Neoadjuvant Chemotherapy and Immunotherapy for Estrogen Receptor-Positive Human Epidermal Growth Factor 2-Negative Breast Cancer.

Journal of Clinical Oncology

Guidelines for administering gadolinium-based contrast agents to patients with renal dysfunction (Version 3: Revised May 20th, 2024).

Clinical and Experimental Nephrology

Sepsis often leads to vasoplegia and a hyperdynamic cardiac state, with treatment focused on restoring vascular tone. However, sepsis can also cause reversible myocardial dysfunction, particularly in the elderly with pre-existing heart conditions. The Surviving Sepsis Campaign Guidelines recommend using dobutamine with norepinephrine or epinephrine alone for patients with septic shock with cardiac dysfunction and persistent hypoperfusion despite adequate fluid resuscitation and stable blood pressure. However, the definition of cardiac dysfunction and hypoperfusion in these guidelines remains controversial, leading to varied clinical interpretations. Cardiac dysfunction with persistent hypoperfusion despite restoring adequate preload and afterload is often considered a cardiogenic shock. Therefore, sepsis complicated by new-onset myocardial dysfunction or worsening of underlying myocardial dysfunction due to sepsis-induced cardiomyopathy, resulting in cardiogenic shock, can be defined as "Sepsis-induced cardiogenic shock (SICS)". SICS is known to be associated with significantly higher mortality. A history of cardiac dysfunction is a strong predictor of SICS, highlighting the need for precise diagnosis and management given the aging population and rising cardiovascular disease prevalence. Therefore, SICS might benefit from early invasive hemodynamic monitoring with a pulmonary artery catheter (PAC), unlike those with septic shock alone. While routine PAC monitoring for all septic patients is impractical, echocardiography could be a useful screening tool for high-risk individuals. If echocardiography indicates cardiogenic shock, PAC might be warranted for continuous monitoring. The role of inotropes in SICS remains uncertain. Mechanical circulatory support (MCS) might be considered for severe cases, as high-dose vasopressors and inotropes are associated with worse outcomes. Correct patient selection is the key to improving outcomes with MCS. Engaging a cardiogenic shock team for a multidisciplinary approach can be beneficial. In summary, addressing the evidence gaps in SICS diagnosis and management is crucial. Echocardiography for screening, advanced monitoring with PAC, and careful patient selection for MCS are important for optimal patient care.

Sepsis-induced cardiogenic shock: controversies and evidence gaps in diagnosis and management.

Journal of Intensive Care

Diuretic drugs act on electrolyte transporters in the kidney to induce diuresis and are often used in chronic kidney disease (CKD), given that nephron loss creates a deficit in the ability to excrete dietary sodium, which promotes an increase in plasma volume. This rise in plasma volume is exacerbated by CKD-induced systemic and intra-renal activation of the renin-angiotensin-aldosterone-system, which further limits urinary sodium excretion. In the absence of a compensatory decrease in systemic vascular resistance, increases in plasma volume induced by sodium retention can manifest as a rise in systemic arterial blood pressure. Management of sodium and volume overload in patients with CKD is therefore typically based on restriction of dietary sodium intake and the use of diuretic agents to enhance urinary sodium excretion. Thiazide and thiazide-type diuretics are foundational therapies for the management of hypertension, whereas loop diuretics are often needed for volume overload, which might also require combination therapies. Mineralocorticoid receptor antagonists have an important role in the management of diuretic-resistant volume overload or treatment-resistant hypertension. Additionally, diuretics can be used for the diagnosis of kidney diseases and in the management of hyperkalaemia or hypokalaemia, hyponatraemia, hypercalcaemia and hypomagnesaemia.

Diuretics in patients with chronic kidney disease.

Nature Reviews. Nephrology

Ketamine, an N-methyl-D-aspartic acid receptor antagonist that was first discovered in 1962, has become established in anaesthesia providing dose-dependent anaesthetic, sedative, and analgesic effects. Ketamine, however, also acts on a wide range of other cellular targets, resulting in interesting and diverse effects on both physiological and pathological processes. Potential beneficial properties of ketamine include cardiovascular stability for patients undergoing sedation or anaesthesia, analgesia in both acute and chronic pain, bronchodilation in severe refractory asthma, anti-inflammatory properties particularly in sepsis, tumour inhibition, and antidepressant properties with marked ability to reverse suicidal ideation. The reluctance to adopt ketamine into routine practice is likely attributable in part to the stigma and negative reputation associated with its perceived side-effects and potential for abuse. This review explores the diverse properties and therapeutic potentials of ketamine being investigated across different fields whilst also identifying areas for ongoing and future research. Given the diverse range of potential benefits and promising early work, ketamine should be the focus of ongoing research in multiple different specialty areas. This includes areas relevant to anaesthesia and perioperative medicine, such as acute and chronic pain management, ICU sedation, and even tumour suppression in those undergoing surgical resection of malignancies.

The diverse effects of ketamine, a jack-of-all-trades: a narrative review.

