Biodegradable polymer nanocomposites for ligament/tendon tissue engineering.

Ligaments and tendons are fibrous tissues with poor vascularity and limited regeneration capacity. Currently, a ligament/tendon injury often require a surgical procedure using auto- or allografts that present some limitations. These inadequacies combined with the significant economic and health impact have prompted the development of tissue engineering approaches. Several natural and synthetic biodegradable polymers as well as composites, blends and hybrids based on such materials have been used to produce tendon and ligament scaffolds. Given the complex structure of native tissues, the production of fiber-based scaffolds has been the preferred option for tendon/ligament tissue engineering. Electrospinning and several textile methods such as twisting, braiding and knitting have been used to produce these scaffolds. This review focuses on the developments achieved in the preparation of tendon/ligament scaffolds based on different biodegradable polymers. Several examples are overviewed and their processing methodologies, as well as their biological and mechanical performances, are discussed.

Real-World Clinical Experience With Idebenone in the Treatment of Leber Hereditary Optic Neuropathy.

BACKGROUND: Leber hereditary optic neuropathy (LHON) leads to bilateral central vision loss. In a clinical trial setting, idebenone has been shown to be safe and to provide a trend toward improved visual acuity, but long-term evidence of effectiveness in real-world clinical practice is sparse. METHODS: Open-label, multicenter, retrospective, noncontrolled analysis of long-term visual acuity and safety in 111 LHON patients treated with idebenone (900 mg/day) in an expanded access program. Eligible patients had a confirmed mitochondrial DNA mutation and had experienced the onset of symptoms (most recent eye) within 1 year before enrollment. Data on visual acuity and adverse events were collected as per normal clinical practice. Efficacy was assessed as the proportion of patients with either a clinically relevant recovery (CRR) or a clinically relevant stabilization (CRS) of visual acuity. In the case of CRR, time to and magnitude of recovery over the course of time were also assessed. RESULTS: At time of analysis, 87 patients had provided longitudinal efficacy data. Average treatment duration was 25.6 months. CRR was observed in 46.0% of patients. Analysis of treatment effect by duration showed that the proportion of patients with recovery and the magnitude of recovery increased with treatment duration. Average gain in best-corrected visual acuity for responders was 0.72 logarithm of the minimal angle of resolution (logMAR), equivalent to more than 7 lines on the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Furthermore, 50% of patients who had a visual acuity below 1.0 logMAR in at least one eye at initiation of treatment successfully maintained their vision below this threshold by last observation. Idebenone was well tolerated, with most adverse events classified as minor. CONCLUSIONS: These data demonstrate the benefit of idebenone treatment in recovering lost vision and maintaining good residual vision in a real-world setting. Together, these findings indicate that idebenone treatment should be initiated early and be maintained more than 24 months to maximize efficacy. Safety results were consistent with the known safety profile of idebenone.

Prevalence of Anxiety and Depression in Persons With Ostomies: A Cross-sectional Study.

PURPOSE: The purpose of this study was to measure the prevalence of anxiety and depression in adults with ostomies and to identify associated factors. DESIGN: A descriptive cross-sectional study. SUBJECTS AND SETTING: The sample comprised 120 adults; all reside in a health region in the state of Minas Gerais in southeastern Brazil. METHODS: Participants responded to a questionnaire designed for purposes of this study. The questionnaire included 2 validated instruments-the Beck Depression Inventory and the Beck Anxiety Inventory. In addition to measuring the prevalence of depression and anxiety, we used logistic regression models to identify factors associated with depression and anxiety. A backward method was adopted and the goodness-of-fit of the model was evaluated through the Hosmer and Lemeshow goodness-of-fit test. An odds ratio (OR) with a 95% confidence interval (95% CI) was used to measure the effect size of these associations. RESULTS: The prevalence of depression in our sample was 26.7% (n = 32; 95% CI, 18.6-34.6). Slightly more than half of respondents (53.1%, n = 17) had mild depression, 34.3% (n = 11) had moderate depression, and 12.6% (n = 4) had had severe depression. The prevalence of anxiety in our sample was 52.5% (n = 63; 95% CI, 43.4-61.5). Slightly less than half 47.6% (n = 30) had mild anxiety; 36.5% (n = 23) reported moderate and 15.9% (n = 10) reported severe anxiety. The final multiple logistic regression model indicated that respondents with less supportive family relationships were more likely to have depression than respondents with greater family support (OR, 3.83; 95% CI, 1.30-11.25). Similarly, respondents with anxiety were more likely to experience depression when compared to individuals reporting no anxiety (OR, 6.32; 95% CI, 2.26-17.65). CONCLUSIONS: Anxiety and depression are prevalent in adults living with an ostomy; anxiety was more prevalent than depression. Respondents with less support from their family and those with anxiety were more likely to experience depression.

