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Background: There is no consensus on the best intervention for topical management of bleeding in malignant wounds. Although surgical hemostatic dressings are recommended, the use of calcium alginate (CA) is frequent among practitioners., Objective: The aim of this study was to evaluate the hemostatic efficacy of oxidized regenerated cellulose (ORC) and CA dressing in the management of bleeding from malignant wounds resulting from breast cancer., Methods: This was a randomized open clinical trial. The outcomes measured were total time to hemostasis and the number of hemostatic products used., Results: Sixty-one patients were potentially eligible for the study, 1 did not consent, and 32 were assessed to be ineligible, resulting in a sample of 28 who were randomized to 2 study groups. Total time to hemostasis was 93.8 seconds in the ORC group, with an average of 30.1 seconds (95% confidence interval, 18.6-189 seconds), and 67 seconds in the CA group, with an average of 30.4 seconds (confidence interval, 21.7 seconds to imprecise upper limit). The main difference was 26.8 seconds. Kaplan-Meier log-rank test, and Cox model showed no statistical significance ( P = 0.894). A total of 18 hemostatic products were used in the CA group and 34 in the ORC group. No adverse effects were identified., Conclusions: Although no significant differences were identified in terms of time, more hemostatic products were used in the ORC group, highlighting the effectiveness of CA., Implications for Practice: Calcium alginate may be the first choice in the management of bleeding in malignant wounds, favoring nursing in the most immediate hemostatic actions., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Obesity is a relevant risk factor in breast cancer (BC), but little is known about the effects of overweight and obesity in surgical outcomes of BC patients. The aim of this study is to analyse surgical options and associated overall survival (OS) in overweight and obese women with BC. In this study, 2143 women diagnosed between 2012 and 2016 at the Portuguese Oncology Institute of Porto (IPO-Porto) were included, and the clinicopathological information was retrieved from the institutional database. Patients were stratified by body mass index (BMI). Statistical analysis included Pearson's chi-squared test with statistical significance set at p < 0.05. Multinomial, binary logistic regression and cox proportional-hazards model were also performed to calculate odd ratios and hazard ratios with 95% confidence intervals for adjusted and non-adjusted models. The results revealed no statistical difference in histological type, topographic localization, tumour stage and receptor status and in the number of surgical interventions. Overweight women have increased probability to be subjected to sentinel node biopsy. Obese and overweight women are more likely to be submitted to conservative surgery and contrariwise, less likely to undergo total mastectomy. Patients submitted to conservative surgery and not submitted to total mastectomy had a favourable OS although without statistical significance. No significant differences were observed in OS when stratified by BMI. Our results revealed significant variations regarding the surgical options in overweight and obese patients, but these were not translated in OS difference. More research is recommended to better address treatment options in overweight and obese BC patients., (© 2023. The Author(s).)

Introduction: Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD)., Methods: A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD., Results: 43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6-82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3-96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8-14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8-8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9-2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively., Conclusions: TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres., Competing Interests: Conflict of interest: H. Novais Bastos has received support from Sociedade Portuguesa de Pneumologia, as well as grants or contracts from Fundação para a Ciência e Tecnologia and Fundação Amélia de Mello/CUF; consulting fees from Boehringer-Ingelheim and Roche; payment or honoraria for lectures, presentations, speakers’ bureaus, manuscript writing or educational events from Boehringer-Ingelheim and Roche; support for attending meetings and/or travel from Boehringer-Ingelheim; and equipment, materials, drugs, medical writing, gifts or other services from Boehringer-Ingelheim, all outside the submitted work. The remaining authors have nothing to disclose., (Copyright ©The authors 2022.)

