Real-world effectiveness and safety of apremilast in psoriasis at 52 weeks: a retrospective, observational, multicentre study by the Spanish Psoriasis Group.

BACKGROUND: Little has been published on the real-world effectiveness and safety of apremilast in psoriasis. OBJECTIVES: To evaluate the effectiveness, safety and drug survival of apremilast at 52 weeks in patients with moderate to severe plaque psoriasis or palmoplantar psoriasis in routine clinical practice. METHODS: Retrospective, multicentre study of adult patients with moderate to severe plaque psoriasis or palmoplantar psoriasis treated with apremilast from March 2016 to March 2018. RESULTS: We studied 292 patients with plaque psoriasis and 85 patients with palmoplantar psoriasis. The mean (SD) Psoriasis Area and Severity Index (PASI) score was 10.7 (7.0) at baseline and 3.0 (4.2) at 52 weeks. After 12 months of treatment, 73.6% of patients had a PASI score of 3 or less. In terms of relative improvement by week 52, 49.7% of patients achieved PASI-75 (≥75% reduction in PASI score) and 26.5% achieved PASI-90. The mean physician global assessment score for palmoplantar psoriasis fell from 4.2 (5.2) at baseline to 1.3 (1.3) at week 52. Overall drug survival after 1 year of treatment with apremilast was 54.9 %. The main reasons for treatment discontinuation were loss of efficacy (23.9%) and adverse events (15.9%). Almost half of the patients in our series (47%) experienced at least one adverse event. The most common events were gastrointestinal problems. CONCLUSIONS: Apremilast may be a suitable alternative for the treatment of moderate to severe psoriasis and palmoplantar psoriasis. Although the drug has a good safety profile, adverse gastrointestinal effects are common.

Improvement of a dry formulation of Pseudomonas fluorescens EPS62e for fire blight disease biocontrol by combination of culture osmoadaptation with a freeze-drying lyoprotectant.

AIMS: To study the effect of lyoprotectants and osmoadaptation on viability of Pseudomonas fluorescens EPS62e during freeze-drying and storage and to evaluate the formulation in terms of efficacy in biocontrol and fitness on pear flowers. METHODS AND RESULTS: A wettable powder formulation of a biocontrol agent of fire blight was optimized by means of lyoprotectants and culture osmoadaptation. Freeze-drying was used to obtain dehydrated cells, and the best viability (70% of survival) was obtained using lactose as lyoprotectant. Survival during lyophilization was additionally improved using physiological adaptation of cells during cultivation under salt-amended medium (osmoadaptation). The procedure increased the survival of cells after freeze-drying attaining viability values close to a 100% in the lactose-formulated product (3 × 10(11) CFU g(-1) ), and through the storage period of 1 year at 4°C. The dry formulation showed also an improved biocontrol efficacy and survival of EPS62e on pear flowers under low relative humidity conditions. CONCLUSIONS: Cell viability after freeze-drying was improved using lactose as lyoprotectant combined with a procedure of osmoadaptation during cultivation. The powder-formulated product remained active for 12 months and retained biocontrol levels similar to that of fresh cells. The formulation showed an improved survival of EPS62e on flowers and an increase of the efficacy of biocontrol of fire blight at low relative humidity. SIGNIFICANCE AND IMPACT OF THE STUDY: The results have a potential value for commercial application in biocontrol agents not only of fire blight but also of other plant diseases.

Postinfection Activity of Synthetic Antimicrobial Peptides Against Stemphylium vesicarium in Pear.

