Effect of Diflunisal in Patients with Transthyretin Cardiomyopathy: A Pilot Study.

Background: ATTR-CM is becoming more prevalent, and disease-modifying therapy has been investigated in recent years with promising results. Diflunisal has shown TTR-stabilizing properties assessed by biomarkers and echocardiography, but there are no trials addressing the evolution of morphological changes with CMR. Methods and Results: AMILCA-DIFLU is an exploratory pilot study prospective, single-center, non-randomized, open-label clinical trial. Patients diagnosed with ATTR-CM underwent clinical, functional, biochemical and imaging assessment before and one year after diflunisal therapy initiation. Of the twelve ATTR-CM patients included, only nine patients completed treatment and study protocol in 12 months. To increase the sample size, we included seven real-world patients with one year of diflunisal treatment. Among the group of patients who completed treatment, diflunisal therapy did not show improvement in cardiac disease status as assessed by many cardiac and inflammatory biomarkers, 6MWT and CMR parameters after one year of treatment. However, a non-significant trend towards stabilization of CMR parameters such as LVEF, ECV and T2 at one year was found. When comparing the group of patients who completed diflunisal therapy and those who did not, a significant decrease in the distance performed in the 6MWT was found in the group of patients who completed treatment at one year (-14 ± 81.8 vs. -173 ± 122.2; p = 0.032). Diflunisal was overall well tolerated, showing only a statistically significant worsening in renal function in the group of diflunisal-treatment patients with no clinical relevance or need for treatment discontinuation. Conclusions: In patients with ATTR-CM, treatment with diflunisal was overall well tolerated and tended to stabilize or slow down amyloid cardiac disease progression assessed by CMR parameters, cardiac and inflammatory biomarkers and functional capacity.

Use and Benefit of Sacubitril/Valsartan in Elderly Patients with Heart Failure with Reduced Ejection Fraction.

Background: Heart failure (HF) is a highly prevalent syndrome in elderly subjects. Currently, multiple drugs have shown clinical benefits in patients with HF and reduced ejection fraction (HFrEF). However, evidence is scarce in elderly patients (beyond 75 years old), even more so for the latest drugs, such as angiotensin receptor-neprilysin inhibitors (ARNIs). This study aims to evaluate the use and benefits of ARNIs in elderly patients with HFrEF. Methods: A prospective observational cohort study was designed. Patients with left ventricular systolic dysfunction (defined by left ventricular ejection fraction [LVEF] < 40%) and age ≥ 75 years from January 2016 to December 2020 were prospectively included. Patients with an indication for ARNIs at inclusion or throughout follow-up were selected. Clinical, electrocardiographic and echocardiographic variables were collected. Results: A total of 616 patients were included, 34.4% of them female, with a mean age of 83.3 years, mean LVEF of 28.5% and ischemic etiology in 53.9% of patients. Only 14.3% of patients were taking ARNIs. After a mean follow-up of 34 months, 50.2% of patients died, and 62.2% had a cardiac event (total mortality or hospital admission due to HF). Multivariate Cox regression analysis showed that the use of ARNIs was independently and significantly associated with lower rates of mortality [HR 0.36 (95% CI 0.21-0.61)], with similar results in relation to all-cause mortality in a propensity-score-matched analysis [HR 0.33 (95% CI 0.19-0.57)]. Conclusions: We observed an important underuse of ARNIs in a cohort of elderly HFrEF patients, in which treatment with ARNIs was associated with a significant reduction in mortality. Greater implementation of clinical practice guidelines in this group of patients could improve their prognosis.

Impact of SGLT2 Inhibitors on Very Elderly Population with Heart Failure with Reduce Ejection Fraction: Real Life Data.

