Risk scores' performance and their impact on operative decision-making in left-sided endocarditis: a cohort study.

The accuracy of contemporary risk scores in predicting perioperative mortality in infective endocarditis (IE) remains controversial. The aim is to evaluate the performance of existent mortality risk scores for cardiovascular surgery in IE and the impact on operability at high-risk thresholds. A single-center retrospective review of adult patients diagnosed with acute left-sided IE undergoing surgery from May 2014 to August 2019 (n = 142) was done. Individualized risk calculation was obtained according to the available mortality risk scores: EuroScore I and II, PALSUSE, Risk-E, Costa, De Feo-Cotrufo, AEPEI, STS-risk, STS-IE, APORTEI, and ICE-PCS scores. A cross-validation analysis was performed on the score with the best area under the curve (AUC). The 30-day survival was 96.5% (95%CI 91-98%). The score with worse area under the curve (AUC = 0.6) was the STS-IE score, while the higher was for the RISK-E score (AUC = 0.89). The AUC of the majority of risk scores suggested acceptable performance; however, statistically significant differences in expected versus observed mortalities were common. The cross-validation analysis showed that a large number of survivors (> 75%) would not have been operated if arbitrary high-risk threshold estimates had been used to deny surgery. The observed mortality in our cohort is significantly lower than is predicted by contemporary risk scores. Despite the reasonable numeric performance of the analyzed scores, their utility in judging the operability of a given patient remains questionable, as demonstrated in the cross-validation analysis. Future guidelines may advise that denial of surgery should only follow a highly experienced Endocarditis Team evaluation.

Echocardiography and FDG-PET/CT scan in Gram-negative bacteremia and cardiovascular infections.

PURPOSE OF REVIEW: Current evidence on cardiovascular infections in Gram-negative blood stream infections (GNBSI) with focus on the use of transesophageal echocardiography (TEE) and 18F-Fluorodeoxyglucose - positron emission tomography/Computed tomography (FDG-PET/CT) in the diagnostic workup. RECENT FINDINGS: Most evidence focuses on characteristics of diagnosed cardiovascular infections and the proportion caused by GNBSI. These proportions are low (1-5%) when it comes to native and prosthetic valve endocarditis as well as cardiac implantable electronic device (CIED) infections whereas the proportion of vascular graft infections caused by GNBSI seems substantially higher (30-40%). Information on the prevalence of cardiovascular infection in patients with GNBSI is limited to a few studies finding around 3% endocarditis in patients with GNBSI and a prosthetic heart valve and 4-16% device-related infection in patients with CIED and GNBSI. SUMMARY: Patients with GNBSI and native or prosthetic valves should only undergo work-up for endocarditis (TEE and FDG-PET/CT) if they present GNBSI relapse or signs suggestive of endocarditis. CIED patients with GNBSI with Pseudomonas or Serratia spp. should undergo TEE and PET/CT because of the high prevalence of device-related infection. In other GNBs without IE suggestive signs, normal BSI treatment is reasonable and only cases with relapse need work-up. GNBSI in patients with vascular grafts should lead to consideration of PET/CT.

COVID-19: from epidemiology to treatment.

The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.

Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain.

BACKGROUND AND PURPOSE: Chitinase 3-like 1 (CHI3L1) and neurofilament light chain (NF-L) are promising biomarkers of disability in multiple sclerosis (MS). However, their role in cognitive dysfunction remains elusive. Here, we aimed to correlate cerebrospinal fluid (CSF) levels of CHI3L1 and NF-L with cognitive status in MS. METHODS: Fifty one recently diagnosed patients were cognitively evaluated and CSF was collected. Levels of CHI3L1 and NF-L were determined by ELISA. Spearman's partial correlation coefficient was performed. RESULTS: After adjusting cognitive scores by age, anxiety and EDSS, association was detected between CHI3L1 levels and Trail Making Test A (rs = 0.348; p = 0.016) and between NF-L levels and Word List Generation (rs = -0.324; p = 0.025). CONCLUSION: High levels of CSF CHI3L1 and NF-L are associated with cognitive impairment in the early phases of MS.

