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Abstract Background Septic shock (SS) and cardiogenic shock (CS) are two types of circulatory shock with a different etiology. Several studies have described the molecular alterations in SS patients, whereas the molecular factors involved in CS have been poorly investigated. We aimed to assess in the whole blood of CS and SS patients, using septic patients without shock (SC) as controls, transcriptomic modifications that occur over 1 week after ICU admission and are common to the two types of shock. Methods We performed whole blood RNA sequencing in 21 SS, 11 CS, and 5 SC. In shock patients, blood samples were collected within 16 h from ICU admission (T1), 48 h after ICU admission (T2), and at day 7 or before discharge (T3). In controls, blood samples were available at T1 and T2. Gene expression changes over time have been studied in CS, SS, and SC separately with a paired analysis. Genes with p value

Background: No study investigated the association between stress exposure in different stages of life and metabolic dysfunction.Aim: We explore the association between stress exposure and several biomarkers related to glucose metabolism (insulin, c-peptide, GIP, GLP-1, glucagon) in a group of 72 healthy individuals.Method: We used the Childhood Experience of Care and Abuse-Questionnaire (CECA-Q) and a modified version of the Life Events Scale to define exposure to stress, according to four categories: no exposure to childhood trauma (CT) nor to stressful life events (SLEs) (46%), only to CT (25%), only to SLEs (21%), to both (8%).Results: We found that c-peptide (p = 0.006) and insulin (p = 0.002) levels differed among the four categories: 0.77 ng/ml (SD 0.27) and 0.21 ng/ml (SD 0.06) for none, 0.77 (SD 0.37) and 0.20 (SD 0.08) for only SLEs, 0.88 (SD 0.39) and 0.27 (SD 0.12) for only CT, 1.33 (SD 0.57) and 0.40 (SD 0.28) for both, respectively. The highest levels of biomarkers were found in subjects exposed to both CT and SLEs.Conclusion: Our preliminary results seem to suggest that CT might be specifically associated with a dysfunction of glucose metabolism, which might increase the risk of poorer health outcomes in adulthood. This association seems to be even stronger in individuals additionally exposed to SLEs in adulthood. In conclusion, if confirmed in other studies, subjects exposed to both CT and SLEs appear the most vulnerable individuals, for whom preventative interventions, such as healthy lifestyle education programs, might ameliorate the risk of developing metabolic abnormalities.

In late January 2020, the first cases of Covid-19 were diagnosed in Italy. A month later the epidemic broke out in Lombardy bringing along dire consequences. Up to January 23rd 2021, the region counted 522,000 cases, and 26.518 deaths on a population of nearly 10 million. For many weeks thereafter tens of emergency COVID-19 patients were admitted every day through the ED requiring further adjustments in the organization of the Hospital, always in close cooperation with the out-of-hospital Emergency network. Among these, important and time-sensitive changes took place in the role of Residents in Emergency Medicine. As residents who worked through the first and second wave of the Sars-CoV-2 pandemic in the Emergency Department, we would like to discuss the consequences of our massive involvement on the front line of the healthcare effort to fight it.

Background ECG abnormalities are associated with adverse outcomes in the general population, but their prognostic significance in severe mental illness (SMI) remains unexplored. We investigated associations between no, minor, and major ECG abnormalities and fatal cardiovascular disease (CVD) among patients with SMI compared with controls without mental illness. Methods and Results We cross‐linked data from Danish nationwide registries and included primary care patients with digital ECGs from 2001 to 2015. Patients had SMI if they were diagnosed with schizophrenia, bipolar disorder, or severe depression before ECG recording. Controls were required to be without any prior mental illness or psychotropic medication use. Fatal CVD was assessed using hazard ratios (HRs) with 95% CIs and standardized 10‐year absolute risks. Of 346 552 patients, 10 028 had SMI (3%; median age, 54 years; male, 45%), and 336 524 were controls (97%; median age, 56 years; male, 48%). We observed an interaction between SMI and ECG abnormalities on fatal CVD (P

Objective The proportion and characteristics of Italian patients affected by venous thromboembolism (VTE) treated with direct oral anticoagulants (DOACs) or vitamin K antagonists (VKAs), and complications occurring during follow-up.Design A prospective cohort of 2728 VTE patients included in the Survey on anticoagulaTed pAtients RegisTer (START2-Register) from January 2014 to June 2018 was investigated. Characteristics of patients, type of treatment and complications occurring during 2962 years of follow-up were analysed.Setting About 60 Italian anticoagulation and thrombosis centres participated in the observational START2-RegisterParticipants 2728 adult patients with VTE of a lower limb and/or pulmonary embolism (PE), with a follow-up after the initial phase treatment.Interventions Patients could receive DOACs or VKAs; both prescribed by the National and Regional Health Systems for patients with VTE.Outcomes measures Efficacy: rate of VTE recurrence (all thrombotic complications were also recorded). Safety: the rate of major and clinically relevant non-major bleeding events.Results Almost 80% of patients were treated with DOACs. The prevalence of symptomatic PE and impaired renal function was higher in patients receiving VKAs. Duration of anticoagulation was >180 days in approximately 70% of patients. Bleeding events were similar in both treatment groups. The overall eventuality of recurrence was significantly higher in DOAC cohorts versus VKA cohorts (HR 2.15 (1.14–4.06), p=0.018); the difference was almost completely due to recurrences occurring during extended treatment (2.73% DOAC vs 0.49% VKA, p