(1) Background: The validation of new lines of therapy for the elderly is required due to the progressive ageing of the world population and scarce evidence in elderly patients with HF with reduced ejection fraction (HFrEF). The purpose of our study is to analyze the effect of SGLT2 inhibitors (SGLT2i) in this subgroup of patients. (2) Methods: A single-center, real-world observational study was performed. We consecutively enrolled all patients aged ≥ 75 years diagnosed with HFrEF and for treatment with SGLT2i, and considered the theoretical indications. (3) Results: A total of 364 patients were recruited, with a mean age of 84.1 years. At inclusion, the mean LVEF was 29.8%. Median follow-up was 33 months, and there were 122 deaths. A total of 55 patients were under SGLT2i treatment. A multivariate Cox logistic regression test for all-cause mortality was performed, and only SGLT2i (HR 0.39 [0.19-0.82]) and glomerular filtration rate (HR 0.98 [0.98-0.99]) proved to be protective factors. In parallel, we conducted a propensity-score-matched analysis, where a significant reduction in all-cause mortality was associated with the use of SGLT2i treatment (HR 0.39, [0.16-0.97]). (4) Conclusions: Treatment with SGLT2i in elderly patients with HFrEF was associated with a lower rate of all-cause mortality. Our data show that SGLT2i therapy could improve prognosis in the elderly with HFrEF in a real-world study.

Bioimpedance analysis predicts worsening events in outpatients with heart failure and reduced ejection fraction.

AIMS: Heart failure (HF) with reduced left ventricle ejection fraction (LVEF) is an entity with poor prognosis characterized by decompensations. Bioelectrical impedance analysis (BIA) is used to assess volume overload (VO) and may be useful to identify apparently stable HF outpatients at risk of decompensation. The aim of this study is to analyse whether VO assessed by BIA is associated with worsening heart failure (WHF) in stable outpatients with HF and reduced LVEF (HFrEF). METHODS AND RESULTS: This is a prospective single-centre observational study. Consecutive stable HF outpatients with LVEF below 40% underwent BIA, transthoracic echocardiography, blood sampling, and physical examination and were followed up for 3 months. VO was defined as the difference between the measured weight and the dry weight assessed by BIA. Demographic, clinical, anthropometric, echocardiographic, and analytical parameters were recorded. The primary endpoint was WHF, defined by visits to the emergency department for HF or hospitalization for HF. A total of 100 patients were included. The median VO was 0.5 L (interquartile range 0-1.6 L). Eleven patients met the primary endpoint. Univariate binary logistic regression analysis showed that left ventricle filling pressures assessed by E/e', N-terminal pro B-type natriuretic peptide, inferior vena cava dilatation (≥21 mm), signs of congestion, and VO were associated with the primary endpoint. Binary logistic regression multivariate analysis showed that VO was the only independent predictor for the primary endpoint (adjusted OR 2.7; 95% CI 1.30-5.63, P = 0.008). Multivariate Cox regression analysis also showed an adjusted hazard ratio (HR) for VO of 2.03; 95% CI 1.37-3.02, P < 0.001. Receiver-operating characteristic curve analysis showed an area under the curve for VO of 0.88 (95% CI 0.79-0.97, P < 0.001) with an optimal cut-off of 1.2 L. CONCLUSIONS: VO assessed by BIA is independently associated with WHF in stable outpatients with HFrEF at 3 months.

Cardiac Rehabilitation Increases Plasma Klotho Levels.

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome.

OBJECTIVE: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. METHODS: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. RESULTS: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. CONCLUSIONS: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

