Impact of the COVID-19 pandemic on orthopaedic and trauma surgery training in Europe.

PURPOSE: This study aimed to evaluate the impact of the coronavirus disease 2019 (COVID-19) pandemic on orthopaedic and trauma surgery training in Europe by conducting an online survey among orthopaedic trainees. METHODS: The survey was conducted among members of the Federation of Orthopaedic and Trauma Trainees in Europe (FORTE). It consisted of 24 questions (single-answer, multiple-answer, Likert scales). Orthopaedic trainees' demographic data (six questions), clinical role changes (four questions), institutional changes due to the COVID-19 pandemic (nine questions), and personal considerations (five questions) were examined. RESULTS: Three hundred and twenty-seven trainees from 23 European countries completed the survey. Most trainees retained their customary clinical role (59.8%), but a significant number was redeployed to COVID-19 units (20.9%). A drastic workload decrease during the pandemic was reported at most institutions. Only essential activities were performed at 57.1% of institutions and drastic disruptions were reported at 36.0%. Of the respondents, 52.1% stated that faculty-led education was restricted and 46.3% pursued self-guided learning, while 58.6% stated that surgical training was significantly impaired. Concerns about the achievement of annual training goals were expressed by 58.2% of the participants, while 25.0% anticipated the need for an additional year of training. CONCLUSIONS: The SARS-CoV-2 pandemic significantly affected orthopaedic and trauma training in Europe. Most trainees felt the decrease in clinical, surgical, and educational activities would have a detrimental effect on their training. Many of them consulted remote learning options to compensate training impairment, stating that after the COVID-19 pandemic electronic educational approaches may become more relevant in future.

An Ocean-Colour Time Series for Use in Climate Studies: The Experience of the Ocean-Colour Climate Change Initiative (OC-CCI).

Ocean colour is recognised as an Essential Climate Variable (ECV) by the Global Climate Observing System (GCOS); and spectrally-resolved water-leaving radiances (or remote-sensing reflectances) in the visible domain, and chlorophyll-a concentration are identified as required ECV products. Time series of the products at the global scale and at high spatial resolution, derived from ocean-colour data, are key to studying the dynamics of phytoplankton at seasonal and inter-annual scales; their role in marine biogeochemistry; the global carbon cycle; the modulation of how phytoplankton distribute solar-induced heat in the upper layers of the ocean; and the response of the marine ecosystem to climate variability and change. However, generating a long time series of these products from ocean-colour data is not a trivial task: algorithms that are best suited for climate studies have to be selected from a number that are available for atmospheric correction of the satellite signal and for retrieval of chlorophyll-a concentration; since satellites have a finite life span, data from multiple sensors have to be merged to create a single time series, and any uncorrected inter-sensor biases could introduce artefacts in the series, e.g., different sensors monitor radiances at different wavebands such that producing a consistent time series of reflectances is not straightforward. Another requirement is that the products have to be validated against in situ observations. Furthermore, the uncertainties in the products have to be quantified, ideally on a pixel-by-pixel basis, to facilitate applications and interpretations that are consistent with the quality of the data. This paper outlines an approach that was adopted for generating an ocean-colour time series for climate studies, using data from the MERIS (MEdium spectral Resolution Imaging Spectrometer) sensor of the European Space Agency; the SeaWiFS (Sea-viewing Wide-Field-of-view Sensor) and MODIS-Aqua (Moderate-resolution Imaging Spectroradiometer-Aqua) sensors from the National Aeronautics and Space Administration (USA); and VIIRS (Visible and Infrared Imaging Radiometer Suite) from the National Oceanic and Atmospheric Administration (USA). The time series now covers the period from late 1997 to end of 2018. To ensure that the products meet, as well as possible, the requirements of the user community, marine-ecosystem modellers, and remote-sensing scientists were consulted at the outset on their immediate and longer-term requirements as well as on their expectations of ocean-colour data for use in climate research. Taking the user requirements into account, a series of objective criteria were established, against which available algorithms for processing ocean-colour data were evaluated and ranked. The algorithms that performed best with respect to the climate user requirements were selected to process data from the satellite sensors. Remote-sensing reflectance data from MODIS-Aqua, MERIS, and VIIRS were band-shifted to match the wavebands of SeaWiFS. Overlapping data were used to correct for mean biases between sensors at every pixel. The remote-sensing reflectance data derived from the sensors were merged, and the selected in-water algorithm was applied to the merged data to generate maps of chlorophyll concentration, inherent optical properties at SeaWiFS wavelengths, and the diffuse attenuation coefficient at 490 nm. The merged products were validated against in situ observations. The uncertainties established on the basis of comparisons with in situ data were combined with an optical classification of the remote-sensing reflectance data using a fuzzy-logic approach, and were used to generate uncertainties (root mean square difference and bias) for each product at each pixel.

