Refractory Chylothorax Secondary to Sizeable Azygos Vein Hemangioma: Tailored Multimodal Treatment of a Challenging Case Report.

BACKGROUND: Mediastinal hemangiomas are rare, and their etiology remains unclear. Most patients affected have no pathognomonic clinical symptoms, and the diagnosis is often incidental. Due to the paucity of the available literature regarding the management of this disease, the choice and timing of treatment remains controversial. CASE PRESENTATION: Herein, we report the case of a hemangioma of the azygos vein arch in a 66-year-old woman who presented with dyspnea, chest discomfort, dysphagia, and weight loss. A simultaneous right chylothorax refractory to conservative management was found. A CT-guided biopsy of the mass was performed, and it confirmed the vascular nature of the lesion. Therefore, the patient underwent an angiography followed by endo-vascular embolization. Three days later, thoracoscopic surgical resection of the mass and the repair of the chyle leakage were performed safely. The patient was discharged uneventfully on postoperative day seven, with complete resolution of all the presenting symptoms. CONCLUSIONS: Treatment of symptomatic mediastinal hemangiomas could be mandatory, but a thorough multidisciplinary approach to these rare malformations is essential. Despite the risk of intraoperative bleeding, selective endovascular embolization followed by thoracoscopic surgery allowed for a complete and safe resection with a good outcome.

Assessing the impact of defining a global priority research agenda to address HIV-associated tuberculosis.

OBJECTIVES: In 2010, the WHO issued 77 priority research questions (PRQs) to address HIV-associated TB. Objective of the this study was to assess the impact of defining the research agenda in stimulating and directing research around priority research questions. METHODS: We used number and type of scientific publications as a proxy to quantitatively assess the impact of research agenda setting. We conducted 77 single systematic reviews - one for every PRQ - building 77 different search strategies using PRQs' keywords. Multivariate logistic regression models were applied to assess the quantity and quality of research produced over time and accounting for selected covariates. RESULTS: In 2009-2015, PRQs were addressed by 1631 publications (median: 11 studies published per PRQ, range 1-96). The most published area was 'Intensified TB case finding' (median: 23 studies/PRQ, range: 2-74). The majority (62.1%, n = 1013) were published as original studies, and more than half (58%, n = 585) were conducted in the African region. Original studies' publication increased over the study period (P trend = <0.001). They focused more on the 'Intensified TB case finding' (OR = 2.17, 95% CI: 1.56-2.93) and 'Drug-resistant TB and HIV infection' (OR = 2.12, 95% CI: 1.47-3.06) areas than non-original studies. Original studies were published in journals of lower impact factor and received a smaller number of citations than non-original studies (OR = 0.54, 95% CI: 0.42-0.69). CONCLUSION: The generation of evidence to address PRQs has increased over time particularly in selected fields. Setting a priority research agenda for HIV-associated TB might have positively influenced the direction and the conduct of research and contributed to the global response to such a major threat to health.

Evaluation of the Effects of CHF6001, an Inhaled PDE4 Inhibitor, on Cardiac Repolarization and Cardiac Arrhythmias in Healthy Volunteers.

Chronic obstructive pulmonary disease (COPD) is a multicomponent condition characterized by airway inflammation and associated to comorbidities, including cardiovascular diseases. Among anti-inflammatory agents in development for COPD, the phosphodiesterase inhibitors administrated by inhalation have the potential for increased efficacy and reduced systemic side effects. CHF6001 is an inhaled PDE4 inhibitor with proven anti-inflammatory properties in animal models. This randomized, double-blind, placebo-controlled study was aimed to demonstrate its cardiovascular safety and tolerability in healthy male volunteers with normal electrocardiogram and cardiac parameters. Single and multiple ascending doses (7 days of administration) of CHF6001 were administered. Three electrocardiograms were recorded at several pharmacokinetic time points and at each time points, postdose heart rate, QRS and PR intervals, and presence of arrhythmia were evaluated. In single ascending dose, QTcF intervals did not increase more than 30 milliseconds from the baseline, all heart rate was between 45 and 100 bpm, and no statistically significant differences were observed in PR and QRS intervals. In multiple ascending dose, cardiac parameters did not differ significantly from baseline. In the pharmacokinetic/pharmacodynamic analysis, no medically or clinically significant changes were found. Further studies are ongoing to demonstrate that CHF6001 is safe and well tolerated in COPD patients as well.