Early in vitro development of daptomycin non-susceptibility in high-level aminoglycoside-resistant Enterococcus faecalis predicts the efficacy of the combination of high-dose daptomycin plus ampicillin in an in vivo model of experimental endocarditis.

Background: Previous studies showed development of daptomycin non-susceptibility (DNS: MIC >4 mg/L) in Enterococcus faecalis infections. However, no studies have assessed the efficacy of the combination of daptomycin/ampicillin against E. faecalis strains developing DNS in the experimental endocarditis (EE) model. Objectives: To assess the in vitro and in vivo efficacy of daptomycin at 10 mg/kg/day, daptomycin/ampicillin and ampicillin/ceftriaxone against two high-level aminoglycoside-resistant E. faecalis strains, one developing DNS after in vitro exposure to daptomycin and another that did not (DS). Methods: Subculture of 82 E. faecalis strains from patients with endocarditis with daptomycin MICs, time-kill and in vivo experiments using the EE model. Results: 33% of the strains (27 of 82) displayed DNS after subculture with daptomycin. Daptomycin MIC rose from 0.5-2 to 8-16 mg/L. In time-kill experiments, when using a high inoculum (10 8 cfu/mL), daptomycin/ampicillin was synergistic for one-third of DS strains and none of DNS strains, while ampicillin/ceftriaxone retained synergy in all cases. In the EE model, daptomycin did not significantly reduce cfu/g from vegetations compared with control against either strain, while daptomycin/ampicillin reduced significantly more cfu/g than daptomycin against the DS strain, but not against the DNS strain [2.9 (2.0-4.1) versus 6.1 (4.5-8.0); P = 0.002]. Ampicillin/ceftriaxone was synergistic and bactericidal against both strains, displaying the same activity as daptomycin/ampicillin against the DS strain. Conclusions: Performance of an Etest for daptomycin MIC after subculture with daptomycin inhibitory doses on strains of high-level aminoglycoside-resistant E. faecalis endocarditis may be an easy test to predict the in vivo efficacy of daptomycin/ampicillin.

Choice of the specialty of diagnostic radiology by results of the competitive examination to assign residency positions from 2006 to 2015. / Análisis de la elección de la especialidad de radiodiagnóstico en el examen MIR desde el año 2006 hasta 2015.

OBJECTIVE: To analyze the profile of residency candidates choosing the specialty of diagnostic radiology in function of variables related to the positions available in different years. MATERIAL AND METHODS: We compiled the data published on the Spanish Ministry of Health's website during the acts celebrated to allow residency candidates to choose positions based on the results of the competitive examinations held from 2006 to 2015, comparing the specialty of diagnostic radiology with the other specialties available in terms of positions available, net questions, sex, nationality, and order of choice of the position. RESULTS: The specialty of diagnostic radiology occupied the 16th position in the ranking of specialties according to the median number of order in the choice for each of the positions offered in the years studied. The first diagnostic radiology residency position was usually assigned after 75 candidates had chosen other specialties, and the last position was usually assigned after 3700 to 4100 candidates had chosen their positions. During the period studied, of those who chose diagnostic radiology 58% were women and 76% were Spanish nationality. Candidates preferred hospitals in the Autonomous Community of Madrid, and the hospital chosen with the lowest median position (highest score on the competitive examination) was the Hospital Clínic de Barcelona. CONCLUSIONS: Diagnostic radiology is chosen by candidates with good positioning in the ranking according to official examination results, is less likely than other specialties to be chosen by women, and is chosen mostly by Spanish physicians. Candidates prefer large hospitals in provincial capitals.

Extensive sequence analysis of CFTR, SCNN1A, SCNN1B, SCNN1G and SERPINA1 suggests an oligogenic basis for cystic fibrosis-like phenotypes.