Interaction of Native Cyclodextrins and Their Hydroxypropylated Derivatives with Carbamazepine in Aqueous Solution. Evaluation of Inclusion Complexes and Aggregates Formation.

A detailed comprehensive study on how the formation of soluble and insoluble carbamazepine/cyclodextrins (CBZ/CD) complexes (with consequent changes in the solid-phase composition) depends on the CD structure is not yet available. Moreover, the study of possible influence of this drug on the tendency of CDs and their complexes to self-aggregate is still lacking. Phase-solubility studies demonstrated that CDs and CBZ form a range of soluble (AL-type: αCD, ßCD, and hydroxypropylated CDs) and insoluble (BS-type: γCD) complexes depending on CD used. HPßCD proved to be the best CD solubilizer for CBZ forming the most stable complex with highest apparent solubility, whereas γCD was shown to be the best native CD. For the native CDs, CBZ solubilization increases with increasing CD cavity diameter (αCD ≪ ßCD < γCD). Solid phases collected from phase-solubility studies were characterized by Fourier-transformed infrared spectroscopy, differential scanning calorimetry, and X-ray powder diffraction to elucidate their composition and crystalline structure. They provided similar conclusions being overall supportive of phase-solubility, osmolality, and permeation studies results. Solid CBZ was the only detected component for AL-type profiles over the CD concentration range studied, whereas precipitation of poorly soluble CBZ/γCD complexes (BS-type) was observed (i.e., at and beyond plateau region). Osmometry and permeation studies were applied to evaluate the effect of CBZ on the aggregate formation and also to elucidate their influence on CD complex solubility and permeation profile. Permeation method was shown to be the most effective method to detect and evaluate aggregate formation in aqueous γCD and HPßCD solutions containing CBZ. CBZ did not affect the HPßCD tendency to self-aggregate but CBZ did modify the aggregation behavior of γCD decreasing the apparent critical aggregation concentration value from 4.2% (w/v) (in pure aqueous γCD solution) to 2.5% (w/v) (when CBZ was present).

Self-association of cyclodextrins and cyclodextrin complexes in aqueous solutions.

Cyclodextrins (CDs) are oligosaccharides that self-assemble in aqueous solutions to form transient clusters, nanoparticles and small microparticles. The critical aggregation concentration (cac) of the natural αCD, ßCD and γCD in pure aqueous solutions was estimated to be 25, 8 and 9 mg/ml, respectively. The cac of 2-hydroxypropyl-ß-cyclodextrin (HPßCD), that consists of mixture of isomers, was estimated to be significantly higher or 118 mg/ml. Addition of chaotropic agents (i.e. that disrupts non-covalent bonds such as hydrogen bonds) to the aqueous media increases the cac. Formation of drug/CD complexes can increase or decrease the cac. Due to the transient nature of the CD clusters and nanoparticles they can be difficult to detect and their presence is frequently ignored. However, they have profound effect on the physiochemical properties of CDs and their pharmaceutical applications. For example, the values of stability constants of drug/CD complexes can be both concentration dependent and method dependent. Like in the case of micelles water-soluble polymers can enhance the solubilizing effect of CDs. Also, formation of drug/CD complex nanoparticles appears to increase the ability of CDs to enhance drug delivery through some mucosal membranes.

Electromagnetic Rod in Lower Limb Lengthening: A Technical Note for Shaft Osteotomy.

