New and future heart failure drugs.

In the past decade, our understanding of heart failure pathophysiology has advanced significantly, resulting in the development of new medications such as angiotensin-neprilysin inhibitors, sodium-glucose cotransporter-2 inhibitors and oral soluble guanylate cyclase stimulators. Backed by positive findings from large randomized controlled trials, recommendations for their use were recently included in the 2022 AHA/ACC/HFSA guidelines and 2023 ESC guidelines for management of heart failure. Promising drugs for future heart failure treatment include agents that modulate the neurohormonal system, vasodilators, anti-inflammatory drugs, mitotropes, which improve deranged energy metabolism of the failing heart, and myotropes, which increase cardiac contractility by affecting cardiac sarcomere function.

Global Assessment of Training Needs in Addiction Medicine.

Introduction: A minority of addiction patients receive appropriate treatment directly from trained professionals in addiction medicine. Most countries have not recognized addiction medicine (AM) as a specialty in its own right or within psychiatry/other specialties. Therefore, the effectiveness and organization of AM training around the world need to be improved.

Stakeholder Perspectives on a Heart Failure With Reduced Ejection Fraction Polypill: A Multi-Center Mixed Methods Study.

Background: A polypill containing all 4 classes of guideline-directed medical therapy for heart failure with reduced ejection fraction (HFrEF) has been proposed to change the heart failure treatment paradigm. The acceptability, appropriateness, and feasibility of a HFrEF polypill-based strategy are unknown. The purpose of this study was to elicit patients' and providers' priorities in the design of HFrEF polypills.

Uncovering the Hidden: Investigating Influences on Sexual Victimization Among 439 Transgender and Gender Diverse Individuals Behind Bars.

Despite repeated reports of sexual victimization by transgender and gender diverse (TGD) people who are incarcerated, there remains little literature on the source of this sexual assault and the factors that heightened likelihood of experiencing assault while incarcerated. The current research ( = 439) is the first known study aimed at understanding whether individual and state-level factors influence sexual assault while incarcerated. Utilizing data from the 2015 United States Transgender Survey and Malkin and DeJong's (2018) PREA compliance study, analyses were conducted to understand whether individual differences and the number of transgender-specific PREA policies were associated with the likelihood of experiencing sexual assault while incarcerated.

Heart failure with preserved ejection fraction.

Heart failure with preserved ejection fraction (HFpEF) accounts for nearly half of all heart failure cases and has a prevalence that is expected to rise with the growing ageing population. HFpEF is associated with significant morbidity and mortality. Specific HFpEF risk factors include age, diabetes, hypertension, obesity and atrial fibrillation.

Converging cytokine and metabolite networks shape asymmetric T cell fate at the term human maternal-fetal interface.

Placentation presents immune conflict between mother and fetus, yet in normal pregnancy maternal immunity against infection is maintained without expense to fetal tolerance. This is believed to result from adaptations at the maternal-fetal interface (MFI) which affect T cell programming, but the identities (i.e.

Artificial intelligence for natural product drug discovery.

Developments in computational omics technologies have provided new means to access the hidden diversity of natural products, unearthing new potential for drug discovery. In parallel, artificial intelligence approaches such as machine learning have led to exciting developments in the computational drug design field, facilitating biological activity prediction and de novo drug design for molecular targets of interest. Here, we describe current and future synergies between these developments to effectively identify drug candidates from the plethora of molecules produced by nature.

Previous missed visits and independent risk of loss to follow-up in the high-risk neonatal follow-up clinic.

Background: Neonatal intensive care unit (NICU) patients are at high risk for developmental delays. As a result, many are seen in neonatal follow-up (NFU) clinics. Disparities in NFU follow-up rates by social determinants of health exist.

"I Just Wanted Nothing More Than to Get in a Real Shower": Patient Experience of the Inpatient Wait for a Heart Transplant.

Background: Patients waiting for heart transplant may be hospitalized for weeks to months before undergoing transplantation. This high-stress period is further complicated by restrictions of daily privileges including diet, rooming, access to the outdoors, and hygiene (eg, limited in ability to shower). However, there is a paucity of research on the experience of this waiting period.

The Inflation Reduction Act and Out-of-Pocket Drug Costs for Medicare Beneficiaries With Cardiovascular Disease.

Background: High out-of-pocket costs can impede access to guideline-directed cardiovascular drugs. The 2022 Inflation Reduction Act (IRA) will eliminate catastrophic coinsurance and cap annual out-of-pocket costs for Medicare Part D patients by 2025.

Objectives: This study sought to estimate the IRA's impact on out-of-pocket costs for Part D beneficiaries with cardiovascular disease.

Intersurgeon Variability in Local Treatment Planning for Patients with Initially Unresectable Colorectal Cancer Liver Metastases: Analysis of the Liver Expert Panel of the Dutch Colorectal Cancer Group.

Background: Consensus on resectability criteria for colorectal cancer liver metastases (CRLM) is lacking, resulting in differences in therapeutic strategies. This study evaluated variability of resectability assessments and local treatment plans for patients with initially unresectable CRLM by the liver expert panel from the randomised phase III CAIRO5 study.

