Postmortem imaging reveals patterns of medial temporal lobe vulnerability to tau pathology in Alzheimer's disease.

Our current understanding of the spread and neurodegenerative effects of tau neurofibrillary tangles (NFTs) within the medial temporal lobe (MTL) during the early stages of Alzheimer's Disease (AD) is limited by the presence of confounding non-AD pathologies and the two-dimensional (2-D) nature of conventional histology studies. Here, we combine ex vivo MRI and serial histological imaging from 25 human MTL specimens to present a detailed, 3-D characterization of quantitative NFT burden measures in the space of a high-resolution, ex vivo atlas with cytoarchitecturally-defined subregion labels, that can be used to inform future in vivo neuroimaging studies. Average maps show a clear anterior to poster gradient in NFT distribution and a precise, spatial pattern with highest levels of NFTs found not just within the transentorhinal region but also the cornu ammonis (CA1) subfield. Additionally, we identify granular MTL regions where measures of neurodegeneration are likely to be linked to NFTs specifically, and thus potentially more sensitive as early AD biomarkers.

TAV-in-TAV in patients with prosthesis embolization: Impact of commissural alignment and global outcomes.

BACKGROUND: Optimal strategies to manage embolization of transcatheter aortic valve implantation (TAVI) devices are unclear; valve-in-valve (ViV) is often used. We aimed to describe through one-single center experience its rate, causes, consequences, and management as well as the rate and relevance of commissural alignment (CA) in this context. METHODS: We identified across 1038 TAVI cases, those cases requiring ViV for the management of first device embolization. CA (absence or mild misalignment) after first and second device was assessed by CT or fluoroscopy. RESULTS: A total of 23 cases (2.2%) were identified, 52.3% embolized towards the aorta and 47.7% towards the ventricle. Suboptimal implant height (38%) and embolization at the time of post-dilation (23%) were the most frequent mechanisms together with greater rate of bicuspid valve (p < 0.001) and a trend to greater annular eccentricity. Procedural and 1-year death occurred in 13% and 34%, respectively (vs. 1.1% and 7.8% in the global cohort, p < 0.001). CA was present in 76.9% of the prostheses initially implanted but was only spontaneously achieved in 30.8% of the second ViV device. Adequate CA of both prostheses was identified in only two cases (8.7%). There were no cases of coronary obstruction. CONCLUSIONS: TAVI device embolization mechanisms can often be predicted and prevented. Mortality following bail-out ViV is higher than in regular TAVI procedures but 2/3 of these patients survived beyond 1-year follow-up. In them, valve degeneration or coronary re-access might be particularly challenging since CA was rarely achieved with both devices suggesting that greater efforts should be made in this regard.

T-Type Ca2+ Channels Mediate a Critical Period of Plasticity in Adult-Born Granule Cells.

Adult-born granule cells (abGCs) exhibit a transient period of elevated synaptic plasticity that plays an important role in hippocampal function. Various mechanisms have been implicated in this critical period for enhanced plasticity, including minimal GABAergic inhibition and high intrinsic excitability conferred by T-type Ca2+ channels. Here we assess the contribution of synaptic inhibition and intrinsic excitability to long-term potentiation (LTP) in abGCs of adult male and female mice using perforated patch recordings. We show that the timing of critical period plasticity is unaffected by intact GABAergic inhibition such that 4-6-week-old abGCs exhibit LTP that is absent by 8 weeks. Blocking GABAA receptors, or partial blockade of GABA release from PV and nNos-expressing interneurons by a µ-opioid receptor agonist, strongly enhances LTP in 4-week-old GCs, suggesting that minimal inhibition does not underlie critical period plasticity. Instead, the closure of the critical period coincides with a reduction in the contribution of T-type Ca2+ channels to intrinsic excitability, and a selective T-type Ca2+ channel antagonist prevents LTP in 4-week-old but not mature GCs. Interestingly, whole-cell recordings that facilitate T-type Ca2+ channel activity in mature GCs unmasks LTP (with inhibition intact) that is also sensitive to a T-type Ca2+ channel antagonist, suggesting T-type channel activity in mature GCs is suppressed by native intracellular signaling. Together these results show that abGCs use T-type Ca2+ channels to overcome inhibition, providing new insight into how high intrinsic excitability provides young abGCs a competitive advantage for experience-dependent synaptic plasticity.

