Increased flexibility of CA3 memory representations following environmental enrichment.

Environmental enrichment (EE) improves memory, particularly the ability to discriminate similar past experiences.1,2,3,4,5,6 The hippocampus supports this ability via pattern separation, the encoding of similar events using dissimilar memory representations.7 This is carried out in the dentate gyrus (DG) and CA3 subfields.8,9,10,11,12 Upregulation of adult neurogenesis in the DG improves memory through enhanced pattern separation.1,2,3,4,5,6,11,13,14,15,16 Adult-born granule cells (abGCs) in DG are suggested to contribute to pattern separation by driving inhibition in regions such as CA3,13,14,15,16,17,18 leading to sparser, nonoverlapping representations of similar events (although a role for abGCs in driving excitation in the hippocampus has also been reported16). Place cells in the hippocampus contribute to pattern separation by remapping to spatial and contextual alterations to the environment.19,20,21,22,23,24,25,26,27 How spatial responses in CA3 are affected by EE and input from increased numbers of abGCs in DG is, however, unknown. Here, we investigate the neural mechanisms facilitating improved memory following EE using associative recognition memory tasks that model the automatic and integrative nature of episodic memory. We find that EE-dependent improvements in difficult discriminations are related to increased neurogenesis and sparser memory representations across the hippocampus. Additionally, we report for the first time that EE changes how CA3 place cells discriminate similar contexts. CA3 place cells of enriched rats show greater spatial tuning, increased firing rates, and enhanced remapping to contextual changes. These findings point to more precise and flexible CA3 memory representations in enriched rats, which provides a putative mechanism for EE-dependent improvements in fine memory discrimination.

Enhancing Safety on Construction Sites: A UWB-Based Proximity Warning System Ensuring GDPR Compliance to Prevent Collision Hazards.

Construction is known as one of the most dangerous industries in terms of worker safety. Collisions due the excessive proximity of workers to moving construction vehicles are one of the leading causes of fatal and non-fatal accidents on construction sites internationally. Proximity warning systems (PWS) have been proposed in the literature as a solution to detect the risk for collision and to alert workers and equipment operators in time to prevent collisions. Although the role of sensing technologies for situational awareness has been recognised in previous studies, several factors still need to be considered. This paper describes the design of a prototype sensor-based PWS, aimed mainly at small and medium-sized construction companies, to collect real-time data directly from construction sites and to warn workers of a potential risk of collision accidents. It considers, in an integrated manner, factors such as cost of deployment, the actual nature of a construction site as an operating environment and data protection. A low-cost, ultra-wideband (UWB)-based proximity detection system has been developed that can operate with or without fixed anchors. In addition, the PWS is compliant with the General Data Protection Regulation (GDPR) of the European Union. A privacy-by-design approach has been adopted and privacy mechanisms have been used for data protection. Future work could evaluate the PWS in real operational conditions and incorporate additional factors for its further development, such as studies on the timely interpretation of data.

Definition of an Indoor Air Sampling Strategy for SARS-CoV-2 Detection and Risk Management: Case Study in Kindergartens.

In the last two years, the world has been overwhelmed by SARS-CoV-2. One of the most important ways to prevent the spread of the virus is the control of indoor conditions: from surface hygiene to ventilation. Regarding the indoor environments, monitoring the presence of the virus in the indoor air seems to be promising, since there is strong evidence that airborne transmission through infected droplets and aerosols is its dominant transmission route. So far, few studies report the successful detection of SARS-CoV-2 in the air; moreover, the lack of a standard guideline for air monitoring reduces the uniformity of the results and their usefulness in the management of the risk of virus transmission. In this work, starting from a critical analysis of the existing standards and guidelines for indoor air quality, we define a strategy to set-up indoor air sampling plans for the detection of SARS-CoV-2. The strategy is then tested through a case study conducted in two kindergartens in the metropolitan city of Milan, in Italy, involving a total of 290 children and 47 teachers from 19 classrooms. The results proved its completeness, effectiveness, and suitability as a key tool in the airborne SARS-CoV-2 infection risk management process. Future research directions are then identified and discussed.

Soluble ST2 and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction.

