Vegetable substrates as an alternative for the inclusion of lactic acid bacteria with probiotic potential in food matrices.

Vegetable substrates are food matrices with micronutrients, antioxidants, and fiber content with a high potential for bioprocesses development. In addition, they have been recognized as essential sources of a wide range of phytochemicals that, individually or in combination, can act as bioactive compounds with potential benefits to health due to their antioxidant and antimicrobial activity and recently due to their status as prebiotics in the balance of the human intestinal microbiota. This systematic review explores the benefits of lactic fermentation of plant matrices such as fruits, vegetables, legumes, and cereals by bacteria with probiotic potential, guaranteeing cell viability (106-107 CFU/mL) and generating bioactive metabolic products for modulation of the gut microbiome.

Bio-yogurt with the inclusion of phytochemicals from carrots (Daucus carota): a strategy in the design of functional dairy beverage with probiotics.

The development of yogurt with functional characteristics from bioactive compounds such as fiber, antioxidants, and probiotics represents a novel strategy in designing value-added dairy beverages. However, biotechnological challenges are present in these bioprocesses, such as the selection of probiotic strains, as well as the correlation with the physicochemical characteristics of the fermentative metabolism of probiotic microorganisms. Therefore, yogurt could be a vehicle for including probiotic bacteria, bioactive compounds, and phytochemicals that allow synergistic effects in the development of bioprocesses with potential benefits for the host's health. Therefore, this article aims to review the current conditions of bio-yogurt production, discuss the physicochemical and bioactive composition (sugars, fiber, vitamins), and include phytochemicals from carrots to establish synergistic relationships with probiotic microorganisms to obtain a functional dairy beverage.

What do Spanish registries report about worsening events in chronic heart failure? Needs and challenges.

INTRODUCTION: Worsening heart failure (HF) is associated with a high risk of death and rehospitalization. Despite that, real world evidence about the impact of worsening HF on clinical practice is scarce. AREAS COVERED: A narrative review about registries addressing recent worsening HF events in Spain, with special emphasis on patients recently hospitalized for HF was performed. EXPERT OPINION: Worsening HF can be defined as situations where the patient's HF deteriorates to the extent that it necessitates initiation or intensification of diuretic treatment (mainly intravenous). The events can occur at the outpatient level, generally in the day hospital, in the emergency department or even hospitalization. Early identification of worsening HF events is essential to establish appropriate treatment as soon as possible. In this context, robust clinical benefits have been reported for renin-angiotensin system inhibitors, sacubitril-valsartan, beta-blockers, mineralocorticoid receptor antagonists, SGLT2 inhibitors, and vericiguat. In Spain, several registries of patients with HF have been developed, some of them including patients recently hospitalized for HF, but not with recent worsening HF events. Therefore, registries addressing recent worsening events would be desirable. Using a practical approach, this review analyzes the importance of worsening HF events, with special emphasis on Spanish data.

Influence of the medical treatment schedule in new diagnoses patients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) guidelines recommend treating all patients with HF and reduced ejection fraction (HFrEF) with quadruple therapy, although they do not establish how to start it. This study aimed to evaluate the implementation of these recommendations, analyzing the efficacy and safety of the different therapeutic schedules. METHODS AND RESULTS: Prospective, observational, and multicenter registry that evaluated the treatment initiated in patients with newly diagnosed HFrEF and its evolution at 3 months. Clinical and analytical data were collected, as well as adverse reactions and events during follow-up. Five hundred and thirty-three patients were included, selecting four hundred and ninety-seven, aged 65.5 ± 12.9 years (72% male). The most frequent etiologies were ischemic (25.5%) and idiopathic (21.1%), with a left ventricular ejection fraction of 28.7 ± 7.4%. Quadruple therapy was started in 314 (63.2%) patients, triple in 120 (24.1%), and double in 63 (12.7%). Follow-up was 112 days [IQI 91; 154], with 10 (2%) patients dying. At 3 months, 78.5% had quadruple therapy (p < 0.001). There were no differences in achieving maximum doses or reducing or withdrawing drugs (< 6%) depending on the starting scheme. Twenty-seven (5.7%) patients had any emergency room visits or admission for HF, less frequent in those with quadruple therapy (p = 0.02). CONCLUSION: It is possible to achieve quadruple therapy in patients with newly diagnosed HFrEF early. This strategy makes it possible to reduce admissions and visits to the emergency room for HF without associating a more significant reduction or withdrawal of drugs or significant difficulty in achieving the target doses.

