Impact of the pericapsular nerve group (PENG) block on postoperative analgesia and functional recovery following total hip arthroplasty: a randomised, observer-masked, controlled trial.

The pericapsular nerve group (PENG) block is a novel regional anaesthesia technique that aims to provide hip analgesia with preservation of motor function, although evidence is currently lacking. In this single-centre, observer-masked, randomised controlled trial, patients undergoing total hip arthroplasty received pericapsular nerve group block or no block (control group). Primary outcome measure was maximum pain scores (0-10 numeric rating scale) measured in the first 48 h after surgery. Secondary outcomes included postoperative opioid consumption; patient mobilisation assessments; and length of hospital stay. Sixty patients were randomly allocated equally between groups. The maximum pain score of patients receiving the pericapsular nerve group block was significantly lower than in the control group at all time-points, with a median (IQR [range]) of 2.5 (2.0-3.7 [0-7]) vs. 5.5 (5.0-7.0 [2-8]) at 12 h; 3 (2.0-4.0 [0-7]) vs. 6 (5.0-6.0 [2-8]) at 24 h; and 2.0 (2.0-4.0 [0-5]) vs. 3.0 (2.0-4.7 [0-6]) at 48 h; all p < 0.001. Moreover, the pericapsular nerve group showed a significant reduction in opioid consumption, better range of hip motion and shorter time to ambulation. Although no significant difference in hospital length of stay was detected, our results suggest improved postoperative functional recovery following total hip arthroplasty in patients who received pericapsular nerve group block.

The Italian coronavirus disease 2019 outbreak: recommendations from clinical practice.

Novel coronavirus 2019 is a single-stranded, ribonucleic acid virus that has led to an international pandemic of coronavirus disease 2019. Clinical data from the Chinese outbreak have been reported, but experiences and recommendations from clinical practice during the Italian outbreak have not. We report the impact of the coronavirus disease 2019 outbreak on regional and national healthcare infrastructure. We also report on recommendations based on clinical experiences of managing patients throughout Italy. In particular, we describe key elements of clinical management, including: safe oxygen therapy; airway management; personal protective equipment; and non-technical aspects of caring for patients diagnosed with coronavirus disease 2019. Only through planning, training and team working will clinicians and healthcare systems be best placed to deal with the many complex implications of this new pandemic.

Assessing the Quality of in Silico Produced Biomolecules: The Discovery of a New Conformer.

The computational procedures for predicting the 3D structure of aptamers interacting with different biological molecules have gained increasing attention in recent years. The information acquired through these methods represents a crucial input for research, especially when relevant crystallographic data are not available. A number of software programs able to perform macromolecular docking are currently accessible, leading to the prediction of the quaternary structure of complexes formed by two or more interacting biological macromolecules. Nevertheless, the scoring protocols employed for ranking the candidate structures do not always produce satisfactory results, making difficult the identification of structures that are most likely to occur in nature. In this paper, we propose a novel procedure to improve the predictive performances of computational scoring protocols, using a maximum likelihood estimate based on topological and electrical properties of interacting biomolecules. The reliability of the new computational approach, enabling the ranking of aptamer-protein configurations produced by an open source docking program, has been assessed by its successful application to a set of antiangiopoietin aptamers, for which experimental data highlighting the sequence-dependent affinity toward the target protein are available. The procedure led to the identification of two main types of aptamer conformers involved in angiopoietin binding. Interestingly, one of these reproduces the arrangement of angiopoietin with its natural target, tyrosine kinase, while the other one is completely unexpected. The possible scenarios related to these results have been discussed. The methodology here described can be used to refine the outcomes of different computational procedures and can be applied to a wide range of biological molecules, thus representing a new tool for guiding the design of bioinspired sensors with enhanced selectivity.