BACKGROUND: Identifying patients at risk of poor diuretic response in acute heart failure (AHF) is critical to make prompt adjustments in therapy. The objective of this study was to investigate whether the circulating levels of soluble ST2 predict the cumulative diuretic efficiency (DE) at 24 and 72 hours in patients with AHF and concomitant renal dysfunction. METHODS AND RESULTS: This is a post hoc analysis of the IMPROVE-HF trial, in which we enrolled 160 patients with AHF and renal dysfunction (estimated glomerular filtrate rate of <60 mL/min/1.73 m2). DE was calculated as the net fluid output produced per 40 mg of furosemide equivalents. The association between sST2 and DE was evaluated by using multivariate linear regression analysis. The median cumulative DE at 24 and 72 hour was 747 mL (interquartile range 490-1167 mL) and 1844 mL (interquartile range 1142-2625 mL), respectively. The median sST2 and mean estimated glomerular filtrate rate were 72 ng/mL (interquartile range 47-117 ng/mL), and 34.0 ± 8.5 mL/min/1.73 m2, respectively. In a multivariable setting, higher sST2 were significant and nonlinearly related to lower DE both at 24 and 72 hours (P = .002 and P = .019, respectively). CONCLUSIONS: In patients with AHF and renal dysfunction at presentation, circulating levels of sST2 were independently and negatively associated with a poor diuretic response, both at 24 and 72 hours.

Early urinary sodium trajectory and risk of adverse outcomes in acute heart failure and renal dysfunction.

INTRODUCTION AND OBJECTIVES: Urinary sodium (UNa+) has emerged as a useful biomarker of poor clinical outcomes in acute heart failure (AHF). Here, we sought to evaluate: a) the usefulness of a single early determination of UNa+ for predicting adverse outcomes in patients with AHF and renal dysfunction, and b) whether the change in UNa+ at 24hours (ΔUNa24h) adds any additional prognostic information over baseline values. METHODS: This is a post-hoc analysis of a multicenter, open-label, randomized clinical trial (IMPROVE-HF) (ClinicalTrials.gov NCT02643147) that randomized 160 patients with AHF and renal dysfunction on admission to a) the standard diuretic strategy, or b) a carbohydrate antigen 125-guided diuretic strategy. The primary end point was all-cause mortality and total all-cause readmissions. RESULTS: The mean age was 78±8 years, and the mean glomerular filtration rate was 34.0±8.5mL/min/1.73 m2. The median UNa+ was 90 (65-111) mmol/L. At a median follow-up of 1.73 years [interquartile range, 0.48-2.35], 83 deaths (51.9%) were registered, as well as 263 all-cause readmissions in 110 patients. UNa+ was independently associated with mortality (HR, 0.75; 95%CI, 0.65-0.87; P <.001) and all-cause readmissions (HR, 0.92; 95%CI, 0.88-0.96; P <.001). The prognostic usefulness of the ΔUNa24h varied according to UNa+ at admission (P for interaction <.05). The ΔUNa24h was inversely associated with both end points only in the group with UNa+ ≤ 50 mmol/L. Conversely, no effect was found in the group with UNa+> 50 mmol/L. CONCLUSIONS: In patients with AHF and renal dysfunction, a single early determination of UNa+ ≤ 50 mmol/L identifies patients with a higher risk of all-cause mortality and readmission. The ΔUNa24h adds prognostic information over baseline values only when UNa+ at admission is ≤ 50 mmol/L.

Early Spot Urinary Sodium and Diuretic Efficiency in Acute Heart Failure and Concomitant Renal Dysfunction.

OBJECTIVE: In acute heart failure (AHF), early assessment of spot urinary sodium (UNa) has emerged as a useful biomarker for risk stratification and monitoring. The objective of this study was to investigate (a) whether early spot UNa predicts 24-h diuretic efficiency and (b) the clinical factors associated with early spot UNa in patients with AHF and concomitant renal dysfunction (RD). METHODS: This is a post hoc analysis of the IMPROVE-HF trial, in which 160 patients with AHF and RD (estimated glomerular filtrate rate [eGFR] <60 mL/min/1.73 m2) were included. Diuretic efficiency was calculated as the net fluid output produced per 40 mg of furosemide equivalents in 24 h. The association between early spot UNa and diuretic efficiency and clinical variables associated with UNa were evaluated using multivariate linear regression analysis. The contribution of the exposures in the predictability of the models was assessed with the coefficient of determination (R2). RESULTS: The mean age of the study population was 78 ± 8 years. The median (interquartile range) diuretic efficiency, early spot UNa, aminoterminal pro-brain natriuretic peptide, and eGFR were 747 (490-1,167) mL, 90 mmol/L (65-111), 7,765 pg/mL (3,526-15,369), and 33.7 ± 11.3 mL/min/1.73 m2, respectively. In a multivariate setting, lower UNa was significantly and nonlinearly associated with lower diuretic efficiency (p = 0.001), explaining the 44.4% of the model predictability. Natremia and surrogates of congestion emerged as the main factors related to UNa. CONCLUSIONS: In patients with AHF and RD at presentation, early spot UNa was inversely related to 24-h diuretic efficiency.

