Sex-based Differences in Heart Failure Biomarkers.

PURPOSE OF REVIEW: Differences in HF biomarker levels by sex may be due to hormonal, genetic, and fat distribution differences. Knowledge of these differences is scarce, and it is not well established whether they may affect their usefulness in the management of HF. RECENT FINDINGS: The different biomarker profiles in women and men have been confirmed in recent studies: in women, markers of cardiac stretch and fibrosis (NP and galectin-3) are higher, whereas in men, higher levels of markers of cardiac injury and inflammation (cTn and sST2) are found. The use of new biomarkers, together with growing evidence that a multimarker approach can provide better risk stratification, raises the question of building models that incorporate sex-specific diagnostic criteria. More and more research are being devoted to understanding sex-related differences in HF. The aim of this review is to review the dynamics of HF biomarkers according to sex and in different situations, to learn whether these sex differences may affect their use in the diagnosis and follow-up of HF patients.

Analysis of the activity of the telephone nursing consultation on demand for patients with heart failure.

OBJECTIVE: Analyzing the most frequent reasons for telephone demand in the heart failure nurse's consultation and to evaluate the response resolution capacity after the call. METHOD: Descriptive, retrospective study of all telephone calls recorded between June 2020 and April 2021 in a specific nursing consultation for heart failure care. The main sociodemographic and clinical variables, reason for calling and action carried out by the nurse were extracted from the electronic medical records. For its subsequent descriptive análisis. RESULTS: 643 calls were analyzed, 354 (55.1%) were made by the patients. The most frequent reason for calling was to consult symptoms 45.8% (n = 162). 71.6% (n = 116) of the consultations were resolved by adjusting the pharmacological treatment by telephone, 24.7% (n = 40) required a face-to-face visit in the nurse's consultation, 22 (13.6%) needed emergency care. 5 due to worsening heart failure. The patients who consulted for symptoms had a worse functional class (p = 0.007) and had been referred from hospitalization (p = 0.023). CONCLUSIONS: The telephone consultation was shown to be useful for patients with heart failure, being mainly demanded by users who present symptoms of worsening of their disease.

Craniofacial and three-dimensional palatal analysis in cleft lip and palate patients treated in Spain.

Growth alterations have been described in patients operated on for oral clefts. The purpose of this work was to analyze the craniofacial and palate morphology and dimensions of young adults operated on for oral clefts in early childhood in Spain. Eighty-three patients from eight different hospitals were divided into four groups based on their type of cleft: cleft lip (CL, n = 6), unilateral cleft lip and palate (UCLP, n = 37), bilateral cleft lip and palate (BCLP, n = 16), and cleft palate only (CPO, n = 24). A control group was formed of 71 individuals. Three-dimensional (3D) digital models were obtained from all groups with an intraoral scanner, together with cephalometries and frontal, lateral, and submental facial photographs. Measurements were obtained and analyzed statistically. Our results showed craniofacial alterations in the BCLP, UCLP, and CPO groups with an influence on the palate, maxilla, and mandible and a direct impact on facial appearance. This effect was more severe in the BCLP group. Measurements in the CL group were similar to those in the control group. Cleft characteristics and cleft type seem to be the main determining factors of long-term craniofacial growth alterations in these patients. Prospective research is needed to clearly delineate the effects of different treatments on the craniofacial appearance of adult cleft patients.

Transforming growth factor ß3 deficiency promotes defective lipid metabolism and fibrosis in murine kidney.

Glomerulosclerosis and tubulointerstitial fibrosis are pathological features of chronic kidney disease. Transforming growth factor ß (TGFß) is a key player in the development of fibrosis. However, of the three known TGFß isoforms, only TGFß1 has an established role in fibrosis, and the pathophysiological relevance of TGFß2 and TGFß3 is unknown. Because Tgfb3 deficiency in mice results in early postnatal lethality, we analyzed the kidney phenotype of heterozygous Tgfb3-knockout mice (Tgfb3+/-) and compared it with that of matched wild-type mice. Four-month-old Tgfb3+/- mice exhibited incipient renal fibrosis with epithelial-mesenchymal transition, in addition to glomerular basement membrane thickening and podocyte foot process effacement associated with albuminuria. Also evident was insulin resistance and oxidative stress at the renal level, together with aberrant renal lipid metabolism and mitochondrial function. Omics analysis revealed toxic species, such as diacylglycerides and ceramides, and dysregulated mitochondrial metabolism in Tgfb3+/- mice. Kidneys of Tgfb3+/- mice showed morphological alterations of mitochondria and overactivation of non-canonical MAPK ERK1/2 and JNK cascades. Our study indicates that renal TGFß3 might have antifibrotic and renoprotective properties, opposing or counteracting the activity of TGFß1. This article has an associated First Person interview with the first author of the paper.

