Metabolomics and Cardiovascular Risk in Patients with Heart Failure: A Systematic Review and Meta-Analysis.

The associations of plasma metabolites with adverse cardiovascular (CV) outcomes are still underexplored and may be useful in CV risk stratification. We performed a systematic review and meta-analysis to establish correlations between blood metabolites and adverse CV outcomes in patients with heart failure (HF). Four cohorts were included, involving 83 metabolites and 37 metabolite ratios, measured in 1158 HF patients. Hazard ratios (HR) of 42 metabolites and 3 metabolite ratios, present in at least two studies, were combined through meta-analysis. Higher levels of histidine (HR 0.74, 95% CI [0.64; 0.86]) and tryptophan (HR 0.82 [0.71; 0.96]) seemed protective, whereas higher levels of symmetric dimethylarginine (SDMA) (HR 1.58 [1.30; 1.93]), N-methyl-1-histidine (HR 1.56 [1.27; 1.90]), SDMA/arginine (HR 1.38 [1.14; 1.68]), putrescine (HR 1.31 [1.06; 1.61]), methionine sulfoxide (HR 1.26 [1.03; 1.52]), and 5-hydroxylysine (HR 1.25 [1.05; 1.48]) were associated with a higher risk of CV events. Our findings corroborate important associations between metabolic imbalances and a higher risk of CV events in HF patients. However, the lack of standardization and data reporting hampered the comparison of a higher number of studies. In a future clinical scenario, metabolomics will greatly benefit from harmonizing sample handling, data analysis, reporting, and sharing.

The extent of postpartum cardiac reverse remodeling is reflected in urine proteome.

The association of postpartum cardiac reverse remodeling (RR) with urinary proteome, particularly in pregnant women with cardiovascular (CV) risk factors who show long-term increased risk of cardiovascular disease and mortality is unknown. We aim to profile the urinary proteome in pregnant women with/without CV risk factors to identify proteins associated with postpartum RR. Our study included a prospective cohort of 32 healthy and 27 obese and/or hypertensive and/or diabetic pregnant women who underwent transthoracic echocardiography, pulse-wave-velocity, and urine collection at the 3rd trimester and 6 months postpartum. Shotgun HPLC-MS/MS profiled proteins. Generalized linear mixed-effects models were used to identify associations between urinary proteins and left ventricle mass (LVM), a surrogate of RR. An increase in arterial stiffness was documented from 3rd trimester to 6 months after delivery, being significantly elevated in women with CV risk factors. In addition, the presence of at least one CV risk factor was associated with worse LVM RR. We identified 6 and 11 proteins associated with high and low LVM regression, respectively. These proteins were functionally linked with insulin-like growth factor (IGF) transport and uptake regulation by IGF binding-proteins, platelet activation, signaling and aggregation and the immune system's activity. The concentration of IGF-1 in urine samples was associated with low LVM regression after delivery. Urinary proteome showed a predicting potential for identifying pregnant women with incomplete postpartum RR.

Impact of right ventricle-pulmonary artery coupling in patients undergoing transcatheter aortic valve implantation.

Right ventricle-pulmonary artery (RV-PA) coupling has been linked to clinical outcomes in patients with severe aortic stenosis (AS) undergoing transcatheter valve implantation (TAVI). However, the best timing for prognostic assessment remains uncertain. Our aim was to determine the impact of RV longitudinal function parameters and RV-PA coupling on mortality in patients undergoing TAVI.  Retrospective, single center, analysis including patients with AS who underwent TAVI between 2007 and 2021. Echocardiographic evaluation was performed before, shortly after the procedure, and during follow-up. RV-PA uncoupling was defined as a TAPSE/PASP ratio<0.55 (severe RV uncoupling was defined as TAPSE/PASP ratio<0.32. The effect of RV parameters on all-cause mortality up to 12 months was assessed.  Among the 577 patients included, pre-procedural TAPSE/PASP ratio data were available for 205. RV-PA uncoupling was present in 113 patients (55.1%), with severe uncoupling observed in 31 (15.1%). Within the first 12 months after TAVI, 51 patients (9%) died. Severe RV-PA uncoupling was associated with mortality in univariable Cox regression; however, this association was lost after adjusting for EuroSCORE II. A significant association was found between the TAPSE/PASP ratio (per 0.1-unit increase) after the procedure and the primary endpoint (HR: 0.73; 95% CI: 0.56, 0.97; p=0.029). Higher postprocedural PASP (HR: 1.04; 95% CI: 1.02, 1.06; p<0.001 was also associated with all-cause mortality.  V-PA uncoupling and PASP after TAVI are associated with all-cause mortality in patients and may be valuable for patient selection and for planning post-procedural care.