Sex-Related Differences in Heart Failure Diagnosis.

PURPOSE OF REVIEW: The literature on the importance of sex in heart failure diagnosis is scarce. This review aims to summarize current knowledge on sex differences regarding the diagnosis of heart failure. RECENT FINDINGS: Comorbidities are frequent in patients with heart failure, and their prevalence differs between sexes; some differences in symptomatology and diagnostic imaging techniques were also found. Biomarkers also usually show differences between sexes but are not significant enough to establish sex-specific ranges. This article outlines current information related to sex differences in HF diagnosis. Research in this field remains to be done. Maintaining a high diagnostic suspicion, actively searching for the disease, and considering the sex is relevant for early diagnosis and better prognosis. In addition, more studies with equal representation are needed.

Fragilidad y pronóstico de los pacientes mayores con insuficiencia cardiaca / Frailty and prognosis of older patients with chronic heart failure

Introducción y objetivos: La insuficiencia cardiaca (IC) es prevalente en edades avanzadas. Nuestro objetivo es conocer el impacto de la fragilidad en la mortalidad a 1 año en pacientes mayores con IC ambulatorios. Métodos: El estudio «Impacto de la fragilidad y otros síndromes geriátricos en el manejo clínico y pronóstico del paciente anciano ambulatorio con insuficiencia cardiaca» (FRAGIC) es un registro prospectivo multicéntrico, realizado en 16 centros españoles, que incluyó pacientes con IC ambulatorios de edad ≥ 75 años seguidos por cardiología en España. Resultados: Se incluyó a 499 pacientes (media de edad, 81,4±4,3 años; 193 [38%] mujeres); 268 (54%) tenían una fracción de eyección del ventrículo izquierdo <40% y el 84,6% estaba en clase funcional II de la NYHA. La escala FRAIL identificó a 244 pacientes prefrágiles (49%) y 111 frágiles (22%). Los pacientes frágiles tenían una media de edad significativamente mayor, eran más frecuentemente mujeres (ambos, p <0,001) y presentaban mayores comorbilidad según el índice de Charlson (p=0,017) y prevalencia de síndromes geriátricos (p <0,001). Tras una mediana de seguimiento de 371 [361-387] días, fallecieron 58 pacientes (11,6%). En el análisis multivariado (modelo de regresión de Cox), la fragilidad mediante la escala FRAIL se asoció marginalmente con la mortalidad (HR=2,35; IC95%, 0,96-5,71; p=0,059); la identificada mediante la escala visual de movilidad (HR=2,26; IC95%, 1,16-4,38; p=0,015) fue predictor independiente de mortalidad, cuya asociación se mantuvo tras ajustar por variables confusoras (HR=2,13; IC95%, 1,08-4,20; p=0,02). Conclusiones: En pacientes mayores ambulatorios con IC, la fragilidad es predictor independiente de mortalidad a 1 año de seguimiento. Debe identificarse como parte del abordaje integral de estos pacientes.(AU)

Introduction and objectives: Heart failure (HF) is prevalent in advanced ages. Our objective was to assess the impact of frailty on 1-year mortality in older patients with ambulatory HF. Methods: Our data come from the FRAGIC study (Spanish acronym for “Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly outpatients with heart failure”), a multicenter prospective registry conducted in 16 Spanish hospitals including outpatients ≥ 75 years with HF followed up by cardiology services in Spain. Results: We included 499 patients with a mean age of 81.4±4.3 years, of whom 193 (38%) were women. A total of 268 (54%) had left ventricular ejection fraction <40%, and 84.6% was in NYHA II functional class. The FRAIL scale identified 244 (49%) pre-frail and 111 (22%) frail patients. Frail patients were significantly older, were more frequently female (both, P <.001), and had higher comorbidity according to the Charlson index (P=.017) and a higher prevalence of geriatric syndromes (P <.001). During a median follow-up of 371 [361-387] days, 58 patients (11.6%) died. On multivariate analysis (Cox regression model), frailty detected with the FRAIL scale was marginally associated with mortality (HR=2.35; 95%CI, 0.96-5.71; P=.059), while frailty identified by the visual mobility scale was an independent predictor of mortality (HR=2.26; 95%CI, 1.16-4.38; P=.015); this association was maintained after adjustment for confounding variables (HR=2.13; 95%CI, 1.08-4.20; P=.02). Conclusions: In elderly outpatients with HF, frailty is independently associated with mortality at 1 year of follow-up. It is essential to identify frailty as part of the comprehensive approach to elderly patients with HF.(AU)

Sex differences in the impact of frailty in elderly outpatients with heart failure.