Brown spot of pear is a fungal disease of economic importance caused by Stemphylium vesicarium that affects the pear crops in Europe. Due to the characteristics of this disease and the moderate efficacy of available fungicides, the effectiveness of control measures is very limited; however, synthetic antimicrobial peptides (AMPs) may be a complement to these fungicides. In the present study, 12 AMPs of the CECMEL11 library were screened for fungicidal activity against S. vesicarium. In vitro experiments showed that eight AMPs significantly reduced the germination of conidia. The most effective peptides, BP15, BP22, and BP25, reduced fungal growth and sporulation at concentrations below 50 µM. Leaf assays showed that preventive application of BP15 and BP22 did not reduce infection; however, when the peptides were applied curatively, infection was significantly reduced. The use of a BP15 fluorescein 5-isothiocyanate conjugate revealed that the peptide binds to hyphae and germ tubes and produces malformations that irreversibly stop their development.

Prospects and limitations of microbial pesticides for control of bacterial and fungal pomefruit tree diseases.

The tree constitutes an ecosystem in which microorganisms play an essential role in its functionality. Interactions that microorganisms establish with plants may be beneficial or detrimental and are of extreme importance in the exploitation of trees in agriculture as crop production systems. Fruit trees, especially pomefruit trees including apple, pear and several ornamentals are of great economic importance but its production is affected by several diseases. Fungal and bacterial fruit tree diseases are mainly controlled with chemical fungicides and bactericides, but health and environmental concerns about the use of chemical pesticides have result in strong regulatory actions and have stimulated the development of beneficial microorganisms as microbial pesticides. Up to now, several microorganisms have been registered in different countries and in the EU as biocontrol agents (BCA) covering mainly fire blight, soil-borne fungal diseases and postharvest fruit fungal rot. The key aspects in the success of this technology for disease control are related to biosafety and environmental impact of biocontrol agents, the traceability and fate in the environment and food chain, the improvement by physiological, genetic engineering or the use of mixtures or formulations as well as the industrial production and development of delivery systems for treatment application to trees.

Improvement of fitness and efficacy of a fire blight biocontrol agent via nutritional enhancement combined with osmoadaptation.

The efficacy of Pseudomonas fluorescens EPS62e in the biocontrol of Erwinia amylovora was improved by a procedure of physiological adaptation to increase colonization and survival in the phytosphere of rosaceous plants. The procedure consisted of osmoadaptation (OA) and nutritional enhancement (NE). OA was based on saline stress and osmolyte amendment of the growth medium during inoculum preparation. NE consisted of addition of glycine and Tween 80 to the formulation. NE and OA increased the growth rate and carrying capacity of EPS62e under high-relative-humidity (RH) conditions and improved survival at low RH on flowers under controlled environmental conditions. NE did not promote growth or affect infection capacity of E. amylovora. The effect of both methods was tested in the field by following the population of EPS62e using quantitative PCR (Q-PCR) (total population) and CFU counting (culturable population) methods. Following field application, EPS62e colonized blossoms, but it was stressed, as indicated by a sharp decrease in culturable compared to total population levels. However, once established in flowers and at the end of bloom, almost all the total population was culturable. The physiological adaptation treatments increased population levels of EPS62e over those of nonadapted cells during the late stage of the flowering period. Control of fire blight infections in flowers and immature fruits was tested by field application of EPS62e and subsequent inoculation with E. amylovora under controlled-environment conditions. The efficacy of fire blight control increased significantly with the combination of nutritional enhancement and osmoadaptation, in comparison with the absence of physiological adaptation.

Need for lung resection in patients with intact or ruptured hydatid cysts.