Response of water yield to silvicultural treatments in a temperate forest in northern Mexico.

Forest management modifies tree cover, directly influencing various ecosystem services, such as water regulation. Evapotranspiration, water interception, surface runoff, stemflow, and throughfall are among those processes that depend on tree cover. The objective of this study was to evaluate the changes in water yield, defined as the difference between precipitation and evapotranspiration, after the application of silvicultural treatments in a temperate forest ecosystem in northern Mexico. Fifteen experimental plots were established in which the following treatments were applied: intensive management (clearcutting), semi-intensive management (selection, tree cutting of 59-61% of basal area), conservative management (selection, tree cutting of 29-31% of basal area), and no treatment (control group). Incident precipitation, throughfall, stemflow, net precipitation, interception, and surface runoff were analyzed. Results show that conservative management treatments increase water yield between 2 to 3.6 mm per m-2 ha-1 of tree basal area removed. Water flow distribution, in relation to the incident precipitation, ranged from 72.3 to 91.8% for throughfall, 0.2 to 0.4% for stemflow, 72.7 to 91.8% for net precipitation, 8.19 to 27.42% for interception or evaporation, and 0.54 to 1.93% for surface runoff. The conservative management treatment was the most viable alternative for increasing water yield without compromising timber harvesting and loss of soil due to hydric erosion.

Percutaneous paravalvular leak closure after transcatheter aortic valve implantation: the international PLUGinTAVI Registry.

BACKGROUND: Data regarding the safety and long-term effectiveness of percutaneous closure of paravalvular leak (PVL) after transcatheter aortic valve implantation (TAVI) are scarce. AIMS: This study aims to present a large multicentre international experience of percutaneous post-TAVI PVL closure. METHODS: All patients who underwent percutaneous post-TAVI PVL closure in 14 hospitals across Europe and North America between January 2018 and October 2022 were included. RESULTS: Overall, 45 patients (64% male) were enrolled. The median age was 80 years (75-84). Among them, 67% and 33% had self-expanding and balloon-expandable valve implantations, respectively. Baseline post-TAVI PVL was severe in 67% of cases and moderate in the rest. The time from index TAVI to PVL closure procedure was 16.1 (8.7-34.8) months. Most patients were in NYHA Class III and IV (73%) before the procedure, and 40% had referred hospitalisations for heart failure between TAVI and the PVL closure procedure. Successful PVL closure was achieved in 94%, reducing regurgitation to ≤mild in 91% and moderate in the rest. The Amplatzer Valvular Plug III was the most frequently used device (27 cases), followed by the Amplatzer Valvular Plug 4. The incidence of severe adverse events was 11%. None of the patients died during the index hospitalisation. During long-term follow-up (21.7±16.2 months), the all-cause mortality rate was 14%, and patients presented improvement in functional status and a significant reduction in the rate of hospitalisation for heart failure (from 40% to 6%). CONCLUSIONS: Percutaneous PVL closure is a feasible and safe option for treating post-TAVI leaks. Successful PVL reduction to mild or less could be associated with acute and long-lasting improvements in clinical outcomes.

Ex vivo, in situ perfusion protocol for human brain fixation compatible with microscopy, MRI techniques, and anatomical studies.