Therapeutic benefit of idebenone in patients with Leber hereditary optic neuropathy: The LEROS nonrandomized controlled trial.

Leber hereditary optic neuropathy (LHON) is a mitochondrial disease leading to rapid and severe bilateral vision loss. Idebenone has been shown to be effective in stabilizing and restoring vision in patients treated within 1 year of onset of vision loss. The open-label, international, multicenter, natural history-controlled LEROS study (ClinicalTrials.gov NCT02774005) assesses the efficacy and safety of idebenone treatment (900 mg/day) in patients with LHON up to 5 years after symptom onset (N = 199) and over a treatment period of 24 months, compared to an external natural history control cohort (N = 372), matched by time since symptom onset. LEROS meets its primary endpoint and confirms the long-term efficacy of idebenone in the subacute/dynamic and chronic phases; the treatment effect varies depending on disease phase and the causative mtDNA mutation. The findings of the LEROS study will help guide the clinical management of patients with LHON.

[Pain assessment and training: the impact on pain control after cardiac surgery]. / Treinamento e avaliação sistematizada da dor: impacto no controle da dor do pós-operatório de cirurgia cardíaca.

We analyzed the effects of training and the application of a form for the systematized assessment of pain control after cardiac surgery on pain intensity and supplementary use of morphine. Three patient groups underwent a non-randomized clinical trial with standardized analgesic prescription. In Group I, the nursing staff did not receive specific training regarding the assessment and management of pain, and patients were treated following the established protocol of the institution. In Groups II and III, the nursing staff received targeted training. In Group II the nursing staff used a form for the systematized assessment of pain, which was not used in Group III. Group II presented a lower intensity of pain and greater consumption of supplementary morphine compared to Groups I and II. Training associated with the systematized assessment form increased the chance of identifying pain and influenced nurses' decision-making process, thus promoting pain relief among patients.

Biocompatible 3D-Printed Tendon/Ligament Scaffolds Based on Polylactic Acid/Graphite Nanoplatelet Composites.

Three-dimensional (3D) printing technology has become a popular tool to produce complex structures. It has great potential in the regenerative medicine field to produce customizable and reproducible scaffolds with high control of dimensions and porosity. This study was focused on the investigation of new biocompatible and biodegradable 3D-printed scaffolds with suitable mechanical properties to assist tendon and ligament regeneration. Polylactic acid (PLA) scaffolds were reinforced with 0.5 wt.% of functionalized graphite nanoplatelets decorated with silver nanoparticles ((f-EG)+Ag). The functionalization of graphene was carried out to strengthen the interface with the polymer. (f-EG)+Ag exhibited antibacterial properties against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), an important feature for the healing process and prevention of bacterial infections. The scaffolds' structure, biodegradation, and mechanical properties were assessed to confirm their suitability for tendon and ligamentregeneration. All scaffolds exhibited surface nanoroughness created during printing, which was increased by the filler presence. The wet state dynamic mechanical analysis proved that the incorporation of reinforcement led to an increase in the storage modulus, compared with neat PLA. The cytotoxicity assays using L929 fibroblasts showed that the scaffolds were biocompatible. The PLA+[(f-EG)+Ag] scaffolds were also loaded with human tendon-derived cells and showed their capability to maintain the tenogenic commitment with an increase in the gene expression of specific tendon/ligament-related markers. The results demonstrate the potential application of these new 3D-printed nanocomposite scaffolds for tendon and ligament regeneration.