Introduction: Frailty is common among patients with heart failure (HF). Our aim was to address the role of frailty in the management and prognosis of elderly men and women with HF. Methods and results: Prospective multicenter registry that included 499 HF outpatients ≥75 years old. Mean age was 81.4 ± 4.3 years, and 193 (38%) were women. Compared with men, women were older (81.9 ± 4.3 vs. 81.0 ± 4.2 years, p = 0.03) and had higher left ventricular ejection fraction (46 vs. 40%, p < 0.001) and less ischemic heart disease (30 vs. 57%, p < 0.001). Women had a higher prevalence of frailty (22 vs. 10% with Clinical Frailty Scale, 34 vs. 15% with FRAIL, and 67% vs. 46% with the mobility visual scale, all p-values < 0.001) and other geriatric conditions (Barthel index ≤90: 14.9 vs. 6.2%, p = 0.003; malnutrition according to Mini Nutritional Assessment Short Formulary ≤11: 55% vs. 42%, p = 0.007; Pfeiffer cognitive test's errors: 1.6 ± 1.7 vs. 1.0 ± 1.6, p < 0.001; depression according to Yesavage test; p < 0.001) and lower comorbidity (Charlson index ≥4: 14.1% vs. 22.1%, p = 0.038). Women also showed worse self-reported quality of life (6.5 ± 2.1 vs. 6.9 ± 1.9, on a scale from 0 to 10, p = 0.012). In the univariate analysis, frailty was an independent predictor of mortality in men [Hazard ratio (HR) 3.18, 95% confidence interval (CI) 1.29-7.83, p = 0.012; HR 4.53, 95% CI 2.08-9.89, p < 0.001; and HR 2.61, 95% CI 1.23-5.43, p = 0.010, according to FRAIL, Clinical Frailty Scale, and visual mobility scale, respectively], but not in women. In the multivariable analysis, frailty identified by the visual mobility scale was an independent predictor of mortality (HR 1.95, 95% CI 1.04-3.67, p = 0.03) and mortality/readmission (HR 2.06, 95% CI 1.05-4.04, p = 0.03) in men. Conclusions: In elderly outpatients with HF frailty is more common in women than in men. However, frailty is only associated with mortality in men.

Síndrome de Claude: III par incompleto y ataxia contralateral / Claude syndrome: Incomplete third cranial nerve palsy and contralateral ataxia

Resumen Los accidentes cerebrovasculares mesencefálicos son poco frecuentes y por lo general están acompañados de otras lesiones concomitantes. La presencia simultánea de signos ipsi y contrala terales obliga a pensar en un síndrome alterno por compromiso del tronco encefálico. La resonancia magnética nuclear es el estudio de elección para caracterizar y localizar la lesión. Presentamos el caso de un hombre de 71 años que sufrió parálisis del tercer par derecho y hemiataxia izquierda, cuadro infrecuente, conocido como síndrome de Claude.

Abstract Midbrain strokes are rare and are usually accompanied by other concomitant injuries. The simultaneous presence of ipsi and contralateral signs makes it necessary to think of a brainstem syndrome due to involvement of the brainstem. Mag netic nuclear resonance is the study of choice to characterize and locate the lesion. We report the case of a 71-year-old man who presented right third cranial nerve palsy and hemiataxia, a rare condition known as Claude's syndrome.

Mycobacterium abscessus Infected Neutrophils as an In Vitro Model for Bronchiectasis. Neutrophils Prevent Mycobacterial Aggregation

No disponible

Experience with the potassium binder patiromer in hyperkalaemia management in heart failure patients in real life.