Sex-based differences and risk of recurrence in patients with atrial fibrillation undergoing pulmonary vein isolation.

INTRODUCTION: Studies suggest increased likelihood of atrial fibrillation (AF) recurrence after catheter ablation (CA) in women than in men, indicating that sex may be an independent risk factor for recurrence. Nevertheless, the influence of sex on AF recurrence and underlying mechanisms remains unclear. METHODS: Retrospective, single-centre study including patients undergoing AF CA between 2017 and 2021. Late recurrence (LR) was defined as AF recurrence ≥90 days after ablation, whereas early recurrence (ER) occurred within 90 days. RESULTS: 656 patients (32% women) were included, with a median follow-up period of 26 months. Compared to men, women undergoing CA were older, had higher body mass indexes, and had higher rates of hypertension, thyroid dysfunction, and valvular disease. Women also had increased LR risk after CA (HR 1.76, 95% CI [1.19, 2.59]). A time-split multivariable analysis at one year of follow-up showed no difference in LR risk during the first 12 months after CA (HR 1.19, 95% CI [0.73, 1.94]); however, LR risk increased in women (HR 2.90, 95% CI [1.68, 5.01]) after 12 months. In a sex-stratified analysis, coronary calcium score (CCS) >100 was associated with increased LR risk in men (HR 1.81, 95% CI [1.06, 3.08]), but not in women. Cardiac adipose tissue volume was not associated with increased LR risk. CONCLUSIONS: Fewer women underwent CA than men and LR was more frequent in women, particularly one year after the procedure. CCS was associated with increased LR risk in men.

Stretch-induced compliance mechanism in pregnancy-induced cardiac hypertrophy and the impact of cardiovascular risk factors.

Pressure overload-induced hypertrophy compromises cardiac stretch-induced compliance (SIC) after acute volume overload (AVO). We hypothesized that SIC could be enhanced by physiological hypertrophy induced by pregnancy's chronic volume overload. This study evaluated SIC-cardiac adaptation in pregnant women with or without cardiovascular risk (CVR) factors. Thirty-seven women (1st trimester, 1stT) and a separate group of 31 (3rd trimester, 3rdT) women [healthy or with CVR factors (obesity and/or hypertension and/or with gestational diabetes)] underwent echocardiography determination of left ventricular end-diastolic volume (LVEDV) and E/e' before (T0), immediately after (T1), and 15 min after (T2; SIC) AVO induced by passive leg elevation. Blood samples for NT-proBNP quantification were collected before and after the AVO. Acute leg elevation significantly increased inferior vena cava diameter and stroke volume from T0 to T1 in both 1stT and 3rdT, confirming AVO. LVEDV and E/e' also increased immediately after AVO (T1) in both 1stT and 3rdT. SIC adaptation (T2, 15 min after AVO) significantly decreased E/e' in both trimesters, with additional expansion of LVEDV only in the 1stT. NT-pro-BNP increased slightly after AVO but only in the 1stT. CVR factors, but not parity or age, significantly impacted SIC cardiac adaptation. A distinct functional response to SIC was observed between 1stT and 3rdT, which was influenced by CVR factors. The LV of 3rdT pregnant women was hypertrophied, showing a structural limitation to dilate with AVO, whereas the lower LV filling pressure values suggest increased diastolic compliance.NEW & NOTEWORTHY The sudden increase of volume overload triggers an acute myocardial stretch characterized by an immediate rise in contractility by the Frank-Starling mechanism, followed by a progressive increase known as the slow force response. The present study is the first to characterize echocardiographically the stretch-induced compliance (SIC) mechanism in the context of physiological hypertrophy induced by pregnancy. A distinct functional adaptation to SIC was observed between first and third trimesters, which was influenced by cardiovascular risk factors.

The impact of echocardiographic indexation to evaluate cardiac reverse remodeling throughout pregnancy and postpartum.