Oral decontamination with colistin plus neomycin in solid organ transplant recipients colonized by multidrug-resistant Enterobacterales: a multicentre, randomized, controlled, open-label, parallel-group clinical trial.

OBJECTIVES: To evaluate the efficacy of oral colistin-neomycin in preventing multidrug-resistant Enterobacterales (MDR-E) infections in solid organ transplant (SOT) recipients. METHODS: Multicentre, open-label, parallel-group, controlled trial with balanced (1:1) randomization in five transplant units. SOT recipients were screened for MDR-E intestinal colonization (extended-spectrum ß-lactamase or carbapenemase producing) before transplantation and +7 and + 14 days after transplantation and assigned 1:1 to receive treatment with colistin sulfate plus neomycin sulfate for 14 days (decolonization treatment (DT) group) or no treatment (no decolonization treatment (NDT) group). The primary outcome was diagnosis of an MDR-E infection. Safety outcomes were appearance of adverse effects, mainly diarrhoea, rash, nausea and vomiting. Patients were monitored weekly until 30 days after treatment. Intention-to-treat analysis was performed. RESULTS: MDR-E rectal colonization was assessed in 768 SOT recipients; 105 colonized patients were included in the clinical trial, 53 receiving DT and 52 NDT. No significant decrease in the risk of infection by MDR-E was observed in the DT group (9.4%, 5/53) compared to the NDT group (13.5%, 7/52) (relative risk 0.70; 95% confidence interval 0.24-2.08; p 0.517). Four patients (5.6%), three (5.6%) in the DT group and one (1.9%) in the NDT group, developed colistin resistance. Twelve patients (22.7%) in the DT group had diarrhoea, eight related to treatment (15.0%); one patient (1.8%) developed skin rash and another (1.8%) nausea and vomiting. Two patients (3.8%) in the NDT group developed diarrhoea. CONCLUSIONS: DT does not reduce MDR-E infections in SOT. Colistin resistance and adverse effects such as diarrhoea are a potential issue that must be taken seriously.

Health-Related Quality of Life and Use of Hospital Services by Patients with Heart Failure and Their Family Caregivers: A Multicenter Case-Control Study.

BACKGROUND: Heart failure (HF) causes high rates of hospital admissions. It is known that disease progression impacts the health-related quality of life (HRQoL) of both patients and caregivers, yet to date, this finding is based on cross-sectional studies with limited samples. OBJECTIVES: The study aim is to analyze the relationship between HF patients' use of hospital services (a proxy for disease progression) and the HRQoL of their family caregivers. METHODS: This work is a multicenter nested case-control study on a population of patients admitted to hospitals in southern Spain due to heart failure. The sample comprised 530 patient-caregiver dyads. Hospital admission data were retrospectively collected for the 5 years prior to inclusion in the study. Bivariate analyses and multivariate logistic regression were used to determine associations between patient deterioration and caregivers' quality of life. RESULTS: Patients' use of hospital services was associated with worsened quality of life for family caregivers, with an overall OR of 1.48 (95% CI: 1.23-1.79). A positive correlation was found between patients' perceptions of their physical health and the perceived mental health of caregivers (r = 0.127, p = 0.004) and between the perceived mental health of both (r = 0.291; p <0.0001). CONCLUSIONS: Greater use of hospital services by patients with HF is an independent predictor of deterioration of family caregivers' HRQoL. The physical and mental components of patients' and their family caregivers' HRQoL interact and influence each other. Additional factors, such as the nature and intensity of care provided, also determine the worsening of a family caregiver's HRQoL. CLINICAL RELEVANCE: These results can be used to identify family caregivers of people with heart failure at risk of suffering a deterioration in their health-related quality of life. Increased use of hospital services is an independent predictor of the deterioration of the family caregivers' health-related quality of life. Since clinical nurses are the main provider who gives support and education to family caregivers, they should be alert to this situation and individualize interventions to prevent this deterioration.

Role of age and comorbidities in mortality of patients with infective endocarditis.