BACKGROUND: Lung hydatid cyst caused by Echinococcus granulosus is endemic in many areas of the world. We aimed to compare the outcome of surgical treatment in intact and ruptured (infected or noninfected) cysts. METHODS: We reviewed the medical records of 115 patients with lung hydatid disease who were surgically treated between 2001 and 2005 in a tertiary hospital in Lima, Peru. Patients were divided into 3 groups based on cyst characteristics: intact cysts (n = 41), ruptured noninfected cysts (n = 47) and ruptured infected cysts (n = 27). If a patient had more than one type of cyst, the most severe form of disease was recorded. Data related to symptoms, morbidity and mortality were recorded and compared. We also calculated direct patient costs. RESULTS: Mean age of patients was 23.6 +/- 15.1 years old. Ruptured cysts were present in 64 % of patients and giant cysts (> 10 cm diameter) were present in 26 % of patients. Hemoptysis was present in 47.0 % of patients and was more frequent in patients with ruptured infected cysts. Lung resection was performed in 58 % of patients. The most common postoperative complication was infection of the operative wound (6.08 %). Perioperative mortality was zero. Patients with ruptured cysts had a longer hospitalization time and higher total cost (12.28 +/- 0.92 days, US$ 890.34 +/- 303.35) than patients with intact cysts (10.17 +/- 0.79 days, US$ 724.81 +/- 14.38). CONCLUSION: Surgical treatment of lung hydatid disease is safe, with a good outcome and a low mortality rate. The lung resection rate was higher than most published series and reflects the relatively high proportion of patients with giant and ruptured infected cysts.

Evaluation of ISO enrichment real-time PCR methods with internal amplification control for detection of Listeria monocytogenes and Salmonella enterica in fresh fruit and vegetables.

AIMS: To provide with a quick method for qualitative detection, in less than three days, of Salmonella enterica and Listeria monocytogenes in fresh fruit and vegetables. METHODS AND RESULTS: The method was based on coupling International Standard Organization (ISO) enrichment to a real-time PCR with internal amplification control (IAC), in a duplex format, without additional DNA purification. The performance was tested on different plant products. Both bacterial pathogens were consistently detected with a limit of detection (LOD) of 1 CFU in 25 g after enrichment, except for soybean sprouts. Levels of S. enterica, ranging from 1 to 10 CFU in 25 g after enrichment were detected with different enrichment broths. CONCLUSIONS: For both pathogens, the LOD was similar to that of the corresponding ISO method, while decreasing the analysis time and handling needs. SIGNIFICANCE AND IMPACT OF THE STUDY: The agreement between standard ISO and the enrichment real-time PCR(IAC)-based methods make the latter method as a promising alternative for quick and reliable detection of food-borne pathogens in fresh fruit and vegetables in routine laboratories.

Pleural empyema as a late complication of liver cystectomy for hydatid cyst.

Cystectomy without capitonnage is a widely used surgical technique for liver hydatid disease. A residual cavity can be left during the procedure, which can turn into an abscess. We report the case of a patient who developed right pleural empyema as a late complication of this procedure. She was successfully managed with antibiotics and a right thoracotomy.

Effect of Relative Humidity and Interrupted Wetness Periods on Brown Spot Severity of Pear Caused by Stemphylium vesicarium.

ABSTRACT Field observations in four pear orchards during 5 years from April to October indicated that days with uninterrupted wetness of variable length represented 83.9% of the total days studied. However, days with surface wetness interruptions and with high relative humidity (RH) (>/=90%) without wetness occurred with a frequency of 7.1 and 6.2%, respectively. Accordingly, the effect of interruption of 24-h wetness periods by dry periods of high or low RH on infections caused by Stemphylium vesicarium on pear was determined. Pear plants inoculated with conidia of S. vesicarium were exposed to a 12-h wet period followed by a dry period of variable length (0, 3, 6, 12, 18, or 24 h) and a second wet period of 12 h. The dry period consisted either of low (60%) or high (96%) RH. The infection process was irreversibly stopped under low RH during dry periods between wetness, but continued at high RH. The effect of high RH on disease severity in the absence of wetness was also determined. Pear plants inoculated with S. vesicarium were exposed to periods of variable length (3 to 24 h) either at high RH (96%) in the presence of wetness or at high RH (96%) without wetness. No infections were observed on plants incubated under high RH without wetness, indicating that conidia of S. vesicarium require the presence of a water film in the plant surface to develop infections on pear.

Changes in cholesterol levels after coronary artery bypass surgery.

