Planning for end of life in the past and present: historical, legal and clinical perspectives on ReSPECT.

The ReSPECT ('Recommended Summary Plan for Emergency Care and Treatment') process was developed in the UK to guide and document conversations and decision-making with patients and their relatives around intervention during critical deterioration. This includes advising whether resuscitation should be attempted when a person dies. Current medical preparation for death is qualitatively different to social behaviours by people in the past and presents some controversies when considering the legal status of death-related decisions.

Geo-demographic trends in nontraumatic subarachnoid hemorrhage-related mortality among older adults in the United States, 1999-2020.

Introduction: Nontraumatic subarachnoid hemorrhage (ntSAH) often results from a ruptured aneurysm and correlates with significant morbidity and mortality, particularly among the older population. Despite its impact, limited comprehensive studies evaluate the longitudinal trends in ntSAH-related mortality in older adults in the United States (US).

Methods: The authors conducted a retrospective analysis using the CDC WONDER database from 1999 to 2020, analyzing Multiple Cause-of-Death Public Use death certificates to identify ntSAH as a contributing factor in the death of adults aged 65 years and older.

Distal Ventricular Pacing for Drug-Refractory Mid-Cavity Obstructive Hypertrophic Cardiomyopathy: A Randomized, Placebo-Controlled Trial of Personalized Pacing.

Background: Patients with refractory, symptomatic left ventricular (LV) mid-cavity obstructive (LVMCO) hypertrophic cardiomyopathy have few therapeutic options. Right ventricular pacing is associated with modest hemodynamic and symptomatic improvement, and LV pacing pilot data suggest therapeutic potential. We hypothesized that site-specific pacing would reduce LVMCO gradients and improve symptoms.

Management of cardiac sarcoidosis.

Cardiac sarcoidosis (CS) is a form of inflammatory cardiomyopathy associated with significant clinical complications such as high-degree atrioventricular block, ventricular tachycardia, and heart failure as well as sudden cardiac death. It is therefore important to provide an expert consensus statement summarizing the role of different available diagnostic tools and emphasizing the importance of a multidisciplinary approach. By integrating clinical information and the results of diagnostic tests, an accurate, validated, and timely diagnosis can be made, while alternative diagnoses can be reasonably excluded.

Hypoxia-inducible factor 1 recruits FACT and RNF20/40 to mediate histone ubiquitination and transcriptional activation of target genes.

Hypoxia-inducible factor 1 (HIF-1) is a transcriptional activator that mediates cellular adaptation to decreased oxygen availability. HIF-1 recruits chromatin-modifying enzymes leading to changes in histone acetylation, citrullination, and methylation at target genes. Here, we demonstrate that hypoxia-inducible gene expression in estrogen receptor (ER)-positive MCF7 and ER-negative SUM159 human breast cancer cells requires the histone H2A/H2B chaperone facilitates chromatin transcription (FACT) and the H2B ubiquitin ligase RING finger protein 20/40 (RNF20/40).

Sentinel report of uniquely paired collision tumors: glioblastoma multiforme and coexistent intraventricular subependymoma. Illustrative case.

Background: The presence of intracranial collision tumors, histologically distinct tumors occurring in anatomical proximity, is quite rare. Herein, the authors describe the sentinel case of a contiguous collision tumor combination consisting of glioblastoma multiforme and intraventricular subependymoma.

Observations: A 67-year-old male presented with several months of progressive fatigue superimposed on more recently noted word-finding difficulty, slight left-sided weakness, and episodic confusion.

The role of the right to life in respect of deaths caused by negligence in the healthcare context.

This article investigates the question of whether a death caused by negligence in the healthcare context is capable of violating the right to life under Article 2 of the European Convention on Human Rights. This provision imposes extensive positive obligations upon Contracting States, including an operational duty to take reasonable steps to save a life that they know, or ought to know, is at risk. This article addresses the question of exactly when such an operational duty arises, with particular focus on the healthcare context in which deaths caused by medical negligence have not traditionally been regarded as amounting to violations of the right to life.

Novel insights into diminished cardiac reserve in non-obstructive hypertrophic cardiomyopathy from four-dimensional flow cardiac magnetic resonance component analysis.

Aims: Hypertrophic cardiomyopathy (HCM) is characterized by hypercontractility and diastolic dysfunction, which alter blood flow haemodynamics and are linked with increased risk of adverse clinical events. Four-dimensional flow cardiac magnetic resonance (4D-flow CMR) enables comprehensive characterization of ventricular blood flow patterns. We characterized flow component changes in non-obstructive HCM and assessed their relationship with phenotypic severity and sudden cardiac death (SCD) risk.

Assessment of Cardiac Energy Metabolism, Function, and Physiology in Patients With Heart Failure Taking Empagliflozin: The Randomized, Controlled EMPA-VISION Trial.

Background: Sodium-glucose co-transporter 2 inhibitors (SGLT2i) have emerged as a paramount treatment for patients with heart failure (HF), irrespective of underlying reduced or preserved ejection fraction. However, a definite cardiac mechanism of action remains elusive. Derangements in myocardial energy metabolism are detectable in all HF phenotypes, and it was proposed that SGLT2i may improve energy production.

Plexin-B3 expression stimulates MET signaling, breast cancer stem cell specification, and lung metastasis.

Intratumoral hypoxia is a microenvironmental feature that promotes breast cancer progression and is associated with cancer mortality. Plexin B3 (PLXNB3) is highly expressed in estrogen receptor-negative breast cancer, but the underlying mechanisms and consequences have not been thoroughly investigated. Here, we report that PLXNB3 expression is increased in response to hypoxia and that PLXNB3 is a direct target gene of hypoxia-inducible factor 1 (HIF-1) in human breast cancer cells.