Production of GMP-Compliant Clinical Amounts of Copper-61 Radiopharmaceuticals from Liquid Targets.

PET imaging has gained significant momentum in the last few years, especially in the area of oncology, with an increasing focus on metal radioisotopes owing to their versatile chemistry and favourable physical properties. Copper-61 (t1/2 = 3.33 h, 61% ß+, Emax = 1.216 MeV) provides unique advantages versus the current clinical standard (i.e., gallium-68) even though, until now, no clinical amounts of 61Cu-based radiopharmaceuticals, other than thiosemicarbazone-based molecules, have been produced. This study aimed to establish a routine production, using a standard medical cyclotron, for a series of widely used somatostatin analogues, currently labelled with gallium-68, that could benefit from the improved characteristics of copper-61. We describe two possible routes to produce the radiopharmaceutical precursor, either from natural zinc or enriched zinc-64 liquid targets and further synthesis of [61Cu]Cu-DOTA-NOC, [61Cu]Cu-DOTA-TOC and [61Cu]Cu-DOTA-TATE with a fully automated GMP-compliant process. The production from enriched targets leads to twice the amount of activity (3.28 ± 0.41 GBq vs. 1.84 ± 0.24 GBq at EOB) and higher radionuclidic purity (99.97% vs. 98.49% at EOB). Our results demonstrate, for the first time, that clinical doses of 61Cu-based radiopharmaceuticals can easily be obtained in centres with a typical biomedical cyclotron optimised to produce 18F-based radiopharmaceuticals.

Cardiac Abnormalities in COVID-19 Patients: Should a Cardiac Echocardiogram be Routine?

Current scientific evidence shows that SARS-CoV-2 infection is associated with an increased risk of thromboembolic events. In patients with ischaemic heart disease and heart failure, thrombi of the left ventricle can increase patient mortality, mainly due to the risk of systemic embolization. Given the hypercoagulable state associated with COVID-19, such events may be more likely. We describe a patient hospitalized for congestive heart failure and SARS-CoV-2 infection who was diagnosed with a thrombus in the left ventricle. After the thrombus was identified on echocardiography and treated with anticoagulation, it completely resolved and cardiac function improved. LEARNING POINTS: SARS-CoV-2 infection has been frequently associated with thromboembolic phenomena and intracardiac thrombi.Echocardiographic evaluation in patients with SARS-CoV-2 infection is important, especially in cases with known or new-onset cardiac pathology which predisposes to thromboembolic phenomena.The timely diagnosis and treatment of intracardiac thrombi can prevent complications and improve patient prognosis.

Idiopathic Hypereosinophilic Syndrome Presenting With Embolic Stroke.

Hypereosinophilic syndrome is a rare condition characterized by eosinophilia associated with organ damage, most commonly affecting the skin, lung, gastrointestinal, cardiovascular and central nervous system. The idiopathic form is characterized by the absence of other conditions associated with hypereosinophilia such as allergies, infectious, hematological, immunological, endocrine or neoplasm diseases. The authors present a clinical case of a 70-year-old man with no relevant history, who went to the emergency department for neurological deficits and nonspecific chest pain. Laboratory tests revealed marked eosinophilia, elevation of cardiac enzymes with normal electrocardiogram. Computed tomography of the head showed multiple bilateral ischemic lesions. Upon further investigation for the cerebrovascular disease, transesophageal echocardiogram showed a thrombus at the aortic arch, as a probable embolic source. Despite anticoagulant therapy and corticosteroids, the patient's status deteriorated, with multiple successive ischemic strokes and worsening neurological deficits. After a thorough investigation, the diagnosis of idiopathic eosinophilia was established.

