Hard endpoints

Driving pressure (∆P) is a core therapeutic component of mechanical ventilation (MV). Varying levels of ∆P have been employed during MV depending on the type of underlying pathology and severity of injury. However, ∆P levels have also been shown to closely impact hard endpoints such as mortality. Considering this, conducting an in-depth review of ∆P as a unique, outcome-impacting therapeutic modality is extremely important. There is a need to understand the subtleties involved in making sure ∆P levels are optimized to enhance outcomes and minimize harm...

OBJECTIVESLiver trauma is common and can be treated non-operatively, through radiological embolisation, or surgically. Non-operative management (NOM) is preferred when possible, but specific criteria remain unclear. This retrospective study at a level I trauma centre assessed the evolution and outcomes of liver injury management over more than 20 years.METHODSData from January 1996 to June 2020 were analysed for liver trauma cases. Variables were evaluated, including the type of injury, diagnostic modalities, liver injury grade, transfer from other hospitals, treatment type and length of hospital stay...

INTRODUCTION: Diabetic retinopathy (DR), diabetic kidney disease (DKD) and distal symmetric polyneuropathy (DSPN) share common pathophysiology and pose an additive risk of early mortality. RESEARCH DESIGN AND METHODS: In adults with type 1 diabetes, 49 metabolites previously associated with either DR or DKD were assessed in relation to presence of DSPN. Metabolites overlapping in significance with presence of all three complications were assessed in relation to microvascular burden severity (additive number of complications-ie, presence of DKD±DR±DSPN) using linear regression models...

The multi-cohort phase 2 trial NCT02203513 was designed to evaluate the clinical activity of the CHK1 inhibitor (CHK1i) prexasertib in patients with breast or ovarian cancer. Here we report the activity of CHK1i in platinum-resistant high-grade serous ovarian carcinoma (HGSOC) with measurable and biopsiable disease (cohort 5), or without biopsiable disease (cohort 6). The primary endpoint was objective response rate (ORR). Secondary outcomes were safety and progression-free survival (PFS). 49 heavily pretreated patients were enrolled (24 in cohort 5, 25 in cohort 6)...

BACKGROUND: Despite the improvements in hemodialysis (HD) technology, 20-30% of sessions are still complicated by hypotension or hypotension-related symptoms. Biofeedback systems have proven to reduce the occurrence of such events, but no conclusive findings can lead to wider adoption of these systems. We conducted this systematic review and meta-analysis of randomized clinical trials to establish whether the use of blood volume tracking systems compared to conventional hemodialysis (C-HD) reduces the occurrence of intradialytic hypotension...

BACKGROUND: Ewing sarcoma (EwS) is a rare and highly malignant bone tumor primarily affecting children, adolescents, and young adults. The pelvis, trunk, and lower extremities are the most common sites, while EwS of the sacrum as a primary site is very rare, and only few studies focusing on this location are published. Due to the anatomical condition, local treatment is challenging in sacral malignancies. We analyzed factors that might influence the outcome of patients suffering from sacral EwS...

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats ( n  = 25) for 1, 3 and 6 weeks...

Interval walking training (IWT) is a free-living, training intervention involving alternating fast and slow walking cycles. IWT is efficacious in improving physical fitness, muscle strength, and reducing factors associated with lifestyle-related diseases. In individuals with type 2 diabetes, IWT improves glycemic control directly through enhanced glucose effectiveness, challenging conventional views on mechanisms behind training-induced improvements in glycemic control. Whereas adherence to IWT in short-term studies is high, ensuring long-term adherence remains a challenge, particularly in populations with chronic diseases and/or overweight/obesity...

BACKGROUND: Urinary tract infections (UTIs) are commonly treated in the emergency department (ED), and unfortunately, resistance to first-line agents is increasing. OBJECTIVES: To characterize treatment of pyelonephritis in a nationally representative sample of ED patients and to identify patient- and treatment-specific factors associated with receiving initial inactive antibiotics. METHODS: We conducted a multicentre, observational cohort study utilizing the Emergency Medicine PHARMacotherapy Research NETwork (EMPHARM-NET), comprising 15 geographically diverse US EDs...

OBJECTIVE: In conjunction with appropriate wound care, negative pressure wound therapy with instillation and dwell time (NPWTi-d) may be used as an adjunct therapy for acute or hard-to-heal (chronic) wounds, especially when infected. However, there are very few data on the use of NPWTi-d in the treatment of fibrinous wounds that are difficult to debride mechanically. The main objective of this study was to describe changes in the fibrin area of such wounds, before and after treatment with NPWTi-d...

