoagulation, driving disparities in stroke outcomes and identifying factors reducing mortality among minority groups is critical to improving overall AF care in the largest integrated US health system.Adjusted Hazard Ratios of Study Outcomes

The feasibility of double stent strategy in left main true bifurcation with small and large angle change between diastole and systole: The Milan and New-Tokyo (MITO) registry.

Provisional single stenting strategy (PSS) is a default strategy for percutaneous coronary intervention (PCI) of unprotected left main distal bifurcation lesions (ULMD). Previous study reported that a bifurcation angle change (BAC) between end diastole and systole was associated with outcomes after PCI with double stent strategy (DSS) for ULMD. However, there are no data comparing outcomes after PCI with PSS versus DSS according the degree of BAC. We evaluated outcomes after PCI with PSS versus DSS for true ULMD with small and large BAC. We identified 566 patients with true ULMD underwent PCI in three high-volume centers. We calculated the BAC in ULMD between end-diastole and systole before stenting with 2-dimensional quantitative coronary angiographic assessment. We defined small (BAC < 7.0°) and large BAC (≥7.0°) group. We compared clinical outcomes after PCI with PSS versus DSS in each cohort after propensity score adjustment. The primary endpoint was target-lesion failure (TLF), which was defined as a composite of cardiac death, target lesion revascularization, and myocardial infarction. In small BAC cohort, TLF rate was significantly lower in DSS group than in PSS group (12.5% vs. 20.1%, adjusted HR 0.45; 95% CI, 0.26-0.79; p = 0.006). In contrast, in large BAC cohort, TLF rate was significantly higher in DSS group than in PSS group (54.9% vs. 29.0%, adjusted HR 2.25; 95% CI, 1.50-3.38; p < 0.001). The TLF rate after PCI with DSS was significantly lower in true ULMD with small BAC compared to PSS even after propensity score adjustment. In contrast, it was significantly higher in those with large BAC.

Normothermic Ex Vivo Perfusion Before Transplantation of the Kidney (NEXT-Kidney): A Single-center, Nonrandomized Feasibility Study.

There is conflicting evidence regarding the efficacy of normothermic machine perfusion (NMP) in suboptimal deceased donor kidneys. We aimed to assess the feasibility and short-term efficacy of brief preimplantation NMP in circulatory death (DCD) kidneys. In this nonrandomized, single-center, prospective clinical trial, DCD kidneys underwent 1 to 3 h of NMP before implantation, aiming to achieve short ischemic times off NMP. The primary outcomes included feasibility and safety. Secondary outcomes included efficacy outcomes (delayed graft function and estimated glomerular filtration rate (eGFR) at 1, 6, and 12 mo), which were compared with the contralateral kidney that did not receive NMP. Eighteen DCD kidneys underwent NMP between 2020 and 2022, with at least 1 h completed in 16 (88.9%) of these kidneys (median 1 h); one kidney was removed after 5 min because of cannula failure and another at 54 min because of a sudden drop in blood flows. There was no episode of graft loss on the machine or postoperative vascular thromboses. All 18 kidneys were transplanted, with no cases of PNF or graft loss at 12 mo. Seventeen of the contralateral CS kidneys were transplanted. Compared with the contralateral kidneys, a lower incidence of delayed graft function (23.5% versus 64.7%; P = 0.046) was observed. There were no differences in the eGFR slopes between the two groups over time (P = 0.254). NMP is safe, feasible and efficacious in the Australian setting, with this relatively small cohort demonstrating good early outcomes compared to CS alone in our study of DCD kidneys.

Preliminary Characterisation of Immune Cell Populations in the Oral Mucosa of a Small Cohort of Healthy Dogs (Canis lupus familiaris).

Pre-determined anatomical locations in the oral cavity were biopsied, and their histomorphology was characterised using haematoxylin and eosin staining (H&E). The most abundant cell type was of dendritic morphology. Lymphocyte foci were not evident in the palatoglossal folds or the gingiva. Immunohistochemical staining (IHC) for validated leukocyte markers followed, including CD3, CD20, CD79α, CD204, andIba1. Consistent with H&E findings, CD204 immunoreactivity predominated amongst all niches. With the exception of the alveolar mucosa and palatoglossal folds, we also demonstrate a significant difference in the population of macrophages by region for only the Iba1 antigen (p < 0.0001). B lymphocytes were found, and a significant difference was noted in the sub-epithelium where CD20-positive cells outnumbered those labelled as CD79a positive (p = 0.001), suggesting the possibility that these cells are in an active state in health. A similar significant difference was found in the subepithelial tissue for myeloid cells, as there were more cells labelled as CD204 positive over Iba1, which, along with their distribution pattern, indicates a possible functional and morphological overlap between these cells. No significant difference was found in epithelial tissues for cells of either myeloid or lymphoid origins. The results from this study suggest different regions of the oral cavity exhibit variations in the distribution of immune cells, particularly macrophages and B lymphocytes. Though more studies would be needed to confirm these findings, these differences may have implications for the immune response and overall health of the oral mucosa.