Vasodilator Stress CMR and All-Cause Mortality in Stable Ischemic Heart Disease: A Large Retrospective Registry.

OBJECTIVES: This study explored the association of ischemic burden, as measured by vasodilator stress cardiovascular magnetic resonance (CMR), with all-cause mortality and the effect of revascularization on all-cause mortality in patients with stable ischemic heart disease (SIHD). BACKGROUND: In patients with SIHD, the association of ischemic burden, derived from vasodilator stress CMR, with all-cause mortality and its role for decision-making is unclear. METHODS: The registry consisted of 6,389 consecutive patients (mean age: 65 ± 12 years; 38% women) who underwent vasodilator stress CMR for known or suspected SIHD. The ischemic burden (at stress first-pass perfusion imaging) was computed (17-segment model). The effect of CMR-related revascularization (within the following 3 months) on all-cause mortality was retrospectively explored using the electronic regional health system registry. RESULTS: During a 5.75-year median follow-up, 717 (11%) deaths were documented. In multivariable analyses, more extensive ischemic burden (per 1-segment increase) was independently related to all-cause mortality (hazard ratio: 1.04; 95% confidence interval: 1.02 to 1.07; p < 0.001). In 1,032 1:1 matched patients using a limited number of variables (516 revascularized, 516 non-revascularized), revascularization within the following 3 months was associated with less all-cause mortality only in patients with extensive CMR-related ischemia (>5 segments, n = 432; 10% vs. 24%; p = 0.01). CONCLUSIONS: In a large retrospective registry of unselected patients with known or suspected SIHD who underwent vasodilator stress CMR, extensive ischemic burden was related to a higher risk of long-term, all-cause mortality. Revascularization was associated with a protective effect only in the restricted subset of patients with extensive CMR-related ischemia. Further research will be needed to confirm this hypothesis-generating finding.

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.

Diuretic Strategies in Acute Heart Failure and Renal Dysfunction: Conventional vs Carbohydrate Antigen 125-guided Strategy. Clinical Trial Design.

INTRODUCTION AND OBJECTIVES: The optimal treatment of patients with acute heart failure (AHF) and cardiorenal syndrome type 1 (CRS-1) is far from being well-defined. Arterial hypoperfusion in concert with venous congestion plays a crucial role in the pathophysiology of CRS-I. Plasma carbohydrate antigen 125 (CA125) has emerged as a surrogate of fluid overload in AHF. The aim of this study was to evaluate the clinical usefulness of CA125 for tailoring the intensity of diuretic therapy in patients with CRS-1. METHODS: Multicenter, open-label, parallel clinical trial, in which patients with AHF and serum creatinine ≥ 1.4mg/dL on admission will be randomized to: a) standard diuretic strategy: titration-based on conventional clinical and biochemical evaluation, or b) diuretic strategy based on CA125: high dose if CA125 > 35 U/mL, and low doses otherwise. The main endpoint will be renal function changes at 24 and 72hours after therapy initiation. Secondary endpoints will include: a) clinical and biochemical changes at 24 and 72hours, and b) renal function changes and major clinical events at 30 days. RESULTS: The results of this study will add important knowledge on the usefulness of CA125 for guiding diuretic treatment in CRS-1. In addition, it will pave the way toward a better knowledge of the pathophysiology of this challenging situation. CONCLUSIONS: We hypothesize that higher levels of CA125 will identify a patient population with CRS-1 who could benefit from the use of a more intense diuretic strategy. Conversely, low levels of this glycoprotein could select those patients who would be harmed by high diuretic doses.

Randomized comparison between the invasive and conservative strategies in comorbid elderly patients with non-ST elevation myocardial infarction.