PURPOSE: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. METHODS: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. RESULTS: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. CONCLUSION: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.

Maternal folic acid supplementation reduces the severity of cleft palate in Tgf-ß3 null mutant mice.

BACKGROUND: Cleft palate (CP) constitutes the most frequently seen orofacial cleft and is often associated with low folate status. Folate plays an essential role in the human body as a major coenzyme in one-carbon metabolism, including DNA synthesis, repair, and methylation. Whether the administration of isolated folic acid (FA) supplements prevents the CP caused by genetic mutations is unknown, as is its effect on the mechanisms leading to palate fusion. METHODS: FA was administered to females from two different strains of transforming growth factor ß3 heterozygous mice. Null mutant progeny of these mice exhibit CP in 100% of cases of varying severity. We measured cleft length, height of palatal shelf adhesion, and the number of proliferating mesenchymal cells. Immunohistochemistry was also carried for collagen IV, laminin, fibronectin, cytokeratin-17, and EGF. RESULTS: FA supplementation significantly reduced CP severity and improved palatal shelf adhesion in both strains both in vivo and in vitro. Medial edge epithelium proliferation increased, and its differentiation was normalized as indicated by the presence and disposition of collagen IV, laminin, fibronectin, and cytokeratin-17. CONCLUSIONS: A maternal FA supplementation reduces the CP appearance by improving the mechanisms leading to palatal shelf adhesion.

Transforming Growth Factor-ß3 Regulates Adipocyte Number in Subcutaneous White Adipose Tissue.

White adipose tissue (WAT) mass is determined by adipocyte size and number. While adipocytes are continuously turned over, the mechanisms controlling fat cell number in WAT upon weight changes are unclear. Herein, prospective studies of human subcutaneous WAT demonstrate that weight gain increases both adipocyte size and number, but the latter remains unaltered after weight loss. Transcriptome analyses associate changes in adipocyte number with the expression of 79 genes. This gene set is enriched for growth factors, out of which one, transforming growth factor-ß3 (TGFß3), stimulates adipocyte progenitor proliferation, resulting in a higher number of cells undergoing differentiation in vitro. The relevance of these observations was corroborated in vivo where Tgfb3+/- mice, in comparison with wild-type littermates, display lower subcutaneous adipocyte progenitor proliferation, WAT hypertrophy, and glucose intolerance. TGFß3 is therefore a regulator of subcutaneous adipocyte number and may link WAT morphology to glucose metabolism.

Craniofacial structure alterations of foetuses from folic acid deficient pregnant mice.

INTRODUCTION: Craniofacial development in mammals is a complex process that involves a coordinated series of molecular and morphogenetic events. Folic acid (FA) deficiency has historically been associated with congenital spinal cord malformations, but the effect that a maternal diet deficient in FA has on the development of other structures has been poorly explored. In the present study, the objective was to describe and quantify the alterations of craniofacial structures presented in mouse foetuses from dams fed a FA deficient (FAD) diet compared with controls that were given a regular maternal diet. MATERIAL AND METHODS: E17 mouse foetuses were removed from dams that were fed with a control diet or with a FAD diet for several weeks. Foetuses with maternal FAD diets were selected for the study when they showed an altered tongue or mandible. Histological sections were used to quantify the dimensions of the head, tongue, mandibular bone and masseter muscle areas using ImageJ software. The muscles of the tongue, suprahyoid muscles, lingual septum, submandibular ducts, and lingual arteries were also analysed. RESULTS: The heads of malformed foetuses were smaller than the heads of the controls, and they showed different types of malformations: microglossia with micrognathia (some of which were combined with cleft palate) and aglossia with either micrognathia or agnathia. Lingual and suprahyoid muscles were affected in different forms and degrees. We also found alterations in the lingual arteries and in the ducts of the submandibular glands. Summarised we can state that pharyngeal arches-derived structures were affected, and the main malformations observed corroborate the vulnerability of cranial neural crest cells to FA deficiency. CONCLUSION: The present study reveals alterations in the development of craniofacial structures in FAD foetuses. This study provides a new focus for the role of FA during embryological development.

[Clinical simulation for quality improvement in the care of postpartum haemorrhage]. / Simulación clínica para la mejora de la calidad en la atención a la hemorragia posparto.

