Cell state transitions are prevalent in biology, playing a fundamental role in development, homeostasis and repair. Dysregulation of cell state transitions can lead to or occur in a wide range of diseases. In this letter, I explore and highlight the role of post-transcriptional regulatory mechanisms in determining the dynamics of cell state transitions. I propose that regulation of protein levels after transcription provides an under-appreciated regulatory route to obtain fast and sharp transitions between distinct cell states. This article is part of a discussion meeting issue 'Causes and consequences of stochastic processes in development and disease'.

Control of cell state transitions by post-transcriptional regulation.

Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences

The prevalence of obesity in older adults (people aged &gt;60 years) is increasing in line with the demographic shift in global populations. Despite knowledge of obesity-related complications in younger adults (increased risk of type 2 diabetes, liver and cardiovascular disease and malignancy), these considerations may be outweighed, in older adults, by concerns regarding weight-loss induced reduction in skeletal muscle and bone mass, and the awareness of the 'obesity paradox'. Obesity in the elderly contributes to various obesity-related complications from cardiometabolic disease and cancer, to functional decline, worsening cognition, and quality of life, that will have already suffered an age-related decline. Lifestyle interventions remain the cornerstone of obesity management in older adults, with emphasis on resistance training for muscle strength and bone mineral density preservation. However, in older adults with obesity refractory to lifestyle strategies, pharmacotherapy, using anti-obesity medicines (AOMs), can be a useful adjunct. Recent evidence suggests that intentional weight loss in older adults with overweight and obesity is effective and safe, hence a diminishing reluctance to use AOMs in this more vulnerable population. Despite nine AOMs being currently approved for the treatment of obesity, limited clinical trial evidence in older adults predominantly focuses on incretin therapy with glucagon-like peptide-1 receptor agonists (liraglutide, semaglutide, and tirzepatide). AOMs enhance weight loss and reduce cardiometabolic events, while maintaining muscle mass. Future randomised controlled trials should specifically evaluate the effectiveness of novel AOMs for long-term weight management in older adults with obesity, carefully considering the impact on body composition and functional ability, as well as health economics.

Obesity pharmacotherapy in older adults: a narrative review of evidence.

International Journal of Obesity

During surgery, various haemodynamic variables are monitored and optimised to maintain organ perfusion pressure and oxygen delivery - and to eventually improve outcomes. Important haemodynamic variables that provide an understanding of most pathophysiologic haemodynamic conditions during surgery include heart rate, arterial pressure, central venous pressure, pulse pressure variation/stroke volume variation, stroke volume, and cardiac output. A basic physiologic and pathophysiologic understanding of these haemodynamic variables and the corresponding monitoring methods is essential. We therefore revisit the pathophysiologic rationale for intraoperative monitoring of haemodynamic variables, describe the history, current use, and future technological developments of monitoring methods, and finally briefly summarise the evidence that haemodynamic management can improve patient-centred outcomes.

Haemodynamic monitoring during noncardiac surgery: past, present, and future.

Journal of Clinical Monitoring and Computing

Some of the most common conditions affecting people are kidney diseases. Among them, we distinguish chronic kidney disease and acute kidney injury. Both entities pose serious health risks, so new drugs are still being sought to treat and prevent them. In recent years, such a role has begun to be assigned to sodium-glucose cotransporter-2 (SGLT2) inhibitors. They increase the amount of glucose excreted in the urine. For this reason, they are currently used as a first-line drug in type 2 diabetes mellitus. Due to their demonstrated cardioprotective effect, they are also used in heart failure treatment. As for the renal effects of SGLT2 inhibitors, they reduce intraglomerular pressure and decrease albuminuria. This results in a slower decline in glomelular filtration rate (GFR) in patients with kidney disease. In addition, these drugs have anti-inflammatory and antifibrotic effects. In the following article, we review the evidence for the effectiveness of this group of drugs in kidney disease and their nephroprotective effect. Further research is still needed, but meta-analyses indicate SGLT2 inhibitors' efficacy in kidney disease, especially the one caused by diabetes. Development of new drugs and clinical trials on specific patient subgroups will further refine their nephroprotective effects.

SGLT2 Inhibitors in Kidney Diseases-A Narrative Review.