Conceptos generales en bioestadística y epidemiología clínica: estudios observacionales con diseños transversal y ecológico / General concepts in biostatistics and clinical epidemiology: observational studies with cross-sectional and ecological designs

Los estudios observacionales analizan las variables de interés en la muestra o en la población, sin intervenir en ellas. Pueden ser meramente descriptivos si se focalizan en la descripción de las variables, o analíticos, en el caso de presentar grupos de comparación para establecer asociaciones mediante la inferencia estadística. Los estudios transversales y los estudios ecológicos, también llamados correlacionales, son dos diseños metodológicos observacionales. Los estudios transversales recogen los datos de la variable exposición y desenlace en un mismo momento, para describir sus características y eventualmente estudiar asociaciones. Los estudios ecológicos describen y analizan las correlaciones entre distintas variables, pero su unidad de análisis corresponde a datos agregados de múltiples individuos. En ambos casos no puede inferirse una relación causal, pero sí pueden establecerse asociaciones de gran interés para la investigación biomédica. Esta revisión es la segunda entrega de una serie metodológica sobre conceptos generales en bioestadística y epidemiología clínica desarrollada por la Cátedra de Metodología de la Investigación Científica de la Escuela de Medicina de la Universidad de Valparaíso, Chile. En este artículo se abordan conceptos teóricos generales sobre estudios transversales y estudios ecológicos, considerando sus aplicaciones, medidas de asociación, ventajas, desventajas y reporte. Finalmente, se discuten algunos conceptos de relevancia sobre diseños observacionales para los estudiantes de pre y posgrado de ciencias de la salud.

Observational studies evaluate variables of interest in a sample or a population, without intervening in them. They can be descriptive if they focus on the description of variables, or analytical when comparison between groups is made to establish associations through statistical inference. Cross-sectional studies and ecological­also called correlational­studies are two observational methodological designs. Cross-sectional studies collect the data of the exposure variable and the outcome at the same time, to describe characteristics of the sample or to study associations. Ecological studies describe and analyze correlations among different variables, and the unit of analysis is aggregated data from multiple individuals. In both types of studies, associations of interest for biomedical research can be established, but no causal relationships should be inferred. This is the second of a methodological series of articles on general concepts in biostatistics and clinical epidemiology developed by the Chair of Scientific Research Methodology at the School of Medicine, University of Valparaíso, Chile. In this review, we address general theoretical concepts about cross-sectional and ecological studies, including applications, measures of association, advantages, disadvantages, and reporting guidelines. Finally, we discuss some concepts about observational designs relevant to undergraduate and graduate students of health sciences.

A validation strategy for in silico generated aptamers.

The selection of high-affinity aptamers is of paramount interest for clinical and technological applications. A novel strategy is proposed to validate the reliability of the 3D structures of a group of anti- Angiopoietin-2 aptamers, produced in silico by using free software. In a previous literature these aptamers were processed both in vitro and in silico, by using an approach different from that here presented, and finally tested with a SPS experiment. Computational expectations and experimental outcomes did not agree. The procedure here proposed consists of three steps: a. the production of a large set of conformations for each candidate aptamer; b. the rigid docking upon the receptor; c. the topological and electrical characterization of the products. Steps a. and b. allow a global binding score of the ligand-receptor complexes based on the distribution of the "effective affinity", i.e. the sum of the conformational and the docking energies. Step c. employs a complex network approach (Proteotronics) to characterize the electrical properties of the aptamers and the ligand-receptor complexes. Finally, the results are discussed and compared with the literature on the same aptamers. The computational predictions are in good agreement with the known experimental measurements.

Effects of overweight and obesity on motor and mental development in infants and toddlers.