OBJECTIVE: To analyse and redesign the care process for patients with severe post-partum haemorrhage using simulation and a human factors approach. METHODS: The project was developed between June 2016 and May 2017. The working group was created following the participatory leadership method and included professionals with knowledge and position to influence the organisation. The existing process and clinical protocols were reviewed. An in situ simulation was used to observe team performance in the hospital recovery room. Information was expanded through an open and structured interview with professionals selected for their experience in the subject matter. Task analysis was used to document the process, and a failure mode and effects analysis was made to assess system vulnerabilities. Results were mapped using a flow chart. RESULTS: The analysis identified six groups of people working on different tasks, their activities and sequence of action, the importance of naming an explicit coordinator, the way in which information is disseminated and transformed, and the stages where it is necessary to share information and make key clinical decisions. The existing clinical protocols and the aids established in order to use the available resources were integrated, including blood draws and haemostatic agents, as well as an administration guide. CONCLUSIONS: The analysis of the patient care process in post-partum haemorrhage using in situ simulation with a human factors perspective, including an analysis of the interaction between professionals and the system where they work, established a detailed and personalised map of the components that determine how work flows through the organisation.

Tongue Abnormalities Are Associated to a Maternal Folic Acid Deficient Diet in Mice.

It is widely accepted that maternal folic acid (FA) deficiency during pregnancy is a risk factor for abnormal development. The tongue, with multiple genes working together in a coordinated cascade in time and place, has emerged as a target organ for testing the effect of FA during development. A FA-deficient (FAD) diet was administered to eight-week-old C57/BL/6J mouse females for 2-16 weeks. Pregnant dams were sacrificed at gestational day 17 (E17). The tongues and heads of 15 control and 210 experimental fetuses were studied. In the tongues, the maximum width, base width, height and area were compared with width, height and area of the head. All measurements decreased from 10% to 38% with increasing number of weeks on maternal FAD diet. Decreased head and tongue areas showed a harmonic reduction (Spearman nonparametric correlation, Rho = 0.802) with respect to weeks on a maternal FAD diet. Tongue congenital abnormalities showed a 10.9% prevalence, divided in aglossia (3.3%) and microglossia (7.6%), always accompanied by agnathia (5.6%) or micrognathia (5.2%). This is the first time that tongue alterations have been related experimentally to maternal FAD diet in mice. We propose that the tongue should be included in the list of FA-sensitive birth defect organs due to its relevance in several key food and nutrition processes.

Risk factors and outcomes for nosocomial infection after prosthetic vascular grafts.

OBJECTIVE: The objective of this study was to determine risk factors for nosocomial infections (NIs) and predictors of mortality in patients with prosthetic vascular grafts (PVGs). METHODS: This was a prospective cohort study of all consecutive patients who underwent PVG of the abdominal aorta with or without iliac-femoral involvement and peripheral PVG from April 2008 to August 2009 at a university hospital. Patients younger than 15 years and those with severe immunodeficiency were excluded. The follow-up period was until 3 years after surgery or until death. RESULTS: There were 261 patients included; 230 (88.12%) were male, and the mean age was 67.57 (standard deviation, 10.82) years. The reason for operation was aortic aneurysm in 49 (18.77%) patients or lower limb arteriopathy in 212 (81.23%) patients. NIs occurred in 71 (27.20%) patients. Of these, 42 were surgical site infections (SSIs), of which 61.9% occurred in the lower extremities (14 superficial, 10 deep, and 2 PVG infections) and 38.1% in the abdomen (7 superficial, 7 deep, and 2 PVG infections); 15 were respiratory tract infections; and 15 were urinary tract infections. Active lower extremity skin and soft tissue infection (SSTI) at the time of surgery was a significant predictor of NI for both types of PVG (abdominal aortic PVG: adjusted odds ratio [OR], 12.6; 95% confidence interval [CI], 1.15-138.19; peripheral PVG: adjusted OR, 2.43; 95% CI, 1.08-5.47). Other independent predictors of NI were mechanical ventilation (adjusted OR, 55.96; 95% CI, 3.9-802.39) for abdominal aortic PVG and low hemoglobin levels on admission (adjusted OR, 0.84; 95% CI, 0.71-0.99) and emergent surgery (adjusted OR, 4.39; 95% CI, 1.51-12.74) for peripheral PVG. The in-hospital mortality rate was 1.92%. The probability of surviving the first month was 0.96, and significant predictors of mortality were active lower extremity SSTI (adjusted risk ratio [RR], 12.07; 95% CI, 1.04-154.75), high postsurgical glucose levels (adjusted RR, 1.02; 95% CI, 1.00-1.04), and noninfectious surgical complications (adjusted RR, 19.38; 95% CI, 2.25-167.29). The long-term mortality rate was 11.88%. The probability of surviving at 12, 24, and 36 months was 0.94, 0.92, and 0.87, respectively. Variables significantly associated with long-term death were older age (adjusted RR, 1.08; 95% CI, 1.01-1.15), high values of creatinine on discharge (adjusted RR, 1.91; 95% CI, 1.08-3.38), and an SSI with the highest adjusted RR (6.35; 95% CI, 1.87-21.53). CONCLUSIONS: SSI was the primary NI. The risk of NI depended primarily on the presence of a lower extremity SSTI at the time of surgery, whereas mortality was determined by age, surgical complications during the operation, and SSI. These findings suggest that in those cases in which surgery is reasonably delayed, surgery should be deferred until the lower extremity SSTIs are resolved.

