Search

Acute myeloid leukemia (AML) is a heterogeneous blood-related neoplasm that predominantly afflicts older adults with a poor prognosis due to their physical condition and the presence of medical accompanying comorbidities, adverse biological disease features, and suitability for induction intensive chemotherapy and allogenic stem cells transplantation. Recent research into the molecular and biological factors contributing to disease development and progression has led to significant advancements in treatment approaches for older patients with AML. This review article discusses the latest biological and therapeutic developments that are transforming the management of AML in older adults.

Abstract Aims Artificial intelligence (AI) has emerged as a potential useful tool to support clinical treatment of heart failure, including the setting of mechanical circulatory support (MCS). Modern Impella pumps are equipped with advanced technology (SmartAssist), enabling real‐time acquisition and display of data related to both pump performance and the patient's haemodynamic status. These data emerge as an ‘ideal’ source for data‐driven AI applications to predict the clinical course of an ongoing therapeutic protocol. Yet, no evidence of effective application of AI tools in the setting of Impella support is available. On this background, we aimed at identifying possible future applications of AI‐based tools in the setting of temporary MCS with an Impella device. Methods We explored the state of research and development at the intersection of AI and Impella support and derived future potential applications of AI in routine Impella clinical management. Results We identified different areas where the future implementation of AI tools may contribute to addressing important clinical challenges in the setting of Impella support, including (i) early identification of the best suited pathway of care according to patients' conditions at presentation and intention to treat, (ii) prediction of therapy outcomes according to different possible therapeutic actions, (iii) optimization of device implantation procedures and evaluation of proper pump position over the whole course of support and (iv) prevention and/or rationale management of haemocompatibility‐related adverse events. For each of those areas, we discuss the potential advantages, challenges and implications of harnessing AI‐driven insights in the setting of MCS with an Impella device. Conclusions Temporary MCS with an Impella device has great potential to benefit from the integration of AI‐based tools. Such tools may indeed translate into groundbreaking innovation supporting clinical decision‐making and therapy regulation, in particular in complex scenarios such as the multidevice MCS strategy.

This work explores the geometry of extremal Kerr-Newman black holes by analyzing their mass/energy relationships and the conditions ensuring black hole existence. Using differential geometry in E3, we examine the topology of the event horizon surface and identify two distinct families of extremal black holes, each defined by unique proportionalities between their core parameters: mass (m), charge (Q), angular momentum (L), and the irreducible mass (mir). In the first family, these parameters are proportionally related to the irreducible mass by irrational numbers, with a characteristic flat Gaussian curvature at the poles. In the second family, we uncover a more intriguing structure where m, Q, and L are connected to mir through coefficients involving the golden ratio −ϕ−. Within this family lies a unique black hole whose physical parameters converge on the golden ratio, including the irreducible mass and polar Gauss curvature. This black hole represents the highest symmetry achievable within the constraints of the Kerr-Newman metric. This remarkable symmetry invites further speculation about its implications, such as the potential determination of the dark energy density parameter ΩΛ for Kerr-Newman-de Sitter black holes. Additionally, we compute the maximum energy that can be extracted through reversible transformations. We have determined that the second, golden-ratio-linked family allows for a greater energy yield than the first.

Italy is divided into 773 Agricultural Regions (ARs) based on shared physical and agronomic characteristics. These regions offer a valuable tool for analyzing various geographical, socio-economic, and environmental aspects of agriculture, including the climate. However, the ARs have lacked geospatial data, limiting their analytical potential. This study introduces the “Italian ARs Dataset”, a georeferenced shapefile defining the boundaries of each AR. This dataset facilitates geographical assessments of Italy’s complex agricultural sector. It also unlocks the potential for integrating AR data with other datasets like the Farm Accounting Data Network (FADN) dataset, in Italy represented by the Rete di Informazione Contabile Agricola (RICA), which samples hundreds of thousands of farms annually. To demonstrate the dataset’s utility, a large sample of RICA data encompassing 179 irrigated crops from 2011 to 2021, covering all of Italy, was retrieved. Validation confirmed successful assignment of all ARs present in the RICA sample to the corresponding shapefile. Additionally, to encourage the use of the ARs Dataset with gridded data, different spatial-scale resolutions are tested to identify a suitable threshold. The minimal spatial scale identified is 0.11 degrees, a commonly adopted scale by several climate datasets within the EURO-CORDEX and COPERNICUS programs.