INTRODUCTION AND OBJECTIVES: Echocardiography guidelines suggest normalizing left ventricular (LV) volumes and mass (LVM) to body size. During pregnancy, continuous weight variation impacts on body surface area (BSA) calculation, limiting the longitudinal analysis of cardiac remodeling (CR) and reverse remodeling (RR) variables. Our aim was to identify the most common indexing methodologies in the literature on pregnant populations through a systematic review; and, to compare four scaling methods: (i) none (absolute values); (ii) indexing to the BSA before pregnancy; (iii) allomeric indexing; and (iv) indexing to BSA measured at the same day of cardiac assessment, using an illustrative example. METHODS: We performed a systematic review of CR and RR during pregnancy and post-partum, using two databases. We included studies reporting longitudinal echocardiographic analysis of cardiac chamber volumes in humans. We used a prospective cohort study of healthy pregnant women who underwent four echocardiographic evaluations during pregnancy and postpartum, as an illustrative example. RESULTS: Twenty-seven studies were included, most studies indexed to BSA measured at each evaluation moment (n=21). Within-subjects design was the most reported to analyse longitudinal data (n=17). Indexation to the pre-pregnancy BSA or application of allometric indexes revealed a higher effect than BSA measured at each evaluation and an equal effect to not indexing using within-subjects design. The within-subjects designs also revealed a higher effect size value than the between-subjects design for longitudinal analysis of LVM adaptations during pregnancy and postpartum. CONCLUSION(S): This study concludes that indexation methods do not impact the clinical interpretation of longitudinal echocardiographic assessment but highlights the need to harmonize normalization procedures during pregnancy.

Phenotyping patients with ischaemic heart disease at risk of developing heart failure: an analysis of the HOMAGE trial.

AIMS: We aim to characterize the clinical and proteomic profiles of patients at risk of developing heart failure (HF), with and without coronary artery disease (CAD) or prior myocardial infarction (MI). METHODS AND RESULTS: HOMAGE evaluated the effect of spironolactone on plasma and serum markers of fibrosis over 9 months of follow-up in participants with (or at risk of having) CAD, and raised natriuretic peptides. In this post hoc analysis, patients were classified as (i) neither CAD nor MI; (ii) CAD; or (iii) MI. Proteomic between-group differences were evaluated through logistic regression and narrowed using backward stepwise selection and bootstrapping. Among the 527 participants, 28% had neither CAD or MI, 31% had CAD, and 41% had prior MI. Compared with people with neither CAD nor MI, those with CAD had higher baseline plasma concentrations of matrix metalloproteinase-7 (MMP-7), galectin-4 (GAL4), plasminogen activator inhibitor 1 (PAI-1), and lower plasma peptidoglycan recognition protein 1 (PGLYRP1), whilst those with a history of MI had higher plasma MMP-7, neurotrophin-3 (NT3), pulmonary surfactant-associated protein D (PSPD), and lower plasma tumour necrosis factor-related activation-induced cytokine (TRANCE). Proteomic signatures were similar for patients with CAD or prior MI. Treatment with spironolactone was associated with an increase of MMP7, NT3, and PGLYRP1 at 9 months. CONCLUSIONS: In patients at risk of developing HF, those with CAD or MI had a different proteomic profile regarding inflammatory, immunological, and collagen catabolic processes.

Digital flashcards and medical physiology performance: a dose-dependent effect.

Use of digital flashcards promotes active recall, spaced repetition, and self-assessment academic principles. This work explores the association and dose-dependent effect of this study method and locomotor (LP) and cardiovascular physiology (CP) grades. A single-faculty cohort study of medical LP and CP students was conducted, and 155 and 676 flashcards, respectively, were created through Moodle. An exploratory analysis examined three exam results (2019), and a confirmatory study used a fourth exam (2021) in another CP cohort. Of 685 students enrolled, 558 participated in the exploratory analysis: 319 (69%) for LP and 311 (84%) for CP, of which 203 LP and 267 CP students were flashcard users. Median grades were higher among flashcard users, and the number of cards reviewed was positively correlated with grades (r = 0.275 to 0.388 for LP and r = 0.239 to 0.432 for CP, P < 0.001). Multiple linear regression models confirmed a positive dose-dependent association between results and the number of flashcards studied: for every 100 LP cards reviewed, exam grades increased 0.44-0.75 on a 0-20 scale range (P < 0.001), and for every 1,000 CP flashcards, results raised 0.81-1.08 values (P < 0.05). These findings were confirmed in the 2021 CP cohort of 269 participants, of whom 67% were flashcard users. Digital flashcard revision has a consistent positive dose-dependent association on LP and CP grades.NEW & NOTEWORTHY Implementing flashcard-based strategies is a feasible way to promote active recall, spaced repetition, and self-assessment, and students are highly adherent to these initiatives. There is a positive dose-dependent association between the number of flashcards reviewed and physiology grades. These results are consistent across different physiology subjects, under different cohorts, over short and medium terms.

