Electrospun composite-coated endotracheal tubes with controlled siRNA and drug delivery to lubricate and minimize upper airway injury.

Endotracheal Tubes (ETTs) maintain and secure a patent airway; however, prolonged intubation often results in unintended injury to the mucosal epithelium and inflammatory sequelae which complicate recovery. ETT design and materials used have yet to adapt to address intubation associated complications. In this study, a composite coating of electrospun polycaprolactone (PCL) fibers embedded in a four-arm polyethylene glycol acrylate matrix (4APEGA) is developed to transform the ETT from a mechanical device to a dual-purpose device capable of delivering multiple therapeutics while preserving coating integrity. Further, the composite coating system (PCL-4APEGA) is capable of sustained delivery of dexamethasone from the PCL phase and small interfering RNA (siRNA) containing polyplexes from the 4APEGA phase. The siRNA is released rapidly and targets smad3 for immediate reduction in pro-fibrotic transforming growth factor-beta 1 (TGFϐ1) signaling in the upper airway mucosa as well as suppressing long-term sequelae in inflammation from prolonged intubation. A bioreactor was used to study mucosal adhesion to the composite PCL-4APEGA coated ETTs and investigate continued mucus secretory function in ex vivo epithelial samples. The addition of the 4APEGA coating and siRNA delivery to the dexamethasone delivery was then evaluated in a swine model of intubation injury and observed to restore mechanical function of the vocal folds and maintain epithelial thickness when observed over 14 days of intubation. This study demonstrated that increase in surface lubrication paired with surface stiffness reduction significantly decreased fibrotic behavior while reducing epithelial adhesion and abrasion.

Endotracheal tubes with dexamethasone eluting electrospun coating improve tissue mechanical function after upper airway injury.

Corticosteroid-eluting endotracheal tubes (ETTs) were developed and employed in a swine laryngotracheal injury model to maintain airway patency and provide localized drug delivery to inhibit fibrotic scarring. Polycaprolactone (PCL) fibers with or without dexamethasone were electrospun onto the ETT surface PCL-only coated ETTs and placed in native airways of 18 Yorkshire swine. Regular and dexamethasone-PCL coated ETTs were placed in airways of another 18 swine injured by inner laryngeal mucosal abrasion. All groups were evaluated after 3, 7 and 14 days (n = 3/treatment/time). Larynges were bisected and localized stiffness determined by normal indentation, then sequentially matched with histological assessment. In the native airway, tissue stiffness with PCL-only ETT placement increased significantly from 3 to 7 days (p = 0.0016) and 3 to 14 days (p < 0.0001) while dexamethasone-PCL ETT placement resulted in stiffness decreasing from 7 to 14 days (p = 0.031). In the injured airway, localized stiffness at 14 days was significantly greater after regular ETT placement (23.1 ± 0.725 N/m) versus dexamethasone-PCL ETTs (17.10 ± 0.930 N/m, p < 0.0001). Dexamethasone-loaded ETTs were found to reduce laryngotracheal tissue stiffening after simulated intubation injury compared to regular ETTs, supported by a trend of reduced collagen in the basement membrane in injured swine over time. Findings suggest localized corticosteroid delivery allows for tissue stiffness control and potential use as an approach for prevention and treatment of scarring caused by intubation injury.

Changes in vocal fold gene expression and histology after injection augmentation in a recurrent laryngeal nerve injury model.

OBJECTIVE: To investigate changes in neuroregenerative pathways with vocal fold denervation in response to vocal fold augmentation. METHODS: Eighteen Yorkshire crossbreed swine underwent left recurrent laryngeal nerve transection, followed by observation or augmentation with carboxymethylcellulose or calcium hydroxyapatite at two weeks. Polymerase chain reaction expression of genes regulating muscle growth (MyoD1, MyoG and FoxO1) and atrophy (FBXO32) were analysed at 4 and 12 weeks post-injection. Thyroarytenoid neuromuscular junction density was quantified using immunohistochemistry. RESULTS: Denervated vocal folds demonstrated reduced expression of MyoD1, MyoG, FoxO1 and FBXO32, but overexpression after augmentation. Healthy vocal folds showed increased early and late MyoD1, MyoG, FoxO1 and FBXO32 expression in all animals. Neuromuscular junction density had a slower decline in augmented compared to untreated denervated vocal folds, and was significantly reduced in healthy vocal folds contralateral to augmentation. CONCLUSION: Injection augmentation may slow neuromuscular degeneration pathways in denervated vocal folds and reduce compensatory remodelling in contralateral healthy vocal folds.

