IFNγ Production by Functionally Reprogrammed Tregs Promotes Antitumor Efficacy of OX40/CD137 Bispecific Agonist Therapy.

Unlabelled: Regulatory T cells (Treg) are highly enriched within many tumors and suppress immune responses to cancer. There is intense interest in reprogramming Tregs to contribute to antitumor immunity. OX40 and CD137 are expressed highly on Tregs, activated and memory T cells, and NK cells.

Reversal or Repletion Treatment Strategies and Outcomes of Patients With Major Bleeding Events Managed in the Emergency Department: Large Real-Life Investigation in the Northwestern Healthcare District of Tuscany.

Objective: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment.

Methods: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K).

Endpoint: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding.

Acquisition of suppressive function by conventional T cells limits antitumor immunity upon T depletion.

Regulatory T (T) cells contribute to immune homeostasis but suppress immune responses to cancer. Strategies to disrupt T cell-mediated cancer immunosuppression have been met with limited clinical success, but the underlying mechanisms for treatment failure are poorly understood. By modeling T cell-targeted immunotherapy in mice, we find that CD4 Foxp3 conventional T (T) cells acquire suppressive function upon depletion of Foxp3 T cells, limiting therapeutic efficacy.

IL-2 is inactivated by the acidic pH environment of tumors enabling engineering of a pH-selective mutein.

Cytokines interact with their receptors in the extracellular space to control immune responses. How the physicochemical properties of the extracellular space influence cytokine signaling is incompletely elucidated. Here, we show that the activity of interleukin-2 (IL-2), a cytokine critical to T cell immunity, is profoundly affected by pH, limiting IL-2 signaling within the acidic environment of tumors.

Clinical and Virological Response to Convalescent Plasma in a Chronic Lymphocytic Leukemia Patient with COVID-19 Pneumonia.

The burden of COVID-19 remains unchanged for immunocompromised patients who do not respond to vaccines. Unfortunately, Omicron sublineages are resistant to monoclonal antibodies authorized in Europe so far, and small chemical antivirals have contraindications and toxicities that have not been studied in these patients. We report here the successful treatment of COVID-19 pneumonia lasting for 4 months after the transfusion of COVID-19 convalescent plasma (CCP) in a patient with severe immunosuppression due to both chronic lymphocytic leukemia and venetoclax treatment.

CCR8 marks highly suppressive Treg cells within tumours but is dispensable for their accumulation and suppressive function.

CD4 regulatory T (Treg) cells, dependent upon the transcription factor Foxp3, contribute to tumour immunosuppression but are also required for immune homeostasis. There is interest in developing therapies that selectively target the immunosuppressive function of Treg cells within tumours without disrupting their systemic anti-inflammatory function. High levels of expression of chemokine (C-C motif) receptor 8 (CCR8) discriminate Treg cells within tumours from those found in systemic lymphoid tissues.

Bleeding Events in Patients 75 Years of Age and Older Under Long-term Anticoagulant Therapy: A Real-life Study.

Objective: To investigate the risk of bleeding events in older patients under oral anticoagulant with a 4-year survey of a catchment area with 197,722 inhabitants of whom 15,267 were on warfarin and 10,397 on direct oral anticoagulants (DOACs).

Methods: Patients presented to the Emergency Department with major bleeding were enrolled and stratified according to age ≥75 years and ongoing warfarin or DOACs. Primary endpoint was 1-month death.

Role of Hypertension and Other Clinical Variables in Prognostication of Patients Presenting to the Emergency Department With Major Bleeding Events.

Background: Clinical variables including hypertension could be linked with major bleeding events and death beyond vitamin K antagonist (warfarin) or direct oral anti-coagulants (DOACs) treatment strategy.

Methods: Subgroup analysis of major bleeding (primary endpoint) associated with clinical variables, site of bleeding, ongoing antithrombotics, reversal treatment or blood transfusion, outcomes (secondary endpoints) was performed in patients with bleeding events submitted to hard 5:1 propensity-score matching for hypertension.

Results: Enrolled patients were 2,792 (mean age, 65.

Short and long-term mortality of patients presenting with bleeding events to the Emergency Department.

Background: Death of patients presenting with bleeding events to the Emergency Department still represent a major problem. We sought to analyze clinical characteristics associated with worse outcomes including short- and long-term death, beyond antithombotic treatment strategy.

Methods: Patients presenting with any bleeding events during 2016-2017years were enrolled.

Point-of-Care Ultrasonography for Evaluation of Acute Dyspnea in the ED.

Background: Acute dyspnea is a common symptom in the ED. The standard approach to dyspnea often relies on radiologic and laboratory results, causing excessive delay before adequate therapy is started. Use of an integrated point-of-care ultrasonography (PoCUS) approach can shorten the time needed to formulate a diagnosis, while maintaining an acceptable safety profile.

SOFA score in septic patients: incremental prognostic value over age, comorbidities, and parameters of sepsis severity.

Several widely used scoring systems for septic patients have been validated in an ICU setting, and may not be appropriate for other settings like Emergency Departments (ED) or High-Dependency Units (HDU), where a relevant number of these patients are managed. The purpose of this study is to find reliable tools for prognostic assessment of septic patients managed in an ED-HDU. In 742 patients diagnosed with sepsis/severe sepsis/septic shock, not-intubated, admitted in ED between June 2008 and April 2016, SOFA, qSOFA, PIRO, MEWS, Charlson Comorbidity Index, MEDS, and APACHE II were calculated at ED admission (T0); SOFA and MEWS were also calculated after 24 h of ED-High-Dependency Unit stay (T1).