BACKGROUND: The clinical picture of coronavirus disease 2019 (COVID-19)-associated sepsis is similar to that of sepsis of other aetiologies. The present study aims to analyse the role of syndecan-1 (SDC-1) as a potential predictor of septic shock in critically ill patients with COVID-19. METHODS: This is a prospective study of 86 critically ill patients due to COVID-19 infection. Patients were followed until day 28 of hospitalization. Vascular biomarkers, such as vascular cell adhesion protein-1, SDC-1, angiopoietin-1 and angiopoietin-2, were quantified upon admission and associated with the need for vasopressors in the first 7 d of hospitalization. RESULTS: A total of 86 patients with COVID-19 (mean age 60±16 y; 51 men [59%]) were evaluated. Thirty-six (42%) patients died during hospitalization and 50 (58%) survived. The group receiving vasopressors had higher levels of D-dimer (2.46 ng/ml [interquartile range {IQR} 0.6-6.1] vs 1.01 ng/ml [IQR 0.62-2.6], p=0.019) and lactate dehydrogenase (929±382 U/l vs 766±312 U/l, p=0.048). The frequency of deaths during hospitalization was higher in the group that received vasoactive amines in the first 24 h in the intensive care unit (70% vs 30%, p=0.002). SDC-1 levels were independently associated with the need for vasoactive amines, and admission values >269 ng/ml (95% CI 0.524 to 0.758, p=0.024) were able to predict the need for vasopressors during the 7 d following admission. CONCLUSIONS: Syndecan-1 levels predict septic shock in critically ill patients with COVID-19.

Endothelial Biomarkers in Critically Ill COVID-19 Patients: Potential Predictors of the Need for Dialysis.

INTRODUCTION: The aim of this was to evaluate the function of vascular biomarkers to predict the need for hemodialysis in critically ill patients with COVID-19. METHODS: This is a prospective study with 58 critically ill patients due to COVID-19 infection. Laboratory tests in general and vascular biomarkers, such as VCAM-1, syndecan-1, angiopoietin-1, and angiopoietin-2, were quantified on intensive care unit (ICU) admission. RESULTS: There was a 40% death rate. VCAM and Ang-2/Ang-1 ratio on ICU admission were associated with the need for hemodialysis. Vascular biomarkers (VCAM-1, syndecan-1, angiopoietin-2/angiopoietin-1 ratio) were predictors of death and their cutoff values were useful to stratify patients with a worse prognosis. In the multivariate cox regression analysis with adjusted models, VCAM-1 (OR 1.13 [CI 95%: 1.01-1.27]; p = 0.034) and Ang-2/Ang-1 ratio (OR 4.87 [CI 95%: 1.732-13.719]; p = 0.003) were associated with the need for dialysis. CONCLUSION: Vascular biomarkers, mostly VCAM-1 and Ang-2/Ang-1 ratio, showed better efficiency to predict the need for hemodialysis in critically ill COVID-19 patients.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge

ABSTRACT In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Treatment For Infected Frozen Elephant Trunk Prosthesis Caused by Propionibacterium acnes: A Surgical Challenge.

In this article, we present the case of a 47-year-old man who underwent Bentall-Bono procedure and frozen elephant trunk prosthesis implantation due to severe aortic regurgitation and aortic dilatation with a second-time endovascular stent-graft repair in descending aorta. Over eight years, a subacute graft infection by Propionibacterium acnes was developed, culminating in cardiogenic shock secondary to severe aortic regurgitation due to a complete aortic root dehiscence because of multiple aortic pseudoaneurysms. The patient underwent emergency surgery in which the replacement of the graft by a biological valve tube was performed accompanied by a complete debranching of the three supra-aortic vessels.

Nucleotide-selective amplification and array-based detection for identifying multiple somatic mutations.

In the context of personalized and cost-effective treatment, knowledge of the mutational status of specific genes is advantageous to predict which patients are responsive to therapies. As an alternative to one-by-one detection or massive sequencing, the presented genotyping tool determines multiple polymorphic sequences that vary a single nucleotide. The biosensing method includes an effective enrichment of mutant variants and selective recognition by colorimetric DNA arrays. The proposed approach is the hybridization between sequence-tailored probes and products from PCR with SuperSelective primers to discriminate specific variants in a single locus. A fluorescence scanner, a documental scanner, or a smartphone captured the chip images to obtain spot intensities. Hence, specific recognition patterns identified any single-nucleotide change in the wild-type sequence overcoming qPCR methods and other array-based approaches. Studied mutational analyses applied to human cell lines provided high discrimination factors, the precision was 95%, and the sensitivity was 1% mutant of total DNA. Also, the methods showed a selective genotyping of the KRAS gene from tumorous samples (tissue and liquid biopsy), corroborating results by NGS. The developed technology supported on low-cost robust chips and optical reading provides an attractive pathway toward implementing fast, cheap, reproducible discrimination of oncological patients.