BACKGROUND: A consequence of childhood obesity may be poor developmental outcomes. OBJECTIVES: This study aimed to examine the relationship between weight and developmental delays in young children. METHODS: We conducted a secondary analysis of the Early Childhood Longitudinal Study Birth Cohort data. Logistic regression models quantified the association between different weight statuses (normal weight <85th, overweight ≥90th, obese ≥95th percentile for weight) and delays in motor and mental development. RESULTS: Children classified as overweight in both waves had higher percentages of delays in wave 2 (motor [7.5 vs. 6.2-6.4%], mental [8.6 vs. 5.9-6.7%]), as well as wave 1 and/or wave 2 (motor [14.8 vs. 10.9-13.0%], mental [11.9 vs. 9.0-10.1%]), compared with other children. This association was also found in children who were obese at both time points in wave 2 (motor delay [8.9 vs. 4.9-7.3%], mental delay [10.3 vs. 6.0-7.2%]), as well as wave 1 and/or wave 2 (motor delay [14.5 vs. 10.9-12.9%], mental delay [14.1 vs. 9.4-10.1%]). In the adjusted models, children classified as always obese were more likely to have a mental delay in wave 2 (adjusted odds ratio [aOR] 1.89, 95% confidence interval [CI]: 1.21-2.95) as well as wave 1 and/or wave 2 (aOR 1.56, 95% CI: 1.08-2.26). These children were also more likely to have motor delay (aOR 1.47, 95% CI: 1.02-2.13) in wave 1 and/or wave 2. CONCLUSION: Overweight children are more likely than their normal-weight peers to have motor and mental developmental delays. Preventing obesity during infancy may facilitate reducing developmental delays in young children.

Transactivation activity and nucleocytoplasmic transport of ß-catenin are independently regulated by its C-terminal end.

The key protein in the canonical Wnt pathway is ß-catenin, which is phosphorylated both in absence and presence of Wnt signals by different kinases. Upon activation in the cytoplasm, ß-catenin can enter into the nucleus to transactivate target gene expression, many of which are cancer-related genes. The mechanism governing ß-catenin's nucleocytoplasmic transport has been recently unvealed, although phosphorylation at its C-terminal end and its functional consequences are not completely understood. Serine 646 of ß-catenin is a putative CK2 phosphorylation site and lies in a region which has been proposed to be important for its nucleocytoplasmic transport and transactivation activity. This residue was mutated to aspartic acid mimicking CK2-phosphorylation and its effects on ß-catenin activity as well as localization were explored. ß-Catenin S6464D did not show significant differences in both transcriptional activity and nuclear localization compared to the wild-type form, but displayed a characteristic granular nuclear pattern. Three-dimensional models of nuclei were constructed which showed differences in number and volume of granules, being those from ß-catenin S646D more and smaller than the wild-type form. FRAP microscopy was used to compare nuclear export of both proteins which showed a slightly higher but not significant retention of ß-catenin S646D. Altogether, these results show that C-terminal phosphorylation of ß-catenin seems to be related with its nucleocytoplasmic transport but not transactivation activity.

Force and pressure distribution using Macintosh and GlideScope laryngoscopes in normal airway: an in vivo study.

BACKGROUND: Forces applied on oropharyngeal soft tissues by direct laryngoscopy may cause damage to the patients. The aim of this study was to measure the forces applied during the manoeuvres to achieve glottis visualization and tracheal intubation, comparing direct laryngoscopy and videolaryngoscopy in vivo. METHODS: Thirty adult patients (ASA physical status 1 or 2, BMI between 18 and 30 kg/m2, no difficulty to intubate) were randomly and blindly assigned to one of two groups. Forces and pressure distribution applied during glottis visualization and intubation were measured using film pressure transducers, comparing Macintosh direct laryngoscope and GlideScope videolaryngoscope. RESULTS: Fifteen patients from each group, all with Cormack-Lehane grade 1 view, were analyzed. Forces applied during the intubation with the GlideScope were significantly lower than forces applied with the Macintosh (8+4 N vs. 40+14 N, respectively, P<0.001). Considering the Macintosh laryngoscope, the minimal force applied for glottis visualization was significantly lower than the one applied for intubation (16+6 N vs. 40+14 N, respectively, P<0.005). When using the Macintosh laryngoscope, forces were concentrated mostly on the tip, whereas with the GlideScope forces' concentration in a particular area was not observed. CONCLUSION: Our study shows that in patients with normal airways the GlideScope allows a view of glottis and permits a successful tracheal intubation applying lower force (significantly in intubation) as compared to the Macintosh laryngoscope. Also, the GlideScope probe distributes the forces more homogeneously to the tissue thus further reducing the potential for tissue damage.

