Background
Coronavirus disease 2019 (COVID‐19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and shows a broad clinical presentation ranging from ...asymptomatic infection to fatal disease. A very prominent feature associated with severe COVID‐19 is T cell lymphopenia. However, homeostatic and functional properties of T cells are ill‐defined in COVID‐19.
Methods
We prospectively enrolled individuals with mild and severe COVID‐19 into our multicenter cohort and performed a cross‐sectional analysis of phenotypic and functional characteristics of T cells using 40‐parameter mass cytometry, flow cytometry, targeted proteomics, and functional assays.
Results
Compared with mild disease, we observed strong perturbations of peripheral T cell homeostasis and function in severe COVID‐19. Individuals with severe COVID‐19 showed T cell lymphopenia and redistribution of T cell populations, including loss of naïve T cells, skewing toward CD4+T follicular helper cells and cytotoxic CD4+ T cells, and expansion of activated and exhausted T cells. Extensive T cell apoptosis was particularly evident with severe disease and T cell lymphopenia, which in turn was accompanied by impaired T cell responses to several common viral antigens. Patients with severe disease showed elevated interleukin‐7 and increased T cell proliferation. Furthermore, patients sampled at late time points after symptom onset had higher T cell counts and improved antiviral T cell responses.
Conclusion
Our study suggests that severe COVID‐19 is characterized by extensive T cell dysfunction and T cell apoptosis, which is associated with signs of homeostatic T cell proliferation and T cell recovery.
In severe COVID‐19 T cell populations show perturbations, including loss of naïve T cells, CD4+ T cell skewing toward T follicular helper and cytotoxic phenotypes and expansion of activated and exhausted T cells. Apoptosis and migration contribute to the lymphopenia of severe disease, which is accompanied by Interleukin‐7 elevation. Functional responses to viral antigens are reduced in severe COVID‐19.
Abbreviations: COVID‐19, coronavirus disease 2019; CyTOF, cytometry by time‐of‐flight; TFH, T follicular helper cell
Heart failure (HF) is a major cause of mortality, hospitalizations, and reduced quality of life and a major burden for the healthcare system. The number of patients that progress to an advanced stage ...of HF is growing. Only a limited proportion of these patients can undergo heart transplantation or mechanical circulatory support. The purpose of this review is to summarize medical management of patients with advanced HF. First, evidence‐based oral treatment must be implemented although it is often not tolerated. New therapeutic options may soon become possible for these patients. The second goal is to lessen the symptomatic burden through both decongestion and haemodynamic improvement. Some new treatments acting on cardiac function may fulfil both these needs. Inotropic agents acting through an increase in intracellular calcium have often increased risk of death. However, in the recent Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial, omecamtiv mecarbil was safe and effective in the reduction of the primary outcome of cardiovascular death or HF event compared with placebo (hazard ratio, 0.92; 95% confidence interval, 0.86–0.99; P = 0.03) and its effects were larger in those patients with more severe left ventricular dysfunction. Patients with severe HF who received omecamtiv mecarbil experienced a significant treatment benefit, whereas patients without severe HF did not (P = 0.005 for interaction). Lastly, clinicians should take care of the end of life with an appropriate multidisciplinary approach. Medical treatment of advanced HF therefore remains a major challenge and a wide open area for further research.
The B cell response to different pathogens uses tailored effector mechanisms and results in functionally specialized memory B (B
) cell subsets, including CD21
resting, CD21
CD27
activated and CD21
...CD27
B
cells. The interrelatedness between these B
cell subsets remains unknown. Here we showed that single severe acute respiratory syndrome coronavirus 2-specific B
cell clones showed plasticity upon antigen rechallenge in previously exposed individuals. CD21
B
cells were the predominant subsets during acute infection and early after severe acute respiratory syndrome coronavirus 2-specific immunization. At months 6 and 12 post-infection, CD21
resting B
cells were the major B
cell subset in the circulation and were also detected in peripheral lymphoid organs, where they carried tissue residency markers. Tracking of individual B cell clones by B cell receptor sequencing revealed that previously fated B
cell clones could redifferentiate upon antigen rechallenge into other B
cell subsets, including CD21
CD27
B
cells, demonstrating that single B
cell clones can adopt functionally different trajectories.
Heart failure with preserved ejection fraction (HFpEF) has a high prevalence, affecting more than 50% of patients with heart failure. HFpEF is associated with multiple comorbidities, and obesity is ...one of the most common. A distinct phenotype has been proposed for obese patients with HFpEF. Recent data show the beneficial role of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) for weight loss in diabetic and non‐diabetic patients with obesity or overweight when given as adjunctive therapy to diet and exercise. The mechanisms of action are related to paracrine and endocrine signalling pathways within the gastrointestinal tract, pancreas, and central nervous system that delay gastric emptying, decrease appetite, augment pancreatic beta‐cell insulin secretion, and suppress pancreatic glucagon release. These drugs are therefore potentially indicated for treatment of patients with HFpEF and obesity or overweight. Efficacy and safety need to be shown by clinical trials with a first one, Semaglutide Treatment Effect in People with obesity and heart failure with preserved ejection fraction (STEP HFpEF), recently concluded. The aim of the present review is to provide the pathophysiological and pharmacological rationale for GLP‐1 RA administration to obese patients with HFpEF.