We present a method for human brain fixation based on simultaneous perfusion of 4% paraformaldehyde through carotids after a flush with saline. The left carotid cannula is used to perfuse the body with 10% formalin, to allow further use of the body for anatomical research or teaching. The aim of our method is to develop a vascular fixation protocol for the human brain, by adapting protocols that are commonly used in experimental animal studies. We show that a variety of histological procedures can be carried out (cyto- and myeloarchitectonics, histochemistry, immunohistochemistry, intracellular cell injection, and electron microscopy). In addition, ex vivo, ex situ high-resolution MRI (9.4T) can be obtained in the same specimens. This procedure resulted in similar morphological features to those obtained by intravascular perfusion in experimental animals, provided that the postmortem interval was under 10 h for several of the techniques used and under 4 h in the case of intracellular injections and electron microscopy. The use of intravascular fixation of the brain inside the skull provides a fixed whole human brain, perfectly fitted to the skull, with negligible deformation compared to conventional techniques. Given this characteristic of ex vivo, in situ fixation, this procedure can probably be considered the most suitable one available for ex vivo MRI scans of the brain. We describe the compatibility of the method proposed for intravascular fixation of the human brain and fixation of the donor's body for anatomical purposes. Thus, body donor programs can provide human brain tissue, while the remainder of the body can also be fixed for anatomical studies. Therefore, this method of human brain fixation through the carotid system optimizes the procurement of human brain tissue, allowing a greater understanding of human neurological diseases, while benefiting anatomy departments by making the remainder of the body available for teaching purposes.

Latest-iteration balloon- and self-expandable transcatheter valves for severe bicuspid aortic stenosis: the TRITON study.

INTRODUCTION AND OBJECTIVES: No comparisons have been published yet regarding the newest iteration of balloon- and self-expandable transcatheter heart valves for the treatment of bicuspid aortic valve (BAV) stenosis. METHODS: Multicenter registry of consecutive patients with severe BAV stenosis treated with balloon-expandable transcatheter heart valves (Myval and SAPIEN 3 Ultra, S3U) or self-expanding Evolut PRO+(EP+). TriMatch analysis was carried out to minimize the impact of baseline differences. The primary endpoint of the study was 30-day device success, and the secondary endpoints were the composite and individual components of early safety at 30 days. RESULTS: A total of 360 patients (age 76.6±7.6 years, 71.9% males) were included: 122 Myval (33.9%), 129 S3U (35.8%), and 109 EP+(30.3%). The mean STS score was 3.6±1.9%. There were no cases of coronary artery occlusion, annulus rupture, aortic dissection, or procedural death. The primary endpoint of device success at 30 days was significantly higher in the Myval group (Myval: 100%; S3U: 87.5%; and EP+: 81.3%), mainly due to higher residual aortic gradients with S3U and greater≥moderate aortic regurgitation (AR) with EP+. No significant differences were found in the unadjusted rate of pacemaker implantation. CONCLUSIONS: In patients with BAV stenosis deemed unsuitable for surgery, Myval, S3U and EP+showed similar safety but balloon-expandable Myval had better gradients than S3U, and both balloon-expandable devices had lower residual AR than EP+, suggesting that, taking into consideration the patient-specific risks, any of these devices can be selected with optimal outcomes.

Circadian regulation of dentate gyrus excitability mediated by G-protein signaling.

The central circadian regulator within the suprachiasmatic nucleus transmits time of day information by a diurnal spiking rhythm driven by molecular clock genes controlling membrane excitability. Most brain regions, including the hippocampus, harbor similar intrinsic circadian transcriptional machinery, but whether these molecular programs generate oscillations of membrane properties is unclear. Here, we show that intrinsic excitability of mouse dentate granule neurons exhibits a 24-h oscillation that controls spiking probability. Diurnal changes in excitability are mediated by antiphase G-protein regulation of potassium and sodium currents that reduce excitability during the Light phase. Disruption of the circadian transcriptional machinery by conditional deletion of Bmal1 enhances excitability selectively during the Light phase by removing G-protein regulation. These results reveal that circadian transcriptional machinery regulates intrinsic excitability by coordinated regulation of ion channels by G-protein signaling, highlighting a potential novel mechanism of cell-autonomous oscillations.