Coronavirus disease 2019 (Covid-19), caused by a novel enveloped RNA betacoronavirus, has recently been declared a public health emergency by the World Health Organization (WHO). The lack of knowledge at the beginning of the pandemics, associated with the inherent risk of infective spreading, makes initial recognition and management particularly complex, in terms of defining effective diagnostic and therapeutic protocols. In the Emergency setting, Lung Ultrasound (LUS) can play an important role in the management of patients with SARS-CoV2-related pneumonia, expanding from the initial diagnosis to the subsequent monitoring and follow-up. Among many other potential advantages (such has the absence of ionizing radiation, its inherent costeffectiveness, and bedside repeatability), LUS provides immediate diagnostic response and might prevent the risk of spreading the infection by moving the patient from the Emergency Room to the Radiology facilities. Aim of this short review is to define the potential role of lung ultrasound in Covid-19 patients, according to the evidence in the medical literature

Abstract Background Septic shock is the most severe complication of sepsis and this syndrome is associated with high mortality. Treatment of septic shock remains largely supportive of hemodynamics and tissue perfusion. Early changes in organ function assessed by the Sequential Organ Function Assessment (SOFA) score are highly predictive of the outcome. However, the individual patient’s response to supportive therapy is very heterogeneous, and the mechanisms underlying this variable response remain elusive. The aim of the study was to investigate the transcriptome of whole blood in septic shock patients with different responses to early supportive hemodynamic therapy assessed by changes in SOFA scores within the first 48 h from intensive care unit (ICU) admission. Methods We performed whole blood RNA sequencing in 31 patients: 17 classified as responders (R) and 14 as non-responders (NR). Gene expression was investigated at ICU admission (time point 1, or T1), comparing R with NR [padj

Integrating video clips in the discharge process may enhance patients' understanding and awareness of their condition. To determine the effect of video clip-integrated discharge discussion on patient comprehension of atrial fibrillation (AF) and deep vein thrombosis (DVT), and their main complications (stroke and pulmonary embolism), we designed a multicentre, pragmatic, parallel groups, randomised clinical trial, that was conducted at two Emergency Units in Italy. A convenience sample of 144 adult patients (or their caregivers) discharged home with either AF or DVT were randomised to receive standard verbal instructions (control) or video clip-integrated doctor-patient discharge discussion. Participants were guided by the discharging physician through the clip. Mean score for primary outcome (knowledge of the diagnosis and its potential complication) (range 0–18) was 5.87 (95% CI, 5.02–6.72] in the control group and 8.28 (95% CI, 7.27–9.31) in the intervention group (mean difference, −2.41; 95% CI, −3.73 to −1.09; p < 0.001). Among secondary outcomes, mean score for knowledge of the prescribed therapy (range 0–6) was 2.98 (95% CI, 2.57–3.39) in the control group and 3.20 (95% CI, 2.73–3.67) in the study group (mean difference, −0.22; 95% CI, −0.84 to 0.39). Mean score for satisfaction (range 0–12) was 7.34 (95% CI, 6.45–8.23) in the control arm and 7.97 (95% CI, 7.15–8.78) in the intervention arm (mean difference, −0.625; 95% CI −1.82 to 0.57). Initiation rate of newly prescribed anticoagulants was 80% (36/45) in the control group and 90.2% (46/51) in the intervention group. Among 109 patients reached at a median follow up of 21 (IQR 16–28) months, 5.55% (3/54) in the control arm and 1.82% (1/55) in the intervention arm had developed stroke or pulmonary embolism. In this trial, video clip-integrated doctor-patient discharge discussion, improved participants comprehension of AF and DVT and their main complications. Physicians should consider integrating these inexpensive tools during the discharge process of patients with AF or DVT. Trial Registration: ClinicalTrials.gov Identifier "NCT03734406". [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) describes the individual variation in cardiac cycle duration and is a measure of vagal control of heart rate. Here, the authors identify seventeen single-nucleotide polymorphisms associated with HRV, lending new insight into the vagal regulation of heart rhythm.