AIMS: Hyperkalaemia (HK) is common in heart failure (HF) patients, related to renal dysfunction and medical treatment. It limits medical therapy optimization, which impacts prognosis. New potassium (K) binders help control HK, allowing better medical management of HF. METHODS AND RESULTS: A retrospective multicentre register included all outpatients with HF and HK (K ≥ 5.1 mEq/L) treated with patiromer according to current recommendations. We evaluated analytic and clinical parameters before starting the treatment and at 7, 30 and 90 days, as well as adverse events related to patiromer and treatment optimization. We included 74 patients (71.6% male) with a mean age of 70.8 years (SD 9.2). Sixty-seven patients (90.5%) presented HK in the previous year. Forty patients (54.1%) underwent down-titration of a renin-angiotensin-aldosterone inhibitor (RAASi) or a mineralocorticoid receptor antagonist (MRA), and 27 (36.5%) stopped any of them due to HK. Initial K was 5.5 mEq/L (SD 0.6), with a significantly reduction at 7 days (4.9 mEq/L (SD 0.8); P < 0.001), maintained at 90 days (4.9 mEq/L (SD 0.8); P < 0.001). There were no other electrolyte disturbances, with a slight improvement in renal function [glomerular filtration rate 39.6 mL/min (SD 20.4) to 42.7 mL/min (SD 23.2); P = 0.005]. Adverse events were reported in 33.9% of patients, the most common being hypomagnesaemia (16.3%), gastrointestinal disturbances (14.9%) and HK (2.8%). Withdrawal of patiromer was uncommon (12.2%) due to gastrointestinal disturbances in 66.7% of cases. Nine patients (12.2%) started on a RAASi, and 15 patients (20.3%) on an MRA during the follow-up. Forty-five patients (60.8%) increased the dose of RAASi or MRA, increasing to target doses in 5.4 and 10.8% of patients, respectively. At 90 days, NTproBNP values were reduced from 2509.5 pg/mL [IQR 1311-4,249] to 1396.0 pg/mL [IQR 804-4263]; P = 0.003, but the reduction was only observed in those who optimized HF medical treatment [NTproBNP from 1950.5 pg/mL (IQR 1208-3403) to 1349.0 pg/mL (IQR 804-2609); P < 0.01]. NYHA functional class only improved in 7.5% of patients, corresponding with those who optimized HF medical treatment. Compared with the previous 3 months before patiromer treatment, the rate of hospitalization was reduced from 28.4 to 10.9% (P < 0.01), and the emergency room visits from 18.9 to 5.4% (P < 0.01). CONCLUSIONS: In a real-life cohort of patients with HF, patiromer reduced and maintained K levels during 3 months of follow-up. The most common adverse events were hypomagnesaemia and gastrointestinal disturbances. Patiromer helps optimize medical treatment, increasing the percentage of patients treated with RAASi and MRA at target doses. At the end of follow-up, natriuretic peptides values and hospital visits were reduced, suggesting the benefit of optimizing HF medical treatment.

Increased serum concentrations of estrogen-induced growth factors Midkine and FGF2 in NF1 patients with plexiform neurofibroma.

Neurofibromatosis type 1 (NF1) predisposes to the development of dermal and plexiform neurofibromas and serum of NF1 patients stimulates neurofibroma proliferation in vitro. This study aimed to determine whether, in NF1 patients, serum levels of midkine (MK) and fibroblast growth factor 2 (FGF2) were associated with the number and/or type of neurofibromas. In addition, their concentrations were correlated with serum levels of dehydroepiandrosterone sulfate (DHEAS), a neurosteroid secreted by the peripheral nervous system. We performed a case control-study and measured, by ELISA assay, serum concentrations of MK, FGF2, and DHEAS in 20 NF1 patients and 30 controls. We found increased serum levels of MK and FGF2 in NF1 patients between 30 and 50 years old. Their concentrations were significantly higher in NF1 patients with plexiform neurofibromas than in controls (P=0.003 for MK and P=0.008 for FGF2). As an underlying hormonal regulation was suspected, DHEAS serum levels were measured but no difference was observed between patients and controls. We also observed a strong association between MK and FGF2 levels (P=0.0001) in NF1 patients and controls. In conclusion, we point out MK and FGF2 as biomarkers for plexiform neurofibroma in NF1 patients. As both growth factors are estrogen-responsive genes and neurofibromin is a co-repressor of estrogen receptor alpha activity, we suggest that the increased serum levels of MK and FGF2 observed in NF1 patients might be due to estradiol hypersensitivity.

Frailty and prognosis of older patients with chronic heart failure.