Correlation between urinary and serum NT-proBNP in acute bronchiolitis: A pilot study.

BACKGROUND AND AIMS: We aimed to analyze the correlation of urinary with serum N-terminal pro-brain natriuretic peptide (NT-proBNP) concentrations and its association with severity in acute bronchiolitis. MATERIAL AND METHODS: A pilot observational study was conducted between October 1, 2021 and March 31, 2022 including acute bronchiolitis cases who attended our institution. Serum and urinary NT-proBNP concentrations were determined using the Alere i NT-proBNP assay in time-matched urine and blood samples. The Mann-Whitney U test, Spearman's correlations, and simple linear regression were utilized to analyze the association of urine NT-proBNP levels with serum NT-proBNP and with variables indicative of severe bronchiolitis. RESULTS: Seventeen infants (median age 68 [IQR: 36-91] days) with 36 time-matched samples were included. The urine NT-proBNP was positively and strongly correlated with the serum NT-proBNP concentrations (Spearman's ρ = 0.81 & R2  coefficient = 0.751; p < 0.001), and increased with higher C-reactive protein, (p = 0.004), procalcitonin (p = 0.001), and pCO2 (p = 0.029) levels. The initial urinary NT-proBNP concentrations were higher in those infants that required ventilatory support compared with those without this outcome (1.85 [IQR: 1.16-2.44] vs. 0.63 [IQR: 0.45-0.84] pg/mg); p < 0.001); and resulted positively and strongly correlated with the duration of the ventilatory support (Spearman's ρ = 0.76; p < 0.001) and the length of stay hospitalization (Spearman's ρ = 0.84; p < 0.001). CONCLUSION: The urinary NT-proBNP concentrations could be a reliable surrogate for serum NT-proBNP levels and resulted elevated in cases of acute bronchiolitis with complicated evolution, suggesting a potential as a noninvasive tool to assess severity in this setting.

Validation of Quantitative Flow Ratio-Derived Virtual Angioplasty with Post-Angioplasty Fractional Flow Reserve-The QIMERA-I Study.

Background: Quantitative flow ratio (QFR) virtual angioplasty with pre-PCI residual QFR showed better results compared with an angiographic approach to assess post-PCI functional results. However, correlation with pre-PCI residual QFR and post-PCI fractional flow reserve (FFR) is lacking. Methods: A multicenter prospective study including consecutive patients with angiographically 50-90% coronary lesions and positive QFR results. All patients were evaluated with QFR, hyperemic and non-hyperemic pressure ratios (NHPR) before and after the index PCI. Pre-PCI residual QFR (virtual angioplasty) was calculated and compared with post-PCI fractional flow reserve (FFR), QFR and NHPR. Results: A total of 84 patients with 92 treated coronary lesions were included, with a mean age of 65.5 ± 10.9 years and 59% of single vessel lesions being the left anterior descending artery in 69%. The mean vessel diameter was 2.82 ± 0.41 mm. Procedural success was achieved in all cases, with a mean number of implanted stents of 1.17 ± 0.46. The baseline QFR value was 0.69 ± 0.12 and baseline FFR and NHPR were 0.73 ± 0.08 and 0.82 ± 0.11, respectively. Mean post-PCI FFR increased to 0.87 ± 0.05 whereas residual QFR had been estimated as 0.95 ± 0.05, showing poor correlation with post-PCI FFR (0.163; 95% CI:0.078-0.386) and low diagnostic accuracy (30.9%, 95% CI:20-43%). Conclusions: In this analysis, the results of QFR-based virtual angioplasty did not seem to accurately correlate with post-PCI FFR.

Ventilator-associated events in children: A multicentre prospective cohort study.