Agency Building with Early Research Exposure: A Study of an Undergraduate Science Education Exposure Program

Undergraduate research exposure provides students with opportunities to positively perceive their association with their scientific discipline through agentic experiences, and thereby fostering their disciplinary identity building. In the present study, we explore students’ experiences of participating in an undergraduate level research exposure camp in Chemistry discipline. The camp is organized under a national level nurture initiative for undergraduate science and engineering students in India. It is a two-week long residential camp in which students are engaged in lectures on theoretical topics in chemistry, problem solving sessions, long laboratory exercises, abstract writing session, and students’ seminars. The camp also serves as a first step to select a small cohort of students based on their performance in the different activities during the camp for extended research projects opportunities. We apply the critical science agency framework to examine students’ experiences during the camp, and how understand how students connect their prior experiences and future career related choices with their camp experiences. The qualitative analysis describes students’ accounts of the emergence of agentic personalities at the entry, during, and beyond the camp. We noted instances in which students’ decisions and subsequent actions of applying to and attending the camp surfaced, and through students’ narration interpreted how some of these were markers of critical science agency. Based on authors’ understanding, this is the first, and one of the few studies conducted using critical science agency framework with science undergraduate students about their early research experiences. The study provides insights about potential programmatic features for similar undergraduate research camps in India as well as on a global platform.

Hepatic Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor Levels Decline in Hepatitis C but Are Not Associated with Progression of Hepatocellular Carcinoma.

Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) is an antagonist of transforming growth factor (TGF)-β type 1 signaling. BAMBI functions as an anti-fibrotic protein and exerts pro- as well as anti-cancerogenic activities. Our study aimed to correlate hepatocyte BAMBI protein levels in hepatocellular carcinoma (HCC) with T stage, lymph node invasion, vessel invasion, grading, tumor size and Union for International Cancer Control (UICC) stage, as well as with liver inflammation and fibrosis stages. Hepatocyte BAMBI protein expression was assessed by immunohistochemistry in HCC tissues of 320 patients and non-tumor tissues of 51 patients. In the HCC tissues of the whole cohort and sex-specific analysis, BAMBI protein was not related to T stage, vessel invasion, lymph node invasion, histologic grade, UICC stage and tumor size. Accordingly, BAMBI was not associated with overall survival, recurrence-free and metastasis-free survival. BAMBI protein levels in tumor and non-tumor tissues were not related to inflammation and fibrosis grade. BAMBI protein levels in HCC tissues and non-tumor tissues from HCC patients, which were analyzed by immunoblot in a small cohort and by immunohistochemistry in the tissues of patients described above, were similar. Notably, BAMBI protein was low-abundant in HCC tissues of hepatitis C virus (HCV) compared to hepatitis B virus (HBV)-infected patients with comparable disease severity. Immunoblot analysis revealed reduced BAMBI protein in non-tumor tissues of patients with HCV in comparison to patients with HBV and normal human liver tissues. In summary, this analysis showed that hepatocyte BAMBI protein levels of patients with HCC are related to HCV infection rather than the severity of the underlying liver disease and cancer staging.

Underwater Techniques in Gastrointestinal Endoscopy: Diving into the Depths

The endoscopic resection of gastrointestinal tract lesions embraces different types of techniques, ranging from conventional polypectomy/endoscopic mucosal resection (EMR) to the field of third-space endoscopy, including endoscopic submucosal dissection (ESD), full-thickness resection and peroral endoscopic myotomy (POEM). Parallelly, the advent of underwater techniques has served as an add-on for both basic and advanced procedures, since its first report in 2012. We aimed to provide a comprehensive update on the state of the art about the feasibility of underwater basic and advanced techniques for GI endoscopy. Underwater EMR (U-EMR) has proved effective and safe in treating &gt; 10 mm sessile or flat or all-size recurrent colonic lesions. Conversely, although data show good effectiveness and safety for &lt;10 mm lesions, it is preferred when high-grade dysplasia is suspected, favouring cold snare polypectomy for all other cases. Moreover, promising data are emerging regarding the feasibility of U-ESD for difficult-to-resect colonic lesions. U-EMR represents a standard of care for treating &lt; 25 mm superficial non-ampullary duodenal epithelial tumours. Data regarding oesophageal, gastric and ampullary lesions remains limited to small cohorts. Finally, using water immersion for POEM has shown a reduction in procedure time compared to the CO2 insufflation technique for vessel coagulation, albeit in a single-centre experience. Based on these results, U-EMR has become a standard for treating intermediate-size colonic and non-ampullary duodenal lesions, as highlighted also in the European Society of Gastrointestinal Endoscopy guidelines. Promising results have been shown in third-space endoscopy studies, even though further prospective studies are awaited to standardise the technique for both ESD and POEM.

Limited Value of HBV-RNA for Relapse Prediction After Nucleos(t)ide Analogue Withdrawal in HBeAg-negativeHepatitis B Patients.