Can non-invasive ventilation modify central venous pressure? Comparison between invasive measurement and ultrasonographic evaluation.

Central venous pressure (CVP) is primarily measured to assess intravascular volume status and heart preload. In clinical practice, the measuring device most commonly used in emergency departments and intensive care units, is an electronic transducer that interconnects a central venous catheter (CVC) with a monitoring system. Non-invasive ventilation (NIV) consists in a breathing support that supplies a positive pressure in airways through a mask or a cask though not using an endotracheal prosthesis.

Utility of repeat head computed tomography after mild head trauma: influence on short- and long-term prognosis and health-related quality of life.

The aim of this study was to investigate the utility of repeat head CT in a large population of patients with non-isolated blunt mild head trauma (MTBI), especially in the presence of intracranial injury. This is a study of a cohort of 478 non-isolated MTBI patients admitted to the High Dependency Unit of the Emergency Department of the University-Hospital of Florence from July 2008 to December 2013. Results of initial and subsequent head CT scans, and indications for repeat head CT scan (routine vs.

High-frequency QRS analysis superior to conventional ST-segment analysis of women with chest pain.

Background: The novel analysis of high-frequency QRS components (HF/QRS) has been proposed in patients with chest pain (CP) referred for exercise tolerance test (ex-ECG). We sought to evaluate the prognostic role of exercise high-frequency QRS-analysis (ex-HF/QRS) in patients with recent-onset stable CP, in the emergency setting.

Methods: Patients with CP underwent ex-ECG.

Coronary atherosclerosis and adverse outcomes in patients with recent-onset atrial fibrillation and troponin rise.

Background: The relationship between troponin and atrial fibrillation (AF) without acute coronary syndrome is still unclear. We sought to investigate the presence of coronary atherosclerosis and adverse outcomes in patients with AF.

Methods: Consecutive patients with recent-onset AF and without severe comorbidities were enrolled between 2004 and 2013.

High-frequency QRS analysis compared to conventional ST-segment analysis in patients with chest pain and normal ECG referred for exercise tolerance test.

Background: The novel analysis of high-frequency QRS components (HFQRS-analysis) has been proposed in patients with chest pain (CP) and normal electrocardiography (ECG) referred for exercise tolerance test (ex-ECG). The aim of the study was to compare the diagnostic value of ex-ECG with ex-HFQRS-analysis.

Methods: Patients with CP and normal ECG, troponin, and echocardiography were considered.

Quality of life after mild to moderate trauma.

Introduction: To evaluate potential reduction in health-related quality of life (HRQOL) after a mild to moderate trauma.

Materials And Methods: Follow-up study of a cohort of 153 trauma patients admitted to the High Dependency Unit of the Emergency Department of the University-Hospital of Florence from July 2008 to February 2012. After 6 months from the event, a telephone interview using the Physical (PCS) and Mental (MCS) Health Composite Score (SF12) was conducted.

Comparison of exercise electrocardiogram and exercise echocardiography in intermediate-risk chest pain patients.

Background: The novel exercise computer-assisted high-frequency QRS analysis (HF/QRS) has demonstrated improved sensitivity and specificity over the conventional ST/electrocardiogram-segment analysis (ST/ECG) in the detection of myocardial ischemia. The aim of the present study was to compare the diagnostic value of the validated exercise echocardiography (ex-Echo) with the novel exercise ECG (ex-ECG) including HF/QRS and ST/ECG analysis.

Methods: A prospective cohort study was conducted in the emergency department of a tertiary care teaching Hospital.

Hypertension and atrial fibrillation: prognostic aspects of troponin elevations in clinical practice.

Background: Hypertension and atrial fibrillation (AFib) frequently coexist in clinical practice. However, it is unclear whether this association per se or in combination with coronary artery disease (CAD) is a predictor of adverse outcomes.

Aim: The aim of this study is to recognize and treat CAD in patients with hypertension and AFib.

Nuclear scan strategy and outcomes in chest pain patients value of stress testing with dipyridamole or adenosine.

Objective: To update the prognostic value of scan strategy with pharmacological stress agent in chest pain (CP) patients presenting with normal electrocardiography (ECG) and troponin.

Methods: Two consecutive nonrandomized series of patients with CP and negative first-line workup inclusive of serial ECG, serial troponin, and echocardiography underwent myocardial perfusion imaging single photon emission computed tomography (SPECT) in the emergency department. Of 170 patients enrolled, 52 patients underwent dipyridamole-SPECT and 118 adenosine-SPECT.

Long-term prognostic value of stress echocardiography in patients presenting to the ED with spontaneous chest pain.

Purpose: The aims of this study were to evaluate the long-term prognostic value of stress echocardiography (SE) in patients evaluated in emergency department (ED) and to determine SE parameters that best predicted outcome.

Methods: Between June 2008 and July 2012, 626 patients with an episode of spontaneous chest pain underwent SE (exercise stress echocardiography or dobutamine stress echocardiography [DSE]). Between December 2012 and January 2013, all patients were contacted to verify the occurrence of cardiac events.

Role of masked coronary heart disease in patients with recent-onset atrial fibrillation and troponin elevations.

Background: Patients with recent-onset atrial fibrillation (AF) and cardiac troponin I (cTnI) elevations show poor outcomes. Coronary heart disease might be a cause, consequence, or an innocent bystander.

Objective: The aim of this study was to recognize and treat coronary heart disease to avoid adverse events.