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.

Use of biological treatments in patients with hidradenitis suppurativa.

INTRODUCTION: Hidradenitis suppurativa (HS) is a chronic skin disease which causes a great impact in the quality of life. Multiple therapeutic options have been proposed, and recently the potential use of biological drugs in severe cases has been postulated. MATERIAL AND METHODS: A retrospective study from seven tertiary Spanish centers reviewing the charts of patients with HS treated with biological drugs was performed. Retrieved information included epidemiological data, clinical features, pain intensity, Hurley stage, laboratory data and therapeutic outcomes. RESULTS: Nineteen patients were included in the study; 10 men (52.6%) and 9 women. Eight patients (42%) showed a Hurley severity stage II and 11 a stage III (57.8%). Adalimumab was prescribed as the first biological treatment in nine out of 19 cases (47.3%), whereas infliximab was prescribed in seven cases (36.8%), ustekinumab in two cases (10.5%) and etanercept in one (5.2%). A complete response was observed in three patients (two cases with infliximab and one case with ustekinumab), a partial improvement in 10 patients and in six patients no clinical improvement was noted. One patient referred worsening of the skin symptoms. In 6 cases, a second biological treatment was prescribed. In three of such cases, a partial improvement was noted, whereas in three cases no clinical improvement was observed. In two cases a switch to a third biological drug was indicated, with a partial improvement in one case. DISCUSSION AND CONCLUSIONS: Biological drugs could be a potential and effective therapeutic option for patients with severe HS. Complete and persistent clinical responses are rarely obtained (15%) and partial responses are achieved in approximately 50% of patients. No specific markers for a therapeutic response have been identified. No definitive conclusions regarding the most effective biological drug for HS could be drawn. Higher dosage schedules seem to be associated with higher response rates. The lack of response of one particular drug does not preclude a potential efficacy to another biological treatment.

Postoperative pyoderma gangrenosum: diagnostic value of 16s ribosomal RNA sequencing and review of the literature.

BACKGROUND: Pyoderma gangrenosum (PG) is an uncommon condition, but can lead to the diagnosis of an underlying systemic disease. It can appear spontaneously or as a result of the pathergy phenomenon after trauma or surgery. METHODS: We review three patients with postoperative PG (PPG) and the relevant literature. We also report an accurate method for microbial detection by 16S ribosomal (r)RNA sequencing. RESULTS: A 47-year-old woman and two men aged 54 and 48 years, respectively, presented with sterile ulcerations after surgery. Associated conditions (Crohn's disease and leukaemia) were present. Surgical wound infection was suspected and systemic empirical antibiotics were prescribed. After infection was excluded, PPG was diagnosed and corticosteroids were started. DISCUSSION: PPG should be considered in the differential diagnosis of postsurgical wound complications. Recognition of this condition may prevent unnecessary administration of antimicrobial treatment and development of more extensive ulcerations. It may also be the clue for the diagnosis of an underlying systemic disease. We discuss the usefulness of 16S rRNA sequencing for microbial detection and identification in order to exclude a causative infection in patients who have previously received antibiotic treatment.

Cervico-thoracic lipoma associated with occult syringohydromyelia.

Cutaneous lesions in the midline may be hallmarks of an occult spinal dysraphism. They rarely may occur in the cervical and thoracic regions. We report a 9-year-old girl with a cervico-thoracic lipoma associated with an underlying syringohydromyelia. Early detection of potentially complicated conditions can prevent the occurrence of irreversible neurologic damage.

Distribution of polycyclic aromatic hydrocarbons in riverine waters after Mediterranean forest fires.

Extensive forest fires occurred in Catalonia, northern Spain, in 1994. In our study, concentrations and profiles of 12 parent polycyclic aromatic hydrocarbons (PAHs) were determined in riverine waters, ash and sediment samples at nine sampling sites (W1-W9) and at three sampling dates from Llobregat hydrographic basin: in August, 1994, one month after the extensive forest fires; in September, 1994, after the first heavy autumn rainfalls and in January, 1995, six months after forest fires. In August 1994, the total concentrations of 12 PAHs measured in riverine waters varied from 2 ng/l to 336 ng/l. In September 1994, the total PAH concentrations decreased to 0.2-31 ng/l and in January 1995, from 9 ng/l to 73 ng/l. In August, the composition pattern of PAHs showed a distribution dominated by 4-ring PAHs (pyrene, chrysene+triphenylene, benzo(a)anthracene) at W3-W6, W8 and W9 and 3-ring PAHs (phenanthrene) at W1, W2 and W7. In September, a preference by 3-ring PAHs (phenanthrene) at all sampling sites except W5 was shown and in January was clearly dominated by 4-ring PAHs (chrysene+triphenylene, pyrene, benzo(a)anthracene) at all sampling sites. In ash and sediment samples, the total concentrations of 12 PAHs ranged from 1.3 ng/g to 19 ng/g. The dominant compound was phenanthrene.