The term cystic fibrosis (CF)-like disease is used to describe patients with a borderline sweat test and suggestive CF clinical features but without two CFTR(cystic fibrosis transmembrane conductance regulator) mutations. We have performed the extensive molecular analysis of four candidate genes (SCNN1A, SCNN1B, SCNN1G and SERPINA1) in a cohort of 10 uncharacterized patients with CF and CF-like disease. We have used whole-exome sequencing to characterize mutations in the CFTR gene and these four candidate genes. CFTR molecular analysis allowed a complete characterization of three of four CF patients. Candidate variants in SCNN1A, SCNN1B, SCNN1G and SERPINA1 in six patients with CF-like phenotypes were confirmed by Sanger sequencing and were further supported by in silico predictive analysis, pedigree studies, sweat test in other family members, and analysis in CF patients and healthy subjects. Our results suggest that CF-like disease probably results from complex genotypes in several genes in an oligogenic form, with rare variants interacting with environmental factors.

Clinical features in adult patient with Wolf-Hirschhorn syndrome.

The Wolf-Hirschhorn syndrome (WHS) encompasses deletions at the distal part of the short arm of one chromosome 4 (4p16 region). Clinical signs frequently include a typical facial appearance, mental retardation, intrauterine and postnatal growth retardation, hypotonia with decreased muscle bulk and seizures besides congenital heart malformations, midline defects, urinary tract malformations and brain, hearing and ophthalmologic malformations. Pathogenesis of WHS is multigenic and many factors are involved in prediction of prognosis such as extent of deletion, the occurrence of severe chromosome anomalies, the severe of seizures, the existence of serious internal, mainly cardiac, abnormalities and the degree of mental retardation. The phenotype of adult with WHS is in general similar to that of childhood being facial dysmorphism, growth retardation and mental retardation the rule in both adults and children. Avoid long-term complications and provide rehabilitation programs and genetic counseling may be essential in these patients.

A two-years real-word study with fingolimod: early predictors of efficacy and an association between EBNA-1 IgG titers and multiple sclerosis progression.

Background: Although fingolimod, a sphingosine 1-phosphate receptor agonist, has shown to be an effective treatment reducing relapse rate and also slowing down the disability progression in relapsing-remitting multiple sclerosis (RRMS) patients, it is important to quickly identify those suboptimal responders. Objective: The main objective was to assess different clinical, radiological, genetic and environmental factors as possible early predictors of response in MS patients treated with fingolimod for 24 months. The secondary objective was to analyze the possible contribution of the environmental factors analyzed to the progression and activity of the disease along the 2-years of follow-up. Methods: A retrospective study with 151 patients diagnosed with MS, under fingolimod treatment for 24 months, with serum samples at initiation and six months later, and with clinical and radiological data at initiation and 24 months later, were included in the study. Clinical and radiological variables were collected to establish NEDA-3 (no evidence of disease activity: patients without relapses, disability progression and new T2 lesions or Gd+ lesions) and EDA (evidence of disease activity: patients with relapses and/or progression and/or new T2 lesions or gadolinium-positive [Gd+] lesions) conditions. Human leukocyte antigen II (HLA-II), EBNA-1 IgG and VCA IgG from Epstein-Barr virus (EBV) and antibody titers against Human herpesvirus 6A/B (HHV-6A/B) were also analyzed. Results: A total of 151 MS patients fulfilled the inclusion criteria: 27.8% was NEDA-3 (37.5% among those previously treated with high efficacy therapies >24 months). The following early predictors were statistically significantly associated with NEDA-3 condition: sex (male; p=0.002), age at baseline (older; p=0.009), relapses 2-years before fingolimod initiation ≤1 (p=0.010), and absence of Gd+ lesions at baseline (p=0.006). Regarding the possible contribution of the environmental factors included in the study to the activity or the progression of the disease, we only found that EBNA-1 IgG titers decreased in 20.0% of PIRA (progression independent from relapse activity) patients vs. 73.3% of RAW (relapse-associated worsening) patients (p=0.006; O.R. = 11.0). Conclusion: MS patients that are male, older, and with a low clinical and radiological activity at fingolimod initiation have a greater probability to reach NEDA-3 condition after two years with this therapy. An intriguing association of EBV with the progression of the disease has also been described, but it should be further study in a larger cohort to confirm these results.

