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Introduction Burnout syndrome refers to the physical and psychological fatigue suffered by workers as a result of their professional activity. It has three main characteristics: emotional exhaustion, depersonalization and lack of personal fulfillment. Purpose To determine the prevalence of burnout syndrome among Andalusian ophthalmologists, both consultants and residents, analyzing its relationship with several sociodemographic variables. Material and methods Descriptive cross-sectional study. All the sociodemographic variables were included in a Google® form together with the standardized questionnaire Maslach Burnout Inventory-Human Services Survey (MBI-HSS). This form was sent to the Andalusian ophthalmological community by different electronic means (Andalusian Society of Ophthalmology, instant messaging mobile apps, etc.). Results 142 ophthalmologists answered the form, with a similar distribution by sex and a mean age of 43,77 years, with 67,1% of them meeting criteria of burnout syndrome. Its prevalence was higher among young ophthalmologists, with fewer years of clinical practice, divorced / separated, those with fewer children, belonging to centers in the province of Huelva, workers in rural / regional areas, those with exclusive public activity, consultants with temporary contracts and four-year residents. Regarding subspecialties, its prevalence was higher among those who focused on cornea-ocular surface-refractive surgery. Conclusions This study quantify for the first time in Andalusia the prevalence of burnout syndrome among ophthalmologists. The fact that two thirds of the analyzed sample meet criteria proves the need to implement improvements in the clinical and professional conditions of our group.

OBJECTIVE There is a paucity of data regarding financial trends for procedural reimbursements in otolaryngology. The purpose of this study was to evaluate monetary trends in Medicare reimbursement rates for the 20 most commonly billed otolaryngology procedures from 2000 to 2019. STUDY DESIGN Analysis of physician reimbursement. METHODS The American Academy of Otolaryngology-Head and Neck Surgery database was queried to determine the 20 most performed otolaryngology procedures. Next, the Physician Fee Schedule Look-Up Tool from the Centers for Medicare and Medicaid Services was utilized to assess each of the top 20 most utilized Current Procedural Terminology (CPT) codes in otolaryngology, and reimbursement data was extracted. All monetary data was adjusted for inflation to 2019 U.S. dollars using changes to consumer price index. Average annual and total percentage change in reimbursement were calculated based on adjusted values for all included procedures. RESULTS After adjusting for inflation, the average reimbursement for the total 20 procedures decreased by 37.63% from 2000 to 2019. The greatest single mean decrease was seen in CPT code 61782 for stereotaxis procedures on the skull, meninges, and brain (-59.96%), whereas the smallest mean decrease was in CPT code 30520 for septoplasty (-1.50%). From 2000 to 2019, the adjusted reimbursement rate for the combined procedures decreased by an average of 2.33% each year. CONCLUSION Medicare reimbursement for included procedures has decreased from 2000 to 2019. Increased awareness and consideration of these trends will be important for policy makers, hospitals, and surgeons in order to assure continued access to meaningful otolaryngology care in the United States. LEVEL OF EVIDENCE 4 Laryngoscope, 131:496-501, 2021.

There are several methods to assess the function of the autonomic nervous system. Among them, heart rate recovery (HRR) is an accepted, easy, low-cost technique. Different pathological conditions have been related to the development of autonomic dysfunction. Our study aimed to evaluate the relationship between HRR and HRR-derived parameters in ambulatory patients with asthma or type 2 diabetes followed at the National Institutes of Health in Mexico City. A total of 78 participants, 50 women and, 28 men were enrolled; anthropometric, respiratory evaluations, and fasting blood samples were taken before participants performed a 6-min walking test (6MWT). Abnormal HRR was defined as a drop of ≤8 and ≤11 beats/min at 1 or 2 min and correlated negatively with basal oxygen saturation at 1 min. Heart rate at 1 min, correlated negatively with final oxygen saturation (p < 0.01). Statistically significant negative correlations were also observed between red cell count and white blood cell count and HOMA-IR with a p < 0.01. Since discrete hematological but significant changes correlated with HRR and HRR-derived parameters, we consider that these measures are helpful in clinical settings to identify subclinical autonomic dysfunction that permits us to prevent or anticipate chronic and fatal clinical outcomes.

The following brief report summarized the results of a study where Ultra-widefield images analysis demonstrated superior capability and reliability than indirect ophthalmoscopy, during the clinical assessment of patients with type 1 Boston Keratoprosthesis.

Pulmonary hypertension is a rare condition that impairs patients’ quality of life and life expectancy. The development of noninvasive instruments may help elucidate the prognosis of this cardiorespiratory disease. We aimed to evaluate the utility of routinely performed noninvasive test results as prognostic markers in patients with pulmonary hypertension. We enrolled 198 patients with mean pulmonary artery pressure &gt, 25 mmHg measured at cardiac catheterisation or echocardiographic pulmonary artery systolic pressure &gt, 40 mmHg and tricuspid regurgitation Vmax &gt, 2.9 m/s, and clinical information regarding management and follow-up studies from the date of diagnosis. Multivariate analysis revealed that female sex [HR: 0.21, (95% CI: 0.07–0.64), p = 0.006], the presence of collagenopathies [HR: 8.63, (95% CI: 2.38–31.32), p = 0.001], an increased red blood cell distribution width [HR: 1.25, (95% CI: 1.04–1.49), p = 0.017] and an increased electrocardiographic P axis (P°)/T axis (T°) ratio [HR: 0.93, (95% CI: 0.88–0.98), p = 0.009] were severity-associated factors, while older age [HR: 1.57, (95% CI: 1.04–1.28), p = 0.006], an increased QRS axis (QRS°)/T° ratio [HR: 1.21, (95% CI: 1.09–1.34), p &lt, 0.001], forced expiratory volume in 1 s [HR: 0.94, (95% CI: 0.91–0.98), p = 0.01] and haematocrit [HR: 0.93, (95% CI: 0.87–0.99), p = 0.04] were mortality-associated factors. Our results support the importance of red blood cell distribution width, electrocardiographic ratios and collagenopathies for assessing pulmonary hypertension prognosis.