Background and Objectives: Percutaneous coronary intervention (PCI) is a proven therapy for acute myocardial infarction (AMI) cardiogenic shock (CS). Dual anti-platelet therapy (i.e., aspirin plus an oral P2Y12 inhibitor) is recommended in patients treated with PCI. However, CS patients present severe hemodynamic instability, deranged hemostatic balance, and the need for invasive mechanical circulatory support (MCS) alongside invasive procedures, resulting in an increased risk of both bleeding and thrombotic complications, leaving uncertainty about the best anti-thrombotic treatment. Recently, the parenteral short-acting P2Y12 inhibitor has been increasingly used in the acute cardiac care setting, mainly in light of its favourable pharmacokinetic profile and organ-independent metabolism. Materials and Methods: In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we performed a systematic review and single-arm meta-analysis of the safety and efficacy outcomes (i.e., rates of major bleeding, occurrence of stent/any thrombosis, and hospital survival) of all existing original studies reporting on the intravenous administration of cangrelor in AMI-CS patients. Results: Ten studies (678 patients with CS) published between 2017 and 2023 were included in the present review: nine were observational and one had a randomized design. Percutaneous revascularization was performed in >80% of patients across the studies. Moreover, 26% of patients were treated with temporary MCS, and in all studies, concomitant systemic anticoagulation was performed. Cangrelor was administered intravenously at the dosage of 4 mcg/kg/min in 57% of patients, 0.75 mcg/kg/min in 37% of patients, and Conclusions: Cangrelor administration in AMI-CS patients was feasible and safe with a low rate of thromboembolic complications. Haemorrhagic complications were more frequent than thrombotic events. Nevertheless, to date, the optimal dosage of cangrelor in this clinical context still remains not universally recognized.

AimsImpella 5.0 and 5.5 are promising low-invasive left ventricle (LV) temporary mechanical circulatory supports (tMCS) for cardiogenic shock due to LV mechanical unloading and are paired with powerful hemodynamic support. This study aimed to analyze data and destinies of patients supported with Impella 5.0/5.5 at a national referral center for cardiogenic shock and to assess the parameters associated with myocardial recovery and successful weaning.MethodsA single-center observational study was conducted on all patients treated with Impella 5.0 or 5.5 from March 2018 to July 2023.ResultsA total of 59 patients underwent Impella 5.0/5.5 implantation due to profound cardiogenic shock, with acute myocardial infarction being the most frequent cause of shock (42 patients, 71%). The median duration of Impella support was 13 days (maximum duration of 52 days). Axillary cannulation was feasible in almost all patients, and 36% were mobilized during support. A total of 44 patients (75%) survived to the next therapy/recovery: 21 patients experienced recovery and 15 and 8 were bridged to long-term LVAD and heart transplantation, respectively. The global survival rate was 66%. The predictors of native heart recovery at multivariate analysis were the number of days on tMCS before upgrade to Impella 5.0/5.5 [hazard ratio (HR) 0.68 (0.51–9) p = 0.0068] and improvement of LVEF within the first 7–10 days of support [HR 4.72 (1.34–16.7), p = 0.016].ConclusionsTranscatheter systems such as Impella 5.0/5.5 revolutionized the field of tMCS. Myocardial recovery is the primary clinical target. Its prognostication and promotion are key to ensure the most proficuous course for each patient from cardiogenic shock to long-term event-free survival.

Summary: Exercise training and cold exposure both improve systemic metabolism, but the mechanisms are not well established. Here, we tested the hypothesis that inguinal white adipose tissue (iWAT) adaptations are critical for these beneficial effects and determined the impact of exercise-trained and cold-exposed iWAT on systemic glucose metabolism and the iWAT proteome and secretome. Transplanting trained iWAT into sedentary mice improves glucose tolerance, while cold-exposed iWAT transplantation shows no such benefit. Compared to training, cold leads to more pronounced alterations in the iWAT proteome and secretome, downregulating >2,000 proteins but also boosting the thermogenic capacity of iWAT. In contrast, only training increases extracellular space and vesicle transport proteins, and only training upregulates proteins that correlate with favorable fasting glucose, suggesting fundamental changes in trained iWAT that mediate tissue-to-tissue communication. This study defines the unique exercise training- and cold exposure-induced iWAT proteomes, revealing distinct mechanisms for the beneficial effects of these interventions on metabolic health.

