Molecular profile of MSH6-associated colorectal carcinomas shows distinct features from other Lynch syndrome-associated colorectal carcinomas.

Gastroenterology

The influence of restrictive fluid resuscitation and the early administration of vasopressors on the clinical outcomes in patients with septic shock is not fully understood. The purpose of this study was to evaluate the effects of restrictive fluid management on mortality and organ dysfunction in patients with septic shock.

This study included consecutive patients with septic shock in need of fluid resuscitation. Based on the fluid management provided in the initial resuscitation phase, a comparison was made between a restrictive group and a standard fluid management group. The primary outcome was in-hospital death, while secondary outcomes included organ dysfunction and other adverse events.

A total of 238 patients were included in this study. Restrictive fluid management was administered to 59.2% of patients, while 40.8% received standard fluid management. Restrictive resuscitation was associated with a lower in-hospital mortality rate (24.8% vs. 52.6%), as well as a shorter median ICU stay (8.0 vs. 11.0 days). The restrictive strategy was associated with a significantly lower prevalence of new-onset acute kidney injury (25.5% vs. 51.5%) and a decrease in the incidence of renal replacement therapy (20.6% vs. 40.2%). The standard group had a higher risk of the need for mechanical ventilation and a significantly lower median number of days without a ventilator than the restrictive group. The median duration of vasopressor-free days in the restrictive group was significantly longer than that in the standard group (25.0 vs. 18.0). The administration rate of inotropes in the restrictive group was significantly lower than that in the standard group. A multivariate logistic regression model showed that restrictive fluid management (OR 0.312; 95% CI 0.098-0.994) and vasopressor-free days (OR 0.807; 95% CI 0.765-0.851) protect against in-hospital death, whereas APACHE II scores (OR 1.121; 95% CI 1.018-1.234) were independent risk factors for in-hospital death.

Restrictive fluid resuscitation and early vasopressor protocol in patients with septic shock are associated with better outcomes, indicating that this regimen is feasible and safe.

Restrictive fluid resuscitation in septic shock patients has lower mortality and organ dysfunction rates than standard therapy.

Shock

Ketoacidosis induced by sodium-glucose cotransporter 2 inhibitor (SGLT2i) treatment has been consistently observed in clinical practice in patients with type 2 diabetes despite minimal indication from the landmark cardiovascular outcome trials. It has been postulated that individuals without diabetes will not develop this complication due to an adequate insulin secretory capacity, which will protect against significant ketone formation. Cardiovascular outcome trials examining SGLT2i use in individuals with heart failure but not diabetes have not reported ketoacidosis.

We describe the first two case reports of severe nondiabetic ketoacidosis after initiation of an SGLT2i for the treatment of heart failure with reduced ejection fraction, and we describe the management strategies employed and implication for the pathophysiology of SGLT2i-associated ketoacidosis.

Each individual presented with ketoacidosis triggered by reduced oral nutrition intake. For both individuals, ketoacidosis resolved with intravenous glucose administration, encouragement of consumption of oral glucose-containing fluid, and minimal insulin administration.

These two cases demonstrate that SGLT2i-associated ketoacidosis is possible in individuals without diabetes.

Euglycemic Ketoacidosis in Two Patients Without Diabetes After Introduction of Sodium-Glucose Cotransporter 2 Inhibitor for Heart Failure With Reduced Ejection Fraction.

Diabetes Care

Urinary tract infections are the most common bacterial infections worldwide. Infections can range from mild, recurrent (rUTI) to complicated (cUTIs), and are predominantly caused by uropathogenic Escherichia coli (UPEC). Antibiotic therapy is important to tackle infection; however, with the continued emergence of antibiotic resistance there is an urgent need to monitor the use of effective antibiotics through better stewardship measures. Currently, clinical diagnosis of UTIs relies on empiric methods supported by laboratory testing including cellular analysis (of both human and bacterial cells), dipstick analysis and phenotypic culture. Therefore, development of novel, sensitive and specific diagnostics is an important means to rationalise antibiotic therapy in patients. This review discusses the current diagnostic landscape and highlights promising novel diagnostic technologies in development that could aid in treatment and management of antibiotic-resistant UTIs.

Urinary tract infections: a review of the current diagnostics landscape.

Journal of Medical Microbiology

Heart failure (HF) with preserved ejection fraction (HFpEF) is a clinical syndrome in which patients have signs and symptoms of HF due to high left ventricular (LV) filling pressure despite normal or near normal LV ejection fraction. It is more common than HF with reduced ejection fraction (HFrEF), and its diagnosis and treatment are more challenging than HFrEF. Although hypertension is the primary risk factor, coronary artery disease and other comorbidities, such as atrial fibrillation (AF), diabetes, chronic kidney disease (CKD), and obesity, also play an essential role in its formation. This review summarizes current knowledge about HFpEF, its pathophysiology, clinical presentation, diagnostic challenges, current treatments, and promising novel treatments. It is essential to continue to be updated on the latest treatments for HFpEF so that patients always receive the most therapeutic treatments. The use of GnRH agonists in the management of HFpEF, infusion of Apo a-I nanoparticle, low-level transcutaneous vagal stimulation (LLTS), and estrogen only in post-menopausal women are promising strategies to prevent diastolic dysfunction and HFpEF; however, there is still no proven curative treatment for HFpEF yet.

Heart Failure With Preserved Ejection Fraction: An Evolving Understanding.

Curēus

Chronic kidney disease (CKD) is a common occurrence in patients with diabetes mellitus (DM), occurring in approximately 40% of cases. DM is also an important risk factor for cardiovascular disease (CVD), but CKD is an important mediator of this risk. Multiple CVD outcomes trials have revealed a greater risk for CVD events in patients with diabetes with CKD versus those without. Thus, reducing the risk of CKD in diabetes should result in improved CVD outcomes. To date, of blood pressure (BP) control, glycemic control, and inhibition of the renin-angiotensin system (RASI), glycemic control appears to have the best evidence for preventing CKD development. In established CKD, especially with albuminuria, RASI slows the progression of CKD. More recently, sodium glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide receptor agonists (GLP1RA) have revolutionized the care of patients with diabetes with and without CKD. SGLT2i and GLP1RA have proven to reduce mortality, heart failure (HF) hospitalizations, and worsening CKD in patients with diabetes with and without existing CKD. The future of limiting CVD in diabetes and CKD is promising, and more evidence is forthcoming regarding combinations of evidence-based therapies to further minimize CVD events.

Molecular profile of MSH6-associated colorectal carcinomas shows distinct features from other Lynch syndrome-associated colorectal carcinomas.

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Molecular profile of MSH6-associated colorectal carcinomas shows distinct features from other Lynch syndrome-associated colorectal carcinomas.

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