Multinational evidence-based recommendations for the diagnosis and management of gout: integrating systematic literature review and expert opinion of a broad panel of rheumatologists in the 3e initiative.

We aimed to develop evidence-based multinational recommendations for the diagnosis and management of gout. Using a formal voting process, a panel of 78 international rheumatologists developed 10 key clinical questions pertinent to the diagnosis and management of gout. Each question was investigated with a systematic literature review. Medline, Embase, Cochrane CENTRAL and abstracts from 2010-2011 European League Against Rheumatism and American College of Rheumatology meetings were searched in each review. Relevant studies were independently reviewed by two individuals for data extraction and synthesis and risk of bias assessment. Using this evidence, rheumatologists from 14 countries (Europe, South America and Australasia) developed national recommendations. After rounds of discussion and voting, multinational recommendations were formulated. Each recommendation was graded according to the level of evidence. Agreement and potential impact on clinical practice were assessed. Combining evidence and clinical expertise, 10 recommendations were produced. One recommendation referred to the diagnosis of gout, two referred to cardiovascular and renal comorbidities, six focused on different aspects of the management of gout (including drug treatment and monitoring), and the last recommendation referred to the management of asymptomatic hyperuricaemia. The level of agreement with the recommendations ranged from 8.1 to 9.2 (mean 8.7) on a 1-10 scale, with 10 representing full agreement. Ten recommendations on the diagnosis and management of gout were established. They are evidence-based and supported by a large panel of rheumatologists from 14 countries, enhancing their utility in clinical practice.

[Human Papillomavirus infection and vaccination: knowledge and attitudes of Italian general practitioners]. / Infezione da Papillomavirus umano e vaccinazione: conoscenze e ruolo dei medici di medicina generale.

OBJECTIVE: To assess General Pratictioner's (GPs) knowledge and attitudes about HPV infection and prevention. DESIGN AND PARTICIPANTS: A semi-structured survey was conducted from November to December 2013 among Italian GPs. Descriptive and univariate analyses were carried out. MAIN OUTCOME MEASURES AND RESULTS: 938 GPs were included in the study. 15% participated in continuing medical education courses focusing on HPV. GPs identified as HPV transmission routes: sexual (100%), cutaneous (15%), transplacental (13%), haematic (9%) and by air (2%); they considered HPV-related diseases: cervical (98%), vulvar and vaginal (42%), anal (39%), penile (38%) and oral (38%) cancer, genital warts (79%) and respiratory papillomatosis (12%). They knew HPV vaccination is to prevent HPV-associated cancer (60%), in particular cervical cancer (35%), genital warts (3%) and sexually transmitted diseases (2%). A total of 73% were aware of the existence of both available vaccines, 69% believed that immunization target population should be females before initiation of sexual activity, 87% knew the age of vaccine administration. No significant difference in knowledge was retrieved by age, gender, level of education or region of origin. CONCLUSION: We report a lack of knowledge on HPV infection and vaccination in GPs. GPs have a key role in the Italian health system. Although 12-year old patients are a small percentage of their patients, it is of fundamental importance to promote medical education and training among GPs in order to meet HPV coverage targets and control HPV-associated diseases.

Giant intracranial aneurysms: morphology and clinical presentation.

The purpose of this study was to correlate the morphology of giant intracranial aneurysms (GIA) with their clinical presentation. Eighty patients with GIA, 14 males and 66 females, were studied. Univariate and multivariate analyses were made to test the associations between morphological and clinical features. The main locations of the unruptured GIA included the carotid cavernous segment, and for the ruptured GIA, the most frequent were the carotid supraclinoid and middle cerebral arteries. There was a significant association among communicating arteries (CA) of "bad" quality and presence of thrombus and calcification (TC). The risk of rupture is 8 times higher in patients with CA of "bad" quality and 11 times higher in patients without TC. GIA are more frequent in the cavernous segment. There is a high rupture risk in the middle cerebral artery. CA of "bad" quality are associated with TC. The rupture risk is significantly higher in patients without TC.