Purpose To describe characteristics of choroidal osteomas (CO), using ocular ultrasound, fluorescein angiography, ultra-widefield retinal imaging, ultra-widefield autofluorescence, optical coherence tomography, enhanced-depth-imaging OCT, and OCT angiography (OCT-A). Methods Retrospective, observational case series study. Clinical records from patients with diagnosis of CO who underwent complete imaging evaluation were analyzed. Results Sixteen eyes from 11 patients were included. Mean patient age was 33.4 years (range 20–61), 72.7% were female, 100% were Hispanic, and 54.5% had unilateral CO. Median visual acuity was 20/150 (range 20/20–2000). CO was completely calcified in 25%, partially decalcified in 50%, and decalcified in 25%. Other features included choroidal neovascularization (18.75%), focal choroidal excavation (12.5%), choroidal depression associated to decalcification (18.75%), thinning of outer retina and photoreceptor layers over decalcified tumor (75%). Decreased fluorescence on FAF was observed in decalcified regions while relatively preserved fluorescence was observed in calcified regions. Conclusions Nowadays, diagnostic tests provide important information about each stage of choroidal osteoma. Progressive decalcification of the tumor might have a common pathogenic role for development of FCE or choroidal depression. OCT-A/FA proved to be valuable tools for detection of CNV in patients with CO.

Objective To report the design and outcomes obtained during the first operational years of the Orthogeriatric Unit (OGU) established in the Zaragoza-1 (Spain) Health-Sector. Materials and methods A total of 494 patients >70 years old treated in the OGU from February 2009 to December 2012. An analysis was performed using the following variables: demography, previous functional level, comorbidities, surgical delay, fracture type and surgical technique, complications, hospital stay, functional outcomes, destination after hospital discharge, and short- and long-term mortality. Results Mean age 85.22 years. High incidence of comorbidities (Charlson Index): 24.3%. Dementia: 38.5%. Surgical delay: 2.57 days. Mean hospital stay between admission and discharge/transfer to convalescence unit, 20.9 days (Traumatology 6.45 + OGU 14.49). More than a third (34.6%) of patients suffered from delirium. Mean functional improvement (Barthel index at hospital discharge–Barthel index at hospital admission): 27.25 points. Montebello index: 0.49. In-hospital mortality: 6.9%. Conclusion Hip fracture is such a frequent and disabling pathology among the geriatric population that its treatment requires an interdisciplinary approach. This must be managed by the geriatrician, who has to assure the continuity and integration of the diverse treatment and care schedules, with the participation of the entire professional team in the decision-making process. We are very satisfied with the creation of our interdisciplinary Unit that enables us to report competitive outcomes. We believe that the progression of this Unit from providing subacute to acute care will improve the general outcomes in the future.

PURPOSE To determine the short-term safety of intravitreal bevacizumab by multifocal electroretinography testing. METHODS Thirty-one eyes with choroidal neovascularization, proliferative diabetic retinopathy, and retinal vein occlusion received intravitreal bevacizumab (2.5 mg/0.1 mL). All patients underwent best-corrected visual acuity measurement, retinal fluorescein angiography, optical coherence tomography, and multifocal electroretinography at baseline and 1 month after the treatment. RESULTS Subjects undergoing multifocal electroretinography testing had no statistically significant changes in electrophysiologic responses 1 month after the intravitreal injection of bevacizumab. CONCLUSION Multifocal electrophysiologic testing did not demonstrate any short-term cone photoreceptor toxicity after intravitreal bevacizumab.

BACKGROUND: Literature about long implants used together with a minimally invasive spine surgery (MISS) technique is scarce. Our objective is to contribute our surgical experience in this field and to specifically focus on several technical details. PATIENTS AND METHODS: A digitally-dissected canal along the paravertebral muscles was created linking the stab wounds on each side in relation with the pedicles to be cannulated. Screws were inserted following the percutaneous technique. Long rods were modelled, threaded through the extender sleeves along the paravertebral canal and pushed into the screw heads with the reduction forceps. When fusion was needed, the facet complex was decorticated with a drill. To insert a cross-link, a canal between the 2 rods was digitally created and the spinous process was drilled. RESULTS: 8 patients underwent surgery (age range: 25–77 years). Indications were postosteomyelitis kyphosis in 3 patients, bone tumor in 3, and spine fracture in 2. No blood transfusions were necessary during or after surgery. A cross-link was inserted in 2 patients. Posterolateral bone fusion was attempted in 4, but radiologically identifiable in none. In one patient a cantilever manoeuvre was done to correct kyphosis. Mean duration of surgery was 4 h. There were no clinical complications related to the operation or the hardware (mean follow-up of 7.14 months, range: 1–15 months). CONCLUSION: The application of MISS techniques can be broadened to long spinal constructs to assess fractures, tumors or deformity, especially in elderly or debilitated patients. Nevertheless, posterolateral fusion is still a challenge through these limited exposures.