To determine the factors responsible for the dramatic fall in cholesterol levels after coronary artery bypass surgery (CABG), the authors reviewed, in a retrospective study, the cholesterol levels of 36 patients who underwent CABG surgery during 1987 and compared their levels with those of a control group of 30 patients who underwent cholecystectomies during the same time. In a prospective study, the authors measured the lipids and the hematocrit levels of 15 patients undergoing CABG surgery before the initiation of cardiopulmonary bypass, after 5 minutes of extracorporeal circulation (ECC), and at the end of ECC. In the CABG group, the plasma cholesterol level fell from 211 +/- 63 mg/dl (mean +/- SE) to 70 +/- 48 mg/dl (p less than 0.01), a 77% decrease within 24 hours of surgery. In the cholecystectomy group, the plasma cholesterol fell from 192.3 +/- 8.9 mg/dl to 158 +/- 76 mg/dl (p less than 0.01), an 18% decrease within 24 hours of surgery. To estimate the contribution of hemodilution or blood loss to the fall in cholesterol, changes in hematocrit were recorded. In the CABG group, hematocrit fell from 39.5 +/- 0.7% to 23.5 +/- 0.7% 24 hours after surgery (41% decrease) (p less than 0.01), whereas in the cholecystectomy group hematocrit fell from 39.4 +/- 0.8% to 37.1 +/- 0.9% on the first postoperative day (6% decrease). There was a positive correlation between the fall in cholesterol and the fall in hematocrit in the CABG group (correlation coefficient 0.472), suggesting that hemodilution was a major factor in the decrease in cholesterol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Development and Field Evaluation of a Model to Estimate the Maturity of Pseudothecia of Pleospora allii on Pear.

The effect of temperature and of two levels of relative humidity (RH) on maturity of pseudothecia of Pleospora allii (teleomorph of Stemphylium vesicarium) was studied under controlled environmental conditions at temperatures of 5, 10, 15, 20, 25, and 30°C and high (≥98%) and low (≈60%) RH. Pseudothecia developed only at high RH, and the optimum temperature was between 10 and 15°C. A regression model of the form ln(1/1 - y) = 0.12550 + 0.005048x, which related the proportion of mature pseudothecia (y) to cumulative degree-days (x), was developed with data from two controlled environment experiments. Maturation of pseudothecia also was studied in leaf debris in pear orchards affected by brown spot of pear in seven field trials during 4 years. Asci with mature ascospores were observed in leaf debris from mid-January to May. A significant linear relationship was observed between the predicted values according to the monomolecular model and observed values of the percentage of mature pseudothecia in the field trials (r 2 = 0.91, intercept=8.718, and slope=0.903). This model can be used to predict the onset of ascospore discharge and for determining the initiation of fungicide applications to control the primary inoculum and prevent primary infections.

Evaluation of BSPcast Disease Warning System in Reduced Fungicide Use Programs for Management of Brown Spot of Pear.

A forecasting model (BSPcast) developed for prediction of brown spot (Stemphylium vesicarium) of pear was evaluated as an advisory system for reduced fungicide use in disease management programs. Eleven trials were performed during 1995, 1996, and 1997 in five orchards in two different climatic areas in Catalunya (Spain) and Emilia-Romagna (Italy). Values of 3-day cumulative daily infection risk (CR) provided by the model were used to determine risk periods during the growing season of pear and were taken as thresholds to schedule fungicide sprays. The fungicide application programs tested using the model consisted of guided schedules with CR action thresholds of 0.4, 0.5, or 0.6, and fixed sprays following a standard commercial schedule. In nine out of 10 trials, no significant differences were observed in disease incidence on fruit at harvest between the fixed-spray commercial schedule and guided sprays using thresholds of 0.4 or 0.5. The average savings in number of fungicide sprays applied using BSPcast compared with the fixed-spray schedule were 20 to 70% when using fungicides with a 15-day protection period (kresoxim-methyl or procymidone) and ranged from 20 to 50% when using a fungicide with a 7-day protection period (thiram).

[Detection of early cytomegalovirus antigen in cell culture]. / Detección de antígeno temprano de citomegalovirus en cultivo celular.