Lung ultrasound and diuretic therapy in chronic heart failure: a randomised trial.

BACKGROUND: Lung congestion is frequent in heart failure (HF) and is associated with symptoms and poor prognosis. Lung ultrasound (LUS) identification of B-lines may help refining congestion assessment on top of usual care. Three small trials comparing LUS-guided therapy to usual care in HF suggested that LUS-guided therapy could reduce urgent HF visits. However, to our knowledge, the usefulness of LUS in influencing loop diuretic dose adjustment in ambulatory chronic HF has not been studied. AIMS: To study whether to show or not LUS results to the HF assistant physician would change loop diuretic adjustments in "stable" chronic ambulatory HF patients. METHODS: Prospective randomised single-blinded trial comparing two strategies: (1) open 8-zone LUS with B-line results available to clinicians, or (2) blind LUS. The primary outcome was change in loop diuretic dose (up- or down-titration). RESULTS: A total of 139 patients entered the trial, 70 were randomised to blind LUS and 69 to open LUS. The median (percentile25-75) age was 72 (63-82) years, 82 (62%) were men, and the median LVEF was 39 (31-51) %. Randomisation groups were well balanced. Furosemide dose changes (up- and down-titration) were more frequent among patients in whom LUS results were open to the assistant physician: 13 (18.6%) in blind LUS vs. 22 (31.9%) in open LUS, OR 2.55, 95%CI 1.07-6.06. Furosemide dose changes (up- and down-titration) were more frequent and correlated significantly with the number of B-lines when LUS results were open (Rho = 0.30, P = 0.014), but not when LUS results were blinded (Rho = 0.19, P = 0.13). Compared to blind LUS, when LUS results were open, clinicians were more likely to up-titrate furosemide dose if the result "presence of pulmonary congestion" was identified and more likely to decrease furosemide dose in the case of an "absence of pulmonary congestion" result. The risk of HF events or cardiovascular death did not differ by randomisation group: 8 (11.4%) in blind LUS vs. 8 (11.6%) in open LUS. CONCLUSIONS: Showing the results of LUS B-lines to assistant physicians allowed more frequent loop diuretic changes (both up- and down-titration), which suggests that LUS may be used to tailor diuretic therapy to each patient congestion status.

Prognostic value of flow-status in severe aortic stenosis patients undergoing percutaneous intervention.

PURPOSE: Low-flow status is a mortality predictor in severe aortic stenosis (SAS) patients, including after transcatheter aortic valve implantation (TAVI) treatment. However, the best parameter to assess flow is unknown. Recent studies suggest that transaortic flow rate (FR) is superior to currently used stroke volume index (SVi) in defining low-flow states. Therefore, we aimed to evaluate the prognostic value of FR and SVi in patients undergoing TAVI. METHODS: A single-centre retrospective analysis of all consecutive patients treated with TAVI for SAS between 2011 and 2019 was conducted. Low-FR was defined as < 200 mL/s and low-SVi as < 35 mL/m2. Primary endpoint was all-cause five-year mortality, analyzed using Kaplan-Meier curves and Cox regression models. Secondary endpoint was variation of NYHA functional class six months after procedure. Patients were further stratified according to ejection fraction (EF < 50%). RESULTS: Of 489 cases, 59.5% were low-FR, and 43.1% low-SVi. Low-flow patients had superior surgical risk, worse renal function, and had a higher prevalence of coronary artery disease. Low-FR was associated with mortality (hazard ratio 1.36, p = 0.041), but not after adjustment to EuroSCORE II. Normal-SVi was not associated with survival, despite a significative p-trend for its continuous value. No associations were found for flow-status and NYHA recovery. When stratifying according to preserved and reduced EF, both FR and SVi did not predict all-cause mortality. CONCLUSION: In patients with SAS undergoing TAVI, a low-FR state was associated with higher mortality, as well as SVi, but not at a 35 mL/m2 cut off.

