Fibroblast-growth-factor receptors (FGFRs), members of the tyrosine-kinase receptor family, play a crucial role in signal transduction and development. Recently, unique mutations in three human FGFR-encoding genes (FGFR1-3) have been identified as the cause of a variety of skeletal disorders. Comparison of these specific mutations with the resulting phenotypes is now providing new insight into the role of these receptors in normal and abnormal bone development.

Fibroblast-growth-factor receptor mutations in human skeletal disorders.

Trends in Genetics : TIG

The number of people living with type 2 diabetes (T2D) and its complications worldwide is increasing at an alarming rate. Fortunately, our understanding of the benefits of glucose-lowering agents from the sodium-glucose co-transporter-2 (SGLT2) inhibitor and glucagon-like peptide-1 (GLP-1) receptor agonist classes on cardiovascular and kidney outcomes is advancing; this means we now have new options to mitigate the risks of these complications in patients with T2D. The SGLT2 inhibitors have consistently demonstrated benefits on atherosclerotic cardiovascular disease (ASCVD), chronic kidney disease (CKD) and heart failure (HF) events in dedicated outcome trials. Large guidelines groups now recommend SGLT2 inhibitors as a standard of care in patients with T2D and comorbid ASCVD, CKD and/ or HF. Evolving evidence additionally indicates kidney and HF benefits of SGLT2 inhibitors in populations without diabetes. These agents likely provide heart and kidney benefits through multiple mechanisms, as their impact on heart and kidney outcomes cannot be fully explained by their direct metabolic effects. On-going work to elucidate the beneficial mechanisms at play with SGLT2 inhibitors will help further optimize these life-saving therapies in patients with and without T2D.

Clinical Evidence and Proposed Mechanisms for Cardiovascular and Kidney Benefits from Sodium-Glucose Co-transporter-2 Inhibitors.

TouchREVIEWS in endocrinology.

Management of Latent Tuberculosis Infection.

JAMA

There is no all-encompassing or universally accepted definition of the difficult airway, and it has traditionally been approached as a problem chiefly rooted in anesthesiology. However, with airway obstruction reported as the second leading cause of mortality on the battlefield and first-pass success (FPS) rates for out-of-hospital endotracheal intubation (ETI) as low as 46.4%, the need to better understand the difficult airway in the context of the prehospital setting is clear. In this review, we seek to redefine the concept of the "difficult airway" so that future research can target solutions better tailored for prehospital, and more specifically, combat casualty care. Contrasting the most common definitions, which narrow the scope of practice to physicians and a handful of interventions, we propose that the difficult airway is simply one that cannot be quickly obtained. This implies that it is a situation arrived at through a multitude of factors, namely the Patient, Operator, Setting, and Technology (POST), but also more importantly, the interplay between these elements. Using this amended definition and approach to the difficult to manage airway, we outline a target-specific approach to new research questions rooted in this system-based approach to better address the difficult airway in the prehospital and combat casualty care settings.

The Difficult Airway Redefined.

Prehospital and Disaster Medicine

Antiplatelet drugs, as the cornerstone of the treatment of coronary heart disease, control the progression of the disease, but bring a higher risk of gastrointestinal bleeding. Relevant guidelines recommend the use of proton pump inhibitors (PPIs) to minimize the risk of gastrointestinal bleeding in patients receiving dual antiplatelet therapy. But for people at low risk of gastrointestinal bleeding, the harms associated with routine use of PPIs may far outweigh the benefits. PPIs increase the risk of lower gastrointestinal bleeding, inhibit the effect of antiplatelet drugs, impair vascular endothelial function, meanwhile induce hypomagnesemia, iron deficiency, vitamins D and K deficiency, etc. Eventually, PPIs may lead to an increase in cardiovascular events. However, the situation is that PPIs are often overused. This review elucidates the mechanisms by which PPIs increase cardiovascular events, thereby reminding clinicians to rationally prescribe PPIs.

Inappropriate Use of Proton Pump Inhibitors Increases Cardiovascular Events in Patients with Coronary Heart Disease.

International Journal of General Medicine

Misdiagnosis in the Emergency Department: Time for a System Solution.

Intravenous fluids and vasopressor agents are commonly used in early resuscitation of patients with sepsis, but comparative data for prioritizing their delivery are limited.

In an unblinded superiority trial conducted at 60 U.S. centers, we randomly assigned patients to either a restrictive fluid strategy (prioritizing vasopressors and lower intravenous fluid volumes) or a liberal fluid strategy (prioritizing higher volumes of intravenous fluids before vasopressor use) for a 24-hour period. Randomization occurred within 4 hours after a patient met the criteria for sepsis-induced hypotension refractory to initial treatment with 1 to 3 liters of intravenous fluid. We hypothesized that all-cause mortality before discharge home by day 90 (primary outcome) would be lower with a restrictive fluid strategy than with a liberal fluid strategy. Safety was also assessed.

A total of 1563 patients were enrolled, with 782 assigned to the restrictive fluid group and 781 to the liberal fluid group. Resuscitation therapies that were administered during the 24-hour protocol period differed between the two groups; less intravenous fluid was administered in the restrictive fluid group than in the liberal fluid group (difference of medians, -2134 ml; 95% confidence interval [CI], -2318 to -1949), whereas the restrictive fluid group had earlier, more prevalent, and longer duration of vasopressor use. Death from any cause before discharge home by day 90 occurred in 109 patients (14.0%) in the restrictive fluid group and in 116 patients (14.9%) in the liberal fluid group (estimated difference, -0.9 percentage points; 95% CI, -4.4 to 2.6; P&#x2009;=&#x2009;0.61); 5 patients in the restrictive fluid group and 4 patients in the liberal fluid group had their data censored (lost to follow-up). The number of reported serious adverse events was similar in the two groups.

Among patients with sepsis-induced hypotension, the restrictive fluid strategy that was used in this trial did not result in significantly lower (or higher) mortality before discharge home by day 90 than the liberal fluid strategy. (Funded by the National Heart, Lung, and Blood Institute; CLOVERS ClinicalTrials.gov number, NCT03434028.).

Fibroblast-growth-factor receptor mutations in human skeletal disorders.

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Fibroblast-growth-factor receptor mutations in human skeletal disorders.

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