Prevalence of heart failure is increasing worldwide mainly due to the ageing of the population and the improvement in diagnosis and treatment. In recent years, huge progress has been made in the ...management of heart failure patients. A new definition of chronic heart failure based on left ventricular ejection fraction and its possible trajectories has been reported. New drug classes have been introduced for the treatment of chronic heart failure. In particular, the prognostic benefit of sodium glucose co-transporter 2 inhibitors was demonstrated across all the heart failure phenotypes. Therapies for patients with advanced heart failure (long-term mechanical circulatory supports and heart transplantation) are now indicated also in the case of mild-to-moderate symptoms but with high risk of progression. In patients with acute heart failure, monitoring of urinary sodium and the use of acetazolamide may lead to better decongestion. Importantly, pre- and postdischarge assessment should lead to optimal treatment. Devices and telemonitoring can also be of help. Cardiovascular and noncardiovascular comorbidities are major determinants of the clinical course and need proper management. This review will summarize these important advances.
During the first years of the HIV pandemic, the virus diffusion was responsible for discriminatory behavior from medical and dental care workers towards HIV-infected patients, as described by our ...research group in 2009. The aim of the current study was to provide an update on the previous data, investigating the presence of discriminatory behaviors, evaluating the level of dentists’ knowledge about the virus and proposing strategies to be implemented to avoid professional exposure and cross-infections. This study was a cross-sectional, online, national survey on dentists, members of the main national dental associations (ANDI and AIO). The questionnaire was divided into four major sections, with the same structure as the questionnaire administered in 2009. The differences between groups were analyzed using the software program IBM SPSS Statistic, version 21.0. A total of 1054 dentists filled out the questionnaire completely. Among them 0.04% revealed a discriminatory attitude towards HIV-infected patients. The univariate analysis showed that discrimination towards HIV + patients was statistically associated with personal experiences and the level of fear associated with treating them (p = 0.001) and with the type of dental treatments performed (p = 0.01). This cross-sectional study revealed the persistence of dentists who still discriminate against HIV + patients, and the percentage of these dentists was only slightly lower than that in the previous survey (4.3% in the present survey vs. 4.5%). The survey also depicted other information worthy of consideration, such as a perceived ability to detect HIV + patients based on their appearance, complaints about not having received adequate training for treating HIV + individuals, and a lack of scientific knowledge about the virus. From the evidence reported by the present survey, it can be argued that universities, professional boards, and training institutions must increase their efforts in spreading correct knowledge about HIV among all dental care workers.
The aim of this study was to report the prevalence, clinical features and outcomes of patients with ST-elevation myocardial infarction (STEMI) hospitalized during the Corona-Virus Disease 2019 ...(COVID-19) outbreak compared with those admitted in a previous equivalent period.
Eighty-five patients admitted for STEMI at a high-volume Italian centre were included. Patients hospitalized during the COVID-19 outbreak (21 February-10 April 2020) (40%) were compared with those admitted in pre-COVID-19 period (3 January-20 February 2020) (60%). A 43% reduction in STEMI admissions was observed during the COVID-19 outbreak compared with the previous period. Time from symptom onset to first medical contact (FMC) and time from FMC to primary percutaneous coronary intervention (PPCI) were longer in patients admitted during the COVID-19 period compared with before 148 (79-781) versus 130 (30-185) min; P = 0.018, and 75 (59-148) versus 45 (30-70) min; P < 0.001. High-sensitive troponin T levels on admission were also higher. In-hospital mortality was 12% in the COVID-19 phase versus 6% in the pre-COVID-19 period. Incidence of the composite end-point, including free-wall rupture, severe left ventricular dysfunction, left ventricular aneurysm, severe mitral regurgitation and pericardial effusion, was higher during the COVID-19 than the pre-COVID-19 period (19.6 versus 41.2%; P = 0.030; odds ratio = 2.87; 95% confidence interval 1.09-7.58).
The COVID-19 pandemic had a significant impact on the STEMI care system reducing hospital admissions and prolonging revascularization time. This translated into a worse patient prognosis due to more STEMI complications.