Background: The echocardiogram is a useful method for monitoring the cardiovascular complications of chronic obstructive pulmonary disease (COPD), but it is not clear if morphological and functional cardiac variables are able to identify patients with unfavorable COPD progression., Objective: The aim of this study was to investigate morphological and functional echocardiographic variables associated with exacerbation of the disease, pulmonary function parameters and functional capacity evaluation in COPD patients., Method: A longitudinal observational study including 91 patients diagnosed with COPD, who were stratified in two groups according to their basal right ventricle diastolic diameter (RVDD) measuring greater and less than 35 mm. They underwent clinical evaluation, echocardiography, spirometry and 6-minute walking-test (6MWT)., Results: The study found that patients with RVDD greater than 35 mm showed worse functional capacity in the 6MWT (p = 0.05) and more exacerbation of the disease during the one-year follow-up (p = 0.05). There were correlations of greater RVDD vs forced vital capacity (R = -0.27; p = 0.02) and distance in the 6MWT (R = 0.55; p = 0.03) in patients with exacerbation. In the univariate regression analysis, the RVDD was responsible for 55% of the variation in distance in the 6MWT (-0.75 m) in COPD patients., Conclusion: The RV dilation is associated with unfavorable prognostic markers in COPD, such as the worsening of the functional capacity and more frequent exacerbations. The echocardiogram may be a useful tool to identify patients who need more aggressive strategies to control the evolution of the disease with potential impact in pulmonary rehabilitation., Competing Interests: Declaration of Competing Interest There is no conflict of interest in this manuscript., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Prediabetes individuals may present incipient signals of cardiovascular injury and evaluate with unfavorable outcome. The aim of this study was to identify early ultrasonographic markers of cardiac dysfunction and arterial stiffness among glucose intolerant patients compared to healthy individuals., Methods: Cross-sectional study with the composition of two groups: Prediabetes (PD) who met the criteria for pre-diabetes and Normoglycemic (NG): presented no criteria of pre-diabetes and diabetes mellitus in all applied tests. Clinical evaluation, assessment of cardiac function by transthoracic echocardiogram, carotid intima-media thickness by carotid ultrasonographic and evaluation of arterial stiffness by SphygmoCor® device was performed., Results: Eighty adults were included in this study: PD (n = 43) and NG (n = 37). PD patients were more dyslipidemic and presented early alterations in echocardiographic variables, like: peak mitral velocity E (E (cm/sec): NG 84 ± 13 vs. PD 77 ± 11, P = 0.03), E/A Tricuspid inflow (NG: 1.5 ± 0.4 vs. PD 1.3 ± 0.3, P = 0.03), Tricuspid tissue Doppler E' (E'tric (cm/sec): NG 15.2 ± 4.4 vs. PD 13.4 ± 3.2, P = 0.04) and increased arterial stiffness (Pulse Wave Velocity: PWV (m/s): NG 7.2 ± 1.5 vs. PD 7.9 ± 1.7, P = 0.03). In the regression analysis, having an impaired oral glucose test was shown to be independently associated with reduced E Mitral, even after adjusting for a set of confounding factors., Conclusions: PD patients showed early signals of an impaired cardiac function and an increased pulse wave velocity when compared with healthy individuals. These results point to treatment optimization strategies, especially when considering preventive measures for cardiovascular outcomes, like diabetic cardiomyopathy., (Copyright © 2021. Published by Elsevier Inc.)

Background: Nitazoxanide exerts antiviral activity in vitro and in vivo and anti-inflammatory effects, but its impact on patients hospitalized with COVID-19 pneumonia is uncertain., Methods: A multicentre, randomized, double-blind, placebo-controlled trial was conducted in 19 hospitals in Brazil. Hospitalized adult patients requiring supplemental oxygen, with COVID-19 symptoms and a chest computed tomography scan suggestive of viral pneumonia or positive RT-PCR test for COVID-19 were enrolled. Patients were randomized 1:1 to receive nitazoxanide (500 mg) or placebo, 3 times daily, for 5 days, and were followed for 14 days. The primary outcome was intensive care unit admission due to the need for invasive mechanical ventilation. Secondary outcomes included clinical improvement, hospital discharge, oxygen requirements, death, and adverse events within 14 days., Results: Of the 498 patients, 405 (202 in the nitazoxanide group and 203 in the placebo group) were included in the analyses. Admission to the intensive care unit did not differ between the groups (hazard ratio [95% confidence interval], 0.68 [0.38-1.20], p = 0.179); death rates also did not differ. Nitazoxanide improved the clinical outcome (2.75 [2.21-3.43], p < 0.0001), time to hospital discharge (1.37 [1.11-1.71], p = 0.005), and reduced oxygen requirements (0.77 [0.64-0.94], p = 0.011). C-reactive protein, D-dimer, and ferritin levels were lower in the nitazoxanide group than the placebo group on day 7. No serious adverse events were observed., Conclusions: Nitazoxanide, compared with placebo, did not prevent admission to the intensive care unit for patients hospitalized with COVID-19 pneumonia., Clinical Trial Registration: Brazilian Registry of Clinical Trials (REBEC) RBR88bs9x; ClinicalTrials.gov, NCT04561219., Competing Interests: CM was employeed by AAC&T Research Consulting LTDA. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Rocco, Silva, Cruz, Tierno, Rabello, Junior, Haag, de Ávila, da Silva, Mamede, Buchele, Barbosa, Cabral, Junqueira, Araújo-Filho, da Costa, Alvarenga, Moura, Carajeleascow, de Oliveira, Silva, Soares, Fernandes, Fonseca, Camargos, Reis, Franchini, Luiz, Morais, Sverdloff, Martins, Felix, Mattos-Silva, Nogueira, Caldeira, Pelosi and Lapa-e-Silva.)