PURPOSE: Long bone lengthening procedures are paramount in the treatment of limb length discrepancies. We witnessed a revolution in the treatment paradigm of this pathology with the development of expandable intramedullary rods. Endomedular nailing might be technically demanding and some steps are critical for success. The aim of authors is to describe a technical note of the PRECICE system that may ease femoral nailing and fixation: the nail can be advanced through the femur and proximal and distal fixation performed previous to complete femoral osteotomy. MATERIALS AND METHODS: The authors present a case series of XX patients in which the limb lengthening has been performed with partial osteotomy with Gigli saw, nail advancement, proximal and distal fixation, and osteotomy completion at the end of the procedure. RESULTS: After 18 consecutive limb (femoral) lengthening operations with this technical variation in PRECICE, nail patients presented no significant lower limb length discrepancy. There were no records of rotational deformities, nonunion, or infection. Material failure was not reported. CONCLUSION: This technical note is another positive variable that can help to ease the procedure, minimise possible complications, and confirm magnetic expandable nails as the gold standard technique in limb lengthening procedures and it might be applied to other nailing systems for limb lengthening procedures. HOW TO CITE THIS ARTICLE: Lopes M, Nunes B, Couto A, et al. Electromagnetic Rod in Lower Limb Lengthening: A Technical Note for Shaft Osteotomy. Strategies Trauma Limb Reconstr 2019;14(3):139-141.

Pyogenic Sacroiliitis in a Pediatric Patient: A Rare Case of Infection by Streptococcus intermedius.

This is a case report of pyogenic sacroiliitis in a pediatric patient caused by Streptococcus intermedius. The patient is a 16-year-old boy who presented to an emergency department with sudden onset of back pain radiating to the left lower extremity. The diagnosis was confounded by the presence of isthmic spondylolisthesis. Plain radiography demonstrated mild isthmic spondylolisthesis but no radiographic signs of tumor, trauma, infection, arthritis, or other developmental problems. The C-reactive protein level was 23 mg/L. Over the next 24 hours, the patient developed fever, and the C-reactive protein level increased to 233 mg/L. Sacroiliitis and an iliopsoas abscess were identified on MRI. Blood cultures grew S intermedius. The patient responded to antibiotic treatment and needle aspiration under CT guidance. Sacroiliitis is an uncommon condition and, to our knowledge, there is only one other case report of its being caused by S intermedius. The previous report was in an adult.

2-Hydroxypropyl-ß-Cyclodextrin Aggregates: Identification and Development of Analytical Techniques.

It is extremely important for pharmaceutical formulators to have analytical methodology that provides efficient detection and quantification of HPßCD aggregates. Five different methods were then evaluated for their potential to detect these aggregates and to determine critical aggregation concentration (cac): osmometry, viscometry, tensiometry, dynamic light scattering (DLS), and permeability studies. Overall, tensiometry was an inadequate method with which to study HPßCD aggregation, since the addition of HPßCD to water resulted in only minor changes in surface tension. Osmolality and viscosity studies have shown that for HPßCD, solute⁻solvent interactions are the main contributors for the observed deviation from ideality. These deviations might be related to the presence of aggregates. The DLS method proved to be an effective method with which to detect HPßCD aggregates and estimate their hydrodynamic diameter, although it presented some limitations concerning their quantification. In terms of the assessed methods, permeation studies were shown to be the best to study HPßCD aggregation phenomena, since they were the only method where the detection of aggregates and the determination of apparent cac values was possible. Also, it was the least invasive for the HPßCD samples and the method that provided more conclusive data. Results suggested that HPßCD, as expected, has less tendency to form aggregates than ßCD.

Ochronotic arthropathy-a rare clinical case.

Ochronotic arthropathy is a rare condition found in patients with alkaptonuria that results from the accumulation of ochronotic pigment. We present the case of a 65-year-old woman who presented for medical evaluation due to hip and knee chronic pain. The physical and radiographic findings were compatible with an end-stage hip osteoarthritis and knee osteoarthritis. During total hip arthroplasty it was noticed that the articular capsule and the cartilage of the femoral head were black. In the postoperative period she was diagnosed with alkaptonuria. Later, a total knee arthroplasty was performed and once more the presence of black cartilage was noted. Alkaptonuria usually appears after age 30 and is usually asymptomatic until the involvement of the spine, hip, knee and shoulder joints. Therefore, orthopaedic surgeons must be suspicious of an atypical arthropathy in order to not be overwhelmed during surgery with the presence of darkened cartilage.

Two consecutive limb lengthenings with the same PRECICE nail: a technical note.