International Journal of Molecular Sciences

Albumin is commonly employed across a wide range of clinical settings to improve hemodynamics, facilitate fluid removal, and manage complications of cirrhosis. The International Collaboration for Transfusion Medicine Guidelines developed guidelines for the use of albumin in patients requiring critical care, undergoing cardiovascular surgery, kidney replacement therapy, or experiencing complications of cirrhosis.

Co-chairs oversaw the guideline development process and the panel included researchers, clinicians, methodologists, and a patient representative. The evidence informing this guideline arises from a systematic review of randomized clinical trials and systematic reviews, in which multiple databases were searched (inception to November 23, 2022). The panel reviewed the data and formulated the guideline recommendations using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The guideline was revised after public consultation.

The panel made 14 recommendations on albumin use in adult critical care (3 recommendations), pediatric critical care (1 recommendation), neonatal critical care (2 recommendations), cardiovascular surgery (2 recommendations), kidney replacement therapy (1 recommendation), and complications of cirrhosis (5 recommendations). Of the 14 recommendations, 2 had moderate certainty of evidence, 5 had low certainty of evidence, and 7 had very low certainty of evidence. Two of the 14 recommendations suggested conditional use of albumin for patients with cirrhosis undergoing large volume paracentesis or with spontaneous bacterial peritonitis. Twelve of 14 recommendations did not suggest albumin use in a wide variety of clinical situations where albumin is commonly transfused.

There are currently few evidence-based indications that support the routine use of albumin in clinical practice to improve patient outcomes. This guideline provides clinicians with actionable recommendations on the use of albumin.

Use of Intravenous Albumin: A Guideline from the International Collaboration for Transfusion Medicine Guidelines.

Chest

Antibiotics have played a pivotal role in modern medicine, drastically reducing mortality rates associated with bacterial infections. Despite their significant contributions, the emergence of antibiotic resistance has become a formidable challenge, necessitating a re-evaluation of antibiotic use practices. The widespread belief in clinical practice that bactericidal antibiotics are inherently superior to bacteriostatic ones lacks consistent support from evidence in randomized controlled trials (RCTs). With the latest evidence, certain infections have demonstrated equal or even superior efficacy with bacteriostatic agents. Furthermore, within clinical practice, there is a tendency to indiscriminately order urine cultures for febrile patients, even in cases where alternative etiologies might be present. Consequently, upon obtaining a positive urine culture result, patients often receive antimicrobial prescriptions despite the absence of clinical indications warranting such treatment.&#xa0;Furthermore, it is a prevailing notion among physicians that extended durations of antibiotic therapy confer potential benefits and mitigate the emergence of antimicrobial resistance. Contrary to this belief, empirical evidence refutes such assertions. This article aims to address common myths and misconceptions within the field of infectious diseases.

''Myth Busting in Infectious Diseases'': A Comprehensive Review.

Curēus

The CHEST Antithrombotic Therapy for Venous Thromboembolism Disease evidencebased guidelines are now updated in a more frequent, focused manner. Guidance statements from the most recent full guideline and two subsequent updates have not been gathered into a single source. METHODS An international panel of experts with experience in prior Antithrombotic Therapy guideline development reviewed the 2012 CHEST Antithrombotic Therapy guideline and its two subsequent updates. All guideline statements, and their associated Patient, Intervention, Comparator, Outcome questions were assembled. A modified Delphi process was used to select statements considered relevant to current clinical care. The panel further endorsed minor phrasing changes to match the standard language for guidance statements using the modified GRADE format endorsed by the CHEST Guidelines Oversight Committee. The panel appended comments following statements as deemed relevant, including suggesting which statements be updated in future guidelines due to interval evidence. RESULTS We include 58 guidance statements from prior versions of the antithrombotic therapy guidelines, with updated phrasing as needed to adhere to contemporary nomenclature. Statements are classified as strong or weak recommendations based on high, moderate, and low-certainty evidence, using GRADE methodology. The panel suggests that 5 statements are no longer relevant to current practice. CONCLUSION As CHEST continues to update guidance statements relevant to antithrombotic therapy for VTE disease, this manuscript serves as a unified collection of currently relevant statements from the preceding three guidelines. Suggestions are made to update specific statements in future publications.

Control of cell state transitions by post-transcriptional regulation.

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