Tension Pneumothorax as Initial Manifestation of Granulomatosis with Polyangiitis (GPA).

Granulomatosis with polyangiitis (Wegener's granulomatosis) is a systemic vasculitis that primarily affects small and medium vessels. Its manifestations are usually confined to the upper airway, lower airway and kidney. It can also affect other organs and systems, although this is unusual. We describe the case of a 67-year-old woman who presented with a tension pneumothorax due to rupture of a pulmonary cavity. This pulmonary cavity proved to be secondary to systemic disease which also caused a tumour in her kidney. Biopsy showed non-necrotizing granulomatosis, and even though antineutrophil cytoplasmic antibodies (ANCA) were negative, the diagnosis of granulomatosis with polyangiitis was made. LEARNING POINTS: Granulomatosis with polyangiitis (GPA) can be a challenging diagnosis when the initial manifestation is atypical, so a careful history and physical examination are needed to make the diagnosis.It is not uncommon for patients with multisystemic inflammatory disease to attend several different specialty clinics before the diagnosis is reached.GPA with negative ANCA is rare, and occurs more frequently in non-severe forms of the disease.

Artery of Percheron Occlusion: A Diagnostic Challenge.

Artery of Percheron occlusion is a rare cause of ischaemic stroke characterized by bilateral thalamus infarction. Presentation is varied and non-specific, with the most frequent manifestations being altered level of consciousness, hypersomnolence or altered oculomotor movements. We describe the case of a 37-year-old man hospitalized for hypersomnia and hypomnesia with 3 days of evolution, who was diagnosed with a bilateral thalamus stroke due to artery of Percheron occlusion. LEARNING POINTS: Stroke is frequently encountered but can present a diagnostic challenge when presentation is non-specific or a lesion is not identified.Artery of Percheron stenosis has a varied and often non-specific presentation, which can lead to delayed diagnosis and treatment of these patients.It is important that doctors recognize this entity for timely diagnosis and treatment, and for the best prognosis.

Poly(Lactic Acid)/Graphite Nanoplatelet Nanocomposite Filaments for Ligament Scaffolds.

The anterior cruciate ligament (ACL) is one of the most prone to injury in the human body. Due to its insufficient vascularization and low regenerative capacity, surgery is often required when it is ruptured. Most of the current tissue engineering (TE) strategies are based on scaffolds produced with fibers due to the natural ligament's fibrous structure. In the present work, composite filaments based on poly(L-lactic acid) (PLA) reinforced with graphite nanoplatelets (PLA+EG) as received, chemically functionalized (PLA+f-EG), or functionalized and decorated with silver nanoparticles [PLA+((f-EG)+Ag)] were produced by melt mixing, ensuring good filler dispersion. These filaments were produced with diameters of 0.25 mm and 1.75 mm for textile-engineered and 3D-printed ligament scaffolds, respectively. The resulting composite filaments are thermally stable, and the incorporation of graphite increases the stiffness of the composites and decreases the electrical resistivity, as compared to PLA. None of the filaments suffered significant degradation after 27 days. The composite filaments were processed into 3D scaffolds with finely controlled dimensions and porosity by textile-engineered and additive fabrication techniques, demonstrating their potential for ligament TE applications.

Palliative care consultation team: symptom relief in first 48 hours of hospitalization.