British Journal of Anaesthesia

Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired reasoning. It is the leading cause of dementia in older adults, marked by the pathological accumulation of amyloid-beta plaques and neurofibrillary tangles. These pathological changes lead to widespread neuronal damage, significantly impacting daily functioning and quality of life.

This comprehensive review aims to explore various aspects of Alzheimer's disease, including its epidemiology, risk factors, clinical presentation, diagnostic advancements, management strategies, caregiving challenges, and emerging therapeutic interventions.

A systematic literature review was conducted across multiple electronic databases, including PubMed, MEDLINE, Cochrane Library, and Scopus, from their inception to May 2024. The search strategy incorporated a combination of keywords and Medical Subject Headings (MeSH) terms such as "Alzheimer's disease," "epidemiology," "risk factors," "symptoms," "diagnosis," "management," "caregiving," "treatment," and "novel therapies." Boolean operators (AND, OR) were used to refine the search, ensuring a comprehensive analysis of the existing literature on Alzheimer's disease.

AD is significantly influenced by genetic predispositions, such as the apolipoprotein E (APOE) &#x3b5;4 allele, along with modifiable environmental factors like diet, physical activity, and cognitive engagement. Diagnostic approaches have evolved with advances in neuroimaging techniques (MRI, PET), and biomarker analysis, allowing for earlier detection and intervention. The National Institute on Aging and the Alzheimer's Association have updated diagnostic criteria to include biomarker data, enhancing early diagnosis.

The management of AD includes pharmacological treatments, such as cholinesterase inhibitors and NMDA receptor antagonists, which provide symptomatic relief but do not slow disease progression. Emerging therapies, including amyloid-beta and tau-targeting treatments, gene therapy, and immunotherapy, offer potential for disease modification. The critical role of caregivers is underscored, as they face considerable emotional, physical, and financial burdens. Support programs, communication strategies, and educational interventions are essential for improving caregiving outcomes. While significant advancements have been made in understanding and managing AD, ongoing research is necessary to identify new therapeutic targets and enhance diagnostic and treatment strategies. A holistic approach, integrating clinical, genetic, and environmental factors, is essential for addressing the multifaceted challenges of Alzheimer's disease and improving outcomes for both patients and caregivers.

Alzheimer's disease: a comprehensive review of epidemiology, risk factors, symptoms diagnosis, management, caregiving, advanced treatments and associated challenges.

Frontiers in Medicine

Diabetic kidney disease (DKD) is a prevalent and complex disease among patients with diabetes in Korea, requiring comprehensive treatment strategies. Traditional management strategies targeting blood pressure, blood sugar, lipid, and lifestyles are foundational approaches of DKD treatment, each of them still holding importance in current paradigms. The four pillars, renin-angiotensin system(RAS) inhibitors, sodium-glucose cotransporter-2 (SGLT2) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and non-steroidal mineralocorticoid receptor antagonists (nsMRA) can enhance DKD treatment. Expanding beyond these pillars with future-oriented pillars including precision medicine, digital health, gut health, anti-inflammatory/fibrotic agents, psychosocial/behavioral health, and regenerative medicine can further advance DKD treatment strategies, offering a more cohesive framework which shifts a disease-centered approach to a patient-centered approach.

A New Era in Diabetic Kidney Disease Treatment: The Four Pillars and Strategies to Build Beyond.

Electrolyte & Blood Pressure : E & BP

Concise definitive review of the use of induction agents in critically ill patients undergoing tracheal intubation and their association with outcomes.

Original publications were retrieved through a PubMed search with search terms related to induction agents for tracheal intubation in critically ill patients.

We included randomized controlled trials and observational studies that reported patient outcomes.

Data from included studies, including choice of induction agents and clinically relevant outcomes, were extracted.

Etomidate and ketamine have been the most studied induction agents in critical care during last years. Recent studies on etomidate investigated the clinical impact of its recognized adrenal suppression in terms of morbidity and mortality. Etomidate may carry a non-negligible mortality risk without definitive hemodynamic benefits compared with ketamine. Available data then support the use of ketamine over etomidate, since the difference in the hemodynamic profile seems to be of minor clinical relevance. No multicenter randomized studies are available comparing propofol to other induction agents but evidence from a large observational study identified an association of propofol with post-intubation cardiovascular instability in critically ill patients. Despite the observational nature of these findings cannot exclude the role of confounders, the association of propofol with post-induction cardiovascular instability is pharmacologically plausible, justifying its avoidance in favor of drugs with a better safety profile in critical care such as ketamine.

Although no definitive conclusions can be drawn based on the available evidence, recent evidence pointed out the potential negative effect of etomidate on survival and the association of propofol with cardiovascular instability. Ketamine may be considered the drug with a safer profile, widespread availability and low cost but future research should provide definitive data on optimal drug selection, its dosage in the context of critical illness and concomitant interventions to minimize the risk of peri-intubation complications.

Neoadjuvant Chemotherapy and Immunotherapy for Estrogen Receptor-Positive Human Epidermal Growth Factor 2-Negative Breast Cancer.

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