Generating a minimal set of templates for the hippocampal region in MR neuroimages.

OBJECTIVES: We detail a procedure for generating a set of templates for the hippocampal region in magnetic resonance (MR) images, representative of the clinical conditions of the population under investigation. METHODS: The first step is robust standardization of the intensity scale of brain MR images, belonging to patients with different degrees of neuropathology (Alzheimer's disease). So similar tissues have similar intensities, even across images coming from different sources. After the automatic extraction of the hippocampal region from a large dataset of images, we address template generation, choosing by clusterization methods a small number of the extracted regions. RESULTS: We assess that template generation is largely independent on the clusterization method and on the number and the clinical condition of the patients. The templates are chosen as the most representative images in a population. The estimation of the "minimum" number of templates for the hippocampal region can be proposed, using a metric based on the geometrical position of the extracted regions. CONCLUSIONS: This study describes a simple and easily reproducible procedure to generate templates for the hippocampal region. It can be generalized and applied to other brain regions, which may be relevant for neuroimaging studies.

Force and pressure distribution using Macintosh and GlideScope laryngoscopes in normal and difficult airways: a manikin study.

BACKGROUND: The forces applied to the soft tissues of the upper airway may have a deleterious effect. This study was designed to evaluate the performance of the GlideScope compared with the Macintosh laryngoscope. METHODS: Twenty anaesthetists and 20 trainees attempted tracheal intubation of a Laerdal SimMan manikin. Forces and pressure distribution applied by both laryngoscope blades onto the soft upper airway tissues were measured using film pressure transducers. The minimal force needed to achieve a successful intubation, in the same simulated scenario, was measured; additionally, we considered the visualization score achieved by using the Cormack-Lehane grades. RESULTS: All participants applied, on average, lower force with the GlideScope than with the Macintosh in each simulated scenario. Forces [mean (sd)] applied in the normal airway scenario [anaesthetists: Macintosh 39 (22) N and GlideScope 27 (15) N; trainees: Macintosh 45 (24) N and GlideScope 21 (15) N] were lower than forces applied in the difficult airway scenario [anaesthetists: Macintosh 95 (22) N and GlideScope 66 (20) N; trainees: Macintosh 100 (38) N and GlideScope 48 (16) N]. All the intubations using the GlideScope were successful, regardless of the scenario and previous intubation experience. The average pressure on the blades was 0.13 MPa for the Macintosh and 0.07 MPa for the GlideScope, showing a higher uniformity for the latter. CONCLUSIONS: The GlideScope allowed the participants to obtain a successful intubation applying a lower force. A flatter and more uniform pressure distribution, a higher successful rate, and a better glottic view were observed with the GlideScope.

New devices and techniques for airway management.

Innovation over the past 25 years in the field of the airway management has led to the proliferation of new and improved techniques and devices. It is important to emphasize that the definition of a failed airway must include the inability to maintain acceptable oxygenation and not only the evidence of unsuccessful laryngoscopy and impossible intubation. We must ask ourselves: is it always necessary to intubate? Is it necessary in all patients? Our answer is absolutely ''no." Patients' oxygenation is the absolute priority, where the choice of whether or not to intubate represents only a technical problem. The existing literature primarily supports the use of the classic laryngeal mask airway (LMA) for providing effective ventilation and oxygenation; it suggests the use of the intubating LMA as an important rescue device and the use of the Combitube as a well-established emergency airway. The role in managing complex airway problems of many new extraglottic devices has not yet been completely investigated and will likely be better defined in the coming years. The videolaryngoscopes seem to be an interesting and promising option in the field of airway management. Furthermore, the applicability of associated techniques could represent an efficacious strategy to overcome the limitations of the single device by strengthening their capabilities and chances of successful airway management. To date there is no technique found to be effective in every case or that can solve all airway problems. It is not the latest device or the latest technique that can solve an airway management problem, but the operator's experience and skill with the device and technique that he knows best and uses daily.