OBJECTIVE: To compare the relief of symptoms provided by palliative care consultation team (PCCT) compared to the traditional care team (TC), in patients with advanced cancer in the first 48 hours of hospitalization. METHOD: Allocated to PCCT Group and TC Group, this study assessed 290 patients according to the Edmonton Symptom Assessment System (ESAS) within the first 48 hours of hospitalization. The main outcome was a minimum 2-point reduction in symptom intensity. RESULTS: At 48 hours, the PCCT Group had a 2-point reduction in the mean differences (p <0.001) in pain, nausea, dyspnea, and depression; and TC Group, on nausea and sleep impairment (p <0.001). Multiple Logistic Regression found for the PCCT Group a greater chance of pain relief (OR 2.34; CI 1.01-5.43; p = 0.049). CONCLUSION: There was superiority of the PCCT Group for pain relief, dyspnea and depression. There is a need for more studies that broaden the understanding of team modalities.

Translation and content validation of the Geriatric Institutional Assessment Profile for Brazil.

OBJECTIVE: to describe the process of content adaptation and validation of the Geriatric Institutional Assessment Profile (GIAP) for nurses working in the health care for older adults in Brazilian hospitals. METHOD: methodological study conducted in five stages: initial translation, synthesis of initial translation, back translation, evaluation by committee of judges, and pre-test for cultural adaptation of the instrument. RESULTS: the instrument evaluation had good agreement between the judges, with general content validity of 0.94. The items of the translated version evaluated as unsatisfactory by the judges were reformulated from the professionals' considerations in each group. Thirty-one subjects participated in the study. They considered the instrument easy-to-understand and suggested minor adjustments in some items. CONCLUSION: the content of the Brazilian version of the GIAP is considered adapted and validated, with potential use in hospital institutions. The next stage will be to submit the instrument to the evaluation process of its psychometric properties for use in Brazilian populations.

[Development of a multivariable predictive model for postoperative nausea and vomiting after cancer surgery in adults]. / Desenvolvimento de um modelo preditivo multivariado para náusea e vômito no pós­operatório de cirurgia oncológica em adultos.

BACKGROUND AND OBJECTIVES: Predicting postoperative nausea and vomiting risk is the cornerstone for deciding prophylaxis. Apfel's score does not define how long a person must be abstinent from smoking to be considered a non-smoker, and the use of intraoperative spinal opioids as a risk factor for predicting postoperative nausea and vomiting is also not addressed. The aim of this study was to quantify predicting postoperative nausea and vomiting risk by an ordinal smoking status and the use of intraoperative opioids (systemic or neuraxial), and to develop a new predictive model. METHODS: Patients scheduled for cancer surgery were prospectively evaluated for predicting postoperative nausea and vomiting in the first 24h after surgery. RESULTS: Of 2014 initially included patients, 185 participants were excluded. Smoking status classification was associated with predicting postoperative nausea and vomiting incidence rates of 14.1%, 18.1%, 24.7%, 29.4% and 33.9% for smokers, patients who stopped smoking up to 1 month prior to surgery, one to 6 months prior, more than 6 months prior or patients who never smoked, respectively, which was significant in the multiple comparisons analysis (adjusted p=0.015). The multiple comparisons-adjusted hypothesis tests for association with predicting postoperative nausea and vomiting for sex, age, previous predicting postoperative nausea and vomiting, chemotherapy-induced nausea, and ordinal smoking status had p-values of <0.001. The type of surgery (p=0.04), total fentanyl consumption (p=0.04), both intraoperative and postoperative, were significant predictors. A new model was developed and showed higher discriminative power than Apfel's score (AUC 67.9% vs. 63.7%, p<0.001). CONCLUSION: Smoking status showed a significant and linear impact on predicting postoperative nausea and vomiting incidence, and we developed a new model that uses unambiguous smoking and opioid predictors.

Associated factors with the knowledge of nurses of a high complexity oncology centre in Brazil, on the management of cancer pain.