BACKGROUND: Comorbid elderly patients with non-ST-elevation myocardial infarction (non-STEMI) are underrepresented in randomized trials and undergo fewer cardiac catheterizations according to registries. Our aim was to compare the conservative and invasive strategies in these patients. METHODS: Randomized multicenter study, including 106 patients (January 2012-March 2014) with non-STEMI, over 70years and with comorbidities defined by at least two of the following: peripheral artery disease, cerebral vascular disease, dementia, chronic pulmonary disease, chronic renal failure or anemia. Patients were randomized to invasive (routine coronary angiogram, n=52) or conservative (coronary angiogram only if recurrent ischemia or heart failure, n=54) strategy. Medical treatment was identical. The main endpoint was the composite of all-cause mortality, reinfarction and readmission for cardiac cause (postdischarge revascularization or heart failure), at long-term (2.5-year follow-up). Analysis of cumulative event rate (incidence rate ratio=IRR) and time to first event (hazard ratio=HR), were performed. RESULTS: Cardiac catheterization/revascularization rates were 100%/58% in the invasive versus 20%/9% in the conservative arm. There were no differences between groups in the main endpoint (invasive vs conservative: IRR=0.946, 95% CI 0.466-1.918, p=0.877) at long-term. The invasive strategy, however, tended to improve 3-month outcomes in terms of mortality (HR=0.348, 95% CI 0.122-0.991, p=0.048), and of mortality or ischemic events (reinfarction or postdischarge revascularization) (HR=0.432, 95% CI 0.190-0.984, p=0.046). This benefit declined during follow-up. CONCLUSIONS: Invasive management did not modify long-term outcome in comorbid elderly patients with non-STEMI. The finding of a tendency towards an improvement in the short-term needs confirmation in larger studies (clinicaltrials.govNCT1645943).

Bioelectrical impedance vector analysis and clinical outcomes in patients with acute heart failure.

AIMS: Fluid overload is a hallmark in acute heart failure (AHF). Bioelectrical impedance vector analysis (BIVA) has emerged as a noninvasive method for quantifying patients' hydration. We aimed to evaluate the effect of BIVA hydration status (BHS) measured before discharge on mortality and rehospitalization for AHF. METHODS: We included 369 consecutive patients discharged from the cardiology department from a third-level hospital with a diagnosis of AHF. On the basis of BHS, patients were grouped into three categories: hyper-hydration (>74.3%), normo-hydration (72.7-74.3%) and dehydration (<72.7%). Appropriate survival techniques were used to evaluate the association between BHS and the risk of death and readmission for AHF. RESULTS: At a median follow-up of 12 months (interquartile range, IQR: 5-19), 80 (21.7%) deaths and 93 (25.2%) readmissions for AHF were registered. The mortality and readmission rates for the BHS categories were hyper-hydration (3.28 and 3.83 per 10 persons-years); normo-hydration (1.43 and 2.68 per 10 persons-years); and dehydration (2.24 and 2.53 per 10 persons-years) (P < 0.05 for all comparisons). In an adjusted analysis, BHS displayed a significant association with mortality (P = 0.004), with a higher mortality risk in those with hyperhydration. Likewise, BHS showed to linearly predict AHF-readmission risk [hazard ratio 1.06 (1.03-1.10); P = 0.001 per increase in 1%]. CONCLUSION: In patients admitted with AHF, BHS assessed before discharge was independently associated with the risk of death and AHF-readmission.

Differential Effect of Glycosylated Hemoglobin Value and Antidiabetic Treatment on the Risk of 30-day Readmission Following a Hospitalization for Acute Heart Failure.