[Assisted techniques for the endovascular treatment of complex or atypical cerebral aneurysms]. / Técnicas asistidas para el tratamiento endovascular de aneurismas cerebrales complejos o atípicos.

In the last ten years, the endovascular approach to the management of cerebral aneurysms has gone from being an alternative to surgery to being the first-choice technique in the vast majority of cases. The continuous development of new assisted techniques and of new materials for embolization have multiplied its therapeutic possibilities, so that safe and efficacious endovascular treatment is now possible for aneurysms that would have required surgery only a few years ago. These continuous technological advances require the professionals that treat patients with cerebral aneurysms to achieve a high degree of specialization and to keep up to date through continuous training. In this article, we review some of the most widely used assisted techniques in the endovascular treatment of cerebral aneurysms, discussing their main indications, their advantages over conventional embolization techniques, and their possible limitations.

Mild clinical and biochemical phenotype in two patients with PMM2-CDG (congenital disorder of glycosylation Ia).

Phosphomannomutase 2 deficiency (PMM2-CDG) patients may present as mild phenotypes, with the cerebellum frequently involved. In those cases, false-negative results in screening may occur when applying conventional biochemical procedures. Our aim was to report two patients with a diagnosis of PMM2-CDG presenting with mild clinical phenotype. Patient 1-at 9 months of age, she presented with just psychomotor delay, tremor, hypotonia, and slight lipodystrophy. Patient 2-she presented at 8 months of age with psychomotor delay, hand stereotypes, hypotonia, convergent bilateral strabismus, and tremor but no lipodystrophy. Routine biochemical parameters including blood count, clotting factors, proteins, and thyroid hormone were normal in both cases. Cranial MRI evidenced mild cerebellar atrophy with moderate vermis hypoplasia. In case 1, sialotransferrin pattern showed very slightly increased disialotransferrin with no asialotransferrin, and in case 2, the transferrin pattern was impaired in the first study but nearly normal in the second. Nevertheless, in all the samples, quantification of the patterns obtained by capillary zone electrophoresis analysis gave results out of the control range. High residual PMM2 activity was observed in both cases and the genetic analysis showed that patient 1 was heterozygous for c.722G>C (p.C241S) and c.368G>A (p.R123Q) mutations, and patient 2 showed the c.722G>C and the c.470T>C (p.F157S) mutations in the PMM2 gene. We would like to stress the importance of the use of sensitive semiquantitative methods of screening for CDG in order to achieve early identification of patients with mild phenotypes. Intentional tremor was an atypical but remarkable clinical feature in both cases, and the global cerebellar atrophy with vermis hypoplasia reinforced the early clinical suspicion of a PMM2-CDG disease.

Paediatric adverse drug reactions reported to the Spanish Pharmacovigilance System from 2004 to 2009.

PURPOSE: This study was conducted to evaluate relevant new information about ADRs reported in the Spanish paediatric population over a 6-year period. METHODS: Adverse drug reactions (ADRs) for individuals aged 0-17 years reported to the Spanish Pharmacovigilance System from 2004 to 2009 were analysed with respect to time, age and sex, category of ADR [System Organ Class (SOC)], seriousness, suspected medicines [level 2 of the Anatomical Therapeutic Chemical (ATC) Classification System] and type of reporter. RESULTS: In total, 4,279 ADR reports corresponding to 8,196 ADRs were analysed, approximately two ADRs per report. The rate of paediatric ADR reports in 2009 was 165 per million, of which nearly half (46 %) were for children (age group 2-11 years). Similar total numbers of ADRs were reported for boys and girls. The most frequent ADRs reported were from the following SOCs: general disorders and administration site conditions (34 %); skin and subcutaneous tissue disorders (15 %); nervous system disorders (14 %). Reports encompassed medicines from various ATC groups: vaccines and anti-infectives for systemic use (67 %); nervous system (9 %); respiratory system (9 %). On average, 37 % of ADRs were classified as serious. There were 33 fatal ADRs, and 35 % of the paediatric population associated with the ADR notifications required hospitalization or extended hospital stay. CONCLUSIONS: In Spain, ADR reporting rate in the paediatric population has increased since 2004. The proportion of suspected ADR reports related to vaccines was predominant, which highlights the important role played by nurses. ADR notification of congenital malformations in newborn infants highlights the need for joint action between the Spanish System of Pharmacovigilance of Medicines for Human Use (SEFV-H) and paediatricians, obstetricians and gynaecologists. The publication of safety reports by regulatory agencies is determinant for the increased number of ADR notifications.

