[2022 Practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension]. / Guía práctica sobre el diagnóstico y tratamiento de la hipertensión arterial en España, 2022. Sociedad Española de Hipertensión - Liga Española para la Lucha contra la Hipertensión Arterial (SEH-LELHA).

Hypertension is the most important risk factor for global disease burden. Detection and management of hypertension are considered as key issues for individual and public health, as adequate control of blood pressure levels markedly reduces morbidity and mortality associated with hypertension. Aims of these practice guidelines for the management of arterial hypertension of the Spanish Society of Hypertension include offering simplified schemes for diagnosis and treatment for daily practice, and strategies for public health promotion. The Spanish Society of Hypertension assumes the 2018 European guidelines for management of arterial hypertension developed by the European Society of Cardiology and the European Society of Hypertension, although relevant aspects of the 2017 American College of Cardiology/American Heart Association guidelines and the 2020 International Society of Hypertension guidelines are also commented. Hypertension is defined as a persistent elevation in office systolic blood pressure ≥ 140 and/or diastolic blood pressure ≥ 90 mmHg, and assessment of out-of-office blood pressure and global cardiovascular risk are considered of key importance for evaluation and management of hypertensive patients. The target for treated blood pressure should be < 130/80 for most patients. The treatment of hypertension involves lifestyle interventions and drug therapy. Most people with hypertension need more than one antihypertensive drug for adequate control, so initial therapy with two drugs, and single pill combinations are recommended for a wide majority of hypertensive patients.

Do Innovation Metrics Reflect Sustainable Policy Making in Europe? A Comparative Study Case on the Carpathian and Alpine Mountain Regions

This paper questions the evaluation of innovation systems and innovation measurements and the effectiveness of innovation policies applied at the territorial level by assessing whether the existing European regional scoreboard is effective in providing accurate inputs for decision-makers in mountainous regions. The aim of the research is to provide, through comparative analysis by using statistical multi-methods of two mountainous macro-regions (the Alps and the Carpathians), a possible and available path to develop novel perspectives and alternative views on innovation systems' performance for informed and territorial-based policy making by using the indicators of the Regional Innovation Scoreboard. The methodology used includes descriptive statistics, chi-square bivariate test, Student's t test, one-way ANOVA with Bonferroni post hoc multiple comparisons, multilinear regression analysis, and decision tree with CRT (classification and regression trees) algorithm. Our results emphasize the similarities and differences between the Alpine and Carpathian mountain regions, find the best predictors for each mountain region, and provide a scientific basis for the development of a holistic approach linking measurement theory, innovation systems, innovation policies, and their territorial approach toward sustainable development of mountain areas. The paper's contribution is relevant in the context of remote, rural, and mountain areas, which are usually left behind in terms of innovation chances and in the context of the COVID-19 aftermath with budget constraints. The present results are pertinent for designing effective smart specialization strategies in these regions due to the difficulties that most remote areas and less developed regions are facing in developing innovation policies. © 2023 by the authors.

Hemoperfusion With Seraph-100 Is Not Associated With Improved Survival in Severe COVID-19 Patients

Background: Seraph-100 Blood Filter (ExThera Medical) is a hemoperfusion device designed to treat bloodstream infections. Its membrane binds pathogens, reducing bacterial and viral blood titers. The device received an authorization for emergency use in critically-ill COVID-19 patients by the FDA. We summarize the efficacy and safety profile of the device in a sample of COVID-19 ICU patients. Method(s): 25 consecutive COVID-19 patients admitted in the ICU between Nov 2021 and Feb 2022 were retrospectively reviewed. 11 patients received a single treatment with Seraph-100 plus standard care. Subjects in the control group received standard care only. Result(s): We found no differences between groups regarding age, sex or comorbidities. Treatment with Seraph was well tolerated and was associated with no modifications of leukocyte count or CRP levels. No differences regarding in-hospital mortality (LR=0.37;P=0.54) or length of ICU stay were observed. Patients treated with Seraph suffered Gram-positive associated pneumonia less frequently. Conclusion(s): Seraph hemoperfusion was not associated with better results in our sample. This may be due to small sample size and high heterogeneity present in parameters such as disease severity, other complications, length of ICU stay or hemoperfusion dosage. To improve results it is necessary to better define the most appropriate timing and dosage for each case.