Freezing of gait is a frequent phenomenon and can be one of the most debilitating motor impairments in Parkinson’s disease, especially in the advanced stages. It is currently defined as a brief episodic absence or any marked reduction in the forward progression of the feet, despite the intention to walk. Greater severity of freezing of gait has been associated with more frequent falls, postural instability, and executive dysfunction. However, botulinum neurotoxin is one of the most widely administered therapies for motor and non-motor symptoms, including freezing of gait, in parkinsonism. To date, the literature has had conflicting results on the use of botulinum toxin in the treatment of freezing of gait in Parkinson’s disease patients. In light of this, we reviewed the findings of past studies that specifically investigated the effects of botulinum toxin on freezing of gait in Parkinson’s disease in order to better understand this issue.

Introduction: Growing evidence supports extracorporeal cardiopulmonary resuscitation (ECPR) for refractory out-of-hospital cardiac arrest (OHCA) patients, especially in experienced centres. We present characteristics, treatments, and outcomes of patients treated with ECPR in a high-volume cardiac arrest centre in the metropolitan area of Milan, Italy and determine prognostic factors. Methods: Refractory OHCA patients treated with ECPR between 2013 and 2022 at IRCCS San Raffaele Scientific Institute in Milan had survival and neurological outcome assessed at hospital discharge. Results: Out of 307 consecutive OHCA patients treated with ECPR (95% witnessed, 66% shockable, low-flow 70 [IQR 58–81] minutes), 17% survived and 9.4% had favourable neurological outcome. Survival and favourable neurological outcome increased to 51% (OR = 8.7; 95% CI, 4.3–18) and 28% (OR = 6.3; 95% CI, 2.8–14) when initial rhythm was shockable and low-flow (time between CPR initiation and ROSC or ECMO flow) ≤60 minutes and decreased to 9.5% and 6.3% when low-flow exceeded 60 minutes (72% of patients). At multivariable analysis, shockable rhythm (aOR for survival = 2.39; 95% CI, 1.04–5.48), shorter low-flow (aOR = 0.95; 95% CI, 0.94–0.97), intermittent ROSC (aOR = 2.5; 95% CI, 1.2–5.6), and signs of life (aOR = 3.7; 95% CI, 1.5–8.7) were associated with better outcomes. Survival reached 10% after treating 104 patients (p for trend

Cestrum parqui L’Herit. (Solanaceae family) is a species of forest shrub, self-incompatible and specialized in pollination, widespread in the subtropical area of the planet, and now widely distributed also in the Mediterranean area. The constituents of its leaves have antimicrobial, anticancer, insecticidal, antifeedant, molluscicidal, and herbicidal properties. The spread of this species represents a valuable source of compounds with high biological value. Various research groups are engaged in defining the chemical composition of the different parts of the plant and in defining its properties in view of important and promising commercial applications. To date, there are only a few incomplete reports on the potential applications of C. parqui extracts as selective natural pesticides and on their potential phytotoxic role. Scientific knowledge and the use of extraction techniques for these components are essential for commercial applications. This article summarizes the research and recent studies available on the botany, phytochemistry, functional properties, and commercial applications of C. parqui.

Artificial Intelligence (AI) applications and Machine Learning (ML) methods have gained much attention in recent years for their ability to automatically detect patterns in data without being explicitly taught rules. Specific features characterise the ECGs of patients with Brugada Syndrome (BrS); however, there is still ambiguity regarding the correct diagnosis of BrS and its differentiation from other pathologies.This work presents an application of Echo State Networks (ESN) in the Recurrent Neural Networks (RNN) class for diagnosing BrS from the ECG time series.12-lead ECGs were obtained from patients with a definite clinical diagnosis of spontaneous BrS Type 1 pattern (Group A), patients who underwent provocative pharmacological testing to induce BrS type 1 pattern, which resulted in positive (Group B) or negative (Group C), and control subjects (Group D). One extracted beat in the V2 lead was used as input, and the dataset was used to train and evaluate the ESN model using a double cross-validation approach. ESN performance was compared with that of 4 cardiologists trained in electrophysiology.The model performance was assessed in the dataset, with a correct global diagnosis observed in 91.5 % of cases compared to clinicians (88.0 %). High specificity (94.5 %), sensitivity (87.0 %) and AUC (94.7 %) for BrS recognition by ESN were observed in Groups A + B vs. C + D.Our results show that this ML model can discriminate Type 1 BrS ECGs with high accuracy comparable to expert clinicians. Future availability of larger datasets may improve the model performance and increase the potential of the ESN as a clinical support system tool for daily clinical practice.

