Initiation and sequencing of guideline-directed medical therapy for heart failure across the ejection fraction spectrum.

Strong evidence supports the importance of rapid sequence or simultaneous initiation of quadruple guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) for substantially reducing risk of mortality and hospitalization. Barring absolute contraindications for each individual medication, employing the strategy of rapid sequence, simultaneous, and/or in-hospital initiation at the time of HF diagnosis best ensures patients with HFrEF have the opportunity to benefit from proven medications and achieve large absolute risk reductions for adverse clinical outcomes. However, despite guideline recommendations supporting this approach, implementation in clinical practice remains persistently low, with less than one-fifth of eligible patients being prescribed the quadruple GDMT regimen.

Daratumumab plus lenalidomide/dexamethasone in untreated multiple myeloma: analysis of key subgroups of the MAIA study.

In the MAIA study (median follow-up, 56.2 months), daratumumab plus lenalidomide and dexamethasone (D-Rd) significantly improved progression-free survival (PFS) and overall survival versus lenalidomide and dexamethasone (Rd) alone in transplant-ineligible newly diagnosed multiple myeloma (NDMM). In this post hoc analysis of clinically important subgroups in MAIA (median follow-up, 64.

Proteolysis-targeting influenza vaccine strains induce broad-spectrum immunity and in vivo protection.

Generating effective live vaccines from intact viruses remains challenging owing to considerations of safety and immunogenicity. Approaches that can be applied in a systematic manner are needed. Here we created a library of live attenuated influenza vaccines by using diverse cellular E3 ubiquitin ligases to generate proteolysis-targeting (PROTAR) influenza A viruses.

A novel human fetal lung-derived alveolar organoid model reveals mechanisms of surfactant protein C maturation relevant to interstitial lung disease.

Alveolar type 2 (AT2) cells maintain lung health by acting as stem cells and producing pulmonary surfactant. AT2 dysfunction underlies many lung diseases, including interstitial lung disease (ILD), in which some inherited forms result from the mislocalization of surfactant protein C (SFTPC) variants. Lung disease modeling and dissection of the underlying mechanisms remain challenging due to complexities in deriving and maintaining human AT2 cells ex vivo.

The clinical effect of bone perforations in periodontal regeneration and alveolar socket preservation: a systematic review with meta-analysis.

Objectives: The present systematic review aimed to evaluate if cortical bone perforation is effective in enhancing periodontal surgery and guided bone regeneration (GBR) in humans.

Materials And Methods: Electronic search was performed in PubMed, Scopus and Cochrane CENTRAL up to October 31st, 2023. Grey literature was also searched.

"They knew the same struggles": perceptions of a group coping skills intervention in patients with chronic graft-versus-host disease.

Purpose: Chronic graft-versus-host-disease (cGVHD), an inflammatory condition affecting allogeneic hematopoietic cell transplantation (HCT) survivors, is associated with a range of debilitating physical and psychological sequela. Yet HCT recipients with cGVHD are virtually absent from survivorship intervention research. We conducted a randomized clinical trial to evaluate the feasibility and preliminary efficacy of a multidisciplinary group coping skills intervention (Horizons) tailored to meet these patients' unique needs.

Prolonged persistence of mutagenic DNA lesions in somatic cells.

DNA is subject to continual damage, leaving each cell with thousands of individual DNA lesions at any given moment. The efficiency of DNA repair means that most known classes of lesion have a half-life of minutes to hours, but the extent to which DNA damage can persist for longer durations remains unknown. Here, using high-resolution phylogenetic trees from 89 donors, we identified mutations arising from 818 DNA lesions that persisted across multiple cell cycles in normal human stem cells from blood, liver and bronchial epithelium.

Treatment of patients with tumor/treatment-related hypothalamic obesity in the first two years following surgical treatment or radiotherapy.

Survivors of sellar/suprasellar tumors involving hypothalamic structures face a risk of impaired quality of life, including tumor- and/or treatment-related hypothalamic obesity (TTR-HO) defined as abnormal weight gain resulting in severe persistent obesity due to physical, tumor- and/or treatment related damage of the hypothalamus. We analyze German claims data to better understand treatment pathways for patients living TTR-HO during the two years following the index surgical treatment. A database algorithm identified patients with TTR-HO in a representative German payer claims database between 2010 and 2021 (n = 5.

Early-life cognitively stimulating activities and late-life cognitive function in the St. Louis Baby Tooth Later Life Health Study.

Childhood cognitively stimulating activities have been associated with higher cognitive function in late life. Whether activities in early or late childhood are more salient, and whether activities are associated with specific cognitive domains is unknown. Participants retrospectively reported cognitively stimulating activities at ages 6, 12, and 18 years.

Long-term exposure to ambient air pollution and epigenetic age acceleration in children.

Long-term exposure to ambient air pollution has been associated with epigenetic age acceleration (EAA) in adults, but its impact on children remains less understood. This study analyzed data from 457 children (mean age: 7.9 years) in the Project Viva cohort (2007-2010, eastern Massachusetts, USA).

Validation of Diagnosis Codes for Low Birth Weight and Small-for-Gestational Age in the Medicaid Analytic Extract Database.

Background: The accuracy of low birth weight (LBW) and small for gestational age (SGA) in administrative healthcare records is crucial for perinatal studies but has few validity studies.