COVID-19 DISEASE SEVERITY AND RISK OF 12-MONTH CKD PROGRESSION

BACKGROUND AND AIMS: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has been in our daily practice for almost 2 years now. Since the beginning of the pandemic, we have aimed to study its most immediate effects on patients to find the best line of treatment or, at least, mitigate its worst outcomes. Nevertheless, we also know some long-term health consequences such as fatigue, sleep difficulties, headache, among others, but its long-term kidney effects are not entirely clear yet. The aim of this study was to describe if coronavirus disease's (COVID- 19) severity increases the risk of chronic kidney disease (CKD) progression after a previous hospitalization and observe if there are any additional risk factors that could help us predict this outcome. METHOD: In this study, a sample of consecutive patients who required admission due to COVID-19 during the first wave of the pandemic (from March to May of 2020) was recruited. Patients were followed for 12 months since initial admission. The composite outcome of the study included either death or CKD progression. CKD progression was defined as incremental progression to a higher KDIGO CKD stage compared to baseline pre COVID-19 renal function [(in mL/min/1.73 m2): estimated glomerular filtration rate (eGFR) ≥60;stage 3a: 45-59;stage 3b: 30-44;stage 4: 15-29;stage 5: <15], or dialysis initiation. Cardiovascular disease was defined as a history of myocardial infarction, stroke, or peripheral vascular disease. Chronic lung diseases included asthma, chronic obstructive pulmonary disease and chronic bronchitis. RESULTS: The sample was composed of 93 patients, of which 14 (15.1%) died during follow-up. Of those alive 12 months after initial admission, 17 (21.5%) suffered CKD progression. No patient required renal replacement therapy. Patients that suffered the composite outcome presented a higher prevalence of cancer, tended to be slightly older and suffered from additional comorbidities more frequently (Table). In multivariate logistic regression analysis, previous history of CKD [odds ratio (OR): 1.066 (0.433- 2.624);P = 0.889], severe or critical COVID-19 on admission [OR: 0.657 (0.24-1.8);P =0.414] or ICU admission [OR: 0.986 (0.082-11.898);P = 0.991] failed to predict the composite outcome. CONCLUSION: Our main hypothesis was that COVID-19 sequelae should be due to an exaggerated activation of the immune system against the virus. Thus, patients that suffered severe COVID-19 should be expected to develop more long-term health consequences of the infection when compared with those with milder disease. However, we failed to prove any link between COVID-19 severity and long-term CKD progression. History of CKD or ICU admission was also unable to predict the composite outcome. Previous studies have described a relationship between COVID-19 severity and adverse renal outcomes, a relationship that we failed to observe. These discrepancies could be due to the small sample size of our study and the different definition of CKD progression applied. In addition, age could act as a potential modifier of CKD progression after admission due to COVID. More studies are required to further clarify the mechanisms and long-term renal consequences of COVID-19 and define potential lines of treatment. (Table Presented).