INTRODUCTION AND OBJECTIVES: In patients with heart failure and type 2 diabetes, low glycosylated hemoglobin has been related with higher risk of mortality but information regarding morbidity is scarce. We sought to evaluate the association between glycosylated hemoglobin and 30-day readmission in patients with type 2 diabetes and acute heart failure. METHODS: Glycosylated hemoglobin was measured before discharge in 835 consecutive patients with acute heart failure and type 2 diabetes. Cox regression analysis adapted for competing events was used. RESULTS: Mean (standard deviation) age was 72.9 (9.6) years and median glycosylated hemoglobin was 7.2% (6.5%-8.0%). Patients treated with insulin or insulin/sulfonylurea/meglitinides were 41.1% and 63.2% of the cohort, respectively. At 30 days post-discharge, 109 (13.1%) patients were readmitted. A multivariate analysis revealed that the effect of glycosylated hemoglobin on the risk of 30-day readmission was differentially affected by the type of treatment (P for interaction<.01). Glycosylated hemoglobin (per 1% decrease) was inversely associated with higher risk in those receiving insulin (hazard ratio = 1.45; 95% confidence interval, 1.13-1.86; P=.003) or insulin/sulfonylurea/meglitinides (hazard ratio = 1.44; 95% confidence interval, 1.16-1.80; P=.001). Conversely, glycosylated hemoglobin (per 1% increase) had no effect in non-insulin dependent diabetes (hazard ratio = 1.01; 95% confidence interval, 0.87-1.17; P=.897) or even a positive effect in patients not receiving insulin/sulfonylurea/meglitinides (hazard ratio = 1.12; 95% confidence interval, 1.03-1.22; P=.011). CONCLUSIONS: In acute heart failure, glycosylated hemoglobin showed to be inversely associated to higher risk of 30-day readmission in insulin-dependent or those treated with insulin/sulfonylurea/meglitinides. A marginal effect was found in the rest. Whether this association reflects a treatment-related effect or a surrogate of more advanced disease should be clarified in further studies.

Frailty and other geriatric conditions for risk stratification of older patients with acute coronary syndrome.

BACKGROUND: Geriatric conditions may predict outcomes beyond age and standard risk factors. Our aim was to investigate a wide spectrum of geriatric conditions in survivors after an acute coronary syndrome. METHODS: A total of 342 patients older than 65 years were included. At hospital discharge, 5 geriatric conditions were evaluated: frailty (Fried and Green scores), physical disability (Barthel index), instrumental disability (Lawton-Brody scale), cognitive impairment (Pfeiffer questionnaire), and comorbidity (Charlson and simple comorbidity indexes). The outcomes were postdischarge mortality and the composite of death/myocardial infarction during a 30-month median follow-up. RESULTS: Seventy-four (22%) patients died and 105 (31%) suffered from the composite end point. Through univariable analysis, all individual geriatric indexes were associated with outcomes, mainly mortality. Of all of them, frailty using the Green score had the strongest discriminative accuracy (area under the receiver operating characteristic curve 0.76 for mortality). After full adjustment including clinical and geriatric data, the Green score was the only independent predictive geriatric condition (per point; mortality: hazard ratio 1.25, 95% CI 1.15-1.36, P = .0001; composite end point: hazard ratio 1.16, 95% CI 1.09-1.24, P = .0001). A Green score ≥ 5 points was the strongest mortality predictor. The addition of the Green score to the clinical model improved discrimination (area under the receiver operating characteristic curve 0.823 vs 0.846) and significantly reclassified mortality risk (net reclassification improvement 26.3, 95% CI 1.4-43.5; integrated discrimination improvement 4.0, 95% CI 0.8-9.0). The incremental predictive information was even greater over the GRACE score. CONCLUSIONS: Frailty captures most of the prognostic information provided by geriatric conditions after acute coronary syndromes. The Green score performed better than the other geriatric indexes.

High-sensitivity versus conventional troponin for management and prognosis assessment of patients with acute chest pain.

OBJECTIVES: High-sensitivity troponin (hs-cTn) is substituting conventional cTn for evaluation of chest pain. Our aim was to assess the impact on patient management and outcome. METHODS: A total of 1372 consecutive patients presenting at the emergency department with non-ST-elevation acute chest pain were divided into two periods according to the cTn assay used, conventional (n=699, March 2008 to July 2010) or hs-cTn (n=673, November 2010 to March 2013). Management policies were similar and according to guidelines. The primary endpoint was major adverse cardiac events (MACE) at 6 months (death, myocardial infarction, readmission by unstable angina or postdischarge revascularisation). RESULTS: There were minor differences in baseline characteristics. In the hs-cTn period, more patients elevated cTn (73% vs 37%, p=0.0001) leading to more coronary angiograms (77% vs 55%, p=0.0001) and revascularisations (45% vs 31%, p=0.0001); conversely, fewer patients were initially assigned to exercise testing (14% vs 36%, p=0.0001) and, therefore, discharged early after a negative result (7% vs 22%, p=0.0001). At 6 months, 135 patients suffered MACE, including 54 deaths. After adjusting for a Propensity Score, hs-cTn use was not significantly associated with MACE (HR=0.99; 95% CI 0.70 to 1.41; p=0.98) or mortality (HR=1.02; 95% CI 0.59 to 1.77; p=0.95), though the risk of longer hospitalisation stay increased at the index episode (OR=1.35, 95% CI 1.07 to 1.71, p=0.02). CONCLUSIONS: hs-cTn simplified chest pain triage on avoiding a more complex evaluation with non-invasive tests in the chest pain unit, but prompted longer hospitalisations and more invasive procedures without impacting on the 6-month outcomes.