Quality of life in patients with hereditary haemorrhagic telangiectasia (HHT).

BACKGROUND: There are very few studies about general quality of life parameters, standards for the description of health status and comparison with general population data on patients with Hereditary hemorrhagic telangiectasia (HHT), a rare disease in which epistaxis is a cardinal symptom. PURPOSE: To assess the quality of life in a population of Spanish patients with HHT and compare it with the general population. DESIGN AND METHODS: Between January 1st 2005 and December 31st 2013, 187 adult patients diagnosed with HHT who were admitted to the HHT Unit of the Hospital Sierrallana, completed on their first visit, the EuroQol 5D-3L (five dimensions and three levels) quality of life descriptive test and the visual analog scale (VAS). The numerical social index value was also determined and the subjective effect of the nasal epistaxis on their quality of life was estimated classified as mild, moderate or severe. RESULTS: Patients with HHT had greater problems than the general population in the five dimensions of the EuroQol 5D-3L, particularly considering pain/discomfort and anxiety/depression. In the VAS and the social index value, patients with HHT also scored lower than the general population, particularly older patients, males, and patients with HHT2. They also had values similar to those of populations with chronic illnesses. The subjective perception of the severity of epistaxis correlated strongly with the VAS and social index values. CONCLUSIONS: The quality of life of patients with HHT, estimated using the EuroQol 5D-3L scale, is affected across all dimensions. The scores are similar to those seen in cases of other chronic diseases. Older patients, males and the carriers of the ACVRL1 mutation generally have worse scores on these scales. The VAS and the social index value are index that correlate well with the severity of the clinical symptoms associated mainly with epistaxis.

Screening pulmonary arteriovenous malformations in a large cohort of Spanish patients with hemorrhagic hereditary telangiectasia.

BACKGROUND AND OBJECTIVES: Because of the serious nature of potential complications, screening for pulmonary arteriovenous malformations is required in patients with hereditary hemorrhagic telangiectasia. The aim of this study was to evaluate the utility of contrast echocardiography and compare the performance of two contrast agents: agitated saline and Gelofusine. MATERIAL AND METHODS: Two hundred and five patients screened for PAVMs using TTCE and computed tomography (CT) performed with an interval of less than 180days. Contrast echocardiography studies were graded on a 4-point semiquantitative scale based on the amount of microbubbles seen in left heart chambers. RESULTS: Positive TTCE findings were seen in 137 (66.8%) patients, whereas CT confirmed PAVMs in 59 (43.1%). Two of 67 grade 1 patients; 18 of 42 grade 2; 17 of 22 grade 3 and all grade 4 had PAVMs on CT. Embolotherapy was feasible in 38.9% patients in grade 2 and 82.3% and 95.2% in grades 3-4. No patients in grade 1 were embolized. The mean cardiac cycle in which bubbles were first seen in the left heart in patients without and with PAVMs on CT was 6.1 and 3.9 (p<0.0001). Compared to saline, Gelofusine produced an overall increase in grade. CONCLUSIONS: No grade 1 patients had treatable PAVMs. There is a need for improvement in the selection of patients for CT in grade 2, where less than half have PAVMs on CT. The cardiac cycle may help to differentiate between patients with and without PAVMs. Gelofusine was not better than saline for PAVM screening.

Clinical usefulness and safety of an age-adjusted D-dimer cutoff levels to exclude pulmonary embolism: a retrospective analysis.