Methods: The liver panel, comprising surgeons and radiologists, evaluated resectability by predefined criteria at baseline and 2-monthly thereafter.

A Dutch prediction tool to assess the risk of incidental gallbladder cancers after cholecystectomies for benign gallstone disease.

Background: Despite the increasing implementation of selective histopathologic policies for post-cholecystectomy evaluation of gallbladder specimens in low-incidence countries, the fear of missing incidental gallbladder cancer (GBC) persists. This study aimed to develop a diagnostic prediction model for selecting gallbladders that require additional histopathological examination after cholecystectomy.

Methods: A registration-based retrospective cohort study of nine Dutch hospitals was conducted between January 2004 and December 2014.

The role of tumour biological factors in technical anatomical resectability assessment of colorectal liver metastases following induction systemic treatment: An analysis of the Dutch CAIRO5 trial.

Background: Large inter-surgeon variability exists in technical anatomical resectability assessment of colorectal cancer liver-only metastases (CRLM) following induction systemic therapy. We evaluated the role of tumour biological factors in predicting resectability and (early) recurrence after surgery for initially unresectable CRLM.

Methods: 482 patients with initially unresectable CRLM from the phase 3 CAIRO5 trial were selected, with two-monthly resectability assessments by a liver expert panel.

Fluxomics reveals cellular and molecular basis of increased renal ammoniagenesis.

The kidney plays a critical role in excreting ammonia during metabolic acidosis and liver failure. The mechanisms behind this process have been poorly explored. The present study combines results of in vivo experiments of increased total ammoniagenesis with systems biology modeling, in which eight rats were fed an amino acid-rich diet (HD group) and eight a normal chow diet (AL group).

Long-term follow-up of a randomized trial of biliary drainage in perihilar cholangiocarcinoma.

Background And Aims: The DRAINAGE trial was a randomized controlled trial comparing preoperative endoscopic (EBD) and percutaneous biliary drainage (PTBD) in patients with potentially resectable, perihilar cholangiocarcinoma (pCCA). The aim of this study was to compare the long-term outcomes.

Methods: Patients were randomized in four tertiary referral centers.

'I Am Not The Doctor For You': Physicians' Attitudes About Caring For People With Disabilities.

People with disabilities face barriers when attempting to gain access to health care settings. Using qualitative analysis of three physician focus groups, we identified physical, communication, knowledge, structural, and attitudinal barriers to care for people with disabilities. Physicians reported feeling overwhelmed by the demands of practicing medicine in general and the requirements of the Americans with Disabilities Act of 1990 specifically; in particular, they felt that they were inadequately reimbursed for accommodations.

Trends in Early and Late Mortality in Patients With Severe Acute Pancreatitis Admitted to ICUs: A Nationwide Cohort Study.

Objectives: To investigate national mortality trends over a 12-year period for patients with severe acute pancreatitis (SAP) admitted to Dutch ICUs. Additionally, an assessment of outcome in SAP was undertaken to differentiate between early (< 14 d of ICU admission) and late (> 14 d of ICU admission) mortality.

Design: Data from the Dutch National Intensive Care Evaluation and health insurance companies' databases were extracted.

Defining Textbook Outcome in liver surgery and assessment of hospital variation: A nationwide population-based study.

Introduction: Textbook outcome (TO) is a composite outcome measure covering the surgical care process in a single outcome measure. TO has an advantage over single outcome parameters with low event rates, which have less discriminating impact to detect differences between hospitals. This study aimed to assess factors associated with TO, and evaluate hospital and network variation after case-mix correction in TO rates for liver surgery.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

Objective: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited.

Design: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents.

Endoscopic Versus Surgical Step-Up Approach for Infected Necrotizing Pancreatitis (ExTENSION): Long-term Follow-up of a Randomized Trial.

Background & Aims: Previous randomized trials, including the Transluminal Endoscopic Step-Up Approach Versus Minimally Invasive Surgical Step-Up Approach in Patients With Infected Pancreatic Necrosis (TENSION) trial, demonstrated that the endoscopic step-up approach might be preferred over the surgical step-up approach in patients with infected necrotizing pancreatitis based on favorable short-term outcomes. We compared long-term clinical outcomes of both step-up approaches after a period of at least 5 years.

Methods: In this long-term follow-up study, we reevaluated all clinical data on 83 patients (of the originally 98 included patients) from the TENSION trial who were still alive after the initial 6-month follow-up.

Interobserver Variability in CT-based Morphologic Tumor Response Assessment of Colorectal Liver Metastases.

Purpose To evaluate interobserver variability in the morphologic tumor response assessment of colorectal liver metastases (CRLM) managed with systemic therapy and to assess the relation of morphologic response with gene mutation status, targeted therapy, and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 measurements. Materials and Methods Participants with initially unresectable CRLM receiving different systemic therapy regimens from the randomized, controlled CAIRO5 trial (NCT02162563) were included in this prospective imaging study.