COVID-19 mainly presents as a respiratory disease with flu-like symptoms, however, recent findings suggest that non-respiratory symptoms can occur early in the infection and cluster together in different groups in different regions. We collected surveillance data among COVID-19 suspected cases tested in mainland Portugal during the first wave of the pandemic, March-April 2020. A multivariable logistic-regression analysis was performed to ascertain the effects of age, sex, prior medical condition and symptoms on the likelihood of testing positive and hospitalisation. Of 25,926 COVID-19 suspected cases included in this study, 5,298 (20%) tested positive. Symptoms were grouped into ten clusters, of which two main ones: one with cough and fever and another with the remainder. There was a higher odds of a positive test with increasing age, myalgia and headache. The odds of being hospitalised increased with age, presence of fever, dyspnoea, or having a prior medical condition although these results varied by region. Presence of cough and other respiratory symptoms did not predict COVID-19 compared to non-COVID respiratory disease patients in any region. Dyspnoea was a strong determinant of hospitalisation, as well as fever and the presence of a prior medical condition, whereas these results varied by region., Competing Interests: The authors have declared that no competing interests exist.

Context: Topical management is the main form of control of signs and symptoms regarding malignant wounds (MWs) arising from tumor progression on the skin. Nevertheless, few studies have explored this theme and evidence on the effectiveness of the methods used to control bleeding is unknown, leading to a lack of consensus to support clinical practice., Objectives: Identify and evaluate current evidence on topical MW hemostasis from breast cancer and suggest new topics for future research., Methods: This review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes. Seven indexed databases were consulted using the terms: "breast neoplasms"; "breast cancer"; "malignant fungating wounds"; "malignant wounds"; "bleeding.", Results: From the 112 articles identified in total, six were included in this review: a descriptive cohort study (n = 32), two case series (n = 21) and three case reports (n = 3). Fifty-six patients were exposed to 11 types of topical treatments using calcium alginate, surgical hemostats, adrenaline, nonadherent dressings, silver nitrate, modified Mohs Paste, and 10% formalin. There were no reports of significant adverse effects., Conclusion: Although studies have promoted positive results of topical hemostasis, scientific evidence is still weak and arises from studies with poor methodological quality. Randomized controlled trials were not identified. The results highlight the crucial need for pilot studies to evaluate effect size, study procedures, and measurable results., (Published by Elsevier Inc.)

Purpose: To validate tools to identify patients at risk for perioperative complications to implement prehabilitation programmes in head and neck surgery (H&N)., Methods: Retrospective cohort including 128 patients submitted to H&N, with postoperative Intermediate Care Unit admittance. The accuracy of the risk calculators ASA, P-POSSUM, ACS-NSQIP and ARISCAT to predict postoperative complications and mortality was assessed. A multivariable analysis was subsequently performed to create a new risk prediction model for serious postoperative complications in our institution., Results: Our 30-day morbidity and mortality were 45.3% and 0.8%, respectively. The ACS-NSQIP failed to predict complications and had an acceptable discrimination ability for predicting death. The discrimination ability of ARISCAT for predicting respiratory complications was acceptable. ASA and P-POSSUM were poor predictors for mortality and morbidity. Our new prediction model included ACS-NSQIP and ARISCAT (area under the curve 0.750, 95% confidence intervals: 0.63-0.87)., Conclusion: Despite the insufficient value of these risk calculators when analysed individually, we designed a risk tool combining them which better predicts the risk of serious complications.