2022 EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in adults with autoimmune inflammatory rheumatic diseases

To develop EULAR recommendations for screening and prophylaxis of chronic and opportunistic infections in patients with autoimmune inflammatory rheumatic diseases (AIIRD). An international Task Force (TF) (22 members/15 countries) formulated recommendations, supported by systematic literature review findings. Level of evidence and grade of recommendation were assigned for each recommendation. Level of agreement was provided anonymously by each TF member. Four overarching principles (OAP) and eight recommendations were developed. The OAPs highlight the need for infections to be discussed with patients and with other medical specialties, in accordance with national regulations. In addition to biologic/ targeted synthetic disease-modifying antirheumatic drugs (DMARDs) for which screening for latent tuberculosis (TB) should be performed, screening could be considered also before conventional synthetic DMARDs, glucocorticoids and immunosuppressants. Interferon gamma release assay should be preferred over tuberculin skin test, where available. Hepatitis B (HBV) antiviral treatment should be guided by HBV status defined prior to starting antirheumatic drugs. All patients positive for hepatitis-C-RNA should be referred for antiviral treatment. Also, patients who are non-immune to varicella zoster virus should be informed about the availability of postexposure prophylaxis should they have contact with this pathogen. Prophylaxis against Pneumocystis jirovecii seems to be beneficial in patients treated with daily doses >15­30mg of prednisolone or equivalent for >2­4 weeks. These recommendations provide guidance on the screening and prevention of chronic and opportunistic infections. Their adoption in clinical practice is recommended to standardise and optimise care to reduce the burden of opportunistic infections in people living with AIIRD.

Cardiovascular risk factors during pregnancy impact the postpartum cardiac and vascular reverse remodeling.

Pregnant women with cardiovascular risk (CVR) factors are highly prone to develop cardiovascular disease later in life. Thus, recent guidelines suggest extending the follow-up period to 1 yr after delivery. We aimed to evaluate cardiovascular remodeling during pregnancy and determine which CVR factors and potential biomarkers predict postpartum cardiac and vascular reverse remodeling (RR). Our study included a prospective cohort of 76 healthy and 54 obese and/or hypertensive and/or with gestational diabetes pregnant women who underwent transthoracic echocardiography, pulse-wave velocity (PWV), and blood collection at the 1st trimester (1T) and 3rd trimester (3T) of pregnancy as well as at the 1st/6th/12th mo after delivery. Generalized linear mixed-effects models was used to evaluate the extent of RR and its potential predictors. Pregnant women develop cardiac hypertrophy, as confirmed by a significant increase in left ventricular mass (LVM). Moreover, ventricular filling pressure (E/e') and atrial volume increased significantly during gestation. Significant regression of left ventricular (LV) volume, LVM, and filling pressures was observed as soon as 1 mo postpartum. The LV global longitudinal strain worsened slightly and recovered at 6 mo postpartum. PWV decreased significantly from 1T to 3T and normalized at 1 mo postpartum. We found that arterial hypertension, smoking habits, and obesity were independent predictors of increased LVM during pregnancy and postpartum. High C-reactive protein (CRP) and low ST2/IL33-receptor levels are potential circulatory biomarkers of worse LVM regression. Arterial hypertension, age, and gestational diabetes positively correlated with PWV. Altogether, our findings pinpoint arterial hypertension as a critical risk factor for worse RR and CRP, and ST2/IL33 receptors as potential biomarkers of postpartum hypertrophy reversal.NEW & NOTEWORTHY This study describes the impact of cardiovascular risk factors (CVR) in pregnancy-induced remodeling and postpartum reverse remodeling (up to 1 yr) by applying advanced statistic methods (multivariate generalized linear mixed-effects models) to a prospective cohort of pregnant women. Aiming to extrapolate to pathological conditions, this invaluable "human model" allowed us to demonstrate that arterial hypertension is a critical CVR for worse RR and that ST2/IL33-receptors and CRP are potential biomarkers of postpartum hypertrophy reversal.

First report of Nalanthamala vermoesenii causing pink rot of Phoenix canariensis in Mexico.