The incidence of Clostridium difficile infection in North America and Europe has increased in the last years, generating concern among health professionals. A new strain of C. difficile has been identified in recent nosocomial outbreaks and community-acquired infections. This new strain, characterized as toxigenic type III, PCR ribotype 027 (C. difficile 027), presents higher pathogenicity because of increased exotoxin production, and a characteristic antibiotic resistance profile. Since 2003, several European countries have notified cases of C. difficile 027-associated disease, a fact that demonstrates its rapid dissemination. In this article, we review the latest nosocomial outbreaks associated with this new strain, which illustrate the need for a standardized surveillance system for early detection and implementation of control measures aimed at reducing the spread of this microorganism.

Purpose To assess the short-term complications of a single dose of intravitreal bevacizumab in patients with proliferative diabetic retinopathy (PDR). Methods Retrospective review of 343 patients with PDR who were treated with intravitreal injection of bevacizumab (2.5 mg/0.1 mL). Results Five patients (1.45%) presented tractional retinal detachment 1 to 6 weeks (mean 3 weeks) after intravitreal injection. All cases underwent pars plana vitrectomy, removal of all epiretinal fibrovascular membranes, further endolaser panretinal photocoagulation, and silicone tamponade. Conclusion Tractional retinal detachment may occur in a short time post intravitreal injection of bevacizumab in patients with proliferative diabetic retinopathy with extensive areas of ischemia and fibrovascular proliferations, and may require prompt vitreoretinal surgery.

Blood circulation is dependent on heart valves to direct blood flow through the heart and great vessels. Valve development relies on epithelial to mesenchymal transition (EMT), a central feature of embryonic development and metastatic cancer. Abnormal EMT and remodeling contribute to the etiology of several congenital heart defects. Leptin and its receptor were detected in the mouse embryonic heart. Using an ex vivo model of cardiac EMT, the inhibition of leptin results in a signal transducer and activator of transcription 3 and Snail/vascular endothelial cadherin–independent decrease in EMT and migration. Our data suggest that an Akt signaling pathway underlies the observed phenotype. Furthermore, loss of leptin phenocopied the functional inhibition of αvβ3 integrin receptor and resulted in decreased αvβ3 integrin and matrix metalloprotease 2, suggesting that the leptin signaling pathway is involved in adhesion and migration processes. This study adds leptin to the repertoire of factors that mediate EMT and, for the first time, demonstrates a role for the interleukin 6 family in embryonic EMT.

Objective— Pleiotrophin (PTN) is a cytokine that is expressed by monocytes/macrophages in ischemic tissues and that promotes neovascularization, presumably by stimulating proliferation of local endothelial cells. However, the effect of PTN on monocytes/macrophages remains unknown. We investigated the role of PTN in regulating the phenotype of monocytes/macrophages. Methods and Results— RT-PCR, real-time PCR, and fluorescence-activated cell sorter analysis revealed that the expression of PTN by monocytic cells led to a downregulation of CD68, c-fms , and CD14 monocytic cell markers and an upregulation of FLK-1, Tie-2, vascular endothelial-cadherin, platelet endothelial cell adhesion molecule-1, endothelial NO synthase, von Willebrand factor, CD34, GATA-2, and GATA-3 endothelial cell markers. Fibrin gel assays showed that the treatment of mouse and human monocytic cells with PTN led to the formation of tube-like structures. In vivo studies showed that PTN-expressing monocytic cells incorporated into the blood vessels of the quail chorioallantoic membrane. The intracardial injection of PTN-expressing monocytic cells into chicken embryos showed that cells integrated only into the developing vasculature. Finally, the injection of PTN-expressing monocytes into a murine ischemic hindlimb model significantly improved perfusion of the ischemic tissue. Conclusions— PTN expression by monocytes/macrophages led to a downregulation of their monocytic cell markers and an upregulation of endothelial cell characteristics, thus inducing the transdifferentiation of monocytes into functional endothelial cells.

To present a unique case of a 33-year-old woman using paroxetine who presented with acute unilateral visual loss due to chronic angle-closure glaucoma.Case report.A 33-year-old women who had been under paroxetine treatment for the past four months presented at the emergency room due to a sudden loss of visual acuity (VA) in the left eye (LE). Narrow anterior chamber was detected. Intraocular pressure (IOP) was 29 mmHg right eye (RE) and 42 mm Hg LE. A fundus exam revealed a cup-to-disc ratio of 0.9-1 for the LE and of 0.1-0.2 for the RE. Paroxetine treatment was suspended, and after 48 h IOP was 10 mm Hg in both eyes (BE). ND-YAG laser iridotomy was performed in BE. In the subsequent visit, IOP was 25 mm Hg in the RE and 41 mm Hg in the LE; on her own initiative the patient had resumed paroxetine treatment. After requesting the patient again to stop taking the anti-depressant, IOP was 10 mm Hg in BE in the next exam 48 h later.As far as we are aware, there are no other reports of chronic angle-closure glaucoma related to the use of paroxetine. We thus consider that, before initiating treatment with this drug, patients should be informed of its potential ocular risks and they should be subjected to an ophthalmologic examination before its use is authorized.