Epidemiological and descriptive research on malignant wounds (MWs) is scarce. The objective of this study was to identify the prevalence of MWs and analyze the characteristics and associated factors of MWs in hospitalized patients at an oncological institution. An epidemiological, cross-sectional, and descriptive study, which was derived from a larger study that collected data on the prevalence of different types of wounds in 341 adults hospitalized in a large oncological hospital, was conducted. The present study comprehensively analyzed data related to MWs. Information was obtained through participant interviews, physical examination, and medical record review. The study was approved by the ethics committee of the institution where the study was conducted. Fourteen MWs were identified in 13 patients, who were primarily married (58%) and men (75%), with a mean age of 60.5 ± 15.1 years. Malignant wounds were predominantly located in the head and neck region (43%) and classified as 1N (50%) according to the Staging of Malignant Cutaneous Wounds instrument. Malignant wounds were characterized as painful (83.3%), with significant pain present during dressing changes (93%). The presence of MWs was associated with the use of antidepressants (odds ratio [OR] = 4.95; p = .012), upper-limb edema (OR = 8.39; p = .003), and infection (OR = 12.16; p = .051). The prevalence of MWs in hospitalized patients was 3.8%. Associated clinical variables were related to the degree of disease progression. This information provides evidence of the need for research identifying and investigating nursing interventions for patients with MW to assist with pain control during dressing changes.

Objective: to evaluate the nursing team knowledge of a cancer hospital on care for patients with Malignant Fungating Wounds (MFW) and to analyze associated sociodemographic and educational factors., Method: an observational and cross-sectional study, conducted between September and October 2015, after approval by the Research Ethics Committee. A questionnaire was applied containing sociodemographic, educational and related components to the accomplishment of dressings, dressings choice and orientation. Data were analyzed by using Chi-square, Fisher's exact test, Student's t-Test and Pearson's correlation., Results: 37 professionals participated in the study, most of whom were technicians (56.8%), women (91.9%) and with a mean age of 32 years. The professionals presented 56.5% of correct answers. There were no statistically significant associations between sociodemographic/educational variables and number of correct answers., Conclusion: there was a lack of important knowledge about care for patients with MFW, which should guide strategies for the oncology staff training.

Objective: Malignant wounds due to breast cancer can present with recurrent episodes of bleeding in the tumour tissue. This study will compare the efficacy of a calcium alginate dressing (Biatain, Coloplast A/S, Denmark) and a regenerated oxidised cellulose dressing (Surgicel, Ethicon, LLC, Puerto Rico)., Protocol: A total of 24 patients with breast cancer and bleeding, malignant wounds will be enrolled in the randomised, controlled, open study, conducted at a hospital specialising in breast cancer treatment and at another hospital specialising in palliative care. Patients over 18 years old, with bleeding and willing to undergo venipuncture for blood collection will be included. All enrolled patients will be randomised for allocation to an experimental group (regenerated oxidised cellulose dressing) or a control group (calcium alginate dressing). The main intervention will consist of the application of the haemostatic product, assessment of digital pressure and estimation of the time required for haemostasis., Outcomes: Key outcome measures will be the percentage of patients with haemostasis within 20 minutes, observation of haemostasis after three, five and 10 minutes, in addition to recurrence of bleeding and the quantity of product used., Discussion: To our knowledge, this is the first study to evaluate the effectiveness of haemostatic products in malignant wounds. This type of wound is poorly explored in the literature and, among its signs and symptoms, bleeding is poorly studied. The completion of this study will provide a more robust rationale for clinical decision-making related to the control of bleeding in malignant breast cancer wounds in the context of evidence-based nursing practices.

Background: In suspected Crohn's disease (CD), non-diagnostic ileocolonoscopies are often followed by small bowel capsule endoscopy (SBCE). Adequate pre-selection of patients for SBCE is a key to optimize allocation of resources. We aimed to establish a rational approach for the CD diagnostic workflow, based on biochemical profile of patients with suspected CD, targeting an optimization of patients' selection for SBCE. Methods: Multicenter cohort study includes consecutive patients with suspected undergoing SBCE after non-diagnostic ileocolonoscopy. Minimum follow-up period after the capsule enteroscopy was six months. The outcome was confirmation of CD diagnosis. Univariate analysis and logistic regression were performed. Results: In included 220 patients, 62.3% of women were with a mean age of 41 years [26-54]. A confirmed diagnosis of CD was established in 98 patients (44.5%). The initial univariate analysis identified variables above the threshold of marginal statistical association toward CD diagnosis ( p  < .15). The regression model identified high CRP levels (OR 1.028 p  = .128) and low serum Iron (OR 0.990 p  = .025) as the independent variables with consistent correlation with CD diagnosis. Those two variables present a suitable discriminative power (AUC = 0.669, p  < .001) for the diagnosis of CD. Conclusion: In suspected CD, low serum iron and elevated CRP had a statistically significant association with CD diagnosis, being helpful to identify patients with higher CD probability before SBCE. However, the lack of a proper validation of the model leads us to currently recommend SBCE to all patients with suspected CD and negative ileocolonoscopy, as no specific biochemical profile can be used to confidently exclude small bowel CD.