International guidelines suggest cessation of nucleos(t)ide analogues (NA) independent of HBsAg loss in HBeAg-negative patients after 2-3 years of viral suppression. Detectable HBV-RNA levels at the time of NA cessation were linked to a better prediction of relapse after NA withdrawal in small cohorts of HBeAg-negative patients. This study proves the impact of HBV-RNA levels in the prediction of relapse in a large cohort of HBeAg-negative patients, mainly infected with genotype B or C. Serum levels of HBV-RNA, HBsAg, anti-HBc and HBcrAg were determined before NA withdrawal in 154 HBeAg-negative patients, participating either in a therapeutic vaccination trial (NCT02249988) or in an observational register trial (NCT03643172). Importantly, vaccination showed no impact on relapse. Endpoints of the study were virological relapse (HBV-DNA > 2000 IU/mL) or biochemical relapse (attendant ALT levels ≥ 2 × ULN) 24 weeks after NA cessation. Virological relapse occurred in 54.5% of patients (N = 84/154), including eight patients (10%) developing an ALT flare. Baseline HBV-RNA level did not differ significantly between relapsers and off-treatment responders (p = 0.92). No significant difference occurred in proportions of detectable HBV-RNA levels between off-treatment responders (N = 27/70; 38.6%) and relapsers (N = 31/84; 36.9%) (p = 0.99). Combining predefined HBsAg cut-offs (100 IU/mL, p = 0.0013), anti-HBc cut-offs (325 IU/mL, p = 0.0117) or HBcrAg cut-offs (2 log U/mL, p = 0.66) with undetectable HBV-RNA (HBsAg, p = 0.0057; anti-HBc, p = 0.085; HBcrAg, p = 0.60) did not improve relapse prediction. The value of HBV-RNA levels at timepoint of NA cessation for the prediction of relapse is limited in HBeAg-negative patients. Trial Registration: ABX 203-002: NCT02249988; Terminator 2: NCT03643172.

Ultrasound Microvessel Imaging of the Human Placenta Demonstrates Altered Vessel Densities in Fetal Growth Restriction With Vascular and Immune Pathologies: A Pilot Case-Control Study.

Fetal growth restriction (FGR) is commonly associated with placental dysfunction, increasing perinatal morbidity and mortality. Visualizing placental vessels in utero would be advantageous for identifying functional FGR cause and determining proper management strategies. We aimed to utilize high-sensitivity ultrasound microvessel imaging (HUMI) for quantifying placental vessel density (VD) in pregnancies diagnosed with FGR. This pilot case-control study enrolled subjects in the third trimester with a diagnosis of FGR (n = 40) and gestational age-matched controls with normal fetal growth (n = 20) at a 2:1 ratio, respectively. The Verasonics Vantage ultrasound system was used to perform HUMI on each participant at one timepoint. Scanning involved randomized singular value decomposition-based clutter filtering to identify the villous tree, followed by step-by-step scanning to acquire 3-dimensional-like data. Mean VD was calculated from three ultrasound measurements per subject. Additional clinical and pathology data were also collected and compared. Sixteen participants were utilized to establish the scanning protocol and 2 met exclusion criteria at delivery. Thus, VD was successfully measured on 42 pregnancies scanned at 35 weeks 5 days on average. In FGR (n = 24), placental VD was significantly reduced compared to controls (P < .01). VD measures were as good at predicting FGR as systolic/diastolic (S/D) ratios (area under the curve 0.86 versus 0.80). In a smaller cohort, VD in placentas with a diagnosis of inflammatory villitis (n = 10) by histology showed an increase in VD compared to those without inflammation (P = .01). Low VD was correlated with increased S/D ratios (P = .03). HUMI is useful for identifying altered placental vascularization in utero for FGR. VD may be a valuable indicator for placental health and could lead to improved risk stratification methods considering underlying biology.

Trends of common laboratory biomarkers after SARS-CoV-2 infection

Most studies that explore the long-term effects of COVID-19 are based on subjectively reported symptoms, while laboratory-measured biomarkers are mainly examined in studies of relatively small cohorts. This study investigates the long-term effects of SARS-CoV-2 infection on common laboratory biomarkers. We utilized a retrospective cohort of SARS-CoV-2 infected individuals and rigorously matched controls based on demographic and clinical characteristics, examining 63 common laboratory biomarkers. Additional lab-specific cohorts were matched with an additional criterion of baseline biomarker values. Differences in biomarkers over a 12-month follow-up were analyzed using standardized mean difference-in-differences. The general cohort included 361,061 matched pairs, with 26M laboratory results. The effects on most biomarkers lasted 1-4 months and were consistent with anticipated changes after acute viral infections. Some biomarkers presented prolonged effects, consistent across the general and lab-specific cohorts. One group of such findings included a 7-8 month decrease in WBC counts, mainly driven by decreased counts of neutrophils, monocytes, and basophils. Potassium levels were decreased for 3-5 months. Vaccinated individuals' data suggested potentially smaller effects on WBCs, but cohort sizes limited this analysis. This study explores SARS-CoV-2 infection effects on common laboratory biomarkers, characterizing the direction and duration of these effects on the largest infected cohort to date. The effects of most biomarkers resolve in the first months following infection. The most notable longer-lasting effects involved the immune system. Further research is required to characterize the magnitude of these effects among specific individuals.