The reference technique for the diagnosis of active cytomegalovirus infection is the isolation in cellular culture. Its major drawback is the interval between the inoculation of the sample and the development of the characteristic cytopathic effect. Occasionally, this delay may be longer than four weeks. The centrifugation of the sample on the cell monolayer at the time of inoculation and the use of a fluorescein-labeled monoclonal antibody for the detection of the early antigen in cells may considerable reduce the time required for the diagnosis of cytomegalovirus infection. In the present study the technique of detection of the early antigen by immunofluorescence was compared with conventional cell culture in 258 clinical samples referred to the laboratory for study. Fifty-one of them were positive: 28 with both techniques, 12 only with cell culture and 11 only with immunofluorescence. The mean time to obtain positive results was 25 hours for immunofluorescence and 13 days for culture.

[Folliculitis caused by Pityrosporum]. / Foliculitis por Pityrosporum.

During the summer months three young patients were examined by us for an asymptomatic cutaneous eruption of erythematous papules located on neck, shoulders and back. They were heat-resistant to several antiseptics and systemic antibiotic treatment. The mechanical expression of these lesions did not reveal the appearance of pus, but a hard keratinous matter. The histopathological findings of the lesions show a non specific folliculitis, but the PAS stain shows numerous spores of yeast forms within the keratinous material of the follicle. The culture of this material in bacteriological and mycological ordinary media is negative, but the culture in the Dixon media reveals the growth of typical colonies of Pityrosporum orbiculare. The patients responded successfully to a 3 weeks course of ketoconazole (200 mgr/d).

Change in Size of Chromatium minus Cells in Relation to Growth Rate, Sulfur Content, and Photosynthetic Activity: A Comparison of Pure Cultures and Field Populations.

The size frequency distribution of planktonic cells of purple sulfur phototrophic bacteria was measured at several depths in a bacterial layer of Lake Cisó (Spain). The bacterioplankton was dominated by Chromatium minus (87 to 94% of the total biomass). The largest cells of C. minus were found in the top part of the bacterial layer. In addition, the in situ and potential specific photosynthetic activity (CO(2) fixation and acetate uptake) and specific pigment content were measured in relation to several key environmental parameters that determine the activity of cells. Potential growth rates were estimated from production rates and biomass. A maximal specific growth rate of 0.074 h was found for the top part of the bacterial layer. Photosynthesis versus light and versus sulfide curves among field samples indicated that light was the main limiting factor controlling the activity of C. minus in Lake Cisó. The specific bacteriochlorophyll a content was very high in all samples (0.27 to 0.36 mug mug of C). Results of laboratory experiments performed with pure cultures indicated that the average cell volume changes from 5.9 to 20.0 mum and that differences in growth rate, breakdown, or synthesis of sulfur and glycogen and degradation of the photosynthetic apparatus are the main factors accounting for the observed changes in cell volume across the bacterial layer.

Comparison between direct methods for determination of microbial cell volume: electron microscopy and electronic particle sizing.

Size frequency distributions of different phototrophic and heterotrophic microorganisms were determined by means of scanning and transmission electron microscopy and electronic particle sizing. Statistically significant differences existed among the three techniques used in this study. Cells processed for electron microscopy showed lower mean cellular volumes than those processed for electronic particle sizing, reflecting a shrinkage by factors ranging from 1.1 to 6.2 (mean, 2.3). Processing of cells for scanning electron microscopy caused higher shrinkage than processing for transmission electron microscopy. Shrinkage was dependent neither on the size nor on the cell wall type of the microorganism. When processed for scanning electron microscopy, phototrophic bacteria were strongly shrunken, whereas heterotrophic microorganisms were less affected. A direct relationship existed among phototrophic bacteria between percentage of shrinkage and specific pigment content. This was probably a consequence of the pigment extraction by organic solvents during the dehydration process, previous to the critical point drying, necessary to examine the specimens under the scanning electron microscope.