Abstract Pathophysiological substrate(s) and progression of Parkinson’s disease (PD) with mild cognitive impairment (PD-MCI) are still matter of debate. Baseline cerebrospinal fluid (CSF) neurochemical profile and cognitive changes after 2 years were investigated in a retrospective series of PD-MCI (n = 48), cognitively normal PD (PD-CN, n = 40), prodromal Alzheimer’s disease (MCI-AD, n = 25) and cognitively healthy individuals with other neurological diseases (OND, n = 44). CSF biomarkers reflecting amyloidosis (Aβ42/40 ratio, sAPPα, sAPPβ), tauopathy (p-tau), neurodegeneration (t-tau, NfL, p-NfH), synaptic damage (α-syn, neurogranin) and glial activation (sTREM2, YKL-40) were measured. The great majority (88%) of PD-MCI patients was A-/T-/N-. Among all biomarkers considered, only NfL/p-NfH ratio was significantly higher in PD-MCI vs. PD-CN (p = 0.02). After 2 years, one-third of PD-MCI patients worsened; such worsening was associated with higher baseline levels of NfL, p-tau, and sTREM2. PD-MCI is a heterogeneous entity requiring further investigations on larger, longitudinal cohorts with neuropathological verification.

Background: Hematological patients are a highly vulnerable population with an increased risk of developing severe COVID-19 symptoms due to their immunocompromised status. COVID-19 has proven to cause serious mental health issues, such as stress, anxiety, and depression in the general population. However, data on the psycho-social impact of COVID-19 on hematological patients are lacking. Objectives: This study aims to examine the psychological well-being of hematological patients in Italy during the initial period of the COVID-19 pandemic. Furthermore, it seeks to explore the association between modifications in the management of hematological diseases and employment status of these patients during the COVID-19 pandemic and the resulting mental health outcomes. Design and Methods: A survey using the DASS-21 questionnaire was administered to 1105 hematological patients. Data analysis was conducted using the R software, and logistic regression analysis was performed to predict the association between hematological patient/general population and employment status with DASS scores. Results: The hematological patient population reported significantly higher levels of depression (OR 0.947, 95% CI 0.966–0.982, p

Health-related quality of life (HRQoL) is an important goal of therapy for patients with myelodysplastic syndromes (MDS); however, little is known about HRQoL of these patients at clinical presentation. We report HRQoL profile of newly diagnosed patients with MDS across both the the International Prognostic Scoring System (IPSS) and IPSS-Revised (IPSS-R) classifications, stratified by sex and age group categories, aiming to also establish European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core30 (EORTC QLQ-C30) reference values for these patients. Analysis was based on 927 patients with a median age of 73.3 years (interquartile range, 66.0–79.2), of whom 506 and 421 with lower- and higher-risk disease respectively, according to the IPSS classification. HRQoL was assessed with the EORTC QLQ-C30 and substantial differences by age groups and sex, between and within lower- and higher-risk disease categories were observed. For example, within higher-risk disease patients, the youngest group (ie, 30–59 years) tended to report clinically meaningful worse outcomes across various functional and symptom domains compared with older age groups. We also developed 2 regression models allowing for the prediction of EORTC QLQ-C30 reference scores for patients classified according to either the IPSS or the IPSS-R. Investigation of prevalence rates for clinically important problems and symptoms at diagnosis revealed a substantial burden of the disease with >50% of patients reporting clinically important problems with physical functioning and dyspnea in both lower- and higher-risk disease. Our findings may help to enhance the interpretation of HRQoL outcomes in future MDS studies and to better contextualize HRQoL data from routine practice settings.