Ultrasound features of tophi in chronic tophaceous gout.

OBJECTIVE: To describe the different and lesser-known ultrasound features of tophi in chronic tophaceous gout. METHODS: Ultrasound images of 138 affected areas were analyzed from 31 patients with gout, using high-quality broadband linear transducers (frequency range of 8-14 MHz). Tophi were classified relative to echogenicity, echotexture, contours, number and the presence or absence of hypoechoic halo. The duration of illness was correlated with the presence of calcifications in tophi. RESULTS: Hyperechoic tophi were seen in 133 areas (96.3%); these were most frequently hyperechoic and heterogeneous (37.6%) or hyperechoic and heterogeneous with calcification (32.6%). Contours were found to be poorly defined in 115 (83.3%) areas. Multiple grouped tophi were seen in 85 areas (61.6%) and 50 areas (36.2%) had individual tophi. In 77 examined areas (55.8%), there was a hypoechoic halo around the tophi. There was no correlation between illness duration and presence of calcifications on tophi. CONCLUSIONS: Tophi are generally hyperechoic, heterogeneous, with poorly defined contours, multiple grouped and surrounded by an anechoic halo. Individual tophus and the absence of association between illness duration and the presence of calcification are newly described features. This study of tophaceous gout by ultrasound may contribute to the diagnostic elucidation of patients with clinically atypical gout and show its diverse characteristic forms of presentation.

The ethics of organizational change in healthcare.

The article addresses the increasingly important issue of organizational ethics in healthcare. Assuming that the governance of organizational change consists of a seriousness of continuous choices and of objectives to be determined and achieved, a possible definition of this new discipline is then deepened, and its fields of application are identified. In the discussion therefore emerge the close link between ethical choice in organization and legality, passing through transparency and prevention of corruptive phenomena. After a focus on the strategic role played by the Medical Doctor of the healthcare management team, in conclusion, the need arises to support a strengthened supervisory and evaluation system and a culture of the ethical organizational choice of health managers, a rooting of the sense of identity and belonging to the healthcare organization and its mission by Professionals. Also governing this last aspect is the new challenge for the management of public healthcare enterprises.

Project design for surgical department reorganization at hospital-university of Parma.

The article explains the main technical and methodological references of the reorganization of the main surgical activities (for production volumes and case mixes) of the Parma University Hospital. In defining the organizational design we considered the compliance with national laws and regional guidelines, the vision of the Public Enterprise Strategic Management, the attempt to bring the continuity of care through hospital paths, the valorization of the high technical specialty of a hub university center, the recognition of the ability and vocations of Professionals and the search for efficiency of a complex public production system. The project has also responded to the need to pursue greater production efficiency by the entire local health system of Parma, optimizing, at the same time, training courses for Medical Students and Health Professions of the University of Parma transversely with respect to surgical clinical pathways and clinical research.

A Study of the Pharmacokinetic Properties and the In Vivo Kinetics of Erythrocytes Loaded With Dexamethasone Sodium Phosphate in Healthy Volunteers.

The objectives of this 2-phase study were to elucidate pharmacokinetics (PK), in vivo 24-hour recovery, and red blood cell (RBC) survival properties of RBC-encapsulated dexamethasone sodium phosphate (DSP) prepared using the EryDex System (EDS). The 24-hour RBC recovery and T50 survival phase studied subjects were randomized to receive autologous RBCs loaded with either 15-20 mg DSP (Group 1A) or sham saline (Group 2A). Loaded RBCs were radiolabeled with 51-Cr, and the labeled RBCs were followed over time in vivo. The PK phase evaluated dose levels of 2.5-5 mg (Group 1B) and 15-20 mg (Group 2B) DSP encapsulated in RBCs infused into healthy randomized subjects. The mean ± SD 24-hour RBC recovery was 77.9% ± 3.3% and 72.7% ± 10.5% for Groups 1A and 2A, respectively. The mean ± SD RBC life span was 84.3 ± 8.3 days in Group 1A and 88.9 ± 6.2 days in Group 2A. The PK phase actual DSP loading doses (mean ± SEM) were 4.2 ± 0.27 mg and 16.9 ± 0.90 mg in Groups 1B and 2B, respectively. Release of dexamethasone from RBCs in vivo peaked at 1 hour, and a sustained release of dexamethasone could be detected until 35 days after the single intravenous infusion in Group 2B. The mean RBC in vivo recovery for DSP-loaded processed cells compares similarly to the 24-hour recovery of regulated RBC products intended for transfusion. There was a minimal but acceptable adverse impact on the survival of EDS-processed RBCs. DSP-loaded autologous RBCs, prepared using the EDS, delivered a sustained dose of dexamethasone in vivo.