Effect of continuous local dexamethasone on tissue biomechanics and histology after inhalational burn in a preclinical model.

Objective: Inhalational burns frequently lead to dysphonia and airway stenosis. We hypothesize local dexamethasone delivery via a novel drug-eluting electrospun polymer-mesh endotracheal tube (ETT) reduces biomechanical and histologic changes in the vocal folds in inhalational burn. Methods: Dexamethasone-loaded polymer mesh was electrospun onto ETTs trimmed to transglottic endolaryngeal segments and secured in nine Yorkshire Crossbreed swine with directed 150°C inhalation burns. Uncoated ETTs were implanted in nine additional swine with identical burns. ETT segments were maintained for 3 and 7 days. Vocal fold (VF) structural stiffness was measured using automated-indentation mapping and compared across groups and to four uninjured controls, and matched histologic assessment performed. Statistical analysis was conducted using two-way ANOVA with Tukey's post hoc test and Wilcoxon rank-sum test. Results: VF stiffness after burn decreased with longer intubation, from 19.4 (7.6) mN/mm at 3 days to 11.3 (5.2) mN/mm at 7 days (p < .0001). Stiffness similarly decreased with local dexamethasone, from 25.9 (17.2) mN/mm at 3 days to 18.1 (13.0) mN/mm at 7 days (p < .0001). VF stiffness in the dexamethasone group was increased compared to tissues without local dexamethasone (p = .0002), and all groups with ETT placement had higher tissue stiffness at 3 days (p < .001). No significant change in histologic evidence of epithelial ulceration or fibrosis was noted, while an increased degree of inflammation was noted in the dexamethasone group (p = .04). Conclusion: Local dexamethasone delivery increases VF stiffness and degree of inflammation compared to uncoated ETTs in an acute laryngeal burn model, reflected in early biomechanical and histologic changes in an inhalational burn model.

Papel de la psicoterapia en la reducción del absentismo sobre trabajadores con depresión y/o ansiedad: revisión Sistemática / Role of psychotherapy in reducing absenteeism in workers with depression and/or anxiety: a systematic review

Objetivo: Sintetizar la evidencia encontrada sobre la efectividad de diferentes tipos de psicoterapia destinadas a reducir la ausencia por enfermedad en trabajadores con trastorno depresivo y/o de ansiedad. Material y Métodos: Se realizó una revisión sistemática en las bases de datos electrónicas de MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus, Web of Science. Resultados: En total se incluyeron 3121pacientes. El diagnóstico de la enfermedad se realiza basándose en el DSM-IV o CIE 10. Para la reducción de síntomas ansioso/depresivos, los resultados han variado entre un máximo del 78% de recuperación a un mínimo del 22 % dependiendo del tipo de psicoterapia empleada. En cuanto al ámbito laboral, se ha observado una disminución del absentismo con máxima del 53%. Conclusiones: El uso de diferentes tipos de psicoterapia en los pacientes con trastorno depresivo y/o ansiedad, reducen las ausencias por enfermedad en los trabajadores. (AU)

Objective: To synthesize the evidence found on the effectiveness of different types of psychotherapy aimed to reduce sickness absence in workers with depressive and/or anxiety disorder. Material and Method: A systematic review was performed using the electronic data base from MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus and Web of Science Results: 3121 patients were included. The diagnosis is made mostly based on the DSM-IV or ICD 10. In terms for the reduction of anxious/depressive symptoms after therapy, the results have varied between a maximum of 78% recovery to a minimum of 22% depending on the type of psychotherapy used. In relation to the workplace, it has been measured by the decrease in absenteeism, with a maximum reduction of 53%. Conclusions: The use of different types of psychotherapy in patients with depressive and/or anxiety disorders reduces absences due to illness in workers. (AU)

Augmentation and vocal fold biomechanics in a recurrent laryngeal nerve injury model.