INTRODUCTION AND OBJECTIVES: Heart failure (HF) is prevalent in advanced ages. Our objective was to assess the impact of frailty on 1-year mortality in older patients with ambulatory HF. METHODS: Our data come from the FRAGIC study (Spanish acronym for "Study of the impact of frailty and other geriatric syndromes on the clinical management and prognosis of elderly outpatients with heart failure"), a multicenter prospective registry conducted in 16 Spanish hospitals including outpatients ≥ 75 years with HF followed up by cardiology services in Spain. RESULTS: We included 499 patients with a mean age of 81.4±4.3 years, of whom 193 (38%) were women. A total of 268 (54%) had left ventricular ejection fraction <40%, and 84.6% was in NYHA II functional class. The FRAIL scale identified 244 (49%) pre-frail and 111 (22%) frail patients. Frail patients were significantly older, were more frequently female (both, P <.001), and had higher comorbidity according to the Charlson index (P=.017) and a higher prevalence of geriatric syndromes (P <.001). During a median follow-up of 371 [361-387] days, 58 patients (11.6%) died. On multivariate analysis (Cox regression model), frailty detected with the FRAIL scale was marginally associated with mortality (HR=2.35; 95%CI, 0.96-5.71; P=.059), while frailty identified by the visual mobility scale was an independent predictor of mortality (HR=2.26; 95%CI, 1.16-4.38; P=.015); this association was maintained after adjustment for confounding variables (HR=2.13; 95%CI, 1.08-4.20; P=.02). CONCLUSIONS: In elderly outpatients with HF, frailty is independently associated with mortality at 1 year of follow-up. It is essential to identify frailty as part of the comprehensive approach to elderly patients with HF.

[Claude syndrome: Incomplete third cranial nerve palsy and contralateral ataxia]. / Síndrome de Claude: III par incompleto y ataxia contralateral.

Midbrain strokes are rare and are usually accompanied by other concomitant injuries. The simultaneous presence of ipsi and contralateral signs makes it necessary to think of a brainstem syndrome due to involvement of the brainstem. Magnetic nuclear resonance is the study of choice to characterize and locate the lesion. We report the case of a 71-year old man who presented right third cranial nerve palsy and hemiataxia, a rare condition known as Claude's syndrome.

Los accidentes cerebrovasculares mesencefálicos son poco frecuentes y por lo general están acompañados de otras lesiones concomitantes. La presencia simultánea de signos ipsi y contralaterales obliga a pensar en un síndrome alterno por compromiso del tronco encefálico. La resonancia magnética nuclear es el estudio de elección para caracterizar y localizar la lesión. Presentamos el caso de un hombre de 71 años que sufrió parálisis del tercer par derecho y hemiataxia izquierda, cuadro infrecuente, conocido como síndrome de Claude.

Mycobacterium avium complex infected cells promote growth of the pathogen Pseudomonas aeruginosa.

Bronchiectasis is considered a consequence of the neutrophilic inflammatory response to infection. Mycobacterial infections, mainly from the Mycobacterium avium complex and M. abscessus, have been inextricably linked to bronchiectasis development. The most important pathogen that infect patients with bronchiectasis is Pseudomonas aeruginosa, associated with an increased risk of death. Patients with bronchiectasis are often co-infected with P. aeruginosa and M. avium complex, and it was studied whether they interacted in immune cell cultures. Peripheral blood mononuclear cells from healthy volunteers were infected overnight with clinical isolates of mycobacteria, 18 h later co-infected with P. aeruginosa and Pseudomonas multiplication was quantified. Inoculated P. aeruginosa multiply faster when cells were previously infected in vitro with M. avium complex or M. tuberculosis, but not with M. kansasii or M. gordonae, mycobacteria not regularly isolated from patients with bronchiectasis. The interaction between mycobacteria and P. aeruginosa also takes place in the absence of cells, but to a lower degree. Growth of Staphylococcus aureus, less frequently co-isolated with mycobacteria, was not affected by previous infection with mycobacteria. Surprisingly, multiplication of P. aeruginosa in neutrophil cultures did not vary in the presence of mycobacteria. Nevertheless, co-infection of mycobacteria and P. aeruginosa induced the production of IL-1ß, a mediator of neutrophilic inflammation. P. aeruginosa stimulation by mycobacteria provides evidence for explaining their common clinical association. Strategies to control mycobacteria may be useful to impair P. aeruginosa colonization.

Effect of high intensity ultrasound on main bioactive compounds, antioxidant capacity and color in orange juice.

Ultrasound is a useful alternative to thermal processing that can be applied to many food products and juices to aid with enzymes and microorganism inactivation and to improve the efficiency of unit operations generally applied in the food industry. The aim of this study was to evaluate the effect of a high-intensity sonication treatment (frequency 20 kHz; intensity 39.4 W/cm2) applied for treatment times from 0 to 105 min on the content of polyphenols, vitamin C, organic acids, and carotenoids, and on the hydrophilic and lipophilic antioxidant capacity and color of orange juice. Treatments were performed in triplicate and data was statistically analyzed. Sonication time did not have a significant effect (P > 0.05) on total polyphenols, total vitamin C, organic acid, and carotenoid contents, lipophilic antioxidant capacity, or juice color. The hydrophilic antioxidant activity and the lutein content increased significantly (P < 0.05) with increased sonication time. These results may be useful as a baseline for the development of sonication treatments that could be used in combination with other traditional and emerging processing approaches to protect the most important bioactive compounds and quality properties of orange juice.