In Mexico City, the Canary Island date palm (Phoenix canariensis Chabaud) is an important plant forming part of its landscape identity. In February 2022, pink rot disease symptoms were observed on 16 P. canariensis plants in Mexico City (19°25'43.98"N, 99° 9'49.41"W). The incidence was 27%, while the severity 12%. External symptoms included necrotic lesions that advanced from the petiole towards the rachis. Internal symptoms were rotted, dark brown discoloration in bud, petiole, and rachis. Abundant conidial masses were developed on the infected tissues. Pieces of diseased tissues (5-mm cubes) were surface sterilized for 2 min in 3% sodium hypochlorite, rinsed with sterilized distilled water, plated onto potato dextrose agar (PDA), and incubated at 24°C and 12-h photoperiod, 20 pink fungal colonies were developed with sparse aerial mycelia on PDA. Conidiophores were hyaline, dimorphic, penicillate, and Acremonium-like. Conidia were dimorphic, typically with somewhat truncated ends, 4.5 to 5.7 × 1.9 to 2.3 µm (mean 4.99 × 2.15, n = 100), borne in long chains on penicillate conidiophores; on Acremonium-like conidiophores conidia were cylindrical, straight, and slightly curved, 4.55 to 10.1 × 1.2 to 2.35 µm (mean 8.2 × 1.7, n = 100). These morphological characteristics resembled those of Nalanthamala vermoesenii (Biourge) Schroers (Schroers et al. 2005). Genomic DNA was extracted from the mycelia of a representative isolate CP-SP53. The internal transcribed spacer (ITS) region and the large subunit of ribosomal ribonucleic acid (LSU) were amplified and sequenced. The sequences were deposited in GenBank with accession numbers OQ581472 (ITS) and OQ581465 (LSU). Phylogenetic trees based on ITS and LSU sequences of Nalanthamala species were reconstructed using maximum likelihood and Bayesian inference methods. Isolate CP-SP53 was placed in the clade of Nalanthamala vermoesenii. The pathogenicity test was carried out twice with isolate CP-SP53 on five 3-year-old P. canariensis plants. Four petioles per plant were surface disinfected with 75% ethanol, and wounded with a sterilized scalpel (shallow cuts 0.5 cm wide). A mycelial plug (5 mm in diam.) of a 1-week-old PDA culture was placed on each wounded site. Sterile PDA plugs were used for five non-inoculated control plants. All plants were maintained at 22 ± 2°C and a 12-h photoperiod. Twenty-five days after inoculation (dai), wounded petioles showed the same symptoms observed in the field, whereas control plants remained healthy. Forty-five dai, all inoculated plants died. Pink conidial masses developed on symptomatic tissues. To fulfill Koch's postulates, the pathogen was reisolated by placing the pink conidial masses onto PDA. The colony characteristics and morphometric measurements were identical to those of isolate CP-SP53. Nalanthamala vermoesenii has been reported on P. canariensis in Greece and United States (Feather et al. 1979; Ligoxigakis et al. 2013) and Syagrus romanzoffiana in Egypt (Mohamed et al. 2016). To our knowledge, this is the first report of Nalanthamala vermoesenii as the causal agent of pink rot on P. canariensis in Mexico. This plant is the most commonly planted ornamental palm in Mexico City. The spread of N. vermoesenii could be a threat for the estimated 15 thousand palms, therefore dramatically change the urban landscape.

Optimization of a Green Microwave-Assisted Extraction Method to Obtain Multifunctional Extracts of Mentha sp.

A microwave-assisted extraction (MAE) procedure has been optimized to simultaneously provide multifunctional extracts of Mentha sp. leaves with improved antioxidant properties and, for the first time, with optimal antimicrobial activity. Among the solvents evaluated, water was selected as the extractant in order to develop a green procedure and also for its improved bioactive properties (higher TPC and Staphylococcus aureus inhibition halo). MAE operating conditions were optimized by means of a 3-level factorial experimental design (100 °C, 14.7 min, 1 g of dry leaves/12 mL of water and 1 extraction cycle), and further applied to the extraction of bioactives from 6 different Mentha species. A comparative LC-Q MS and LC-QToF MS analysis of these MAE extracts was carried out for the first time in a single study, allowing the characterization of up to 40 phenolics and the quantitation of the most abundant. Antioxidant, antimicrobial (Staphylococcus aureus, Escherichia coli and Salmonella typhimurium) and antifungal (Candida albicans) activities of MAE extracts depended on the Mentha species considered. In conclusion, the new MAE method developed here is shown as a green and efficient approach to provide multifunctional Mentha sp. extracts with an added value as natural food preservatives.

An Electroactive and Self-Assembling Bio-Ink, based on Protein-Stabilized Nanoclusters and Graphene, for the Manufacture of Fully Inkjet-Printed Paper-Based Analytical Devices.