Fatty liver disease is now recognized as a major health burden, due to the greater number of cases that are being diagnosed. This trend could partly be explained by the increased use of liver ultrasonography in asymptomatic patients for various reasons, mainly persistent transaminase elevation. The most commonly reported risk factors associated with fatty liver disease are chronic alcohol intake, obesity, type 2 diabetes mellitus, hyperlipidemia, and some drugs. When these factors have been ruled out in a patient with a fatty liver, less frequent causes such as certain inherited metabolic disorders should be considered. Familial hypobetalipoproteinemia is characterized by an alteration of apolipoprotein B (apo B) synthesis, leading to the secretion of truncated forms of the protein, which in turn leads to a marked reduction in excretion of very low-density lipoproteins from the liver and consequently to lipid deposits, especially triglycerides, in the hepatocytes. We report the case of a 23-year-old man who met the diagnostic criteria for heterozygous familial hypobetalipoproteinemia. He presented with mild transaminase elevation and fatty liver. Total cholesterol, low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and apo B were below normal limits, while levels of high-density lipoprotein cholesterol were normal. Lipid profile determination and liver ultrasonography of first and second-degree relatives were also performed. Molecular studies of the index case revealed an unaffected apo B gene.

On 6 October 2014, a case of Ebola virus disease (EVD) acquired outside Africa was detected in Madrid in a healthcare worker who had attended to a repatriated Spanish missionary and used proper personal protective equipment. The patient presented with fever

Somatostatin receptors type 2 (sst2) are expressed in high concentration on numerous neudoendocrine tumors. The successful use of radiolabeled somatostatin analogs in imaging promoted further studies in utilizing them in radiopeptide therapy. The somatostatin analog [90Y–DOTA–D-Phe1–Try3]octreotide (DOTATOC) (DOTA: 1,4,7,10-tetraazacyclododecane-N,N′,N″,N‴-tetraacetic acid) possesses favorable characteristic for its therapeutic use; shows high affinity for sst2, moderately high affinity for sst5, and intermediate affinity for sst3; high hydrophilicity; stable and facile labeling with 111 In and 90 Y. In this article we report our experience with 90Y–DOTATOC in neuroendocrine tumors. Eighty-seven patients with neuroendocrine tumors were treated with a cumulated activity ranging from 7.4 to 20.2 GBq. Most patients responded with stabilization of disease (48%); however, objective responses were observed in 28% of patients (5% complete response). No major acute reactions were observed up to the activity of 5.55 GBq per cycle. The dose limiting was bone marrow toxicity and the maximal tolerated dose was defined as 5.18 GBq. © 2003 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 66: 393–398, 2002

Improved time to quality of life deterioration in patients with progressive midgut neuroendocrine tumors treated with 177Lu-DOTATATE : The NETTER-1 phase III trial

PURPOSE To present a case report of a patient diagnosed with cone dystrophy, with an uncommon presentation of paracentral involvement, tapetallike sheen, and Mizuo phenomenon. METHODS The patient underwent complete ophthalmic examination, repeated electroretinograms, fluorescein angiography, spectral-domain optical coherence tomography, autofluorescence, and different techniques for fundus photographs (color, infrared, red free). PATIENT Twenty-year-old male patient who manifested slight photofobia but was otherwise asymptomatic. RESULTS The patient had 20/20 vision in both eyes. Upon indirect ophthalmoscopy, the retina presented a metalliclike sheen. Sequential electroretinograms and multifocal electroretinogram demonstrated a decreasing photopic response, with paracentral involvement. Autofluorescence and spectral-domain optical coherence tomography allowed a better visualization of the atrophic parafoveal cones. Red-free photographs help document the tapetallike sheen and Mizuo phenomenon after 3-hour dark adaptation. CONCLUSION The final diagnosis of cone dystrophy, paracentral, with tapetallike sheen was established. Spectral-domain optical coherence tomography and red-free photographs will help better understand the pathophysiology and clinical manifestations of this uncommon disease.

El sangrado gastrointestinal es una complicación potencial del paciente que se hospitaliza. Como las descripciones iniciales en cuidados intensivos relacionaban el sangrado por úlceras de estrés con alta mortalidad, la investigación fue creciente en los pacientes críticos. No sucedió lo mismo con los hospitalizados y los trabajos disponibles son escasos. Los principales factores de riesgo se han descrito en los críticos (ventilación mecánica más de 48 horas y coagulopatía). La eficacia de la terapia no se ha demostrado en aquellos en la sala general. La evidencia indirecta muestra utilidad marginal de estos medicamentos en la prevención del sangrado gastrointestinal. En los casos críticos hay abundante información pero la interpretación es confusa. Se ha documentado una tasa alta de formulación para prevenir el sangrado en los hospitalizados, la mayoría sin indicación clara, lo cual puede exponer al paciente a eventos adversos innecesarios y gastos adicionales al sistema de salud. Se recomiendan estrategias para implementación de guías para el uso racional de estos fármacos. Abreviaturas: SGI, sangrado gastrointestinal; SRMD, stress-related mucosal disease; AINES, antiinflamatorios no esteroideos; ASHP, American Society of Health-System Pharmacists; FDA, Food and Drug Ad- ministration; ERGE, enfermedad por reflujo gastroesofágico.