Fewer than half of patients treated with hemodialysis survive 5 years. Multiple therapeutics are used to address the complications of advanced chronic kidney disease but most have not been found to improve clinical outcomes. Clinical trials of treatment innovations for chronic kidney diseases and dialysis care have been suboptimal in number and quality. Recent trials are changing this trend. Practice and policy change when new evidence emerges remains frequently impeded by resource and organizational constraints and accordingly, clinical practice guidelines are updated years or decades after definitive evidence is produced...

BACKGROUND: The development of atopic dermatitis (AD) drugs is confronted by many disease phenotypes and trial design options, which are hard to explore experimentally. OBJECTIVE: Optimize AD trial design using simulations. METHODS: We constructed a quantitative systems pharmacology (QSP) model of AD and standard of care (SoC) treatments and generated a phenotypically diverse virtual population whose parameter distribution is a) derived from known relationships between AD biomarkers and disease severity and b) calibrated using disease severity evolution under SoC regimens...

BACKGROUND AND AIMS: Transient increases (overshoot) in respiratory gas analyses have been observed during exercise recovery, but their clinical significance is not clearly understood. An overshoot phenomenon of the respiratory exchange ratio (RER) is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET), but it has been found reduced in patients with heart failure with reduced ejection fraction (HFrEF). The aim of the study was to analyze the clinical significance of these RER recovery parameters and to understand if these may improve the risk stratification of patients with HFrEF...

Cerebral amyloid angiopathy (CAA) is a type of cerebrovascular disorder characterised by the accumulation of amyloid within the leptomeninges and small/medium-sized cerebral blood vessels. Typically, cerebral haemorrhages are one of the first clinical manifestations of CAA, posing a considerable challenge to the timely diagnosis of CAA as the bleedings only occur during the later disease stages. Fluid biomarkers may change prior to imaging biomarkers, and therefore, they could be the future of CAA diagnosis...

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) accounts for >50% of heart failure cases and is associated with significant morbidity and health system burden. To date, there have been limited treatment options proven to improve outcomes in these patients, with sodium glucose co-transporter 2 (SGLT2) inhibitors the first class of drug to demonstrate significant clinical benefits, including reductions in heart failure hospitalisation. Obesity is associated with all forms of heart failure and has been linked with worse clinical outcomes...

Objective. The benefit of percutaneous coronary intervention (PCI) in chronic complete coronary artery occlusion (CTO) remains controversial. PCI is currently indicated only for symptom and myocardial ischemia abolition, but large chronically occluded vessels with extensive afferent myocardial territories may benefit most from this procedure. The noninvasive evaluation of myocardial perfusion is critical before and after revascularization, and positron emission tomography (PET) can determine absolute myocardial perfusion...

Nanosized titanium dioxide (nTiO2 ) is widely used in products, warranting its discharge from various sources into surface water bodies. However, nTiO2 co-occurs in surface waters with other contaminants, such as metals. Studies with nTiO2 and metals have indicated that the presence of natural organic matter (NOM) can mitigate their toxicity to aquatic organisms. In addition, "aging" of nTiO2 can affect toxicity. However, it is a research challenge, particularly when addressing sublethal responses from dietary exposure over multiple generations...

BACKGROUND: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs thermal ablation on PV narrowing after AF ablation. METHODS: ADVENT was a multicenter, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation - force-sensing RF or cryoballoon (CB) - to treat drug-refractory paroxysmal AF...

Psoriasis is an immune-mediated inflammatory disease associated with an increased risk of cardiovascular disease (CVD). The risk of CVD increases with the severity of psoriasis, and exposure to systemic inflammation may partly explain the increased risk of CVD in these patients. This raises the question of whether anti-psoriatic treatment, in addition to treating the skin lesions, also lowers the risk of developing CVD. Different types of studies have examined the impact of systemic anti-psoriatic treatments on the risk of CVD in patients with psoriasis and epidemiological observational studies with, e...

In the last decades, several classifications and definitions have been proposed for advanced heart failure (ADVHF) patients, including clinical, functional, hemodynamic, imaging, and electrocardiographic features. Despite different inclusion criteria, ADVHF is characterized by some common items, such as drug intolerance, low arterial pressure, multiple organ dysfunction, chronic kidney disease, and diuretic use dependency. Additional features include fatigue, hypotension, hyponatremia, and unintentional weight loss associated with a specific laboratory profile reflecting systemic multiorgan dysfunction...