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American Heart Journal Jun 2024Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes)...
BACKGROUND
Hypertensive disorders of pregnancy (HDP) are associated with increased long-term risk for cardiometabolic risk factors (chronic hypertension [HTN], obesity, diabetes) and heart failure. Exercise capacity is a known predictor of heart failure in patients with normal resting cardiac filling pressures. In this prospective observational cohort study, we sought to identify predictors of reduced postpartum exercise capacity in participants with normotensive vs. preeclamptic pregnancies.
METHODS
Preeclampsia (PreE) and normotensive subjects were enrolled to undergo bedside echocardiography within 48 hours of delivery, and rest/exercise echocardiography 12 weeks postpartum.
RESULTS
Recruited subjects (n=68) were grouped according to their blood pressure as: a) normotensive pregnancy n=15; b) PreE with normotensive postpartum (PreE-Resolved, n=36); c) PreE with persistent postpartum HTN (PreE-HTN, n=17). At enrollment, a significantly higher percentage of subjects in the PreE-HTN group were Black. Compared to normotensive and PreE-Resolved subjects, those with PreE-HTN demonstrated higher resting systolic blood pressure (SBP, 112 [normotensive] vs 112 [PreE-Resolved] vs 134 [PreE-HTN], p<0.001) and diastolic blood pressure (DBP, 70.0 vs 72.5 vs 85.0, p<0.001), and significantly less postpartum weight loss (9.6% vs 13.6% vs 3.8%, p<0.001). Following Bruce protocol stress testing, PreE-HTN subjects demonstrated achieved significantly lower exercise duration (10.4 vs 10.2 vs 7.9 minutes, p = 0.001). Subjects with PreE-HTN also demonstrated evidence of exercise-induced diastolic dysfunction as assessed by peak exercise lateral e' (18.0 vs 18.0 vs 13.5, p=0.045) and peak exercise tricuspid regurgitation velocity (TR Vm, 2.4 vs 3.0 vs 3.1, p = 0.045). Exercise duration was negatively associated with gravidity (R=-0.27, p=0.029) and postpartum LV mass index (R=-0.45, p<0.001), resting average E/e' (R=-0.51, p<0.001), BMI (R=-0.6, p<0.001) and resting SBP (R=-0.51, p<0.001).
CONCLUSIONS
Postpartum exercise stress testing capacity is related to readily available clinical markers including pregnancy factors, echocardiographic parameters and unresolved cardiometabolic risk factors.
PubMed: 38944263
DOI: 10.1016/j.ahj.2024.06.002 -
American Heart Journal Jun 2024This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct...
OBJECTIVES
This study aims to evaluate the efficacy and cost-effectiveness of sonothrombolysis delivered pre and post primary percutaneous coronary intervention (pPCI) on infarct size assessed by cardiac MRI, in patients presenting with STEMI, when compared against sham procedure.
BACKGROUND
More than a half of patients with successful pPCI have significant microvascular obstruction and residual infarction. Sonothrombolysis is a therapeutic use of ultrasound with contrast enhancement that may improve microcirculation and infarct size. The benefits and real time physiological effects of sonothrombolysis in a multicentre setting are unclear.
METHODS
The REDUCE (Restoring microvascular circulation with diagnostic ultrasound and contrast agent) trial is a prospective, multicentre, patient and outcome blinded, sham-controlled trial. Patients presenting with STEMI will be randomized to one of two treatment arms, to receive either sonothrombolysis treatment or sham echocardiography before and after pPCI. This tailored design is based on preliminary pilot data from our centre, showing that sonothrombolysis can be safely delivered, without prolonging door to balloon time. Our primary endpoint will be infarct size assessed on day 4±2 on Cardiac Magnetic Resonance (CMR). Patients will be followed up for six months post pPCI to assess secondary endpoints. Sample size calculations indicate we will need 150 patients recruited in total.
CONCLUSIONS
This multicentre trial will test whether sonothrombolysis delivered pre and post primary PCI can improve patient outcomes and is cost-effective, when compared with sham ultrasound delivered with primary PCI. The results from this trial may provide evidence for the utilization of sonothrombolysis as an adjunct therapy to pPCI to improve cardiovascular outcomes in STEMI. ANZ Clinical Trial Registration number: ACTRN 12620000807954.
PubMed: 38944262
DOI: 10.1016/j.ahj.2024.06.008 -
American Journal of Infection Control Jun 2024Candida auris is an emerging multidrug-resistant fungus associated with catheter-related bloodstream infections (CRBSI). In-vitro efficacy of chlorhexidine (CHX) and...