Summary: Physical activity is important for type 2 diabetes treatment, yet the underlying mechanisms for these beneficial effects of exercise are not fully understood. Here, we investigated the effects of exercise training on biphasic β-cell insulin secretory function, a key factor regulating blood glucose. Adults with type 2 diabetes (7F/3M, age 49 ± 5 years, BMI 30 ± 3 kg/m2) completed a 10-week moderate-intensity exercise program and multiple components of glucose homeostasis were measured. Training improved glycemic control, insulin sensitivity, and processing of proinsulin-to-insulin. Training increased late phase β-cell function by 38% (p = 0.01), which was correlated with changes in VO2peak suggesting training response-dependent effects. Ras-Responsive Element Binding Protein 1 (RREB1) concentrations, a protein postulated to increase type 2 diabetes risk, were inversely correlated with increases in training-induced late-phase disposition index, consistent with an inhibitory role of RREB1 on insulin secretion. Moderate-intensity exercise training improves late-phase β-cell function and glycemic control in adults with type 2 diabetes.

IntroductionCataract surgery is one of the most common surgical procedures performed worldwide. Intraocular lens (IOL) implants are placed routinely in the capsular bag after successful cataract extraction. However, in the absence of adequate capsular support, IOL may be placed in the anterior chamber, fixated to the iris or fixated to the sclera. The purpose of this study is to report the clinical outcomes and safety profile of a trans-scleral sutured intraocular lens (IOL) technique using scleral flaps, vitrectomy, and Gore-Tex suture to place posterior chamber IOL.MethodsRetrospective, interventional case series of eyes undergoing scleral fixation of an IOL using Gore-Tex suture with concurrent vitrectomy. Ocular examination with the logarithm of the minimum angle of resolution visual acuity (logMAR BCVA), tonometry, and slit-lamp biomicroscopy was performed on all patients at 1, 3, 6, and 12 months after the operation. All post-operative complications were recorded.ResultsTwenty-five eyes of 25 patients were included. Mean logMAR BCVA improved from 0.43 ± 0.36 (20\40 Snellen equivalent) preoperatively to 0.13 ± 0.18 (20\25 Snellen equivalent) postoperatively at 12 months (p

We propose a new tool for estimating the complexity of a time series: the entropy of difference (ED). The method is based solely on the sign of the difference between neighboring values in a time series. This makes it possible to describe the signal as efficiently as prior proposed parameters, such as permutation entropy (PE) or modified permutation entropy (mPE). Firstly, this method reduces the size of the sample that is necessary to estimate the parameter value, and secondly it enables the use of the Kullback–Leibler divergence to estimate the “distance” between the time series data and random signals.

Abstract Background Radiofrequency ablation has been shown to be a safe and effective treatment for scar-related ventricular arrhythmias (VA). Recent preliminary studies have shown that real time integration of late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images with electroanatomical map (EAM) data may lead to increased procedure efficacy, efficiency, and safety. Methods VOYAGE is a prospective, randomized, multicenter controlled open label study designed to compare in terms of efficacy, efficiency, and safety a CMR aided/guided workflow to standard EAM-guided ventricular tachycardia (VT) ablation. Patients with an ICD or with ICD implantation expected within 1 month, with scar related VT, suitable for CMR and multidetector computed tomography (MDCT) will be randomized to a CMR-guided or CMR-aided approach, whereas subjects unsuitable for imaging or with image quality deemed not sufficient for postprocessing will be allocated to standard of care ablation. Primary endpoint is defined as VT recurrences (sustained or requiring appropriate ICD intervention) during 12 months follow-up, excluding the first month of blanking period. Secondary endpoints will include procedural efficiency, safety, impact on quality of life and comparison between CMR-guided and CMR-aided approaches. Patients will be evaluated at 1, 6 and 12 months. Discussion The clinical impact of real time CMR-guided/aided ablation approaches has not been thoroughly assessed yet. This study aims at defining whether such workflow results in more effective, efficient, and safer procedures. If proven to be of benefit, results from this study could be applied in large scale interventional practice. Trial registrationClinicalTrials.gov, NCT04694079, registered on January 1, 2021.

Summary: Inguinal white adipose tissue (iWAT) is essential for the beneficial effects of exercise training on metabolic health. The underlying mechanisms for these effects are not fully understood, and here, we test the hypothesis that exercise training results in a more favorable iWAT structural phenotype. Using biochemical, imaging, and multi-omics analyses, we find that 11 days of wheel running in male mice causes profound iWAT remodeling including decreased extracellular matrix (ECM) deposition and increased vascularization and innervation. We identify adipose stem cells as one of the main contributors to training-induced ECM remodeling, show that the PRDM16 transcriptional complex is necessary for iWAT remodeling and beiging, and discover neuronal growth regulator 1 (NEGR1) as a link between PRDM16 and neuritogenesis. Moreover, we find that training causes a shift from hypertrophic to insulin-sensitive adipocyte subpopulations. Exercise training leads to remarkable adaptations to iWAT structure and cell-type composition that can confer beneficial changes in tissue metabolism.