INCIDENCE OF AKI AMONG HOSPITALIZED COVID-19 PATIENTS DURING THE FIRST AND SIXTH WAVES OF THE PANDEMIC

BACKGROUND AND AIMS: During the last 2 years, we have witnessed several waves of the COVID-19 pandemic characterized by massive infections among the general population, sudden increases in the number of hospitalizations and variable rates of complications and mortality among patients. Acute kidney injury (AKI) has been described as a common and serious complication of COVID-19. However, multiple factors that are involved in the development of this complication have been modified throughout these months, including the appearance of new variants of the virus, the modification of treatment protocols or the advancement of vaccination among the general population. In this study, we aimed to compare the rates of AKI among patients who required admission due to COVID-19 in the first and current (sixth) waves of the pandemic. METHOD: Consecutive patients that required admission due to COVID-19 in a tertiary referral hospital during the first (March to May 2020) and current (December 2021) waves of the pandemic were enrolled in the study. Patient characteristics, rates of AKI incidence, 28-day mortality and in-hospital length of stay were compared between groups. Viral infection was confirmed by real-time RT-qPCR in all cases. AKI was defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines using peak serum creatinine and acute dialysis criteria. Multivariate logistic regression was performed to define potential predictors of AKI. RESULTS: Table 1 summarizes demographic and clinical characteristics among enrolled patients. Compared with the current wave, patients admitted during the first wave were older, had higher baseline serum creatinine and lower baseline eGFR. During the first wave, patients presented higher peak serum creatinine values and a higher incidence of in-hospital AKI. Age, male sex, hypertension, diabetes, CKD and pandemic wave were included in multivariate logistic regression analysis as potential predictors of AKI. Only past history of hypertension [OR 2.867;95% confidence interval (95% CI) 1.279-6.424;P-value: .011] and CKD (OR 2.418;95% CI 1.237-4.73;P-value: .01) independently predicted AKI in the sample. CONCLUSION: Despite multiple changes that have occurred throughout the pandemic, including new treatment protocols, the appearance of new variants of the virus with different clinical profiles or the extensive application of vaccines, these changes have not translated into a significant decrease in the risk of AKI among patients admitted due to COVID-19, which appears to still be conditioned mainly by comorbidities of each patient, including past history of CKD. (Table Presented).

COVID-19 in patients on kidney replacement therapy-clinical characteristics at triage associated with admission, readmission and Shortterm outcomes

BACKGROUND AND AIMS: Patients on kidney replacement therapy (KRT) are at high risk of developing severe COVID-19 illness and often require high intensity care and utilisation of hospital resources. During the ongoing pandemic, the optimal care pathway and triage for KRT patients presenting with varying severity of COVID-19 illness is unknown. We studied clinical factors and outcomes associated with admission, readmission and short-term outcomes. METHOD: Data from the European Renal Association COVID-19 Database (ERACODA) was analysed. This database includes granular data on dialysis patients and kidney transplant recipients with COVID-19 from all over Europe. The clinical and laboratory features at first presentation of hospitalized and non-hospitalized patients and those who returned for second presentation were studied. In addition, possible predictors of outcome in those who were not hospitalized at first presentation were identified. RESULTS: Among 1,423 KRT patients (haemodialysis;1017/kidney transplant;406) with COVID-19, 25% (n=355) were not hospitalized at first presentation. Of them, only 10% (n=36), presented for a second time in the hospital. The median interval between the first and second presentation was 5 days (Interquartile interval: 2-7 days). Patients who re-presented had worsening of pulmonary symptoms, a fall in oxygen saturation (97% to 90%), and an increase in C-reactive protein (26 mg/L to 73 mg/L) between their attendances. Patients who re-presented after initial assessment were older (72 vs. 63 years) and initially more often had pulmonary symptoms and abnormalities on lung imaging compared with those who did not present for a second time. The 28-day mortality rate of patients admitted at the second presentation was similar to that of patients admitted at first presentation (26.5% vs. 29.7%, p=0. 61). Among patients who were not hospitalized at first presentation (mortality 6%), age, prior smoking, clinical frailty scale, and shortness of breath at first presentation were identified as predictors of mortality. CONCLUSION: KRT patients with COVID-19 and mild pulmonary abnormalities and no signs of pulmonary insufficiency can be safely returned without hospitalization. These patients should be advised to seek immediate contact when they develop respiratory distress. Our findings provide support for a risk-stratified clinical approach to admissions of KRT patients presenting with COVID-19. The study findings may be valuable for clinical triage and optimising hospital capacity utilisation during the ongoing pandemic.