Antigen carbohydrate 125 and creatinine on admission for prediction of renal function response following loop diuretic administration in acute heart failure.

BACKGROUND: The use of loop diuretics in acute heart failure (AHF) is largely empirical and has been associated with renal function impairment by reducing renal perfusion but also renal improvement by decreasing renal venous congestion. Antigen carbohydrate 125 (CA125) has emerged as a proxy for fluid overload. We sought to evaluate whether the early changes in creatinine (ΔCr) induced by intravenous furosemide doses (ivFD) differ among clinical groups defined by overload status (CA125) and creatinine on admission (Cr). METHODS AND RESULTS: We included 526 consecutive patients admitted for AHF. All patients received intravenous furosemide for the first 48 hours. CA125 and Cr were dichotomized at 35 U/ml and 1.4 mg/dl, respectively, and grouped as follows: C1 [Cr <1.4, CA125 ≤ 35 (n=151)]; C2 [Cr <1.4, CA125 >35 (n=241)]; C3 [Cr ≥ 1.4, CA125 ≤ 35 (n=45)]; and C4 [Cr ≥ 1.4, CA125 >35 (n=89)]. Clinicians in charge of the management of patients were blind to CA125 values. ΔCr was estimated as the absolute difference in Cr between admission and 48-72 hours. Multivariable linear regression analysis was used for modeling purposes. The adjusted analysis showed a differential effect of ivFD on ΔCr. Per increase in 20mg/day of ivFD, the mean ΔCr was 0.010 mg/dl (p=0.464) in C1, 0.002 mg/dl (p=0.831) in C2, 0.045 mg/dl (p=0.032) in C3, and -0.045 mg/dl (p<0.001) in C4 (omnibus p<0.001). A similar pattern of response was observed in a validation cohort. CONCLUSIONS: In patients with AHF, the magnitude and direction of ΔCr attributable to ivFD were differentially associated with values of CA125 and Cr on admission.

Higiene del cordón umbilical con alcohol comparado con secado natural y baño antes de su caída, en recién nacidos de término: ensayo clínico controlado aleatorizado / Alcohol versus bath and natural drying for term newborns' umbilical cord care: a prospective randomized clinical trial

El cuidado e higiene del cordón umbilical (CU) es motivo de preocupación para los padres. Objetivos. Principal: comparar la efectividad del secado natural del CU, con la práctica habitual (alcohol), en la reducción del tiempo de caída del CU y la incidencia de infecciones en el recién nacido (RN). Secundarios: comparar la colonización bacteriana intrahospitalaria del CU, y el grado de satisfacción de los padres en ambos grupos. Población. RN de término asistidos en el Servicio de Neonatología del Hospital Privado del Sur, cuyos padres consintieron participar. Material y métodos. Estudio clínico prospectivo, controlado, abierto, aleatorizado, en dos grupos: Grupo Estudio (secado natural y baño diario con jabón neutro) y Grupo Control (alcohol 70%). Variables principales: tiempo de caída del CU; presencia de infecciones en piel o conjuntivas en el primer mes de vida; colonización del cordón y satisfacción parental. Análisis por intención de tratamiento. Resultados. Se analizaron 362 RN, 181 en cada grupo. La higiene con baño se asoció con una mayor frecuencia de colonización intrahospitalaria del CU (OR 1,92 [1,22 - 3,12], p <0,01) y caída del cordón más temprana (mediana [rango intercuartílico]= 6,00 [3] vs. 7,00 [4] días en el grupo control; p <0,001). No se observó un mayor riesgo de infecciones. El grado de satisfacción parental fue similar y elevado en ambos grupos. Conclusiones. El secado natural y baño redujo el tiempo de caída del CU; aun cuando la frecuencia de colonización fue mayor en el grupo estudio, no se encontró un riesgo mayor de infecciones en el primer mes.

