In vitro display techniques are powerful tools to select polypeptide binders against various target molecules. Novel applications include maturation of protein affinity and stability, selection for enzymatic activity, and the display of cDNA and random polypeptide libraries. Taken together, these display techniques have great potential for biotechnological, medical and proteomic applications.

In vitro display technologies: novel developments and applications.

Current Opinion in Biotechnology

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

Hematological emergencies are critical medical conditions that require immediate attention due to their rapid progression and life-threatening nature. As various examples, hypercalcemia, often associated with cancers such as multiple myeloma, can lead to severe neurological and cardiac dysfunction. Hyperleukocytosis, common in acute myeloid leukemias, increases the risk of leukostasis and multiorgan failure. Sickle cell crisis, a common complication in sickle cell disease, results from vaso-occlusion, leading to acute pain and tissue ischemia. Tumor lysis syndrome, reported in cases of rapid destruction of cancer cells, causes electrolyte imbalances and acute kidney injury. Acute transfusion reactions, fundamental in hematological conditions, can range from mild allergic responses to severe hemolysis and shock, requiring prompt management. Disseminated intravascular coagulation, involving excessive coagulation and bleeding, is commonly triggered by hematological malignancies, common in the first phases of acute promyelocytic leukemia. Recently, in the era of bispecific antibodies and chimeric antigen receptor T cells, cytokine release syndrome is a manifestation that must be recognized and promptly treated. Understanding the pathophysiology, recognizing the clinical manifestations, and ensuring adequate diagnostic strategies and management approaches for each condition are central to early intervention in improving patient outcomes and reducing mortality.

Emergencies in Hematology: Why, When and How I Treat?

Journal of Clinical 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.

Induction Agents for Tracheal Intubation in Critically Ill Patients.

Critical Care Medicine

Point-of-care ultrasound (POCUS) is changing the practice of nearly all specialties and is increasingly being incorporated as a bedside tool by more gastroenterologists and hepatologists. POCUS is most often used to answer focused clinical questions, supplement the traditional physical examination, and guide performance of invasive bedside procedures. This review describes several common POCUS applications used in gastroenterology and hepatology, as well as some novel applications that warrant further investigation.

Point-of-care ultrasound in Gastroenterology and Hepatology.

Clinical Gastroenterology and Hepatology

Systemic lupus erythematosus (SLE) is an autoimmune disease that more commonly affects African American people, although it is seen in people of all racial backgrounds. This condition is characterized by a dysregulated immune response resulting in widespread inflammation. Clinical manifestations caused by this inflammation include arthritis, anemia, cutaneous rashes, pleuritis, and nephritis. Treatment for SLE aims to reduce disease activity and maintain a state of low inflammation. In this regard, numerous treatments are used, such as hydroxychloroquine, glucocorticoids, and non-glucocorticoid immunosuppressants such as methotrexate. Related to these drugs resulting in significant adverse effects and being ineffective in controlling SLE symptoms in some patients, new biologic agents have been created in hopes of better treating SLE. This includes belimumab and anifrolumab, monoclonal antibodies directed against the cytokine, and type 1 interferon receptor, respectively. These agents are indicated in patients with SLE whose symptoms are inadequately controlled by standard therapy alone. Clinical trials have shown that these agents effectively reduce SLE symptoms as judged using standardized metrics of disease activity. These biological agents have also been shown to have generally mild side effects when taken by patients with SLE, making them safe for use. In addition to the above medications, new treatments are being developed for SLE patients, such as cenerimod, litifilimab, chimeric antigen receptor&#xa0;T cells, and DS-7011a (anti-toll-like receptor 7&#xa0;monoclonal antibody). These new treatments have shown promise in clinical trials. However, more information regarding their safety and efficacy is needed before they are available for the treatment of SLE.

In vitro display technologies: novel developments and applications.

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In vitro display technologies: novel developments and applications.

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