Absence of High Lipoprotein(a) Levels Is an Independent Predictor of Acute Myocardial Infarction without Coronary Lesions.

The pathophysiological mechanisms underlying Myocardial Infarction with Non-Obstructive Coronary Artery Disease (MINOCA) are still under debate. Lipoprotein (a) [Lp(a)] has proinflammatory and prothrombotic actions and has been involved in the pathogenesis of atherosclerosis. However, no previous studies have linked Lp(a) levels with the probability of developing MINOCA. Moreover, the relationship between MINOCA and the plasma levels of other proatherogenic and proinflammatory molecules such as Interleukin-18 (IL18) and proprotein convertase subtilisin/kexin type 9 (PCSK9) has not been studied. We conducted a prospective, multicenter study involving 1042 patients with acute myocardial infarction (AMI). Seventy-six patients had no significant coronary lesions. All patients underwent plasma analysis on admission. MINOCA patients were younger (57 (47-68) vs. 61 (52-72) years; p = 0.010), more frequently female (44.7% vs. 21.0%; p < 0.001), and had lower rates of diabetes and of Lp(a) > 60 mg/dL (9.2% vs. 19.8%; p = 0.037) than those with coronary lesions; moreover, High Density Lipoprotein cholesterol (HDL-c) levels were higher in MINOCA patients. The absence of Lp(a) > 60 mg/dL and of diabetes were independent predictors of MINOCA, as well as female sex, high HDL-c levels, and younger age. IL-18 and PCSK9 levels were not predictors of MINOCA. During a follow-up of 5.23 (2.89, 7.37) years, the independent predictors of the primary outcome (acute ischemic events or death) in the whole sample were Lp(a) > 60 mg/dL, older age, low estimated Glomerular Filtration rate (eGFR), hypertension, previous heart failure (HF), coronary artery bypass graft, use of insulin, and no therapy with acetylsalicylic acid. In conclusion, in AMI patients, the absence of high Lp(a) levels, as well high HDL-c levels, were independent predictors of the inexistence of coronary artery disease. High Lp (a) levels were also an independent predictor of ischemic events or death.

ELMO CPAP: an innovative type of ventilatory support for COVID-19-related acute respiratory distress syndrome / ELMO-CPAP: um suporte ventilatório inovador para síndrome do desconforto respiratório agudo por COVID-19

ABSTRACT Objective: To assess whether the use of ELMO, a helmet for noninvasive ventilation created in Brazil, had a positive impact on the prognosis of patients with hypoxemic respiratory failure caused by severe COVID-19. Methods: This is a retrospective study of 50 critically ill COVID-19 patients. Epidemiological, clinical, and laboratory data were collected on ICU admission, as well as before, during, and after ELMO use. Patients were divided into two groups (success and failure) according to the outcome. Results: ELMO use improved oxygenation parameters such as Pao2, Fio2, and the Pao2/Fio2 ratio, and this contributed to a gradual reduction in Fio2, without an increase in CO2, as determined by arterial blood gas analysis. Patients in the success group had significantly longer survival (p < 0.001), as determined by the Kaplan-Meier analysis, less need for intubation (p < 0.001), fewer days of hospitalization, and a lower incidence of acute kidney injury in comparison with those in the failure group. Conclusions: The significant improvement in oxygenation parameters, the longer survival, as reflected by the reduced need for intubation and by the mortality rate, and the absence of acute kidney injury suggest that the ELMO CPAP system is a promising tool for treating ARDS and similar clinical conditions.