Background: Prognosis is one of the most challenging questions with which physicians are confronted. Accuracy in the prediction of survival is necessary for clinical, ethical, and organizational reasons., Aim: Evaluate young doctors' clinical prediction of survival and the aids they could get: expert opinion, Palliative Prognostic score, and Palliative Prognostic Index., Design: Prospective, observational study., Setting/participants: Advanced cancer patients under observation of an inhospital palliative care team, from April to July 2014. A total of 38 patients were included, mostly male (65.8%), average age 68.5 years. Average survival time was 24 days. Follow-up concluded with death or after 90 days., Results: Young doctors' clinical prediction of survival was adequate at 10.5%, with 55.3% severe errors in an optimistic direction. Palliative care experts were more adequate (23.7%) and made less severe errors (42.1%). Palliative Prognostic score and Palliative Prognostic Index were even more adequate (47% and 55%, respectively) and made even less severe errors (0% and 11%, respectively). The best correlation with observed survival was achieved when palliative care experts used palliative prognostic score ( r s  = -0.629; p < 0.01)., Conclusion: Young doctors' clinical prediction of survival is often inadequate. Palliative Prognostic score, which includes clinical prediction of survival, calculated by palliative care experts had the best performance. Our results support the recommendation of using clinical prediction of survival together with prognostic scores.

Background: The Lewis Score (LS) aims to standardize the method of quantification of small bowel inflammatory activity detected by the small bowel capsule endoscopy (SBCE). The aim of this study was to evaluate the diagnostic accuracy of the LS in patients with suspected CD undergoing SBCE., Methods: We performed a retrospective study including patients who underwent SBCE for suspected CD between September 2006 and February 2013. Patients were grouped according to the criteria of the International Conference on Capsule Endoscopy for the definition of suspected CD. Inflammatory activity on SBCE was objectively assessed by determining the LS., Results: Ninety-five patients were included. Group 1: 37 patients not fulfilling International Conference on Capsule Endoscopy criteria; Group 2: 58 patients with ≥ 2 International Conference on Capsule Endoscopy criteria. The diagnosis of CD was established in 38 patients (40%): 8 (21.6%) from group 1 and 30 from group 2 (51.7%) (P = 0.003). Among those patients, 34 had LS ≥ 135 (73.9%) and 4 had LS <135 (8.2%) at SBCE (P < 0.001). The LS ≥ 135 had an overall diagnostic accuracy of 83.2% with a sensitivity, specificity, positive predictive value, and negative predictive value for the diagnosis of CD of 89.5%, 78.9%, 73.9%, and 91.8%, respectively., Conclusions: The application of LS ≥ 135 as the cutoff value for the presence of significant inflammatory activity in patients undergoing SBCE for suspected CD may be useful to establish the diagnosis of CD. In patients with LS < 135, the probability of having CD confirmed on follow-up is low.

Phenytoin is an anticonvulsant that has been used in wound healing. The objectives of this study were to describe how the scientific production presents the use ofphenytoinas a healing agent and to discuss its applicability in wounds. A literature review and hierarchy analysis of evidence-based practices was performed. Eighteen articles were analyzed that tested the intervention in wounds such as leprosy ulcers, leg ulcers, diabetic foot ulcers, pressure ulcers, trophic ulcers, war wounds, burns, preparation of recipient graft area, radiodermatitis and post-extraction of melanocytic nevi. Systemic use ofphenytoinin the treatment of fistulas and the hypothesis of topical use in the treatment of vitiligo were found. In conclusion, topical use ofphenytoinis scientifically evidenced. However robust research is needed that supports a protocol for the use ofphenytoinas another option of a healing agent in clinical practice.