Objectives/hypothesis: Composite vocal fold (VF) biomechanical data are lacking for augmentation after recurrent laryngeal nerve (RLN) injury. We hypothesize resulting atrophy decreases VF stiffness and augmentation restores native VF biomechanics. Methods: Sixteen Yorkshire Crossbreed swine underwent left RLN transection and were observed or underwent carboxymethylcellulose (CMC) or calcium hydroxyapatite (CaHa) augmentation at 2 weeks. Biomechanical measurements (structural stiffness, displacement, and maximum load) were measured at 4 or 12 weeks. Thyroarytenoid (TA) muscle cross-sectional area was quantified and compared with two-way ANOVA with Tukey's post hoc test. Results: After 4 weeks, right greater than left structural stiffness (mean ± SE) was observed (49.6 ± 0.003 vs. 28.4 ± 0.002 mN/mm), left greater than right displacement at 6.3 mN (0.54 ± 0.01 vs. 0.46 ± 0.01 mm, p < .01) was identified, and right greater than left maximum load (72.3 ± 0.005 vs. 40.8 ± 0.003 mN) was recorded. TA muscle atrophy in the injured group without augmentations was significant compared to the noninjured side, and muscle atrophy was seen at overall muscle area and individual muscle bundles. CMC augmentation appears to maintain TA muscle structure in the first 4 weeks with atrophy present at 12 weeks. Conclusions: VF biomechanical properties match TA muscle atrophy in this model, and both CMC and CaHa injection demonstrated improved biomechanical properties and slower TA atrophy compared to the uninjured side. Taken together, these data provide a quantifiable biomechanical basis for early injection laryngoplasty to improve dysphonia and potentially improve healing in reversible unilateral vocal fold atrophy. Level of evidence: N/A.

Effect of Intrawound Vancomycin Powder in Operatively Treated High-risk Tibia Fractures: A Randomized Clinical Trial.

Importance: Despite the widespread use of systemic antibiotics to prevent infections in surgically treated patients with fracture, high rates of surgical site infection persist. Objective: To examine the effect of intrawound vancomycin powder in reducing deep surgical site infections. Design, Setting, and Participants: This open-label randomized clinical trial enrolled adult patients with an operatively treated tibial plateau or pilon fracture who met the criteria for a high risk of infection from January 1, 2015, through June 30, 2017, with 12 months of follow-up (final follow-up assessments completed in April 2018) at 36 US trauma centers. Interventions: A standard infection prevention protocol with (n = 481) or without (n = 499) 1000 mg of intrawound vancomycin powder. Main Outcomes and Measures: The primary outcome was a deep surgical site infection within 182 days of definitive fracture fixation. A post hoc comparison assessed the treatment effect on gram-positive and gram-negative-only infections. Other secondary outcomes included superficial surgical site infection, nonunion, and wound dehiscence. Results: The analysis included 980 patients (mean [SD] age, 45.7 [13.7] years; 617 [63.0%] male) with 91% of the expected person-time of follow-up for the primary outcome. Within 182 days, deep surgical site infection was observed in 29 of 481 patients in the treatment group and 46 of 499 patients in the control group. The time-to-event estimated probability of deep infection by 182 days was 6.4% in the treatment group and 9.8% in the control group (risk difference, -3.4%; 95% CI, -6.9% to 0.1%; P = .06). A post hoc analysis of the effect of treatment on gram-positive (risk difference, -3.7%; 95% CI, -6.7% to -0.8%; P = .02) and gram-negative-only (risk difference, 0.3%; 95% CI, -1.6% to 2.1%; P = .78) infections found that the effect of vancomycin powder was a result of its reduction in gram-positive infections. Conclusions and Relevance: Among patients with operatively treated tibial articular fractures at a high risk of infection, intrawound vancomycin powder at the time of definitive fracture fixation reduced the risk of a gram-positive deep surgical site infection, consistent with the activity of vancomycin. Trial Registration: ClinicalTrials.gov Identifier: NCT02227446.