Risk management: the new normative scenario and the role of training and education.

The article focuses on the important issue of Risk Management in health. In particular, it describes and critically appraises the new Italian law on patients' safety and professional responsibility, and expand on the educational and training needs to implement it on the ground. On the basis of the new law the role of Risk Managers, responsible for quality and safety of healthcare services, becomes of crucial importance in both public and private hospitals in Italy. In such context, education and training of risk managers should be multi disciplinary, ad hoc designed on recent regulations, and, more in general, help to build a new era in healthcare management.

Non-protein-bound iron detection in small samples of biological fluids and tissues.

Interest in the pro-oxidative nature of non-protein-bound-iron (NPBI) led to the development of an assay for its detection. The aim was to set up a reliable method of detecting NPBI in small samples of biological fluids and tissue. The method was based on preferential chelation of NPBI by a large excess of the low-affinity ligand nitrilotriacetic acid. To separate NPBI, a two-step filtration procedure was used. All glassware and plasticware were treated to minimize iron contamination. Measurements were performed in plasma, amniotic fluid, bronchoalveolar lavage, and brain tissues. The analytic system detected iron as ferric nitrate standard down to a concentration of 0.01 microM. The 1,2-dimethyl-3-hydroxy-4(1H)-pyridone-Fe(DHP-Fe) complex eluted with a retention time of about 2.6 min. The standard curve for the DHP-Fe complex was linear between 0.01 and 400 microMin water as well as in plasma, bronchoalveolar lavage, brain tissue, and amniotic fluid. The detection limit was 0.01 muM for all biological fluids and brain tissue. The data show that reliable measurements of NPBI are possible in studies on oxidative stress under experimental and clinical conditions. The possibility of investigating NPBI involvement in free-radical injury might be useful in all human diseases in which oxidative stress occur.

Long-term heart rate variability as a predictor of patient age.

Patients age has been estimated in healthy population by means of the heart rate variability (HRV) parameters to assess the potentiality of HRV indexes as a biomarker of age. A long-term analysis of HRV has been performed, computing linear time and frequency domain parameters as well as non-linear metrics, in a dataset of 113 healthy subjects (age range 20-85 years old). The principal component analysis has been used to capture age-related influence on HRV and then three different models have been applied to predict subjects age: a robust linear regressor (RLR), a feedforward neural network (FFNN) and a radial basis function neural network (RBFNN). A good prediction of patient age has been obtained (using all principal components, the Pearson correlation coefficient between predicted and real age: RLR=0.793; FFNN=0.872; RBFNN=0.829), even if an overestimation in younger subjects and an underestimation in older ones may be observed. The important and complementary contribution of non-linear indexes to aging related HRV modifications has also been underlined.

Effectiveness of interventions that apply new media to improve vaccine uptake and vaccine coverage.