Hundreds of new electrochemical sensors are reported in literature every year. However, only a few of them makes it to the market. Manufacturability, or rather the lack of it, is the parameter that dictates if new sensing technologies will remain forever in the laboratory in which they are conceived. Inkjet printing is a low-cost and versatile technique that can facilitate the transfer of nanomaterial-based sensors to the market. Herein, an electroactive and self-assembling inkjet-printable ink based on protein-nanomaterial composites and exfoliated graphene is reported. The consensus tetratricopeptide proteins (CTPRs), used to formulate this ink, are engineered to template and coordinate electroactive metallic nanoclusters (NCs), and to self-assemble upon drying, forming stable films. The authors demonstrate that, by incorporating graphene in the ink formulation, it is possible to dramatically improve the electrocatalytic properties of the ink, obtaining an efficient hybrid material for hydrogen peroxide (H2 O2 ) detection. Using this bio-ink, the authors manufactured disposable and environmentally sustainable electrochemical paper-based analytical devices (ePADs) to detect H2 O2 , outperforming commercial screen-printed platforms. Furthermore, it is demonstrated that oxidoreductase enzymes can be included in the formulation, to fully inkjet-print enzymatic amperometric biosensors ready to use.

Non-Cirrhotic Portal Hypertension in Systemic Lupus Erythematosus.

We report the case of idiopathic non-cirrhotic portal hypertension associated with systemic lupus erythematosus in a 43-year-old woman who suffered from breast cancer. We review this rare condition, as well as its diagnostic and therapeutic approaches.

The impact of heart failure therapy in patients with mildly reduced ejection fraction: a network meta-analysis.

BACKGROUND: Recent heart failure (HF) guidelines have re-classified HF patients with left ventricular ejection fraction (LVEF) between 41% and 49% as HF with mildly reduced ejection fraction (HFmrEF). HFmrEF treatment is often considered a grey zone as no randomized controlled trials (RCTs) were conducted exclusively on these patients. AIMS: A network meta-analysis (NMA) was performed to compare treatment effect of mineralocorticoid receptor antagonists (MRA), angiotensin receptor neprilysin inhibitor (ARNi), angiotensin receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEi), sodium-glucose cotransporter-2 inhibitors (SGLT2i), and beta-blockers (BB) in HFmrEF cardiovascular (CV) outcomes. METHODS AND RESULTS: RCTs sub-analyses evaluating the efficacy of pharmacological treatment in HFmrEF patients were searched. Hazard ratios (HRs) and their variance were extracted from each RCT for (i) composite of CV death or HF hospitalizations, (ii) CV death, and (iii) HF hospitalizations. A random-effects NMA was performed to compare and assess the treatment efficiency. Six RCTs with subgroup analysis according to participants' ejection fraction, a patient-level pooled meta-analysis of two RCTs, and an individual patient-level analysis of eleven BB RCTs were included, totalling 7966 patients. To our primary endpoint, SGLT2i vs. placebo was the only comparison with significant results, with a 19% risk reduction in the composite of CV death or HF hospitalizations [HR 0.81, 95% confidence interval (CI) 0.67-0.98]. In HF hospitalizations, the impact of the pharmacological therapies was more notorious, and ARNi reduced in 40% the risk of HF hospitalizations (HR 0.60, 95% CI 0.39-0.92), SGLT2i in 26% (HR 0.74, 95% CI 0.59-0.93) and renin-angiotensin system inhibition (RASi) with ARB and ACEi in 28% (HR 0.72, 95% CI 0.53-0.98). Although BBs were globally less beneficial, they were the only class that supported a reduced risk of CV death (HR vs. placebo: 0.48, 95% CI 0.24-0.95). We did not observe a statistically significant difference in any comparison between active treatments. There was a sound reduction with ARNi on the primary endpoint (HR vs. BB: 0.81, 95% CI 0.47-1.41; HR vs. MRA 0.94, 95% CI 0.53-1.66) and on HF hospitalizations (HR vs. RASi 0.83, 95% CI 0.62-1.11; HR vs. SGLT2i 0.80, 95% CI 0.50-1.30). CONCLUSIONS: In addition to SGLT2i, pharmacological treatment recommended for HF with reduced LVEF, namely, ARNi, MRA, and BB, can also be effective in HFmrEF. This NMA did not show significant superiority over any pharmacological class.