Leptin is a hormone that regulates food intake, and its receptor (OB-Rb) is expressed primarily in the hypothalamus. Here, it is shown that OB-Rb is also expressed in human vasculature and in primary cultures of human endothelial cells. In vitro and in vivo assays revealed that leptin has angiogenic activity. In vivo, leptin induced neovascularization in corneas from normal rats but not in corneas from fa/fa Zucker rats, which lack functional leptin receptors. These observations indicate that the vascular endothelium is a target for leptin and suggest a physiological mechanism whereby leptin-induced angiogenesis may facilitate increased energy expenditure.

Summary Two 3-week-old Limousin x Retinta calves from extensive farms in the south of Spain died suddenly. Microscopic examination of the spleen and lymph nodes revealed an intense lymphoid proliferation; the germinal centres were prominent and were surrounded by areas of haemorrhage. Parasitic forms, similar to Koch's bodies, were observed in only a small number of lymphoid cells and macrophages. In the myocardium a severe myocarditis was found. Inflammatory cells were in close contact with damaged myocytes, sometimes surrounding fragments of cells. In some areas the vessels had intraluminal deposits of fibrin. The endothelial damage and thrombosis may have contributed to the damage observed in the myocytes, together with the cytotoxic mechanism associated with the presence of an intense inflammatory infiltrate. The active multiplication of parasites may be due to the age of the animals and their breed, since they are not an autochthonous breed and present low resistance to infection.

The glomerular alterations observed in a dog with acute spontaneous infectious canine hepatitis (ICH) are described. Histologic changes of the glomeruli were enlargement of the mesangium with presence of intranuclear inclusion bodies and without proliferation of mesangial cells. Electron microscopy revealed adenovirus replication sites in glomerular mesangial cells and in endothelial cells of glomerular capillaries, as well as a focal mesangial-sclerosing glomerulonephritis associated with electron dense deposits which were closely related with extracellular ICH viral particles and immunohistochemically reactive for immunoglobulin (Ig) G, IgA, IgM and C3c complement components.

Bacteraemia secondary to orotracheal intubation has been reported to occur in 0-5.3% of patients. Bacteraemia detection is dependent upon several factors including the volume of blood per culture and the number of cultures. Prior studies used small volumes of blood and one or two cultures, and may therefore have underestimated the incidence of bacteraemia. Sixty-two adult patients who underwent direct laryngoscopy and endotracheal intubation were studied. Baseline blood cultures were sterile in all patients. After intubation, four blood cultures were obtained in ten minutes, with 10 ml being evenly divided between aerobic and anaerobic media. Two patients (3.2%) became bacteraemic. This is a lower incidence than occurs in association with other procedures for which The American Heart Association does not recommend administration of prophylactic antibiotics. Therefore, prophylactic antibiotics are not recommended prior to direct laryngoscopy. However, when a prophylactic antibiotic is administered prior to surgery, it would be best to administer the antibiotic prior to direct laryngoscopy and intubation.

The effects of African swine fever (ASF) virus infection on bone marrow hematopoiesis and microenvironment were determined by studying the sequential development of ultrastructural lesions of bone marrow and blood cell changes. Eight pigs (two pigs/infected group) were inoculated by intramuscular route with 105 50% hemadsorbing doses (HAD50) of the Malawi'83 ASF virus isolate. Two uninfected pigs were used as controls. Ultrastructural changes developed by day 3 postinoculation (PI), persisted through day 7 PI, and were characterized by activation of macrophages. From day 5 PI, viral replication was observed in monocytes/macrophages, reticular cells, immature neutrophils, and promonocytes. Also viral replication was detected in megakaryocytes, endothelial cells, and pericytes at day 7 PI. Vascular alterations consisted of activation of sinusoidal endothelial cells, intravascular coagulation, and fibrin strands interspersed among microenvironment and hematopoietic cells. No significant changes were observed in total white blood cells counts, percentage of monocytes, and platelet counts; however, severe lymphopenia and neutrophilia were detected from day 3 PI. Results of this experiment indicate that there is increased hematopoiesis in bone marrow during acute ASF, coinciding with macrophage activation. Neither vascular changes nor viral replication in different bone marrow cell populations gave rise to impaired bone marrow function. Increased hematopoiesis would exert a positive influence by preventing the early onset of thrombocytopenia and would exert a negative influence by stimulating the spread of the virus via neutrophils. Increased hematopoiesis would be unable to compensate for the lymphopenia.

Formalin-fixed, paraffin embedded tissues obtained from 40 pigs inoculated with a field isolate of hog cholera virus were examined for the presence of Gp55, a major structural protein of the virus envelope, using a monoclonal antibody-based immunohistochemical test with the avidin-biotin-peroxidase complex method. Immunoreactivity was detected in hog cholera virus-infected tissues but not in control pigs tissues, African swine fever virus-infected tissues, or bovine viral diarrhea virus-infected porcine or bovine tissues. The first positive reactions were seen in lymphatic tissues, digestive tract and skin on postinoculation day (pid) 4, respiratory and urinary tissues on pid 5, nervous tissues on pid 6, and endocrine tissues on pid 7. These staining reactions persisted until the last observation on pid 18. Hog cholera virus antigen was not detected in heart tissue at any time. The highest levels of antigen detection were found in tonsils, spleen, and pancreas, although the esophageal mucosa and skin epithelial cells were also intensely and widely stained. The cellular staining pattern of Gp55 had a ubiquitous distribution. It was found in epithelial cells, macrophages and circulating monocytes, endothelial cells, lymphoid cells, and glial cells. The results showed a high specificity and high sensitivity for detecting hog cholera Gp55 in formalin-fixed, paraffin embedded tissue samples. This method allows precise association of Gp55 with specific cells, tissues, and histologic lesions, making the technique suitable for use in routine diagnosis of hog cholera.