Extracellular Matrix Assembly in Diatoms (Bacillariophyceae) (II. 2,6-Dichlorobenzonitrile Inhibition of Motility and Stalk Production in the Marine Diatom Achnanthes longipes).

The cellulose synthesis inhibitor 2,6-dichlorobenzonitrile (DCB) and the DCB analogs 2-chloro-6-fluorobenzonitrile, 3-amino-2,6-dichlorobenzonitrile, and 5-dimethylamino-naphthalene-1-sulfonyl-(3-cyano-2, 4-dichloro)aniline (DCBF) inhibited extracellular adhesive production in the marine diatom Achnanthes longipes, resulting in a loss of motility and a lack of permanent adhesion. The effect was fully reversible upon removal of the inhibitor, and cell growth was not affected at concentrations of inhibitors adequate to effectively interrupt the adhesion sequence. Video microscopy revealed that the adhesion sequence was mediated by the export and assembly of polymers, and consisted of initial attachment followed by cell motility and eventual production of permanent adhesive structures in the form of stalks that elevated the diatom above the substratum. A. longipes adhesive polymers are primarily composed of noncellulosic polysaccharides (B.A. Wustman, M.R. Gretz, and K.D. Hoagland [1997] Plant Physiol 113: 1059-1069). These results, together with the discovery of DCB inhibition of extracellular matrix assembly in noncellulosic red algal unicells (S.M. Arad, O. Dubinsky, and B. Simon [1994] Phycologia 33: 158-162), indicate that DCB inhibits synthesis of noncellulosic extracellular polysaccharides. A fluorescent probe, DCBF, was synthesized and shown to inhibit adhesive polymer production in the same manner as DCB. DCBF specifically labeled an 18-kD polypeptide isolated from a membrane fraction. Inhibition of adhesion by DCB and its analogs provides evidence of a direct relationship between polysaccharide synthesis and motility and permanent adhesion.

Bioassay techniques for evaluating pesticides against Dermatophagoides spp. (Acari: Pyroglyphidae).

Three bioassay techniques for testing pesticides against the American house dust mite, Dermatophagoides farinae Hughes, and the European house dust mite, Dermatophagoides pteronyssinus (Trouessart), were evaluated using cypermethrin as a standard. All 3 bioassay techniques gave linear responses, and can be used for evaluation of different properties of compounds. The slide dip technique tests for contact activity, the plastic petri dish technique for residual activity on a nonporous surface, and the fabric technique for residual activity on a porous surface. The 2 species of house dust mites responded similarly to all 3 bioassays, indicating that these 2 species are equally susceptible to cypermethrin under a variety of test conditions. In further tests with the fabric technique, the composition of the fabrics used did not significantly affect the toxicity of the compound tested.

Dispersal of American house dust mites (Acari:Pyroglyphidae) in a residence.

American house dust mites, Dermatophagoides farinae Hughes, were marked by adding a 4% solution of Sudan Red 7B, a microbiological stain, to mite rearing media. Marked mites were released onto a downstairs couch in a 2-story residence. Two children sat on the couch for approximately 3 h after which their clothes were examined for stained mites. Various parts of the house and family vehicle were vacuum sampled, and dust samples examined for presence of marked mites. Results of 2 trials showed the presence of marked mites on clothing, upstairs in the residence, as well as in the family vehicle. Clothing is shown to be a significant factor in the dispersal of American house dust mites. Even if concentrated in a small area (1 couch), mites were able to disperse throughout the house and into a family vehicle within a matter of weeks.

Evaluation of German cockroach (Orthoptera:Blattellidae) allergen and seasonal variation in low-income housing.

Six apartments in a low-income housing project were evaluated for German cockroach. Blattella germanica (L.), infestation and concentration of an allergen derived from these cockroaches (Bla g II). Kitchen and living room samples were collected monthly for 1 yr. In addition, airborne sampling was carried out in 5 kitchens. The kitchen had the highest allergen concentration in 65% of visits and the highest number of cockroaches trapped in 69% of visits. In the kitchen, the highest cockroach levels were seen in June, whereas the values for Bla g II peaked in August. In keeping with this, the closest correlation was between Bla g II (microgram/g dust) and the number of cockroaches found 2 mo earlier. Airborne samples were assayed for 2 separate allergens. Bla g II and Bla g I. No allergen was detectable in the absence of disturbance. By contrast, during disturbance with a vacuum cleaner both Bla g II and Bla g I were detectable in the air of each apartment. Results suggest that immunochemical assay of a major allergen in dust samples from the kitchen floor may be used to monitor exposure to German cockroaches, also that cockroach levels may be used as an indicator or predictor of allergen in dust.