AIM: To define the possible beneficial impact of probiotics oral supplementation on patients affected by chalazion. METHODS: Prospective comparative pilot study on 20 adults suffering from chalazion randomly divided into two groups. The first group (n=10) received conservative treatment with lid hygiene, warm compression, and dexamethasone/tobramycin ointment for at least 20d. The second group (n=10), in addition to the conservative treatment, received a mixture of probiotic microorganisms of Streptococcus thermophilus ST10 (DSM 25246), Lactococcus lactis LLC02 (DSM 29536) and Lactobacillus delbrueckii (DSM 16606) once a day up to 3mo. Chalazia were classified according to their size into three groups: small (

Abstract Background Reducing percutaneous endoscopic gastrostomies with jejunal extension tubes (PEG-J) related complications is vital to the long-term preservation of duodenal levodopa infusion (DLI) in advanced Parkinson’s disease (APD). Here, we provide data on the frequency of complications for both the standard “pull” and the non-endoscopic, radiologic assisted, “push” replacement PEG-J techniques in APD. Methods We retrospectively identified all patients treated with DLI from October 2009 to January 2020 at the Movement Disorders Center. Patients features and demographics, PEG-J procedures, causes for any discontinuation, reported complications and mortality were collected. In this cohort, PEG-J replacements were performed using the standard “pull” procedure or the radiologic assisted “push” method. Descriptive statistical analysis, t-test and paired t-test with False Discovery Rate correction was performed. Results This retrospective study included 30 APD patients [median age 72 ± 5.6 years; mean disease duration 17.2 + 5.7 years]. Mean treatment duration was 35.6 (30.6) months. Overall, 156 PEG-J procedures were performed, and Nineteen patients (63.3%) had a total of 185 reported complications, 85 of which were peristomal complications. 17 (56.6%) underwent 100 replacement procedures due to complications. The most commonly reported complication for replacement was J-tube dislocation (36%). One patient discontinued treatment after 6 months, due to peripheral neuropathy. Six patients died for causes not related to DLI. PEG-J replacements performed with the “push” method had a higher turnover (5.6 vs. 7.6 mo.), but fewer reported complications (67 vs. 75%). Conclusion The overall rate of complications was lower for “push” technique. This result might have been due to a higher replacement turnover that acted as a protective factor.

Background: Limited data are available about the predictors and outcomes associated with prolonged SARS-CoV-2 RNA shedding (VS). Methods: A retrospective study including COVID-19 patients admitted to an Italian hospital between March 1 and July 1, 2020. Predictors of viral clearance (VC) and prolonged VS from the upper respiratory tract were assessed by Poisson regression and logistic regression analyses. The causal relation between VS and clinical outcomes was evaluated through an inverse probability weighted Cox model. Results: The study included 536 subjects. The median duration of VS from symptoms onset was 18 days. The estimated 30-day probability of VC was 70.2%. Patients with comorbidities, lymphopenia at hospital admission, or moderate/severe respiratory disease had a lower chance of VC. The development of moderate/severe respiratory failure, delayed hospital admission after symptoms onset, baseline comorbidities, or D-dimer >1000 ng/mL at admission independently predicted prolonged VS. The achievement of VC doubled the chance of clinical recovery and reduced the probability of death/mechanical ventilation. Conclusions: Respiratory disease severity, comorbidities, delayed hospital admission and inflammatory markers negatively predicted VC, which resulted to be associated with better clinical outcomes. These findings highlight the importance of prompt hospitalization of symptomatic patients, especially where signs of severity or comorbidities are present.