Twelve miniature pigs were infected experimentally with the moderately-virulent Spanish isolate of African swine fever virus E75. The disease was reproduced acutely and subacutely, and six days after infection the animals showed severe clinical and pathological signs characterised by diffuse haemorrhages in lymphoid and non-lymphoid organs. An immunohistopathological study, using two different methods, and a monoclonal antibody (mAb) (18BG3) were used to analyse the distribution of the virus protein 73 (VP73) and IgM and IgG. VP73 was observed primarily in cells of the mononuclear phagocyte system, and in many megakaryocytes, some tubular epithelial cells of the kidneys, tonsillar epithelium, some hepatocytes, and in a few endothelial cells and neutrophils in the later stages of the infection. The histological findings and the distribution of VP73 and IgM and IgG indicated that the virus caused haemorrhagic lesions through its effect on various haemostatic mechanisms.

• Background: Cysticercosis is one of the parasitic diseases that most frequently affects the eye. The most common and severe manifestations of ocular infection are secondary to posterior segment involvement, which often leads to blindness and atrophy of the eye. The pathogenesis of ocular injury in this disease is poorly understood. The authors have developed an experimental animal model for intravitreous cysticercosis using New Zealand rabbits and Taenia crassiceps cysticerci. • Methods: Twelve rabbits were divided into two groups. Rabbits in group I were inoculated with one living cysticercus in the vitreous cavity. Rabbits in group II received an intramuscular dose of steroids prior to inoculation of parasites • Results: An intense inflammatory reaction, which lead to a severe ocular injury, was observed in rabbits of group I, while rabbits ing roup II had minimal inflammatory changes. Histopathological studies showed a severe histiocytic infiltrate with generalized retinal damage in group I, and a mild inflammatory infiltrate, limited to the area of direct contact with the parasite in group II. The ocular lesions found in rabbits which did not receive steroids (group I) resembled those found in human ocular cysticercosis. • Conclusion: These observations indicate that ocular damage in this parasitic disease might be directly related to inflammatory changes produced by the presence of cysticerci. This model appears to be useful for future investigations.

The pathological effect of haemorrhagic fever viruses on the kidney have not been clearly documented. This study reports glomerular lesions in African swine fever. In the acute form of the disease there was an acute diffuse proliferative glomerulonephritis, which was believed to be related to virus replication in circulating monocytes and glomerular mesangial cells, and to the presence of abundant circulating cell debris resulting from viral replication at other sites. In the subacute form, the proliferative mesangial glomerulonephritis observed may have been associated with systemic immune-mediated phenomena, and with subendothelial and mesangial deposits of immunoglobulins and complement components.

The spleens of four psittacine birds suffering from natural type II avian adenoviral infection were studied by histopathological, immunohistochemical and ultrastructural techniques to determine the target cells of this virus in the spleen. Typical adenoviral replication sites were found in lymphocytes and dendritic cells.

African swine fever is an acute haemorrhagic disease of pigs which may serve as a model for the study of the pathogenesis of other viral haemorrhagic fevers. This paper describes an ultrastructural study of the sequence of lesions produced in the perisinusoidal functional unit of the liver of pigs inoculated with the Malawi '83 strain of African swine fever virus, which is classified as haemadsorbing and highly virulent. Virus replication was observed in Kupffer cells and monocytes from three days after inoculation, in hepatocytes and fat-storing cells at five and seven days after inoculation, and in sinusoidal endothelial cells at seven days after inoculation. Further observations included intravascular coagulation, which peaked at five days after inoculation, and fibroblast and myofibroblast transformation of fat-storing cells at seven days after inoculation. These results suggest that activated cells of the mononuclear phagocyte system may play a major role in this sequence of lesions and the possible role of the cytokines that may be released by these cells is discussed.

NETTER-1 phase III in patients with midgut neuroendocrine tumors treated with 177Lu-dotatate : Efficacy, safety, QoL results and subgroup analysis

This is the first study of the lesions produced by Elaeophora elaphi, a filarial worm first reported in 1986. Only the morphologic characteristics of this species have been described previously. Samples for the study were taken from 74 red deer ( Cervus elaphus), 1-10 years old, slaughtered in central Spain. Grossly, filariae were observed in the transverse, left, or right branches of the portal vein of 18 animals. In addition to filariae, whitish thrombi were found in the right and left branches of the portal vein in nine animals. Thrombi of similar characteristics were also observed in 12 deer in which no adult filariae were found. Microscopic changes were observed only in the right and left branches of the portal vein and consisted of thickening of the intima with surface formation of villi. Stroma of villi contained a moderate to intense infiltrate composed mainly of eosinophils and mononuclear cells. The tunica media of affected vessels was uniformly hypertrophic and in some cases presented a moderate inflammatory infiltrate similar to that observed in the stroma of villi. Thrombi consisted of a central area containing calcified filariae or cuticle debris, surrounded by giant cells and numerous lymphoid cells forming clearly defined nodules resembling lymphoid follicles. Thrombi were externally surrounded by a strip of connective tissue and beyond by endothelial cells that were occasionally continuous with the tunica intima. Other lesions probably associated with the infestation were multifocal granulomas in the periportal areas, lymphoid tissue formations in the hepatic parenchyma, and an interstitial nephritis.