The antimicrobial effectiveness of chlorhexidine and chlorhexidine-silver sulfadiazine impregnated central venous catheters against the emerging fungal pathogen Candida auris.
BACKGROUND
Candida auris is an emerging multidrug-resistant fungus associated with catheter-related bloodstream infections (CRBSI). In-vitro efficacy of chlorhexidine (CHX) and CHX/silver sulfadiazine-impregnated (CHX-S) antimicrobial central venous catheters (CVCs) against C. auris was investigated.
MATERIAL AND METHODS
Minimum inhibitory (MIC) and bactericidal (MBC) CHX concentrations were determined against nineteen C. auris isolates. To assess extraluminal efficacy, segments from CVCs impregnated externally (CHX-S1) and both externally and internally (CHX-S2) were plasma-conditioned for 1- and 6-days, and to assess intraluminal efficacy CHX-S2 CVCs were pre-conditioned with saline-lock for 6-days, followed by 24-hour C. auris inoculation and microbial adherence determination on impregnated and non-impregnated CVCs.
RESULTS
CHX inhibited all C. auris isolates with MIC and MBC range of 8-128 μg/mL. C. auris adherence was reduced on CHX-S1 and CHX-S2 extraluminally by 100% on day-1, 86.96%-100% on day-7, and intraluminally on CHX-S2 by 56.86%-90.52% on day-7.
DISCUSSION
CHX and CHX-S CVCs performance against C. auris observed in this study is consistent with antimicrobial benefits observed in prior pre-clinical and randomized controlled clinical studies.
CONCLUSIONS
CHX showed strong inhibitory and cidal effects on C. auris. CHX-S CVCs proved highly efficacious against this pathogen under in vitro conditions. Additional studies, however, are required to confirm clinical benefit.
PubMed: 38944155
DOI: 10.1016/j.ajic.2024.06.015 -
Journal of the Neurological Sciences Jun 2024This paper describes the development, content, structure, and implementation of a case-based collaborative learning, flipped classroom, integrated preclinical neurology,...
This paper describes the development, content, structure, and implementation of a case-based collaborative learning, flipped classroom, integrated preclinical neurology, neuroanatomy, and neuroscience course for first year medical students at Harvard Medical School. We report the methods for pre-class preparation, in-class instruction, and evaluation; student feedback with respect to content, teaching method, and learning environment; and several lessons learned regarding how to optimize preparatory and in-class learning in a case-based flipped classroom course.
PubMed: 38943894
DOI: 10.1016/j.jns.2024.123097 -
Biomaterials Jun 2024The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide...
The widespread application of nanoparticles (NPs) in various fields has raised health concerns, especially in reproductive health. Our research has shown zinc oxide nanoparticles (ZnONPs) exhibit the most significant toxicity to pre-implantation embryos in mice compared to other common NPs. In patients undergoing assisted reproduction technology (ART), a significant negative correlation was observed between Zn concentration and clinical outcomes. Therefore, this study explores the impact of ZnONPs exposure on pre-implantation embryonic development and its underlying mechanisms. We revealed that both in vivo and in vitro exposure to ZnONPs impairs pre-implantation embryonic development. Moreover, ZnONPs were found to reduce the pluripotency of mouse embryonic stem cells (mESCs), as evidenced by teratoma and diploid chimera assays. Employing multi-omics approaches, including RNA-Seq, CUT&Tag, and ATAC-seq, the embryotoxicity mechanisms of ZnONPs were elucidated. The findings indicate that ZnONPs elevate H3K9me3 levels, leading to increased heterochromatin and consequent inhibition of gene expression related to development and pluripotency. Notably, Chaetocin, a H3K9me3 inhibitor, sucessfully reversed the embryotoxicity effects induced by ZnONPs. Additionally, the direct interaction between ZnONPs and H3K9me3 was verified through pull-down and immunoprecipitation assays. Collectively, these findings offer new insights into the epigenetic mechanisms of ZnONPs toxicity, enhancing our understanding of their impact on human reproductive health.
PubMed: 38943823
DOI: 10.1016/j.biomaterials.2024.122679 -
Psychiatry Research Jun 2024The 17-item Hamilton Rating Scale for Depression (HRSD-17) is the most popular depression measure in antidepressant clinical trials. Prior evidence indicates poor...
Evaluating the psychometric structure of the Hamilton Rating Scale for Depression pre- and post-treatment in antidepressant randomised trials: Secondary analysis of 6843 individual participants from 20 trials.
