Circulating endocannabinoid levels in SARS-CoV-2 infection and their potential role in the inflammatory response.

Plasma levels of endocannabinoids (eCBs) are very dynamic and variable in different circumstances and pathologies. The aim of the study was to determine the levels of the main eCBs and N-acylethanolamines (NAEs) in COVID-19 patients during the acute and post-acute phase of SARS-CoV-2 infection. Samples collected before December 31, 2020 were used for the determination of circulating eCB levels by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The association between plasma eCB measurements and biochemical and hematological parameters, as well as serum IL-6 levels, was evaluated. Samples of 64 individuals were analysed, n = 18 healthy donors, n = 30 acute, and n = 16 post-acute patients. Plasma levels of 2-arachidonoylglycerol (2-AG), were significantly elevated in COVID-19 patients when compared to healthy individuals. Plasma N-palmitoylethanolamide (PEA) and N-arachidonoylethanolamide (AEA) levels were found to be decreased in post-acute patient samples. These results suggest that 2-AG plays an important role in the inflammatory cascade in COVID-19 disease; in addition, eCBs might be involved in the post-acute pathogenesis of COVID-19. This study provides evidence of altered levels of circulating eCBs as a consequence of SARS-CoV-2 infection.

Consensus on lipoprotein(a) of the Spanish Society of Arteriosclerosis. Literature review and recommendations for clinical practice. / Consenso sobre lipoproteína (a) de la Sociedad Española de Arteriosclerosis. Revisión bibliográfica y recomendaciones para la práctica clínica.

The irruption of lipoprotein(a) (Lp(a)) in the study of cardiovascular risk factors is perhaps, together with the discovery and use of proprotein convertase subtilisin/kexin type 9 (iPCSK9) inhibitor drugs, the greatest novelty in the field for decades. Lp(a) concentration (especially very high levels) has an undeniable association with certain cardiovascular complications, such as atherosclerotic vascular disease (AVD) and aortic stenosis. However, there are several current limitations to both establishing epidemiological associations and specific pharmacological treatment. Firstly, the measurement of Lp(a) is highly dependent on the test used, mainly because of the characteristics of the molecule. Secondly, Lp(a) concentration is more than 80% genetically determined, so that, unlike other cardiovascular risk factors, it cannot be regulated by lifestyle changes. Finally, although there are many promising clinical trials with specific drugs to reduce Lp(a), currently only iPCSK9 (limited for use because of its cost) significantly reduces Lp(a). However, and in line with other scientific societies, the SEA considers that, with the aim of increasing knowledge about the contribution of Lp(a) to cardiovascular risk, it is relevant to produce a document containing the current status of the subject, recommendations for the control of global cardiovascular risk in people with elevated Lp(a) and recommendations on the therapeutic approach to patients with elevated Lp(a).

SEA 2024 Standards for Global Control of Vascular Risk. / Estándares de la Sociedad Española de Arteriosclerosis 2024 para el control global del riesgo vascular.

One of the objectives of the Spanish Society of Arteriosclerosis is to contribute to the knowledge, prevention and treatment of vascular diseases, which are the leading cause of death in Spain and entail a high degree of disability and health expenditure. Atherosclerosis is a multifactorial disease and its prevention requires a global approach that takes into account the associated risk factors. This document summarises the current evidence and includes recommendations for patients with established vascular disease or at high vascular risk: it reviews the symptoms and signs to evaluate, the laboratory and imaging procedures to request routinely or in special situations, and includes the estimation of vascular risk, diagnostic criteria for entities that are vascular risk factors, and general and specific recommendations for their treatment. Finally, it presents aspects that are not usually referenced in the literature, such as the organisation of a vascular risk consultation.

Modified SADI-S in non-obese diabetic rats: Description of the surgical technique.

Background: Single anastomosis duodenoileal bypass with sleeve gastrectomy (SADI-S) is a predominantly malabsorptive technique that has shown excellent results in morbid obese patients. The aim of this study is to establish a rodent model modifying the SADI-S technique by performing a proximal duodenojejunal anastomosis. This model can be useful for the study of glucose metabolism without malabsorption observed after the SADI-S technique. Methods: Goto-Kakizaki rats, a genetic model of non-obese and non-hypertensive type 2 diabetes mellitus, that develop hyperglycemia at an early age was used. Surgery consisted in a sleeve gastrectomy, duodenojejunal anastomosis and duodenal exclusion using three different techniques: duodenal transection (DT), duodenal ligation with hem-o-lock (DLH), and duodenal ligation with suture (DLS). Surgery time, weight loss, morbidity and mortality were recorded. Results: A total of 16 animals were subjected to surgical intervention and overall mortality was 25 %, with the DT group showing the highest mortality rate (42.9 %). No differences were observed among groups in terms of weight loss. Conclusion: The surgical technique described in this work is feasible and reproducible. Weight loss is comparable regardless of the technique used for duodenal exclusion.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: what parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Neuropathic post-COVID pain symptomatology is not associated with serological biomarkers at hospital admission and hospitalization treatment in COVID-19 survivors.