The aim of the No Pain in Labour (NoPiL) study was to evaluate the stress and clinical outcome of infants vaginally born without maternal analgesia and after maternal epidural or systemic analgesia. We studied 120 healthy term infants, 41 in the no analgesia group, 38 in the epidural analgesia group, and 41 in the systemic analgesia group. Cortisol, beta-endorphin, oxidative stress markers (ie: total hydroperoxide (TH) and advanced oxidation protein products (AOPP)), interleukin-1beta (IL-1beta), and interleukin-8 (IL-8) cytokines were measured in arterial cord blood samples. Infants in the 3 groups had similar Apgar score, cord blood pH and occurrence of hypoglycaemia, hyperbilirubinemia, and respiratory depression. Cortisol and endorphin plasma levels did not differ in the groups, nor did TH and AOPP values. IL-1beta and IL-8 cytokine were higher in infants born after maternal epidural analgesia than in other groups. Short-term outcome and stress were similar in infants vaginally born without maternal analgesia and after epidural and systemic analgesia. The possible implications of the highest interleukin levels in the epidural analgesia group deserve further study.

The present work aimed at the development and application of transferrin receptor (TrfR)-targeted sterically stabilized liposomes encapsulating anti-BCR-ABL siRNA or asODN. Transferrin was coupled to the surface of liposomes encapsulating siRNA or asODN through the postinsertion method. Cell association and internalization were assessed by flow cytometry and confocal microscopy, respectively. BCR-ABL mRNA and Bcr-Abl protein levels were evaluated by qRT-PCR and Western blot, respectively. Cell viability was assessed using the resazurin reduction method. The amount of coupled transferrin and the size and stability over time of the liposomes were very satisfactory and reproducible. The siRNA encapsulation yield was dependent on the concentration of the encapsulation buffer used (20 or 300 mM), as opposed to asODN encapsulation yield which was high for both concentrations tested. Cell association and internalization studies were performed in leukemia cell lines treated with liposomes coupled to Trf (Trf-liposomes) or albumin (BSA-liposomes) or with nontargeted liposomes (NT-liposomes) encapsulating fluorescently labeled siRNA (Cy3-siRNA). These experiments clearly indicated that BSA- and NT-liposomes have no ability to promote the delivery of the encapsulated nucleic acids and that the Trf-liposomes deliver the nucleic acids by a Trf receptor-dependent mechanism. The Trf-liposomes encapsulating siRNA or asODN promote sequence-specific down-regulation of the BCR-ABL mRNA, although a certain extent of nonspecific sequence effects at the protein and cell viability level were observed. Overall, our results indicate that Trf-liposomes encapsulating gene silencing tools allow combining molecular and cellular targeting, which is a valuable approach for cancer treatment.

We performed a randomized study in preterm lambs to assess the hypothesis that the treatment with natural surfactant combined with beclomethasone might decrease pulmonary oxidative stress in an animal model of respiratory distress syndrome (RDS). Animals received 200 mg/kg of porcine natural surfactant or 200 mg/kg of natural surfactant combined with 400 or 800 microg/kg of beclomethasone. Lung tissue oxidation was studied by measuring total hydroperoxide (TH), advanced oxidation protein products (AOPP), and non-protein bound iron (NPBI) in bronchial aspirate samples. In addition, lung mechanics was evaluated. TH was lower in the groups treated with surfactant plus 400 or 800 microg/kg of beclomethasone than in the surfactant group; AOPP was lower in the group treated with surfactant plus 800 microg/kg of beclomethasone than in the other groups; NPBI was similar in all groups. Surfactant treatment was followed by a sustained improvement of tidal volume (TV) and airway resistance, while dynamic compliance did not vary. However, the mean airway pressure needed to obtain similar values of TV was lower in the group treated with surfactant plus 800 microg/kg of beclomethasone than in other groups. We concluded that natural surfactant combined with beclomethasone at 800 microg/kg is effective in reducing the oxidative lung stress and improving the respiratory function in an animal model of RDS.

Despite the role of reactive oxygen species in the development of respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) in preterm infants, the anti-oxidant properties of commercial surfactants have never been studied. We measured the superoxide dismutase (SOD) and catalase (CAT) activity, the scavenger activity against hydrogen peroxide (H(2)O(2)), and its changes after the addition of SOD and CAT in four natural surfactants, namely Infasurf, Curosurf, Survanta, and Alveofact. We found that they contain measurable amount of SOD and CAT. Curosurf and Survanta seem to have higher antioxidant effect than Infasurf and Alveofact. Moreover, the highest phospholipid concentration and recommended dose of Curosurf imply that its scavenger activity for each treatment dose in preterm infants is likely higher than that of Survanta. Finally, the supplementation with SOD and CAT induced a remarkable increase of antioxidant action in all studied surfactants.