RESUMO Objetivo: Avaliar se o uso do ELMO, um capacete para ventilação não invasiva criado no Brasil, teve impacto positivo no prognóstico de pacientes com insuficiência respiratória hipoxêmica por COVID-19 grave. Métodos: Estudo retrospectivo com 50 pacientes críticos com COVID-19. Dados epidemiológicos, clínicos e laboratoriais foram coletados na admissão na UTI e antes, durante e após o uso do ELMO. Os pacientes foram divididos em dois grupos (sucesso e falha) de acordo com o desfecho. Resultados: O uso do ELMO melhorou parâmetros de oxigenação como Pao2, Fio2 e relação Pao2/Fio2, e isso contribuiu para uma redução gradual da Fio2, sem aumento do CO2, conforme determinado pela gasometria arterial. Os pacientes do grupo sucesso apresentaram sobrevida significativamente maior (p < 0,001), conforme determinado pela análise de Kaplan-Meier, menor necessidade de intubação (p < 0,001), menos dias de hospitalização e menor incidência de lesão renal aguda em comparação com os do grupo falha. Conclusões: A significativa melhora nos parâmetros de oxigenação, a maior sobrevida, refletida pela menor necessidade de intubação e pela taxa de mortalidade, e a ausência de lesão renal aguda sugerem que o sistema ELMO CPAP é uma ferramenta promissora para o tratamento da SDRA e de condições clínicas semelhantes.

Diabetes-Related Excess Mortality in Mexico: A Comparative Analysis of National Death Registries Between 2017-2019 and 2020.

OBJECTIVE: To estimate diabetes-related mortality in Mexico in 2020 compared with 2017-2019 after the onset of the coronavirus disease 2019 (COVID-19) pandemic. RESEARCH DESIGN AND METHODS: This retrospective, state-level study used national death registries of Mexican adults aged ≥20 years for the 2017-2020 period. Diabetes-related death was defined using ICD-10 codes listing diabetes as the primary cause of death, excluding certificates with COVID-19 as the primary cause of death. Spatial and negative binomial regression models were used to characterize the geographic distribution and sociodemographic and epidemiologic correlates of diabetes-related excess mortality, estimated as increases in diabetes-related mortality in 2020 compared with average 2017-2019 rates. RESULTS: We identified 148,437 diabetes-related deaths in 2020 (177 per 100,000 inhabitants) vs. an average of 101,496 deaths in 2017-2019 (125 per 100,000 inhabitants). In-hospital diabetes-related deaths decreased by 17.8% in 2020 versus 2017-2019, whereas out-of-hospital deaths increased by 89.4%. Most deaths were attributable to type 2 diabetes (130 per 100,000 inhabitants). Compared with 2018-2019 data, hyperglycemic hyperosmolar state and diabetic ketoacidosis were the two contributing causes with the highest increase in mortality (128% and 116% increase, respectively). Diabetes-related excess mortality clustered in southern Mexico and was highest in states with higher social lag, rates of COVID-19 hospitalization, and prevalence of HbA1c ≥7.5%. CONCLUSIONS: Diabetes-related deaths increased among Mexican adults by 41.6% in 2020 after the onset of the COVID-19 pandemic, occurred disproportionately outside the hospital, and were largely attributable to type 2 diabetes and hyperglycemic emergencies. Disruptions in diabetes care and strained hospital capacity may have contributed to diabetes-related excess mortality in Mexico during 2020.

FLOWERING REPRESSOR AAA+ ATPase 1 is a novel regulator of perennial flowering in Arabis alpina.