Objective: Evidence suggests that individuals who had survived to coronavirus disease, 2019 (COVID-19) could develop neuropathic post-COVID pain. This study investigated the association of serological biomarkers and treatments received during hospitalization with development of neuropathic-associated symptoms. Methods: One hundred and eighty-three (n = 183) previously hospitalized COVID-19 survivors during the first wave of the pandemic were assessed in a face-to-face interview 9.4 months after hospitalization. Nineteen serological biomarkers, hospitalization data, and treatment during hospitalization were obtained from medical records. Neuropathic pain symptoms (Self-Report Leeds Assessment of Neuropathic Scale), sleep quality (Pittsburgh Sleep Quality Index), pain catastrophizing (Pain Catastrophizing Scale) and anxiety/depressive levels (Hospital Anxiety and Depression Scale) were assessed. Results: The prevalence of post-COVID pain was 40.9% (n = 75). Fifteen (20%) patients reported neuropathic symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence or not of neuropathic-associated symptoms. Patients with post-COVID pain had the highest neutrophil count, and post hoc analysis revealed that patients with neuropathic post-COVID associated symptoms had lower neutrophil count (p = 0.04) compared with those without neuropathic pain, but differences were small and possible not clinically relevant. No differences in fatigue, dyspnea, brain fog, anxiety or depressive levels, poor sleep, or pain catastrophism between patients with and without neuropathic symptoms were found. Conclusion: It seems that neuropathic-like post-COVID pain symptoms are not associated with neither of assessed serological biomarkers at hospital admission nor hospitalization treatments received in this cohort of hospitalized COVID-19 survivors.

Serological Biomarkers at Hospital Admission and Hospitalization Treatments Are Not Related to Sensitization-Associated Symptoms in Patients with Post-COVID Pain.

Current evidence suggests that a group of patients who had survived coronavirus disease, 2019 (COVID-19) and developed post-COVID pain can exhibit altered nociceptive processing. The role of serological biomarkers and hospitalization treatments in post-COVID pain is unclear. This study aimed to investigate the association of serological biomarkers and treatments received during hospitalization with sensitization-associated symptoms in COVID-19 survivors with post-COVID pain. One hundred and eighty-three (n = 183) patients who had been hospitalized due to COVID-19 in one urban hospital of Madrid (Spain) during the first wave of the pandemic were assessed in a face-to-face interview 9.4 (SD 3.4) months after hospitalization. Levels of 19 serological biomarkers, hospitalization data, and treatments during hospitalization were obtained from hospital records. Sensitization-associated symptoms (Central Sensitization Inventory, CSI), sleep quality (Pittsburgh Sleep Quality Index, PSQI), pain catastrophism (Pain Catastrophizing Scale), and anxiety/depressive level (Hospital Anxiety and Depression Scale, HADS) were assessed. The prevalence of post-COVID pain was 40.9% (n = 75). Twenty-nine (38.6%) patients had sensitization-associated symptoms. Overall, no differences in hospitalization data and serological biomarkers were identified according to the presence of sensitization-associated symptoms. The analysis revealed that patients with sensitization-associated symptoms exhibited higher lymphocyte count and lower urea levels than those without sensitization-associated symptoms, but differences were small. Pain catastrophism and depressive levels, but not fatigue, dyspnea, brain fog, anxiety levels, or poor sleep, were higher in individuals with sensitization-associated symptoms. In conclusion, this study revealed that sensitization-associated post-COVID pain symptoms are not associated with serological biomarkers at hospital admission and hospitalization treatments received.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

The Spanish Scientific Societies before the ESC 2021 guidelines on vascular disease prevention: Generalizing the measurement of albuminuria to identify vascular risk and prevent vascular disease.