Our aim was to evaluate if the combined inhalation of both nitric oxide (iNO) and aerosolized prostacyclin or iNO and adrenomedullin (ADM) is more effective in lowering pulmonary arterial pressure (PAP) and improving oxygenation than nitric oxide alone in an animal model with pulmonary hypertension (PH). Moreover, we studied the effect on pulmonary mechanics, surfactant activity, and pulmonary oxidative stress of the different treatments. Twenty-eight piglets with acute lung injury induced by lung lavages with saline were randomized to receive nitric oxide, nitric oxide plus prostacyclin, nitric oxide plus ADM or saline, after. Dynamic compliance, tidal volume, and airway resistance were measured. Lung tissue oxidation was evaluated by measuring total hydroperoxide and advanced oxidation protein products in bronchial aspirate samples. Surface surfactant activity was studied using Capillary Surfactometer. Inhaled nitric oxide combined with prostacyclin or ADM was more effective than nitric oxide alone in lowering PAP and improving oxygenation. Nitric oxide alone or combined increased lung compliance and tidal volume, and decreased airway resistance. No effects on surfactant surface activity and lung tissue oxidation were observed. The treatment with nitric oxide alone or combined with prostacyclin or ADM were effective in decreasing mean PAP and improving oxygenation in a piglet model of PH. However, nitric oxide plus prostacyclin and nitric oxide plus ADM were more effective than nitric oxide alone. The combination of aerosolized prostacyclin and ADM with nitric oxide might have a role in the treatment of infants with PH refractory to nitric oxide alone., ((c) 2007 Wiley-Liss, Inc.)

Objectives: To compare the ultrasound examination with pH-metry in order to evaluate the diagnostic accuracy of sonography for diagnosis of gastro-oesophageal reflux (GOR) in preterm infants., Methods: A prospective study was conducted on 31 premature infants <34 weeks with clinically diagnosed GOR. First, they underwent 24-hour pH-monitoring; successively, the sonographic assessment was performed within 12 h after pH-monitoring. The two operators who performed the pH-monitoring and sonography respectively, were unaware of each other's results., Results: Twenty-one patients (67.7%) had significant GOR with a reflux index >5 (GOR group). The median (range) reflux index in this group was 9.19% (6.04-20.1). Ten newborns (32.3%) did not have significant GOR with a reflux index <5. Sonography was positive for GOR in 8 patients (25.8%); all 8 infants with sonographic diagnosis of GOR had a reflux index >5. Therefore, sonographic diagnosis did not produce false positives. Sonography was negative in 23 newborns (74.2%); 13 of these were positive to pH-monitoring and may therefore be considered as false negatives. Respect to continuous 24-hour pH-monitoring, sonography showed a specificity of 100% but a very low sensitivity of 38% with a positive prediction value of 100% and a negative prediction value of 43%., Conclusions: Sonography should not replace 24-hour pH monitoring for detecting GOR in preterm infants. However, sonography has a very high specificity and a positive predictive value of 100%. When clinicians suspect GOR in preterm infants, it could be useful for selection of cases to refer for pH-metry., (Copyright (c) 2007 S. Karger AG, Basel.)

Aim: To test the hypothesis that inhaled nitric oxide therapy can decrease the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome; to evaluate the possible predictive factors for the response to inhaled nitric oxide therapy., Methods: Preterm infants (less than 30 weeks' gestation) were randomized to receive during the first week of life inhaled nitric oxide, or nothing, if they presented severe respiratory distress syndrome. Then, the treated infants were classified as non responders and responders., Results: Twenty infants were enrolled in the inhaled nitric oxide therapy group and 20 in the control group. Bronchopulmonary dysplasia and death were less frequent in the inhaled nitric oxide group than in the control group (50 vs. 90%, p=0.016). Moreover, nitric oxide treatment was found to decrease as independent factor the combined incidence of death and BPD (OR=0.111; 95% C.I. 0.02-0.610). A birth weight lower than 750 grams had a significant predictive value for the failure of responding to inhaled nitric oxide therapy (OR 12; 95% C.I. 1.3-13.3)., Conclusion: Inhaled nitric oxide decreases the incidence of bronchopulmonary dysplasia and death in preterm infants with severe respiratory distress syndrome. Birth weight may influence the effectiveness of inhaled nitric oxide therapy in promoting oxygenation improvement in preterm infants.