PURPOSE: The most significant advance in our time about limb lengthening is the magnetic lengthening nail, as the first reports appeared to show good results with accurate lengthening rates and good regenerate bone formation. The described complication rate is generally low. They avoid external fixation elements, and are activated transcutaneously, so the patient's pain and discomfort are reduced and the rehabilitation is faster and more effective. The aim of authors is to describe a special technical issue of the PRECICE system: the nail can be extended inside the patient limb (after the osteotomy), but it also can be retracted inside the limb after achieving the bone union. METHODS: The authors present a case in which the limb lengthening has been performed in consecutive lengthening periods using the same nail. The nail was extended and retracted by altering the settings on the external remote control as well as accurately setting the rate of distraction. RESULTS: After two consecutive femoral lengthening with the same PRECICE nail, the patient no longer has a significant lower limb length discrepancy and patient satisfaction was high. During this clinical case, we were not confronted with any type of complications. CONCLUSION: This technique utilizes the principles and advantages of lengthening over an magnetic lengthening nail, avoids the necessity of nail removal and minimizes the complication rates and the overall time for complete recovery. LEVEL OF EVIDENCE: Level IV.

Self-Assembly of α-Cyclodextrin and ß-Cyclodextrin: Identification and Development of Analytical Techniques.

Recently, it has been shown that cyclodextrins (CDs) self-assemble in aqueous solutions to form aggregates. Such aggregation can give rise to formation of particulate matter in aqueous solutions. However, the analytical methodology available to detect and quantify these aggregates is still quite inadequate. Here, 5 different methods for evaluation of CD aggregate formation and determination of the critical aggregation concentration are evaluated: osmometry, viscosity, surface tension, dynamic light scattering, and permeability studies. Both the viscosity and surface tension methods applied were inadequate for aggregate detection, whereas the osmometry method can be used to study CD aggregation but with some limitations. Dynamic light scattering has also some limitations although it can be applied to detect CD aggregates and to estimate their hydrodynamic diameter. Overall, permeation studies proved to be the best method to detect and determine critical aggregation concentration. These results suggested that ß-cyclodextrin (ßCD) has higher tendency to aggregate than α-cyclodextrin (αCD). Filtration of αCD and ßCD solutions affected the aggregate size distribution by breaking larger aggregates in to smaller ones that then reassembled to regenerate the larger ones upon storage. The osmolality studies showed that in aqueous αCD and ßCD solutions, solute-solute interactions are favored over solute-solvent interactions with consequent CD aggregate formation.

The self-assemble of natural cyclodextrins in aqueous solutions: Application of miniature permeation studies for critical aggregation concentration (cac) determinations.

Permeation techniques can be applied to determine the critical aggregation concentration (cac) of natural cyclodextrins (CDs) in aqueous solutions although the method is both laborious and time consuming. In the present study, the permeation technique was modified and the influence of osmotic pressure, sampling time, CD concentration and molecular weight-cut off (MWCO) of the membrane were investigated in two different permeation units, that is Franz diffusion cells and Slide-A-Lyzer™ MINI Dialysis. While both the osmotic pressure and CD concentration affect the steady state flux in both permeation units, effects of sampling time and the MWCO of the mounted membrane were only observed in the Franz diffusion cells. The osmotic effect was negligible in the Slide-A-Lyzer™ MINI Dialysis units. The modified permeation technique using Slide-A-Lyzer™ MINI Dialysis units was then used to determine the cac of natural CDs in water. The cac of αCD, ßCD and γCD was 1.19±0.17, 0.69±0.05 and 0.93±0.04% (w/v), respectively. The results indicated that the cac values depended on their intrinsic solubility. Moreover, the cac value of γCD in aqueous hydrocortisone/γCD inclusion complex solution was identical to the γCD cac value determined in pure water.

Self-Assembly of Cyclodextrins and Their Complexes in Aqueous Solutions.

Cyclodextrins (CDs) are enabling pharmaceutical excipients that can be found in numerous pharmaceutical products worldwide. Because of their favorable toxicologic profiles, CDs are often used in toxicologic and phase I assessments of new drug candidates. However, at relatively high concentrations, CDs can spontaneously self-assemble to form visible microparticles in aqueous mediums and formation of such visible particles may cause product rejections. Formation of subvisible CD aggregates are also known to affect analytical results during product development. How and why these CD aggregates form is largely unknown, and factors contributing to their formation are still not elucidated. The physiochemical properties of CDs are very different from simple amphiphiles and lipophilic molecules that are known to self-assemble and form aggregates in aqueous solutions but very similar to those of linear oligosaccharides. In general, negligible amounts of aggregates are formed in pure CD solutions, but the aggregate formation is greatly enhanced on inclusion complex formation, and the extent of aggregation increases with increasing CD concentration. The diameter of the aggregates formed is frequently less than about 300 nm, but visible aggregates can also be formed under certain conditions.