The 2021 guidelines on the prevention of vascular disease (VD) in clinical practice published by the European Society of Cardiology (ESC) and supported by 13 other European scientific societies recognize the key role of screening for chronic kidney disease (CKD) in the prevention of VD. Vascular risk in CKD is categorized based on measurements of estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (ACR). Thus, moderate CKD is associated with a high vascular risk and severe CKD with a very high vascular risk requiring therapeutic action, and there is no need to apply other vascular risk scores when vascular risk is already very high due to CKD. Moreover, the ESC indicates that vascular risk assessment and the subsequent decision algorithm should start with measurement of eGFR and ACR. To optimize the implementation of the ESC 2021 guidelines on the prevention of CVD in Spain, we consider that: 1) Urine testing for albuminuria using ACR should be part of the clinical routine at the same level as blood glucose, cholesterolemia, and GFR estimation when these are used to make decisions on CVD risk. 2) Spanish public and private health services should have the necessary means and resources to optimally implement the ESC 2021 guidelines for the prevention of CVD in Spain, including ACR testing.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories: What parameters should a basic lipid profile include?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Consensus document for lipid profile testing and reporting in Spanish clinical laboratories.

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Trajectory of Gastrointestinal Symptoms in Previously Hospitalized COVID-19 Survivors: The Long COVID Experience Multicenter Study.

This multicenter cohort study used Sankey plots and exponential bar plots to visualize the fluctuating evolution and the trajectory of gastrointestinal symptoms in previously hospitalized COVID-19 survivors during the first 18 months after acute SARS-CoV-2 infection. A total of 1266 previously hospitalized COVID-19 survivors were assessed at four points: hospital admission (T0), at 8.4 months (T1), at 13.2 months (T2), and at 18.3 months (T3) after hospitalization. Participants were asked about their overall gastrointestinal symptoms and particularly diarrhea. Clinical and hospitalization data were collected from hospital medical records. The prevalence of overall gastrointestinal post-COVID symptomatology was 6.3% (n = 80) at T1, 3.99% (n = 50) at T2 and 2.39% (n = 32) at T3. The prevalence of diarrhea decreased from 10.69% (n = 135) at hospital admission (T0), to 2.55% (n = 32) at T1, to 1.04% (n = 14) at T2, and to 0.64% (n = 8) at T3. The Sankey plots revealed that just 20 (1.59%) and 4 (0.32%) patients exhibited overall gastrointestinal post-COVID symptoms or diarrhea, respectively, throughout the whole follow-up period. The recovery fitted exponential curves revealed a decreasing prevalence trend, showing that diarrhea and gastrointestinal symptoms recover during the first two or three years after COVID-19 in previously hospitalized COVID-19 survivors. The regression models did not reveal any symptoms to be associated with the presence of gastrointestinal post-COVID symptomatology or post-COVID diarrhea at hospital admission or at T1. The use of Sankey plots revealed the fluctuating evolution of gastrointestinal post-COVID symptoms during the first two years after infection. In addition, exponential bar plots revealed the decreased prevalence of gastrointestinal post-COVID symptomatology during the first three years after infection.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe. METHODS: This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography. RESULTS: The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (P<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

Consensus document for lipid profile determination and reporting in Spanish clinical laboratories. What parameters should be included in a basic lipid profile? / Documento de consenso para la determinación e informe del perfil lipídico en laboratorios clínicos españoles: ¿Qué parámetros debe incluir un perfil lipídico básico?

Cardiovascular diseases (CVD) continue to be the main cause of death in our country. Adequate control of lipid metabolism disorders is a key challenge in cardiovascular prevention that is far from being achieved in real clinical practice. There is a great heterogeneity in the reports of lipid metabolism from Spanish clinical laboratories, which may contribute to its poor control. For this reason, a working group of the main scientific societies involved in the care of patients at vascular risk, has prepared this document with a consensus proposal on the determination of the basic lipid profile in cardiovascular prevention, recommendations for its realization and unification of criteria to incorporate the lipid control goals appropriate to the vascular risk of the patients in the laboratory reports.

Tenofovir Disoproxil Fumarate/Emtricitabine and Baricitinib for Patients at High Risk of Severe Coronavirus Disease 2019: The PANCOVID Randomized Clinical Trial.