[Our experience in the diagnosis and treatment of cerebral pseudoaneurysms]. / Nuestra experiencia en el diagnóstico y tratamiento de los seudoaneurismas cerebrales.

OBJECTIVE: To present our experience in the diagnosis and intravascular treatment of cerebral pseudoaneurysms. MATERIAL AND METHODS: We present 11 pseudoaneurysms (2 traumatic, 2 mycotic, 3 iatrogenic, and 4 with other causes). We analyze the methods and diagnostic criteria, radiological and clinical outcome, the criteria used in making decisions about treatment, the method of treatment, and the complications. RESULTS: Digital subtraction angiography is the gold standard for the diagnosis of cerebral pseudoaneurysms; the diagnostic criteria in the literature include: aneurysms with early morphological changes and distal aneurysms or proximal aneurysms associated with another distal one, in the context of the right symptoms and signs. In the nine patients treated with endovascular techniques, the treatment objective was achieved and rebleeding did not occur. CONCLUSIONS: In cases with clinical suspicion of a pseudoaneurysm, the patient should undergo angiography. This is especially important in patients with inexplicable cerebral hemorrhage and in those with septicemia. CT angiography and MR angiography have good diagnostic accuracy and can replace conventional angiography. However, the treatment of choice is endovascular and treatment should not be delayed unless access to the pseudoaneurysm is impeded, usually due to severe cerebral vasospasm.

Prostaglandin E2 modulates proximal tubule Na+-ATPase activity: cooperative effect between protein kinase A and protein kinase C.

Previous data showed that prostaglandin E2 (PGE2) mediates the inhibitory effect of bradykinin (BK) on proximal tubule (PT) Na+-ATPase activity. The aim of this work was to investigate the molecular mechanisms involved in the effect of PGE2 on PT Na+-ATPase. We used isolated basolateral membrane (BLM) from pig PT, which expresses several components of different signaling pathways. The inhibitory effect of PGE2 on PT Na+-ATPase activity involves G-protein and the activation of protein kinase A (PKA) because: (1) PGE2 increased [³5S]GTPγS binding; (2) GDPßS abolished the inhibitory effect of PGE2; (3) PGE2 increased PKA activity; (4) the inhibitory effect of PGE2 was abolished by PKA inhibitor peptide. We observed that the PKA-mediated inhibitory effect of PGE2 on PT Na+-ATPase activity requires previous activation of protein kinase C. In addition, we observed that PGE2 stimulates Ca²+-independent phospholipase A2 activity representing an important positive feedback to maintain the inhibition of the enzyme. These results open new perspectives to understanding the mechanism involved in the effect of PGE2 on proximal tubule sodium reabsorption.

Association of Taq 1B CETP polymorphism with insulin and HOMA levels in the population of the Canary Islands.