4005Background: There are limited therapeutic options for patients with advanced midgut NETs progressing on first-line somatostatin analog therapy. The purpose of this phase III trial was to evalua...

Summary African swine fever is a viral disease of pigs characterized predominantly by haemorrhagic lesions. This paper reports the lesions observed in the renal interstitial capillaries of pigs inoculated with African swine fever virus strains of differing virulence: the Malawi'83 strain (haemadsorbent and highly virulent) and the Dominican Republic'78 strain (haemadsorbent and moderately virulent). In pigs infected with the Malawi'83 strain, petechial haemorrhages and microhaemorrhages were observed 5 days after inoculation and lesions were evident in the renal capillaries. Signs of phagocyte activation were noticeable in endothelial cells, with enlarged fenestrations and even loss of endothelium, leaving the basement membrane of the vessels exposed. Platelet plugs and microthrombi were also observed in these vessels. At 7 days after inoculation these lesions had intensified, and were accompanied by virus replication in the endothelial cells. In pigs infected with the Dominican Republic'78 strain, haemorrhages were more abundant and more extensive, and although no endothelial cell lesions were observed, there was intense vasodilation with diapedesis of erythrocytes.

PURPOSE Multiple, bilateral areas of congenital hypertrophy of the retinal pigment epithelium (CHRPE) have been described in association with familial adenomatous polyposis (FAP). Histopathologic findings have suggested a generalized effect of the FAP gene on the RPE, which could impair the functional integrity of the RPE. The clinical, psychophysical, electrophysiologic, and fluorescein angiographic findings in CHRPE in subjects with FAP were assessed. METHODS RPE function was assessed in 7 subjects with CHRPE and a family history of FAP. Four had documented FAP (mean age = 22.25 years) and the other three were siblings of affected subjects, with a 50% risk of developing FAP (mean age = 6.33 years). All subjects underwent comprehensive ophthalmologic examination. RESULTS All subjects showed mild hyperopia (mean, +1.13 D; best corrected visual acuity, 20/20 or better). On perimetry, there were scotomas corresponding to some lesions. ERG showed normal rod, maximal, single-flash cone, and flicker responses. Light-dark ratio was within the normal range on EOG. Fluorescein angiography demonstrated normal retinal vasculature overlying the CHRPE lesions, which blocked background choroidal fluorescence. A normal choriocapillaris was observed through some hypopigmented lacuna. CONCLUSION CHRPE has been related to generalized expression of an abnormal gene in RPE, but its functional abnormalities tend to be localized.

Core and organ temperatures in the rat have been found to be subject to regular periodic oscillations (with a frequency of ca 12 cycles per day, i.e. 143 mu Hz) within set limits, by using a chronic thermocouple implant procedure. These cycles consisted of consecutive warming (the temperature increased steadily) and cooling periods (the temperature decreased regularly). There were sustained temperature differences between several tissues and that of the aortic blood (core temperature), higher for brown adipose tissue, kidney and liver, and lower for muscle, white adipose tissue and skin. Organ blood flows and cardiac output were measured by a radioactive microsphere retention method applied to unanaesthetized rats. Blood flow measurements were done on unaware rats (see Methods), during either the warming or cooling phases. During the warming phases, there was a higher blood flow across the brown adipose tissue, kidney and skin, with a cardiac output about twice that found in the cooling periods. The haemodynamic changes observed, as well as the organ temperature differences observed with respect to the blood, suggest that periodic changes in blood flow are an essential part of the operation of the thermogenic system.

We describe the clinical and epidemiological characteristics of patients hospitalised with confirmed 2009 pandemic influenza A(H1N1) in Spain from April to December 2009 and the risk factors associated with a worse outcome (admission to an intensive care unit or death) in adults. Case-based epidemiological information was collected as part of the national strategy for the surveillance of severe cases. Of 3,025 patients, 852 were admitted to an intensive care unit and overall, 200 died. The median patient age was 38 years (range: 0–94). A total of 662 (26%) patients had no underlying risk conditions. Antiviral therapy was initiated within 48 hours after symptom onset in only 35.2% (n=711); the median length of time before treatment was four days. In a multivariate analysis, the start of antiviral therapy more than 48 hours after symptom onset (odds ratio (OR) 2.39; 95% confidence interval (CI): 1.79 to 3.2), morbid obesity (OR: 2.01; 95% CI 1.38 to 2.94), cardiovascular disease (OR: 1.79; 95% CI: 1.2 to 2.67) and chronic obstructive pulmonary disease (OR: 1.51; 95% CI: 1.03 to 2.2) were significantly associated with a worse outcome in adults.

Angiogenesis is a dynamic process that requires an interaction of pro-and antiangiogenic factors. It is known that the cytokine leptin stimulates endothelial cell growth and angiogenesis, but further quantitative analysis is necessary to understand leptin angiogenic effects. The quail chorioallantoic membrane (CAM) assay has been used to study angiogenesis in vivo by focusing on morphometric parameters that quantify vascular complexity and density. We quantify the angiogenic activity of leptin using the CAM assay by digital morphometry and a computer-assisted image analysis to evaluate more precisely vessel length, diameter, branching, and tortuousity. CAM images are obtained from ex ovo cultures of E8-E9 quail embryos. MATLAB and custom software are used for our analysis. The effects of leptin, vascular endothelial growth factor-165 (VEGF(165)), and their corresponding neutralizing antibodies are compared. Our results show that CAM treated with leptin and VEGF(165) has a significant increase in vascular complexity and density. A corresponding decrease is observed using neutralizing antibodies. Notably, leptin induced more significant changes than VEGF in vessel length and tortuousity. Conversely, VEGF induced a greater increase in vessel branching than leptin. These results underscore the importance of using multiparametric quantitative methods to assess several aspects of angiogenesis and enable us to understand the proangiogenic effects of leptin.