Male sex is associated with in-hospital death in non-dialysis CKD patients with COVID-19

BACKGROUND AND AIMS: Coronavirus disease (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus 2 (SARS-CoV-2) can lead to significant organ injury. CKD has been associated with increased mortality in previous epidemics, and male sex has been correlated with worse outcomes during COVID-19 in the general population. Our aim was to describe the differential effect of sex as a risk factor for in-hospital mortality among non-dialysis CKD subjects. METHOD: Multicenter, observational cohort study including 136 adult patients with CKD and 136 age- and sex-matched controls who required admission for COVID-19 in three academic hospitals in Spain. Viral infection was confirmed by real-time RTqPCR and/or serologic testing in all cases. Disease severity on admission was classified according to the WHO-China Joint Mission Report on COVID-19. The presence of CKD was defined as sustained eGFR <60 and >15 ml/min/1.73m2 within the 6 months prior to COVID-19 hospitalization. Demographic and clinical data were gathered from medical records. Outcomes were recorded during the following 28 days after admission. We applied Cox proportional hazards models, adjusted for age, sex, hypertension, diabetes and severe or critical disease at presentation. RESULTS: Due to the matched design, no differences were found regarding age and sex between cohorts. CKD patients suffered more frequently from hypertension and diabetes and presented higher 28-day mortality after hospital admission due to COVID-19 compared with age- and sex-matched controls (40.4 vs. 24.3%;P=0.004). In adjusted Cox regression analysis among CKD patients, only age (HR: 1.087, 95% CI: 1.047-1.128) and male sex (HR: 1.883, 95% CI: 1.045-3.391) were independent predictors of 28-day mortality. Comparatively, among patients without CKD, only age acted as an independent predictor for 28-day mortality (HR: 1.082, 95% CI: 1.033- 1.133). None of the variables included in adjusted regression was able to predict ICU admission in any of the cohorts. CONCLUSION: Male sex is associated with increased mortality, but not with ICU admission, after hospitalization due to COVID-19 among non-dialysis CKD patients. That effect was not observed among hospitalized controls without CKD.

Risk factors for aki during COVID-19 among nondialysis CKD patients

BACKGROUND AND AIMS: AKI is a strong risk factor for adverse outcomes during Coronavirus disease (COVID-19) in the general population. CKD has been correlated with increased risk of AKI both in the outpatient and inpatient settings. We aimed to define potential risk factors for AKI among patients with non-dialysis CKD admitted due to COVID-19. METHOD: Multicenter, observational cohort study including 136 adult patients with CKDand 136 age- and sex-matched controls who required admission for COVID-19 in three academic hospitals. Viral infection was confirmed by real-time RT-qPCR and/or serologic testing in all cases. Disease severity on admission was classified according to the WHO-China Joint Mission Report on COVID-19;briefly subjects with COVID- 19 were divided into mild (laboratory confirmed, without pneumonia), moderate (laboratory confirmed with pneumonia), severe (dyspnea and/or lung infiltrates >50% of the lung field within 24-48 h) and critical (respiratory failure requiring mechanical ventilation, shock, or other organ failure that requires intensive care). AKI was defined using the 2012 KDIGO classification. CKD was defined as sustained eGFR <60 and >15 ml/min/1.73m2 within the 6 months prior to COVID-19 hospitalization. Baseline eGFR was calculated using the CKD-EPI equation. Demographic and clinical data were gathered from medical records. Outcomes were recorded during the following 28 days after admission. We applied logistic regression analysis to describe potential predictors for AKI. RESULTS: Median age was 80 years (IQR: 70-86). 58.8% of patients were males. The most common symptom on admission was fever (68.8%), followed by cough (57.7%). The majority of subjects presented with severe COVID-19 on admission (75.7%). During 28-day follow-up, 87 patients (32%) developed Stage 1 AKI, 17 subjects (6.3%) developed Stage 2 AKI and 12 patients (4.4%) developed Stage 3 AKI. AKI was more frequent (61 vs 24.3%) and more severe (Stage 2 AKI: 10.3 vs 2.2%;Stage 3 AKI: 6.6 vs 2.2%) among CKD patients. In adjusted logistic regression analysis, only disease severity and baseline eGFR were independent predictors for AKI in COVID-19 patients that required hospitalization. CONCLUSION: CKD patients suffer AKI more frequently and of higher severity during COVID-19. Baseline eGFR, along with COVID-19 severity, are strong predictor factors of AKI in this setting.