Background
Clinical markers of cognitive decline in Parkinson's disease (PD) encompass several mental non-motor symptoms such as hallucinations, apathy, anxiety, and depression. Furthermore, freezing ...of gait (FOG) and specific gait alterations have been associated with cognitive dysfunction in PD. Finally, although low cerebrospinal fluid levels of amyloid-β42 have been found to predict cognitive decline in PD, hitherto PET imaging of amyloid-β (Aβ) failed to consistently demonstrate the association between Aβ plaques deposition and mild cognitive impairment in PD (PD-MCI).
Aim
Finding significant features associated with PD-MCI through a machine learning approach.
Patients and methods
Patients were assessed with an extensive clinical and neuropsychological examination. Clinical evaluation included the assessment of mental non-motor symptoms and FOG using the specific items of the MDS-UPDRS I and II. Based on the neuropsychological examination, patients were classified as subjects without and with MCI (noPD-MCI, PD-MCI). All patients were evaluated using a motion analysis system. A subgroup of PD patients also underwent amyloid PET imaging. PD-MCI and noPD-MCI subjects were compared with a univariate statistical analysis on demographic data, clinical features, gait analysis variables, and amyloid PET data. Then, machine learning analysis was performed two times: Model 1 was implemented with age, clinical variables (hallucinations/psychosis, depression, anxiety, apathy, sleep problems, FOG), and gait features, while Model 2, including only the subgroup performing PET, was implemented with PET variables combined with the top five features of the former model.
Results
Seventy-five PD patients were enrolled (33 PD-MCI and 42 noPD-MCI). PD-MCI vs. noPD-MCI resulted in older and showed worse gait patterns, mainly characterized by increased dynamic instability and reduced step length; when comparing amyloid PET data, the two groups did not differ. Regarding the machine learning analyses, evaluation metrics were satisfactory for Model 1 overcoming 80% for accuracy and specificity, whereas they were disappointing for Model 2.
Conclusions
This study demonstrates that machine learning implemented with specific clinical features and gait variables exhibits high accuracy in predicting PD-MCI, whereas amyloid PET imaging is not able to increase prediction. Additionally, our results prompt that a data mining approach on certain gait parameters might represent a reliable surrogate biomarker of PD-MCI.
Severe aortic stenosis (AS) is the most common valvular heart disease with a prevalence rate of more than 4% in 75-year-old people or older. Similarly, cardiac amyloidosis (CA), especially "wild-type ...transthyretin" (wTTR), has shown a prevalence rate ranging from 22% to 25% in people older than 80 years. The detection of the concomitant presence of CA and AS is challenging primarily because of the similar type of changes in the left ventricle caused by AS and CA, which share some morphological characteristics. The aim of this review is to identify the imaging triggers in order to recognize occult wtATTR-CA in patients with AS, clarifying the crucial step of the diagnostic process. Multimodality imaging methods such as echocardiography, cardiac magnetic resonance, cardiac computed tomography, and DPD scintigraphy will be analyzed as part of the available diagnostic workup to identify wtATTR-CA early in patients with AS.
This study sought to investigate the ischemic and bleeding outcomes of patients fulfilling high bleeding risk (HBR) criteria who were randomized to zotarolimus-eluting Endeavor Sprint stent (E-ZES) ...or bare-metal stent (BMS) implantation followed by an abbreviated dual antiplatelet therapy (DAPT) duration for stable or unstable coronary artery disease.
DES instead of BMS use remains controversial in HBR patients, in whom long-term DAPT poses safety concerns.
The ZEUS (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates) is a multinational, randomized single-blinded trial that randomized among others, in a stratified manner, 828 patients fulfilling pre-defined clinical or biochemical HBR criteria-including advanced age, indication to oral anticoagulants or other pro-hemorrhagic medications, history of bleeding and known anemia-to receive E-ZES or BMS followed by a protocol-mandated 30-day DAPT regimen. The primary endpoint of the study was the 12-month major adverse cardiovascular event rate, consisting of death, myocardial infarction, or target vessel revascularization.
Compared with patients without, those with 1 or more HBR criteria had worse outcomes, owing to higher ischemic and bleeding risks. Among HBR patients, major adverse cardiovascular events occurred in 22.6% of the E-ZES and 29% of the BMS patients (hazard ratio: 0.75; 95% confidence interval: 0.57 to 0.98; p = 0.033), driven by lower myocardial infarction (3.5% vs. 10.4%; p < 0.001) and target vessel revascularization (5.9% vs. 11.4%; p = 0.005) rates in the E-ZES arm. The composite of definite or probable stent thrombosis was significantly reduced in E-ZES recipients, whereas bleeding events did not differ between stent groups.
Among HBR patients with stable or unstable coronary artery disease, E-ZES implantation provides superior efficacy and safety as compared with conventional BMS. (Zotarolimus-Eluting Endeavor Sprint Stent in Uncertain DES Candidates ZEUS; NCT01385319).
PDF