BACKGROUND: The Centres for Disease Control and Prevention (CDC) broadened the focus of surveillance from ventilator-associated pneumonia to ventilator-associated event (VAE) for quality purposes. No paediatric definition of VAE (PaedVAE) has been accurately validated. We aimed to analyse the incidence and impact on patient outcomes resulting from the application of the adult and two paediatric VAE (PaedVAE) criteria. SECONDARY OBJECTIVE: to evaluate VAE/PaedVAE as factors associated with increased duration of mechanical ventilation (MV) and Paediatric Intensive Care Unit (PICU) stay. METHODS: Multicentre observational prospective cohort study in 15 PICUs in Spain. VAEs were assessed using the 2013/2015 CDC classification. PaedVAE were assessed using the CDC definition based on mean airway pressure (MAP-PaedVAE) versus a paediatric definition based on positive end-expiratory pressure (PEEP-PaedVAE). Children who underwent MV ≥ 48 h were included. RESULTS: A total of 3626 ventilator-days in 391 patients were analysed. The incidence of VAE, MAP-PaedVAE and PEEP-PaedVAE was 8.55, 5.24 and 20.96 per 1000 ventilator-days, respectively. The median time [IQR] for VAE, MAP-PaedVAE and PEEP-PaedVAE development from the MV onset was 4 [3-12.5], 4 [3-14], and 5 [3-7.75] days, respectively. Among survivors, all three were associated with increased MV duration (> 7 days) and PICU stay (> 10 days) at univariate analysis. Multivariate analysis showed that PEEP-PaedVAE was the only definition independently associated with MV above 7 days [OR = 4.86, 95% CI (2.41-10.11)] and PICU stay [OR = 3.49, 95% CI (1.68-7.80)] above ten days, respectively. CONCLUSIONS: A VAE definition based on slight PEEP increases should be preferred for VAE surveillance in children.

Vitamin D Levels and Cardiopulmonary Status in Infants with Acute Bronchiolitis.

BACKGROUND: To assess association of Vitamin D deficiency with cardiac and pulmonary status in infants with acute bronchiolitis. METHODS: Infants hospitalized with acute bronchiolitis were enrolled and classified as those with serum 25 hydroxyvitamin D (25-OHD) below or equal and above 20 ng/mL. The primary outcomes were cardiopulmonary involvement defined by elevation of NT-ProBNP, alteration of echocardiographic parameters and respiratory support requirements. The secondary outcomes were the need for PICU admission and duration of hospitalization. RESULTS: Ninety two (50 males) infants with median (IQR) age 1 (0.5 - 3) months were included with median (IQR) serum 25 - OHD level 27.4 (11.4 - 40.3) ng/mL. Forty-three (47%) patients had serum below 20 ng/mL with left ventricle dysfunction (P=0.008), right ventricle dysfunction (P=0.008) and pulmonary hypertension (P=0.007) on echocardiography than those with serum 25 - OHD > 20 ng/mL. The median (IQR) serum NT - ProBNP levels were higher in those with low 25 - OHD levels than normal 25 - OHD levels [2232.2 (461.4 - 4313.3) and 830.4 (312.7 - 2579.5)], respectively; P=0.003. Low 25-OHD levels were associated with increased risk for PICU admission (OR 3.9 (95% CI 1.5-10.1); P=0.004), higher rates of non-invasive ventilation, (P= 0.048), mechanical ventilation (P=0.005), and longer duration of hospitalization (P=0.015). CONCLUSION: Low serum vitamin D level was associated with clinical severity and impaired cardiac and pulmonary status in infants with acute bronchiolitis.

Characterization of Cardiopulmonary Interactions and Exploring Their Prognostic Value in Acute Bronchiolitis: A Prospective Cardiopulmonary Ultrasound Study.