Arabis alpina is a polycarpic perennial, in which PERPETUAL FLOWERING1 (PEP1) regulates flowering and perennial traits in a vernalization-dependent manner. Mutagenesis screens of the pep1 mutant established the role of other flowering time regulators in PEP1-parallel pathways. Here we characterized three allelic enhancers of pep1 (eop002, 085 and 091) which flower early. We mapped the causal mutations and complemented mutants with the identified gene. Using quantitative reverse transcriptase PCR and reporter lines, we determined the protein spatiotemporal expression patterns and localization within the cell. We also characterized its role in Arabidopsis thaliana using CRISPR and in A. alpina by introgressing mutant alleles into a wild-type background. These mutants carried lesions in an AAA+ ATPase of unknown function, FLOWERING REPRESSOR AAA+ ATPase 1 (AaFRAT1). AaFRAT1 was detected in the vasculature of young leaf primordia and the rib zone of flowering shoot apical meristems. At the subcellular level, AaFRAT1 was localized at the interphase between the endoplasmic reticulum and peroxisomes. Introgression lines carrying Aafrat1 alleles required less vernalization to flower and reduced number of vegetative axillary branches. By contrast, A. thaliana CRISPR lines showed weak flowering phenotypes. AaFRAT1 contributes to flowering time regulation and the perennial growth habit of A. alpina.

Comorbidity and Prognosis in Octogenarians with Infective Endocarditis.

Background. Infective endocarditis (IE) in older patients is associated with a high morbidity, mortality, and functional impairment. The purpose of this study was to describe the current profile of IE in octogenarians and to analyze the prognostic impact of baseline comorbidities in this population. Methods. Patients ≥ 80 years and definite IE from the Spanish IE Prospective Database were included. The effect of Charlson Comorbidity Index (CCI) on in-hospital and 12-month mortality was analyzed. Results. From 726 patients, 357 (49%) had CCI ≥ 3 and 369 (51%) CCI < 3. A total of 265 patients (36.6%) died during hospital admission and 338 (45.5%) during 1-year follow-up. CCI ≥ 3 was an independent predictor of in-hospital and 1-year mortality (odds ratio 1.46, 95% confidence interval 1.07−1.99, p = 0.017; hazard ratio 1.34, 95% confidence interval 1.08−1.66, p = 0.007, respectively). Surgical management was less common in patients with high comorbidity (CCI ≥ 3 68 [19.0%] vs. CCI < 3 112 ((30.4%) patients, p < 0.01). From 443 patients with surgical indication, surgery was only performed in 176 (39.7%). Patients with surgical indication treated conservatively had higher mortality than those treated with surgery (in-hospital mortality: 147 (55.1%) vs. 55 (31.3%), p < 0.001), (1-year mortality: 172 (64.4%) vs. 68 [38.6%], p < 0.001). Conclusion. About half of octogenarians with IE had high comorbidity with CCI ≥ 3. CCI ≥ 3 was a strong independent predictor of in-hospital and 1-year mortality. Our data suggest that the underperformance of cardiac surgery in this group of patients might have a role in their poor prognosis.

Critically ill COVID-19 patients in northeast Brazil: mortality predictors during the first and second waves including SAPS 3.

BACKGROUND: The Simplified Acute Physiology Score (SAPS) 3 is a reliable score to predict mortality. This study aims to investigate the predictive values of SAPS 3 and other clinical parameters for death in critically ill coronavirus disease 2019 (COVID-19) patients. METHODS: This is a prospective study in a tertiary hospital for patients who required intensive care due to COVID-19 infection in northeast Brazil. Two distinct groups were constructed according to the epidemiological data: first wave and second wave. The severity of patients admitted was estimated using the SAPS 3 score. RESULTS: A total of 767 patients were included: 290 were enrolled in the first wave and 477 in the second wave. Patients in the first wave had more comorbidities, were put on mechanical ventilation and required dialysis and vasopressors more frequently (p<0.05). During the second wave, non-invasive ventilation was more often required (p<0.05). In both periods, older patients and higher SAPS 3 scores on admission were associated with death (p<0.05). Non-invasive ventilation use showed a negative association with death only in the second wave period. In the first wave, the SAPS 3 score was more useful (area under the curve [AUC] 0.897) in predicting death in critically ill COVID-19 patients than in the second wave (AUC 0.810). CONCLUSION: The SAPS 3 showed very reliable predictive values for death during the waves of the COVID-19 pandemic, mostly together with kidney and pulmonary dysfunction.