Summary Attention has already been drawn to the presence of pulmonary intravascular macrophages (PIMs) in species in which the lung plays an important part in the removal of particles from the bloodstream. The stimulation of PIMs under certain conditions has been related to pulmonary oedema and congestion. In order to ascertain whether these cells are found in rabbits, healthy animals were inoculated with a liver homogenate obtained from animals which had- died of rabbit haemorrhagic disease, a condition characterized by vascular phenomena and pulmonary oedema. PIMs were detected both in experimental and healthy control animals. They shared the morphological characteristics reported for other species, particularly with respect to the presence of intercellular junctions with endothelial cells. In experimental animals, PIMs were actively involved in the removal of cell debris which may or may not have been associated with the presence of rabbit haemorrhagic disease virus antigen.

The sudden death of five sulphur-crested cockatoos (Cacatua galerita) with no apparent clinical signs was investigated. The birds had hepatitis with intranuclear inclusion bodies (IIBs), as well as IIBs in mononuclear spleen cells, epithelial cells of the kidney tubules and endothelial cells of the glomerular capillaries. Ultrastructurally, icosahedral herpesvirus-like particles, 110 to 115 nm in diameter were found consistent with Pacheco's disease. This is the first time the disease has been reported in cockatoos in Spain.

Background Baker’s cyst (BC) is synovial fluid accumulation in the gastrocnemius semimembranous bursa that communicates with the knee joint, often secondary to degenerative or inflammatory joint disease. Its breakdown usually produces swelling and pain of the affected lower limb, leading to loss of function. Normally, it does not require treatment unless it is symptomatic. In such cases, the cyst can be aspirated to reduce its size, with subsequent intra-articular administration of 40 mg triamcinolone acetonide to reduce inflammation. Synovectomy and intra-articular methotrexate (IAM) are reserved for refractory cases. However, in the bibliography review, we have only found two citations of IAM. Purpose To describe the tolerability and effectiveness of IAM in the treatment of BC in a patient with rheumatoid arthritis (RA). Material and methods A 54-year-old man with RA, treated with subcutaneous methotrexate 15 mg weekly and intravenous tocilizumab monthly,also presented with a relapsing cyst in the right lower limb aspirated on two previous occasions. In the presence of severe calf muscle damage, the patient was admitted to the hospital. Pig-tail drainage catheter was placed and washes with 20 ml of saline per nursing shift were made. After 3 days without improvement, interventional radiology service in cooperation with internal medicine contacted the hospital pharmacy requesting 25 mg methotrexate and 80 mg methylprednisolone for intra-articular administration. Via the interventional radiology service, precharged syringes of methotrexate and methylprednisolone were administrated by intra-articular injection through the catheter. Results 2 months later, the patient’s disease was under control with an improvement in inflammatory markers: C reactive protein and erythrocyte sedimentation were 1 mg/mL and 12 mm/h, respectively, compared with 94 mg/L and 108 mm/h before methrotexate administration. 6 months later, he has not presented any signs of swelling and the inflammatory markers have remained Conclusion Administration of IAM for the treatment of BC could be considered a well tolerated treatment option in recurrent and refractory cases to conventional treatment. Our patient presented analytical and subjective clinical improvement. However, more experience and follow-up are needed to draw conclusions to apply to clinical practice. References and/or Acknowledgements See explanation to reviewers No conflict of interest.

Clinical signs, histopathological and ultrastructural findings associated with Atoxoplasma spp. natural infection in captive canaries (Serinus canaria) are described. Intracytoplasmic Atoxoplasma-like protozoa were found in the liver and lung. In the liver, protozoa were found in hepatocytes and Kupffer's cells and were associated with granulomatous hepatitis and a marked bile duct hyperplasia. An usual finding was the presence of infected mononuclear cells adhered to the endothelium of the blood vessels in lung. The diagnosis was confirmed by ultrastructural examination of reprocessed paraffin-embedded tissues.

177-Lu-Dotatate significantly improves progression-free survival in patients with midgut neuroendocrine tumours : Results of the phase III NETTER-1 trial

This study aimed at describing influenza vaccination coverage among Spanish children, adults and health care workers (HCWs). We analyzed 27,791 questionnaires on subjects aged 6 months or over, drawn from the 2003 Spanish National Health Survey. As the dependent variable, we took the answer to the question, “Did you (or your child) have a flu shot in the last campaign?”. Independent variables were age group, gender, nationality, occupation (HCWs) and coexistence of chronic conditions. Overall influenza vaccination coverage for the total sample was 19.58%. Coverage for the pediatric population was 5.55%, with 20.74% of those with and 4.67% of those without chronic condition being vaccinated. Vaccination coverages were: 63.7% among subjects aged ≥ 65 years; 30.5% among high-risk subjects aged < 65 years; and 19.65% among HCWs. We conclude that the available results show low levels of influenza vaccination coverage among high-risk subjects aged under 65 years, children in particular, and HCWs.