BACKGROUND: Vaccine-preventable diseases (VPD) are still a major cause of morbidity and mortality worldwide. In high and middle-income settings, immunization coverage is relatively high. However, in many countries coverage rates of routinely recommended vaccines are still below the targets established by international and national advisory committees. Progress in the field of communication technology might provide useful tools to enhance immunization strategies. OBJECTIVE: To systematically collect and summarize the available evidence on the effectiveness of interventions that apply new media to promote vaccination uptake and increase vaccination coverage. DESIGN: We conducted a systematic literature review. Studies published from January 1999 to September 2013 were identified by searching electronic resources (Pubmed, Embase), manual searches of references and expert consultation. Study setting We focused on interventions that targeted recommended vaccinations for children, adolescents and adults and: (1) aimed at increasing community demand for immunizations, or (2) were provider-based interventions. We limited the study setting to countries that are members of the Organisation for Economic Co-operation and Development (OECD). MAIN OUTCOME MEASURES: The primary outcome was a measure of vaccination (vaccine uptake or vaccine coverage). Considered secondary outcomes included willingness to receive immunization, attitudes and perceptions toward vaccination, and perceived helpfulness of the intervention. RESULTS: Nineteen studies were included in the systematic review. The majority of the studies were conducted in the US (74%, n = 14); 68% (n = 13) of the studies were experimental, the rest having an observational study design. Eleven (58%) reported results on the primary outcome. Retrieved studies explored the role of: text messaging (n.7, 37%), smartphone applications (n.1, 5%), Youtube videos (n.1, 5%), Facebook (n.1, 5%), targeted websites and portals (n.4, 21%), software for physicians and health professionals (n.4, 21%), and email communication (n.1, 5%). There is some evidence that text messaging, accessing immunization campaign websites, using patient-held web-based portals and computerized reminders increase immunization coverage rates. Insufficient evidence is available on the use of social networks, email communication and smartphone applications. CONCLUSION: Although there is great potential for improving vaccine uptake and vaccine coverage by implementing programs and interventions that apply new media, scant data are available and further rigorous research - including cost-effectiveness assessments - is needed.

[Achilles tendon xanthoma imaging on ultrasound and magnetic resonance imaging]. / Aspectos de imagem do xantoma do tendão calcâneo na ultrassonografia e ressonância magnética.

The Achilles tendon xanthoma is a rare disease and has a high association with primary hyperlipidemia. An early diagnosis is essential to start treatment and change the disease course. Imaging exams can enhance diagnosis. This study reports the case of a 60-year-old man having painless nodules on his elbows and Achilles tendons without typical gout crisis, followed in the microcrystalline disease clinic of Unifesp for diagnostic workup. Laboratory tests obtained showed dyslipidemia. The ultrasound (US) showed a diffuse Achilles tendon thickening with hypoechoic areas. Magnetic resonance imaging (MRI) showed a diffuse tendon thickening with intermediate signal areas, and a reticulate pattern within. Imaging studies showed relevant aspects to diagnose a xanthoma, thus helping in the differential diagnosis.

Medulloblastoma: evaluation of proliferative index by monoclonal antibody Mib-1, its prognostic correlation and therapeutic implications.

In the past few years, the monoclonal antibody MIB-1 has been used by researchers in order to retrospectively study paraffin imbibed tumor fragments. The medulloblastoma is the most common malignant central nervous system tumor in childhood. The objectives were: determination of the mean Mib-1 LI value from these patients, as well as the prognostic value of the method. This retrospective study represents an analysis of the cellular proliferation index of posterior fossa medulloblastomas collected from 22 patients at A.C. Camargo Hospital, from January 1990 to December 1999. The histopathological diagnosis was confirmed by H&E and proliferative index (LI) was achived with Mib-1 which detects proliferating cells during G1, G2, S and M phases. The results demostrated that the mean Mib-1 was 30,1%, and ranged from 5,2% to 62,0%.In conclusion, this method has prognostic value, has to be used as routine for patients harboring medulloblastomas and the ones who have PI greater than the mean value found in this study, should be treated aggressively.

Anesthesia for awake craniotomy: case report.

BACKGROUND AND OBJECTIVES: Some intracranial procedures are achievable with patients awake, however, there are challenges ranging from patient compliance to homeostasis. The aim of this study is to present a case of intracranial surgery for removal of a tumor in the left parietal lobe with the patient awake during the procedure. CASE REPORT: After patient selection and psychological preparation, the proposed excision of the left parietal lobe lesion in the waking state was clarified and accepted. Continuous infusion of propofol and remifentanil was administered to maintain a Ramsay score of 2-3. The bilateral scalp blockade was performed with ropivacaine. The Mayfield head fixation device was installed and drapes adjusted to maintain the airway and eyes accessible for mapping with electrical stimulation and tumor excision. For dura mater incision, a pad with 2% lidocaine was applied for 3 minutes. The surgery was uneventful. The patient was discharged on the seventh day of hospitalization without presenting complication. CONCLUSION: Although the maintenance of analgesia and hemodynamic stability was a challenge with the patient awake, the target-controlled infusion of propofol provided the desired level of consciousness, remifentanil titrated analgesia and sedation without drug accumulation, and the blockade with ropivacaine provided satisfactory analgesia. We conclude that the anesthetic technique was satisfactory for our patient.