Objective: A major factor in the growing world-wide epidemic of obesity and type 2 diabetes is the increased risk of transmission of metabolic disease from obese mothers to both first (F1) and second (F2) generation offspring. Fortunately, recent pre-clinical studies demonstrate that exercise before and during pregnancy improves F1 metabolic health, providing a potential means to disrupt this cycle of disease. Whether the beneficial effects of maternal exercise can also be transmitted to the F2 generation has not been investigated. Methods: C57BL/6 female mice were fed a chow or high-fat diet (HFD) and housed in individual cages with or without running wheels for 2 wks before breeding and during gestation. Male F1 offspring were sedentary and chow-fed, and at 8-weeks of age were bred with age-matched females from untreated parents. This resulted in 4 F2 groups based on grandmaternal treatment: chow sedentary; chow trained; HFD sedentary; HFD trained. F2 were sedentary and chow-fed and studied up to 52-weeks of age. Results: We find that grandmaternal exercise improves glucose tolerance and decreases fat mass in adult F2 males and females, in the absence of any treatment intervention of the F1 after birth. Grandmaternal exercise also improves F2 liver metabolic function, including favorable effects on gene and miRNA expression, triglyceride concentrations and hepatocyte glucose production. Conclusion: Grandmaternal exercise has beneficial effects on the metabolic health of grandoffspring, demonstrating an important means by which exercise during pregnancy could help reduce the worldwide incidence of obesity and type 2 diabetes.

Context: Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin—a 1:1 ratio protamine sparing effects—but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation. Aims: This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery. Settings and Design: A retrospective observational study in a tertiary care university hospital. Subjects and Methods: We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it. Results: At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction). Conclusion: A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

Abstract Background Short-term exercise training programs that consist of moderate intensity endurance training or high intensity interval training have become popular choices for healthy lifestyle modifications, with as little as two weeks of training being shown to improve cardiorespiratory fitness and whole-body glucose metabolism. An emerging concept in exercise biology is that exercise stimulates the release of cytokines and other factors into the blood that contribute to the beneficial effects of exercise on metabolism, but whether these factors behave similarly in response to moderate and high intensity short term training is not known. Here, we determined the effects of two short-term exercise training programs on the concentrations of select secreted cytokines and Klotho, a protein involved in anti-aging. Methods Healthy, sedentary men (n = 22) were randomized to moderate intensity training (MIT) or sprint intensity training (SIT) treatment groups. SIT consisted of 6 sessions over 2 weeks of 6 × 30 s all out cycle ergometer sprints with 4 min of recovery between sprints. MIT consisted of 6 sessions over 2 weeks of cycle ergometer exercise at 60% VO2peak, gradually increasing in duration from 40 to 60 min. Blood was taken before the intervention and 48 h after the last training session, and glucose uptake was measured using [18F]FDG‐PET/CT scanning. Cytokines were measured by multiplex and Klotho concentrations by ELISA. Results Both training protocols similarly increased VO2peak and decreased fat percentage and visceral fat (P

Abstract Background The detrimental effects of inotropes are well-known, and in many fields they are only used within a goal-directed therapy approach. Nevertheless, standard management in many centers includes administering inotropes to all patients undergoing cardiac surgery to prevent low cardiac output syndrome and its implications. Randomized evidence in favor of a patient-tailored, inotrope-sparing approach is still lacking. We designed a randomized controlled noninferiority trial in patients undergoing cardiac surgery with normal ejection fraction to assess whether an dobutamine-sparing strategy (in which the use of dobutamine was guided by hemodynamic evidence of low cardiac output associated with signs of inadequate tissue perfusion) was noninferior to an inotrope-to-all strategy (in which all patients received dobutamine). Results A total of 160 patients were randomized to the dobutamine-sparing strategy (80 patients) or to the dobutamine-to-all approach (80 patients). The primary composite endpoint of 30-day mortality or occurrence of major cardiovascular complications (arrhythmias, acute myocardial infarction, low cardiac output syndrome and stroke or transient ischemic attack) occurred in 25/80 (31%) patients of the dobutamine-sparing group (p = 0.74) and 27/80 (34%) of the dobutamine-to-all group. There were no significant differences between groups regarding the incidence of acute kidney injury, prolonged mechanical ventilation, intensive care unit or hospital length of stay. Discussion Although it is common practice in many centers to administer inotropes to all patients undergoing cardiac surgery, a dobutamine-sparing strategy did not result in an increase of mortality or occurrence of major cardiovascular events when compared to a dobutamine-to-all strategy. Further research is needed to assess if reducing the administration of inotropes can improve outcomes in cardiac surgery. Trial registration ClinicalTrials.gov, NCT02361801. Registered Feb 2nd, 2015. https://clinicaltrials.gov/ct2/show/NCT02361801