Sobredosis de warfarina: Reporte de caso / Warfarin overdose: case report

La intoxicación por warfarina es poco común, pero puede provocar hemorragias potencialmente mortales. Lo ideal sería la dosis adaptada de vitamina K que da como resultado un INR terapéutico hasta que las concentraciones de warfarina se normalicen. Sin embargo, dicho método de tratamiento puede complicarse con rebote de INR y resistencia a warfarina. Presentamos el caso de un varon de 75 años con historial de hábito alcohólico que inició tratamiento con warfarina, concomitante a fluoxetina. Presentó un INR>10 con hemorragia mayor que se revirtió satisfactoriamente al tratamiento conservador con vitamina K y Plasma fresco congelado. La sobredosis en pacientes con tratamiento de anticoagulación oral asociado a una patología de base hace más complicado el tratamiento por la dificultad de alcanzar una reversión total. La heparinización es una opción adecuada hasta restablecer la warfarinización, pero prolonga la hospitalización. Un evento como el que se presenta puede cursar con diferentes complicaciones, susceptibles de exponer al paciente a una situación crítica con riesgo vital inminente; por lo que, un diagnóstico precoz y acciones terapeúticas oportunas pueden prevenir este riesgo.

Enfermedad periodontal inflamatoria asociada a un absceso pulmonar / Peridental inflammatory Disease associated to lung abscess

A pesar, de que hay reportes de casos en la literatura internacional, que asocian la enfermedad periodontal con enfermedades respiratorias y medidas para la prevención de la enfermedad periodontal inflamatoria, sino se establece un adecuado manejo de esta última, puede evolucionar con una complicación sistémica como es el absceso pulmonar. Objetivo: Ilustrar cómo la enfermedad periodontal inflamatoria puede asociarse a un absceso pulmonar como complicación sistémica en su evolución. Presentación del caso: Se presenta una paciente femenina con antecedentes de absceso periodontal y enfermedad periodontal crónica, los cuales constituyeron las únicas causas demostradas del desarrollo de un absceso pulmonar, tras la aplicación del método clínico. Conclusiones: La enfermedad periodontal inflamatoria puede evolucionar hacia la remisión si se adoptan las medidas protocolizadas para su tratamiento, sin embargo, siempre que esa enfermedad siga su curso natural o no se maneje adecuadamente puede evolucionar a complicaciones sistémicas como lo es el absceso pulmonar(AU)

Although there are in the international literature report of cases, which associate the peridental disease to respiratory diseases and measurements to the prevention of the peridental inflammatory disease, if there is not established an adequate usage of the last one, it can emerge with a systemic complication like lung abscess. Objective: To show how the peridental inflammatory disease can be associated to a lung abscess like a systemic complication in its evolution. Case Presentation: A female patience is presented with antecedents of peridental abscess and chronic peridental disease, which were the unique causes demonstrated in the development of a lung abscess, after the application of the clinic method. Conclusions: The peridental inflammatory disease can emerge towards the remission if some protocolic precautions are adopted for its treatment; nevertheless whenever the disease follows its natural course or it is not properly managed it can emerge to systemic complications like, it is the lung abscess(AU)

Enfermedad periodontal inflamatoria asociada a un absceso pulmonar. Presentación de un caso / Peridental inflammatory Disease associated to lung abscess. Case presentation / Peridental inflammatory Disease associated to lung abscess. Case presentation

Fundamento: A pesar, de que hay reportes de casos en la literatura internacional, que asocian la enfermedad periodontal con enfermedades respiratorias y medidas para la prevención de la enfermedad periodontal inflamatoria, sino se establece un adecuado manejo de esta última, puede evolucionar con una complicación sistémica como es el absceso pulmonar. Objetivo: Ilustrar cómo la enfermedad periodontal inflamatoria puede asociarse a un absceso pulmonar como complicación sistémica en su evolución. Presentación del caso: Se presenta una paciente femenina con antecedentes de absceso periodontal y enfermedad periodontal crónica, los cuales constituyeron las únicas causas demostradas del desarrollo de un absceso pulmonar, tras la aplicación del método clínico. Conclusiones: La enfermedad periodontal inflamatoria puede evolucionar hacia la remisión si se adoptan las medidas protocolizadas para su tratamiento, sin embargo, siempre que esa enfermedad siga su curso natural o no se maneje adecuadamente puede evolucionar a complicaciones sistémicas como lo es el absceso pulmonar.