[Ilio-inguinal Ilio-hypogastic nerve block with a single puncture: an alterantive for anesthesia in emergency inguinal surgery]. / Bloc des nerfs ilio-inguinal et ilio-hypogastrique en une seule ponction: une alternative utile pour l'anesthésie des urgences chirurgicales inguinales.

The authors describe the anaesthetic procedure for a strangulated hernia repair needing resection and anastomosis of the small bowel in an adult patient. This procedure was performed with an ilio-inguinal/ilio-hypogastric nerve block according to a paediatrical simplified technique with a single puncture. For this patient who had relative contraindications for central blocks, this regional technique allowed to avoid general anaesthesia with its gastric aspiration and predictible difficult intubation risks. This block associated with a very light sedation was sufficient for all the surgical procedure, and postoperative analgesia was efficient over 3 hours. This simplified nerve block, better than the conventional approach for the clinical practice, represents a recommended alternative for hernia repair in emergency for high risk patients who could have a general anaesthesia or a central block.

[Acute postinfectious pityriasis rubra pilaris: a superantigen-mediated dermatosis]. / Pitiriasis rubra pilaris aguda postinfecciosa: una dermatosis mediada por superantígenos.

Acute postinfectious pityriasis rubra pilaris (PRP) is a variant of juvenile PRP (Griffiths type III) characterized by no family history, an acute course associated with a prior fever, and good prognosis. Clinical features may resemble other superantigen-mediated diseases, such as scarlatiniform rash or staphylococcal scalded skin syndrome, but its histology and treatment are different. We present 4 cases of acute postinfectious PRP that illustrate the clinical features of this uncommon disease and we review possible underlying pathogenic mechanisms.

[Correlation between the various measurements of obesity and the degree of resistance to insulin]. / Correlación entre las diferentes medidas de obesidad y el grado de resistencia a la insulina.

OBJECTIVE: To determine the correlation between certain obesity measurements and insulin resistance (measured by HOMA). DESIGN: Descriptive cross-sectional study. SETTING: Urban health centre with elderly population. PARTICIPANTS: A random sample of 70 people was chosen from among an adult population with risk factors for DM2 or already diagnosed. MAIN MEASUREMENTS: Parameters of obesity were collected (weight, BMI, body perimeters, waist/hip index, and cutaneous folds), as were clinical parameters (blood pressure and cardiovascular risk), and analyses (glycaemia and insulinaemia--both basal and after 2 hours of oral overload of glucose--, HOMA, lipid profile, and microalbuminuria study). Resistance to insulin (IR) was defined as a HOMA > or =3.8. RESULTS: Individuals with IR had significantly higher values of weight (85.5 vs 75.5 kg), BMI (35.1 vs 29.4 kg/m2), waist perimeter (108 vs 100.3 cm) than those without IR. In neither group were any significant differences as to the waist/hip index found. The BMI and/or waist perimeter values that were more likely to suffer IR were established. In men, the values were waist >107 cm (sensitivity, 43%; specificity, 62%) and BMI>29 (sensitivity, 57%; specificity, 50%). In women, they were a waist >102 cm (sensitivity, 64%; specificity, 89%) and BMI>34 (sensitivity, 91%; specificity, 89%). CONCLUSIONS: In clinical practice the BMI and the diameter of the waist are very good predictors of IR, whilst the waist/hip index and cutaneous folds do not provide any information of value.

[Variability in the calculation of coronary risk in type-2 diabetes mellitus]. / Variabilidad en la estimación del riesgo coronario en la diabetes mellitus tipo 2.