Age-adjusted D-dimer (AADD) appears to increase the proportion of patients in whom pulmonary embolism (PE) can safely be excluded compared with conventional D-dimer (CDD), according to a limited number of studies. The aim if this study was to assess whether the use of an AADD might safely increase the clinical usefulness of CDD for the diagnosis of PE in our setting. Three hundred and sixty two consecutive outpatients with clinically suspected PE in whom plasma samples were obtained to measure D-dimer were included in this post hoc analysis of a previous study. CDD cutoff value was 500 ng/mL and AADD was calculated as (patient's age × 10) ng/mL in patients aged >50. Sensitivity, specificity, clinical usefulness (i.e., proportion of true-negative tests among all patients with suspected PE), and the proportion of false negatives were calculated for both AADD and CDD among patients with low-to-moderate clinical probability of PE according to Well's criteria. PE was confirmed in 98 patients (27%). Among 331 patients with low-to-moderate clinical probability of PE, sensitivity and clinical usefulness were 100 and 27.8% for CDD, respectively, and 100 and 36.5% for AADD, respectively. In 29 patients aged >50 with CDD >500 ng/mL, AADD showed values under its normal cutoff point, without false negatives for the diagnosis of PE (0%, 95% CI 0-11%). AADD increases clinical usefulness notably with respect to that of CDD in patients with clinical suspected PE without losing sensitivity in our cohort. The use of AADD apparently does not reduce the safety of CDD for the exclusion of PE.

Can the tandem measurement of age adjusted D-dimer and tissue plasminagen activator improve the clinical utility of a conventional D-dimer in the pulmonary embolism diagnosis?

BACKGROUND: The aim of this study was to evaluate if a sequential measurement of age adjust D-dimer (ADD) and tissue plasminogen activator (tPA) could increase the clinical utility in patients with suspected pulmonary embolism (PE) compared to a conventional D-dimer. METHODS: We measured a conventional D-dimer (CDD), an ADD alone and a sequential combination ADD and tPA (ADD/tPA combination) in a prospective sample of 127 outpatients with PE suspected. Diagnosis of PE was based on a strict protocol. Plasma sample to measure levels of tPA and D-dimer was obtained at enrollment, and CDD, ADD and tPA were assessed at the end of study. For CDD the cut-off value was 500 ng/mL and for ADD the cut-off value was defined as (patient's age x10) ng/mL in patients aged >50. We compared the sensitivity, specificity and clinical utility obtained for CDD, ADD alone, and ADD/tPA combination. RESULTS: PE was confirmed in 41 patients (32%). The sensitivity, specificity and clinical utility for CDD were 95%, 36% and 28%, respectively. The ADD/tPA combination and ADD alone demonstrated an increased in specificity of +29% and +12% respectively, and increased in clinical utility of +20% and +8%, respectively, compared to CDD, and this was obtained without loss of sensitivity. CONCLUSION: The ADD/tPA combination substantially increased the clinical utility in the PE diagnosis compared with conventional D-dimer, without reducing the security. The ADD/tPA combination could decrease the need for pulmonary vascular imaging for the PE diagnosis in nearly the half. These promising results should be validated prospectively.

26Postoperative diagnosis and outcome in patients with revision arthroplasty for aseptic loosening.

BACKGROUND: The most common cause of implant failure is aseptic loosening (AL), followed by prosthetic joint infection (PJI). This study evaluates the incidence of PJI among patients operated with suspected AL and whether the diagnosis of PJI was predictive of subsequent implant failure including re-infection, at 2 years of follow up. METHODS: Patients undergoing revision hip or knee arthroplasty due to presumed AL from February 2009 to September 2011 were prospectively evaluated. A sonication fluid of prosthesis and tissue samples for microbiology and histopathology at the time of the surgery were collected. Implant failure include recurrent or persistent infection, reoperation for any reason or need for chronic antibiotic suppression. RESULTS: Of 198 patients with pre-and intraoperative diagnosis of AL, 24 (12.1 %) had postoperative diagnosis of PJI. After a follow up of 31 months (IQR: 21 to 38 months), 9 (37.5 %) of 24 patients in the PJI group had implant failure compared to only 1 (1.1 %) in the 198 of AL group (p < 0.0001). Sensitivity of sonicate fluid culture (>20 CFU) and peri-prosthetic tissue culture were 87.5 % vs 66.7 %, respectively. Specificities were 100 % for both techniques (95 % CI, 97.9-100 %). A greater number of patients with PJI (79.1 %) had previous partial arthroplasty revisions than those patients in the AL group (56.9 %) (p = 0.04). In addition, 5 (55.5 %) patients with PJI and implant failure had more revision arthroplasties during the first year after the last implant placement than those patients with PJI without implant failure (1 patient; 6.7 %) (RR 3.8; 95 % CI 1.4-10.1; p = 0.015). On the other hand, 6 (25 %) patients finally diagnosed of PJI were initially diagnosed of AL in the first year after primary arthroplasty, whereas it was only 16 (9.2 %) patients in the group of true AL (RR 2.7; 95 % CI 1.2-6.1; p = 0.03). CONCLUSIONS: More than one tenth of patients with suspected AL are misdiagnosed PJI. Positive histology and positive peri-implant tissue and sonicate fluid cultures are highly predictive of implant failure in patients with PJI. Patients with greater number of partial hip revisions for a presumed AL had more risk of PJI. Early loosening is more often caused by hidden PJI than late loosening.