A expansão recente da produção imobiliária, não só residencial promovida pela conjugação de crescimento econômico, do emprego e da renda das camadas assalariadas, expansão do crédito, reformas institucionais e programas públicos de acesso à moradia, bem como pelas transformações mais estruturais na organização dos capitais imobiliários, (como por exemplo, com a abertura de capitais ligados a este ramo da produção na bolsa de valores) tem impactado as condições de oferta e o consumo de tais bens, seus preços, localizações e agentes de sua produção. A análise aqui proposta será conduzida pelo recorte temporal definido entre o final dos anos de 1990 e a primeira década dos anos 2000, com ênfase nas resultantes espaciais intraurbanas do funcionamento do mercado imobiliário local. Serão considerados os elementos próprios da produção do ambiente construído urbano (suas mudanças e permanências), buscando extrair elementos comuns e diferentes entre as duas cidades, utilizando-se de dados de ofertas imobiliárias, entrevistas com agentes imobiliários diversos.

In this contribution, new data concerning bryophytes, fungi and lichens and of the Italian flora are presented. It includes new records and confirmations for the bryophyte genera Dicranodontium, Fontinalis, Lophocoleaand Riccia, the fungal genus Diplolaeviopsis, the lichen genera Agonimia, Cladonia, Protoparmelia, Rhizocarpon, and Scytinium.

Allogeneic hematopoietic stem cell transplantation is the treatment of choice for autosomal recessive osteopetrosis caused by defects in the TCIRG1 gene. Despite recent progress in conditioning, a relevant number of patients are not eligible for allogeneic stem cell transplantation because of the severity of the disease and significant transplant-related morbidity. We exploited peripheral CD34+ cells, known to circulate at high frequency in the peripheral blood of TCIRG1-deficient patients, as a novel cell source for autologous transplantation of gene corrected cells. Detailed phenotypical analysis showed that circulating CD34+ cells have a cellular composition that resembles bone marrow, supporting their use in gene therapy protocols. Transcriptomic profile revealed enrichment in genes expressed by hematopoietic stem and progenitor cells (HSPCs). To overcome the limit of bone marrow harvest/ HSPC mobilization and serial blood drawings in TCIRG1 patients, we applied UM171-based ex-vivo expansion of HSPCs coupled with lentiviral gene transfer. Circulating CD34+ cells from TCIRG1-defective patients were transduced with a clinically-optimized lentiviral vector (LV) expressing TCIRG1 under the control of phosphoglycerate promoter and expanded ex vivo. Expanded cells maintained long-term engraftment capacity and multi-lineage repopulating potential when transplanted in vivo both in primary and secondary NSG recipients. Moreover, when CD34+ cells were differentiated in vitro, genetically corrected osteoclasts resorbed the bone efficiently. Overall, we provide evidence that expansion of circulating HSPCs coupled to gene therapy can overcome the limit of stem cell harvest in osteopetrotic patients, thus opening the way to future gene-based treatment of skeletal diseases caused by bone marrow fibrosis.

Background Healthcare disparities for psychiatric patients are common. Whether these inequalities apply to postresuscitation management in out‐of‐hospital cardiac arrest (OHCA) is unknown. We investigated differences in in‐hospital cardiovascular procedures following OHCA between patients with and without psychiatric disorders. Methods and Results Using the Danish nationwide registries, we identified patients admitted to the hospital following OHCA of presumed cardiac cause (2001‐2015). Psychiatric disorders were identified using hospital diagnoses or redeemed prescriptions for psychotropic drugs. We calculated age‐ and sex‐standardized incidence rates and incidence rate ratios (IRRs) of cardiovascular procedures during post‐OHCA admission in patients with and without psychiatric disorders. Differences in 30‐day and 1‐year survival were assessed by multivariable logistic regression in the overall population and among 2‐day survivors who received acute coronary angiography (CAG). We included 7288 hospitalized patients who had experienced an OHCA: 1661 (22.8%) had a psychiatric disorder. Compared with patients without psychiatric disorders, patients with psychiatric disorders had lower standardized incidence rates for acute CAG (≤1 day post‐OHCA) (IRR, 0.51; 95% CI, 0.45–0.57), subacute CAG (2–30 days post‐OHCA) (IRR, 0.40; 95% CI, 0.30–0.52), and implantable cardioverter‐defibrillator implantation (IRR, 0.67; 95% CI, 0.48–0.95). Conversely, we did not detect differences in coronary revascularization among patients undergoing CAG (IRR, 1.11; 95% CI, 0.94–1.30). Patients with psychiatric disorders had lower survival even among 2‐day survivors who received acute CAG: (odds ratio of 30‐day survival, 0.68; 95% CI, 0.52–0.91; and 1‐year survival, 0.66; 95% CI, 0.50–0.88). Conclusions Psychiatric patients had a lower probability of receiving post‐OHCA CAG and implantable cardioverter‐defibrillator implantation compared with nonpsychiatric patients but the same probability of coronary revascularization among patients undergoing CAG. However, their survival was lower irrespective of angiographic procedures.