Background: Although there are in the international literature report of cases, which associate the peridental disease to respiratory diseases and measurements to the prevention of the peridental inflammatory disease, if there is not established an adequate usage of the last one, it can emerge with a systemic complication like lung abscess. Objective: To show how the peridental inflammatory disease can be associated to a lung abscess like a systemic complication in its evolution Case Presentation: A female patience is presented with antecedents of peridental abscess and chronic peridental disease, which were the unique causes demonstrated in the development of a lung abscess, after the application of the clinic method Conclusions: The peridental inflammatory disease can emerge towards the remission if some protocolic precautions are adopted for its treatment; nevertheless whenever the disease follows its natural course or it is not properly managed it can emerge to systemic complications like, it is the lung abscess.

[Analysis of Cost-effectiveness of screening for breast cancer with conventional mammography, digital and magnetic resonance imaging]. / Análise de Custo-efetividade do rastreamento do câncer de mama com mamografia convencional, digital e ressonância.

A cost-effectiveness analysis was conducted in screening for breast cancer. The use of conventional mammography, digital and magnetic resonance imaging were compared with natural disease history as a baseline. A Markov model projected breast cancer in a group of 100,000 women for a 30 year period, with screening every two years. Four distinct scenarios were modeled: (1) the natural history of breast cancer, as a baseline, (2) conventional film mammography, (3) digital mammography and (4) magnetic resonance imaging. The costs of the scenarios modeled ranged from R$ 194.216,68 for natural history, to R$ 48.614.338,31, for screening with magnetic resonance imaging. The difference in effectiveness between the interventions ranged from 300 to 78.000 years of life gained in the cohort. The ratio of incremental cost-effectiveness in terms of cost per life-year gains, conventional mammographic screening has produced an extra year for R$ 13.573,07. The ICER of magnetic resonance imaging was R$ 2.904.328,88, compared to no screening. In conclusion, it is more cost-effective to perform the screening with conventional mammography than other technological interventions.

Análise de Custo-efetividade do rastreamento do câncer de mama com mamografia convencional, digital e ressonância / Analysis of Cost-effectiveness of screening for breast cancer with conventional mammography, digital and magnetic resonance imaging

O objetivo deste trabalho foi realizar análise de custo efetividade da intervenção das mamografias convencional e digital e da ressonância magnética no rastreamento de câncer de mama, comparando com o não rastreamento. Foi construído um modelo markoviano, numa uma coorte hipotética de 100 mil mulheres com rastreamento bianual, cuja linha de base é a história natural da doença. Modelaram-se quatro cenários distintos: (1) a história natural do câncer de mama como linha de base; (2) mamografia com filme convencional; (3) mamografia digital e (4) e ressonância magnética. Os custos dos cenários modelados variaram desde R$ 194.216,68 para a história natural, até R$ 48.614.338,31 para o rastreamento com ressonância magnética. As diferenças de efetividade entre as intervenções variaram de 300 até 78.000 anos de vida ganhos, na coorte de 100 mil mulheres. Em relação à Razão de Custo-Efetividade Incremental, em termos de custo por ano de vida ganhos, a estratégia do rastreamento mamográfico convencional produziu um ano extra por R$ 13.573,07. A Razão de Custo Efetividade Incremental (ICER) da ressonância magnética foi de R$ 2.904.328,88 em relação ao não rastreamento. O estudo mostrou que é mais custo-efetivo realizar o rastreamento com a mamografia convencional do que as outras tecnologias de intervenção.

A cost-effectiveness analysis was conducted in screening for breast cancer. The use of conventional mammography, digital and magnetic resonance imaging were compared with natural disease history as a baseline. A Markov model projected breast cancer in a group of 100,000 women for a 30 year period, with screening every two years. Four distinct scenarios were modeled: (1) the natural history of breast cancer, as a baseline, (2) conventional film mammography, (3) digital mammography and (4) magnetic resonance imaging. The costs of the scenarios modeled ranged from R$ 194.216,68 for natural history, to R$ 48.614.338,31, for screening with magnetic resonance imaging. The difference in effectiveness between the interventions ranged from 300 to 78.000 years of life gained in the cohort. The ratio of incremental cost-effectiveness in terms of cost per life-year gains, conventional mammographic screening has produced an extra year for R$ 13.573,07. The ICER of magnetic resonance imaging was R$ 2.904.328,88, compared to no screening. In conclusion, it is more cost-effective to perform the screening with conventional mammography than other technological interventions.