We aimed to delineate cardiopulmonary interactions in acute bronchiolitis and to evaluate the capacity of a combined cardiopulmonary ultrasonography to predict the need for respiratory support. This was a prospective observational single-center study that includes infants <12 month of age admitted to a hospital due to acute bronchiolitis. All the included patients underwent clinical, laboratory and cardiopulmonary ultrasonographic evaluation at the same time point within 24 h of hospital admission. The existence of significant correlation between cardiac and respiratory parameters was the primary outcome. The association of different cardiopulmonary variables with the need of respiratory support higher than O2, the length of stay hospitalization, the PICU stay and the duration of respiratory support were a secondary outcome. We enrolled 112 infants (median age 1 (0.5-3) months; 62% males) hospitalized with acute bronchiolitis. Increased values of the pulmonary variables (BROSJOD score, pCO2 and LUS) showed moderate correlations with NT-proBNP and all echocardiographic parameters indicative of pulmonary hypertension and myocardial dysfunction (Tei index). Up to 36 (32%) infants required respiratory support during the hospitalization. This group presented with higher lung ultrasound score (p < 0.001) and increased values of NT-proBNP (p < 0.001), the Tei index (p < 0.001) and pulmonary artery pressures (p < 0.001). All the analyzed respiratory and cardiac variables showed moderate-to-strong correlations with the LOS of hospitalization and the time of respiratory support. Lung ultrasound and echocardiography showed a moderate-to-strong predictive accuracy for the need of respiratory support in the ROC analysis, with the AUC varying from 0.74 to 0.87. Those cases of bronchiolitis with a worse pulmonary status presented with a more impaired cardiac status. Cardiopulmonary ultrasonography could be a useful tool to easily identify high-risk populations for complicated acute bronchiolitis hospitalization.

Ex vivo MRI atlas of the human medial temporal lobe: characterizing neurodegeneration due to tau pathology.

Tau neurofibrillary tangle (NFT) pathology in the medial temporal lobe (MTL) is closely linked to neurodegeneration, and is the early pathological change associated with Alzheimer's disease (AD). To elucidate patterns of structural change in the MTL specifically associated with tau pathology, we compared high-resolution ex vivo MRI scans of human postmortem MTL specimens with histology-based pathological assessments of the MTL. MTL specimens were obtained from twenty-nine brain donors, including patients with AD, other dementias, and individuals with no known history of neurological disease. Ex vivo MRI scans were combined using a customized groupwise diffeomorphic registration approach to construct a 3D probabilistic atlas that captures the anatomical variability of the MTL. Using serial histology imaging in eleven specimens, we labelled the MTL subregions in the atlas based on cytoarchitecture. Leveraging the atlas and neuropathological ratings of tau and TAR DNA-binding protein 43 (TDP-43) pathology severity, morphometric analysis was performed to correlate regional MTL thickness with the severity of tau pathology, after correcting for age and TDP-43 pathology. We found significant correlations between tau pathology and thickness in the entorhinal cortex (ERC) and stratum radiatum lacunosum moleculare (SRLM). When focusing on cases with low levels of TDP-43 pathology, we found strong associations between tau pathology and thickness in the ERC, SRLM and the subiculum/cornu ammonis 1 (CA1) subfields of the hippocampus, consistent with early Braak stages.

Where association ends. A review of associative learning in invertebrates, plants and protista, and a reflection on its limits.

Since the beginning of the 21st century, the Minimal Cognition approach has emerged vigorously, focusing on the study of the adaptive behavior of the simplest organisms, including bacteria, assuming that they are sentient and information-processing entities. Although Minimal Cognition has occasionally used Pavlovian methods to try to demonstrate Associative Learning, neither the Psychology of Learning nor the Comparative Psychology traditions are prominent in the movement. However, the Psychology of Learning approach, with its highly sophisticated experimental designs, has done a great deal of research on Associative Learning in animals and carried out several studies on plants and unicellular organisms. The present work offers a comprehensive review of these experimental results, among invertebrates, plants and unicellular organisms (paramecia and the amoeba Physarum policephalum) showing that, while there are increasing instances of Associative Learning in many invertebrate phyla (and also many phyla with no data) there is no adequate evidence of it in unicellular protists (despite more than a century of experiments with paramecia and amoeba) or in plants (despite recent results that so claim). We then consider the alternative offered by Minimal Cognition and suggest some complementary ideas, from a Comparative Developmental Psychology approach, which we call "Minimal Development." (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Three-dimensional mapping of neurofibrillary tangle burden in the human medial temporal lobe.