Discrimination of Single-Nucleotide Variants Based on an Allele-Specific Hybridization Chain Reaction and Smartphone Detection.

Massive DNA testing requires novel technologies to support a sustainable health system. In recent years, DNA superstructures have emerged as alternative probes and transducers. We, herein, report a multiplexed and highly sensitive approach based on an allele-specific hybridization chain reaction (AS-HCR) in the array format to detect single-nucleotide variants. Fast isothermal amplification was developed before activating the HCR process on a chip to work with genomic DNA. The assay principle was demonstrated, and the variables for integrating the AS-HCR process and smartphone-based detection were also studied. The results were compared to a conventional polymerase reaction chain (PCR)-based test. The developed multiplex method enabled higher selectivity against single-base mismatch sequences at concentrations as low as 103 copies with a limit of detection of 0.7% of the mutant DNA percentage and good reproducibility (relative error: 5% for intra-assay and 17% for interassay). As proof of concept, the AS-HCR method was applied to clinical samples, including human cell cultures and biopsied tissues of cancer patients. Accurate identification of single-nucleotide mutations in KRAS and NRAS genes was validated, considering those obtained from the reference sequencing method. To conclude, AS-HCR is a rapid, simple, accurate, and cost-effective isothermal method that detects clinically relevant genetic variants and has a high potential for point-of-care demands.

Impacto de la función renal en el valor pronóstico del metabolismo mineral en pacientes con cardiopatía isquémica crónica / Impact of renal function on the prognostic value of mineral metabolism in patients with chronic ischaemic heart disease patients with chronic ischaemic heart disease

INTRODUCCION: La parathormona (PTH) es un componente del metabolismo mineral (MM) que ha demostrado aportar valor pronóstico en los pacientes con cardiopatía isquémica crónica (CIC) y función renal preservada. Sin embargo, la influencia de la función renal en el papel pronóstico de la PTH en los pacientes con CIC aún no se ha demostrado.ObjetivoEvaluar la influencia del filtrado glomerular renal estimado (FGRe) sobre el papel pronóstico de la PTH y otros marcadores del MM en los pacientes con CIC. MÉTODOS: Analizamos el valor pronóstico de distintos componentes del MM (PTH, klotho, fósforo, calcidiol y factor de crecimiento de fibroblastos-23 [FGF23]) en 964 pacientes con CIC incluidos en 5 hospitales de Madrid en función de si presentaban FGRe <60ml/min/1,73m2 (LFGR) o FGRe≥60ml/min/1,73m2 (HFGR). El objetivo primario fue la combinación de muerte con eventos isquémicos (cualquier síndrome coronario agudo, accidente cerebrovascular isquémico o accidente isquémico transitorio). El FGR se calculó mediante el método Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTADOS: La edad era de 60,0 (52,0-72,0) años y el 76,2% de los casos eran varones, con una mediana del FGRe de 80,4 (65,3-93,1)ml/min/1,73m2. El seguimiento fue de 5,39 (2,81-6,92) años. Setecientos noventa pacientes presentaron HGFR y 174 LGFR. En pacientes con HFGR, los predictores del endpoint combinado fueron los niveles plasmáticos de calcidiol (HR=0,023 [0,94-0,99], p=0,023); FGF23 (HR=1,00 [1,00-1,003], p=0,036); colesterol no-HDL (HR=1,01 [1,00-1,01], p=0,026) y troponina de alta sensibilidad (HR=5,12 [1,67-15,59], p=0,004), junto con la edad (HR=1,03 [1,01-1,05], p=0,01), el tratamiento con estatinas (HR=0,36 [0,19-0,68], p=0,002); nitratos (HR=1,13 [1,07-2,79], p=0,027); dihidropiridinas (HR=1,71 [1,05-2,77], p=0,032); verapamilo (HR=5,71 [1,35-24,1], p=0,018) e inhibidores de la bomba de protones (HR=2,23 [1,36-3,68], p=0,002). [...]