BACKGROUND: This study was designed to evaluate if patients with high risk for severe coronavirus disease 2019 (COVID-19) would benefit from treatment with tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) followed by baricitinib in case of hypoxemia and systemic inflammation. METHODS: PANCOVID is an open-label, double-randomized, phase 3 pragmatic clinical trial including adults with symptomatic COVID-19 with ≥2 comorbidities or aged ≥60 years and was conducted between 10 October 2020 and 23 September 2021. In the first randomization, patients received TDF/FTC or no TDF/FTC. In the second randomization, patients with room air oxygen saturation <95% and at least 1 increased inflammatory biomarker received baricitinib plus dexamethasone or dexamethasone alone. The primary endpoint was 28-day mortality. Main secondary endpoint was 28-day disease progression or critical care unit admission or mortality. The trial was stopped before reaching planned sample size due to the decrease in the number of cases and a mortality rate substantially lower than expected. RESULTS: Of the 355 included participants, 97% were hospitalized at baseline. Overall, 28-day mortality was 3.1%. The 28-day mortality relative risk (RR) for participants treated with TDF/FTC was 1.76 (95% confidence interval [CI], .52-5.91; P = .379); it was 0.42 (95% CI, .11-1.59; P = .201) for those treated with baricitinib. The 28-day RR for the main secondary combined endpoint for participants treated with TDF/FTC was 0.95 (95% CI, .66-1.40; P = .774); it was 0.90 (95% CI, .61-1.33; P = .687) for those treated with baricitinib. CONCLUSIONS: Our results do not suggest a beneficial effect of TDF/FTC; nevertheless, they are compatible with the beneficial effect of baricitinib already established by other clinical trials. CLINICAL TRIALS REGISTRATION: EudraCT: 2020-001156-18.

Symptoms Experienced at the Acute Phase of SARS-CoV-2 Infection as Risk Factor of Long-term Post-COVID Symptoms: The LONG-COVID-EXP-CM Multicenter Study.

OBJECTIVE: This multicenter study investigated clinical risk factors associated with the number of long-term symptoms after COVID. METHODS: Clinical features, symptoms at hospital admission, hospitalization data, and the number of symptoms after COVID was systematically assessed for patients who recovered from COVID-19 in 4 hospitals in Madrid (Spain) from February 20 to May 31, 2020. RESULTS: Overall, 1,969 patients (46.5% women, age: 61, SD: 16 years) were randomly assessed 8.4 months (SD 1.5) after hospital discharge. Female gender (odds ratio [OR] 1.82, 95% confidence interval [CI] 1.57-2.10), number of morbidities (OR 1.182, 95% CI 1.08-1.29), number of symptoms at hospital admission (OR 1.309, 95% CI 1.15-1.49) and days at the hospital (OR 1.01, 95% CI 1.007-1.017) were associated (all, p <0.001) with more long-term symptoms after COVID. Further, vomiting (OR 1.78, 95% CI 1.26-2.52), throat pain (OR 1.36, 95% CI 1.02-1.81), diarrhea (OR 1.51, 95% CI 1.25-1.82), dyspnea (OR 1.20, 95% CI 1.01-1.41), or headache (OR 1.50, 95% CI 1.28-1.75) as symptoms at hospital admission were also associated (all, p <0.01) with a higher number of symptoms after COVID. CONCLUSION: This multicenter study found that a higher number of symptoms at hospital admission were the most relevant risk factor for developing more symptoms after COVID, supporting the assumption that a higher symptom load at the acute phase is associated with a greater likelihood of long-term symptoms after COVID.

Sustained low-density lipoprotein-cholesterol <70 mg/dl is associated with improved cardiovascular outcomes in the clinical setting.

BACKGROUND AND AIMS: Clinical trials have shown that intensive low-density lipoprotein cholesterol (LDL-C) lowering improves cardiovascular outcomes among patients with atherosclerotic cardiovascular disease (ASCVD), but data are limited in real clinical practice, particularly for patients with ASCVD informing different territories. METHODS: FRENA was a prospective registry of consecutive outpatients with coronary, cerebrovascular or peripheral artery disease. We compared the incidence of recurrent events in patients with sustained LDL-C levels <70 mg/dl compared with those with ≥70 mg/dl. RESULTS: As of December 2018, 1182 patients were eligible for this study. Among them, 172 (14.5%) had mean LDL-C levels ≤70 mg/dl, and 1010 (85.5%) had <70 mg/dl. Their clinical characteristics at baseline were similar. During 5 years of follow-up, 252 patients (21%) suffered major adverse cardiovascular events (MACE). The incidence rates of MACE were 3.42 events per 100 patient-years (95% confidence interval [95% CI] 2.17-5.14) in patients with levels <70 mg/dl and 5.57 (95% CI, 4.87-6.34) in those with ≥70 mg/dl; the rate ratio was 0.61 (95% CI, 0.39-0.92), p = 0.019. On multivariable analysis, patients with LDL-C levels <70 mg/dl were at lower risk for MACE (hazard ratio [HR]: 0.61 [95% CI, 0.39-0.93] p < 0.05). MACE reduction was driven by a decrease in coronary and peripheral events with no significant effect on stroke. CONCLUSIONS: Long-term sustained LDL-C <70 mg/dl in the clinical practice is associated with reduction in cardiovascular and peripheral vascular events with no apparent effect on stroke.