Pain is one of the most prevalent symptoms in cancer patients and may be directly related to cancer or to the procedures needed for its diagnosis and treatment. It is estimated that about 40% of cancer patients receive inadequate treatment for painful conditions. Among the barriers to adequate pain management are inadequate knowledge and the dysfunctional beliefs of healthcare professionals. Therefore, the present study aims to assess the knowledge of oncology nurses on the management of pain, as well as the factors associated with it. It is a cross-sectional study with 126 nurses working at a High Complexity Oncology Centre in Brazil. Knowledge about the management of cancer pain was evaluated through the instrument 'Nurses' Knowledge on Cancer Pain Management-World Health Organization-developed by Ramos (1994). In the analysis of the association between knowledge about pain management and the independent variables, Poisson regression was used with robust variance, and values of p ≤ 0.05 were considered statistically significant. Adequate knowledge prevalence was 54.1% confidence intervals (CI 5.40%-62.80%). These nurses differed in relation to those with inadequate knowledge regarding the source of knowledge about pain, the ethical aspects in the treatment of the patient with oncologic pain, and non-pharmacological methods (coeliac plexus neuroleptic block) for pain control. Also, the factors associated with adequate knowledge were longer professional experience time ([10-19 years (ratio prevalence (RP) = 1.72, 95% CI: 1.05-2.81), 20-29 years (RP = 2.56, 95% CI: 1.63-4.02), 30-39 years (RP = 3.45, 95% CI: 2.25-5.29]), and not believing that the use of opioids causes harm to patients corresponded with a greater chance prevalence ratio (PR = 1.20, 95% CI: 1.12-1.20) of having adequate knowledge. The findings of the study point to the need for continuing education, updated education, and reflection, especially for nurses with less professional experience.

Análisis de Variables Antropométricas y su Relación con la Fuerza Pinch / Analysis of the Anthropometric Variables and their Relationship with the Pinch Force

Resumen: La evaluación de la fuerza en la mano es utilizada en ámbitos de salud y laborales, está compuesta por la fuerza de agarre y la fuerza de pellizco o fuerza pinch (Palmar Pinch - PP y Key Pinch - KP). La fuerza pinch ha sido poco estudiada y relacionada con variables antropométricas. El objetivo del presente trabajo fue determinar la relación entre la fuerza PP y KP con el género, la dominancia, la edad y variables antropométricas. Haciendo uso de un dinamómetro Jamar y con la participación de 681 sujetos (48,9 % F y 51.1 % M) aparentemente sanos de la Ciudad de Bogotá (Colombia), quienes desempeñaban diferentes actividades ocupacionales, se encontró que las fuerzas PP y KP fueron significativamente más altas en los hombres que en las mujeres tanto en la mano no dominante (8.27 Kgf Vs 6.0 Kgf) como en la mano dominante (8.57 Kgf Vs 6.27 Kgf). Se propusieron modelos predictivos que definieron como variables principales la edad, espesor, circunferencia y circunferencia máxima de la mano. En el género femenino se estableció como variable primordial la edad, mientras que en el masculino en dos modelos se define la circunferencia de la mano y en otros dos la circunferencia máxima de la mano.

Abstract: The evaluation of the force in the hand is used in health and labor fields; it is composed of the grip force and the pinch force (Palmar Pinch - PP and Key Pinch - KP). The pinch force has not had significant amount of studies and connections with anthropometric variables. This work aimed to determine the relationship between the PP and KP strength with gender, dominance, age, and anthropometric variables. Using a Jamar dynamometer and with the participation of 681 subjects apparently healthy (48.9 % F and 51.1 % M) from the City of Bogotá (Colombia), who performed different occupational activities, it was found that the PP and KP forces were significantly higher in men than in women both in the non-dominant hand (8.27 Kgf Vs. 6.0 Kgf) and in the dominant hand (8.57 Kgf Vs 6.27 Kgf). The predictive models proposed in this study defined age, thickness, circumference, and maximum circumference of the hand as the main variables. In the female gender, age was established as the primary variable. At the same time, in the male, the circumference of the hand was defined in two models, and the maximum circumference of the hand in another two.