BACKGROUND: Parathormone (PTH) is a component of the Mineral Metabolism (MM) system that has been shown recently to add prognostic value in pts. with stable coronary artery disease (SCAD) and average renal function. However, the influence of renal function on the prognostic role of PTH in pts. with SCAD has not been shown yet.PurposeTo assess the influence of estimated glomerular filtration rate (eGFR) on the prognostic role of PTH and other MM markers in pts. with SCAD. METHODS: We analyzed the prognostic value of MM markers (PTH, klotho, phosphate, calcidiol [25-hydroxyvitamin D], and fibroblast growth factor-23 [FGF23]) in 964 pts. with SCAD and eGFR<60ml/min/1.73 m2 (LGFR) vs pts. with eGFR≥60ml/min/1.73 m2 (HGFR) included in five hospitals of Madrid. The main outcome was the combination of death with ischemic events (any acute coronary syndrome, ischemic stroke or transient ischemic attack). eGFR was calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). RESULTS: Age was 60.0 (52.0-72.0) years, 76.2% of patients were men, and eGFR was 80.4 (65.3-93.1) ml/min/1,73 m2. Median follow-up was 5.39 (2.81-6.92) years. There were 790 pts. with HGFR and 174 with LGFR. In HGFR pts., predictors of ischemic events or death were plasma levels of calcidiol [HR=0.023 (0.94-0.99) p=0.023], FGF23 [HR=1.00 (1.00-1.003) p=0.036], non-HDL cholesterol [HR=1.01 (1.00-1.01) p=0.026] and high sensitivity troponin I [HR=5.12 (1.67-15.59) p=0.004], along with age [HR=1.03 (1.01-1.05) p=0.01], treatment with statins [HR=0.36 (0.19-0.68) p=0.002], nitrates [HR=1.13 (1.07-2.79) p=0.027], dihydropyridines [HR=1.71 (1.05-2.77) p=0.032], verapamil [HR=5.71 (1.35-24.1) p=0.018], and proton-pump inhibitors [HR=2.23 (1.36-3.68) p= 0.002]. [...]

Prevalence and prognostic value of monoclonal gammopathy in heart failure patients with preserved ejection fraction: A prospective study.

BACKGROUND: Heart failure (HF) with preserved ejection fraction (HFpEF) and monoclonal gammopathy of uncertain significance (MGUS) are two entities that share pathophysiological mechanisms. The aim herein, was to assess the prevalence of MGUS in patients with HFpEF and no left ventricular (LV) hypertrophy, as well as its association with a pre-specified clinical endpoint at 12 months. METHODS: The present study prospectively enrolled 69 patients admitted with HF, with ejection fraction ≥ 50%, and LV wall thickness < 12 mm. All patients were screened for MGUS. Clinical events were determined over a 12 month follow-up. The pre-specified composite clinical endpoint was readmission for HF or death. RESULTS: The prevalence of MGUS in this population was 13%. There were no differences in the incidence of the composite clinical endpoint between patients with and without MGUS. Multivariate analysis showed that treatment with angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) was associated with fewer clinical events (HR: 0.153, 95% CI: 0.037-0.622, p = 0.009) and indicated a trend to lower risk of readmission for HF and death. Beta-blockers were associated with lower rates of the composite clinical endpoint (HR: 0.192, 95% CI: 0.05-0.736, p = 0.016), readmission for HF (HR: 0.272, 95% CI: 0.087-0.851, p = 0.025) and indicated a trend to lower mortality. Moreover, potassium serum levels > 5 mEq/L were associated with higher rates of the composite endpoint (HR: 6.074, 95% CI: 1.6-22.65, p = 0.007). CONCLUSIONS: The prevalence of MGUS in patients with HFpEF without hypertrophy was 3-fold that of the general population. There was no significant correlation between clinical outcomes and the presence of MGUS. Beta-blockers and ACEIs/ARBs reduced the composite of mortality and readmissions for HF in HFpEF patients. Hyperpotassemia was related to worse prognosis.