Tau protein neurofibrillary tangles are closely linked to neuronal/synaptic loss and cognitive decline in Alzheimer's disease and related dementias. Our knowledge of the pattern of neurofibrillary tangle progression in the human brain, critical to the development of imaging biomarkers and interpretation of in vivo imaging studies in Alzheimer's disease, is based on conventional two-dimensional histology studies that only sample the brain sparsely. To address this limitation, ex vivo MRI and dense serial histological imaging in 18 human medial temporal lobe specimens (age 75.3 ± 11.4 years, range 45 to 93) were used to construct three-dimensional quantitative maps of neurofibrillary tangle burden in the medial temporal lobe at individual and group levels. Group-level maps were obtained in the space of an in vivo brain template, and neurofibrillary tangles were measured in specific anatomical regions defined in this template. Three-dimensional maps of neurofibrillary tangle burden revealed significant variation along the anterior-posterior axis. While early neurofibrillary tangle pathology is thought to be confined to the transentorhinal region, we found similar levels of burden in this region and other medial temporal lobe subregions, including amygdala, temporopolar cortex, and subiculum/cornu ammonis 1 hippocampal subfields. Overall, the three-dimensional maps of neurofibrillary tangle burden presented here provide more complete information about the distribution of this neurodegenerative pathology in the region of the cortex where it first emerges in Alzheimer's disease, and may help inform the field about the patterns of pathology spread, as well as support development and validation of neuroimaging biomarkers.

Levels of lactic acid's concordance with pH in pediatric parapneumonic pleural effusion.

Purpose of the article: The indication of pleural drainage in parapneumonic pleural effusion (PPE) is still controversial. Pleural fluid's (PF) pH is widely used as an indicator of the need for pleural drainage. We hypothesized that PF's lactate will have a high concordance with pH, and thus, may be a valuable tool to determine the need for pleural drainage in pediatric PPE. MATERIALS AND METHODS: We performed a descriptive, prospective study sequentially enrolling those pediatric patients admitted to a tertiary University Hospital with a PPE between 2008 and 2018. Patients were classified in two groups: drainable PPE (pH < 7) and non-drainable PPE (pH > 7). Correlation with the pH, the area under the curve (AUC), and the sensitivity and specificity values for lactate and other parameters (glucose, and LDH) were analysed too. RESULTS: 72 patients with a median age of 4 years (interquartile range 2.25-6) were included. Both groups were homogeneous. Lactate levels were higher in the drainable PPE group (p < 0.001), and a strong inverse correlation between pH and lactate was found (r: -0.7; p < 0.001). A lactate cut-off value of 60.5 mmol/L, exhibit an AUC of 0.86 with a sensitivity of 70% and a high specificity (97.9%) to predict a pH < 7. CONCLUSIONS: Our data indicates that lactate in PF presents a strong correlation with pH and could potentially serve as a highly specific biomarker of the need for pleural drainage.

Quantitative assessment of amygdala in Macaca fascicularis monkeys.