Ultrasound characteristics of gouty tophi in the olecranon bursa and evaluation of their reproducibility.

OBJECTIVES: To describe the ultrasound characteristics of gouty tophi in the olecranon bursa and to evaluate their reproducibility. METHODS: A prospective study of the ultrasound features of 35 sites of tophi nodulations in the elbows of 31 men (mean 54.6 years). The findings were evaluated dynamically following pre-established standards. The static images were evaluated by another radiologist and were reviewed by the first examiner. RESULTS: The most frequent characteristics of tophi are: hyperechogenicity (91.7%), poorly defined contours (88.6%), multiple grouped nodules (85.6%) and heterogeneity (68.6%). Intra-observer agreement is almost perfect for echogenicity (K = 1.0), moderate for the involvement of the olecranon bursa (K = 0.47) and fair for other characteristics. Inter-observer agreement is substantial for the echogenicity (K = 0.65), fair for the echotexture (K = 0.27) and the presence of a perilesional hypoechoic halo (K = 0.34) and slight for other characteristics. CONCLUSIONS: The most frequent characteristic of tophi is hyperechogenicity. The intra-observer and inter-observer concordance for echogenicity are almost perfect and substantial, respectively. Knowledge of characteristics of the tophi in the elbow and their intra and inter-observer reproducibility may assist in establishing parameters for monitoring treatment and setting up criteria for differential diagnosis of processes involving the olecraneon bursa.

Metástase hipofisária de adenocarcinoma mamário: relato de caso / Pituitary Metastasis of Mammary Adenocarcinoma: A Case Report

Somente 1% de todas as cirurgias hipofisárias são realizadas para tratar tumores metastáticos desta região. Os focos primários mais comuns são respectivamente mama e pulmão. Neste artigo, descrevemos uma paciente com antecedente de adenocarcinoma mamário, que se apresenta com paralisia oculomotora súbita à direita. O objetivo do trabalho é descrever um caso de metástase mamária para a região selar, evidenciando dados clínicos e radiológicos que tornam tal diagnóstico plausível.

Only 1% of all pituitary surgeries are performed to treat metastatic tumors in this region. The most common primary sites are breast and lung respectively. In this article we describe a patient with previous breast adenocarcinoma presenting with oculomotor palsy sudden right. The objective is to describe a case of breast metastasis to the sellar region, showing clinical and radiological findings that make this plausible diagnosis.

Sonographic description and classification of tendinous involvement in relation to tophi in chronic tophaceous gout.

OBJECTIVE: To describe and classify the varied ultrasound features of tendinous involvement in relation to tophi in chronic tophaceous gout so that they are better recognised. METHODS: Ultrasound images of 138 affected areas from 31 patients with chronic tophaceous gout were analysed using high-quality broadband linear transducers. The relationship between tendon and tophi was classified, and the inter-observer agreement regarding classification was analysed. RESULTS: Tophi envelopment in the tendon was the most frequent characteristic (45%) followed by no relationship between tophi and tendon (41%), tophi at the insertion site of the tendon (7%), extrinsic compression (6%) and tophi within the tendon (1%). The inter-observer concordance on classification of the relationship between tophi and tendon was measured using McNemar's test with P < 0.001 (χ(2) = 30.0, degree of freedom = 9) and kappa test = 0.627 (P < 0.001), indicating substantial inter-observer concordance. CONCLUSION: Tophi generally envelope the tendon or there is no relationship between them. Tophi can also be found at the insertion site of the tendon, cause extrinsic compression or be located inside the tendon. There is substantial inter-observer agreement for ultrasound classification of tendon involvement by tophi. This study contributes to diagnostic elucidation and shows the diverse characteristic forms of tendon involvement by tophi.