Prognostic Value of RV Abnormalities on CMR in Patients With Known or Suspected Cardiac Sarcoidosis.

Background: Left ventricular abnormalities in cardiac sarcoidosis (CS) are associated with adverse cardiovascular events, whereas the prognostic value of right ventricular (RV) involvement found on cardiac magnetic resonance is unclear.

Objectives: This study aimed to systematically assess the prognostic value of right ventricular ejection fraction (RVEF) and RV late gadolinium enhancement (LGE) in known or suspected CS.

Methods: This study was prospectively registered in PROSPERO (CRD42022302579).

NARF is a hypoxia-induced coactivator for OCT4-mediated breast cancer stem cell specification.

Hypoxia is a key characteristic of the breast cancer microenvironment that promotes expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and is associated with poor patient outcome. HIF-1 increases the expression or activity of stem cell pluripotency factors, which control breast cancer stem cell (BCSC) specification and are required for cancer metastasis. Here, we identify nuclear prelamin A recognition factor () as a hypoxia-inducible, HIF-1 target gene in human breast cancer cells.

Recruitment of women in neurosurgery: a 7-year quantitative analysis.

Objective: The authors aimed to characterize which US medical schools have the most female neurosurgery residents and to identify potential associations between medical school characteristics and successful recruitment of women pursuing a neurosurgery career.

Methods: The authors evaluated a total of 1572 residents in US neurosurgery programs accredited by the Accreditation Council for Graduate Medical Education as of February 2021, representing match cohorts from 2014 to 2020. The authors extracted US medical school characteristics and ranked schools based on the percentages of women graduates entering neurosurgery.

Polymeric Nanoparticles in Brain Cancer Therapy: A Review of Current Approaches.

Translation of novel therapies for brain cancer into clinical practice is of the utmost importance as primary brain tumors are responsible for more than 200,000 deaths worldwide each year. While many research efforts have been aimed at improving survival rates over the years, prognosis for patients with glioblastoma and other primary brain tumors remains poor. Safely delivering chemotherapeutic drugs and other anti-cancer compounds across the blood-brain barrier and directly to tumor cells is perhaps the greatest challenge in treating brain cancer.

The Translational Potential of Microglia and Monocyte-Derived Macrophages in Ischemic Stroke.

The immune response to ischemic stroke is an area of study that is at the forefront of stroke research and presents promising new avenues for treatment development. Upon cerebral vessel occlusion, the innate immune system is activated by danger-associated molecular signals from stressed and dying neurons. Microglia, an immune cell population within the central nervous system which phagocytose cell debris and modulate the immune response cytokine signaling, are the first cell population to become activated.

Hypoxia-inducible factors: cancer progression and clinical translation.

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis.

Home Program Matching in Neurosurgical Residency Programs: A 7-Year Study.

Objective: The objective of the study was to determine home program matching percentage (staying in a program affiliated with one's medical school) for each neurosurgical residency program in the United States. Secondarily, it was to elucidate both program-level and resident characteristics associated with home program matching.

Methods: Demographic and bibliometric characteristics were collected for 1572 residents in U.

HIF inhibitor 32-134D eradicates murine hepatocellular carcinoma in combination with anti-PD1 therapy.

Hepatocellular carcinoma (HCC) is a major cause of cancer mortality worldwide and available therapies, including immunotherapies, are ineffective for many patients. HCC is characterized by intratumoral hypoxia, and increased expression of hypoxia-inducible factor 1α (HIF-1α) in diagnostic biopsies is associated with patient mortality. Here we report the development of 32-134D, a low-molecular-weight compound that effectively inhibits gene expression mediated by HIF-1 and HIF-2 in HCC cells, and blocks human and mouse HCC tumor growth.

External Validation of a Neural Network Model in Aneurysmal Subarachnoid Hemorrhage: A Comparison With Conventional Logistic Regression Models.

Background: Interest in machine learning (ML)-based predictive modeling has led to the development of models predicting outcomes after aneurysmal subarachnoid hemorrhage (aSAH), including the Nijmegen acute subarachnoid hemorrhage calculator (Nutshell). Generalizability of such models to external data remains unclear.

Objective: To externally validate the performance of the Nutshell tool while comparing it with the conventional Subarachnoid Hemorrhage International Trialists (SAHIT) models and to review the ML literature on outcome prediction after aSAH and aneurysm treatment.

Which medical schools produce the most neurosurgery residents? An analysis of the 2014-2020 cohort.

Objective: In this study, the authors sought to determine which US medical schools have produced the most neurosurgery residents and to evaluate potential associations between recruitment and medical school characteristics.

Methods: Demographic and bibliometric characteristics were collected for 1572 residents in US-based and Accreditation Council for Graduate Medical Education (ACGME)-accredited neurosurgery programs over the 2014 to 2020 match period using publicly available websites. US medical school characteristics were collected, including class size, presence of a home neurosurgery program, number of clinical neurosurgery faculty, research funding, presence of a neurosurgery interest group, and a top 10 ranking via U.

Incremental value of left atrial booster and reservoir strain in predicting atrial fibrillation in patients with hypertrophic cardiomyopathy: a cardiovascular magnetic resonance study.

Background: Left atrial (LA) size and function are known predictors of new onset atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients. Components of LA deformation including reservoir, conduit, and booster function provide additional information on atrial mechanics. Whether or not LA deformation can augment our ability to predict the risk of new onset AF in HCM patients beyond standard measurements is unknown.