Methods: Using 1999-2010 MAX linked to birth certificates (BC), we identified mother-infant dyads (≥30 days enrollment after delivery, with valid gestational age (GA) and birth weight (BW)). LBW and SGA were identified based on ICD-9-CM codes.

Artificial intelligence-based biomarkers for treatment decisions in oncology.

The development of new therapeutic strategies such as immune checkpoint inhibitors (ICIs) and targeted therapies has increased the complexity of the treatment landscape for solid tumors. At the current rate of annual FDA approvals, the potential treatment options could increase by tenfold over the next 5 years. The cost of personalized medicine technologies limits its accessibility, thus increasing socioeconomic disparities in the treated population.

Penalized G-estimation for effect modifier selection in a structural nested mean model for repeated outcomes.

Effect modification occurs when the impact of the treatment on an outcome varies based on the levels of other covariates known as effect modifiers. Modeling these effect differences is important for etiological goals and for purposes of optimizing treatment. Structural nested mean models (SNMMs) are useful causal models for estimating the potentially heterogeneous effect of a time-varying exposure on the mean of an outcome in the presence of time-varying confounding.

Surgical Bailout in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement: Incidence, Trends, and Clinical Outcomes.

Background: Transcatheter aortic valve replacement (TAVR) harbors the risk of periprocedural complications that require emergent cardiac surgery, or "surgical bailout." Surgical bailout intends to be lifesaving but is associated with high mortality. This has given rise to discussion on the necessity of surgical backup during TAVR.

Hemodynamic Valve Deterioration After Transcatheter Aortic Valve Replacement: Incidence, Predictors, and Clinical Outcomes.

Background: Reports on the durability of transcatheter aortic valve replacement (TAVR) prostheses are scarce and confounded by varying definitions and competing risks of death.

Objectives: The authors sought to determine the incidence, predictors, and clinical outcomes of hemodynamic valve deterioration (HVD) according to the Valve Academic Research Consortium 3 definition after TAVR.

Methods: We analyzed consecutive patients undergoing TAVR in the prospective Bern TAVI (Transcatheter Aortic Valve Implantation) registry between August 2007 and June 2022 for the incidence and predictors of HVD and performed case control-matching to compare outcomes according to HVD.

Clinical Characteristics and Outcomes of Patients Undergoing 3 Aortic Valve Interventions: The THIRD Multicenter Registry.

Background: Lifetime treatment of aortic valve disease is a matter of increasing debate. Although the risks of a second aortic valve intervention are recognized, little attention has been given to the challenges of a third.

Objectives: This study delves into the clinical characteristics, indications, and outcomes of patients undergoing 3 aortic valve interventions.

Early and Late Outcomes With the Absorb Bioresorbable Vascular Scaffold: Final Report From the ABSORB Clinical Trial Program.

Background: The risk-benefit ratio of the Absorb bioresorbable vascular scaffold (BVS) may vary before and after 3 years, the time point of complete bioresorption of the poly-L-lactic acid scaffold.

Objectives: The aim of this study was to determine the time-varying outcomes of the Absorb BVS compared with cobalt-chromium everolimus-eluting stents (EES) from a large individual-patient-data pooled analysis of randomized trials.

Methods: The individual patient data from 5 trials that randomized 5,988 patients undergoing percutaneous coronary intervention to the Absorb BVS vs EES with 5-year follow-up were pooled.

Did Finerenone Improve Health Status in the FINEARTS Trial?: A Critical Reevaluation of the Analysis of Patient-Reported Outcomes in Heart Failure.

Patient-reported health status is an important assessment of patients with heart failure, but current approaches have substantial methodological and analytical limitations. Changes in the Kansas City Cardiomyopathy Questionnaire (KCCQ) are commonly presented as a measure of the effect of drugs and devices, most often as the between-group difference in population means or as the odds of showing threshold changes of 5, 10, 15, and 20 points. However, the presentation of mean differences is based on statistical assumptions that are routinely violated in most trials.

Initial Decline in Glomerular Filtration Rate With Finerenone in HFmrEF/HFpEF: A Prespecified Analysis of FINEARTS-HF.

Background: An initial decline in estimated glomerular filtration rate (eGFR) often leads to reluctance to continue life-saving therapies in patients with heart failure (HF).

Objectives: The goal of this study was to describe the association between initial decline in eGFR and subsequent clinical outcomes in patients randomized to placebo or finerenone.

Methods: In this prespecified analysis of FINEARTS-HF (Finerenone Trial to Investigate Efficacy and Safety Superior to Placebo in Patients with Heart Failure), we examined the association between initial decline in eGFR (≥15%) from randomization to 1 month and subsequent outcomes in patients assigned to finerenone or placebo.

Serum Biomarkers of Pulmonary Damage and Risk for Progression of Rheumatoid Arthritis-Associated Interstitial Lung Disease.

Objective: To investigate baseline and change of pulmonary damage biomarkers (serum Krebs von den Lungen 6 [KL-6], human surfactant protein D [hSP-D], and matrix metalloproteinase 7 [MMP-7]) with rheumatoid arthritis-associated interstitial lung disease (RA-ILD) progression.

Methods: In the Korean Rheumatoid Arthritis Interstitial Lung Disease (KORAIL) cohort, a prospective cohort, we enrolled patients with RA and ILD confirmed by chest computed tomography imaging and followed annually. ILD progression was defined as worsening in physiological and radiological domains of the 2022 American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Society guideline for progressive pulmonary fibrosis (PPF).