Description of the inflammatory profile with 45 cytokines according to ABO blood group in COVID- 19 and its implications on severity and mortality

Background: Severe acute respiratory syndrome coronavirus 2 (SARSCoV- 2) is currently one of the worst pandemics ever. ABO blood groups are associated with different risk of viral infections and they could also play a role in COVID-19 disease. In vitro, studies demonstrated how anti-A and B antibodies neutralized the infectious capacity of SARSCoV- 2. Both SARS-CoV-2 and antibodies let a strong competitive inhibition of angiotensin converting enzyme 2 (ACE2). Those biological mechanisms could be associated with the lower risk of severity and mortality in blood group O patients. Aims: Prospectively perform a cytokine array in plasma samples from COVID-19 patients who were stratified based on their bloody type, in order to describe the inflammatory response and provide a further insight about the possible protective mechanisms elicited by the blood type O. Methods: Prospective and consecutive study including blood samples from 108 adult patients diagnosed with COVID-19 and admitted to the "Hospital Clínico Universitario" (Valladolid, Spain) between March 24 to April 11, 2020. Percentage distribution of ABO blood type correspond to 54.6%, 9.3%, 3.7% and 32.4% for A, B, AB and O group respectively. Patients were divided into 2 groups: i. Blood type O (n=35);ii. Blood types A/B/AB (n=73). Forty-five Cytokines, Chemokines and Growth Factors were measured in duplicate for each patient using a MAGPIX system (Luminex). Statistical analysis was performed using the R statistical package version 4.0.2. Results: In both groups, most frequent comorbidities were hypertension, diabetes and chronic obstructive pulmonary disease. According to analytical profile, blood type O displayed higher lymphocytes (p=0.057) and lower total bilirubin (p=0.009) plasma levels than the A/B/AB group. We found a lower risk (2.16 times) of mechanical ventilation or death in patients with blood type O [Log Rank: p=0.042, Hazard Ratio: 0.463, CI 95% (0.213-1.004), p=0.050]. Moreover, 15 cytokines were over-express (and 1 under-expressed) in blood type O (Image upload. Left boxplots: Group A/B/AB. Right Box-plots: Group O). Last, a multivariate model found BDNF, IL-13 and IL-27 as the best cytokines able to differentiate the immune profile based on the blood type. Discussion: In first place, blood type of the general population covered by our hospital are 42%, 9%, 4% and 47% for blood types A, B, AB and O respectively. Nevertheless, our cohort found increase blood type A (54.6%) and decrease in blood type O (32.4%). Therefore, and according our results, blood type O was not only associated to a lower risk of mortality or mechanical ventilation, but also to the need of hospital admission. In second place, a strong ACE2 downregulation - competitive inhibition of ACE2 by SARS-CoV-2 and anti-A and B antibodies - associates high Ang-II plasma levels which allows the production of inflammatory cytokines and, at the same time, a possible lower infectious capacity by SARS-CoV-2 in O blood type patients. Moreover, the existence of a higher activation status of the immune system could also let a rapid activation of the immune response in patients with the O blood type and associate a quicker viral clearance. Summary/Conclusion: Our cohort showed how blood type O associated with both lower rates of hospital admission and lower risk of intubation or death. Indeed, these patients produced higher amounts of cytokines in response to SARS-CoV-2, hence mounting an effective immune response which allowed them to control the viral infection and therefore decrease the risk of further complications.