BACKGROUND
The 17-item Hamilton Rating Scale for Depression (HRSD-17) is the most popular depression measure in antidepressant clinical trials. Prior evidence indicates poor replicability and inconsistent factorial structure. This has not been studied in pooled randomised trial data, nor has a psychometrically optimal model been developed.
AIMS
To examine the psychometric properties of the HRSD-17 for pre-treatment and post-treatment clinical trial data in a large pooled database of antidepressant randomised controlled trial participants, and to determine an optimal abbreviated version.
METHOD
Data for 6843 participants were obtained from the data repository Vivli.org and randomly split into groups for exploratory (n = 3421) and confirmatory (n = 3422) factor analysis. Invariance methods were used to assess potential sex differences.
RESULTS
The HRSD-17 was psychometrically sub-optimal and non-invariant for all models. High item variances and low variance explained suggested redundancy in each model. EFA failed at baseline and produced four item models for outcome groups (five for placebo-outcome), which were metric but not scalar invariant.
CONCLUSIONS
In antidepressant trial data, the HRSD-17 was psychometrically inadequate and scores were not sex invariant. Neither full nor abbreviated HRSD models are suitable for use in clinical trial settings and the HRSD's status as the gold standard should be reconsidered.
PubMed: 38943787
DOI: 10.1016/j.psychres.2024.116057 -
European Journal of Oncology Nursing :... Jun 2024Self-management is an essential component of the curative treatment trajectory of esophageal cancer patients. The aims of this study were to explore expectations and...
PURPOSE
Self-management is an essential component of the curative treatment trajectory of esophageal cancer patients. The aims of this study were to explore expectations and needs of esophageal cancer patients during curative treatment regarding self-management, relevant aspects of self-management in which they need additional support, and to explore their willingness to use eHealth.
METHODS
Semi-structured interviews were conducted with esophageal cancer patients, who had been treated with neoadjuvant chemo(radio)therapy followed by surgery, maximally 1 year after surgery. Based on the general model of self-management, the following themes were discussed: experience-based knowledge, contribution to care, living with the condition, and organization of care and support. A stepwise systematic text condensation guided the data analysis.
RESULTS
All four domains of the general model of self-management were identified. All participants described a remarkable difference between the pre-operative pathway, when it felt like they were taken by the hand, and the postoperative pathway, when it felt like they were thrown into the deep end. They adjusted to their new life situation by learning new experiences, while dealing with their diminished confidence in their bodies. Patients expressed the need for support from different sources, and were open to the idea of using eHealth in addition to usual care. (digital) Self-management support should be easily accessible, person-centered, confidential, and include personal contact.
CONCLUSION
Differences were found among esophageal cancer patients regarding self-management, self-management support and eHealth for self-management purposes, indicating there is no one approach that will meet the needs of all patients at all times.
PubMed: 38943774
DOI: 10.1016/j.ejon.2024.102638 -
ESMO Open Jun 2024The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone...
Unraveling the clinicopathological and molecular changes induced by neoadjuvant chemotherapy and endocrine therapy in hormone receptor-positive/HER2-low and HER2-0 breast cancer.
BACKGROUND
The characterization and comparison of gene expression and intrinsic subtype (IS) changes induced by neoadjuvant chemotherapy (NACT) and endocrine therapy in hormone receptor-positive (HR+)/human epidermal growth factor receptor 2 (HER2)-low versus HR+/HER2-0 breast cancer (BC) has not been conducted so far. Most evidence on the association of HER2 status with pathologic responses and prognosis in HR+/HER2-negative BC is controversial and restricted to NACT-treated disease. Similarly, a temporal heterogeneity in HER2 status has been described only with NACT.
METHODS
We retrospectively recruited a consecutive cohort of 186 patients with stage I-IIIB HR+/HER2-negative BC treated with neoadjuvant therapy (NAT). Available diagnostic biopsies and surgical samples were characterized for main pathological features, PAM50 IS and ROR-P score, and gene expression. Associations with pathologic complete response, residual cancer burden-0/I, event-free survival (EFS) and overall survival (OS) based on HER2 status were assessed. Pre/post pathologic/molecular changes were analyzed in matched samples.
RESULTS
The HER2-low (62.9%) and HER2-0 (37.1%) cohorts did not differ significantly in main baseline features, treatments administered, breast-conserving surgery, pathologic complete response and residual cancer burden-0/I rates, EFS, and OS. NAT induced, regardless of HER2 status, a significant reduction of estrogen receptor/progesterone receptor and Ki67 levels, a down-regulation of PAM50 proliferation- and luminal-related genes/signatures, an up-regulation of selected immune genes, and a shift towards less aggressive IS and lower ROR-P. Moreover, 25% of HER2-0 changed to HER2-low and 34% HER2-low became HER2-0. HER2 shifts were significant after NACT (P < 0.001), not neoadjuvant endocrine therapy (P = 0.063), with consistent ERBB2 mRNA level dynamics. HER2 changes were not associated with EFS/OS.