Background. Umbilical cord (UC) care is a cause of concern for parents from birth until its separation. Standard practice in Argentina includes frequent cleansing of the UC with alcohol and body bath only two days after its separation. The effect of different methods of UC care on its separation time and on colonization with microorganisms has been insufficiently explored. Objectives. Main: To compare the effect on time of UC separation when using body bath with neutral soap followed by natural drying of the UC vs. standard care. Secondary: a) colonization rates during hospitalization; b) incidence of skin infection and conjunctivitis and c) parental comfort with both types of care. Population. Normal term newborns (>37 weeks), born at the HPS, and whose parents provided informed consent. Methods. Open prospective controlled clinical trial, with random allocation to two groups: study group -natural drying of the UC and body bath with neutral soap-and control group -UC hygiene with alcohol 70% at each diaper change until its separation and bath two days later-. UC separation time; UC colonization during hospital stay and skin and conjunctive infections in the first 30 days of life were monitored. Analysis was by intention-to-treat. Results. 362 newborns were included, 181 in each group. The groups were well balanced in baseline characteristics. Being in the study group was associated with a shorter time to UC separation (median [interquartile range]= 6.00 [3] vs. 7.00 [4] days; p <0.001) and an increased frequency in nosocomial UC colonization (adjusted OR= 1.92 [1.22- 3.12], p= 0.007). No difference in the rate of infections was observed between both groups. Parental comfort was high and similar in both groups. Conclusions. Compared to standard practice in Argentina, body bath with neutral soap and natural drying of the UC reduced the time to cord separation. This practice increased the colonization rate, but the risk of skin and conjunctive infections was apparently not modified by it. However, the study has insufficient power for secondary outcomes. Health care providers should continue to develop evidence to support or eliminate historical practices.

Differential mortality association of loop diuretic dosage according to blood urea nitrogen and carbohydrate antigen 125 following a hospitalization for acute heart failure.

AIMS: Recent observations in chronic stable heart failure suggest that high-dose loop diuretics (HDLDs) have detrimental prognostic effects in patients with high blood urea nitrogen (BUN), but recent findings have also indicated that diuretics may improve renal function. Carbohydrate antigen 125 (CA125) has been shown to be a surrogate of systemic congestion. We sought to explore whether BUN and CA125 modulate the mortality risk associated with HDLDs following a hospitalization for acute heart failure (AHF). METHODS AND RESULTS: We analysed 1389 consecutive patients discharged for AHF. CA125 and BUN were measured at a mean of 72 ± 12 h after admission. HDLDs (≥120 mg/day in furosemide equivalent dose) were interacted to a four-level variable according to CA125 (>35 U/mL) and BUN (above the median), and related to all-cause mortality. At a median follow-up of 21 months, 561 (40.4%) patients died. The use of HDLDs was independently associated with increased mortality [hazard ratio (HR) 1.23, 95% confidence interval (CI) 1.01-1.50], but this association was not homogeneous across CA125-BUN categories (P for interaction <0.001). In patients with normal CA125, use of HDLDs was associated with high mortality if BUN was above the median (HR 2.29, 95% 1.51-3.46), but not in those with BUN below the median (HR 1.22, 95% CI 0.73-2.04). Conversely, in patients with high CA125, HDLDs showed an association with increased survival if BUN was above the median (HR 0.73, 95% CI 0.55-0.98) but was associated with increased mortality in those with BUN below the median (HR 1.94, 95% CI 1.36-2.76). CONCLUSION: The risk associated with HDLDs in patients after hospitalization for AHF was dependent on the levels of BUN and CA125. The information provided by these two biomarkers may be helpful in tailoring the dose of loop diuretics at discharge for AHF.

Differential prognostic effect of revascularization according to a simple comorbidity index in high-risk non-ST-segment elevation acute coronary syndrome.