Gastritis enfisematosa como manifestación de isquemia mesentérica no oclusiva tras coartectomía / Emphysematous gastritis as a manifestation of non-occlusive mesenteric ischemia after coartectomy

Resumen Las intervenciones mayores en cirugía cardiovascular de pacientes con patología aórtica pueden traer como consecuencia el compromiso de la perfusión de órganos distantes al sitio de la cirugía, siendo el tracto gastrointestinal uno de los más sensibles a los cambios hemodinámicos, en especial en grupos extremos de edad con un alto riesgo de morbimortalidad. Se reporta el caso de una lactante con antecedente de síndrome de Turner, quien es llevada a corrección de coartación de aorta más hipoplasia del arco, presentando como complicación posoperatoria un cuadro de gastritis enfisematosa con compromiso sistémico, proceso que fue favorecido por bajo gasto cardiaco posterior a bomba y presencia de urosepsis temprana, todo lo cual fue interpretado como parte del espectro del síndrome de isquemia mesentérica no oclusiva. Su diagnóstico precoz hizo posible una pronta intervención, consistente en soporte nutricional parenteral, freno ácido, antibioticoterapia de amplio espectro y seguimiento radiológico estricto, logrando la resolución completa de su sintomatología, sin complicaciones a corto plazo. Este caso demuestra que la identificación de factores de riesgo de isquemia esplácnica, una alta sospecha clínica y un cuidadoso manejo médico permiten un desenlace favorable para una patología con una alta tasa de mortalidad y muy pocos casos reportados en población pediátrica.

Abstract Major interventions in cardiovascular surgery of patients with aortic pathology can result in the compromise of perfusion of organs distant from the surgery site, the gastrointestinal tract being one of the most sensitive to hemodynamic changes, especially in extreme age groups with a high risk of morbidity and mortality. The case of a young infant is reported, with a history of Turner syndrome, who is led to correction of aortic coarctation plus arch hypoplasia, presenting as a postoperative complication a picture of emphysematous gastritis with systemic compromise, a process that was favored by low cardiac output post-pump and the presence of early urosepsis, all of which was interpreted as part of the spectrum of non-occlusive mesenteric ischemia syndrome. Its early diagnosis made possible a prompt intervention consisting of parenteral nutritional support, acid brake, broad-spectrum antibiotic therapy and strict radiological follow-up, achieving complete resolution of her symptoms, without short-term complications. This case demonstrated that the identification of risk factors for splanchnic ischemia, a high clinical suspicion and careful medical management, allowed a favorable outcome for a disease with a high mortality rate and very few cases reported in the pediatric population.

SGLT2 inhibitors and GLP1 agonists administered without metformin compared to other glucose-lowering drugs in patients with type 2 diabetes mellitus to prevent cardiovascular events: A systematic review.

OBJECTIVES: To assess the efficacy of glucagon-like peptide-1 receptor agonists (GLP1-RAs) and sodium-glucose co-transporter 2 (SGLT2) inhibitors, administered without metformin on cardiovascular outcomes in type 2 diabetes patients. METHODS: A systematic review was performed according to Cochrane's methodological standards. We included randomized clinical trials (RCTs) on adult type 2 diabetes patients, assessing the efficacy of SGLT2 inhibitors and GLP1-RAs compared to other glucose-lowering drugs and/or RCTs that presented data of a subgroup of type 2 diabetes patients without metformin use at baseline. The main outcome was the reduction of the risk of any major adverse cardiovascular events (MACE) reported individually or as a composite outcome. RESULTS: Five RCTs including 50,725 type 2 diabetes patients, of whom 10,013 had not received metformin, were included in this meta-analysis. Three of these studies assessed the efficacy of GLP1-RAs and two of SGLT2 inhibitors. In patients without metformin at baseline, GLP1-RAs in comparison with placebo reduced the risk of MACE significantly by 20% (HR: 0.80; 95% CI: 0.71-0.89). SGLT2 inhibitors also significantly reduced the risk of MACE by 32% (HR: 0.68; 95% CI: 0.57-0.81). CONCLUSIONS: SGLT2 inhibitors and GLP1-RAs provided without metformin at baseline may reduce the risk of MACE in comparison with placebo in type 2 diabetes patients at increased risk of cardiovascular events.