OBJECTIVE: To determine the concordance and predictive capacity of various methods for calculating coronary risk in diabetic patients. DESIGN: Prospective study of cohorts, with a 10-year follow-up. SETTING: Urban health centre in a socially depressed area, with high prevalence of DM2. PARTICIPANTS: Population diagnosed with type-2 diabetes mellitus in 1991-93 (112 individuals, with an average age of 66.7+/-11.6 years, 59% of whom were male). MAIN MEASUREMENTS: At the moment of diagnosis, the parameters normally used to calculate coronary risk were determined. The tables of the Framingham scale '91 and '98, of the United Kingdom Prospective Study (UKPDS) (based on an exclusively diabetic population) and of the REgistre GIroni del COr (REGICOR-Girona Heart Register) (based on a Mediterranean population) were each used to calculate individually coronary risk at 10 years. The coronary events suffered in the 10 years following DM2 diagnosis were recorded. The Kappa indices for concordance of the tables and their predictive capacity were calculated. RESULTS: 18.2% of men and 15.2% of women suffered some coronary event. The coronary risk calculations were, for men and women, 30%-20% (Framingham '91), 36%-21% (Framingham '98), 38%-23% (UKPDS), and 15%-10% (REGICOR). CONCLUSIONS: The various methods for calculating coronary risk in diabetics suffer large variability. We should highlight their low diagnostic value in individual cases, with sensitivities of 25%-75% and low specificity (mainly in men) regarding real risk of coronary disease.

Clinical patterns of cutaneous nontuberculous mycobacterial infections.

BACKGROUND: Cutaneous nontuberculous mycobacterial infections result from external inoculation, spread of a deeper infection, or haematogenous spread of a disseminated infection. There are two species-specific infections (fish-tank or swimming-pool granuloma, due to Mycobacterium marinum, and Buruli ulcer, caused by M. ulcerans). Most infections, however, produce a nonspecific clinical picture. OBJECTIVES: To define clinical patterns of cutaneous disease in nontuberculous mycobacterial infections. METHODS: Fifty-one patients with cutaneous nontuberculous mycobacterial infections were reviewed. Clinical and histopathological features of normal hosts and immunosuppressed patients were compared. Two subgroups of immunosuppressed patients were distinguished: patients with cutaneous infection and patients with a disseminated infection and cutaneous involvement. RESULTS: In immunosuppressed patients the number of lesions was significantly higher. Abscesses and ulceration were also more frequently observed. Different species were found in normal hosts and immunosuppressed patients. Several clinical patterns of cutaneous infection were defined: lymphocutaneous or sporotrichoid lesions; nonlymphocutaneous lesions at the site of trauma; folliculitis and furunculosis involving the lower extremities; disseminated lesions on the extremities in immunosuppressed patients. Two patterns were observed in patients with a disseminated infection: localized cutaneous lesions and disseminated cutaneous and mucosal lesions. CONCLUSIONS: Cutaneous manifestations of nontuberculous mycobacterial infections may be classified according to criteria such as cutaneous lesions and immune status.

A lily stylar pectin is necessary for pollen tube adhesion to an in vitro stylar matrix.

Pollen tube cells adhere to the wall surface of the stylar transmitting tract epidermis in lily. This adhesion has been proposed as essential for the proper delivery of the sperm cells to the ovule. An in vitro adhesion bioassay has been used to isolate two stylar molecules required for lily pollen tube adhesion. The first molecule was determined to be a small, cysteine-rich protein with some sequence similarity to lipid transfer proteins and now called stigma/stylar cysteine-rich adhesin (SCA). The second, larger, molecule has now been purified from style fragments and characterized. Chemical composition, specific enzyme degradations, and immunolabeling data support the idea that this molecule required for pollen tube adhesion is a pectic polysaccharide. In vitro binding assays revealed that this lily stylar adhesive pectin and SCA are able to bind to each other in a pH-dependent manner.

Focal nodular hyperplasia of the liver: assessment with contrast-enhanced TurboFLASH MR imaging.

Twenty-two patients with 25 cases of focal nodular hyperplasia (FNH) proved with pathologic study were imaged with a TurboFLASH (fast low angle shot) sequence combined with bolus administration of gadolinium tetraazacyclododecanetetraacetic acid (DOTA), spin-echo (SE) T2-weighted sequences, and postcontrast T1-weighted sequences. FNH-liver signal-difference-to-noise ratios were quantified; the features of the central scar were qualitatively analyzed. On SE T2-weighted images, all FNHs were hyperintense; in two cases the central scar exhibited a high signal intensity associated with hypointense areas corresponding to fibrous tissue within the branches of the scar. Unenhanced TurboFLASH images always demonstrated the FNHs as hypointense and always depicted the central scar as a hypointense area within the lesion. After bolus injection, arterial enhancement of FNH was clearly seen, and in 10 of 25 lesions, enhancement within the scar was seen 40-80 seconds after injection. Both unenhanced and enhanced TurboFLASH sequences produced the best signal-difference-to-noise ratios in comparison with T2-weighted images.