BACKGROUND AND AIMS: Cholesteryl ester transfer protein (CETP) is an enzyme with a key role in lipoprotein metabolism. A common genetic polymorphism, the Taq 1B, influences CETP activity and HDL-cholesterol levels, with individual homozygotes for the B1 allele exhibiting higher enzyme activity and lower HDL-cholesterol levels than carriers of at least one B2 allele. Our aim was to analyze the influence of Taq 1B CETP polymorphism on cardiovascular risk factors in a representative sample of adult subjects from Canary population. METHODS AND RESULT: A total of 518 adult subjects from the Canary Islands, enrolled in a nutritional survey (the ENCA study), were included. The Taq 1B polymorphism was analyzed by PCR-RFLP. Compared with individuals with at least one B2 allele, and after adjusting for age, sex, BMI, waist perimeter, smoking and alcohol intake, carriers of the B1B1 genotype showed lower HDL-cholesterol levels (geometric mean (95% CI): 46.6 (44.5-48.8) vs. 50.6 (49.1-52.9)mg/dl; P=0.003); and higher insulin (geometric mean (95% CI): 11.1 (10.5-11.9) vs. 10.0 (9.5-10.5µU/ml; P=0.008) and HOMA levels (geometric mean (95% CI): 2.3 (2.1-2.5) vs. 2.1 (1.9-2.1); P=0.009). In addition, the B1B1 genotype was more frequent in individuals who had low levels of HDL-cholesterol according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria (Odds Ratio (OR): 1.563; 95% CI: 1.04-2.34; P=0.030), and in those included in the upper quartile of insulinemia (OR: 1.90; 95% CI: 1.20-3.03; P=0.007) and HOMA (OR: 1.61; 95% CI: 1.02-2.57; P=0.043). CONCLUSION: The observed influence of Taq 1B polymorphism on insulin levels and HOMA highlights the possible role of CETP in the regulation of glucose homeostasis.

[Abdominal ultrasonography versus abdominal CT in the follow-up of testicular germ cell tumors]. / Comparación de la ecografía abdominal con la tomografía computarizada abdominal en el seguimiento del tumor de células germinales testicular.

INTRODUCTION: Testicular germ cell tumors are common in young men. There is a wide consensus regarding the key points in their diagnosis and treatment, although some elements, including the best approach to follow-up, are being reviewed and revised. We present a statistical study that uses tools for the evaluation of diagnostic tests to compare the usefulness of abdominal ultrasonography (US) in comparison with that of abdominal CT, taken as the gold standard, in the detection of liver metastases and retroperitoneal adenopathies in patients with testicular germ cell tumors. MATERIAL AND METHODS: We analyzed a total of 308 diagnostic tests (154 CT studies and 154 US studies) from 59 patients with at least one year's follow-up at our institution. Patients underwent abdominal US before abdominal CT following a standard protocol. RESULTS: Compared to the gold standard, abdominal US had 95% sensitivity, 92% specificity, 82% PPV, and 98% NPV. CONCLUSION: US is very sensitive and can be used in protocols for the follow-up of primary testicular tumors to rule out disease.

Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency.

We screened for PDHA1 mutations in 40 patients with biochemically demonstrated PDHc deficiency or strong clinical suspicion, and found changes with probable pathological significance in 20. Five patients presented new mutations: p.A169V, c.932_938del, c.1143_1144 ins24, c.1146_1159dup and c.510-30G> A, this latter is a new undescribed cause of exon 6 skipping. Another four mutations have been found, and previously reported, in our patients: p.H113D, p.P172L, p.Y243del and p.Y369Q. Eleven patients presented seven known mutations: p.R127Q, p.I166I, p.A198T, p.R263G, p.R302C, p.R378C and c.1142_1145dup. The latter three were found in more than one unrelated patient: p.R302C was detected in a heterozygous girl and a mosaic male, p.R378C in two males and finally, c.1142_1145dup in three females; only one in 20 mothers was found to be a carrier (p.R263G). Apart from those 20 patients, the only alteration detected in one girl with clear PDHc and PDH-E1 deficiency was the silent change c.396A> C (p.R132R), and other eight PDHc deficient patients carry combinations of known infrequent polymorphisms that are overrepresented among our 20 unsolved patients. The importance of these changes on PDH activity is unclear. Investigations in the other PDHc genes are in course in order to elucidate the genetic defect in the unresolved patients.