BACKGROUND: Data on the effect of revascularization on outcome in patients with high-risk non-ST-segment elevation acute coronary syndrome (NSTEACS) and significant comorbidities are scarce. Recently, a simple comorbidity index (SCI) including 5 comorbidities (renal failure, dementia, peripheral artery disease, heart failure, and prior myocardial infarction [MI]) has shown to be a useful tool for risk stratification. Nevertheless, therapeutic implications have not been derived. HYPOTHESIS: We sought to evaluate the prognostic effect attributable to revascularization in NSTEACS according the SCI score. METHODS: We included 1017 consecutive patients with NSTEACS. The effect of revascularization on a combined end point of all-cause mortality or nonfatal MI was evaluated by Cox regression according to SCI categories. RESULTS: A total of 560 (55.1%), 236 (23.2%), and 221 (21.7%) patients showed 0, 1, and ≥2 points according to the SCI, respectively. Coronary angiography was performed in 725 patients (71.5%), and 450 patients (44.3%) underwent revascularization. During a median follow-up of 16 months (interquartile range, 12-36 months), 305 (30%) patients experienced the combined end point (202 deaths [19.9%] and 170 MIs [16.7%]). In multivariate analysis, a differential prognostic effect of revascularization was observed comparing SCI ≥2 vs 0 (P for interaction = 0.008). Thus, revascularization was associated with a greater prognostic benefit in patients with SCI ≥2 (hazard ratio [HR]: 0.51, 95% confidence interval [CI]: 0.29-0.89), P = 0.018), whereas no significant benefit was observed in those with 0 and 1 point (HR: 1.31, 95% CI: 0.88-1.94, P = 0.171 and HR: 1.11, 95% CI: 0.70-1.76, P = 0.651, respectively). CONCLUSIONS: In NSTEACS, the SCI score appears to be a useful tool for identifying a subset of patients with a significant long-term death/MI risk reduction attributable to revascularization.

Tiroides lingual una forma de patologia tiroidea amenazante de la vida / Lingual thyroid a life threatening form of thyroid pathology

Latiroides lingual es lavariante más común de tiroides ectópica benigna. Suele manifestarse en la infancia con hipotiroidismo o síntomas locales, como tos crónica y disfagia. Se diagnostica durante la niñez tras el comienzo de síntomas obstructivos, como la disfagia y disfonías progres ivas, obst rucción respiratoria intermitente, disnea, estridor laríngeo o sensación de cuerpo extraño. El diagnóstico por imagen ideal es la resonancia magnética. El objetivo de este artículo es presentar el caso de una lactante menor de 46 días, presentando estridor laríngeo, cianosis, disnea, secundaria a una disgenesia de tiroides debido a tiroides lingual, la cual la llevó a un hipotiroidismo secundario...(AU)

[Alcohol versus bath and natural drying for term newborns' umbilical cord care: a prospective randomized clinical trial]. / Higiene del cordón umbilical con alcohol comparado con secado natural y baño antes de su caída, en recién nacidos de término: ensayo clínico controlado aleatorizado.

BACKGROUND: Umbilical cord (UC) care is a cause of concern for parents right from birth until its separation. Standard practice in Argentina includes frequent cleansing of the UC with alcohol and body bath only two days after its separation. The effect of different methods of UC care on its separation time and on colonization with microorganisms has been insufficiently explored. OBJECTIVES: Main: To compare the effect on time of UC separation when using body bath with neutral soap followed by natural drying of the UC vs. standard care. Secondary: a) colonization rates during hospitalization; b) incidence of skin infection and conjunctivitis and c) parental comfort with both types of care. POPULATION: Normal term newborns (≥37 weeks), born at the HPS, and whose parents provided informed consent. METHODS: Open prospective controlled clinical trial, with random allocation to two groups: study group -natural drying of the UC and body bath with neutral soap- and control group -UC hygiene with alcohol 70% at each diaper change until its separation and bath two days later-. UC separation time; UC colonization during hospital stay and skin and conjunctive infections in the first 30 days of life were monitored. Analysis was by intention-to-treat. RESULTS: 362 newborns were included, 181 in each group. The groups were well balanced in baseline characteristics. Being in the study group was associated with a shorter time to UC separation (median [interquartile range]= 6.00 [3] vs. 7.00 [4] days; p <0.001) and an increased frequency in nosocomial UC colonization (adjusted OR= 1.92 [1.22- 3.12], p= 0.007). No difference in the rate of infections was observed between both groups. Parental comfort was high and similar in both groups. CONCLUSIONS: Compared to standard practice in Argentina, body bath with neutral soap and natural drying of the UC reduced the time to cord separation. This practice increased the colonization rate, but the risk of skin and conjunctive infections was apparently not modified by it. However, the study has insufficient power for secondary outcomes. Health care providers should continue to develop evidence to support or eliminate historical practices.