MAGIC-5: an Italian mammographic database of digitised images for research.

The implementation of a database of digitised mammograms is discussed. The digitised images were collected beginning in 1999 by a community of physicists in collaboration with radiologists in several Italian hospitals as a first step in developing and implementing a computer-aided detection (CAD) system. All 3,369 mammograms were collected from 967 patients and classified according to lesion type and morphology, breast tissue and pathology type. A dedicated graphical user interface was developed to visualise and process mammograms to support the medical diagnosis directly on a high-resolution screen. The database has been the starting point for developing other medical imaging applications, such as a breast CAD, currently being upgraded and optimised for use in a distributed environment with grid services, in the framework of the Instituto Nazionale di Fisicia Nucleare (INFN)-funded Medical Applications on a Grid Infrastructure Connection (MAGIC)-5 project.

A completely automated CAD system for mass detection in a large mammographic database.

Mass localization plays a crucial role in computer-aided detection (CAD) systems for the classification of suspicious regions in mammograms. In this article we present a completely automated classification system for the detection of masses in digitized mammographic images. The tool system we discuss consists in three processing levels: (a) Image segmentation for the localization of regions of interest (ROIs). This step relies on an iterative dynamical threshold algorithm able to select iso-intensity closed contours around gray level maxima of the mammogram. (b) ROI characterization by means of textural features computed from the gray tone spatial dependence matrix (GTSDM), containing second-order spatial statistics information on the pixel gray level intensity. As the images under study were recorded in different centers and with different machine settings, eight GTSDM features were selected so as to be invariant under monotonic transformation. In this way, the images do not need to be normalized, as the adopted features depend on the texture only, rather than on the gray tone levels, too. (c) ROI classification by means of a neural network, with supervision provided by the radiologist's diagnosis. The CAD system was evaluated on a large database of 3369 mammographic images [2307 negative, 1062 pathological (or positive), containing at least one confirmed mass, as diagnosed by an expert radiologist]. To assess the performance of the system, receiver operating characteristic (ROC) and free-response ROC analysis were employed. The area under the ROC curve was found to be Az = 0.783 +/- 0.008 for the ROI-based classification. When evaluating the accuracy of the CAD against the radiologist-drawn boundaries, 4.23 false positives per image are found at 80% of mass sensitivity.

Lightwand intubation using the Trachlight: a brief review of current knowledge.

PURPOSE: About 1% to 3% of laryngoscopic intubations can be difficult or impossible. Light-guided intubation has been proven to be an effective, safe, and simple technique. This article reviews current knowledge about the newer version lightwand: the Trachlight (TL). SOURCE: To determine its clinical utility and limitations, we reviewed the current literature (book and journal articles) on the TL since its introduction in 1995. PRINCIPAL FINDINGS: TL has been shown to be useful both in oral and nasal intubation for patients with difficult airways. It may also be useful in "emergency" situations or when direct laryngoscopy or fiberoptic endoscopy is not effective, such as with patients who have copious secretions or blood in the oropharynx. TL can also be used for tracheal intubation in conjunction with other devices (laryngeal mask airway -LMA-, intubating LMA, direct laryngoscopy). However, TL should be avoided in patients with tumours, infections, trauma or foreign bodies in the upper airway. CONCLUSIONS: Based on the clinical reports available, the TL has proven to be a useful option for tracheal intubation. In addition, the device can also be used together with other intubating devices, such as the intubating LMA and the laryngoscope, to improve intubating success rates. A clear understanding of the principle of transillumination of the TL, and an appreciation of its indications, contraindications, and limitations, will improve the effectiveness of the device as well as reducing the likelihood of complications. Finally, regular practice with the TL with routine surgical patients requiring tracheal intubation will further improve intubation success rates.