Discovery of CHF-6523, an Inhaled Selective PI3Kδ Inhibitor for the Treatment of Chronic Obstructive Pulmonary Disease.

The design of inhaled selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitors for the treatment of inflammatory lung diseases was pursued. Knowledge-based design of a novel isocoumarin scaffold that was able to adopt a topology ensured the desired PI3Kδ selectivity. Achievement of low nanomolar cellular potencies through hinge binder group optimization, reduction of intrinsic permeability through head group optimization to extend lung retention, and screening of crystalline forms suitable for administration as dry powders culminated in the identification of compound .

The clinical impact of pectoral nerve block in an 'enhanced recovery after surgery' program in breast surgery.

Pectoral nerve block (PECS) is increasingly performed in breast surgery. The study evaluated the clinical impact of these blocks in the postoperative course. In this case-control study, patients undergoing breast surgery with 'enhanced recovery after surgery' pathways were divided into group 1 (57 patients) in whom PECS was performed before general anesthesia, and group 2 (57 patients) in whom only general anesthesia was effected.

The Role of the Recovery Room in Improving Adherence During an Enhanced Recovery After Surgery (ERAS) Implementation Program for Colorectal Surgery: A Single-Center Retrospective Analysis.

Purpose: The purpose of thisstudy was to evaluate the clinical impact of the Recovery Room (RR) in an Enhanced Recovery After Surgery (ERAS) pathway in colorectal surgery.

Design: Single-center retrospective study.

Methods: From November 2019 until September 2021, a total of 149 consecutive patients that underwent to colon-rectal surgery were enrolled.

Combined pericapsular nerve group and lateral femoral cutaneous nerve blocks for hip fracture in a polytraumatized patient-A case report.

Locoregional anesthetic techniques in hip fracture are significant in order to control pain, reduce postoperative opioid use, and perioperative adverse events. Pericapsular nerve group (PENG) block has been described and proved as an effective analgesic method for hip surgery as an alternative to other regional nerve blocks. The association of PENG and lateral femoral cutaneous nerve (LCFN) block can be performed to achieve skin and subcutaneous tissues analgesia or anesthesia.

"In Less than No Time": Feasibility of Rotational Thromboelastometry to Detect Anticoagulant Drugs Activity and to Guide Reversal Therapy.

Anticoagulant drugs (i.e., unfractionated heparin, low-molecular-weight heparins, vitamin K antagonists, and direct oral anticoagulants) are widely employed in preventing and treating venous thromboembolism (VTE), in preventing arterial thromboembolism in nonvalvular atrial fibrillation (NVAF), and in treating acute coronary diseases early.

Questions about COVID-19 associated coagulopathy: possible answers from the viscoelastic tests.

Abnormal coagulation parameters are often observed in patients with coronavirus disease 2019 (COVID-19) and the severity of derangement has been associated with a poor prognosis. The COVID-19 associated coagulopathy (CAC) displays unique features that include a high risk of developing thromboembolic complications. Viscoelastic tests (VETs), such as thromboelastometry (ROTEM), thromboelastography (TEG) and Quantra Hemostasis Analyzer (Quantra), provide "dynamic" data on clot formation and dissolution; they are used in different critical care settings, both in hemorrhagic and in thrombotic conditions.

Antiphospholipid antibodies in critically ill COVID-19 patients with thromboembolism: cause of disease or epiphenomenon?

Coronavirus 2019 disease (COVID-19) is associated with coagulation dysfunction that predisposes patients to an increased risk for both arterial (ATE) and venous thromboembolism (VTE) and consequent poor prognosis; in particular, the incidence of ATE and VTE in critically ill COVID-19 patients can reach 5% and 31%, respectively. The mechanism of thrombosis in COVID-19 patients is complex and still not completely clear. Recent literature suggests a link between the presence of antiphospholipid antibodies (aPLs) and thromboembolism in COVID-19 patients.

Derangement of the coagulation process using subclinical markers and viscoelastic measurements in critically ill patients with coronavirus disease 2019 pneumonia and non-coronavirus disease 2019 pneumonia.

Systemic coagulation abnormalities including clotting activation and inhibition of anticoagulant factors have been observed in patients with pneumonia. In severe coronavirus disease 2019 (COVID-19) the alteration of coagulation parameters was associated with poor prognosis. We evaluated the difference in coagulopathy between critically ill patients with COVID-19 pneumonia (COVID group) and non-COVID-19 pneumonia (non-COVID group), using traditional coagulation markers and rotational thromboelastometry (ROTEM).

Venous thromboembolism and bleeding in critically ill COVID-19 patients treated with higher than standard low molecular weight heparin doses and aspirin: A call to action.

Background: Critically ill COVID-19 patients have a clear pattern of inflammation and hypercoagulable state. The main aim of the study was to evaluate the outcome of severe COVID-19 patients basing on prothrombotic risk factors (i.e.

Risk factors for non-invasive/invasive ventilatory support in patients with COVID-19 pneumonia: A retrospective study within a multidisciplinary approach.

Objectives: To investigate risk factors for non-invasive/invasive ventilatory support (NI/I-VS) in patients with coronavirus disease 2019 (COVID-19).

Methods: All consecutive patients admitted to the Infectious Diseases Unit and Intensive Care Unit (ICU) of Santa Maria Annunziata Hospital (Florence, Italy), from February 25 to April 25, 2020, with a confirmed COVID-19 diagnosis were enrolled in this retrospective cohort study. NI/I-VS was defined as the need for continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BPAP) (non-invasive ventilation) or mechanical ventilation, not including low-flow systems of oxygen therapy such as the Venturi mask or nasal cannula.

Very early postoperative troponin increase and clinical outcome in patients admitted to the recovery room after noncardiac surgery with suspected cardiac events.

We assessed the prognostic meaning of very early (<6 h) troponin increase after noncardiac surgery in a population of patients admitted to the recovery room, for whom troponin measurements were taken because of a suspected cardiac event. Among a total of 296 patients, abnormal troponin was found in 24 (8.1%).

Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia.

Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. We conducted a retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia and we evaluated coagulation function using rotational thromboelastometry (ROTEM) on day of admission (T0) and 5 (T5) and 10 (T10) days after admission to ICU.