Folic acid deficiency induces premature hearing loss through mechanisms involving cochlear oxidative stress and impairment of homocysteine metabolism.

Nutritional imbalance is emerging as a causative factor of hearing loss. Epidemiologic studies have linked hearing loss to elevated plasma total homocysteine (tHcy) and folate deficiency, and have shown that folate supplementation lowers tHcy levels potentially ameliorating age-related hearing loss. The purpose of this study was to address the impact of folate deficiency on hearing loss and to examine the underlying mechanisms. For this purpose, 2-mo-old C57BL/6J mice (Animalia Chordata Mus musculus) were randomly divided into 2 groups (n = 65 each) that were fed folate-deficient (FD) or standard diets for 8 wk. HPLC analysis demonstrated a 7-fold decline in serum folate and a 3-fold increase in tHcy levels. FD mice exhibited severe hearing loss measured by auditory brainstem recordings and TUNEL-positive-apoptotic cochlear cells. RT-quantitative PCR and Western blotting showed reduced levels of enzymes catalyzing homocysteine (Hcy) production and recycling, together with a 30% increase in protein homocysteinylation. Redox stress was demonstrated by decreased expression of catalase, glutathione peroxidase 4, and glutathione synthetase genes, increased levels of manganese superoxide dismutase, and NADPH oxidase-complex adaptor cytochrome b-245, α-polypeptide (p22phox) proteins, and elevated concentrations of glutathione species. Altogether, our findings demonstrate, for the first time, that the relationship between hyperhomocysteinemia induced by folate deficiency and premature hearing loss involves impairment of cochlear Hcy metabolism and associated oxidative stress.

Tissue plasminogen activator as a novel diagnostic aid in acute pulmonary embolism.

BACKGROUND: We evaluated the diagnostic efficacy of tissue plasminogen activator (tPA), using an enzyme-linked immunosorbent assay (ELISA) and compared it with an ELISA D-dimer (VIDAS D-dimer) in acute pulmonary embolism (PE). PATIENTS AND METHODS: We studied 127 consecutive outpatients with clinically suspected PE. The diagnosis of PE was based on a clinical probability pretest for PE and a strict protocol of imaging studies. A plasma sample to measure the levels of tPA and D-dimer was obtained at enrollment. Diagnostic accuracy for tPA and D-dimer was determined by the area under the receiver operating characteristic (ROC) curve. Sensitivity, specificity, predictive values, and the diagnostic utility of tPA with a cutoff of 8.5 ng/mL and D-dimer with a cutoff of 500 ng/mL, were calculated for PE diagnosis. RESULTS: PE was confirmed in 41 patients (32 %). Areas under ROC curves were 0.86 for D-dimer and 0.71 for tPA. The sensitivity/negative predictive value for D-dimer using a cutoff of 500 ng/mL, and tPA using a cutoff of 8.5 ng/mL, were 95 % (95 % CI, 88-100 %)/95 % (95 % CI, 88-100 %) and 95 % (95 % CI, 88-100 %)/94 %), respectively. The diagnostic utility to exclude PE was 28.3 % (95 % CI, 21-37 %) for D-dimer and 24.4 % (95 % CI, 17-33 %) for tPA. CONCLUSIONS: The tPA with a cutoff of 8.5 ng/mL has a high sensitivity and negative predictive value for exclusion of PE, similar to those observed for the VIDAS D-dimer with a cutoff of 500 ng/mL, although the diagnostic utility was slightly higher for the D-dimer.