The amygdaloid complex (AC) is involved in very relevant cognitive and emotional pathways and exhibits changes in aging and in some neurological and psychiatric disorders. The quantitative estimators of AC could be useful to understand the impact of amygdaloid pathology in these processes, both globally and for each nucleus in particular, and their neurons. The present study analyzes morphometric and stereological estimators in the whole AC and its three main nuclei (lateral [La], basal [Ba], and accessory basal [AB]) in six Macaca fascicularis monkeys. All the brains were fixed and sectioned in the coronal plane; Nissl-stained sections were used for estimation of size and form parameters in both, the AC, and the La, Ba, and AB nuclei separately. The study includes stereological estimates of the volume and surface area of the AC; also, volume of the neurons in the amygdaloid nuclei was estimated using the point-sampled intercepts method. Our results show that the AB nucleus is smaller than both the La and Ba nuclei in both morphometric and stereological estimators. Brain hemispheric side had not significant influence on any of quantitative estimates. The neuron volume was higher in the AB nucleus relative to LA and Ba of the nuclei. These data describe some quantitative parameters of the amygdaloid complex and their main nuclei that could help us to detect small changes in neurodegenerative and other pathological processes.

Intraoperative Bacterial Contamination and Activity of Different Antimicrobial Prophylaxis Regimens in Primary Knee and Hip Replacement.

Surgical antimicrobial prophylaxis (SAP) is important for the prevention of prosthetic joint infections (PJIs) and must be effective against the microorganisms most likely to contaminate the surgical site. Our aim was to compare different SAP regimens (cefazolin, cefuroxime, or vancomycin, alone or combined with gentamicin) in patients undergoing total knee (TKA) and hip (THA) arthroplasty. In this preclinical exploratory analysis, we analyzed the results of intraoperative sample cultures, the ratio of plasma antibiotic levels to the minimum inhibitory concentrations (MICs) for bacteria isolated at the surgical wound and ATCC strains, and serum bactericidal titers (SBT) against the same microorganisms. A total of 132 surgical procedures (68 TKA, 64 THA) in 128 patients were included. Cultures were positive in 57 (43.2%) procedures (mostly for coagulase-negative staphylococci and Cutibacterium spp.); the rate was lower in the group of patients receiving combination SAP (adjusted OR 0.475, CI95% 0.229-0.987). The SAP regimens evaluated achieved plasma levels above the MICs in almost all of intraoperative isolates (93/94, 98.9%) and showed bactericidal activity against all of them (SBT range 1:8-1:1024), although SBTs were higher in patients receiving cefazolin and gentamicin-containing regimens. The potential clinical relevance of these findings in the prevention of PJIs remains to be determined.

Do Prosthetic Joint Infections Worsen the Functional Ambulatory Outcome of Patients with Joint Replacements? A Retrospective Matched Cohort Study.

OBJECTIVES: To assess the effect on the functional ambulatory outcome of postoperative joint infection (PJI) cured at the first treatment attempt versus not developing PJI in patients with hip and knee prostheses. METHODS: In a single-hospital retrospectively matched cohort study, each patient with PJI between 2007 and 2016 was matched on age, sex, type of prosthesis and year of implantation with two other patients with uninfected arthroplasties. The definition of a PJI cure included infection eradication, no further surgical procedures, no PJI-related mortality and no suppressive antibiotics. Functional ambulatory status evaluated one year after the last surgery was classified into four simple categories: able to walk without assistance, able to walk with one crutch, able to walk with two crutches, and unable to walk. Patients with total hip arthroplasties (THA), total knee arthroplasties (TKA) and partial hip arthroplasty (PHA) were analysed separately. RESULTS: A total of 109 PJI patients (38 TKA, 41 THA, 30 PHA) and 218 non-PJI patients were included. In a model adjusted for clinically relevant variables, PJI was associated with a higher risk of needing an assistive device for ambulation (vs. walking without aid) among THA (adjusted odds ratio (OR) 3.10, 95% confidence interval (95% CI) 1.26-7.57; p = 0.014) and TKA patients (OR 5.40, 95% CI 2.12-13.67; p < 0.001), and with requiring two crutches to walk or being unable to walk (vs. walking unaided or with one crutch) among PHA patients (OR 3.05, 95% CI 1.01-9.20; p = 0.047). CONCLUSIONS: Ambulatory outcome in patients with hip and knee prostheses with postoperative PJI is worse than in patients who do not have PJI.