CONCLUSIONS
HER2-low and HER2-0 status change after NAT in ∼30% of cases, mostly after NACT. Targeted adjuvant strategies should be investigated accordingly. Molecular downstaging with current chemo/endocrine agents and immunotherapy should not rely on HER2 immunohistochemical levels in HR+/HER2-negative BC. Instead, HER2-low-targeted approaches should be explored to pursue more effective and/or less toxic dimensional downstaging.
PubMed: 38943737
DOI: 10.1016/j.esmoop.2024.103619 -
ESMO Open Jun 2024Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment... (Review)
Review
Current unmet needs in locally advanced (unresectable) or metastatic dedifferentiated liposarcoma, the relevance of progression-free survival as clinical endpoint, and expectations for future clinical trial design: an international Delphi consensus report.
BACKGROUND
Locally advanced (unresectable) or metastatic dedifferentiated liposarcoma (DDLPS) is a common presentation of liposarcoma. Despite established diagnostic and treatment guidelines for DDLPS, critical clinical gaps remain driven by diagnostic challenges, symptom burden and the lack of targeted, safe and effective treatments. The objective of this study was to gather expert opinions from Europe and the United States on the management, unmet needs and expectations for clinical trial design as well as the value of progression-free survival (PFS) in this disease. Other aims included raising awareness and educate key stakeholders across healthcare systems.
MATERIALS AND METHODS
An international panel of 12 sarcoma key opinion leaders (KOLs) was recruited. The study consisted of two rounds of surveys with pre-defined statements. Experts scored each statement on a 9-point Likert scale. Consensus agreement was defined as ≥75% of experts scoring a statement with ≥7. Revised statements were discussed in a consensus meeting.
RESULTS
Consensus was reached on 43 of 55 pre-defined statements across disease burden, treatment paradigm, unmet needs, value of PFS and its association with overall survival (OS), and cross-over trial design. Twelve statements were deprioritised or merged with other statements. There were no statements where experts disagreed.
CONCLUSION
This study constitutes the first international Delphi panel on DDLPS. It aimed to explore KOL perception of the disease burden and unmet need in DDLPS, the value of PFS, and its potential translation to OS benefit, as well as the relevance of a cross-over trial design for DDLPS therapies. Results indicate an alignment across Europe and the United States regarding DDLPS management, unmet needs, and expectations for clinical trials. Raising awareness of critical clinical gaps in relation to DDLPS can contribute to improving patient outcomes and supporting the development of innovative treatments.
PubMed: 38943735
DOI: 10.1016/j.esmoop.2024.103487 -
Journal of Plastic, Reconstructive &... Jun 2024Patient-reported outcome measures (PROM) are collected pre- and post-operatively following cosmetic surgery. Clinicians assess their own outcomes following surgery, but...
Patient-reported outcome measures (PROM) are collected pre- and post-operatively following cosmetic surgery. Clinicians assess their own outcomes following surgery, but without a validated clinician-reported outcome measure (CROM), there is no way to compare the clinical results among clinicians or compare these to PROM. Assessment of clinical outcomes is important to address the patients' expectations in the consenting process and to provide recommendations to patients preoperatively to improve post-operative appearance. To address the lack of validated CROM for cosmetic surgery, the Manchester Cosmetic Clinical Reported Outcome Questionnaire (MCCRO-Q) was developed. This study assessed the inter-rater reliability of assessors using the four-point scale pre- and post-operative MCCRO-Q questionnaires. Fifteen assessors reviewed photos from pre- and post-operative assessments in the UK between July 2016 and February 2020. Ninety-five patients were included in this validation study, with each patient assessed by a minimum of 3 assessors. MCCRO-Q showed consistency between reviewers, with all intra-class coefficient averages >0.5 for pre- and post-operative assessments. Moreover, 26% of preoperative assessments demonstrated perfect agreement, 56% had a maximum one-point difference and 18% had a two-point difference to the median score. Furthermore, 1% of postoperative assessments demonstrated perfect agreement, 36% had a one-point difference and 63% had a maximum point difference of 2 to the median score. The inter-rate agreement showed that MCCRO-Q is a reliable tool when used with 3 or more assessors to judge patient appearance clinically, preoperatively and post-operatively, concerning abdominoplasty.
PubMed: 38943700
DOI: 10.1016/j.bjps.2024.05.050