[Diagnosing type 2 diabetes mellitus: in primary care, fasting plasma glucose and glycosylated haemoglobin do the job]. / Diagnosticando la diabetes mellitus tipo 2: en atención primaria, con la glucemia basal y la hemoglobina glucosilada es suficiente.

OBJECTIVE: To determine the validity of glycosylated hemoglobin (HbA1c) values as a method to diagnose type 2 diabetes mellitus (DM2) in a population at risk seen in primary care. DESIGN: Cross-sectional analytical study. SETTING: Data were obtained for the Raval Sud study population (epidemiologic study of alterations in glucose metabolism in a population at risk). PARTICIPANTS: 454 subjects from this population (mean age, 65 +/- 3 years; 52% male) at high risk for DM2, seen at a primary care center, were included in the study. MAIN MEASURES: We recorded demographic data and laboratory values for fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and HbA1c. The diagnostic criteria used for DM2 were those published by the WHO in 1999. Values for HbA1c were expressed as the number of standard deviations (SD) above the mean. RESULTS: Levels of HbA1c correlated with FPG (r=0.72) and glucose levels 2 h after oral glucose overload (r=0.43). Thirty percent of the patients with FPG between 110 and 125 mg/dL had HbA1c values higher than the reference limits. A combined technique based on FPG>125 mg/dL or FPG 110-125 mg/dL with HbA1c > or = 3 SD (5.94%) showed a sensitivity of 92% and a specificity of 95%. CONCLUSIONS: When FPG is inconclusive (110-125 mg/dL), an HbA1c value more than 3 standard deviations above the mean (>5.94%) is useful in suggesting a likely diagnosis of diabetes and identifying patients who require treatment.

Effects of positive end-expiratory pressure and different tidal volumes on alveolar recruitment and hyperinflation.

BACKGROUND: The morphologic effect of positive end-expiratory pressure (PEEP) and of two tidal volumes were studied by computed tomography to determine whether setting the tidal volume (Vt) at the upper inflection point (UIP) of the pressure-volume (P-V) curve of the respiratory system or 10 ml/kg have different effects on hyperinflation and alveolar recruitment. METHODS: Alveolar recruitment and hyperinflation were quantified by computed tomography in nine patients with the acute respiratory distress syndrome (ARDS). First, end expiration was compared without PEEP and with PEEP set at the lower inflection point of the P-V curve; second, at end inspiration above PEEP, a reduced Vt set at the UIP (rVt) and a standard 10 ml/kg Vt (Vt) ending above the UIP were compared. Three lung zones were defined from computed tomographic densities: hyperdense, normal, and hyperinflated zones. RESULTS: Positive end-expiratory pressure induced a significant decrease in hyperdensities (from 46.8 +/- 18% to 38 +/- 15.1% of zero end-expiratory pressure (ZEEP) area; P < 0.02) with a concomitant increase in normal zones (from 47.3 +/- 20.9% to 56.5 +/- 13.2% of the ZEEP area; P < 0.05), and a significant increase in hyperinflation (from 8.1 +/- 5.9% to 17.8 +/- 12.7% of ZEEP area; P < 0.01). At end inspiration, a significant increase in hyperinflated areas was observed with Vt compared with rVt (33.4 +/- 17.8 vs. 26.8 +/- 17.3% of ZEEP area; P < 0.05), whereas no significant difference was observed for both normal and hyperdense zones. CONCLUSIONS: Positive end-expiratory pressure promotes alveolar recruitment; increasing Vt above the UIP seems to predominantly increase hyperinflation.

A lipid transfer-like protein is necessary for lily pollen tube adhesion to an in vitro stylar matrix.

Flowering plants possess specialized extracellular matrices in the female organs of the flower that support pollen tube growth and sperm cell transfer along the transmitting tract of the gynoecium. Transport of the pollen tube cell and the sperm cells involves a cell adhesion and migration event in species such as lily that possess a transmitting tract epidermis in the stigma, style, and ovary. A bioassay for adhesion was used to isolate from the lily stigma/stylar exudate the components that are responsible for in vivo pollen tube adhesion. At least two stylar components are necessary for adhesion: a large molecule and a small (9 kD) protein. In combination, the two molecules induced adhesion of pollen tubes to an artificial stylar matrix in vitro. The 9-kD protein was purified, and its corresponding cDNA was cloned. This molecule shares some similarity with plant lipid transfer proteins. Immunolocalization data support its role in facilitating adhesion of pollen tubes to the stylar transmitting tract epidermis.