Glucosylceramide Reorganizes Cholesterol-Containing Domains in a Fluid Phospholipid Membrane.

Glucosylceramide (GlcCer), one of the simplest glycosphingolipids, plays key roles in physiology and pathophysiology. It has been suggested that GlcCer modulates cellular events by forming specialized domains. In this study, we investigated the interplay between GlcCer and cholesterol (Chol), an important lipid involved in the formation of liquid-ordered (lo) phases. Using fluorescence microscopy and spectroscopy, and dynamic and electrophoretic light scattering, we characterized the interaction between these lipids in different pH environments. A quantitative description of the phase behavior of the ternary unsaturated phospholipid/Chol/GlcCer mixture is presented. The results demonstrate coexistence between lo and liquid-disordered (ld) phases. However, the extent of lo/ld phase separation is sparse, mainly due to the ability of GlcCer to segregate into tightly packed gel domains. As a result, the phase diagram of these mixtures is characterized by an extensive three-phase coexistence region of fluid (ld-phospholipid enriched)/lo (Chol enriched)/gel (GlcCer enriched). Moreover, the results show that upon acidification, GlcCer solubility in the lo phase is increased, leading to a larger lo/ld coexistence region. Quantitative analyses allowed us to determine the differences in the composition of the phases at neutral and acidic pH. These results predict the impact of GlcCer on domain formation and membrane organization in complex biological membranes, and provide a background for unraveling the relationship between the biophysical properties of GlcCer and its biological action.

Validation of an HPLC Analytical Method for the Quantitative/Qualitative Determination of Fluticasone Propionate in Inhalation Particles on Several Matrices.

Fluticasone propionate is a highly potent corticosteroid used to treat asthma and allergic rhinitis. It is a very effective drug, but has the inconvenient factor of being insoluble in water. Cyclodextrins were used to improve this limitation because of their ability to form inclusion complexes with guest drug molecules as well as increase the stability and bioavailability of the drugs. A rapid and simple HPLC method was developed to detect and quantify fluticasone propionate in inhalation particles on several matrices. Liquid chromatography with a UV detector at a wavelength of 236 nm, using a C18 column, was employed in this study. Isocratic elution was employed using a mixture of acetonitrile and water (60:40, v/v). The analytical method validation was performed in accordance with ICH guidelines, which included selectivity, range, linearity, accuracy, detection limit, quantitation limit, precision, robustness, and stability of solutions. This method showed to be selective and specific. Acceptable assay precision and accuracy (100 ± 5.0%) were obtained at 50- 150% of the analytical concentration of fluticasone propionate at the target concentration of 0.060 mg/mL, and good linearity (0.9958) was achieved over a range of 0.03 to 0.09 mg/mL for fluticasone propionate. The proposed HPLC method proved to be reliable. The validation and application of this method can be adopted for determining the fluticasone propionate in: assays, impingers and impactors, diffusion cells, dissolutions, and other tests. In addition, this method can be adapted and used in the pharmaceutical industry for routine analysis.

Reconstrução imediata de mama com prótese de silicone retromuscular: padronização de retalhos musculares / Immediate breast reconstruction with retromuscular silicone prosthesis: standardization of muscular flaps

As reconstruções tornaram-se parte do tratamento do câncer de mama, dando uma melhor qualidade de vida às pacientes mastectomizadas. Os autores apresentam uma padronização de retalhos musculares de modo a proteger ainda mais a prótese mamária e dar um melhor resultado estético à reconstrução. Uma bolsa muscular é confeccionada utilizando os músculos peitoral maior, serrátil anterior, oblíquo externo e bainha anterior do reto abdominal. Esta técnica tem sido utilizada pelos autores desde 1999. Estes apresentam os resultados obtidos em 42 pacientes operadas, no período de maio de 2001 a junho de 2003. Os resultados são avaliados considerando-se a tolerância da reconstrução aos tratamentos adjuvantes e a qualidade estética, com bons resultados no seguimento a curto, médio e longo prazo.